Expert Perspective

With #Ozempic and #ozempicweightloss continuing to trend on social media, along with the mainstream media focusing on celebrities who rely on Ozempic (semaglutide) for weight loss, the daily requests for this new medication have been increasing.

Accompanying these requests are concerns and questions about potential risks, including this most recent message from one of my patients: “Dr. P – I saw the warnings. Is this medication going to make me get thyroid cancer? Please let me know!”

Let’s look at what we know to date, including recent studies, and how to advise our patients on this very hot topic.
 

Using GLP-1 receptor agonists for obesity

We have extensive prior experience with glucagon-like peptide 1 (GLP-1) receptor agonists, such as semaglutide, for treating type 2 diabetes and now recently as agents for weight loss.

Large clinical trials have documented the benefits of this medication class not only for weight reduction but also for cardiovascular and renal benefits in patients with diabetes. The subcutaneously injectable medications work by promoting insulin secretion, slowing gastric emptying, and suppressing glucagon secretion, with a low risk for hypoglycemia.

The Food and Drug Administration approved daily-injection GLP-1 agonist liraglutide for weight loss in 2014, and weekly-injection semaglutide for chronic weight management in 2021, in patients with a body mass index ≥ 27 with at least one weight-related condition or a BMI ≥ 30.

The brand name for semaglutide approved for weight loss is Wegovy, and the dose is slightly higher (maximum 2.4 mg/wk) than that of Ozempic (maximum 2.0 mg/wk), which is semaglutide approved for type 2 diabetes.

In trials for weight loss, data showed a mean change in body weight of almost 15% in the semaglutide group at week 68 compared with placebo, which is very impressive, particularly compared with other FDA-approved oral long-term weight loss medications.

The newest synthetic dual-acting agent is tirzepatide, which targets GLP-1 but is also a glucose-dependent insulinotropic polypeptide (GIP) agonist. The weekly subcutaneous injection was approved in May 2022 as Mounjaro for treating type 2 diabetes and produced even greater weight loss than semaglutide in clinical trials. Tirzepatide is now in trials for obesity and is under expedited review by the FDA for weight loss.
 

Why the concern about thyroid cancer?

Early on with the FDA approvals of GLP-1 agonists, a warning accompanied the products’ labels to not use this class of medications in patients with medullary thyroid cancer, a family history of medullary thyroid cancer, or multiple endocrine neoplasia syndrome type 2. This warning was based on data from animal studies.

Human pancreatic cells aren’t the only cells that express GLP-1 receptors. These receptors are also expressed by parafollicular cells (C cells) of the thyroid, which secrete calcitonin and are the cells involved in medullary thyroid cancer. A dose-related and duration-dependent increase in thyroid C-cell tumor incidence was noted in rodents. The same relationship was not demonstrated in monkeys. Humans have far fewer C cells than rats, and human C cells have very low expression of the GLP-1 receptor.

Over a decade ago, a study examining the FDA’s database of reported adverse events found an increased risk for thyroid cancer in patients treated with exenatide, another GLP-1 agonist. The reporting system wasn’t designed to distinguish thyroid cancer subtypes.

Numerous subsequent studies didn’t confirm this relationship. The LEADER trial looked at liraglutide in patients with type 2 diabetes and showed no effect of GLP-1 receptor activation on human serum calcitonin levels, C-cell proliferation, or C-cell malignancy. Similarly, a large meta-analysis in patients with type 2 diabetes didn’t find a statistically increased risk for thyroid cancer with liraglutide, and no thyroid malignancies were reported with exenatide.

Two U.S. administrative databases from commercial health plans (a retrospective cohort study and a nested case-control study) compared type 2 diabetes patients who were taking exenatide vs. other antidiabetic drugs and found that exenatide was not significantly associated with an increased risk for thyroid cancer.

And a recent meta-analysis of 45 trials showed no significant effects on the occurrence of thyroid cancer with GLP-1 receptor agonists. Of note, it did find an increased risk for overall thyroid disorders, although there was no clear statistically significant finding pointing to a specific thyroid disorder.

Differing from prior studies, a recent nationwide French health care system study provided newer data suggesting a moderate increased risk for thyroid cancer in a cohort of patients with type 2 diabetes who were taking GLP-1 agonists. The increase in relative risk was noted for all types of thyroid cancer in patients using GLP-1 receptor agonists for 1-3 years.

An accompanying commentary by Caroline A. Thompson, PhD, and Til Stürmer, MD, provides perspective on this study’s potential limitations. These include detection bias, as the study results focused only on the statistically significant data. Also discussed were limitations to the case-control design, issues with claims-based tumor type classification (unavailability of surgical pathology), and an inability to adjust for family history and obesity, which is a risk factor alone for thyroid cancer. There was also no adjustment for exposure to head/neck radiation.

While this study has important findings to consider, it deserves further investigation, with future studies linking data to tumor registry data before a change is made in clinical practice.

No clear relationship has been drawn between GLP-1 receptor agonists and thyroid cancer in humans. Numerous confounding factors limit the data. Studies generally don’t specify the type of thyroid cancer, and they lump medullary thyroid cancer, the rarest form, with papillary thyroid cancer.

Is a detection bias present where weight loss makes nodules more visible on the neck among those treated with GLP-1 agonists? And/or are patients treated with GLP-1 agonists being screened more stringently for thyroid nodules and/or cancer?
 

How to advise our patients and respond to the EMR messages

The TikTok videos may continue, the celebrity chatter may increase, and we, as physicians, will continue to look to real-world data with randomized controlled trials to tailor our decision-making and guide our patients.

It’s prudent to advise patients that if they have a personal or family history of medullary thyroid cancer or multiple endocrine neoplasia syndrome type 2, in particular, they should avoid using this class of medication. Thyroid cancer remains a rare outcome, and GLP-1 receptor agonists remain a very important and beneficial treatment option for the right patient.

A version of this article first appeared on Medscape.com.

With #Ozempic and #ozempicweightloss continuing to trend on social media, along with the mainstream media focusing on celebrities who rely on Ozempic (semaglutide) for weight loss, the daily requests for this new medication have been increasing.

Accompanying these requests are concerns and questions about potential risks, including this most recent message from one of my patients: “Dr. P – I saw the warnings. Is this medication going to make me get thyroid cancer? Please let me know!”

Let’s look at what we know to date, including recent studies, and how to advise our patients on this very hot topic.
 

Using GLP-1 receptor agonists for obesity

We have extensive prior experience with glucagon-like peptide 1 (GLP-1) receptor agonists, such as semaglutide, for treating type 2 diabetes and now recently as agents for weight loss.

Large clinical trials have documented the benefits of this medication class not only for weight reduction but also for cardiovascular and renal benefits in patients with diabetes. The subcutaneously injectable medications work by promoting insulin secretion, slowing gastric emptying, and suppressing glucagon secretion, with a low risk for hypoglycemia.

The Food and Drug Administration approved daily-injection GLP-1 agonist liraglutide for weight loss in 2014, and weekly-injection semaglutide for chronic weight management in 2021, in patients with a body mass index ≥ 27 with at least one weight-related condition or a BMI ≥ 30.

The brand name for semaglutide approved for weight loss is Wegovy, and the dose is slightly higher (maximum 2.4 mg/wk) than that of Ozempic (maximum 2.0 mg/wk), which is semaglutide approved for type 2 diabetes.

In trials for weight loss, data showed a mean change in body weight of almost 15% in the semaglutide group at week 68 compared with placebo, which is very impressive, particularly compared with other FDA-approved oral long-term weight loss medications.

The newest synthetic dual-acting agent is tirzepatide, which targets GLP-1 but is also a glucose-dependent insulinotropic polypeptide (GIP) agonist. The weekly subcutaneous injection was approved in May 2022 as Mounjaro for treating type 2 diabetes and produced even greater weight loss than semaglutide in clinical trials. Tirzepatide is now in trials for obesity and is under expedited review by the FDA for weight loss.
 

Why the concern about thyroid cancer?

Early on with the FDA approvals of GLP-1 agonists, a warning accompanied the products’ labels to not use this class of medications in patients with medullary thyroid cancer, a family history of medullary thyroid cancer, or multiple endocrine neoplasia syndrome type 2. This warning was based on data from animal studies.

Human pancreatic cells aren’t the only cells that express GLP-1 receptors. These receptors are also expressed by parafollicular cells (C cells) of the thyroid, which secrete calcitonin and are the cells involved in medullary thyroid cancer. A dose-related and duration-dependent increase in thyroid C-cell tumor incidence was noted in rodents. The same relationship was not demonstrated in monkeys. Humans have far fewer C cells than rats, and human C cells have very low expression of the GLP-1 receptor.

Over a decade ago, a study examining the FDA’s database of reported adverse events found an increased risk for thyroid cancer in patients treated with exenatide, another GLP-1 agonist. The reporting system wasn’t designed to distinguish thyroid cancer subtypes.

Numerous subsequent studies didn’t confirm this relationship. The LEADER trial looked at liraglutide in patients with type 2 diabetes and showed no effect of GLP-1 receptor activation on human serum calcitonin levels, C-cell proliferation, or C-cell malignancy. Similarly, a large meta-analysis in patients with type 2 diabetes didn’t find a statistically increased risk for thyroid cancer with liraglutide, and no thyroid malignancies were reported with exenatide.

Two U.S. administrative databases from commercial health plans (a retrospective cohort study and a nested case-control study) compared type 2 diabetes patients who were taking exenatide vs. other antidiabetic drugs and found that exenatide was not significantly associated with an increased risk for thyroid cancer.

And a recent meta-analysis of 45 trials showed no significant effects on the occurrence of thyroid cancer with GLP-1 receptor agonists. Of note, it did find an increased risk for overall thyroid disorders, although there was no clear statistically significant finding pointing to a specific thyroid disorder.

Differing from prior studies, a recent nationwide French health care system study provided newer data suggesting a moderate increased risk for thyroid cancer in a cohort of patients with type 2 diabetes who were taking GLP-1 agonists. The increase in relative risk was noted for all types of thyroid cancer in patients using GLP-1 receptor agonists for 1-3 years.

An accompanying commentary by Caroline A. Thompson, PhD, and Til Stürmer, MD, provides perspective on this study’s potential limitations. These include detection bias, as the study results focused only on the statistically significant data. Also discussed were limitations to the case-control design, issues with claims-based tumor type classification (unavailability of surgical pathology), and an inability to adjust for family history and obesity, which is a risk factor alone for thyroid cancer. There was also no adjustment for exposure to head/neck radiation.

While this study has important findings to consider, it deserves further investigation, with future studies linking data to tumor registry data before a change is made in clinical practice.

No clear relationship has been drawn between GLP-1 receptor agonists and thyroid cancer in humans. Numerous confounding factors limit the data. Studies generally don’t specify the type of thyroid cancer, and they lump medullary thyroid cancer, the rarest form, with papillary thyroid cancer.

Is a detection bias present where weight loss makes nodules more visible on the neck among those treated with GLP-1 agonists? And/or are patients treated with GLP-1 agonists being screened more stringently for thyroid nodules and/or cancer?
 

How to advise our patients and respond to the EMR messages

The TikTok videos may continue, the celebrity chatter may increase, and we, as physicians, will continue to look to real-world data with randomized controlled trials to tailor our decision-making and guide our patients.

It’s prudent to advise patients that if they have a personal or family history of medullary thyroid cancer or multiple endocrine neoplasia syndrome type 2, in particular, they should avoid using this class of medication. Thyroid cancer remains a rare outcome, and GLP-1 receptor agonists remain a very important and beneficial treatment option for the right patient.

A version of this article first appeared on Medscape.com.

With #Ozempic and #ozempicweightloss continuing to trend on social media, along with the mainstream media focusing on celebrities who rely on Ozempic (semaglutide) for weight loss, the daily requests for this new medication have been increasing.

Accompanying these requests are concerns and questions about potential risks, including this most recent message from one of my patients: “Dr. P – I saw the warnings. Is this medication going to make me get thyroid cancer? Please let me know!”

Let’s look at what we know to date, including recent studies, and how to advise our patients on this very hot topic.
 

Using GLP-1 receptor agonists for obesity

We have extensive prior experience with glucagon-like peptide 1 (GLP-1) receptor agonists, such as semaglutide, for treating type 2 diabetes and now recently as agents for weight loss.

Large clinical trials have documented the benefits of this medication class not only for weight reduction but also for cardiovascular and renal benefits in patients with diabetes. The subcutaneously injectable medications work by promoting insulin secretion, slowing gastric emptying, and suppressing glucagon secretion, with a low risk for hypoglycemia.

The Food and Drug Administration approved daily-injection GLP-1 agonist liraglutide for weight loss in 2014, and weekly-injection semaglutide for chronic weight management in 2021, in patients with a body mass index ≥ 27 with at least one weight-related condition or a BMI ≥ 30.

The brand name for semaglutide approved for weight loss is Wegovy, and the dose is slightly higher (maximum 2.4 mg/wk) than that of Ozempic (maximum 2.0 mg/wk), which is semaglutide approved for type 2 diabetes.

In trials for weight loss, data showed a mean change in body weight of almost 15% in the semaglutide group at week 68 compared with placebo, which is very impressive, particularly compared with other FDA-approved oral long-term weight loss medications.

The newest synthetic dual-acting agent is tirzepatide, which targets GLP-1 but is also a glucose-dependent insulinotropic polypeptide (GIP) agonist. The weekly subcutaneous injection was approved in May 2022 as Mounjaro for treating type 2 diabetes and produced even greater weight loss than semaglutide in clinical trials. Tirzepatide is now in trials for obesity and is under expedited review by the FDA for weight loss.
 

Why the concern about thyroid cancer?

Early on with the FDA approvals of GLP-1 agonists, a warning accompanied the products’ labels to not use this class of medications in patients with medullary thyroid cancer, a family history of medullary thyroid cancer, or multiple endocrine neoplasia syndrome type 2. This warning was based on data from animal studies.

Human pancreatic cells aren’t the only cells that express GLP-1 receptors. These receptors are also expressed by parafollicular cells (C cells) of the thyroid, which secrete calcitonin and are the cells involved in medullary thyroid cancer. A dose-related and duration-dependent increase in thyroid C-cell tumor incidence was noted in rodents. The same relationship was not demonstrated in monkeys. Humans have far fewer C cells than rats, and human C cells have very low expression of the GLP-1 receptor.

Over a decade ago, a study examining the FDA’s database of reported adverse events found an increased risk for thyroid cancer in patients treated with exenatide, another GLP-1 agonist. The reporting system wasn’t designed to distinguish thyroid cancer subtypes.

Numerous subsequent studies didn’t confirm this relationship. The LEADER trial looked at liraglutide in patients with type 2 diabetes and showed no effect of GLP-1 receptor activation on human serum calcitonin levels, C-cell proliferation, or C-cell malignancy. Similarly, a large meta-analysis in patients with type 2 diabetes didn’t find a statistically increased risk for thyroid cancer with liraglutide, and no thyroid malignancies were reported with exenatide.

Two U.S. administrative databases from commercial health plans (a retrospective cohort study and a nested case-control study) compared type 2 diabetes patients who were taking exenatide vs. other antidiabetic drugs and found that exenatide was not significantly associated with an increased risk for thyroid cancer.

And a recent meta-analysis of 45 trials showed no significant effects on the occurrence of thyroid cancer with GLP-1 receptor agonists. Of note, it did find an increased risk for overall thyroid disorders, although there was no clear statistically significant finding pointing to a specific thyroid disorder.

Differing from prior studies, a recent nationwide French health care system study provided newer data suggesting a moderate increased risk for thyroid cancer in a cohort of patients with type 2 diabetes who were taking GLP-1 agonists. The increase in relative risk was noted for all types of thyroid cancer in patients using GLP-1 receptor agonists for 1-3 years.

An accompanying commentary by Caroline A. Thompson, PhD, and Til Stürmer, MD, provides perspective on this study’s potential limitations. These include detection bias, as the study results focused only on the statistically significant data. Also discussed were limitations to the case-control design, issues with claims-based tumor type classification (unavailability of surgical pathology), and an inability to adjust for family history and obesity, which is a risk factor alone for thyroid cancer. There was also no adjustment for exposure to head/neck radiation.

While this study has important findings to consider, it deserves further investigation, with future studies linking data to tumor registry data before a change is made in clinical practice.

No clear relationship has been drawn between GLP-1 receptor agonists and thyroid cancer in humans. Numerous confounding factors limit the data. Studies generally don’t specify the type of thyroid cancer, and they lump medullary thyroid cancer, the rarest form, with papillary thyroid cancer.

Is a detection bias present where weight loss makes nodules more visible on the neck among those treated with GLP-1 agonists? And/or are patients treated with GLP-1 agonists being screened more stringently for thyroid nodules and/or cancer?
 

How to advise our patients and respond to the EMR messages

The TikTok videos may continue, the celebrity chatter may increase, and we, as physicians, will continue to look to real-world data with randomized controlled trials to tailor our decision-making and guide our patients.

It’s prudent to advise patients that if they have a personal or family history of medullary thyroid cancer or multiple endocrine neoplasia syndrome type 2, in particular, they should avoid using this class of medication. Thyroid cancer remains a rare outcome, and GLP-1 receptor agonists remain a very important and beneficial treatment option for the right patient.

A version of this article first appeared on Medscape.com.

With the rising popularity of weight-loss drug injections, I’ve received many questions from patients about the pros, cons, and costs. While Ozempic (semaglutide) is perhaps the best known, it’s technically an agent approved only for type 2 diabetes that has been used off label for obesity. The same substance, semaglutide, is approved for use in obesity, but at a higher dose, under the brand name Wegovy. Alternatives are available, and results will vary depending on the specific agent used and the individual.

Ultimately, I decided to try these new injections for myself. I am not a paid representative for, nor an advocate of, any of these medications; I’m here only to share my personal experience.

In my discussions with patients about weight, I sometimes felt like an imposter. While I was overweight by medical standards, I fortunately had none of the underlying health problems. I wasn’t on medications for blood pressure nor did I have diabetes, but I was counseling people to lose weight and eat better while not always following my own advice.

Since having children and turning 40, my metabolism, like many other women’s, seems to have plummeted. I tried a number of older weight-loss medications, like phentermine and phendimetrazine, under the supervision of medical professionals.

Each time, the efforts worked for a short while, particularly when I followed good portion control and practiced moderate exercise. Once the side effects (that is, tachycardia, palpitations, mood changes, constipation) became intolerable, or I became tired or fearful of being on the medications too long, I’d stop and I would regain some of the weight.

When the newer subcutaneous injectable medications arrived on the scene and I started to talk to my patients about them, I was intrigued by their novel mode of action and seeming benefits.

These medications, glucagonlike peptide–1 (GLP-1) receptor agonists, were first approved for type 2 diabetes, and it soon became apparent that patients were losing significant amounts of weight taking them, so manufacturers conducted further trials in obesity patients without type 2 diabetes.

The first of these, liraglutide, is injected daily and was first approved as Victoza for type 2 diabetes; it later received an additional approval for obesity, in December 2014, as Saxenda.

Semaglutide, another of the new GLP-1 agonists, was first approved for type 2 diabetes as Ozempic but again was found to lead to substantial weight loss, so a subsequent approval of the drug for obesity, as Wegovy, came in June 2021. Semaglutide is injected once a week.

Semaglutide was branded a “game changer” when it was licensed for obesity because the mean weight loss seen in trials was around 15%, more than for any other drug and approaching what could be achieved with bariatric surgery, some doctors said.

These medications work in a different way from the older weight loss drugs, which had focused on the use of amphetamines. The newer medications became very popular because treating obesity helps lower blood glucose, blood pressure, cholesterol, kidney disease risk, and other comorbidities that occur with diabetes. Plus, for most people, there were fewer side effects.

I first tried Saxenda when it arrived on the market, via some samples that our pharmaceutical representative brought, both out of curiosity and to see if it would help me lose the stubborn baby weight. I ended up stopping the daily injections after my second or third week because of nausea and vomiting. I took a break, got a prescription for antinausea medicine, and tried again because it did indeed decrease my appetite. However, when I took my prescription to the pharmacy, my insurance wouldn’t cover it. It happens to doctors, too.

Fast-forward to 2017-2018. The baby weight was still holding on despite lifestyle changes, diet, and exercising. The newer drug classes hit the market, and again we had samples from our reps. When our rep explained the potential for weight loss in patients without diabetes, I tried Ozempic off label. Within the first 2 weeks, I noticed a 3- to- 5-lb weight loss.

When Ozempic was on backorder, I switched to a low dose of Mounjaro (tirzepatide), a new dual GLP-1 and glucose-dependent insulinotropic polypeptide agonist, approved for type 2 diabetes in May 2022, again using it off label as a weekly injection, as it isn’t currently approved for weight loss. However, it does produce significant weight loss and is awaiting approval for obesity.

With these new medications, I noticed that both my patients and I didn’t complain as much about nausea and vomiting, but I did experience stomach upset, constipation, and acid reflux.

The appetite suppression is effective. It slows down the emptying of the gut so I feel full longer. I’ve lost 30 lb with these weekly injections and would like to lose another 20 lb. I follow a routine of reasonable, portion-controlled eating and moderate exercise (30 minutes of cardiovascular activity at least two to three times a week).

Discontinuing the medications may cause rebound weight gain, especially if I’m no longer following a routine of healthy eating and/or moderate exercise. I deal with minimal constipation by taking stool softeners, and I take antacids for acid reflux.

Here’s what I recommend applying when working with patients who have obesity: First, explain how these medications work. Then conduct a health history to make sure these injections are right for them. Patients with a family history of pancreatic cancer can’t take these medications. You also want to monitor use in patients with a history of hypoglycemia so their blood sugar doesn’t drop too low. It’s also important to make sure your patients are able to afford the medication. My husband takes Ozempic for diabetes, and recently we were told that a refill would cost about $1,500 a month, even with insurance. “Covered” doesn’t necessarily mean affordable.

Take a baseline hemoglobin A1c and repeat it after the patient has been on the medication for 2-3 weeks. Also remind them that they can’t rely solely on the medication but need to practice portion control and healthier eating and to exercise more.

For myself, I want to lose those remaining 20 lb or so by eating healthy and being physically active without having to rely on medication for the rest of my life. Research on these medications is still early so we don’t know the long-term effects yet.

As clinicians, I feel it’s okay to be honest with our patients about our own personal struggles to help them understand that they are not alone and that losing weight is a challenge for everyone.

Dr. Swiner is a family physician in Durham, N.C. She reported no conflicts of interest.

A version of this article first appeared on Medscape.com.

With the rising popularity of weight-loss drug injections, I’ve received many questions from patients about the pros, cons, and costs. While Ozempic (semaglutide) is perhaps the best known, it’s technically an agent approved only for type 2 diabetes that has been used off label for obesity. The same substance, semaglutide, is approved for use in obesity, but at a higher dose, under the brand name Wegovy. Alternatives are available, and results will vary depending on the specific agent used and the individual.

Ultimately, I decided to try these new injections for myself. I am not a paid representative for, nor an advocate of, any of these medications; I’m here only to share my personal experience.

In my discussions with patients about weight, I sometimes felt like an imposter. While I was overweight by medical standards, I fortunately had none of the underlying health problems. I wasn’t on medications for blood pressure nor did I have diabetes, but I was counseling people to lose weight and eat better while not always following my own advice.

