Federal Practitioner

This transcript has been edited for clarity.

I’m Dr. Neil Skolnik, and today I am going to talk about the 2023 update to the Global Strategy for Asthma Management and Prevention. We treat a lot of asthma, and there are some important changes, particularly around the use of albuterol. There are two main guidelines when it comes to asthma, the Global Initiative for Asthma (GINA) guideline and the US National Heart, Lung, and Blood Institute Guidelines. While I had the privilege of serving on the expert working group for the US guidelines, what I like about the GINA guidelines is that they are updated annually, and so they really help us keep up with rapid changes in the field.

Today, I’m going to focus on assessment and treatment.
 

Four Questions to Assess Asthma Control

Because over half of patients with asthma are not well controlled, it is important to assess control at every asthma visit. Asthma control has two domains: symptom control and the risk for future exacerbations. It is not enough to simply ask, “How is your asthma?” because many patients overrate their control and live with ongoing symptoms. There are many assessment tools; the Asthma Control Test (ACT) focuses on symptoms, and the new Asthma Impairment and Risk Questionnaire (AIRQ) assesses both symptoms and risk for exacerbations. The GINA assessment is probably the easiest to implement, with just four questions relevant to the past 4 weeks:

• Have you had daytime symptoms more than twice in one week?
• Have you had any night waking due to asthma?
• Have you needed short-acting beta-agonist (SABA), such as albuterol, rescue more than twice in one week?
• Have you had any activity limitation due to asthma?

Well-controlled asthma is defined as a negative response to all four of these questions, partly controlled asthma is one or two “yes” answers, and uncontrolled asthma is three to four positive responses. You can’t modify a patient’s therapy if you don’t know whether their asthma is well or poorly controlled. You’ll notice that these questions focus on symptom control. It is important also to ask about risk factors for exacerbations, particularly previous exacerbations.
 

Asthma Treatment Changes

The goals of treatment are control of symptoms and avoidance of exacerbations. The GINA guidelines emphasize that even patients with mild asthma can have severe or fatal exacerbations.

GINA recommends two management tracks. The preferred track uses inhaled corticosteroid (ICS)-formoterol as both maintenance and reliever therapy (MART). Track 2, without the use of ICS-formoterol for MART, is also offered, recognizing that the use of ICS-formoterol for MART is not approved by the US Food and Drug Administration. There is an easy-to-follow stepped-care diagram that is worth looking at; it’s on page 66 of the GINA guideline PDF.

For patients who have symptoms less than twice a month, begin with Step 1 therapy:

• Track 1: as-needed low-dose ICS-formoterol.
• Track 2: treatment with albuterol; also use ICS whenever albuterol is used.

For patients with symptoms more than twice a month (but not most days of the week) treatment can start with Step 2 therapy:

• Track 1: as-needed low-dose ICS-formoterol
• Track 2: daily low-dose ICS plus as-needed SABA

An option for rescue therapy for Track 2 across all steps of therapy is to use an ICS whenever a SABA is used for rescue to reduce the likelihood of exacerbation.

For patients with more severe asthma symptoms most days of the week, or whose asthma is waking them from sleep one or more times weekly, then you can start with Step 3 therapy as follows:

• Track 1: low dose ICS-formoterol as MART
• Track 2: low-dose ICS with long-acting beta-agonist (LABA) for maintenance, plus as needed SABA or as needed ICS-SABA

That’s going to cover most of our patients. As we see people back, if escalation of therapy is needed, then Step 4 therapy is:

• Track 1: medium-dose ICS-formoterol as MART
• Track 2: medium-dose ICS-LABA plus as needed SABA or as-needed ICS-SABA

For patients who remain uncontrolled, it’s important to realize that Step 5 gives you the option to add a long-acting muscarinic antagonist (LAMA). In my experience this can be very helpful. We can also consider going to high-dose ICS-LABS for maintenance. At this step, the patient usually has pretty severe, uncontrolled asthma and we can think about checking eosinophil counts, ordering pulmonary function tests, and referring to our specialist colleagues for consideration of biologic therapy.

It is important to see patients back regularly, and to assess asthma control. If a patient is not well controlled or has had exacerbations, consider stepping up therapy, or changing from albuterol alone as rescue to albuterol plus ICS for rescue. If they have been well controlled for a long time, consider de-escalation of therapy among patients on one of the higher therapy steps.

Dr. Skolnik has disclosed the following relevant financial relationships: Serve(d) on the advisory board for AstraZeneca, Teva, Eli Lilly and Company, Boehringer Ingelheim, Sanofi, Sanofi Pasteur, GlaxoSmithKline, Merck; and Bayer; serve(d) as a speaker or a member of a speakers bureau for AstraZeneca, Boehringer Ingelheim, Eli Lilly and Company, GlaxoSmithKline. Received research grant from Sanofi, AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, and Bayer; and received income in an amount equal to or greater than $250 from AstraZeneca, Teva, Eli Lilly and Company, Boehringer Ingelheim, Sanofi, Sanofi Pasteur, GlaxoSmithKline, Merck, and Bayer.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

I’m Dr. Neil Skolnik, and today I am going to talk about the 2023 update to the Global Strategy for Asthma Management and Prevention. We treat a lot of asthma, and there are some important changes, particularly around the use of albuterol. There are two main guidelines when it comes to asthma, the Global Initiative for Asthma (GINA) guideline and the US National Heart, Lung, and Blood Institute Guidelines. While I had the privilege of serving on the expert working group for the US guidelines, what I like about the GINA guidelines is that they are updated annually, and so they really help us keep up with rapid changes in the field.

Today, I’m going to focus on assessment and treatment.
 

Four Questions to Assess Asthma Control

Because over half of patients with asthma are not well controlled, it is important to assess control at every asthma visit. Asthma control has two domains: symptom control and the risk for future exacerbations. It is not enough to simply ask, “How is your asthma?” because many patients overrate their control and live with ongoing symptoms. There are many assessment tools; the Asthma Control Test (ACT) focuses on symptoms, and the new Asthma Impairment and Risk Questionnaire (AIRQ) assesses both symptoms and risk for exacerbations. The GINA assessment is probably the easiest to implement, with just four questions relevant to the past 4 weeks:

• Have you had daytime symptoms more than twice in one week?
• Have you had any night waking due to asthma?
• Have you needed short-acting beta-agonist (SABA), such as albuterol, rescue more than twice in one week?
• Have you had any activity limitation due to asthma?

Well-controlled asthma is defined as a negative response to all four of these questions, partly controlled asthma is one or two “yes” answers, and uncontrolled asthma is three to four positive responses. You can’t modify a patient’s therapy if you don’t know whether their asthma is well or poorly controlled. You’ll notice that these questions focus on symptom control. It is important also to ask about risk factors for exacerbations, particularly previous exacerbations.
 

Asthma Treatment Changes

The goals of treatment are control of symptoms and avoidance of exacerbations. The GINA guidelines emphasize that even patients with mild asthma can have severe or fatal exacerbations.

GINA recommends two management tracks. The preferred track uses inhaled corticosteroid (ICS)-formoterol as both maintenance and reliever therapy (MART). Track 2, without the use of ICS-formoterol for MART, is also offered, recognizing that the use of ICS-formoterol for MART is not approved by the US Food and Drug Administration. There is an easy-to-follow stepped-care diagram that is worth looking at; it’s on page 66 of the GINA guideline PDF.

For patients who have symptoms less than twice a month, begin with Step 1 therapy:

• Track 1: as-needed low-dose ICS-formoterol.
• Track 2: treatment with albuterol; also use ICS whenever albuterol is used.

For patients with symptoms more than twice a month (but not most days of the week) treatment can start with Step 2 therapy:

• Track 1: as-needed low-dose ICS-formoterol
• Track 2: daily low-dose ICS plus as-needed SABA

An option for rescue therapy for Track 2 across all steps of therapy is to use an ICS whenever a SABA is used for rescue to reduce the likelihood of exacerbation.