Since having children and turning 40, my metabolism, like many other women’s, seems to have plummeted. I tried a number of older weight-loss medications, like phentermine and phendimetrazine, under the supervision of medical professionals.

Each time, the efforts worked for a short while, particularly when I followed good portion control and practiced moderate exercise. Once the side effects (that is, tachycardia, palpitations, mood changes, constipation) became intolerable, or I became tired or fearful of being on the medications too long, I’d stop and I would regain some of the weight.

When the newer subcutaneous injectable medications arrived on the scene and I started to talk to my patients about them, I was intrigued by their novel mode of action and seeming benefits.

These medications, glucagonlike peptide–1 (GLP-1) receptor agonists, were first approved for type 2 diabetes, and it soon became apparent that patients were losing significant amounts of weight taking them, so manufacturers conducted further trials in obesity patients without type 2 diabetes.

The first of these, liraglutide, is injected daily and was first approved as Victoza for type 2 diabetes; it later received an additional approval for obesity, in December 2014, as Saxenda.

Semaglutide, another of the new GLP-1 agonists, was first approved for type 2 diabetes as Ozempic but again was found to lead to substantial weight loss, so a subsequent approval of the drug for obesity, as Wegovy, came in June 2021. Semaglutide is injected once a week.

Semaglutide was branded a “game changer” when it was licensed for obesity because the mean weight loss seen in trials was around 15%, more than for any other drug and approaching what could be achieved with bariatric surgery, some doctors said.

These medications work in a different way from the older weight loss drugs, which had focused on the use of amphetamines. The newer medications became very popular because treating obesity helps lower blood glucose, blood pressure, cholesterol, kidney disease risk, and other comorbidities that occur with diabetes. Plus, for most people, there were fewer side effects.

I first tried Saxenda when it arrived on the market, via some samples that our pharmaceutical representative brought, both out of curiosity and to see if it would help me lose the stubborn baby weight. I ended up stopping the daily injections after my second or third week because of nausea and vomiting. I took a break, got a prescription for antinausea medicine, and tried again because it did indeed decrease my appetite. However, when I took my prescription to the pharmacy, my insurance wouldn’t cover it. It happens to doctors, too.

Fast-forward to 2017-2018. The baby weight was still holding on despite lifestyle changes, diet, and exercising. The newer drug classes hit the market, and again we had samples from our reps. When our rep explained the potential for weight loss in patients without diabetes, I tried Ozempic off label. Within the first 2 weeks, I noticed a 3- to- 5-lb weight loss.

When Ozempic was on backorder, I switched to a low dose of Mounjaro (tirzepatide), a new dual GLP-1 and glucose-dependent insulinotropic polypeptide agonist, approved for type 2 diabetes in May 2022, again using it off label as a weekly injection, as it isn’t currently approved for weight loss. However, it does produce significant weight loss and is awaiting approval for obesity.

With these new medications, I noticed that both my patients and I didn’t complain as much about nausea and vomiting, but I did experience stomach upset, constipation, and acid reflux.

The appetite suppression is effective. It slows down the emptying of the gut so I feel full longer. I’ve lost 30 lb with these weekly injections and would like to lose another 20 lb. I follow a routine of reasonable, portion-controlled eating and moderate exercise (30 minutes of cardiovascular activity at least two to three times a week).

Discontinuing the medications may cause rebound weight gain, especially if I’m no longer following a routine of healthy eating and/or moderate exercise. I deal with minimal constipation by taking stool softeners, and I take antacids for acid reflux.

Here’s what I recommend applying when working with patients who have obesity: First, explain how these medications work. Then conduct a health history to make sure these injections are right for them. Patients with a family history of pancreatic cancer can’t take these medications. You also want to monitor use in patients with a history of hypoglycemia so their blood sugar doesn’t drop too low. It’s also important to make sure your patients are able to afford the medication. My husband takes Ozempic for diabetes, and recently we were told that a refill would cost about $1,500 a month, even with insurance. “Covered” doesn’t necessarily mean affordable.

Take a baseline hemoglobin A1c and repeat it after the patient has been on the medication for 2-3 weeks. Also remind them that they can’t rely solely on the medication but need to practice portion control and healthier eating and to exercise more.

For myself, I want to lose those remaining 20 lb or so by eating healthy and being physically active without having to rely on medication for the rest of my life. Research on these medications is still early so we don’t know the long-term effects yet.

As clinicians, I feel it’s okay to be honest with our patients about our own personal struggles to help them understand that they are not alone and that losing weight is a challenge for everyone.

Dr. Swiner is a family physician in Durham, N.C. She reported no conflicts of interest.

A version of this article first appeared on Medscape.com.

With the rising popularity of weight-loss drug injections, I’ve received many questions from patients about the pros, cons, and costs. While Ozempic (semaglutide) is perhaps the best known, it’s technically an agent approved only for type 2 diabetes that has been used off label for obesity. The same substance, semaglutide, is approved for use in obesity, but at a higher dose, under the brand name Wegovy. Alternatives are available, and results will vary depending on the specific agent used and the individual.

Ultimately, I decided to try these new injections for myself. I am not a paid representative for, nor an advocate of, any of these medications; I’m here only to share my personal experience.

In my discussions with patients about weight, I sometimes felt like an imposter. While I was overweight by medical standards, I fortunately had none of the underlying health problems. I wasn’t on medications for blood pressure nor did I have diabetes, but I was counseling people to lose weight and eat better while not always following my own advice.

Since having children and turning 40, my metabolism, like many other women’s, seems to have plummeted. I tried a number of older weight-loss medications, like phentermine and phendimetrazine, under the supervision of medical professionals.

Each time, the efforts worked for a short while, particularly when I followed good portion control and practiced moderate exercise. Once the side effects (that is, tachycardia, palpitations, mood changes, constipation) became intolerable, or I became tired or fearful of being on the medications too long, I’d stop and I would regain some of the weight.

When the newer subcutaneous injectable medications arrived on the scene and I started to talk to my patients about them, I was intrigued by their novel mode of action and seeming benefits.

These medications, glucagonlike peptide–1 (GLP-1) receptor agonists, were first approved for type 2 diabetes, and it soon became apparent that patients were losing significant amounts of weight taking them, so manufacturers conducted further trials in obesity patients without type 2 diabetes.

The first of these, liraglutide, is injected daily and was first approved as Victoza for type 2 diabetes; it later received an additional approval for obesity, in December 2014, as Saxenda.

Semaglutide, another of the new GLP-1 agonists, was first approved for type 2 diabetes as Ozempic but again was found to lead to substantial weight loss, so a subsequent approval of the drug for obesity, as Wegovy, came in June 2021. Semaglutide is injected once a week.

Semaglutide was branded a “game changer” when it was licensed for obesity because the mean weight loss seen in trials was around 15%, more than for any other drug and approaching what could be achieved with bariatric surgery, some doctors said.

These medications work in a different way from the older weight loss drugs, which had focused on the use of amphetamines. The newer medications became very popular because treating obesity helps lower blood glucose, blood pressure, cholesterol, kidney disease risk, and other comorbidities that occur with diabetes. Plus, for most people, there were fewer side effects.

I first tried Saxenda when it arrived on the market, via some samples that our pharmaceutical representative brought, both out of curiosity and to see if it would help me lose the stubborn baby weight. I ended up stopping the daily injections after my second or third week because of nausea and vomiting. I took a break, got a prescription for antinausea medicine, and tried again because it did indeed decrease my appetite. However, when I took my prescription to the pharmacy, my insurance wouldn’t cover it. It happens to doctors, too.

Fast-forward to 2017-2018. The baby weight was still holding on despite lifestyle changes, diet, and exercising. The newer drug classes hit the market, and again we had samples from our reps. When our rep explained the potential for weight loss in patients without diabetes, I tried Ozempic off label. Within the first 2 weeks, I noticed a 3- to- 5-lb weight loss.

When Ozempic was on backorder, I switched to a low dose of Mounjaro (tirzepatide), a new dual GLP-1 and glucose-dependent insulinotropic polypeptide agonist, approved for type 2 diabetes in May 2022, again using it off label as a weekly injection, as it isn’t currently approved for weight loss. However, it does produce significant weight loss and is awaiting approval for obesity.

With these new medications, I noticed that both my patients and I didn’t complain as much about nausea and vomiting, but I did experience stomach upset, constipation, and acid reflux.

The appetite suppression is effective. It slows down the emptying of the gut so I feel full longer. I’ve lost 30 lb with these weekly injections and would like to lose another 20 lb. I follow a routine of reasonable, portion-controlled eating and moderate exercise (30 minutes of cardiovascular activity at least two to three times a week).

Discontinuing the medications may cause rebound weight gain, especially if I’m no longer following a routine of healthy eating and/or moderate exercise. I deal with minimal constipation by taking stool softeners, and I take antacids for acid reflux.

Here’s what I recommend applying when working with patients who have obesity: First, explain how these medications work. Then conduct a health history to make sure these injections are right for them. Patients with a family history of pancreatic cancer can’t take these medications. You also want to monitor use in patients with a history of hypoglycemia so their blood sugar doesn’t drop too low. It’s also important to make sure your patients are able to afford the medication. My husband takes Ozempic for diabetes, and recently we were told that a refill would cost about $1,500 a month, even with insurance. “Covered” doesn’t necessarily mean affordable.

Take a baseline hemoglobin A1c and repeat it after the patient has been on the medication for 2-3 weeks. Also remind them that they can’t rely solely on the medication but need to practice portion control and healthier eating and to exercise more.

For myself, I want to lose those remaining 20 lb or so by eating healthy and being physically active without having to rely on medication for the rest of my life. Research on these medications is still early so we don’t know the long-term effects yet.

As clinicians, I feel it’s okay to be honest with our patients about our own personal struggles to help them understand that they are not alone and that losing weight is a challenge for everyone.

Dr. Swiner is a family physician in Durham, N.C. She reported no conflicts of interest.

A version of this article first appeared on Medscape.com.

Introduction

The COVID-19 pandemic has changed the healthcare system in a multitude of ways, affecting healthcare capacity, treatment of other illnesses, and wellness as well as professional retention of healthcare workers.^1-3 During the peak of the COVID-19 pandemic, healthcare capacity was tested and resources were used up quickly.¹ As the pandemic has progressed, healthcare systems have had to decide how to proceed with lessons learned, reassessing the environment of care delivery, healthcare supply chains, workforce structures, communication systems, and scientific collaboration as well as policy frameworks in healthcare.⁴ 

There have been both immediate effects and long-term consequences of the delay in care for other conditions.^2,5 One stark example of this is in cancer care, where screening and procedures were postponed or canceled due to the pandemic with a resulting predicted 2% increase in cancer mortality in the next 10 years.² The care of heart disease, chronic illnesses, and other viruses has also been similarly negatively impacted by the COVID-19 pandemic due to similar delays in diagnosis and treatment.^5-7 

The impact on healthcare workers has also been profound.³ Occupational stress from the pandemic has correlated with increased depression and posttraumatic stress disorder (PTSD) among other mental health diseases in healthcare workers.³ In a survey of neurosurgery residents, 26.1% of physicians reported feeling burnt out, and 65.8% were worried that they would not be able to reach surgical milestones.^8,9 Among respiratory therapists, a hard hit group during this time, 79% reported burnout.¹⁰ Additionally, more healthcare workers left the field during the pandemic, with 15 million lost jobs. Future recovery of jobs looks bleak in some settings, like long-term care and among assistants and aides.¹¹ Overall, the long-term outcomes of these resource, disease, and mental health disruptions need to be assessed and solutions created to maintain a quality and effective healthcare system, with ample resources and measures to account for disease increases and address the impact on providers. 

Healthcare Capacity and Resources 

With COVID-19 affecting over 100 million in the United States as of March 1, 2023, the impact on healthcare resources since the start of the pandemic has been immense.¹² With 5% to 38% of hospitalized patients being admitted to the intensive care unit (ICU) and 75% to 88% of those patients requiring mechanical ventilation, a huge strain was placed on resources during and after the pandemic.¹ 

The question of balancing resources for other hospital needs while tending to patients with COVID-19 has been an ongoing discussion at many levels.¹ One core resource concern is the lack of staff. In a survey of 77 different countries, including physicians (41%), nurses (40%), respiratory therapists (11%), and advanced practice providers (8%), 15% reported insufficient intensivists and 32% reported insufficient ICU nursing staff during March and April of 2020.¹ A lack of hospital and care space that led to reallocation of limited-care acute care space was a concern. Thirteen percent reported a shortage of hospital ICU beds, while others reported the conversion of postoperative recovery rooms (20%) and operating rooms (12%) for patients with COVID-19.¹ 

Along with staff and care space concerns, hospital survey respondents reported that healthcare equipment was also challenged. Access to COVID-19 testing was one concern, with only 35% of respondents reporting availability for all patients at the beginning of the pandemic, and 56% reporting availability for only select patients based on symptom severity.¹ Access to personal protective equipment (PPE) was also affected, with PPE always available according to 83% to 95% of respondents but just 35% having access to N95 masks.¹ Additionally, 26% reported that there were no respirators in their hospital, and 11% reported limited ventilators.¹ 

Although resource depletion is a problem, studies have looked at public health measures that helped to mitigate this issue. With proper public health planning and implementation, such as physical distancing, aggressive testing, contact tracing, and increased hospital capacity, by freeing up existing resources or adding additional support, public health modeling showed that resources may be able to withstand the increase.¹³ Development of reallocation models at local, state, national, and international levels is an important step to be able to deal with future public health crises.¹⁴

The long-term impact from the pandemic includes disruption in the physical environment of healthcare, production, supply chain, staff structure, and workforce alterations.⁴ For example, the physical shape of healthcare facilities is changing to accommodate increasing volumes and decrease the risk of spreading disease.⁴ To accommodate the burden on staffing structure and workforce alteration, telehealth gained a prominent role.⁴ All in all, the pandemic has changed the healthcare system; however, institutions, organizations, and policy makers need to evaluate which measures were impactful and should be considered for long-term inclusion in healthcare practice. 

Impact on Other Diseases: Cancer, Heart Disease, Chronic Illnesses, and Other Viruses 

The treatment of other new and existing conditions has also been affected by the pandemic. Cancer, especially, is a disease of concern. Elective surgeries and screening were halted or altered during the pandemic, which is modeled to lead to higher cancer mortality in years to come.² The most affected cancers were breast, lung, and colorectal cancer.² A study of colorectal cancer screening showed that colonoscopies were delayed due to COVID-19 and that gastroenterology visits declined by 49% to 61%.¹⁵ This will likely lead to delayed cancer diagnoses and possible increases in mortality.¹⁵ Breast cancer screening was also delayed and many patients continued to avoid it for various reasons such as fears of contracting COVID-19 infection in healthcare facilities, and the economic effects of the pandemic such as job loss and healthcare coverage loss.¹⁶ These delays will result in an estimated potential 0.52% overall increase in breast cancer deaths by 2030.¹⁷

A study of 368 patients from Spain showed a 56.5% decrease in hospital admissions, usually related to heart attacks, in March and April of 2020, compared to January and February 2020.^18,19 For other chronic illnesses, the pandemic resulted in decreased preventative care and management.²⁰ The care of other infections similarly suffered. The World Health Organization announced that the number of patients receiving treatment for tuberculosis (TB) dropped by 1 million, setting the disease mitigation back considerably.²⁰ An estimated 500,000 more people died in 2020 from TB.²¹ The drastic shift in focus to COVID-19 care during this period will continue to have a profound impact on other diseases like these for many years post-pandemic.

Provider Experience and Mental Health Outcomes 

The impact on provider experiences and mental health has been immense. One study of 510 healthcare providers (HCPs) and first responders found that occupational stress from the pandemic correlated with psychiatric symptoms, including depression, PTSD, insomnia, and generalized anxiety.³ Occupational stress also correlated with one’s likelihood to leave the medical field and trouble doing work they had once loved.³ Half of the healthcare workers surveyed indicated a decreased likelihood of staying in their current profession after the pandemic.³ 

Other studies have also looked at specific subspecialties and impact on trainees during the pandemic. In neurosurgery, for example, resident burnout is high, at 26.1%.⁹ Additionally, the lack of surgeries in the pandemic made 65.8% of neurosurgery residents anxious about meeting career milestones.⁹ Respiratory therapists, a highly impacted group, also experienced burnout, reporting higher levels in those who worked more in the ICU. Another study identified several themes in the concerns reported by healthcare workers during the pandemic era including “changes in personal life and enhanced negative affect,” “gaining experience, normalization, and adaptation to the pandemic,” and “mental health considerations.”²² 

Some studies have investigated ways to mitigate this dissatisfaction with the healthcare field post-pandemic. Intrapreneurship, reverse mentoring, and democratized learning all had a reported positive impact on employee experience and retention during this time.²³ Intrapreneurship describes entrepreneurship within an existing organization, while reverse mentoring and democratized learning refer to newer employees teaching older employees and communicative learning on a breadth of topics. Other studies have examined the necessity of having mental health resources available, and that these resources need to be multi-stage and individualistic as well as specific to certain stressors HCPs faced during the pandemic.²² 

Conclusion and Future Directions

The COVID-19 pandemic had stark effects on the healthcare system, impacting resources and capacity, care of other diseases, and provider mental health and experiences.^1-3 After the chaos of the pandemic, many questions remain. What needs to be done now by health systems and HCPs? How can we learn from the challenges and the effects on capacity to change the healthcare workflow in times of crisis and in the present? How do we mitigate the impact of the pandemic on diagnosis and management of diseases? And how do we continue to provide healthcare workers with proper mental health and professional resources now, not just in times of stress, and encourage the future generation to pursue careers in healthcare? 

These are all the questions the pandemic has left us with, and more studies and initiatives are needed to investigate solutions to these issues. The COVID-19 pandemic left behind valuable lessons and changed the healthcare system, disease management, and staffing for many. Now is the time to pick up the pieces and strategize on how to make our existing system more effective for workers and patients post pandemic. 

Introduction

The COVID-19 pandemic has changed the healthcare system in a multitude of ways, affecting healthcare capacity, treatment of other illnesses, and wellness as well as professional retention of healthcare workers.^1-3 During the peak of the COVID-19 pandemic, healthcare capacity was tested and resources were used up quickly.¹ As the pandemic has progressed, healthcare systems have had to decide how to proceed with lessons learned, reassessing the environment of care delivery, healthcare supply chains, workforce structures, communication systems, and scientific collaboration as well as policy frameworks in healthcare.⁴ 

There have been both immediate effects and long-term consequences of the delay in care for other conditions.^2,5 One stark example of this is in cancer care, where screening and procedures were postponed or canceled due to the pandemic with a resulting predicted 2% increase in cancer mortality in the next 10 years.² The care of heart disease, chronic illnesses, and other viruses has also been similarly negatively impacted by the COVID-19 pandemic due to similar delays in diagnosis and treatment.^5-7 

The impact on healthcare workers has also been profound.³ Occupational stress from the pandemic has correlated with increased depression and posttraumatic stress disorder (PTSD) among other mental health diseases in healthcare workers.³ In a survey of neurosurgery residents, 26.1% of physicians reported feeling burnt out, and 65.8% were worried that they would not be able to reach surgical milestones.^8,9 Among respiratory therapists, a hard hit group during this time, 79% reported burnout.¹⁰ Additionally, more healthcare workers left the field during the pandemic, with 15 million lost jobs. Future recovery of jobs looks bleak in some settings, like long-term care and among assistants and aides.¹¹ Overall, the long-term outcomes of these resource, disease, and mental health disruptions need to be assessed and solutions created to maintain a quality and effective healthcare system, with ample resources and measures to account for disease increases and address the impact on providers. 

Healthcare Capacity and Resources 

With COVID-19 affecting over 100 million in the United States as of March 1, 2023, the impact on healthcare resources since the start of the pandemic has been immense.¹² With 5% to 38% of hospitalized patients being admitted to the intensive care unit (ICU) and 75% to 88% of those patients requiring mechanical ventilation, a huge strain was placed on resources during and after the pandemic.¹ 

The question of balancing resources for other hospital needs while tending to patients with COVID-19 has been an ongoing discussion at many levels.¹ One core resource concern is the lack of staff. In a survey of 77 different countries, including physicians (41%), nurses (40%), respiratory therapists (11%), and advanced practice providers (8%), 15% reported insufficient intensivists and 32% reported insufficient ICU nursing staff during March and April of 2020.¹ A lack of hospital and care space that led to reallocation of limited-care acute care space was a concern. Thirteen percent reported a shortage of hospital ICU beds, while others reported the conversion of postoperative recovery rooms (20%) and operating rooms (12%) for patients with COVID-19.¹ 

Along with staff and care space concerns, hospital survey respondents reported that healthcare equipment was also challenged. Access to COVID-19 testing was one concern, with only 35% of respondents reporting availability for all patients at the beginning of the pandemic, and 56% reporting availability for only select patients based on symptom severity.¹ Access to personal protective equipment (PPE) was also affected, with PPE always available according to 83% to 95% of respondents but just 35% having access to N95 masks.¹ Additionally, 26% reported that there were no respirators in their hospital, and 11% reported limited ventilators.¹ 

Although resource depletion is a problem, studies have looked at public health measures that helped to mitigate this issue. With proper public health planning and implementation, such as physical distancing, aggressive testing, contact tracing, and increased hospital capacity, by freeing up existing resources or adding additional support, public health modeling showed that resources may be able to withstand the increase.¹³ Development of reallocation models at local, state, national, and international levels is an important step to be able to deal with future public health crises.¹⁴

The long-term impact from the pandemic includes disruption in the physical environment of healthcare, production, supply chain, staff structure, and workforce alterations.⁴ For example, the physical shape of healthcare facilities is changing to accommodate increasing volumes and decrease the risk of spreading disease.⁴ To accommodate the burden on staffing structure and workforce alteration, telehealth gained a prominent role.⁴ All in all, the pandemic has changed the healthcare system; however, institutions, organizations, and policy makers need to evaluate which measures were impactful and should be considered for long-term inclusion in healthcare practice. 

Impact on Other Diseases: Cancer, Heart Disease, Chronic Illnesses, and Other Viruses 

The treatment of other new and existing conditions has also been affected by the pandemic. Cancer, especially, is a disease of concern. Elective surgeries and screening were halted or altered during the pandemic, which is modeled to lead to higher cancer mortality in years to come.² The most affected cancers were breast, lung, and colorectal cancer.² A study of colorectal cancer screening showed that colonoscopies were delayed due to COVID-19 and that gastroenterology visits declined by 49% to 61%.¹⁵ This will likely lead to delayed cancer diagnoses and possible increases in mortality.¹⁵ Breast cancer screening was also delayed and many patients continued to avoid it for various reasons such as fears of contracting COVID-19 infection in healthcare facilities, and the economic effects of the pandemic such as job loss and healthcare coverage loss.¹⁶ These delays will result in an estimated potential 0.52% overall increase in breast cancer deaths by 2030.¹⁷

A study of 368 patients from Spain showed a 56.5% decrease in hospital admissions, usually related to heart attacks, in March and April of 2020, compared to January and February 2020.^18,19 For other chronic illnesses, the pandemic resulted in decreased preventative care and management.²⁰ The care of other infections similarly suffered. The World Health Organization announced that the number of patients receiving treatment for tuberculosis (TB) dropped by 1 million, setting the disease mitigation back considerably.²⁰ An estimated 500,000 more people died in 2020 from TB.²¹ The drastic shift in focus to COVID-19 care during this period will continue to have a profound impact on other diseases like these for many years post-pandemic.

Provider Experience and Mental Health Outcomes 

The impact on provider experiences and mental health has been immense. One study of 510 healthcare providers (HCPs) and first responders found that occupational stress from the pandemic correlated with psychiatric symptoms, including depression, PTSD, insomnia, and generalized anxiety.³ Occupational stress also correlated with one’s likelihood to leave the medical field and trouble doing work they had once loved.³ Half of the healthcare workers surveyed indicated a decreased likelihood of staying in their current profession after the pandemic.³ 

Other studies have also looked at specific subspecialties and impact on trainees during the pandemic. In neurosurgery, for example, resident burnout is high, at 26.1%.⁹ Additionally, the lack of surgeries in the pandemic made 65.8% of neurosurgery residents anxious about meeting career milestones.⁹ Respiratory therapists, a highly impacted group, also experienced burnout, reporting higher levels in those who worked more in the ICU. Another study identified several themes in the concerns reported by healthcare workers during the pandemic era including “changes in personal life and enhanced negative affect,” “gaining experience, normalization, and adaptation to the pandemic,” and “mental health considerations.”²² 

Some studies have investigated ways to mitigate this dissatisfaction with the healthcare field post-pandemic. Intrapreneurship, reverse mentoring, and democratized learning all had a reported positive impact on employee experience and retention during this time.²³ Intrapreneurship describes entrepreneurship within an existing organization, while reverse mentoring and democratized learning refer to newer employees teaching older employees and communicative learning on a breadth of topics. Other studies have examined the necessity of having mental health resources available, and that these resources need to be multi-stage and individualistic as well as specific to certain stressors HCPs faced during the pandemic.²² 

Conclusion and Future Directions

The COVID-19 pandemic had stark effects on the healthcare system, impacting resources and capacity, care of other diseases, and provider mental health and experiences.^1-3 After the chaos of the pandemic, many questions remain. What needs to be done now by health systems and HCPs? How can we learn from the challenges and the effects on capacity to change the healthcare workflow in times of crisis and in the present? How do we mitigate the impact of the pandemic on diagnosis and management of diseases? And how do we continue to provide healthcare workers with proper mental health and professional resources now, not just in times of stress, and encourage the future generation to pursue careers in healthcare? 

These are all the questions the pandemic has left us with, and more studies and initiatives are needed to investigate solutions to these issues. The COVID-19 pandemic left behind valuable lessons and changed the healthcare system, disease management, and staffing for many. Now is the time to pick up the pieces and strategize on how to make our existing system more effective for workers and patients post pandemic. 

Introduction

The COVID-19 pandemic has changed the healthcare system in a multitude of ways, affecting healthcare capacity, treatment of other illnesses, and wellness as well as professional retention of healthcare workers.^1-3 During the peak of the COVID-19 pandemic, healthcare capacity was tested and resources were used up quickly.¹ As the pandemic has progressed, healthcare systems have had to decide how to proceed with lessons learned, reassessing the environment of care delivery, healthcare supply chains, workforce structures, communication systems, and scientific collaboration as well as policy frameworks in healthcare.⁴ 

There have been both immediate effects and long-term consequences of the delay in care for other conditions.^2,5 One stark example of this is in cancer care, where screening and procedures were postponed or canceled due to the pandemic with a resulting predicted 2% increase in cancer mortality in the next 10 years.² The care of heart disease, chronic illnesses, and other viruses has also been similarly negatively impacted by the COVID-19 pandemic due to similar delays in diagnosis and treatment.^5-7 

The impact on healthcare workers has also been profound.³ Occupational stress from the pandemic has correlated with increased depression and posttraumatic stress disorder (PTSD) among other mental health diseases in healthcare workers.³ In a survey of neurosurgery residents, 26.1% of physicians reported feeling burnt out, and 65.8% were worried that they would not be able to reach surgical milestones.^8,9 Among respiratory therapists, a hard hit group during this time, 79% reported burnout.¹⁰ Additionally, more healthcare workers left the field during the pandemic, with 15 million lost jobs. Future recovery of jobs looks bleak in some settings, like long-term care and among assistants and aides.¹¹ Overall, the long-term outcomes of these resource, disease, and mental health disruptions need to be assessed and solutions created to maintain a quality and effective healthcare system, with ample resources and measures to account for disease increases and address the impact on providers. 

Healthcare Capacity and Resources 

With COVID-19 affecting over 100 million in the United States as of March 1, 2023, the impact on healthcare resources since the start of the pandemic has been immense.¹² With 5% to 38% of hospitalized patients being admitted to the intensive care unit (ICU) and 75% to 88% of those patients requiring mechanical ventilation, a huge strain was placed on resources during and after the pandemic.¹ 

The question of balancing resources for other hospital needs while tending to patients with COVID-19 has been an ongoing discussion at many levels.¹ One core resource concern is the lack of staff. In a survey of 77 different countries, including physicians (41%), nurses (40%), respiratory therapists (11%), and advanced practice providers (8%), 15% reported insufficient intensivists and 32% reported insufficient ICU nursing staff during March and April of 2020.¹ A lack of hospital and care space that led to reallocation of limited-care acute care space was a concern. Thirteen percent reported a shortage of hospital ICU beds, while others reported the conversion of postoperative recovery rooms (20%) and operating rooms (12%) for patients with COVID-19.¹ 

Along with staff and care space concerns, hospital survey respondents reported that healthcare equipment was also challenged. Access to COVID-19 testing was one concern, with only 35% of respondents reporting availability for all patients at the beginning of the pandemic, and 56% reporting availability for only select patients based on symptom severity.¹ Access to personal protective equipment (PPE) was also affected, with PPE always available according to 83% to 95% of respondents but just 35% having access to N95 masks.¹ Additionally, 26% reported that there were no respirators in their hospital, and 11% reported limited ventilators.¹ 

Although resource depletion is a problem, studies have looked at public health measures that helped to mitigate this issue. With proper public health planning and implementation, such as physical distancing, aggressive testing, contact tracing, and increased hospital capacity, by freeing up existing resources or adding additional support, public health modeling showed that resources may be able to withstand the increase.¹³ Development of reallocation models at local, state, national, and international levels is an important step to be able to deal with future public health crises.¹⁴

The long-term impact from the pandemic includes disruption in the physical environment of healthcare, production, supply chain, staff structure, and workforce alterations.⁴ For example, the physical shape of healthcare facilities is changing to accommodate increasing volumes and decrease the risk of spreading disease.⁴ To accommodate the burden on staffing structure and workforce alteration, telehealth gained a prominent role.⁴ All in all, the pandemic has changed the healthcare system; however, institutions, organizations, and policy makers need to evaluate which measures were impactful and should be considered for long-term inclusion in healthcare practice. 

Impact on Other Diseases: Cancer, Heart Disease, Chronic Illnesses, and Other Viruses 

The treatment of other new and existing conditions has also been affected by the pandemic. Cancer, especially, is a disease of concern. Elective surgeries and screening were halted or altered during the pandemic, which is modeled to lead to higher cancer mortality in years to come.² The most affected cancers were breast, lung, and colorectal cancer.² A study of colorectal cancer screening showed that colonoscopies were delayed due to COVID-19 and that gastroenterology visits declined by 49% to 61%.¹⁵ This will likely lead to delayed cancer diagnoses and possible increases in mortality.¹⁵ Breast cancer screening was also delayed and many patients continued to avoid it for various reasons such as fears of contracting COVID-19 infection in healthcare facilities, and the economic effects of the pandemic such as job loss and healthcare coverage loss.¹⁶ These delays will result in an estimated potential 0.52% overall increase in breast cancer deaths by 2030.¹⁷

A study of 368 patients from Spain showed a 56.5% decrease in hospital admissions, usually related to heart attacks, in March and April of 2020, compared to January and February 2020.^18,19 For other chronic illnesses, the pandemic resulted in decreased preventative care and management.²⁰ The care of other infections similarly suffered. The World Health Organization announced that the number of patients receiving treatment for tuberculosis (TB) dropped by 1 million, setting the disease mitigation back considerably.²⁰ An estimated 500,000 more people died in 2020 from TB.²¹ The drastic shift in focus to COVID-19 care during this period will continue to have a profound impact on other diseases like these for many years post-pandemic.

Provider Experience and Mental Health Outcomes 

The impact on provider experiences and mental health has been immense. One study of 510 healthcare providers (HCPs) and first responders found that occupational stress from the pandemic correlated with psychiatric symptoms, including depression, PTSD, insomnia, and generalized anxiety.³ Occupational stress also correlated with one’s likelihood to leave the medical field and trouble doing work they had once loved.³ Half of the healthcare workers surveyed indicated a decreased likelihood of staying in their current profession after the pandemic.³ 

Other studies have also looked at specific subspecialties and impact on trainees during the pandemic. In neurosurgery, for example, resident burnout is high, at 26.1%.⁹ Additionally, the lack of surgeries in the pandemic made 65.8% of neurosurgery residents anxious about meeting career milestones.⁹ Respiratory therapists, a highly impacted group, also experienced burnout, reporting higher levels in those who worked more in the ICU. Another study identified several themes in the concerns reported by healthcare workers during the pandemic era including “changes in personal life and enhanced negative affect,” “gaining experience, normalization, and adaptation to the pandemic,” and “mental health considerations.”²² 

Some studies have investigated ways to mitigate this dissatisfaction with the healthcare field post-pandemic. Intrapreneurship, reverse mentoring, and democratized learning all had a reported positive impact on employee experience and retention during this time.²³ Intrapreneurship describes entrepreneurship within an existing organization, while reverse mentoring and democratized learning refer to newer employees teaching older employees and communicative learning on a breadth of topics. Other studies have examined the necessity of having mental health resources available, and that these resources need to be multi-stage and individualistic as well as specific to certain stressors HCPs faced during the pandemic.²² 

Conclusion and Future Directions

The COVID-19 pandemic had stark effects on the healthcare system, impacting resources and capacity, care of other diseases, and provider mental health and experiences.^1-3 After the chaos of the pandemic, many questions remain. What needs to be done now by health systems and HCPs? How can we learn from the challenges and the effects on capacity to change the healthcare workflow in times of crisis and in the present? How do we mitigate the impact of the pandemic on diagnosis and management of diseases? And how do we continue to provide healthcare workers with proper mental health and professional resources now, not just in times of stress, and encourage the future generation to pursue careers in healthcare? 

These are all the questions the pandemic has left us with, and more studies and initiatives are needed to investigate solutions to these issues. The COVID-19 pandemic left behind valuable lessons and changed the healthcare system, disease management, and staffing for many. Now is the time to pick up the pieces and strategize on how to make our existing system more effective for workers and patients post pandemic. 

Mantle cell lymphoma (MCL) has served as a paradigm of progress among the non-Hodgkin lymphomas over the past 30 years. It was originally defined within the Kiel classification as centrocytic lymphoma, then renamed MCL once the characteristic translocation and resulting cyclin D1 overexpression were identified. These diagnostic markers allowed for the characterization of MCL subtypes as well as the initiation of MCL-focused clinical trials which, in turn, led to regulatory approval of more effective regimens, new therapeutic agents, and an improvement in overall survival (OS) from around 3 years to more than 10 years for many patients.

Despite this progress, virtually all patients relapse, and a cure remains elusive for most. In younger (< 65 to 70 years), medically-fit patients who are transplant-eligible and have symptomatic MCL, a standard of care has been induction chemoimmunotherapy containing high-dose cytarabine followed by ASCT consolidation. For example, a clinical trial of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) alternating with R-DHAP (rituximab, dexamethasone, high-dose cytarabine, cisplatin; 3 cycles each) showed a significant benefit over R-CHOP x 6 cycles; at a median follow-up of 10.6 years, the time-to-treatment failure was 8.4 v 3.9 years. In another trial, all patients received induction R-DHAP (with cisplatin or an alternative platinum agent) x 4 cycles followed by ASCT. Those patients randomized to post-ASCT maintenance rituximab for 3 years had significantly improved, 4-year progression-free survival (PFS) as compared with observation only (83% vs 64%, p < 0.001); maintenance also significantly improved OS. 

Although ASCT consolidation followed by maintenance became widely adopted on the basis of these and other clinical trials, important questions remain:

• First, MCL is biologically and clinically quite heterogeneous. Several prognostic tools such as the MCL International Prognostic Index (MIPI) scoring system and biomarkers are available to define lower- versus higher-risk subtypes, but none is routinely used for treatment planning. About 15% of MCL patients present with a highly-aggressive blastoid or pleomorphic variant that usually carries a TP53 mutation or deletion. Given the short survival and limited benefit from dose-intensive chemotherapy and ASCT in TP53-mutated MCL, should transplant be avoided in these patients?    

• Second, if deep remission is achieved following front-line therapy, defined as positron emission tomography (PET) negative and measurable residual disease (MRD) negative, will high-dose chemotherapy and ASCT provide additional benefits or only toxicity?  This question is being addressed by the ongoing ECOG 4151 study, a risk-adapted trial in which post-induction MRD-negative patients are randomized to standard ASCT consolidation plus maintenance rituximab vs maintenance only. 

Bruton tyrosine kinase inhibitors (BTKi) are now among the most used agents for relapsed MCL. Recent clinical trials testing the integration of a BTKi into first- or second-line therapy have shown increased response rates and variable clinical outcomes and toxicities for the combinations, depending upon the chemotherapy- and non-chemotherapy backbones utilized, as well as the BTKi. Combinations with the BCL2 inhibitor venetoclax plus chemotherapy or BTKi are also showing promise.

The activity of BTKi in MCL led the European MCL Network (EMCL) to design the 3-arm TRIANGLE study to analyze the potential of ibrutinib to improve outcomes when given in conjunction with standard ASCT consolidation, and the ability to replace the need for ASCT. The TRIANGLE results were presented by Dr. Martin Dreyling in the Plenary Session at the December 2022 American Society of Hematology (ASH) Annual Meeting. Transplant-eligible MCL patients < 65 years of age were randomized to the EMCL’s established front-line therapy of alternating R-CHOP/R-DHAP plus ASCT; the same regimen plus oral ibrutinib given with the R-CHOP induction cycles and then post-ASCT ibrutinib maintenance therapy for 2 years (Arm A+I); or the A+I regimen minus ASCT (Arm I). Maintenance rituximab was allowed in each arm, on the basis of the treating centers’ institutional guidelines. Overall, 54%-58% of patients in each study arm received rituximab maintenance, with no differential benefit in efficacy noted for those so treated. 

The results showed that 94%-98% of patients responded by the end of induction (defined as R-chemo and ASCT), with complete remissions in 36%-45% (from computerized tomography imaging, not PET scan). With a median follow-up of 31 months, failure-free survival (FFS; the primary study endpoint) was significantly improved for A+I vs A (3 year FFS of 88% vs 72%, respectively; p = 0.0008). In a subgroup analysis, FFS was notably improved for A+I in patients with high-level TP53 overexpression by immunohistochemistry. Toxicity did not differ during the induction and ASCT periods among the 3 arms regarding cytopenia, gastrointestinal disorders, and infections. However, neutropenia and infections were increased in the ibrutinib-containing arms during maintenance therapy—especially for Arm A+I. 

The authors concluded that ASCT plus ibrutinib (Arm A+I) is superior to ASCT only (Arm A), and that Arm A is not superior to ibrutinib without ASCT (Arm I). No decision can yet be made regarding A+I versus I for which FFS to date remains very similar; however, the authors favor ibrutinib without ASCT due to lower toxicity. OS is trending to favor the ibrutinib arms, but longer follow-up will be needed to fully assess.

Should ASCT consolidation now be replaced by ibrutinib-containing induction R-CHOP/R-DHAP and maintenance ibrutinib, with or without maintenance rituximab? A definitive answer will require the fully-published TRIANGLE results, as well as ongoing analysis with longer follow-up. However, it seems very likely that ASCT indeed will be replaced by the new approach. TP53-mutated MCL should be treated with ibrutinib plus R-CHOP/R-DHAP and ibrutinib maintenance as validated in this trial. 

Many centers have begun using a second-generation BTKi, acalabrutinib or zanubrutinib, rather than ibrutinib due to equivalent response rates with more favorable side effect profiles and fewer treatment discontinuations. Caution is warranted regarding simply adding a BTKi to one’s favored MCL induction regimen and foregoing ASCT—pending additional studies and the safety of such alternative approaches. 

These are indeed exciting times of therapeutic progress, as they have been improving outcomes and providing longer survival outcomes for MCL patients. Targeted agents facilitate this shift to less intensive and chemotherapy-free regimens that provide enhanced response and mitigate short- and longer-term toxicities. More results will be forthcoming for MRD as a treatment endpoint, guiding maintenance therapy, and for risk-adapted treatment of newly-diagnosed and relapsing patients (based upon MCL subtype and biomarker profiles). Enrolling patients into clinical trials is strongly encouraged as the best mechanism to help answer emerging questions in the field and open the pathway to continued progress.

Mantle cell lymphoma (MCL) has served as a paradigm of progress among the non-Hodgkin lymphomas over the past 30 years. It was originally defined within the Kiel classification as centrocytic lymphoma, then renamed MCL once the characteristic translocation and resulting cyclin D1 overexpression were identified. These diagnostic markers allowed for the characterization of MCL subtypes as well as the initiation of MCL-focused clinical trials which, in turn, led to regulatory approval of more effective regimens, new therapeutic agents, and an improvement in overall survival (OS) from around 3 years to more than 10 years for many patients.

Despite this progress, virtually all patients relapse, and a cure remains elusive for most. In younger (< 65 to 70 years), medically-fit patients who are transplant-eligible and have symptomatic MCL, a standard of care has been induction chemoimmunotherapy containing high-dose cytarabine followed by ASCT consolidation. For example, a clinical trial of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) alternating with R-DHAP (rituximab, dexamethasone, high-dose cytarabine, cisplatin; 3 cycles each) showed a significant benefit over R-CHOP x 6 cycles; at a median follow-up of 10.6 years, the time-to-treatment failure was 8.4 v 3.9 years. In another trial, all patients received induction R-DHAP (with cisplatin or an alternative platinum agent) x 4 cycles followed by ASCT. Those patients randomized to post-ASCT maintenance rituximab for 3 years had significantly improved, 4-year progression-free survival (PFS) as compared with observation only (83% vs 64%, p < 0.001); maintenance also significantly improved OS. 

Although ASCT consolidation followed by maintenance became widely adopted on the basis of these and other clinical trials, important questions remain:

• First, MCL is biologically and clinically quite heterogeneous. Several prognostic tools such as the MCL International Prognostic Index (MIPI) scoring system and biomarkers are available to define lower- versus higher-risk subtypes, but none is routinely used for treatment planning. About 15% of MCL patients present with a highly-aggressive blastoid or pleomorphic variant that usually carries a TP53 mutation or deletion. Given the short survival and limited benefit from dose-intensive chemotherapy and ASCT in TP53-mutated MCL, should transplant be avoided in these patients?    

• Second, if deep remission is achieved following front-line therapy, defined as positron emission tomography (PET) negative and measurable residual disease (MRD) negative, will high-dose chemotherapy and ASCT provide additional benefits or only toxicity?  This question is being addressed by the ongoing ECOG 4151 study, a risk-adapted trial in which post-induction MRD-negative patients are randomized to standard ASCT consolidation plus maintenance rituximab vs maintenance only. 

Bruton tyrosine kinase inhibitors (BTKi) are now among the most used agents for relapsed MCL. Recent clinical trials testing the integration of a BTKi into first- or second-line therapy have shown increased response rates and variable clinical outcomes and toxicities for the combinations, depending upon the chemotherapy- and non-chemotherapy backbones utilized, as well as the BTKi. Combinations with the BCL2 inhibitor venetoclax plus chemotherapy or BTKi are also showing promise.

The activity of BTKi in MCL led the European MCL Network (EMCL) to design the 3-arm TRIANGLE study to analyze the potential of ibrutinib to improve outcomes when given in conjunction with standard ASCT consolidation, and the ability to replace the need for ASCT. The TRIANGLE results were presented by Dr. Martin Dreyling in the Plenary Session at the December 2022 American Society of Hematology (ASH) Annual Meeting. Transplant-eligible MCL patients < 65 years of age were randomized to the EMCL’s established front-line therapy of alternating R-CHOP/R-DHAP plus ASCT; the same regimen plus oral ibrutinib given with the R-CHOP induction cycles and then post-ASCT ibrutinib maintenance therapy for 2 years (Arm A+I); or the A+I regimen minus ASCT (Arm I). Maintenance rituximab was allowed in each arm, on the basis of the treating centers’ institutional guidelines. Overall, 54%-58% of patients in each study arm received rituximab maintenance, with no differential benefit in efficacy noted for those so treated. 

The results showed that 94%-98% of patients responded by the end of induction (defined as R-chemo and ASCT), with complete remissions in 36%-45% (from computerized tomography imaging, not PET scan). With a median follow-up of 31 months, failure-free survival (FFS; the primary study endpoint) was significantly improved for A+I vs A (3 year FFS of 88% vs 72%, respectively; p = 0.0008). In a subgroup analysis, FFS was notably improved for A+I in patients with high-level TP53 overexpression by immunohistochemistry. Toxicity did not differ during the induction and ASCT periods among the 3 arms regarding cytopenia, gastrointestinal disorders, and infections. However, neutropenia and infections were increased in the ibrutinib-containing arms during maintenance therapy—especially for Arm A+I. 

The authors concluded that ASCT plus ibrutinib (Arm A+I) is superior to ASCT only (Arm A), and that Arm A is not superior to ibrutinib without ASCT (Arm I). No decision can yet be made regarding A+I versus I for which FFS to date remains very similar; however, the authors favor ibrutinib without ASCT due to lower toxicity. OS is trending to favor the ibrutinib arms, but longer follow-up will be needed to fully assess.

Should ASCT consolidation now be replaced by ibrutinib-containing induction R-CHOP/R-DHAP and maintenance ibrutinib, with or without maintenance rituximab? A definitive answer will require the fully-published TRIANGLE results, as well as ongoing analysis with longer follow-up. However, it seems very likely that ASCT indeed will be replaced by the new approach. TP53-mutated MCL should be treated with ibrutinib plus R-CHOP/R-DHAP and ibrutinib maintenance as validated in this trial. 

Many centers have begun using a second-generation BTKi, acalabrutinib or zanubrutinib, rather than ibrutinib due to equivalent response rates with more favorable side effect profiles and fewer treatment discontinuations. Caution is warranted regarding simply adding a BTKi to one’s favored MCL induction regimen and foregoing ASCT—pending additional studies and the safety of such alternative approaches. 

These are indeed exciting times of therapeutic progress, as they have been improving outcomes and providing longer survival outcomes for MCL patients. Targeted agents facilitate this shift to less intensive and chemotherapy-free regimens that provide enhanced response and mitigate short- and longer-term toxicities. More results will be forthcoming for MRD as a treatment endpoint, guiding maintenance therapy, and for risk-adapted treatment of newly-diagnosed and relapsing patients (based upon MCL subtype and biomarker profiles). Enrolling patients into clinical trials is strongly encouraged as the best mechanism to help answer emerging questions in the field and open the pathway to continued progress.