For patients with more severe asthma symptoms most days of the week, or whose asthma is waking them from sleep one or more times weekly, then you can start with Step 3 therapy as follows:

• Track 1: low dose ICS-formoterol as MART
• Track 2: low-dose ICS with long-acting beta-agonist (LABA) for maintenance, plus as needed SABA or as needed ICS-SABA

That’s going to cover most of our patients. As we see people back, if escalation of therapy is needed, then Step 4 therapy is:

• Track 1: medium-dose ICS-formoterol as MART
• Track 2: medium-dose ICS-LABA plus as needed SABA or as-needed ICS-SABA

For patients who remain uncontrolled, it’s important to realize that Step 5 gives you the option to add a long-acting muscarinic antagonist (LAMA). In my experience this can be very helpful. We can also consider going to high-dose ICS-LABS for maintenance. At this step, the patient usually has pretty severe, uncontrolled asthma and we can think about checking eosinophil counts, ordering pulmonary function tests, and referring to our specialist colleagues for consideration of biologic therapy.

It is important to see patients back regularly, and to assess asthma control. If a patient is not well controlled or has had exacerbations, consider stepping up therapy, or changing from albuterol alone as rescue to albuterol plus ICS for rescue. If they have been well controlled for a long time, consider de-escalation of therapy among patients on one of the higher therapy steps.

Dr. Skolnik has disclosed the following relevant financial relationships: Serve(d) on the advisory board for AstraZeneca, Teva, Eli Lilly and Company, Boehringer Ingelheim, Sanofi, Sanofi Pasteur, GlaxoSmithKline, Merck; and Bayer; serve(d) as a speaker or a member of a speakers bureau for AstraZeneca, Boehringer Ingelheim, Eli Lilly and Company, GlaxoSmithKline. Received research grant from Sanofi, AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, and Bayer; and received income in an amount equal to or greater than $250 from AstraZeneca, Teva, Eli Lilly and Company, Boehringer Ingelheim, Sanofi, Sanofi Pasteur, GlaxoSmithKline, Merck, and Bayer.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

I’m Dr. Neil Skolnik, and today I am going to talk about the 2023 update to the Global Strategy for Asthma Management and Prevention. We treat a lot of asthma, and there are some important changes, particularly around the use of albuterol. There are two main guidelines when it comes to asthma, the Global Initiative for Asthma (GINA) guideline and the US National Heart, Lung, and Blood Institute Guidelines. While I had the privilege of serving on the expert working group for the US guidelines, what I like about the GINA guidelines is that they are updated annually, and so they really help us keep up with rapid changes in the field.

Today, I’m going to focus on assessment and treatment.
 

Four Questions to Assess Asthma Control

Because over half of patients with asthma are not well controlled, it is important to assess control at every asthma visit. Asthma control has two domains: symptom control and the risk for future exacerbations. It is not enough to simply ask, “How is your asthma?” because many patients overrate their control and live with ongoing symptoms. There are many assessment tools; the Asthma Control Test (ACT) focuses on symptoms, and the new Asthma Impairment and Risk Questionnaire (AIRQ) assesses both symptoms and risk for exacerbations. The GINA assessment is probably the easiest to implement, with just four questions relevant to the past 4 weeks:

• Have you had daytime symptoms more than twice in one week?
• Have you had any night waking due to asthma?
• Have you needed short-acting beta-agonist (SABA), such as albuterol, rescue more than twice in one week?
• Have you had any activity limitation due to asthma?

Well-controlled asthma is defined as a negative response to all four of these questions, partly controlled asthma is one or two “yes” answers, and uncontrolled asthma is three to four positive responses. You can’t modify a patient’s therapy if you don’t know whether their asthma is well or poorly controlled. You’ll notice that these questions focus on symptom control. It is important also to ask about risk factors for exacerbations, particularly previous exacerbations.
 

Asthma Treatment Changes

The goals of treatment are control of symptoms and avoidance of exacerbations. The GINA guidelines emphasize that even patients with mild asthma can have severe or fatal exacerbations.

GINA recommends two management tracks. The preferred track uses inhaled corticosteroid (ICS)-formoterol as both maintenance and reliever therapy (MART). Track 2, without the use of ICS-formoterol for MART, is also offered, recognizing that the use of ICS-formoterol for MART is not approved by the US Food and Drug Administration. There is an easy-to-follow stepped-care diagram that is worth looking at; it’s on page 66 of the GINA guideline PDF.

For patients who have symptoms less than twice a month, begin with Step 1 therapy:

• Track 1: as-needed low-dose ICS-formoterol.
• Track 2: treatment with albuterol; also use ICS whenever albuterol is used.

For patients with symptoms more than twice a month (but not most days of the week) treatment can start with Step 2 therapy:

• Track 1: as-needed low-dose ICS-formoterol
• Track 2: daily low-dose ICS plus as-needed SABA

An option for rescue therapy for Track 2 across all steps of therapy is to use an ICS whenever a SABA is used for rescue to reduce the likelihood of exacerbation.

For patients with more severe asthma symptoms most days of the week, or whose asthma is waking them from sleep one or more times weekly, then you can start with Step 3 therapy as follows:

• Track 1: low dose ICS-formoterol as MART
• Track 2: low-dose ICS with long-acting beta-agonist (LABA) for maintenance, plus as needed SABA or as needed ICS-SABA

That’s going to cover most of our patients. As we see people back, if escalation of therapy is needed, then Step 4 therapy is:

• Track 1: medium-dose ICS-formoterol as MART
• Track 2: medium-dose ICS-LABA plus as needed SABA or as-needed ICS-SABA

For patients who remain uncontrolled, it’s important to realize that Step 5 gives you the option to add a long-acting muscarinic antagonist (LAMA). In my experience this can be very helpful. We can also consider going to high-dose ICS-LABS for maintenance. At this step, the patient usually has pretty severe, uncontrolled asthma and we can think about checking eosinophil counts, ordering pulmonary function tests, and referring to our specialist colleagues for consideration of biologic therapy.

It is important to see patients back regularly, and to assess asthma control. If a patient is not well controlled or has had exacerbations, consider stepping up therapy, or changing from albuterol alone as rescue to albuterol plus ICS for rescue. If they have been well controlled for a long time, consider de-escalation of therapy among patients on one of the higher therapy steps.

Dr. Skolnik has disclosed the following relevant financial relationships: Serve(d) on the advisory board for AstraZeneca, Teva, Eli Lilly and Company, Boehringer Ingelheim, Sanofi, Sanofi Pasteur, GlaxoSmithKline, Merck; and Bayer; serve(d) as a speaker or a member of a speakers bureau for AstraZeneca, Boehringer Ingelheim, Eli Lilly and Company, GlaxoSmithKline. Received research grant from Sanofi, AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, and Bayer; and received income in an amount equal to or greater than $250 from AstraZeneca, Teva, Eli Lilly and Company, Boehringer Ingelheim, Sanofi, Sanofi Pasteur, GlaxoSmithKline, Merck, and Bayer.

A version of this article appeared on Medscape.com.

TOPLINE:

Resecting the primary colon tumor before chemotherapy does not improve overall survival compared with chemotherapy alone in patients with metastatic colon cancer not amenable to curative therapy, new data showed.

METHODOLOGY:

• Chemotherapy is the primary treatment in patients with stage IV  (CRC) and unresectable metastases. It’s unclear whether primary tumor resection before chemotherapy prolongs survival.
• Among 393 patients with stage IV colon cancer and unresectable metastases enrolled in the  and  trials, 187 were randomly allocated to undergo primary tumor resection and 206 to upfront chemotherapy.
• The chemotherapy regimen was left up to the treating physician. Overall survival was the primary endpoint. Median follow-up time was 36.7 months.

TAKEAWAY:

• Median overall survival was 16.7 months with primary tumor resection and 18.6 months with upfront chemotherapy (P = .191).
• Comparable overall survival between the study groups was further confirmed on multivariate analysis (hazard ratio, 0.944; P = .65) and across all subgroups.
• Serious adverse events were more common with upfront chemo than surgery (18% vs 10%; P = .027), due mainly to a significantly higher incidence of GI-related events (11% vs 5%; P = .031).
• Overall, 24% of the primary tumor resection group did not receive any chemotherapy.

IN PRACTICE:

“The results of our study provide compelling data that upfront primary tumor resection in treatment-naive stage IV CRC not amenable for curative treatment does not prolong [overall survival]. A relatively low incidence of serious adverse events in patients with an intact primary tumor together with a considerable number of patients who did not receive any chemotherapy in the primary tumor resection group provides further arguments against resection of the primary tumor in this group of patients,” the authors of the combined analysis concluded.