Mantle cell lymphoma (MCL) has served as a paradigm of progress among the non-Hodgkin lymphomas over the past 30 years. It was originally defined within the Kiel classification as centrocytic lymphoma, then renamed MCL once the characteristic translocation and resulting cyclin D1 overexpression were identified. These diagnostic markers allowed for the characterization of MCL subtypes as well as the initiation of MCL-focused clinical trials which, in turn, led to regulatory approval of more effective regimens, new therapeutic agents, and an improvement in overall survival (OS) from around 3 years to more than 10 years for many patients.

Despite this progress, virtually all patients relapse, and a cure remains elusive for most. In younger (< 65 to 70 years), medically-fit patients who are transplant-eligible and have symptomatic MCL, a standard of care has been induction chemoimmunotherapy containing high-dose cytarabine followed by ASCT consolidation. For example, a clinical trial of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) alternating with R-DHAP (rituximab, dexamethasone, high-dose cytarabine, cisplatin; 3 cycles each) showed a significant benefit over R-CHOP x 6 cycles; at a median follow-up of 10.6 years, the time-to-treatment failure was 8.4 v 3.9 years. In another trial, all patients received induction R-DHAP (with cisplatin or an alternative platinum agent) x 4 cycles followed by ASCT. Those patients randomized to post-ASCT maintenance rituximab for 3 years had significantly improved, 4-year progression-free survival (PFS) as compared with observation only (83% vs 64%, p < 0.001); maintenance also significantly improved OS. 

Although ASCT consolidation followed by maintenance became widely adopted on the basis of these and other clinical trials, important questions remain:

• First, MCL is biologically and clinically quite heterogeneous. Several prognostic tools such as the MCL International Prognostic Index (MIPI) scoring system and biomarkers are available to define lower- versus higher-risk subtypes, but none is routinely used for treatment planning. About 15% of MCL patients present with a highly-aggressive blastoid or pleomorphic variant that usually carries a TP53 mutation or deletion. Given the short survival and limited benefit from dose-intensive chemotherapy and ASCT in TP53-mutated MCL, should transplant be avoided in these patients?    

• Second, if deep remission is achieved following front-line therapy, defined as positron emission tomography (PET) negative and measurable residual disease (MRD) negative, will high-dose chemotherapy and ASCT provide additional benefits or only toxicity?  This question is being addressed by the ongoing ECOG 4151 study, a risk-adapted trial in which post-induction MRD-negative patients are randomized to standard ASCT consolidation plus maintenance rituximab vs maintenance only. 

Bruton tyrosine kinase inhibitors (BTKi) are now among the most used agents for relapsed MCL. Recent clinical trials testing the integration of a BTKi into first- or second-line therapy have shown increased response rates and variable clinical outcomes and toxicities for the combinations, depending upon the chemotherapy- and non-chemotherapy backbones utilized, as well as the BTKi. Combinations with the BCL2 inhibitor venetoclax plus chemotherapy or BTKi are also showing promise.

The activity of BTKi in MCL led the European MCL Network (EMCL) to design the 3-arm TRIANGLE study to analyze the potential of ibrutinib to improve outcomes when given in conjunction with standard ASCT consolidation, and the ability to replace the need for ASCT. The TRIANGLE results were presented by Dr. Martin Dreyling in the Plenary Session at the December 2022 American Society of Hematology (ASH) Annual Meeting. Transplant-eligible MCL patients < 65 years of age were randomized to the EMCL’s established front-line therapy of alternating R-CHOP/R-DHAP plus ASCT; the same regimen plus oral ibrutinib given with the R-CHOP induction cycles and then post-ASCT ibrutinib maintenance therapy for 2 years (Arm A+I); or the A+I regimen minus ASCT (Arm I). Maintenance rituximab was allowed in each arm, on the basis of the treating centers’ institutional guidelines. Overall, 54%-58% of patients in each study arm received rituximab maintenance, with no differential benefit in efficacy noted for those so treated. 

The results showed that 94%-98% of patients responded by the end of induction (defined as R-chemo and ASCT), with complete remissions in 36%-45% (from computerized tomography imaging, not PET scan). With a median follow-up of 31 months, failure-free survival (FFS; the primary study endpoint) was significantly improved for A+I vs A (3 year FFS of 88% vs 72%, respectively; p = 0.0008). In a subgroup analysis, FFS was notably improved for A+I in patients with high-level TP53 overexpression by immunohistochemistry. Toxicity did not differ during the induction and ASCT periods among the 3 arms regarding cytopenia, gastrointestinal disorders, and infections. However, neutropenia and infections were increased in the ibrutinib-containing arms during maintenance therapy—especially for Arm A+I. 

The authors concluded that ASCT plus ibrutinib (Arm A+I) is superior to ASCT only (Arm A), and that Arm A is not superior to ibrutinib without ASCT (Arm I). No decision can yet be made regarding A+I versus I for which FFS to date remains very similar; however, the authors favor ibrutinib without ASCT due to lower toxicity. OS is trending to favor the ibrutinib arms, but longer follow-up will be needed to fully assess.

Should ASCT consolidation now be replaced by ibrutinib-containing induction R-CHOP/R-DHAP and maintenance ibrutinib, with or without maintenance rituximab? A definitive answer will require the fully-published TRIANGLE results, as well as ongoing analysis with longer follow-up. However, it seems very likely that ASCT indeed will be replaced by the new approach. TP53-mutated MCL should be treated with ibrutinib plus R-CHOP/R-DHAP and ibrutinib maintenance as validated in this trial. 

Many centers have begun using a second-generation BTKi, acalabrutinib or zanubrutinib, rather than ibrutinib due to equivalent response rates with more favorable side effect profiles and fewer treatment discontinuations. Caution is warranted regarding simply adding a BTKi to one’s favored MCL induction regimen and foregoing ASCT—pending additional studies and the safety of such alternative approaches. 

These are indeed exciting times of therapeutic progress, as they have been improving outcomes and providing longer survival outcomes for MCL patients. Targeted agents facilitate this shift to less intensive and chemotherapy-free regimens that provide enhanced response and mitigate short- and longer-term toxicities. More results will be forthcoming for MRD as a treatment endpoint, guiding maintenance therapy, and for risk-adapted treatment of newly-diagnosed and relapsing patients (based upon MCL subtype and biomarker profiles). Enrolling patients into clinical trials is strongly encouraged as the best mechanism to help answer emerging questions in the field and open the pathway to continued progress.

Psoriatic arthritis (PsA) is a heterogenous inflammatory disease that may involve several different domains, including peripheral joints, entheses, nails, axial skeleton, and skin. A recent increased awareness of PsA has accompanied a large increase in available therapeutic options. In addition to traditional disease-modifying antirheumatic drugs (DMARDs), new biologics and targeted small molecules have now been shown to be effective in PsA. These agents include those targeting pathways involving tumor necrosis factor (TNF), cytotoxic T-lymphocyte–associated protein 4 (CTLA-4), interleukins (IL) 12, 17, 23, janus kinase (JAK), and phosphodiesterase 4 (PDE4). These agents have demonstrated efficacy in outcome measures developed for peripheral arthritis, such as the American College of Rheumatology 20 (ACR20) response. However, an ongoing question is whether these agents are equally effective in axial disease. Based on our experience and the existing literature, we believe that some of these agents, including PDE4 and IL-23 inhibitors, are not effective for axial disease. 

Moll and Wright’s original description of PsA estimated that 5% of patients with PsA had axial disease¹; however, they were describing patients in whom axial arthritis was the predominant, or the only, manifestation. There are many patients for whom axial symptoms are just one of several domains of disease activity. With this in mind, and depending on the cohort studied, the estimated overall prevalence of axial disease ranges from 7% to 32% in patients with PsA.² This is in contrast to peripheral arthritis, a domain that occurs in most patients with PsA and is the most common manifestation of PsA.² We believe there are differences in axial and peripheral response among some of the drugs used to treat PsA; therefore it is critical to consider both the presence and magnitude of axial involvement.  

An absence of axial PsA–specific clinical trials complicates navigating this treatment domain. Most considerations regarding treatment options for axial disease in PsA are extrapolated from ankylosing spondylitis (AS) trials and experience, as is the case for the TNF and JAK inhibitors. To our knowledge, only one high-quality randomized trial, MAXIMISE, looked specifically at the treatment of axial PsA, in this case with the IL-17 inhibitor secukinumab.³ This trial demonstrated efficacy of secukinumab in reducing symptoms and acute phase reactants in patients with PsA who were categorized as having active axial disease using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Other than conclusions drawn from AS trials and from this single axial PsA randomized controlled trial, data on the treatment of axial PsA are drawn entirely from observational and post-hoc analyses. As there are no consensus criteria for axial PsA, the cohorts included in these data may vary. This heterogeneity showcases the diversity in patients with PsA with axial disease but complicates the generalizability of the findings to individual patients. 

Another challenge in understanding axial response to medication is the lack of specific, validated outcome measures for axial PsA. The BASDAI and, more recently, the Assessment in Ankylosing Spondylitis (ASAS) and the Ankylosing Spondylitis Disease Activity Score (ASDAS), all developed specifically for AS, are often used to measure treatment response. The BASDAI incorporates patient-reported symptoms which include fatigue, peripheral joint pain/swelling, tenderness, and morning stiffness not specifically localized to the back. The ASDAS also includes a C-reactive protein measurement.

When used to assess response in PsA, however, these patient-reported outcomes may not be precise enough to separate the impact of axial disease or symptoms from that of peripheral disease. Only question 2 on the BASDAI specifically addresses axial complaints: “How would you describe the overall level of AS-related pain you have had in your neck, back, or hips?” Even this question is vulnerable to confounding from noninflammatory causes of back pain. Although these issues exist with patient-reported outcomes, objective spinal mobility measures used in evaluation of AS, including the modified Schober test, lumbar side flexion, and cervical rotation, have been demonstrated also to perform well in axial PsA.⁴ 

This was corroborated in the INSPIRE study, which showed adequate interobserver reliability in primary AS that was equally reproducible in axial PsA, with most measures, including occiput to wall, modified Schober test, cervical rotation, lateral bending, and hip mobility, performing in a “good to excellent” manner.⁵ Therefore, the inclusion of these objective measures in future therapeutic studies may enhance the external validation of available data. 

The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) has established therapeutic guidelines for psoriatic disease based on currently available literature and data. Similar to previous iterations of guidelines, GRAPPA continues to recommend agents with TNF inhibition or IL-17 inhibition for patients with PsA with axial disease who have failed conservative therapy with nonsteroidal anti-inflammatory drugs (NSAIDs), physical therapy, and/or glucocorticoid injections. Newly recommended in the latest iteration of the GRAPPA guidelines, based on the efficacy of these agents in AS, is the use of JAK inhibitors for axial PsA.⁶ 

Although TNF, IL-17, and JAK targeted therapies have demonstrated more likely benefit, albeit subject to the trial limitations previously discussed, the question remains whether agents targeting PDE4 and IL-23 are an effective option for axial PsA. Studies of both PDE4 and IL-23 inhibitors in AS have not demonstrated adequate benefit, which, importantly, contrasts with the previously mentioned and recommended therapies. Additionally, there are no primary randomized control trials that have directly evaluated the efficacy of IL-23 therapy in axial PsA. 

Existing data about potential benefit come from post-hoc analyses of the PSUMMIT 1 and 2 trials^7-10 with ustekinumab (which inhibits IL-12 and IL-23) and the DISCOVER trials^11-13 with guselkumab (a pure IL-23 inhibitor). However, these analyses relied on a physician-reported diagnosis of axial disease and not on prespecified entry criteria. This lack of uniform diagnostic criteria may introduce bias into the interpretation of the results and limit external validation. All patients in these trials had a significant burden of peripheral arthritis; therefore it is hard to know whether, even in patients with physician-reported axial disease, improvement in general outcome measures were due to true amelioration of axial disease or were confounded by improvement in peripheral and skin domains. The analysis of these trials did look specifically at patient answers to BASDAI question 2 regarding level of neck, back, or hip pain. However, it remains difficult to be certain that the results are truly a reflection of axial symptoms and are not driven by patient-perceived improvement in other disease domains and an overall positive trajectory in well-being. 

In our years of practice, when we turned to biologic agents, the IL-23 inhibitors and the IL-12/23 inhibitor have not been as effective in patients with PsA who have axial-predominant symptoms. The lack of efficacy of these agents in AS, in contrast to their benefit in psoriatic skin and peripheral joint disease, raises questions about the pathophysiologic role of IL-23 in axial disease, which is yet to be fully understood. For patients with a significant burden of axial pain, in concordance with the consensus from GRAPPA,⁶ our strategy is to start with TNF, IL-17, or JAK targeted therapies, with the choice based on patient-specific factors, including patient comorbidities, patient administration preference, and insurance coverage. We do believe it is reasonable to try IL-23–targeted therapies in patients who have mild axial symptoms when their predominant symptoms are in other domains, such as the peripheral joints or skin. In our opinion, more convincing data supporting IL-23 inhibition are required to move this into the forefront of axial-predominant PsA therapy. Clearly the investigation of axial disease in PsA lags behind that of peripheral and skin domains. Specific classification criteria for axial PsA, as are being currently developed by GRAPPA, should facilitate more focused therapeutic trials that can better inform optimal treatment of patients with this subset of disease. 

Psoriatic arthritis (PsA) is a heterogenous inflammatory disease that may involve several different domains, including peripheral joints, entheses, nails, axial skeleton, and skin. A recent increased awareness of PsA has accompanied a large increase in available therapeutic options. In addition to traditional disease-modifying antirheumatic drugs (DMARDs), new biologics and targeted small molecules have now been shown to be effective in PsA. These agents include those targeting pathways involving tumor necrosis factor (TNF), cytotoxic T-lymphocyte–associated protein 4 (CTLA-4), interleukins (IL) 12, 17, 23, janus kinase (JAK), and phosphodiesterase 4 (PDE4). These agents have demonstrated efficacy in outcome measures developed for peripheral arthritis, such as the American College of Rheumatology 20 (ACR20) response. However, an ongoing question is whether these agents are equally effective in axial disease. Based on our experience and the existing literature, we believe that some of these agents, including PDE4 and IL-23 inhibitors, are not effective for axial disease. 

Moll and Wright’s original description of PsA estimated that 5% of patients with PsA had axial disease¹; however, they were describing patients in whom axial arthritis was the predominant, or the only, manifestation. There are many patients for whom axial symptoms are just one of several domains of disease activity. With this in mind, and depending on the cohort studied, the estimated overall prevalence of axial disease ranges from 7% to 32% in patients with PsA.² This is in contrast to peripheral arthritis, a domain that occurs in most patients with PsA and is the most common manifestation of PsA.² We believe there are differences in axial and peripheral response among some of the drugs used to treat PsA; therefore it is critical to consider both the presence and magnitude of axial involvement.  

An absence of axial PsA–specific clinical trials complicates navigating this treatment domain. Most considerations regarding treatment options for axial disease in PsA are extrapolated from ankylosing spondylitis (AS) trials and experience, as is the case for the TNF and JAK inhibitors. To our knowledge, only one high-quality randomized trial, MAXIMISE, looked specifically at the treatment of axial PsA, in this case with the IL-17 inhibitor secukinumab.³ This trial demonstrated efficacy of secukinumab in reducing symptoms and acute phase reactants in patients with PsA who were categorized as having active axial disease using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Other than conclusions drawn from AS trials and from this single axial PsA randomized controlled trial, data on the treatment of axial PsA are drawn entirely from observational and post-hoc analyses. As there are no consensus criteria for axial PsA, the cohorts included in these data may vary. This heterogeneity showcases the diversity in patients with PsA with axial disease but complicates the generalizability of the findings to individual patients. 

Another challenge in understanding axial response to medication is the lack of specific, validated outcome measures for axial PsA. The BASDAI and, more recently, the Assessment in Ankylosing Spondylitis (ASAS) and the Ankylosing Spondylitis Disease Activity Score (ASDAS), all developed specifically for AS, are often used to measure treatment response. The BASDAI incorporates patient-reported symptoms which include fatigue, peripheral joint pain/swelling, tenderness, and morning stiffness not specifically localized to the back. The ASDAS also includes a C-reactive protein measurement.

When used to assess response in PsA, however, these patient-reported outcomes may not be precise enough to separate the impact of axial disease or symptoms from that of peripheral disease. Only question 2 on the BASDAI specifically addresses axial complaints: “How would you describe the overall level of AS-related pain you have had in your neck, back, or hips?” Even this question is vulnerable to confounding from noninflammatory causes of back pain. Although these issues exist with patient-reported outcomes, objective spinal mobility measures used in evaluation of AS, including the modified Schober test, lumbar side flexion, and cervical rotation, have been demonstrated also to perform well in axial PsA.⁴ 

This was corroborated in the INSPIRE study, which showed adequate interobserver reliability in primary AS that was equally reproducible in axial PsA, with most measures, including occiput to wall, modified Schober test, cervical rotation, lateral bending, and hip mobility, performing in a “good to excellent” manner.⁵ Therefore, the inclusion of these objective measures in future therapeutic studies may enhance the external validation of available data. 

The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) has established therapeutic guidelines for psoriatic disease based on currently available literature and data. Similar to previous iterations of guidelines, GRAPPA continues to recommend agents with TNF inhibition or IL-17 inhibition for patients with PsA with axial disease who have failed conservative therapy with nonsteroidal anti-inflammatory drugs (NSAIDs), physical therapy, and/or glucocorticoid injections. Newly recommended in the latest iteration of the GRAPPA guidelines, based on the efficacy of these agents in AS, is the use of JAK inhibitors for axial PsA.⁶ 

Although TNF, IL-17, and JAK targeted therapies have demonstrated more likely benefit, albeit subject to the trial limitations previously discussed, the question remains whether agents targeting PDE4 and IL-23 are an effective option for axial PsA. Studies of both PDE4 and IL-23 inhibitors in AS have not demonstrated adequate benefit, which, importantly, contrasts with the previously mentioned and recommended therapies. Additionally, there are no primary randomized control trials that have directly evaluated the efficacy of IL-23 therapy in axial PsA. 

Existing data about potential benefit come from post-hoc analyses of the PSUMMIT 1 and 2 trials^7-10 with ustekinumab (which inhibits IL-12 and IL-23) and the DISCOVER trials^11-13 with guselkumab (a pure IL-23 inhibitor). However, these analyses relied on a physician-reported diagnosis of axial disease and not on prespecified entry criteria. This lack of uniform diagnostic criteria may introduce bias into the interpretation of the results and limit external validation. All patients in these trials had a significant burden of peripheral arthritis; therefore it is hard to know whether, even in patients with physician-reported axial disease, improvement in general outcome measures were due to true amelioration of axial disease or were confounded by improvement in peripheral and skin domains. The analysis of these trials did look specifically at patient answers to BASDAI question 2 regarding level of neck, back, or hip pain. However, it remains difficult to be certain that the results are truly a reflection of axial symptoms and are not driven by patient-perceived improvement in other disease domains and an overall positive trajectory in well-being. 

In our years of practice, when we turned to biologic agents, the IL-23 inhibitors and the IL-12/23 inhibitor have not been as effective in patients with PsA who have axial-predominant symptoms. The lack of efficacy of these agents in AS, in contrast to their benefit in psoriatic skin and peripheral joint disease, raises questions about the pathophysiologic role of IL-23 in axial disease, which is yet to be fully understood. For patients with a significant burden of axial pain, in concordance with the consensus from GRAPPA,⁶ our strategy is to start with TNF, IL-17, or JAK targeted therapies, with the choice based on patient-specific factors, including patient comorbidities, patient administration preference, and insurance coverage. We do believe it is reasonable to try IL-23–targeted therapies in patients who have mild axial symptoms when their predominant symptoms are in other domains, such as the peripheral joints or skin. In our opinion, more convincing data supporting IL-23 inhibition are required to move this into the forefront of axial-predominant PsA therapy. Clearly the investigation of axial disease in PsA lags behind that of peripheral and skin domains. Specific classification criteria for axial PsA, as are being currently developed by GRAPPA, should facilitate more focused therapeutic trials that can better inform optimal treatment of patients with this subset of disease. 

Psoriatic arthritis (PsA) is a heterogenous inflammatory disease that may involve several different domains, including peripheral joints, entheses, nails, axial skeleton, and skin. A recent increased awareness of PsA has accompanied a large increase in available therapeutic options. In addition to traditional disease-modifying antirheumatic drugs (DMARDs), new biologics and targeted small molecules have now been shown to be effective in PsA. These agents include those targeting pathways involving tumor necrosis factor (TNF), cytotoxic T-lymphocyte–associated protein 4 (CTLA-4), interleukins (IL) 12, 17, 23, janus kinase (JAK), and phosphodiesterase 4 (PDE4). These agents have demonstrated efficacy in outcome measures developed for peripheral arthritis, such as the American College of Rheumatology 20 (ACR20) response. However, an ongoing question is whether these agents are equally effective in axial disease. Based on our experience and the existing literature, we believe that some of these agents, including PDE4 and IL-23 inhibitors, are not effective for axial disease. 

Moll and Wright’s original description of PsA estimated that 5% of patients with PsA had axial disease¹; however, they were describing patients in whom axial arthritis was the predominant, or the only, manifestation. There are many patients for whom axial symptoms are just one of several domains of disease activity. With this in mind, and depending on the cohort studied, the estimated overall prevalence of axial disease ranges from 7% to 32% in patients with PsA.² This is in contrast to peripheral arthritis, a domain that occurs in most patients with PsA and is the most common manifestation of PsA.² We believe there are differences in axial and peripheral response among some of the drugs used to treat PsA; therefore it is critical to consider both the presence and magnitude of axial involvement.  

An absence of axial PsA–specific clinical trials complicates navigating this treatment domain. Most considerations regarding treatment options for axial disease in PsA are extrapolated from ankylosing spondylitis (AS) trials and experience, as is the case for the TNF and JAK inhibitors. To our knowledge, only one high-quality randomized trial, MAXIMISE, looked specifically at the treatment of axial PsA, in this case with the IL-17 inhibitor secukinumab.³ This trial demonstrated efficacy of secukinumab in reducing symptoms and acute phase reactants in patients with PsA who were categorized as having active axial disease using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Other than conclusions drawn from AS trials and from this single axial PsA randomized controlled trial, data on the treatment of axial PsA are drawn entirely from observational and post-hoc analyses. As there are no consensus criteria for axial PsA, the cohorts included in these data may vary. This heterogeneity showcases the diversity in patients with PsA with axial disease but complicates the generalizability of the findings to individual patients. 

Another challenge in understanding axial response to medication is the lack of specific, validated outcome measures for axial PsA. The BASDAI and, more recently, the Assessment in Ankylosing Spondylitis (ASAS) and the Ankylosing Spondylitis Disease Activity Score (ASDAS), all developed specifically for AS, are often used to measure treatment response. The BASDAI incorporates patient-reported symptoms which include fatigue, peripheral joint pain/swelling, tenderness, and morning stiffness not specifically localized to the back. The ASDAS also includes a C-reactive protein measurement.

When used to assess response in PsA, however, these patient-reported outcomes may not be precise enough to separate the impact of axial disease or symptoms from that of peripheral disease. Only question 2 on the BASDAI specifically addresses axial complaints: “How would you describe the overall level of AS-related pain you have had in your neck, back, or hips?” Even this question is vulnerable to confounding from noninflammatory causes of back pain. Although these issues exist with patient-reported outcomes, objective spinal mobility measures used in evaluation of AS, including the modified Schober test, lumbar side flexion, and cervical rotation, have been demonstrated also to perform well in axial PsA.⁴ 

This was corroborated in the INSPIRE study, which showed adequate interobserver reliability in primary AS that was equally reproducible in axial PsA, with most measures, including occiput to wall, modified Schober test, cervical rotation, lateral bending, and hip mobility, performing in a “good to excellent” manner.⁵ Therefore, the inclusion of these objective measures in future therapeutic studies may enhance the external validation of available data. 

The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) has established therapeutic guidelines for psoriatic disease based on currently available literature and data. Similar to previous iterations of guidelines, GRAPPA continues to recommend agents with TNF inhibition or IL-17 inhibition for patients with PsA with axial disease who have failed conservative therapy with nonsteroidal anti-inflammatory drugs (NSAIDs), physical therapy, and/or glucocorticoid injections. Newly recommended in the latest iteration of the GRAPPA guidelines, based on the efficacy of these agents in AS, is the use of JAK inhibitors for axial PsA.⁶ 

Although TNF, IL-17, and JAK targeted therapies have demonstrated more likely benefit, albeit subject to the trial limitations previously discussed, the question remains whether agents targeting PDE4 and IL-23 are an effective option for axial PsA. Studies of both PDE4 and IL-23 inhibitors in AS have not demonstrated adequate benefit, which, importantly, contrasts with the previously mentioned and recommended therapies. Additionally, there are no primary randomized control trials that have directly evaluated the efficacy of IL-23 therapy in axial PsA. 

Existing data about potential benefit come from post-hoc analyses of the PSUMMIT 1 and 2 trials^7-10 with ustekinumab (which inhibits IL-12 and IL-23) and the DISCOVER trials^11-13 with guselkumab (a pure IL-23 inhibitor). However, these analyses relied on a physician-reported diagnosis of axial disease and not on prespecified entry criteria. This lack of uniform diagnostic criteria may introduce bias into the interpretation of the results and limit external validation. All patients in these trials had a significant burden of peripheral arthritis; therefore it is hard to know whether, even in patients with physician-reported axial disease, improvement in general outcome measures were due to true amelioration of axial disease or were confounded by improvement in peripheral and skin domains. The analysis of these trials did look specifically at patient answers to BASDAI question 2 regarding level of neck, back, or hip pain. However, it remains difficult to be certain that the results are truly a reflection of axial symptoms and are not driven by patient-perceived improvement in other disease domains and an overall positive trajectory in well-being. 

In our years of practice, when we turned to biologic agents, the IL-23 inhibitors and the IL-12/23 inhibitor have not been as effective in patients with PsA who have axial-predominant symptoms. The lack of efficacy of these agents in AS, in contrast to their benefit in psoriatic skin and peripheral joint disease, raises questions about the pathophysiologic role of IL-23 in axial disease, which is yet to be fully understood. For patients with a significant burden of axial pain, in concordance with the consensus from GRAPPA,⁶ our strategy is to start with TNF, IL-17, or JAK targeted therapies, with the choice based on patient-specific factors, including patient comorbidities, patient administration preference, and insurance coverage. We do believe it is reasonable to try IL-23–targeted therapies in patients who have mild axial symptoms when their predominant symptoms are in other domains, such as the peripheral joints or skin. In our opinion, more convincing data supporting IL-23 inhibition are required to move this into the forefront of axial-predominant PsA therapy. Clearly the investigation of axial disease in PsA lags behind that of peripheral and skin domains. Specific classification criteria for axial PsA, as are being currently developed by GRAPPA, should facilitate more focused therapeutic trials that can better inform optimal treatment of patients with this subset of disease. 

Do you use nonpharmacologic approaches to treat your patients living with migraines? Which ones do you prefer?
I always like to start with nonpharmacologic approaches (also termed bio-behavioral approaches) with my patients. I talk to patients about sleep hygiene because if they don't sleep well, they're going to have more headaches. Most of my patients have issues with sleep and rarely feel refreshed in the morning. Most of them have middle insomnia; they wake up between 2 am and 4 am and cannot get back to sleep.

I also talk to my patients about eating properly. If patients don't eat on time or miss a meal, they often get headaches.  While timing is probably more critical, what they eat is important also. Poor diet can lead to decreased energy, and patients can become obese. Obesity impacts headache—especially migraine. I am not sure if there are any particularly good or bad foods for migraine patients, but in general, they should eat fewer fatty foods, fewer carbohydrates, more chicken, and fish than red meat, and a lot of fruits, vegetables, salads, nuts, and whole grains. A good trick is to limit the volume of each meal; do not go back for seconds and limit desserts and alcohol. 

Exercise is beneficial to decrease headaches, and the converse is even more true. Patients should start with low-impact, brief exercise like short walks and slowly build up to 20 minutes of cardio as tolerated, 3 to 5 times per week. Like poor diet choices, a sedentary lifestyle can lead to obesity and then not doing well with headaches and so on. 

What are your goals for treating your patients at the start of a migraine attack?

The goals for treating a migraine attack are to reduce the intensity of the pain quickly and, if possible, make the patient pain-free in ≤2 hours. We also try to reduce their most bothersome symptom, which is usually sensitivity to light or nausea, without causing any adverse effects from the treatment. Possibly as important, we want to get the patient back to functioning at work or at home, so they need no further treatment for that attack.

Unfortunately, many of the medicines we have available do cause adverse events, which are sometimes worse than the headache itself.  A patient can't continue to take a medication that causes significant side effects.

It is also critical to stop the headache quickly, as we don't want patients to take the prescribed acute care medicine and then, if they don’t feel like it’s working, proceed to take aspirin and then acetaminophen and then an anti-inflammatory tablet. The more medicine they take, the more likely they'll get medication overuse headache (MOH).  

MOH is not a great name, but it does imply that patients are taking one or many medications per week to stop their headaches, not realizing that this can worsen and prolong their headaches rather than helping them. They can also experience adverse events from taking so much medication. 

Finally, we want the patients to get rid of a headache so that they do not need to go to an emergency room, and we want to use medication that is cost effective and gets the patient functioning. Some medicines and devices are extremely expensive and not well covered by insurance companies but imagine the patient who takes a new medicine or uses a new device and gets better rapidly. If they hadn't done that, they may have lost a day or 2 of pay from missing work, or they might have gone to work and not done a very effective job because they were feeling miserable and couldn’t think or speak well. 

Do you prescribe triptans?

Definitely. The triptans first became available 30 years ago. There are 7 different triptans, and some work better for some patients than others. They come in tablets, injections, and nasal sprays. Sometimes patients need to try 2 or 3 different triptans to see which one is the most effective for them. If a patient has no success with tablets, there's a possibility that an injection or even a nasal spray would be more effective.
There are 2 triptans available as a nasal spray. I happen to like a triptan nasal spray called zolmitriptan, which usually works faster with fewer adverse events than the tablets.

There's also an injection of sumatriptan available, which is the fastest way to get relief from a triptan. Patients usually don't prefer it because it is an injection that they give themselves via an auto injector, and it may hurt and can be a bit complex to administer. There are definitely more adverse events when sumatriptan is given by injection, but because an injection can deliver very fast results that stop the headache reliably, some patients prefer it.

Triptans have been the mainstay treatment to stop an ongoing migraine attack for 30 years. We have always known there is some constriction of blood vessels and triptan-related side effects such as dizziness, drowsiness, and tingling sensations, so not every patient can take them. The newer medications that block calcitonin gene-related peptide (CGRP) do not constrict blood vessels and have fewer adverse events but cost a lot more if not covered by insurance.

Another newer, nontriptan nasal spray is dihydroergotamine (DHE) mesylate for acute care. It is one of the best medications to use if the patient’s migraine has been going on for 24 hours, as it tends to work well for a long-lasting headache. It also works for a long period, giving the patient a rest before their next attack. A nasal spray works faster than a tablet form, as the medication is absorbed from the nasal mucosa and does not have to make its way through the GI tract, then to the liver for metabolism, and finally, up to the brain before it begins to work. There can be some side effects in the nose such as discomfort or stuffiness, but if it works well, patients usually tolerate it. 

There's also a newer class of medicine called ditans. In a recent study, lasmiditan, which comes in a 50-mg and a 100-mg tablet for acute care of migraine, showed no vasoconstrictive effects, suggesting that ditans could be a safe option for patients living with chronic cardio- and cerebrovascular disease. Lasmiditan could be an alternative to triptans when they are contraindicated in patients with blood vessel disease, obesity, high blood pressure or cholesterol levels, or in nonresponsive patients. Lasmiditan does cause some dizziness and drowsiness, so patients cannot drive for 8 hours after taking it. However, it does have good efficacy.

When do you prescribe gepants?

Gepants are small-molecule CGRP receptor blockers. They are tablets that sit on the receptor, preventing the CGRP from docking on the receptor and increasing the headache during a migraine attack. There are 2 gepants that can be used to stop a headache that is just starting or in progress: ubrogepant and rimegepant. 

Ubrogepant is a regular tablet that is available in 50-mg or 100-mg strengths. If the first dose does not make a patient pain free, a second dose is recommended about 2 hours later. Rimegepant is a meltaway tablet and only comes in a 75-mg strength. It should be taken early in the attack, and usually the patient does not need further treatment that day. If they do, they need to switch to another treatment, as rimegepant should not be repeated that day. Rimegepant may be used for both acute care and prevention. It is the only tablet that can be used for both. 

Both drugs have been shown to provide pain freedom for about 20% of patients at 2 hours, which is statistically better than the patients that received the placebo. These drugs generally don’t cause many adverse events but can cause a little nausea or drowsiness in some patients. Ubrogepant has a few contraindications; patients on certain medications such as antibiotics or antifungals cannot take it. If a patient is not doing well on a triptan or should not be given a drug that constricts blood vessels, I often switch them to one of these gepants (if covered by insurance). Both drugs have a plan to let the patient try them at a low cost. 

How are the gepants used acutely?

Gepants are used just like a triptan. As soon as the patient has a migraine headache starting, they take either ubrogepant or rimegepant as quickly as possible. Some patients say they feel the gepant begin to work within an hour or less, and some patients say it doesn't work at all, so I have them try the other gepant. 

Gepants are probably a better option than triptans if the patient is >40 years because triptans can constrict blood vessels. Older patients, and certainly those who have any kind of cardiac or cerebral blood vessel issues or even peripheral blood vessel disease, should not be given triptans.

When do you consider using preventive treatment in migraine?

If a patient has ≥4 moderate-to-severe headache days a month, or fewer with severe disability, or does not respond to acute care medications or those drugs are contraindicated, I consider giving them preventive therapy for migraine. The goal is to decrease the number of migraine days per month and to decrease the intensity, duration, and disability of the attacks.

Which gepants can you use for prevention of migraine?

I discussed rimegepant as an acute care medication, but the same 75-mg meltaway tablet given every other day works preventively to decrease the number of headaches. I like it, as it has few adverse events—<3% of patients experience nausea and abdominal pain—and it can also be used to stop a headache on days the patient did not take a tablet.

Atogepant is a newer, US Food and Drug Administration (FDA)-approved gepant taken once daily by mouth for prevention of migraine, and it works to decrease headache days per month. It has more side effects than the other gepants, including constipation, drowsiness, and nausea. If a patient does not have many adverse events while taking it, it is a good migraine preventive. 

How do you feel about monoclonal antibodies that bind to CGRP or its receptor for migraine preventive treatment?

Before the gepants became available, 4 different pharmaceutical companies were making monoclonal antibodies (mAbs) that bind to either CGRP or its receptor. This class of medication can be quite effective for most patients needing migraine prevention, as these medications last for a long time if the patient keeps taking it. 

Antibodies, when injected, continue to work for 1 to 3 months, making them perfect for migraine prevention, but they must be given either by the patient using an autoinjector with a tiny needle or by intravenous (IV) infusion in a hospital or office. They tend to be quite effective and have few adverse events.  

The first one to come out was erenumab, then frenanezumab, and galcanezumab. The newest one is eptinezumab, given by IV infusion over 30 minutes. Erenumab is the only mAb that sits on the receptor to prevent the CGRP from docking on the receptor, and it's the only one that seems to cause adverse events such as constipation and increased blood pressure in some patients. Eptinezumab is the only drug in this category given by IV infusion; patients must come to the office to receive the injection every 3 months. Even though eptinezumab is a powerful drug, I find that patients generally don't like coming in for IV treatment. I reserve it for when a patient has failed several other preventive treatments. The other 3 drugs (erenumab, fremanezumab, galcanezumab) are subcutaneous injections that the patient can self-administer at home. Fremanezumab can be taken once a month or once every 3 months, depending on the dose prescribed. 

What migraine devices do you like to prescribe?

The device that I tend to have my patients use is called Nerivio®; it has been cleared by the FDA for acute treatment of migraine in patients ≥12 years. An article was just published in the journal Headache on its use in prevention of migraine. The company expects the FDA to clear it very soon for prevention when used for 45 minutes every other day.

Nerivio® is an electrical stimulator that is placed on the upper arm like a blood pressure cuff. It is battery-powered and links to an app on a smartphone. I have my patients turn it up slowly to a higher gain, and when they feel a slight discomfort, they lower down until they do not feel it. That's where I recommend that they keep it for 45 minutes of treatment, starting at the beginning of a migraine attack. 

Nerivio® also has a behavioral medicine program incorporated into the smartphone app that lasts for 25 minutes. While the patient is receiving the 45 minutes of electrical stimulation, they are also being guided through relaxation techniques to help ease the headache. The company has done a controlled study comparing the efficacy of Nerivio® with and without the behavioral treatment and found that the 2 together are more effective than Nerivio® alone. 

The early double-blind studies of this device, as sent to the FDA for clearance, have excellent efficacy data with very few adverse events. Thus, it is used by many patients. The company has arranged a lower cost for the first month of treatment so a patient can see whether the device is effective.

There's also a device called Relivion®, which is worn like a tiara on the head to stimulate 4 nerves above the eyebrows that are part of the trigeminal system and 2 in the back of the head that affect the occipital nerves.

One of the earliest devices to launch is the gammaCore vagal nerve stimulator. It is handheld and controlled by the patient. It is placed on the front and side of the neck in the region of the vagal nerve. For acute care of migraine, the patient stimulates for 2 minutes and then waits several minutes before repeating 2 minutes of treatment. If you want to prescribe it for the prevention of migraine, a patient could do this sequence twice per day. It has been approved for acute care and prevention of migraine and, along with other medication for cluster headaches, it is easy to use and approved for almost any kind of headache. Unfortunately, it is extremely expensive for patients and is not covered well by insurance unless the patient is a veteran or goes to a Veterans Health Administration hospital for care. 

There are a few other devices that also work for migraine. Most electrical stimulation devices are costly, but we do hope that insurance companies will begin to cover them soon. Most devices cause few adverse events, have few contraindications, and will be used more as they become more affordable.

Can you summarize migraine treatment for us in one paragraph?

No, but I will try. We have many acute care treatments for migraine that are effective. Some, such as the triptans, do constrict blood vessels, and certain patients should not be taking medications that affect blood vessels. Some medications cause certain side effects or take too long to work, and we have other options for those patients. If a patient has ≥4 headache days per month or fewer associated with a lot of disability, we need to consider prevention. We have older preventives such as beta blockers and epilepsy medications, which are less expensive and can work but usually have many side effects. Now we have 4 mAbs that bind to CGRP or its receptor, which work well for a month or more with few adverse events. We also have 2 oral gepants for prevention. When you add in several devices, I have so many options for my patients today that I am a lucky neurologist, and my patients are even luckier!

Do you use nonpharmacologic approaches to treat your patients living with migraines? Which ones do you prefer?
I always like to start with nonpharmacologic approaches (also termed bio-behavioral approaches) with my patients. I talk to patients about sleep hygiene because if they don't sleep well, they're going to have more headaches. Most of my patients have issues with sleep and rarely feel refreshed in the morning. Most of them have middle insomnia; they wake up between 2 am and 4 am and cannot get back to sleep.

I also talk to my patients about eating properly. If patients don't eat on time or miss a meal, they often get headaches.  While timing is probably more critical, what they eat is important also. Poor diet can lead to decreased energy, and patients can become obese. Obesity impacts headache—especially migraine. I am not sure if there are any particularly good or bad foods for migraine patients, but in general, they should eat fewer fatty foods, fewer carbohydrates, more chicken, and fish than red meat, and a lot of fruits, vegetables, salads, nuts, and whole grains. A good trick is to limit the volume of each meal; do not go back for seconds and limit desserts and alcohol. 

Exercise is beneficial to decrease headaches, and the converse is even more true. Patients should start with low-impact, brief exercise like short walks and slowly build up to 20 minutes of cardio as tolerated, 3 to 5 times per week. Like poor diet choices, a sedentary lifestyle can lead to obesity and then not doing well with headaches and so on. 

What are your goals for treating your patients at the start of a migraine attack?

The goals for treating a migraine attack are to reduce the intensity of the pain quickly and, if possible, make the patient pain-free in ≤2 hours. We also try to reduce their most bothersome symptom, which is usually sensitivity to light or nausea, without causing any adverse effects from the treatment. Possibly as important, we want to get the patient back to functioning at work or at home, so they need no further treatment for that attack.

Unfortunately, many of the medicines we have available do cause adverse events, which are sometimes worse than the headache itself.  A patient can't continue to take a medication that causes significant side effects.

It is also critical to stop the headache quickly, as we don't want patients to take the prescribed acute care medicine and then, if they don’t feel like it’s working, proceed to take aspirin and then acetaminophen and then an anti-inflammatory tablet. The more medicine they take, the more likely they'll get medication overuse headache (MOH).  

MOH is not a great name, but it does imply that patients are taking one or many medications per week to stop their headaches, not realizing that this can worsen and prolong their headaches rather than helping them. They can also experience adverse events from taking so much medication. 

Finally, we want the patients to get rid of a headache so that they do not need to go to an emergency room, and we want to use medication that is cost effective and gets the patient functioning. Some medicines and devices are extremely expensive and not well covered by insurance companies but imagine the patient who takes a new medicine or uses a new device and gets better rapidly. If they hadn't done that, they may have lost a day or 2 of pay from missing work, or they might have gone to work and not done a very effective job because they were feeling miserable and couldn’t think or speak well. 

Do you prescribe triptans?

Definitely. The triptans first became available 30 years ago. There are 7 different triptans, and some work better for some patients than others. They come in tablets, injections, and nasal sprays. Sometimes patients need to try 2 or 3 different triptans to see which one is the most effective for them. If a patient has no success with tablets, there's a possibility that an injection or even a nasal spray would be more effective.
There are 2 triptans available as a nasal spray. I happen to like a triptan nasal spray called zolmitriptan, which usually works faster with fewer adverse events than the tablets.

There's also an injection of sumatriptan available, which is the fastest way to get relief from a triptan. Patients usually don't prefer it because it is an injection that they give themselves via an auto injector, and it may hurt and can be a bit complex to administer. There are definitely more adverse events when sumatriptan is given by injection, but because an injection can deliver very fast results that stop the headache reliably, some patients prefer it.

Triptans have been the mainstay treatment to stop an ongoing migraine attack for 30 years. We have always known there is some constriction of blood vessels and triptan-related side effects such as dizziness, drowsiness, and tingling sensations, so not every patient can take them. The newer medications that block calcitonin gene-related peptide (CGRP) do not constrict blood vessels and have fewer adverse events but cost a lot more if not covered by insurance.

Another newer, nontriptan nasal spray is dihydroergotamine (DHE) mesylate for acute care. It is one of the best medications to use if the patient’s migraine has been going on for 24 hours, as it tends to work well for a long-lasting headache. It also works for a long period, giving the patient a rest before their next attack. A nasal spray works faster than a tablet form, as the medication is absorbed from the nasal mucosa and does not have to make its way through the GI tract, then to the liver for metabolism, and finally, up to the brain before it begins to work. There can be some side effects in the nose such as discomfort or stuffiness, but if it works well, patients usually tolerate it. 

There's also a newer class of medicine called ditans. In a recent study, lasmiditan, which comes in a 50-mg and a 100-mg tablet for acute care of migraine, showed no vasoconstrictive effects, suggesting that ditans could be a safe option for patients living with chronic cardio- and cerebrovascular disease. Lasmiditan could be an alternative to triptans when they are contraindicated in patients with blood vessel disease, obesity, high blood pressure or cholesterol levels, or in nonresponsive patients. Lasmiditan does cause some dizziness and drowsiness, so patients cannot drive for 8 hours after taking it. However, it does have good efficacy.

When do you prescribe gepants?

Gepants are small-molecule CGRP receptor blockers. They are tablets that sit on the receptor, preventing the CGRP from docking on the receptor and increasing the headache during a migraine attack. There are 2 gepants that can be used to stop a headache that is just starting or in progress: ubrogepant and rimegepant. 

Ubrogepant is a regular tablet that is available in 50-mg or 100-mg strengths. If the first dose does not make a patient pain free, a second dose is recommended about 2 hours later. Rimegepant is a meltaway tablet and only comes in a 75-mg strength. It should be taken early in the attack, and usually the patient does not need further treatment that day. If they do, they need to switch to another treatment, as rimegepant should not be repeated that day. Rimegepant may be used for both acute care and prevention. It is the only tablet that can be used for both. 

Both drugs have been shown to provide pain freedom for about 20% of patients at 2 hours, which is statistically better than the patients that received the placebo. These drugs generally don’t cause many adverse events but can cause a little nausea or drowsiness in some patients. Ubrogepant has a few contraindications; patients on certain medications such as antibiotics or antifungals cannot take it. If a patient is not doing well on a triptan or should not be given a drug that constricts blood vessels, I often switch them to one of these gepants (if covered by insurance). Both drugs have a plan to let the patient try them at a low cost. 

How are the gepants used acutely?

Gepants are used just like a triptan. As soon as the patient has a migraine headache starting, they take either ubrogepant or rimegepant as quickly as possible. Some patients say they feel the gepant begin to work within an hour or less, and some patients say it doesn't work at all, so I have them try the other gepant. 

Gepants are probably a better option than triptans if the patient is >40 years because triptans can constrict blood vessels. Older patients, and certainly those who have any kind of cardiac or cerebral blood vessel issues or even peripheral blood vessel disease, should not be given triptans.

When do you consider using preventive treatment in migraine?

If a patient has ≥4 moderate-to-severe headache days a month, or fewer with severe disability, or does not respond to acute care medications or those drugs are contraindicated, I consider giving them preventive therapy for migraine. The goal is to decrease the number of migraine days per month and to decrease the intensity, duration, and disability of the attacks.

Which gepants can you use for prevention of migraine?

I discussed rimegepant as an acute care medication, but the same 75-mg meltaway tablet given every other day works preventively to decrease the number of headaches. I like it, as it has few adverse events—<3% of patients experience nausea and abdominal pain—and it can also be used to stop a headache on days the patient did not take a tablet.