SOURCE:

The study, with first author Nuh N. Rahbari, MD, University of Ulm, Ulm, Germany, was published online in the Journal of Clinical Oncology.

LIMITATIONS:

Neither study completed their planned patient accrual. Although both trials are nearly identical, differences in the individual study cohorts and trial implementation could have introduced bias. Tumor molecular profiling was not performed.

DISCLOSURES:

The study had no commercial funding. Disclosures for authors are available with the original article.

A version of this article appeared on Medscape.com.

TOPLINE:

Resecting the primary colon tumor before chemotherapy does not improve overall survival compared with chemotherapy alone in patients with metastatic colon cancer not amenable to curative therapy, new data showed.

METHODOLOGY:

• Chemotherapy is the primary treatment in patients with stage IV  (CRC) and unresectable metastases. It’s unclear whether primary tumor resection before chemotherapy prolongs survival.
• Among 393 patients with stage IV colon cancer and unresectable metastases enrolled in the  and  trials, 187 were randomly allocated to undergo primary tumor resection and 206 to upfront chemotherapy.
• The chemotherapy regimen was left up to the treating physician. Overall survival was the primary endpoint. Median follow-up time was 36.7 months.

TAKEAWAY:

• Median overall survival was 16.7 months with primary tumor resection and 18.6 months with upfront chemotherapy (P = .191).
• Comparable overall survival between the study groups was further confirmed on multivariate analysis (hazard ratio, 0.944; P = .65) and across all subgroups.
• Serious adverse events were more common with upfront chemo than surgery (18% vs 10%; P = .027), due mainly to a significantly higher incidence of GI-related events (11% vs 5%; P = .031).
• Overall, 24% of the primary tumor resection group did not receive any chemotherapy.

IN PRACTICE:

“The results of our study provide compelling data that upfront primary tumor resection in treatment-naive stage IV CRC not amenable for curative treatment does not prolong [overall survival]. A relatively low incidence of serious adverse events in patients with an intact primary tumor together with a considerable number of patients who did not receive any chemotherapy in the primary tumor resection group provides further arguments against resection of the primary tumor in this group of patients,” the authors of the combined analysis concluded.

SOURCE:

The study, with first author Nuh N. Rahbari, MD, University of Ulm, Ulm, Germany, was published online in the Journal of Clinical Oncology.

LIMITATIONS:

Neither study completed their planned patient accrual. Although both trials are nearly identical, differences in the individual study cohorts and trial implementation could have introduced bias. Tumor molecular profiling was not performed.

DISCLOSURES:

The study had no commercial funding. Disclosures for authors are available with the original article.

A version of this article appeared on Medscape.com.

TOPLINE:

Resecting the primary colon tumor before chemotherapy does not improve overall survival compared with chemotherapy alone in patients with metastatic colon cancer not amenable to curative therapy, new data showed.

METHODOLOGY:

• Chemotherapy is the primary treatment in patients with stage IV  (CRC) and unresectable metastases. It’s unclear whether primary tumor resection before chemotherapy prolongs survival.
• Among 393 patients with stage IV colon cancer and unresectable metastases enrolled in the  and  trials, 187 were randomly allocated to undergo primary tumor resection and 206 to upfront chemotherapy.
• The chemotherapy regimen was left up to the treating physician. Overall survival was the primary endpoint. Median follow-up time was 36.7 months.

TAKEAWAY:

• Median overall survival was 16.7 months with primary tumor resection and 18.6 months with upfront chemotherapy (P = .191).
• Comparable overall survival between the study groups was further confirmed on multivariate analysis (hazard ratio, 0.944; P = .65) and across all subgroups.
• Serious adverse events were more common with upfront chemo than surgery (18% vs 10%; P = .027), due mainly to a significantly higher incidence of GI-related events (11% vs 5%; P = .031).
• Overall, 24% of the primary tumor resection group did not receive any chemotherapy.

IN PRACTICE:

“The results of our study provide compelling data that upfront primary tumor resection in treatment-naive stage IV CRC not amenable for curative treatment does not prolong [overall survival]. A relatively low incidence of serious adverse events in patients with an intact primary tumor together with a considerable number of patients who did not receive any chemotherapy in the primary tumor resection group provides further arguments against resection of the primary tumor in this group of patients,” the authors of the combined analysis concluded.

SOURCE:

The study, with first author Nuh N. Rahbari, MD, University of Ulm, Ulm, Germany, was published online in the Journal of Clinical Oncology.

LIMITATIONS:

Neither study completed their planned patient accrual. Although both trials are nearly identical, differences in the individual study cohorts and trial implementation could have introduced bias. Tumor molecular profiling was not performed.

DISCLOSURES:

The study had no commercial funding. Disclosures for authors are available with the original article.

A version of this article appeared on Medscape.com.

Syphilis and chlamydia infections were reduced by half among men who have sex with men and transgender women 1 year after San Francisco rolled out doxycycline postexposure prophylaxis (doxy-PEP), according to data presented at the Conference on Retroviruses and Opportunistic Infections (CROI) this week.

After a clinical trial showed that doxy-PEP taken after sex reduced the chance of acquiring syphilis, gonorrhea, and chlamydia by about two-thirds, the San Francisco Department of Public Health released the first guidelines in the country in October 2022. 

The guidelines recommend that a person take two 100-mg pills of doxycycline ideally in the 24 hours after but no more than 72 hours after condomless sex. So far, more than 3700 people in San Francisco have been prescribed doxy-PEP, reports Stephanie Cohen, MD, director of HIV and sexually transmitted infection (STI) prevention in the Disease Prevention and Control Branch of Public Health.

Dr. Cohen and her colleagues spent a year monitoring the uptake of doxy-PEP and used a computer model to predict what the rates of sexually transmitted infection would have been without doxy-PEP. 

In November 2023, 13 months after the guidelines were introduced, they found that monthly chlamydia and early syphilis infections were 50% and 51% lower, respectively, than what was predicted by the model.
 

Fewer Infections

The drop in infections is having a tangible effect on patients in San Francisco, and many clinicians are noting that they are seeing far fewer positive tests. “The results that we’re seeing on a city-wide level are absolutely being experienced by individual providers and patients,” Dr. Cohen said.

However, the analysis showed no effect on rates of gonorrhea. It’s not clear why, although Dr. Cohen points out that doxy-PEP was less effective against gonorrhea in the clinical trial. And “there could be other factors in play,” she added. “Adherence might matter more, or it could be affected by the prevalence of tetracycline resistance in the community.”

With rates of STIs, particularly syphilis, quickly rising in recent years, healthcare providers have been scrambling to find effective interventions. So far, doxy-PEP has shown the most promise. “We’ve known for a while that all of the strategies we’ve been employing don’t seem to be working,” noted Chase Cannon, MD, an infectious disease specialist at the University of Washington in Seattle. “That’s why doxy-PEP is important. We haven’t had anything that can deflect the curve in a long time.”
 

What About the Side Effects?

Some concerns remain, however, about the widespread prophylactic use of antibiotics. There are no long-term safety data on the potential side effects of doxy-PEP, and there is still a lot of stigma around interventions that allow people to have sex the way they want, said Dr. Cannon.

But perhaps, the biggest concern is that doxy-PEP could contribute to antibiotic resistance. Those fears are not misplaced, Dr. Cannon added. The results of one study, presented in a poster at CROI, showed that stool samples from people prescribed doxy-PEP had elevated levels of bacterial genes that can confer resistance to tetracyclines, the class of antibiotics to which doxycycline belongs. There was no change in resistance to other classes of antibiotics and no difference in bacterial diversity over the 6 months of the study.

Dr. Cannon cautioned, however, that we can’t extrapolate these results to clinical outcomes. “We can look for signals [of resistance], but we don’t know if this means someone will fail therapy for chlamydia or syphilis,” he said.

There are still many challenges to overcome before doxy-PEP can be rolled out widely, Dr. Cohen explained. There is a lack of consensus among healthcare professionals about who should be offered doxy-PEP. The clinical trial results and the San Fransisco guidelines only apply to men who have sex with men and to transgender women.

Some clinicians argue that the intervention should be provided to a broader population, whereas others want to see more research to ensure that unnecessary antibiotic use is minimized.