Atogepant is a newer, US Food and Drug Administration (FDA)-approved gepant taken once daily by mouth for prevention of migraine, and it works to decrease headache days per month. It has more side effects than the other gepants, including constipation, drowsiness, and nausea. If a patient does not have many adverse events while taking it, it is a good migraine preventive. 

How do you feel about monoclonal antibodies that bind to CGRP or its receptor for migraine preventive treatment?

Before the gepants became available, 4 different pharmaceutical companies were making monoclonal antibodies (mAbs) that bind to either CGRP or its receptor. This class of medication can be quite effective for most patients needing migraine prevention, as these medications last for a long time if the patient keeps taking it. 

Antibodies, when injected, continue to work for 1 to 3 months, making them perfect for migraine prevention, but they must be given either by the patient using an autoinjector with a tiny needle or by intravenous (IV) infusion in a hospital or office. They tend to be quite effective and have few adverse events.  

The first one to come out was erenumab, then frenanezumab, and galcanezumab. The newest one is eptinezumab, given by IV infusion over 30 minutes. Erenumab is the only mAb that sits on the receptor to prevent the CGRP from docking on the receptor, and it's the only one that seems to cause adverse events such as constipation and increased blood pressure in some patients. Eptinezumab is the only drug in this category given by IV infusion; patients must come to the office to receive the injection every 3 months. Even though eptinezumab is a powerful drug, I find that patients generally don't like coming in for IV treatment. I reserve it for when a patient has failed several other preventive treatments. The other 3 drugs (erenumab, fremanezumab, galcanezumab) are subcutaneous injections that the patient can self-administer at home. Fremanezumab can be taken once a month or once every 3 months, depending on the dose prescribed. 

What migraine devices do you like to prescribe?

The device that I tend to have my patients use is called Nerivio®; it has been cleared by the FDA for acute treatment of migraine in patients ≥12 years. An article was just published in the journal Headache on its use in prevention of migraine. The company expects the FDA to clear it very soon for prevention when used for 45 minutes every other day.

Nerivio® is an electrical stimulator that is placed on the upper arm like a blood pressure cuff. It is battery-powered and links to an app on a smartphone. I have my patients turn it up slowly to a higher gain, and when they feel a slight discomfort, they lower down until they do not feel it. That's where I recommend that they keep it for 45 minutes of treatment, starting at the beginning of a migraine attack. 

Nerivio® also has a behavioral medicine program incorporated into the smartphone app that lasts for 25 minutes. While the patient is receiving the 45 minutes of electrical stimulation, they are also being guided through relaxation techniques to help ease the headache. The company has done a controlled study comparing the efficacy of Nerivio® with and without the behavioral treatment and found that the 2 together are more effective than Nerivio® alone. 

The early double-blind studies of this device, as sent to the FDA for clearance, have excellent efficacy data with very few adverse events. Thus, it is used by many patients. The company has arranged a lower cost for the first month of treatment so a patient can see whether the device is effective.

There's also a device called Relivion®, which is worn like a tiara on the head to stimulate 4 nerves above the eyebrows that are part of the trigeminal system and 2 in the back of the head that affect the occipital nerves.

One of the earliest devices to launch is the gammaCore vagal nerve stimulator. It is handheld and controlled by the patient. It is placed on the front and side of the neck in the region of the vagal nerve. For acute care of migraine, the patient stimulates for 2 minutes and then waits several minutes before repeating 2 minutes of treatment. If you want to prescribe it for the prevention of migraine, a patient could do this sequence twice per day. It has been approved for acute care and prevention of migraine and, along with other medication for cluster headaches, it is easy to use and approved for almost any kind of headache. Unfortunately, it is extremely expensive for patients and is not covered well by insurance unless the patient is a veteran or goes to a Veterans Health Administration hospital for care. 

There are a few other devices that also work for migraine. Most electrical stimulation devices are costly, but we do hope that insurance companies will begin to cover them soon. Most devices cause few adverse events, have few contraindications, and will be used more as they become more affordable.

Can you summarize migraine treatment for us in one paragraph?

No, but I will try. We have many acute care treatments for migraine that are effective. Some, such as the triptans, do constrict blood vessels, and certain patients should not be taking medications that affect blood vessels. Some medications cause certain side effects or take too long to work, and we have other options for those patients. If a patient has ≥4 headache days per month or fewer associated with a lot of disability, we need to consider prevention. We have older preventives such as beta blockers and epilepsy medications, which are less expensive and can work but usually have many side effects. Now we have 4 mAbs that bind to CGRP or its receptor, which work well for a month or more with few adverse events. We also have 2 oral gepants for prevention. When you add in several devices, I have so many options for my patients today that I am a lucky neurologist, and my patients are even luckier!

Do you use nonpharmacologic approaches to treat your patients living with migraines? Which ones do you prefer?
I always like to start with nonpharmacologic approaches (also termed bio-behavioral approaches) with my patients. I talk to patients about sleep hygiene because if they don't sleep well, they're going to have more headaches. Most of my patients have issues with sleep and rarely feel refreshed in the morning. Most of them have middle insomnia; they wake up between 2 am and 4 am and cannot get back to sleep.

I also talk to my patients about eating properly. If patients don't eat on time or miss a meal, they often get headaches.  While timing is probably more critical, what they eat is important also. Poor diet can lead to decreased energy, and patients can become obese. Obesity impacts headache—especially migraine. I am not sure if there are any particularly good or bad foods for migraine patients, but in general, they should eat fewer fatty foods, fewer carbohydrates, more chicken, and fish than red meat, and a lot of fruits, vegetables, salads, nuts, and whole grains. A good trick is to limit the volume of each meal; do not go back for seconds and limit desserts and alcohol. 

Exercise is beneficial to decrease headaches, and the converse is even more true. Patients should start with low-impact, brief exercise like short walks and slowly build up to 20 minutes of cardio as tolerated, 3 to 5 times per week. Like poor diet choices, a sedentary lifestyle can lead to obesity and then not doing well with headaches and so on. 

What are your goals for treating your patients at the start of a migraine attack?

The goals for treating a migraine attack are to reduce the intensity of the pain quickly and, if possible, make the patient pain-free in ≤2 hours. We also try to reduce their most bothersome symptom, which is usually sensitivity to light or nausea, without causing any adverse effects from the treatment. Possibly as important, we want to get the patient back to functioning at work or at home, so they need no further treatment for that attack.

Unfortunately, many of the medicines we have available do cause adverse events, which are sometimes worse than the headache itself.  A patient can't continue to take a medication that causes significant side effects.

It is also critical to stop the headache quickly, as we don't want patients to take the prescribed acute care medicine and then, if they don’t feel like it’s working, proceed to take aspirin and then acetaminophen and then an anti-inflammatory tablet. The more medicine they take, the more likely they'll get medication overuse headache (MOH).  

MOH is not a great name, but it does imply that patients are taking one or many medications per week to stop their headaches, not realizing that this can worsen and prolong their headaches rather than helping them. They can also experience adverse events from taking so much medication. 

Finally, we want the patients to get rid of a headache so that they do not need to go to an emergency room, and we want to use medication that is cost effective and gets the patient functioning. Some medicines and devices are extremely expensive and not well covered by insurance companies but imagine the patient who takes a new medicine or uses a new device and gets better rapidly. If they hadn't done that, they may have lost a day or 2 of pay from missing work, or they might have gone to work and not done a very effective job because they were feeling miserable and couldn’t think or speak well. 

Do you prescribe triptans?

Definitely. The triptans first became available 30 years ago. There are 7 different triptans, and some work better for some patients than others. They come in tablets, injections, and nasal sprays. Sometimes patients need to try 2 or 3 different triptans to see which one is the most effective for them. If a patient has no success with tablets, there's a possibility that an injection or even a nasal spray would be more effective.
There are 2 triptans available as a nasal spray. I happen to like a triptan nasal spray called zolmitriptan, which usually works faster with fewer adverse events than the tablets.

There's also an injection of sumatriptan available, which is the fastest way to get relief from a triptan. Patients usually don't prefer it because it is an injection that they give themselves via an auto injector, and it may hurt and can be a bit complex to administer. There are definitely more adverse events when sumatriptan is given by injection, but because an injection can deliver very fast results that stop the headache reliably, some patients prefer it.

Triptans have been the mainstay treatment to stop an ongoing migraine attack for 30 years. We have always known there is some constriction of blood vessels and triptan-related side effects such as dizziness, drowsiness, and tingling sensations, so not every patient can take them. The newer medications that block calcitonin gene-related peptide (CGRP) do not constrict blood vessels and have fewer adverse events but cost a lot more if not covered by insurance.

Another newer, nontriptan nasal spray is dihydroergotamine (DHE) mesylate for acute care. It is one of the best medications to use if the patient’s migraine has been going on for 24 hours, as it tends to work well for a long-lasting headache. It also works for a long period, giving the patient a rest before their next attack. A nasal spray works faster than a tablet form, as the medication is absorbed from the nasal mucosa and does not have to make its way through the GI tract, then to the liver for metabolism, and finally, up to the brain before it begins to work. There can be some side effects in the nose such as discomfort or stuffiness, but if it works well, patients usually tolerate it. 

There's also a newer class of medicine called ditans. In a recent study, lasmiditan, which comes in a 50-mg and a 100-mg tablet for acute care of migraine, showed no vasoconstrictive effects, suggesting that ditans could be a safe option for patients living with chronic cardio- and cerebrovascular disease. Lasmiditan could be an alternative to triptans when they are contraindicated in patients with blood vessel disease, obesity, high blood pressure or cholesterol levels, or in nonresponsive patients. Lasmiditan does cause some dizziness and drowsiness, so patients cannot drive for 8 hours after taking it. However, it does have good efficacy.

When do you prescribe gepants?

Gepants are small-molecule CGRP receptor blockers. They are tablets that sit on the receptor, preventing the CGRP from docking on the receptor and increasing the headache during a migraine attack. There are 2 gepants that can be used to stop a headache that is just starting or in progress: ubrogepant and rimegepant. 

Ubrogepant is a regular tablet that is available in 50-mg or 100-mg strengths. If the first dose does not make a patient pain free, a second dose is recommended about 2 hours later. Rimegepant is a meltaway tablet and only comes in a 75-mg strength. It should be taken early in the attack, and usually the patient does not need further treatment that day. If they do, they need to switch to another treatment, as rimegepant should not be repeated that day. Rimegepant may be used for both acute care and prevention. It is the only tablet that can be used for both. 

Both drugs have been shown to provide pain freedom for about 20% of patients at 2 hours, which is statistically better than the patients that received the placebo. These drugs generally don’t cause many adverse events but can cause a little nausea or drowsiness in some patients. Ubrogepant has a few contraindications; patients on certain medications such as antibiotics or antifungals cannot take it. If a patient is not doing well on a triptan or should not be given a drug that constricts blood vessels, I often switch them to one of these gepants (if covered by insurance). Both drugs have a plan to let the patient try them at a low cost. 

How are the gepants used acutely?

Gepants are used just like a triptan. As soon as the patient has a migraine headache starting, they take either ubrogepant or rimegepant as quickly as possible. Some patients say they feel the gepant begin to work within an hour or less, and some patients say it doesn't work at all, so I have them try the other gepant. 

Gepants are probably a better option than triptans if the patient is >40 years because triptans can constrict blood vessels. Older patients, and certainly those who have any kind of cardiac or cerebral blood vessel issues or even peripheral blood vessel disease, should not be given triptans.

When do you consider using preventive treatment in migraine?

If a patient has ≥4 moderate-to-severe headache days a month, or fewer with severe disability, or does not respond to acute care medications or those drugs are contraindicated, I consider giving them preventive therapy for migraine. The goal is to decrease the number of migraine days per month and to decrease the intensity, duration, and disability of the attacks.

Which gepants can you use for prevention of migraine?

I discussed rimegepant as an acute care medication, but the same 75-mg meltaway tablet given every other day works preventively to decrease the number of headaches. I like it, as it has few adverse events—<3% of patients experience nausea and abdominal pain—and it can also be used to stop a headache on days the patient did not take a tablet.

Atogepant is a newer, US Food and Drug Administration (FDA)-approved gepant taken once daily by mouth for prevention of migraine, and it works to decrease headache days per month. It has more side effects than the other gepants, including constipation, drowsiness, and nausea. If a patient does not have many adverse events while taking it, it is a good migraine preventive. 

How do you feel about monoclonal antibodies that bind to CGRP or its receptor for migraine preventive treatment?

Before the gepants became available, 4 different pharmaceutical companies were making monoclonal antibodies (mAbs) that bind to either CGRP or its receptor. This class of medication can be quite effective for most patients needing migraine prevention, as these medications last for a long time if the patient keeps taking it. 

Antibodies, when injected, continue to work for 1 to 3 months, making them perfect for migraine prevention, but they must be given either by the patient using an autoinjector with a tiny needle or by intravenous (IV) infusion in a hospital or office. They tend to be quite effective and have few adverse events.  

The first one to come out was erenumab, then frenanezumab, and galcanezumab. The newest one is eptinezumab, given by IV infusion over 30 minutes. Erenumab is the only mAb that sits on the receptor to prevent the CGRP from docking on the receptor, and it's the only one that seems to cause adverse events such as constipation and increased blood pressure in some patients. Eptinezumab is the only drug in this category given by IV infusion; patients must come to the office to receive the injection every 3 months. Even though eptinezumab is a powerful drug, I find that patients generally don't like coming in for IV treatment. I reserve it for when a patient has failed several other preventive treatments. The other 3 drugs (erenumab, fremanezumab, galcanezumab) are subcutaneous injections that the patient can self-administer at home. Fremanezumab can be taken once a month or once every 3 months, depending on the dose prescribed. 

What migraine devices do you like to prescribe?

The device that I tend to have my patients use is called Nerivio®; it has been cleared by the FDA for acute treatment of migraine in patients ≥12 years. An article was just published in the journal Headache on its use in prevention of migraine. The company expects the FDA to clear it very soon for prevention when used for 45 minutes every other day.

Nerivio® is an electrical stimulator that is placed on the upper arm like a blood pressure cuff. It is battery-powered and links to an app on a smartphone. I have my patients turn it up slowly to a higher gain, and when they feel a slight discomfort, they lower down until they do not feel it. That's where I recommend that they keep it for 45 minutes of treatment, starting at the beginning of a migraine attack. 

Nerivio® also has a behavioral medicine program incorporated into the smartphone app that lasts for 25 minutes. While the patient is receiving the 45 minutes of electrical stimulation, they are also being guided through relaxation techniques to help ease the headache. The company has done a controlled study comparing the efficacy of Nerivio® with and without the behavioral treatment and found that the 2 together are more effective than Nerivio® alone. 

The early double-blind studies of this device, as sent to the FDA for clearance, have excellent efficacy data with very few adverse events. Thus, it is used by many patients. The company has arranged a lower cost for the first month of treatment so a patient can see whether the device is effective.

There's also a device called Relivion®, which is worn like a tiara on the head to stimulate 4 nerves above the eyebrows that are part of the trigeminal system and 2 in the back of the head that affect the occipital nerves.

One of the earliest devices to launch is the gammaCore vagal nerve stimulator. It is handheld and controlled by the patient. It is placed on the front and side of the neck in the region of the vagal nerve. For acute care of migraine, the patient stimulates for 2 minutes and then waits several minutes before repeating 2 minutes of treatment. If you want to prescribe it for the prevention of migraine, a patient could do this sequence twice per day. It has been approved for acute care and prevention of migraine and, along with other medication for cluster headaches, it is easy to use and approved for almost any kind of headache. Unfortunately, it is extremely expensive for patients and is not covered well by insurance unless the patient is a veteran or goes to a Veterans Health Administration hospital for care. 

There are a few other devices that also work for migraine. Most electrical stimulation devices are costly, but we do hope that insurance companies will begin to cover them soon. Most devices cause few adverse events, have few contraindications, and will be used more as they become more affordable.

Can you summarize migraine treatment for us in one paragraph?

No, but I will try. We have many acute care treatments for migraine that are effective. Some, such as the triptans, do constrict blood vessels, and certain patients should not be taking medications that affect blood vessels. Some medications cause certain side effects or take too long to work, and we have other options for those patients. If a patient has ≥4 headache days per month or fewer associated with a lot of disability, we need to consider prevention. We have older preventives such as beta blockers and epilepsy medications, which are less expensive and can work but usually have many side effects. Now we have 4 mAbs that bind to CGRP or its receptor, which work well for a month or more with few adverse events. We also have 2 oral gepants for prevention. When you add in several devices, I have so many options for my patients today that I am a lucky neurologist, and my patients are even luckier!

Type 2 diabetes (T2D) is a chronic, progressive disease marked by ongoing decline in insulin sensitivity and beta-cell function over time. Clinical trials have shown that lowering A1C to ∼7.0% (53 mmol/mol), especially after an early diagnosis, can markedly reduce the long-term complications of T2D. Metformin has become the generally recommended first therapeutic agent in treating T2D due to the drug’s long-term experience, effectiveness, and avoidance of hypoglycemia or weight gain. However, it is clear that additional agents are necessary to regain glucose control when metformin eventually fails due to the progressive nature of the disease.

Insufficient data on comparative efficacy and durability of effect has led to uncertainty in recommendations for the preferred second agent. Comparative effectiveness has been reported primarily in industry-sponsored trials of relatively short duration. With this in mind, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) sponsored the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness (GRADE) Study. This landmark, randomized controlled study was initiated in 2013, enrolling patients on metformin alone within 10 years of diagnosis of T2D. It involved 36 research sites in the United States with a mean follow-up of 5 years. The participants were randomized to adding a dipeptidyl peptidase 4 (DPP-4) inhibitor (sitagliptin), a sulfonylurea (glimepiride), basal insulin (glargine), or a glucagon-like peptide 1 receptor agonist (GLP-1 RA) (liraglutide), with the primary outcome being time to A1C over 7.0%.

The GRADE study was unique in several ways: its size, scope, length, and the fact that the financial support and design planning stemmed from a U34 planning grant from the NIDDK. The study population of 5047 participants was very diverse, reflecting the population affected by T2D. A mix of racial and ethnic groups were represented, including 19.8% Black participants and 18.6% Hispanic participants. It is unlikely that a similar comparative effectiveness trial of pharmacologic treatment of T2D will be performed again in the future, considering the high costs and length of time required for such a study amid the dynamic drug development environment today. In fact, the final implementation of study results is somewhat complicated by the subsequent approval of GLP-1 RAs of greater efficacy, weight loss, and convenience, as well as sodium-glucose cotransporter 2 (SGLT2) inhibitors and, most recently, a dual GLP-1/gastric inhibitory polypeptide (GIP) receptor agonist (tirzepatide). Many of these newer agents have demonstrated nonglycemic benefits, such as reduced risk of cardiovascular (CV) events or reduced progression of renal disease. The findings from the GRADE study, however, did provide important insight on the long-term management of T2D.

The GRADE study was the first to compare the efficacy of 4 US Food and Drug Administration–approved drugs for T2D in maintaining blood glucose levels for the longest amount of time in patients with T2D. It also monitored microvascular complications, CV events, and adverse drug effects.

An important message of the study that may be overlooked is that all of the studied agents’ ability to maintain an A1C under 7.0% was quite low—as 71% of all participants reached the primary outcome by 5 years; the best results for a group were 67% for glargine and 68% for liraglutide. In general, the results showed that liraglutide and insulin glargine were superior to glimepiride and sitagliptin in controlling blood sugars. They provided approximately 6 months’ more time with blood glucose levels in the desired range compared with sitagliptin, which was shown to provide the least amount of time in maintaining glucose levels. Fifty-five percent of the sitagliptin group experienced the primary outcome at 1 year. Sitagliptin was particularly ineffective for the patient subgroup with an A1C at baseline of 7.8% or higher, where 70% reached the primary outcome in 1 year. The results were uniform regarding age, race, sex, and ethnicity of the trial participants. The intention-to-treat design of the study limits the conclusions about A1C differences, as failure to maintain an A1C under 7.5% required addition of prandial insulin for the glargine group and the addition of glargine to the other 3 groups. Although subjects receiving glargine had an initial glucose-lowering effect that was less than that seen with liraglutide, the ability to keep titrating the glargine likely had an impact on the long-term benefit of that agent. When the glargine group neared or in some cases even passed the secondary outcome A1C level of 7.5%, the basal insulin was increased to lower the A1C, sometimes even when the protocol would recommend adding prandial insulin.  

The study was not powered specifically for determining the relative risk of CV events. However, there was some evidence that liraglutide was associated with lower CV risk than the other 3 agents by about 30%. There was no difference in microvascular risk among the agents in this study of relatively short-term disease. Side effects were not a major problem and no different than expected. Glargine and glimepiride were associated with less weight loss, while liraglutide had a particular benefit on weight. Glimepiride is associated with significantly more frequent incidents of severe hypoglycemia, though the rates of severe hypoglycemia were quite low. Liraglutide users reported significantly higher rates of nausea and had a higher early drop-out rate, but did not show a difference in continued use by the end of the study.  

In summary, the GRADE trial confirmed that glucose control in T2D is a progressive problem, as the addition of all 4 classes of medication failed to keep most patients in the target glucose range. However, basal insulin and GLP-1 RAs outperformed the other 2 classes. Sitagliptin has the poorest metabolic profile. One could argue that, based on overall metabolic control and concomitant weight benefits, less need for glucose monitoring, simple titration, apparent CV benefit, and insignificant hypoglycemia, GLP-1 RAs offer the best option as an agent to add to metformin. This conclusion is fortified by the fact that the agent used to represent this class in the study appears to be less effective in reducing glucose and weight and offers less convenience than the newer, once-weekly GLP-RAs available today.   

Type 2 diabetes (T2D) is a chronic, progressive disease marked by ongoing decline in insulin sensitivity and beta-cell function over time. Clinical trials have shown that lowering A1C to ∼7.0% (53 mmol/mol), especially after an early diagnosis, can markedly reduce the long-term complications of T2D. Metformin has become the generally recommended first therapeutic agent in treating T2D due to the drug’s long-term experience, effectiveness, and avoidance of hypoglycemia or weight gain. However, it is clear that additional agents are necessary to regain glucose control when metformin eventually fails due to the progressive nature of the disease.

Insufficient data on comparative efficacy and durability of effect has led to uncertainty in recommendations for the preferred second agent. Comparative effectiveness has been reported primarily in industry-sponsored trials of relatively short duration. With this in mind, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) sponsored the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness (GRADE) Study. This landmark, randomized controlled study was initiated in 2013, enrolling patients on metformin alone within 10 years of diagnosis of T2D. It involved 36 research sites in the United States with a mean follow-up of 5 years. The participants were randomized to adding a dipeptidyl peptidase 4 (DPP-4) inhibitor (sitagliptin), a sulfonylurea (glimepiride), basal insulin (glargine), or a glucagon-like peptide 1 receptor agonist (GLP-1 RA) (liraglutide), with the primary outcome being time to A1C over 7.0%.