So far just one study has tested doxy-PEP in another population — in women in Kenya — and it was found to not be effective. But the data suggest that adherence to the protocol was poor in that study, so the results may not be reliable, Dr. Cohen said.

“We need effective prevention tools for all genders, especially cis women who bear most of the morbidity,” she said. “It stands to reason that this should work for them, but without high-quality evidence, there is insufficient information to make a recommendation for cis women.”

The US Centers for Disease Control and Prevention is currently reviewing public and expert comments and refining final guidelines for release in the coming months, which should alleviate some of the uncertainty. “Many providers are waiting for that guidance before they will feel confident moving forward,” Dr. Cohen noted.

But despite the risks and uncertainty, doxy-PEP looks set to be a major part of the fight against STIs going forward. “Doxy-PEP is essential for us as a nation to be dealing with the syphilis epidemic,” Carl Dieffenbach, PhD, director of the Division of AIDS at the National Institute of Allergy and Infectious Disease, said in a video introduction to CROI.

A version of this article appeared on Medscape.com.

Syphilis and chlamydia infections were reduced by half among men who have sex with men and transgender women 1 year after San Francisco rolled out doxycycline postexposure prophylaxis (doxy-PEP), according to data presented at the Conference on Retroviruses and Opportunistic Infections (CROI) this week.

After a clinical trial showed that doxy-PEP taken after sex reduced the chance of acquiring syphilis, gonorrhea, and chlamydia by about two-thirds, the San Francisco Department of Public Health released the first guidelines in the country in October 2022. 

The guidelines recommend that a person take two 100-mg pills of doxycycline ideally in the 24 hours after but no more than 72 hours after condomless sex. So far, more than 3700 people in San Francisco have been prescribed doxy-PEP, reports Stephanie Cohen, MD, director of HIV and sexually transmitted infection (STI) prevention in the Disease Prevention and Control Branch of Public Health.

Dr. Cohen and her colleagues spent a year monitoring the uptake of doxy-PEP and used a computer model to predict what the rates of sexually transmitted infection would have been without doxy-PEP. 

In November 2023, 13 months after the guidelines were introduced, they found that monthly chlamydia and early syphilis infections were 50% and 51% lower, respectively, than what was predicted by the model.
 

Fewer Infections

The drop in infections is having a tangible effect on patients in San Francisco, and many clinicians are noting that they are seeing far fewer positive tests. “The results that we’re seeing on a city-wide level are absolutely being experienced by individual providers and patients,” Dr. Cohen said.

However, the analysis showed no effect on rates of gonorrhea. It’s not clear why, although Dr. Cohen points out that doxy-PEP was less effective against gonorrhea in the clinical trial. And “there could be other factors in play,” she added. “Adherence might matter more, or it could be affected by the prevalence of tetracycline resistance in the community.”

With rates of STIs, particularly syphilis, quickly rising in recent years, healthcare providers have been scrambling to find effective interventions. So far, doxy-PEP has shown the most promise. “We’ve known for a while that all of the strategies we’ve been employing don’t seem to be working,” noted Chase Cannon, MD, an infectious disease specialist at the University of Washington in Seattle. “That’s why doxy-PEP is important. We haven’t had anything that can deflect the curve in a long time.”
 

What About the Side Effects?

Some concerns remain, however, about the widespread prophylactic use of antibiotics. There are no long-term safety data on the potential side effects of doxy-PEP, and there is still a lot of stigma around interventions that allow people to have sex the way they want, said Dr. Cannon.

But perhaps, the biggest concern is that doxy-PEP could contribute to antibiotic resistance. Those fears are not misplaced, Dr. Cannon added. The results of one study, presented in a poster at CROI, showed that stool samples from people prescribed doxy-PEP had elevated levels of bacterial genes that can confer resistance to tetracyclines, the class of antibiotics to which doxycycline belongs. There was no change in resistance to other classes of antibiotics and no difference in bacterial diversity over the 6 months of the study.

Dr. Cannon cautioned, however, that we can’t extrapolate these results to clinical outcomes. “We can look for signals [of resistance], but we don’t know if this means someone will fail therapy for chlamydia or syphilis,” he said.

There are still many challenges to overcome before doxy-PEP can be rolled out widely, Dr. Cohen explained. There is a lack of consensus among healthcare professionals about who should be offered doxy-PEP. The clinical trial results and the San Fransisco guidelines only apply to men who have sex with men and to transgender women.

Some clinicians argue that the intervention should be provided to a broader population, whereas others want to see more research to ensure that unnecessary antibiotic use is minimized.

So far just one study has tested doxy-PEP in another population — in women in Kenya — and it was found to not be effective. But the data suggest that adherence to the protocol was poor in that study, so the results may not be reliable, Dr. Cohen said.

“We need effective prevention tools for all genders, especially cis women who bear most of the morbidity,” she said. “It stands to reason that this should work for them, but without high-quality evidence, there is insufficient information to make a recommendation for cis women.”

The US Centers for Disease Control and Prevention is currently reviewing public and expert comments and refining final guidelines for release in the coming months, which should alleviate some of the uncertainty. “Many providers are waiting for that guidance before they will feel confident moving forward,” Dr. Cohen noted.

But despite the risks and uncertainty, doxy-PEP looks set to be a major part of the fight against STIs going forward. “Doxy-PEP is essential for us as a nation to be dealing with the syphilis epidemic,” Carl Dieffenbach, PhD, director of the Division of AIDS at the National Institute of Allergy and Infectious Disease, said in a video introduction to CROI.

A version of this article appeared on Medscape.com.

Syphilis and chlamydia infections were reduced by half among men who have sex with men and transgender women 1 year after San Francisco rolled out doxycycline postexposure prophylaxis (doxy-PEP), according to data presented at the Conference on Retroviruses and Opportunistic Infections (CROI) this week.

After a clinical trial showed that doxy-PEP taken after sex reduced the chance of acquiring syphilis, gonorrhea, and chlamydia by about two-thirds, the San Francisco Department of Public Health released the first guidelines in the country in October 2022. 

The guidelines recommend that a person take two 100-mg pills of doxycycline ideally in the 24 hours after but no more than 72 hours after condomless sex. So far, more than 3700 people in San Francisco have been prescribed doxy-PEP, reports Stephanie Cohen, MD, director of HIV and sexually transmitted infection (STI) prevention in the Disease Prevention and Control Branch of Public Health.

Dr. Cohen and her colleagues spent a year monitoring the uptake of doxy-PEP and used a computer model to predict what the rates of sexually transmitted infection would have been without doxy-PEP. 

In November 2023, 13 months after the guidelines were introduced, they found that monthly chlamydia and early syphilis infections were 50% and 51% lower, respectively, than what was predicted by the model.
 

Fewer Infections

The drop in infections is having a tangible effect on patients in San Francisco, and many clinicians are noting that they are seeing far fewer positive tests. “The results that we’re seeing on a city-wide level are absolutely being experienced by individual providers and patients,” Dr. Cohen said.

However, the analysis showed no effect on rates of gonorrhea. It’s not clear why, although Dr. Cohen points out that doxy-PEP was less effective against gonorrhea in the clinical trial. And “there could be other factors in play,” she added. “Adherence might matter more, or it could be affected by the prevalence of tetracycline resistance in the community.”

With rates of STIs, particularly syphilis, quickly rising in recent years, healthcare providers have been scrambling to find effective interventions. So far, doxy-PEP has shown the most promise. “We’ve known for a while that all of the strategies we’ve been employing don’t seem to be working,” noted Chase Cannon, MD, an infectious disease specialist at the University of Washington in Seattle. “That’s why doxy-PEP is important. We haven’t had anything that can deflect the curve in a long time.”
 

What About the Side Effects?

Some concerns remain, however, about the widespread prophylactic use of antibiotics. There are no long-term safety data on the potential side effects of doxy-PEP, and there is still a lot of stigma around interventions that allow people to have sex the way they want, said Dr. Cannon.

But perhaps, the biggest concern is that doxy-PEP could contribute to antibiotic resistance. Those fears are not misplaced, Dr. Cannon added. The results of one study, presented in a poster at CROI, showed that stool samples from people prescribed doxy-PEP had elevated levels of bacterial genes that can confer resistance to tetracyclines, the class of antibiotics to which doxycycline belongs. There was no change in resistance to other classes of antibiotics and no difference in bacterial diversity over the 6 months of the study.

Dr. Cannon cautioned, however, that we can’t extrapolate these results to clinical outcomes. “We can look for signals [of resistance], but we don’t know if this means someone will fail therapy for chlamydia or syphilis,” he said.

There are still many challenges to overcome before doxy-PEP can be rolled out widely, Dr. Cohen explained. There is a lack of consensus among healthcare professionals about who should be offered doxy-PEP. The clinical trial results and the San Fransisco guidelines only apply to men who have sex with men and to transgender women.

Some clinicians argue that the intervention should be provided to a broader population, whereas others want to see more research to ensure that unnecessary antibiotic use is minimized.

So far just one study has tested doxy-PEP in another population — in women in Kenya — and it was found to not be effective. But the data suggest that adherence to the protocol was poor in that study, so the results may not be reliable, Dr. Cohen said.

“We need effective prevention tools for all genders, especially cis women who bear most of the morbidity,” she said. “It stands to reason that this should work for them, but without high-quality evidence, there is insufficient information to make a recommendation for cis women.”

The US Centers for Disease Control and Prevention is currently reviewing public and expert comments and refining final guidelines for release in the coming months, which should alleviate some of the uncertainty. “Many providers are waiting for that guidance before they will feel confident moving forward,” Dr. Cohen noted.

But despite the risks and uncertainty, doxy-PEP looks set to be a major part of the fight against STIs going forward. “Doxy-PEP is essential for us as a nation to be dealing with the syphilis epidemic,” Carl Dieffenbach, PhD, director of the Division of AIDS at the National Institute of Allergy and Infectious Disease, said in a video introduction to CROI.

A version of this article appeared on Medscape.com.

TOPLINE:

Treatment modifications, such as dose reductions, schedule changes, or use of less toxic regimens, can improve how well older patients with advanced cancer and aging-related conditions tolerate chemotherapy regimens.

METHODOLOGY:

• Older patients are underrepresented in clinical trials, which means the reported risks associated with standard-of-care regimens typically reflect outcomes in younger, healthier patients. This underrepresentation in clinical trials has also led to uncertainties about the safety of standard chemotherapy regimens in older patients who often have other health conditions to manage, alongside cancer.
• In this secondary analysis, researchers evaluated the association between primary treatment modifications to standard-of-care chemotherapy regimens and treatment tolerability.
• The trial included 609 patients aged ≥ 70 years who had advanced cancer alongside at least one age-related condition, such as impaired cognition, and planned to start a new palliative chemotherapy regimen in the community oncology setting. The most common cancer types were gastrointestinal cancer (37.4%) and lung cancer (28.6%).
• The primary outcome was grade 3-5 adverse events within 3 months of chemotherapy initiation.
• Secondary outcomes included patient-reported functional decline and combined adverse outcomes, which incorporated clinician-rated toxic effects, patient-reported functional decline, and 6-month overall survival.

TAKEAWAY: 

• Overall, 281 patients (46.1%) received a primary treatment modification, most often a dose reduction (71.9%) or a scheduling change (11.7%).
• Patients who received primary treatment modifications had a 15% lower risk for grades 3-5 adverse effects (relative risk [RR], 0.85) and a 20% lower risk for patient-reported functional decline (RR, 0.80) than those who received standard treatment.
• Patients receiving treatment modifications had 32% lower risk for a worse combined adverse outcome (odds ratio, 0.68).
• Cancer type may matter as well. When looking at outcomes by cancer type, patients with gastrointestinal cancers who received a primary treatment modification had a lower risk for toxic effects (RR, 0.82), whereas patients with lung cancer did not (RR, 1.03; 95% CI, 0.88-1.20).

IN PRACTICE:

These findings “can help oncologists to choose the optimal drug regimen, select a safe and effective initial dose, and undertake appropriate monitoring strategies to manage the clinical care of older people with advanced cancer,” the authors said. 

SOURCE:

This study, led by Mostafa R. Mohamed from University of Rochester, New York, was published February 15 in JAMA Network Open.

LIMITATIONS: 

Residual confounding may be present. Extremely healthy older patients may have been excluded due to study criteria, limiting generalizability. There may be variation in toxicities due to inclusion of patients with multiple heterogeneous cancer.

DISCLOSURES:

This work was supported by the National Cancer Institute and the University of Rochester, New York. The authors disclosed financial relationships outside this work.

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

TOPLINE:

Treatment modifications, such as dose reductions, schedule changes, or use of less toxic regimens, can improve how well older patients with advanced cancer and aging-related conditions tolerate chemotherapy regimens.

METHODOLOGY:

• Older patients are underrepresented in clinical trials, which means the reported risks associated with standard-of-care regimens typically reflect outcomes in younger, healthier patients. This underrepresentation in clinical trials has also led to uncertainties about the safety of standard chemotherapy regimens in older patients who often have other health conditions to manage, alongside cancer.
• In this secondary analysis, researchers evaluated the association between primary treatment modifications to standard-of-care chemotherapy regimens and treatment tolerability.
• The trial included 609 patients aged ≥ 70 years who had advanced cancer alongside at least one age-related condition, such as impaired cognition, and planned to start a new palliative chemotherapy regimen in the community oncology setting. The most common cancer types were gastrointestinal cancer (37.4%) and lung cancer (28.6%).
• The primary outcome was grade 3-5 adverse events within 3 months of chemotherapy initiation.
• Secondary outcomes included patient-reported functional decline and combined adverse outcomes, which incorporated clinician-rated toxic effects, patient-reported functional decline, and 6-month overall survival.

TAKEAWAY: 

• Overall, 281 patients (46.1%) received a primary treatment modification, most often a dose reduction (71.9%) or a scheduling change (11.7%).
• Patients who received primary treatment modifications had a 15% lower risk for grades 3-5 adverse effects (relative risk [RR], 0.85) and a 20% lower risk for patient-reported functional decline (RR, 0.80) than those who received standard treatment.
• Patients receiving treatment modifications had 32% lower risk for a worse combined adverse outcome (odds ratio, 0.68).
• Cancer type may matter as well. When looking at outcomes by cancer type, patients with gastrointestinal cancers who received a primary treatment modification had a lower risk for toxic effects (RR, 0.82), whereas patients with lung cancer did not (RR, 1.03; 95% CI, 0.88-1.20).

IN PRACTICE:

These findings “can help oncologists to choose the optimal drug regimen, select a safe and effective initial dose, and undertake appropriate monitoring strategies to manage the clinical care of older people with advanced cancer,” the authors said. 

SOURCE:

This study, led by Mostafa R. Mohamed from University of Rochester, New York, was published February 15 in JAMA Network Open.

LIMITATIONS: 

Residual confounding may be present. Extremely healthy older patients may have been excluded due to study criteria, limiting generalizability. There may be variation in toxicities due to inclusion of patients with multiple heterogeneous cancer.

DISCLOSURES:

This work was supported by the National Cancer Institute and the University of Rochester, New York. The authors disclosed financial relationships outside this work.

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

TOPLINE:

Treatment modifications, such as dose reductions, schedule changes, or use of less toxic regimens, can improve how well older patients with advanced cancer and aging-related conditions tolerate chemotherapy regimens.

METHODOLOGY:

• Older patients are underrepresented in clinical trials, which means the reported risks associated with standard-of-care regimens typically reflect outcomes in younger, healthier patients. This underrepresentation in clinical trials has also led to uncertainties about the safety of standard chemotherapy regimens in older patients who often have other health conditions to manage, alongside cancer.
• In this secondary analysis, researchers evaluated the association between primary treatment modifications to standard-of-care chemotherapy regimens and treatment tolerability.
• The trial included 609 patients aged ≥ 70 years who had advanced cancer alongside at least one age-related condition, such as impaired cognition, and planned to start a new palliative chemotherapy regimen in the community oncology setting. The most common cancer types were gastrointestinal cancer (37.4%) and lung cancer (28.6%).
• The primary outcome was grade 3-5 adverse events within 3 months of chemotherapy initiation.
• Secondary outcomes included patient-reported functional decline and combined adverse outcomes, which incorporated clinician-rated toxic effects, patient-reported functional decline, and 6-month overall survival.