The GRADE study was unique in several ways: its size, scope, length, and the fact that the financial support and design planning stemmed from a U34 planning grant from the NIDDK. The study population of 5047 participants was very diverse, reflecting the population affected by T2D. A mix of racial and ethnic groups were represented, including 19.8% Black participants and 18.6% Hispanic participants. It is unlikely that a similar comparative effectiveness trial of pharmacologic treatment of T2D will be performed again in the future, considering the high costs and length of time required for such a study amid the dynamic drug development environment today. In fact, the final implementation of study results is somewhat complicated by the subsequent approval of GLP-1 RAs of greater efficacy, weight loss, and convenience, as well as sodium-glucose cotransporter 2 (SGLT2) inhibitors and, most recently, a dual GLP-1/gastric inhibitory polypeptide (GIP) receptor agonist (tirzepatide). Many of these newer agents have demonstrated nonglycemic benefits, such as reduced risk of cardiovascular (CV) events or reduced progression of renal disease. The findings from the GRADE study, however, did provide important insight on the long-term management of T2D.

The GRADE study was the first to compare the efficacy of 4 US Food and Drug Administration–approved drugs for T2D in maintaining blood glucose levels for the longest amount of time in patients with T2D. It also monitored microvascular complications, CV events, and adverse drug effects.

An important message of the study that may be overlooked is that all of the studied agents’ ability to maintain an A1C under 7.0% was quite low—as 71% of all participants reached the primary outcome by 5 years; the best results for a group were 67% for glargine and 68% for liraglutide. In general, the results showed that liraglutide and insulin glargine were superior to glimepiride and sitagliptin in controlling blood sugars. They provided approximately 6 months’ more time with blood glucose levels in the desired range compared with sitagliptin, which was shown to provide the least amount of time in maintaining glucose levels. Fifty-five percent of the sitagliptin group experienced the primary outcome at 1 year. Sitagliptin was particularly ineffective for the patient subgroup with an A1C at baseline of 7.8% or higher, where 70% reached the primary outcome in 1 year. The results were uniform regarding age, race, sex, and ethnicity of the trial participants. The intention-to-treat design of the study limits the conclusions about A1C differences, as failure to maintain an A1C under 7.5% required addition of prandial insulin for the glargine group and the addition of glargine to the other 3 groups. Although subjects receiving glargine had an initial glucose-lowering effect that was less than that seen with liraglutide, the ability to keep titrating the glargine likely had an impact on the long-term benefit of that agent. When the glargine group neared or in some cases even passed the secondary outcome A1C level of 7.5%, the basal insulin was increased to lower the A1C, sometimes even when the protocol would recommend adding prandial insulin.  

The study was not powered specifically for determining the relative risk of CV events. However, there was some evidence that liraglutide was associated with lower CV risk than the other 3 agents by about 30%. There was no difference in microvascular risk among the agents in this study of relatively short-term disease. Side effects were not a major problem and no different than expected. Glargine and glimepiride were associated with less weight loss, while liraglutide had a particular benefit on weight. Glimepiride is associated with significantly more frequent incidents of severe hypoglycemia, though the rates of severe hypoglycemia were quite low. Liraglutide users reported significantly higher rates of nausea and had a higher early drop-out rate, but did not show a difference in continued use by the end of the study.  

In summary, the GRADE trial confirmed that glucose control in T2D is a progressive problem, as the addition of all 4 classes of medication failed to keep most patients in the target glucose range. However, basal insulin and GLP-1 RAs outperformed the other 2 classes. Sitagliptin has the poorest metabolic profile. One could argue that, based on overall metabolic control and concomitant weight benefits, less need for glucose monitoring, simple titration, apparent CV benefit, and insignificant hypoglycemia, GLP-1 RAs offer the best option as an agent to add to metformin. This conclusion is fortified by the fact that the agent used to represent this class in the study appears to be less effective in reducing glucose and weight and offers less convenience than the newer, once-weekly GLP-RAs available today.   

Type 2 diabetes (T2D) is a chronic, progressive disease marked by ongoing decline in insulin sensitivity and beta-cell function over time. Clinical trials have shown that lowering A1C to ∼7.0% (53 mmol/mol), especially after an early diagnosis, can markedly reduce the long-term complications of T2D. Metformin has become the generally recommended first therapeutic agent in treating T2D due to the drug’s long-term experience, effectiveness, and avoidance of hypoglycemia or weight gain. However, it is clear that additional agents are necessary to regain glucose control when metformin eventually fails due to the progressive nature of the disease.

Insufficient data on comparative efficacy and durability of effect has led to uncertainty in recommendations for the preferred second agent. Comparative effectiveness has been reported primarily in industry-sponsored trials of relatively short duration. With this in mind, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) sponsored the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness (GRADE) Study. This landmark, randomized controlled study was initiated in 2013, enrolling patients on metformin alone within 10 years of diagnosis of T2D. It involved 36 research sites in the United States with a mean follow-up of 5 years. The participants were randomized to adding a dipeptidyl peptidase 4 (DPP-4) inhibitor (sitagliptin), a sulfonylurea (glimepiride), basal insulin (glargine), or a glucagon-like peptide 1 receptor agonist (GLP-1 RA) (liraglutide), with the primary outcome being time to A1C over 7.0%.

The GRADE study was unique in several ways: its size, scope, length, and the fact that the financial support and design planning stemmed from a U34 planning grant from the NIDDK. The study population of 5047 participants was very diverse, reflecting the population affected by T2D. A mix of racial and ethnic groups were represented, including 19.8% Black participants and 18.6% Hispanic participants. It is unlikely that a similar comparative effectiveness trial of pharmacologic treatment of T2D will be performed again in the future, considering the high costs and length of time required for such a study amid the dynamic drug development environment today. In fact, the final implementation of study results is somewhat complicated by the subsequent approval of GLP-1 RAs of greater efficacy, weight loss, and convenience, as well as sodium-glucose cotransporter 2 (SGLT2) inhibitors and, most recently, a dual GLP-1/gastric inhibitory polypeptide (GIP) receptor agonist (tirzepatide). Many of these newer agents have demonstrated nonglycemic benefits, such as reduced risk of cardiovascular (CV) events or reduced progression of renal disease. The findings from the GRADE study, however, did provide important insight on the long-term management of T2D.

The GRADE study was the first to compare the efficacy of 4 US Food and Drug Administration–approved drugs for T2D in maintaining blood glucose levels for the longest amount of time in patients with T2D. It also monitored microvascular complications, CV events, and adverse drug effects.

An important message of the study that may be overlooked is that all of the studied agents’ ability to maintain an A1C under 7.0% was quite low—as 71% of all participants reached the primary outcome by 5 years; the best results for a group were 67% for glargine and 68% for liraglutide. In general, the results showed that liraglutide and insulin glargine were superior to glimepiride and sitagliptin in controlling blood sugars. They provided approximately 6 months’ more time with blood glucose levels in the desired range compared with sitagliptin, which was shown to provide the least amount of time in maintaining glucose levels. Fifty-five percent of the sitagliptin group experienced the primary outcome at 1 year. Sitagliptin was particularly ineffective for the patient subgroup with an A1C at baseline of 7.8% or higher, where 70% reached the primary outcome in 1 year. The results were uniform regarding age, race, sex, and ethnicity of the trial participants. The intention-to-treat design of the study limits the conclusions about A1C differences, as failure to maintain an A1C under 7.5% required addition of prandial insulin for the glargine group and the addition of glargine to the other 3 groups. Although subjects receiving glargine had an initial glucose-lowering effect that was less than that seen with liraglutide, the ability to keep titrating the glargine likely had an impact on the long-term benefit of that agent. When the glargine group neared or in some cases even passed the secondary outcome A1C level of 7.5%, the basal insulin was increased to lower the A1C, sometimes even when the protocol would recommend adding prandial insulin.  

The study was not powered specifically for determining the relative risk of CV events. However, there was some evidence that liraglutide was associated with lower CV risk than the other 3 agents by about 30%. There was no difference in microvascular risk among the agents in this study of relatively short-term disease. Side effects were not a major problem and no different than expected. Glargine and glimepiride were associated with less weight loss, while liraglutide had a particular benefit on weight. Glimepiride is associated with significantly more frequent incidents of severe hypoglycemia, though the rates of severe hypoglycemia were quite low. Liraglutide users reported significantly higher rates of nausea and had a higher early drop-out rate, but did not show a difference in continued use by the end of the study.  

In summary, the GRADE trial confirmed that glucose control in T2D is a progressive problem, as the addition of all 4 classes of medication failed to keep most patients in the target glucose range. However, basal insulin and GLP-1 RAs outperformed the other 2 classes. Sitagliptin has the poorest metabolic profile. One could argue that, based on overall metabolic control and concomitant weight benefits, less need for glucose monitoring, simple titration, apparent CV benefit, and insignificant hypoglycemia, GLP-1 RAs offer the best option as an agent to add to metformin. This conclusion is fortified by the fact that the agent used to represent this class in the study appears to be less effective in reducing glucose and weight and offers less convenience than the newer, once-weekly GLP-RAs available today.   

John Whyte, MD: Hello, I’m Dr. John Whyte, the Chief Medical Officer of WebMD. The American Cancer Society released some encouraging data recently that showed a decline in some cancers. One of those cancers was pancreatic cancer, which historically has had a very low survival rate. What’s going on here? Are we doing better with diagnosis, treatment, a combination?

Joining me today is Dr. Lynn Matrisian. She is PanCAN’s chief science officer. Dr. Matrisian, thanks for joining me today. It’s great to see you.

Lynn Matrisian, PhD, MBA: Great to be here. Thank you.

Dr. Whyte: Well, tell me what your first reaction was when you saw the recent data from the American Cancer Society. What one word would you use?

Dr. Matrisian: Hopeful. I think hopeful in general that survival rates are increasing, not for all cancers, but for many cancers. We continue to make progress. Research is making a difference. And we’re making progress against cancer in general.

Dr. Whyte: You’re passionate, as our viewers know, about pancreatic cancer. And that’s been one of the hardest cancers to treat, and one of the lowest survival rates. But there’s some encouraging news that we saw, didn’t we?

Dr. Matrisian: Yes. So the 5-year survival rate for pancreatic cancer went up a whole percentage. It’s at 12% now. And what’s really good is it was at 11% last year. It was at 10% the year before. So that’s 2 years in a row that we’ve had an increase in the 5-year survival rate for pancreatic cancer. So we’re hopeful that’s a trajectory that we can really capitalize on is how fast we’re making progress in this disease.

Dr. Whyte: I want to put it into context, Lynn. Because some people might be thinking, 1%? Like you’re excited about 1%? That doesn’t seem that much. But correct me if I’m wrong. A one percentage point increase means 641 more loved ones will enjoy life’s moments, as you put it, 5 years after their diagnosis that otherwise wouldn’t have. What does that practically mean to viewers?

Dr. Matrisian: That means that more than 600 people in the United States will hug a loved one 5 years after that diagnosis of pancreatic cancer. It is a very deadly disease. But we’re going to, by continuing to make progress, it gives those moments to those people. And it means that we’re making progress against the disease in general.

Dr. Whyte: So even 1%, and 1% each year, does have value.

Dr. Matrisian: It has a lot of value.

Dr. Whyte: What’s driving this improvement? Is it better screening? And we’re not so great still in screening a pancreatic cancer. Is it the innovation in cancer treatments? What do you think is accounting for what we hope is this trajectory of increases in 5-year survival?

Dr. Matrisian: Right, so the nice thing the reason that we like looking at 5-year survival rates is because it takes into account all of those things. And we have actually made progress in all of those things. So by looking at those that are diagnosed with pancreatic cancer in general as a whole, and looking at their survival, we are looking at better treatments. People who are getting pancreatic cancer later are living longer as a result of better treatments.

But it’s not just that. It’s also, if you’re diagnosed earlier, your 5-year survival rate is higher. More people who are diagnosed early live to five years than those that are diagnosed later. So within that statistic, there are more people who are diagnosed earlier. And those people also live longer. So it takes into account all of those things, which is why we really like to look at that five-year survival rate for a disease like pancreatic cancer.

Dr. Whyte: Where are we on screening? Because we always want to catch people early. That gives them that greatest chance of survival. Have we made much improvements there? And if we have, what are they?

Dr. Matrisian: Well we have made improvements there are more people that are now diagnosed with localized disease than there were 20 years ago. So that is increasing. And we’re still doing it really by being aware of the symptoms right now. Being aware that kind of chronic indigestion, lower back pain that won’t go away, these are signs and symptoms. And especially things like jaundice ...

Dr. Whyte: That yellow color that they might see.

Dr. Matrisian: Yes, that yellow colors in your eye, that’s a really important symptom that would certainly send people to the doctor in order to look at this. So some of it is being more aware and finding the disease earlier. But what we’re really hoping for is some sort of blood test or some sort of other way of looking through medical records and identifying those people that need to go and be checked.

Dr. Whyte: Now we chatted about that almost two years ago. So tell me the progress that we’ve made. How are we doing?

Dr. Matrisian: Yeah, well there’s a number of companies now that have blood tests that are available. They still need more work. They still need more studies to really understand how good they are at finding pancreatic cancer early. But we didn’t have them a couple of years ago. And so it’s really a very exciting time in the field, that there’s companies that were taking advantage of research for many years and actually turning it into a commercial product that is available for people to check.

Dr. Whyte: And then what about treatments? More treatment options today than there were just a few years ago, but still a lot of progress to be made. So when we talk about even 12% 5-year survival, we’d love to see it much more. And you talk about, I don’t want to misquote, so correct me if I’m wrong. Your goal is 20%. Five-year survival by 2030. That’s not too far. So, Lynn, how are we going to get there?

Dr. Matrisian: Okay, well this is our mission. And that’s exactly our goal, 20% by 2030. So we’ve got some work to do. And we are working at both fronts. You’re right, we need better treatments. And so we’ve set up a clinical trial platform where we can look at a lot of different treatments much more efficiently, much faster, kind of taking advantage of an infrastructure to do that. And that’s called Precision Promise. And we’re excited about that as a way to get new treatments for advanced pancreatic cancer.

And then we’re also working on the early detection end. We think an important symptom of pancreatic cancer that isn’t often recognized is new onset diabetes, sudden diabetes in those over 50 where that person did not have diabetes before. So it’s new, looks like type 2 diabetes, but it’s actually caused by pancreatic cancer.

And so we have an initiative, The Early Detection Initiative, that is taking advantage of that. And seeing if we image people right away based on that symptom, can we find pancreatic cancer early? So we think it’s important to look both at trying to diagnose it earlier, as well as trying to treat it better for advanced disease.

Dr. Whyte: Yeah. You know, at WebMD we’re always trying to empower people with better information so they can also become advocates for their health. You’re an expert in advocacy on pancreatic cancer. So what’s your advice to listeners as to how they become good advocates for themselves or advocates in general for loved ones who have pancreatic cancer?

Dr. Matrisian: Yeah. Yeah. Well certainly, knowledge is power. And so the real thing to do is to call the Pancreatic Cancer Action Network. This is what we do. We stay up on the most current information. We have very experienced case managers who can help navigate the complexities of pancreatic cancer at every stage of the journey.

Or if you have questions about pancreatic cancer, call PanCAN. Go to PanCAN.org and give us a call. Because it’s really that knowledge, knowing what it is that you need to get more knowledge about, how to advocate for yourself is very important in a disease, in any disease, but in particular a disease like pancreatic cancer.

Dr. Whyte: And I don’t want to dismiss the progress that we’ve made, that you’ve just referenced in terms of the increased survival. But there’s still a long way to go. We need a lot more dollars for research. We need a lot more clinical trials to take place. What’s your message to a viewer who’s been diagnosed with pancreatic cancer or a loved one? What’s your message, Lynn, today for them?

Dr. Matrisian: Well, first, get as much knowledge as you can. Call PanCAN, and let us help you help your loved one. But then help us. Let’s do research. Let’s do more research. Let’s understand this disease better so we can make those kinds of progress in both treatment and early detection.

And PanCAN works very hard at understanding the disease and setting up research programs that are going to make a difference, that are going to get us to that aggressive goal of 20% survival by 2030. So there is a lot of things that can be done, raise awareness to your friends and neighbors about the disease, lots of things that will help this whole field.

Dr. Whyte: What’s your feeling on second opinions? Given that this can be a difficult cancer to treat, given that there’s emerging therapies that are always developing, when you have a diagnosis of pancreatic cancer, is it important to consider getting a second opinion?

Dr. Matrisian: Yes. Yes, it is. And our case managers will help with that process. We do think it’s important.

Dr. Whyte: Because sometimes, Lynn, people just want to get started, right? Get it out of me. Get treatment. And sometimes getting a second opinion, doing some genomic testing can take time. So what’s your response to that?

Dr. Matrisian: Yeah. Yeah. Well we say, your care team is very important. Who is on your care team, and it may take a little time to find the right people on your care team. But that is an incredibly important step. Sometimes it’s not just one person. Sometimes you need more than one doctor, more than one nurse, more than one type of specialty to help you deal with this. And taking the time to do that is incredibly important.

Yes, you need to – you do need to act. But act smart. And do it with knowledge. Do it really understanding what your options are, and advocate for yourself.

Dr. Whyte: And surround yourself as you reference with that right care team for you, because that’s the most important thing when you have any type of cancer diagnosis. Dr. Lynn Matrisian, I want to thank you for taking time today.

Dr. Matrisian: Thank you so much, John.

A version of this article first appeared on Medscape.com.

John Whyte, MD: Hello, I’m Dr. John Whyte, the Chief Medical Officer of WebMD. The American Cancer Society released some encouraging data recently that showed a decline in some cancers. One of those cancers was pancreatic cancer, which historically has had a very low survival rate. What’s going on here? Are we doing better with diagnosis, treatment, a combination?

Joining me today is Dr. Lynn Matrisian. She is PanCAN’s chief science officer. Dr. Matrisian, thanks for joining me today. It’s great to see you.

Lynn Matrisian, PhD, MBA: Great to be here. Thank you.

Dr. Whyte: Well, tell me what your first reaction was when you saw the recent data from the American Cancer Society. What one word would you use?

Dr. Matrisian: Hopeful. I think hopeful in general that survival rates are increasing, not for all cancers, but for many cancers. We continue to make progress. Research is making a difference. And we’re making progress against cancer in general.

Dr. Whyte: You’re passionate, as our viewers know, about pancreatic cancer. And that’s been one of the hardest cancers to treat, and one of the lowest survival rates. But there’s some encouraging news that we saw, didn’t we?

Dr. Matrisian: Yes. So the 5-year survival rate for pancreatic cancer went up a whole percentage. It’s at 12% now. And what’s really good is it was at 11% last year. It was at 10% the year before. So that’s 2 years in a row that we’ve had an increase in the 5-year survival rate for pancreatic cancer. So we’re hopeful that’s a trajectory that we can really capitalize on is how fast we’re making progress in this disease.

Dr. Whyte: I want to put it into context, Lynn. Because some people might be thinking, 1%? Like you’re excited about 1%? That doesn’t seem that much. But correct me if I’m wrong. A one percentage point increase means 641 more loved ones will enjoy life’s moments, as you put it, 5 years after their diagnosis that otherwise wouldn’t have. What does that practically mean to viewers?

Dr. Matrisian: That means that more than 600 people in the United States will hug a loved one 5 years after that diagnosis of pancreatic cancer. It is a very deadly disease. But we’re going to, by continuing to make progress, it gives those moments to those people. And it means that we’re making progress against the disease in general.

Dr. Whyte: So even 1%, and 1% each year, does have value.

Dr. Matrisian: It has a lot of value.

Dr. Whyte: What’s driving this improvement? Is it better screening? And we’re not so great still in screening a pancreatic cancer. Is it the innovation in cancer treatments? What do you think is accounting for what we hope is this trajectory of increases in 5-year survival?

Dr. Matrisian: Right, so the nice thing the reason that we like looking at 5-year survival rates is because it takes into account all of those things. And we have actually made progress in all of those things. So by looking at those that are diagnosed with pancreatic cancer in general as a whole, and looking at their survival, we are looking at better treatments. People who are getting pancreatic cancer later are living longer as a result of better treatments.

But it’s not just that. It’s also, if you’re diagnosed earlier, your 5-year survival rate is higher. More people who are diagnosed early live to five years than those that are diagnosed later. So within that statistic, there are more people who are diagnosed earlier. And those people also live longer. So it takes into account all of those things, which is why we really like to look at that five-year survival rate for a disease like pancreatic cancer.

Dr. Whyte: Where are we on screening? Because we always want to catch people early. That gives them that greatest chance of survival. Have we made much improvements there? And if we have, what are they?

Dr. Matrisian: Well we have made improvements there are more people that are now diagnosed with localized disease than there were 20 years ago. So that is increasing. And we’re still doing it really by being aware of the symptoms right now. Being aware that kind of chronic indigestion, lower back pain that won’t go away, these are signs and symptoms. And especially things like jaundice ...

Dr. Whyte: That yellow color that they might see.

Dr. Matrisian: Yes, that yellow colors in your eye, that’s a really important symptom that would certainly send people to the doctor in order to look at this. So some of it is being more aware and finding the disease earlier. But what we’re really hoping for is some sort of blood test or some sort of other way of looking through medical records and identifying those people that need to go and be checked.

Dr. Whyte: Now we chatted about that almost two years ago. So tell me the progress that we’ve made. How are we doing?

Dr. Matrisian: Yeah, well there’s a number of companies now that have blood tests that are available. They still need more work. They still need more studies to really understand how good they are at finding pancreatic cancer early. But we didn’t have them a couple of years ago. And so it’s really a very exciting time in the field, that there’s companies that were taking advantage of research for many years and actually turning it into a commercial product that is available for people to check.

Dr. Whyte: And then what about treatments? More treatment options today than there were just a few years ago, but still a lot of progress to be made. So when we talk about even 12% 5-year survival, we’d love to see it much more. And you talk about, I don’t want to misquote, so correct me if I’m wrong. Your goal is 20%. Five-year survival by 2030. That’s not too far. So, Lynn, how are we going to get there?

Dr. Matrisian: Okay, well this is our mission. And that’s exactly our goal, 20% by 2030. So we’ve got some work to do. And we are working at both fronts. You’re right, we need better treatments. And so we’ve set up a clinical trial platform where we can look at a lot of different treatments much more efficiently, much faster, kind of taking advantage of an infrastructure to do that. And that’s called Precision Promise. And we’re excited about that as a way to get new treatments for advanced pancreatic cancer.

And then we’re also working on the early detection end. We think an important symptom of pancreatic cancer that isn’t often recognized is new onset diabetes, sudden diabetes in those over 50 where that person did not have diabetes before. So it’s new, looks like type 2 diabetes, but it’s actually caused by pancreatic cancer.

And so we have an initiative, The Early Detection Initiative, that is taking advantage of that. And seeing if we image people right away based on that symptom, can we find pancreatic cancer early? So we think it’s important to look both at trying to diagnose it earlier, as well as trying to treat it better for advanced disease.

Dr. Whyte: Yeah. You know, at WebMD we’re always trying to empower people with better information so they can also become advocates for their health. You’re an expert in advocacy on pancreatic cancer. So what’s your advice to listeners as to how they become good advocates for themselves or advocates in general for loved ones who have pancreatic cancer?

Dr. Matrisian: Yeah. Yeah. Well certainly, knowledge is power. And so the real thing to do is to call the Pancreatic Cancer Action Network. This is what we do. We stay up on the most current information. We have very experienced case managers who can help navigate the complexities of pancreatic cancer at every stage of the journey.