TAKEAWAY: 

• Overall, 281 patients (46.1%) received a primary treatment modification, most often a dose reduction (71.9%) or a scheduling change (11.7%).
• Patients who received primary treatment modifications had a 15% lower risk for grades 3-5 adverse effects (relative risk [RR], 0.85) and a 20% lower risk for patient-reported functional decline (RR, 0.80) than those who received standard treatment.
• Patients receiving treatment modifications had 32% lower risk for a worse combined adverse outcome (odds ratio, 0.68).
• Cancer type may matter as well. When looking at outcomes by cancer type, patients with gastrointestinal cancers who received a primary treatment modification had a lower risk for toxic effects (RR, 0.82), whereas patients with lung cancer did not (RR, 1.03; 95% CI, 0.88-1.20).

IN PRACTICE:

These findings “can help oncologists to choose the optimal drug regimen, select a safe and effective initial dose, and undertake appropriate monitoring strategies to manage the clinical care of older people with advanced cancer,” the authors said. 

SOURCE:

This study, led by Mostafa R. Mohamed from University of Rochester, New York, was published February 15 in JAMA Network Open.

LIMITATIONS: 

Residual confounding may be present. Extremely healthy older patients may have been excluded due to study criteria, limiting generalizability. There may be variation in toxicities due to inclusion of patients with multiple heterogeneous cancer.

DISCLOSURES:

This work was supported by the National Cancer Institute and the University of Rochester, New York. The authors disclosed financial relationships outside this work.

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

Bone-modifying agents — most notably denosumab — are often prescribed to prevent skeletal-related complications in patients with metastatic castration-sensitive prostate cancer, but the drugs are not recommended for this indication and can lead to severe toxicities.

How much does Medicare spend each year on non-recommended bone therapy?

The answer, according to a new analysis in JCO Oncology Practice, is more than $44 million, with about $43 million coming from denosumab alone.

Overall, this study found that “the Medicare program pays tens of millions of dollars each year” for bone-modifying agents in patients with metastatic castration-sensitive prostate cancer, “which is not effective and may cause side effects,” lead author Aaron Mitchell, MD, MPH, a medical oncologist at Memorial Sloan Kettering Cancer Center, New York City, and colleagues concluded.

“These findings suggest reducing bone agent overuse could be a rare healthcare ‘win-win.’ Lower costs AND improved patient outcomes,” tweeted Dr. Mitchell. “If I were a payer, I’d be paying attention!”
 

In Prostate Cancer, Bone-Modifying Drug Indications Vary

Bone-modifying drugs are indicated for some patients with prostate cancer.

The American Society of Clinical Oncology has endorsed guidelines that recommend the use of denosumab in men with nonmetastatic prostate cancer at high risk for fracture while taking androgen deprivation therapy.

Among men with metastatic castration-resistant prostate cancer, guidelines also recommend zoledronic acid or denosumab for preventing or delaying skeletal-related events, such as pathologic fractures and spinal cord compression.

For patients with metastatic castration-sensitive disease, however, the bone-modifying agents show no benefit in preventing skeletal-related events and are not recommended for that indication.

In this population, “treatment with bone agents results only in avoidable toxicity and financial cost,” Dr. Mitchell tweeted. In its higher-dose formulation, denosumab comes with a price tag of approximately $40,000 per year in the United States.

An earlier study from Dr. Mitchell and colleagues revealed that the use of bone-modifying drugs to prevent skeletal events in metastatic castration-sensitive prostate cancer is common.

To better understand the costs associated with this inappropriate use, the researchers reviewed Surveillance, Epidemiology, and End Results Program Medicare data from 2011 to 2015. The team identified the frequency and number of doses of zoledronic acid and denosumab prescribed against recommendations in the metastatic castration-sensitive setting, making sure to distinguish between the use of denosumab to prevent osteoporotic fractures (appropriate use) and to prevent skeletal-related events (non-recommended use).

The team found that, among 2627 patients with metastatic castration-sensitive prostate cancer, 42% received at least one dose of denosumab and 18% received at least one dose of zoledronic acid.

The authors also found that unnecessary use of these drugs increased over time — with a little over 17% of patients receiving zoledronic acid between 2007 and 2009 and just over 28% receiving either denosumab (20.3%) or zoledronic acid (8.4%) from 2012 to 2015.

The annual costs to Medicare from non-recommended prescribing came to $44,105,041 for both agents, with the costs associated with denosumab representing the lion’s share at $43,303,078.

Non-recommended use of these agents also came with adverse events, such as femur fracture and hypocalcemia, which cost an estimated $758,450 to treat annually — $682,865 for denosumab and $75,585 for zoledronic acid.

The study focused on the Medicare-age population, which means the estimates are conservative. “Denosumab overuse for younger patients with castration-sensitive prostate cancer would add substantially to this total,” the authors wrote.

“This study contributes new evidence of overuse in the metastatic castrate-sensitive prostate cancer setting, which I must admit reflects my clinical experience in seeing patients for second opinions who are treated in the community,” said Samuel U. Takvorian, MD, of the Division of Hematology and Oncology, Perelman School of Medicine, Philadelphia, who wasn’t involved in the research. “While there are some circumstances in which one would consider using a bone-modifying agent in the metastatic castrate-sensitive prostate cancer setting, most [of these] men don’t need them upfront.”
 

Why Is the Overuse Happening?

One reason for the inappropriate use of bone-modifying drugs could be confusion surrounding the recommendations because the drugs are recommended for some patients with prostate cancer.

Michael R. Laurent, MD, PhD, of Imelda Hospital, Bonheiden, Belgium, explained that the use of bone-modifying drugs is, paradoxically, often overlooked in settings where they are recommended — when patients have an elevated risk for osteoporosis or fracture.

“Guidelines are quite unequivocal in their recommendations to prevent osteoporosis in mostly older men who receive androgen deprivation therapy,” but “I think there is significant undertreatment” in these patients, Dr. Laurent told this news organization.

However, the recommendation for patients at risk for osteoporosis or bone fracture calls for less intense regimens, which may include lower-dose denosumab, administered once every 6 months, zoledronic acid, given yearly, or another lower potency agent, such as oral alendronate weekly, explained Philip J. Saylor, MD, an attending physician at Massachusetts General Hospital and assistant professor at Harvard Medical School, Boston.

Meanwhile, “monthly high-intensity therapy to prevent skeletal events should be reserved specifically for bone metastatic castration-resistant prostate cancer for more than just cost reasons,” Dr. Saylor said.

When it comes to the higher dose, monthly therapy in castration-sensitive prostate cancer, “we have no evidence that it is beneficial,” he said, adding that “when the prostate cancer itself is well controlled by hormonal therapy, there just aren’t very many pathologic fractures or other bone complications.”

Alongside possible confusion over the recommendations, many physicians also likely don’t know how much denosumab costs.

“In our recent physician interview study, we did find that most physicians were very much unaware of the cost of this drug, or the cost difference between denosumab and zoledronic acid, so I do think that lack of cost awareness is a factor,” Dr. Mitchell said.

Part of the reason may be how Medicare covers these agents. Typically, Medicare would not cover non-recommended indications, but “in this case, Medicare coverage is broader and includes both the guideline-recommended and non-recommended uses,” Dr. Mitchell explained.

However, the authors also identified a more cynical reason for non-recommended prescribing — promotional payments from drug makers to physicians.

In another recent paper, Dr. Mitchell said he found about “30% of doctors treating prostate cancer had received payments from Amgen for Xgeva [denosumab] promotion during the last year.”

These payments appeared to influence non-recommended prescribing: Among patients whose doctor had not received payments, 31.4% received non-recommended denosumab, which increased to nearly 50% of patients among doctors who had received payments.

Dr. Mitchell suggested a few ways to help curb inappropriate prescribing.

Medicare could, for instance, change its coverage policy to include only the recommended uses of these agents, Dr. Mitchell said.

More physician education would be another solution. “I think that physician education would be one ‘bottom-up’ approach that could work,” Dr. Mitchell added.

Dr. Mitchell, Dr. Takvorian, and Dr. Saylor had no disclosures to report. Dr. Laurent has received lecture and consultancy fees from Alexion, AM Pharma, Amgen, Galapagos, Kyowa Kirin, Menarini, Orifarm, Pharmanovia, Takeda, UCB, and Will Pharma.
 

A version of this article appeared on Medscape.com.

Bone-modifying agents — most notably denosumab — are often prescribed to prevent skeletal-related complications in patients with metastatic castration-sensitive prostate cancer, but the drugs are not recommended for this indication and can lead to severe toxicities.

How much does Medicare spend each year on non-recommended bone therapy?

The answer, according to a new analysis in JCO Oncology Practice, is more than $44 million, with about $43 million coming from denosumab alone.

Overall, this study found that “the Medicare program pays tens of millions of dollars each year” for bone-modifying agents in patients with metastatic castration-sensitive prostate cancer, “which is not effective and may cause side effects,” lead author Aaron Mitchell, MD, MPH, a medical oncologist at Memorial Sloan Kettering Cancer Center, New York City, and colleagues concluded.

“These findings suggest reducing bone agent overuse could be a rare healthcare ‘win-win.’ Lower costs AND improved patient outcomes,” tweeted Dr. Mitchell. “If I were a payer, I’d be paying attention!”
 

In Prostate Cancer, Bone-Modifying Drug Indications Vary

Bone-modifying drugs are indicated for some patients with prostate cancer.

The American Society of Clinical Oncology has endorsed guidelines that recommend the use of denosumab in men with nonmetastatic prostate cancer at high risk for fracture while taking androgen deprivation therapy.

Among men with metastatic castration-resistant prostate cancer, guidelines also recommend zoledronic acid or denosumab for preventing or delaying skeletal-related events, such as pathologic fractures and spinal cord compression.

For patients with metastatic castration-sensitive disease, however, the bone-modifying agents show no benefit in preventing skeletal-related events and are not recommended for that indication.

In this population, “treatment with bone agents results only in avoidable toxicity and financial cost,” Dr. Mitchell tweeted. In its higher-dose formulation, denosumab comes with a price tag of approximately $40,000 per year in the United States.

An earlier study from Dr. Mitchell and colleagues revealed that the use of bone-modifying drugs to prevent skeletal events in metastatic castration-sensitive prostate cancer is common.

To better understand the costs associated with this inappropriate use, the researchers reviewed Surveillance, Epidemiology, and End Results Program Medicare data from 2011 to 2015. The team identified the frequency and number of doses of zoledronic acid and denosumab prescribed against recommendations in the metastatic castration-sensitive setting, making sure to distinguish between the use of denosumab to prevent osteoporotic fractures (appropriate use) and to prevent skeletal-related events (non-recommended use).

The team found that, among 2627 patients with metastatic castration-sensitive prostate cancer, 42% received at least one dose of denosumab and 18% received at least one dose of zoledronic acid.

The authors also found that unnecessary use of these drugs increased over time — with a little over 17% of patients receiving zoledronic acid between 2007 and 2009 and just over 28% receiving either denosumab (20.3%) or zoledronic acid (8.4%) from 2012 to 2015.

The annual costs to Medicare from non-recommended prescribing came to $44,105,041 for both agents, with the costs associated with denosumab representing the lion’s share at $43,303,078.

Non-recommended use of these agents also came with adverse events, such as femur fracture and hypocalcemia, which cost an estimated $758,450 to treat annually — $682,865 for denosumab and $75,585 for zoledronic acid.

The study focused on the Medicare-age population, which means the estimates are conservative. “Denosumab overuse for younger patients with castration-sensitive prostate cancer would add substantially to this total,” the authors wrote.

“This study contributes new evidence of overuse in the metastatic castrate-sensitive prostate cancer setting, which I must admit reflects my clinical experience in seeing patients for second opinions who are treated in the community,” said Samuel U. Takvorian, MD, of the Division of Hematology and Oncology, Perelman School of Medicine, Philadelphia, who wasn’t involved in the research. “While there are some circumstances in which one would consider using a bone-modifying agent in the metastatic castrate-sensitive prostate cancer setting, most [of these] men don’t need them upfront.”
 

Why Is the Overuse Happening?

One reason for the inappropriate use of bone-modifying drugs could be confusion surrounding the recommendations because the drugs are recommended for some patients with prostate cancer.

Michael R. Laurent, MD, PhD, of Imelda Hospital, Bonheiden, Belgium, explained that the use of bone-modifying drugs is, paradoxically, often overlooked in settings where they are recommended — when patients have an elevated risk for osteoporosis or fracture.

“Guidelines are quite unequivocal in their recommendations to prevent osteoporosis in mostly older men who receive androgen deprivation therapy,” but “I think there is significant undertreatment” in these patients, Dr. Laurent told this news organization.

However, the recommendation for patients at risk for osteoporosis or bone fracture calls for less intense regimens, which may include lower-dose denosumab, administered once every 6 months, zoledronic acid, given yearly, or another lower potency agent, such as oral alendronate weekly, explained Philip J. Saylor, MD, an attending physician at Massachusetts General Hospital and assistant professor at Harvard Medical School, Boston.

Meanwhile, “monthly high-intensity therapy to prevent skeletal events should be reserved specifically for bone metastatic castration-resistant prostate cancer for more than just cost reasons,” Dr. Saylor said.

When it comes to the higher dose, monthly therapy in castration-sensitive prostate cancer, “we have no evidence that it is beneficial,” he said, adding that “when the prostate cancer itself is well controlled by hormonal therapy, there just aren’t very many pathologic fractures or other bone complications.”

Alongside possible confusion over the recommendations, many physicians also likely don’t know how much denosumab costs.

“In our recent physician interview study, we did find that most physicians were very much unaware of the cost of this drug, or the cost difference between denosumab and zoledronic acid, so I do think that lack of cost awareness is a factor,” Dr. Mitchell said.

Part of the reason may be how Medicare covers these agents. Typically, Medicare would not cover non-recommended indications, but “in this case, Medicare coverage is broader and includes both the guideline-recommended and non-recommended uses,” Dr. Mitchell explained.

However, the authors also identified a more cynical reason for non-recommended prescribing — promotional payments from drug makers to physicians.

In another recent paper, Dr. Mitchell said he found about “30% of doctors treating prostate cancer had received payments from Amgen for Xgeva [denosumab] promotion during the last year.”

These payments appeared to influence non-recommended prescribing: Among patients whose doctor had not received payments, 31.4% received non-recommended denosumab, which increased to nearly 50% of patients among doctors who had received payments.

Dr. Mitchell suggested a few ways to help curb inappropriate prescribing.

Medicare could, for instance, change its coverage policy to include only the recommended uses of these agents, Dr. Mitchell said.

More physician education would be another solution. “I think that physician education would be one ‘bottom-up’ approach that could work,” Dr. Mitchell added.

Dr. Mitchell, Dr. Takvorian, and Dr. Saylor had no disclosures to report. Dr. Laurent has received lecture and consultancy fees from Alexion, AM Pharma, Amgen, Galapagos, Kyowa Kirin, Menarini, Orifarm, Pharmanovia, Takeda, UCB, and Will Pharma.
 

A version of this article appeared on Medscape.com.

Bone-modifying agents — most notably denosumab — are often prescribed to prevent skeletal-related complications in patients with metastatic castration-sensitive prostate cancer, but the drugs are not recommended for this indication and can lead to severe toxicities.

How much does Medicare spend each year on non-recommended bone therapy?

The answer, according to a new analysis in JCO Oncology Practice, is more than $44 million, with about $43 million coming from denosumab alone.

Overall, this study found that “the Medicare program pays tens of millions of dollars each year” for bone-modifying agents in patients with metastatic castration-sensitive prostate cancer, “which is not effective and may cause side effects,” lead author Aaron Mitchell, MD, MPH, a medical oncologist at Memorial Sloan Kettering Cancer Center, New York City, and colleagues concluded.

“These findings suggest reducing bone agent overuse could be a rare healthcare ‘win-win.’ Lower costs AND improved patient outcomes,” tweeted Dr. Mitchell. “If I were a payer, I’d be paying attention!”
 

In Prostate Cancer, Bone-Modifying Drug Indications Vary

Bone-modifying drugs are indicated for some patients with prostate cancer.

The American Society of Clinical Oncology has endorsed guidelines that recommend the use of denosumab in men with nonmetastatic prostate cancer at high risk for fracture while taking androgen deprivation therapy.

Among men with metastatic castration-resistant prostate cancer, guidelines also recommend zoledronic acid or denosumab for preventing or delaying skeletal-related events, such as pathologic fractures and spinal cord compression.