Or if you have questions about pancreatic cancer, call PanCAN. Go to PanCAN.org and give us a call. Because it’s really that knowledge, knowing what it is that you need to get more knowledge about, how to advocate for yourself is very important in a disease, in any disease, but in particular a disease like pancreatic cancer.

Dr. Whyte: And I don’t want to dismiss the progress that we’ve made, that you’ve just referenced in terms of the increased survival. But there’s still a long way to go. We need a lot more dollars for research. We need a lot more clinical trials to take place. What’s your message to a viewer who’s been diagnosed with pancreatic cancer or a loved one? What’s your message, Lynn, today for them?

Dr. Matrisian: Well, first, get as much knowledge as you can. Call PanCAN, and let us help you help your loved one. But then help us. Let’s do research. Let’s do more research. Let’s understand this disease better so we can make those kinds of progress in both treatment and early detection.

And PanCAN works very hard at understanding the disease and setting up research programs that are going to make a difference, that are going to get us to that aggressive goal of 20% survival by 2030. So there is a lot of things that can be done, raise awareness to your friends and neighbors about the disease, lots of things that will help this whole field.

Dr. Whyte: What’s your feeling on second opinions? Given that this can be a difficult cancer to treat, given that there’s emerging therapies that are always developing, when you have a diagnosis of pancreatic cancer, is it important to consider getting a second opinion?

Dr. Matrisian: Yes. Yes, it is. And our case managers will help with that process. We do think it’s important.

Dr. Whyte: Because sometimes, Lynn, people just want to get started, right? Get it out of me. Get treatment. And sometimes getting a second opinion, doing some genomic testing can take time. So what’s your response to that?

Dr. Matrisian: Yeah. Yeah. Well we say, your care team is very important. Who is on your care team, and it may take a little time to find the right people on your care team. But that is an incredibly important step. Sometimes it’s not just one person. Sometimes you need more than one doctor, more than one nurse, more than one type of specialty to help you deal with this. And taking the time to do that is incredibly important.

Yes, you need to – you do need to act. But act smart. And do it with knowledge. Do it really understanding what your options are, and advocate for yourself.

Dr. Whyte: And surround yourself as you reference with that right care team for you, because that’s the most important thing when you have any type of cancer diagnosis. Dr. Lynn Matrisian, I want to thank you for taking time today.

Dr. Matrisian: Thank you so much, John.

A version of this article first appeared on Medscape.com.

John Whyte, MD: Hello, I’m Dr. John Whyte, the Chief Medical Officer of WebMD. The American Cancer Society released some encouraging data recently that showed a decline in some cancers. One of those cancers was pancreatic cancer, which historically has had a very low survival rate. What’s going on here? Are we doing better with diagnosis, treatment, a combination?

Joining me today is Dr. Lynn Matrisian. She is PanCAN’s chief science officer. Dr. Matrisian, thanks for joining me today. It’s great to see you.

Lynn Matrisian, PhD, MBA: Great to be here. Thank you.

Dr. Whyte: Well, tell me what your first reaction was when you saw the recent data from the American Cancer Society. What one word would you use?

Dr. Matrisian: Hopeful. I think hopeful in general that survival rates are increasing, not for all cancers, but for many cancers. We continue to make progress. Research is making a difference. And we’re making progress against cancer in general.

Dr. Whyte: You’re passionate, as our viewers know, about pancreatic cancer. And that’s been one of the hardest cancers to treat, and one of the lowest survival rates. But there’s some encouraging news that we saw, didn’t we?

Dr. Matrisian: Yes. So the 5-year survival rate for pancreatic cancer went up a whole percentage. It’s at 12% now. And what’s really good is it was at 11% last year. It was at 10% the year before. So that’s 2 years in a row that we’ve had an increase in the 5-year survival rate for pancreatic cancer. So we’re hopeful that’s a trajectory that we can really capitalize on is how fast we’re making progress in this disease.

Dr. Whyte: I want to put it into context, Lynn. Because some people might be thinking, 1%? Like you’re excited about 1%? That doesn’t seem that much. But correct me if I’m wrong. A one percentage point increase means 641 more loved ones will enjoy life’s moments, as you put it, 5 years after their diagnosis that otherwise wouldn’t have. What does that practically mean to viewers?

Dr. Matrisian: That means that more than 600 people in the United States will hug a loved one 5 years after that diagnosis of pancreatic cancer. It is a very deadly disease. But we’re going to, by continuing to make progress, it gives those moments to those people. And it means that we’re making progress against the disease in general.

Dr. Whyte: So even 1%, and 1% each year, does have value.

Dr. Matrisian: It has a lot of value.

Dr. Whyte: What’s driving this improvement? Is it better screening? And we’re not so great still in screening a pancreatic cancer. Is it the innovation in cancer treatments? What do you think is accounting for what we hope is this trajectory of increases in 5-year survival?

Dr. Matrisian: Right, so the nice thing the reason that we like looking at 5-year survival rates is because it takes into account all of those things. And we have actually made progress in all of those things. So by looking at those that are diagnosed with pancreatic cancer in general as a whole, and looking at their survival, we are looking at better treatments. People who are getting pancreatic cancer later are living longer as a result of better treatments.

But it’s not just that. It’s also, if you’re diagnosed earlier, your 5-year survival rate is higher. More people who are diagnosed early live to five years than those that are diagnosed later. So within that statistic, there are more people who are diagnosed earlier. And those people also live longer. So it takes into account all of those things, which is why we really like to look at that five-year survival rate for a disease like pancreatic cancer.

Dr. Whyte: Where are we on screening? Because we always want to catch people early. That gives them that greatest chance of survival. Have we made much improvements there? And if we have, what are they?

Dr. Matrisian: Well we have made improvements there are more people that are now diagnosed with localized disease than there were 20 years ago. So that is increasing. And we’re still doing it really by being aware of the symptoms right now. Being aware that kind of chronic indigestion, lower back pain that won’t go away, these are signs and symptoms. And especially things like jaundice ...

Dr. Whyte: That yellow color that they might see.

Dr. Matrisian: Yes, that yellow colors in your eye, that’s a really important symptom that would certainly send people to the doctor in order to look at this. So some of it is being more aware and finding the disease earlier. But what we’re really hoping for is some sort of blood test or some sort of other way of looking through medical records and identifying those people that need to go and be checked.

Dr. Whyte: Now we chatted about that almost two years ago. So tell me the progress that we’ve made. How are we doing?

Dr. Matrisian: Yeah, well there’s a number of companies now that have blood tests that are available. They still need more work. They still need more studies to really understand how good they are at finding pancreatic cancer early. But we didn’t have them a couple of years ago. And so it’s really a very exciting time in the field, that there’s companies that were taking advantage of research for many years and actually turning it into a commercial product that is available for people to check.

Dr. Whyte: And then what about treatments? More treatment options today than there were just a few years ago, but still a lot of progress to be made. So when we talk about even 12% 5-year survival, we’d love to see it much more. And you talk about, I don’t want to misquote, so correct me if I’m wrong. Your goal is 20%. Five-year survival by 2030. That’s not too far. So, Lynn, how are we going to get there?

Dr. Matrisian: Okay, well this is our mission. And that’s exactly our goal, 20% by 2030. So we’ve got some work to do. And we are working at both fronts. You’re right, we need better treatments. And so we’ve set up a clinical trial platform where we can look at a lot of different treatments much more efficiently, much faster, kind of taking advantage of an infrastructure to do that. And that’s called Precision Promise. And we’re excited about that as a way to get new treatments for advanced pancreatic cancer.

And then we’re also working on the early detection end. We think an important symptom of pancreatic cancer that isn’t often recognized is new onset diabetes, sudden diabetes in those over 50 where that person did not have diabetes before. So it’s new, looks like type 2 diabetes, but it’s actually caused by pancreatic cancer.

And so we have an initiative, The Early Detection Initiative, that is taking advantage of that. And seeing if we image people right away based on that symptom, can we find pancreatic cancer early? So we think it’s important to look both at trying to diagnose it earlier, as well as trying to treat it better for advanced disease.

Dr. Whyte: Yeah. You know, at WebMD we’re always trying to empower people with better information so they can also become advocates for their health. You’re an expert in advocacy on pancreatic cancer. So what’s your advice to listeners as to how they become good advocates for themselves or advocates in general for loved ones who have pancreatic cancer?

Dr. Matrisian: Yeah. Yeah. Well certainly, knowledge is power. And so the real thing to do is to call the Pancreatic Cancer Action Network. This is what we do. We stay up on the most current information. We have very experienced case managers who can help navigate the complexities of pancreatic cancer at every stage of the journey.

Or if you have questions about pancreatic cancer, call PanCAN. Go to PanCAN.org and give us a call. Because it’s really that knowledge, knowing what it is that you need to get more knowledge about, how to advocate for yourself is very important in a disease, in any disease, but in particular a disease like pancreatic cancer.

Dr. Whyte: And I don’t want to dismiss the progress that we’ve made, that you’ve just referenced in terms of the increased survival. But there’s still a long way to go. We need a lot more dollars for research. We need a lot more clinical trials to take place. What’s your message to a viewer who’s been diagnosed with pancreatic cancer or a loved one? What’s your message, Lynn, today for them?

Dr. Matrisian: Well, first, get as much knowledge as you can. Call PanCAN, and let us help you help your loved one. But then help us. Let’s do research. Let’s do more research. Let’s understand this disease better so we can make those kinds of progress in both treatment and early detection.

And PanCAN works very hard at understanding the disease and setting up research programs that are going to make a difference, that are going to get us to that aggressive goal of 20% survival by 2030. So there is a lot of things that can be done, raise awareness to your friends and neighbors about the disease, lots of things that will help this whole field.

Dr. Whyte: What’s your feeling on second opinions? Given that this can be a difficult cancer to treat, given that there’s emerging therapies that are always developing, when you have a diagnosis of pancreatic cancer, is it important to consider getting a second opinion?

Dr. Matrisian: Yes. Yes, it is. And our case managers will help with that process. We do think it’s important.

Dr. Whyte: Because sometimes, Lynn, people just want to get started, right? Get it out of me. Get treatment. And sometimes getting a second opinion, doing some genomic testing can take time. So what’s your response to that?

Dr. Matrisian: Yeah. Yeah. Well we say, your care team is very important. Who is on your care team, and it may take a little time to find the right people on your care team. But that is an incredibly important step. Sometimes it’s not just one person. Sometimes you need more than one doctor, more than one nurse, more than one type of specialty to help you deal with this. And taking the time to do that is incredibly important.

Yes, you need to – you do need to act. But act smart. And do it with knowledge. Do it really understanding what your options are, and advocate for yourself.

Dr. Whyte: And surround yourself as you reference with that right care team for you, because that’s the most important thing when you have any type of cancer diagnosis. Dr. Lynn Matrisian, I want to thank you for taking time today.

Dr. Matrisian: Thank you so much, John.

A version of this article first appeared on Medscape.com.

Multiple sclerosis (MS) is one of the most common causes of neurological disability in young adults, occurring more frequently in women than men. The development of anti-cluster of differentiation 20 (CD20) monoclonal antibodies (mAbs) in recent years has significantly changed the way we treat MS. Compared to older standards of care, such as chemotherapy and immunosuppressive drugs, anti-CD20 mAbs have been shown to be more effective in treating MS with fewer side effects. 

Data have shown that B cells play a crucial role in the pathogenesis of MS via antigen-driven autoantibody responses and the cross-regulation of T-helper cells. CD20 is a protein that is expressed on the surface of B cells. Since B cells express the surface molecule CD20 at all points of differentiation, they provide a specific target for mAbs and are used to treat certain types of cancer and autoimmune disorders, including MS.

In people living with MS, the immune system mistakenly attacks the myelin sheath, a protective layer that surrounds nerve fibers in the central nervous system. This attack can cause inflammation and damage to the myelin sheath, leading to the development of various symptoms such as muscle weakness, vision problems, and issues with coordination and balance.

Anti-CD20 antibodies work by targeting and destroying B cells, which play a role in the immune system's attack on the myelin sheath. By targeting and destroying these cells, anti-CD20 antibodies may help to reduce the inflammation and damage to the myelin sheath and improve symptoms of MS.

There are several anti-CD20 mAbs used for the treatment of MS, including ocrelizumab, ofatumumab, ublituximab, and rituximab. Each drug has a unique mechanism of action and safety profile and distinct monitoring requirements. These therapies have been shown to deplete circulating B cells significantly for a certain amount of time, and they may be used in combination with other medications to treat MS. 

Ocrelizumab, a humanized anti-CD20 mAb administered by intravenous (IV) infusion, was approved in March 2017 by the US Food and Drug Administration (FDA) and is the first proven treatment to reduce disability progression in both primary progressive MS and relapsing MS. Interestingly, ocrelizumab binds to a CD20 epitope that overlaps partially with the epitope to which rituximab binds.

Ofatumumab is the first fully human anti-CD20 mAb and was approved by the FDA in August 2020 for treating relapsing forms of MS. The approval was on the basis of data from the phase 3 ASCLEPIOS I and II trials, which compared ofatumumab with teriflunomide, an oral agent that reduces the activity of proliferating T lymphocytes and B lymphocytes, mitigating the overall inflammatory response in MS. Subcutaneous ofatumumab demonstrated better efficacy than oral teriflunomide in reducing the annualized relapse rate in patients with MS. 

Ublituximab was recently approved by the FDA for treatment of relapsing forms of MS, including relapsing-remitting MS and active secondary progressive MS. Ublituximab works much like other anti-CD20 antibodies; however, it has been glycoengineered so that certain altered sugar molecules attached to the antibody increase its effectiveness. 

Rituximab is a chimeric monoclonal B-cell–depleting anti-CD20 antibody that has also showed promise as an escalation and as a first-line therapy for MS. The FDA has not approved it for this specific use yet, so its use is considered “off label.” A 2017 study showed that ofatumumab was more effective at depleting B cells than high doses of IV rituximab. 

It is important to note that anti-CD20 antibodies are not a cure for MS, and although they show promise for some patients, these agents do not work for everyone. The progress, severity, and specific symptoms of MS in any individual cannot yet be predicted; however, advances in research and treatment are leading to better understanding and moving us closer to curing this unpredictable, debilitating disease.

Multiple sclerosis (MS) is one of the most common causes of neurological disability in young adults, occurring more frequently in women than men. The development of anti-cluster of differentiation 20 (CD20) monoclonal antibodies (mAbs) in recent years has significantly changed the way we treat MS. Compared to older standards of care, such as chemotherapy and immunosuppressive drugs, anti-CD20 mAbs have been shown to be more effective in treating MS with fewer side effects. 

Data have shown that B cells play a crucial role in the pathogenesis of MS via antigen-driven autoantibody responses and the cross-regulation of T-helper cells. CD20 is a protein that is expressed on the surface of B cells. Since B cells express the surface molecule CD20 at all points of differentiation, they provide a specific target for mAbs and are used to treat certain types of cancer and autoimmune disorders, including MS.

In people living with MS, the immune system mistakenly attacks the myelin sheath, a protective layer that surrounds nerve fibers in the central nervous system. This attack can cause inflammation and damage to the myelin sheath, leading to the development of various symptoms such as muscle weakness, vision problems, and issues with coordination and balance.

Anti-CD20 antibodies work by targeting and destroying B cells, which play a role in the immune system's attack on the myelin sheath. By targeting and destroying these cells, anti-CD20 antibodies may help to reduce the inflammation and damage to the myelin sheath and improve symptoms of MS.

There are several anti-CD20 mAbs used for the treatment of MS, including ocrelizumab, ofatumumab, ublituximab, and rituximab. Each drug has a unique mechanism of action and safety profile and distinct monitoring requirements. These therapies have been shown to deplete circulating B cells significantly for a certain amount of time, and they may be used in combination with other medications to treat MS. 

Ocrelizumab, a humanized anti-CD20 mAb administered by intravenous (IV) infusion, was approved in March 2017 by the US Food and Drug Administration (FDA) and is the first proven treatment to reduce disability progression in both primary progressive MS and relapsing MS. Interestingly, ocrelizumab binds to a CD20 epitope that overlaps partially with the epitope to which rituximab binds.

Ofatumumab is the first fully human anti-CD20 mAb and was approved by the FDA in August 2020 for treating relapsing forms of MS. The approval was on the basis of data from the phase 3 ASCLEPIOS I and II trials, which compared ofatumumab with teriflunomide, an oral agent that reduces the activity of proliferating T lymphocytes and B lymphocytes, mitigating the overall inflammatory response in MS. Subcutaneous ofatumumab demonstrated better efficacy than oral teriflunomide in reducing the annualized relapse rate in patients with MS. 

Ublituximab was recently approved by the FDA for treatment of relapsing forms of MS, including relapsing-remitting MS and active secondary progressive MS. Ublituximab works much like other anti-CD20 antibodies; however, it has been glycoengineered so that certain altered sugar molecules attached to the antibody increase its effectiveness. 

Rituximab is a chimeric monoclonal B-cell–depleting anti-CD20 antibody that has also showed promise as an escalation and as a first-line therapy for MS. The FDA has not approved it for this specific use yet, so its use is considered “off label.” A 2017 study showed that ofatumumab was more effective at depleting B cells than high doses of IV rituximab. 

It is important to note that anti-CD20 antibodies are not a cure for MS, and although they show promise for some patients, these agents do not work for everyone. The progress, severity, and specific symptoms of MS in any individual cannot yet be predicted; however, advances in research and treatment are leading to better understanding and moving us closer to curing this unpredictable, debilitating disease.

Multiple sclerosis (MS) is one of the most common causes of neurological disability in young adults, occurring more frequently in women than men. The development of anti-cluster of differentiation 20 (CD20) monoclonal antibodies (mAbs) in recent years has significantly changed the way we treat MS. Compared to older standards of care, such as chemotherapy and immunosuppressive drugs, anti-CD20 mAbs have been shown to be more effective in treating MS with fewer side effects. 

Data have shown that B cells play a crucial role in the pathogenesis of MS via antigen-driven autoantibody responses and the cross-regulation of T-helper cells. CD20 is a protein that is expressed on the surface of B cells. Since B cells express the surface molecule CD20 at all points of differentiation, they provide a specific target for mAbs and are used to treat certain types of cancer and autoimmune disorders, including MS.

In people living with MS, the immune system mistakenly attacks the myelin sheath, a protective layer that surrounds nerve fibers in the central nervous system. This attack can cause inflammation and damage to the myelin sheath, leading to the development of various symptoms such as muscle weakness, vision problems, and issues with coordination and balance.

Anti-CD20 antibodies work by targeting and destroying B cells, which play a role in the immune system's attack on the myelin sheath. By targeting and destroying these cells, anti-CD20 antibodies may help to reduce the inflammation and damage to the myelin sheath and improve symptoms of MS.

There are several anti-CD20 mAbs used for the treatment of MS, including ocrelizumab, ofatumumab, ublituximab, and rituximab. Each drug has a unique mechanism of action and safety profile and distinct monitoring requirements. These therapies have been shown to deplete circulating B cells significantly for a certain amount of time, and they may be used in combination with other medications to treat MS. 

Ocrelizumab, a humanized anti-CD20 mAb administered by intravenous (IV) infusion, was approved in March 2017 by the US Food and Drug Administration (FDA) and is the first proven treatment to reduce disability progression in both primary progressive MS and relapsing MS. Interestingly, ocrelizumab binds to a CD20 epitope that overlaps partially with the epitope to which rituximab binds.

Ofatumumab is the first fully human anti-CD20 mAb and was approved by the FDA in August 2020 for treating relapsing forms of MS. The approval was on the basis of data from the phase 3 ASCLEPIOS I and II trials, which compared ofatumumab with teriflunomide, an oral agent that reduces the activity of proliferating T lymphocytes and B lymphocytes, mitigating the overall inflammatory response in MS. Subcutaneous ofatumumab demonstrated better efficacy than oral teriflunomide in reducing the annualized relapse rate in patients with MS. 

Ublituximab was recently approved by the FDA for treatment of relapsing forms of MS, including relapsing-remitting MS and active secondary progressive MS. Ublituximab works much like other anti-CD20 antibodies; however, it has been glycoengineered so that certain altered sugar molecules attached to the antibody increase its effectiveness. 

Rituximab is a chimeric monoclonal B-cell–depleting anti-CD20 antibody that has also showed promise as an escalation and as a first-line therapy for MS. The FDA has not approved it for this specific use yet, so its use is considered “off label.” A 2017 study showed that ofatumumab was more effective at depleting B cells than high doses of IV rituximab. 

It is important to note that anti-CD20 antibodies are not a cure for MS, and although they show promise for some patients, these agents do not work for everyone. The progress, severity, and specific symptoms of MS in any individual cannot yet be predicted; however, advances in research and treatment are leading to better understanding and moving us closer to curing this unpredictable, debilitating disease.

This transcript has been edited for clarity.

Welcome to Impact Factor, your weekly dose of commentary on a new medical study. I’m Dr F. Perry Wilson of the Yale School of Medicine.

With SARS-CoV-2 sidestepping monoclonal antibodies faster than a Texas square dance, the need for new therapeutic options to treat – not prevent – COVID-19 is becoming more and more dire.

courtesy Dr. F. Perry Wilson

courtesy of the New England Journal of Medicine

courtesy Dr. F. Perry Wilson

courtesy of the New England Journal of Medicine

courtesy of the New England Journal of Medicine

courtesy of the New England Journal of Medicine

Dr. Perry Wilson is associate professor, department of medicine, and director, Clinical and Translational Research Accelerator, at Yale University, New Haven, Conn. He disclosed no relevant conflicts of interest.

A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity.

Welcome to Impact Factor, your weekly dose of commentary on a new medical study. I’m Dr F. Perry Wilson of the Yale School of Medicine.

With SARS-CoV-2 sidestepping monoclonal antibodies faster than a Texas square dance, the need for new therapeutic options to treat – not prevent – COVID-19 is becoming more and more dire.

courtesy Dr. F. Perry Wilson

courtesy of the New England Journal of Medicine

courtesy Dr. F. Perry Wilson

courtesy of the New England Journal of Medicine

courtesy of the New England Journal of Medicine

courtesy of the New England Journal of Medicine

Dr. Perry Wilson is associate professor, department of medicine, and director, Clinical and Translational Research Accelerator, at Yale University, New Haven, Conn. He disclosed no relevant conflicts of interest.

A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity.

Welcome to Impact Factor, your weekly dose of commentary on a new medical study. I’m Dr F. Perry Wilson of the Yale School of Medicine.

With SARS-CoV-2 sidestepping monoclonal antibodies faster than a Texas square dance, the need for new therapeutic options to treat – not prevent – COVID-19 is becoming more and more dire.

courtesy Dr. F. Perry Wilson

courtesy of the New England Journal of Medicine

courtesy Dr. F. Perry Wilson

courtesy of the New England Journal of Medicine

courtesy of the New England Journal of Medicine

courtesy of the New England Journal of Medicine

Dr. Perry Wilson is associate professor, department of medicine, and director, Clinical and Translational Research Accelerator, at Yale University, New Haven, Conn. He disclosed no relevant conflicts of interest.

A version of this article first appeared on Medscape.com.