For patients with metastatic castration-sensitive disease, however, the bone-modifying agents show no benefit in preventing skeletal-related events and are not recommended for that indication.

In this population, “treatment with bone agents results only in avoidable toxicity and financial cost,” Dr. Mitchell tweeted. In its higher-dose formulation, denosumab comes with a price tag of approximately $40,000 per year in the United States.

An earlier study from Dr. Mitchell and colleagues revealed that the use of bone-modifying drugs to prevent skeletal events in metastatic castration-sensitive prostate cancer is common.

To better understand the costs associated with this inappropriate use, the researchers reviewed Surveillance, Epidemiology, and End Results Program Medicare data from 2011 to 2015. The team identified the frequency and number of doses of zoledronic acid and denosumab prescribed against recommendations in the metastatic castration-sensitive setting, making sure to distinguish between the use of denosumab to prevent osteoporotic fractures (appropriate use) and to prevent skeletal-related events (non-recommended use).

The team found that, among 2627 patients with metastatic castration-sensitive prostate cancer, 42% received at least one dose of denosumab and 18% received at least one dose of zoledronic acid.

The authors also found that unnecessary use of these drugs increased over time — with a little over 17% of patients receiving zoledronic acid between 2007 and 2009 and just over 28% receiving either denosumab (20.3%) or zoledronic acid (8.4%) from 2012 to 2015.

The annual costs to Medicare from non-recommended prescribing came to $44,105,041 for both agents, with the costs associated with denosumab representing the lion’s share at $43,303,078.

Non-recommended use of these agents also came with adverse events, such as femur fracture and hypocalcemia, which cost an estimated $758,450 to treat annually — $682,865 for denosumab and $75,585 for zoledronic acid.

The study focused on the Medicare-age population, which means the estimates are conservative. “Denosumab overuse for younger patients with castration-sensitive prostate cancer would add substantially to this total,” the authors wrote.

“This study contributes new evidence of overuse in the metastatic castrate-sensitive prostate cancer setting, which I must admit reflects my clinical experience in seeing patients for second opinions who are treated in the community,” said Samuel U. Takvorian, MD, of the Division of Hematology and Oncology, Perelman School of Medicine, Philadelphia, who wasn’t involved in the research. “While there are some circumstances in which one would consider using a bone-modifying agent in the metastatic castrate-sensitive prostate cancer setting, most [of these] men don’t need them upfront.”
 

Why Is the Overuse Happening?

One reason for the inappropriate use of bone-modifying drugs could be confusion surrounding the recommendations because the drugs are recommended for some patients with prostate cancer.

Michael R. Laurent, MD, PhD, of Imelda Hospital, Bonheiden, Belgium, explained that the use of bone-modifying drugs is, paradoxically, often overlooked in settings where they are recommended — when patients have an elevated risk for osteoporosis or fracture.

“Guidelines are quite unequivocal in their recommendations to prevent osteoporosis in mostly older men who receive androgen deprivation therapy,” but “I think there is significant undertreatment” in these patients, Dr. Laurent told this news organization.

However, the recommendation for patients at risk for osteoporosis or bone fracture calls for less intense regimens, which may include lower-dose denosumab, administered once every 6 months, zoledronic acid, given yearly, or another lower potency agent, such as oral alendronate weekly, explained Philip J. Saylor, MD, an attending physician at Massachusetts General Hospital and assistant professor at Harvard Medical School, Boston.

Meanwhile, “monthly high-intensity therapy to prevent skeletal events should be reserved specifically for bone metastatic castration-resistant prostate cancer for more than just cost reasons,” Dr. Saylor said.

When it comes to the higher dose, monthly therapy in castration-sensitive prostate cancer, “we have no evidence that it is beneficial,” he said, adding that “when the prostate cancer itself is well controlled by hormonal therapy, there just aren’t very many pathologic fractures or other bone complications.”

Alongside possible confusion over the recommendations, many physicians also likely don’t know how much denosumab costs.

“In our recent physician interview study, we did find that most physicians were very much unaware of the cost of this drug, or the cost difference between denosumab and zoledronic acid, so I do think that lack of cost awareness is a factor,” Dr. Mitchell said.

Part of the reason may be how Medicare covers these agents. Typically, Medicare would not cover non-recommended indications, but “in this case, Medicare coverage is broader and includes both the guideline-recommended and non-recommended uses,” Dr. Mitchell explained.

However, the authors also identified a more cynical reason for non-recommended prescribing — promotional payments from drug makers to physicians.

In another recent paper, Dr. Mitchell said he found about “30% of doctors treating prostate cancer had received payments from Amgen for Xgeva [denosumab] promotion during the last year.”

These payments appeared to influence non-recommended prescribing: Among patients whose doctor had not received payments, 31.4% received non-recommended denosumab, which increased to nearly 50% of patients among doctors who had received payments.

Dr. Mitchell suggested a few ways to help curb inappropriate prescribing.

Medicare could, for instance, change its coverage policy to include only the recommended uses of these agents, Dr. Mitchell said.

More physician education would be another solution. “I think that physician education would be one ‘bottom-up’ approach that could work,” Dr. Mitchell added.

Dr. Mitchell, Dr. Takvorian, and Dr. Saylor had no disclosures to report. Dr. Laurent has received lecture and consultancy fees from Alexion, AM Pharma, Amgen, Galapagos, Kyowa Kirin, Menarini, Orifarm, Pharmanovia, Takeda, UCB, and Will Pharma.
 

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has granted new approvals for the use of amivantamab-vmjw (Rybrevant, Janssen Biotech Inc.) in certain patients with locally advanced or metastatic non-small cell lung cancer (NSCLC). 

Specifically, the FDA approved the first-line use of the agent in combination with carboplatin and pemetrexed in patients with locally advanced or metastatic NSCLC with epidermal growth factor receptor (EGFR) exon 20 insertion mutations, as detected by an FDA-approved test. 

The FDA also granted traditional approval for use in these patients after their cancer has progressed on or following platinum-based chemotherapy. The original accelerated approval for this indication occurred in 2021. At that time, the FDA also approved Guardant360^® CDx (Guardant Health, Inc.) as a companion diagnostic test for amivantamab-vmjw. 

The first-line approval, which followed priority review, was based on the randomized, open-label PAPILLON trial, which revealed a statistically significant improvement in progression-free survival (PFS) among the 153 patients who received amivantamab-vmjw plus carboplatin and pemetrexed vs the 155 who received the chemotherapy combination alone. Median PFS was 11.4 months in the amivantamab-vmjw arm vs 6.7 months in the control arm (hazard ratio, 0.40).

Data for overall survival, a key secondary endpoint of the study, were immature at the time of the latest analysis, but “no trend toward a detriment was observed,” according to an FDA approval announcement.

Common adverse reactions, occurring in at least 20% of patients in the study, were rash, nail toxicity, stomatitis, infusion-related reaction, fatigue, edema, constipation, decreased appetite, nausea, diarrhea, and vomiting. Weight-based dosing guidance can be found in the full prescribing information.
 

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has granted new approvals for the use of amivantamab-vmjw (Rybrevant, Janssen Biotech Inc.) in certain patients with locally advanced or metastatic non-small cell lung cancer (NSCLC). 

Specifically, the FDA approved the first-line use of the agent in combination with carboplatin and pemetrexed in patients with locally advanced or metastatic NSCLC with epidermal growth factor receptor (EGFR) exon 20 insertion mutations, as detected by an FDA-approved test. 

The FDA also granted traditional approval for use in these patients after their cancer has progressed on or following platinum-based chemotherapy. The original accelerated approval for this indication occurred in 2021. At that time, the FDA also approved Guardant360^® CDx (Guardant Health, Inc.) as a companion diagnostic test for amivantamab-vmjw. 

The first-line approval, which followed priority review, was based on the randomized, open-label PAPILLON trial, which revealed a statistically significant improvement in progression-free survival (PFS) among the 153 patients who received amivantamab-vmjw plus carboplatin and pemetrexed vs the 155 who received the chemotherapy combination alone. Median PFS was 11.4 months in the amivantamab-vmjw arm vs 6.7 months in the control arm (hazard ratio, 0.40).

Data for overall survival, a key secondary endpoint of the study, were immature at the time of the latest analysis, but “no trend toward a detriment was observed,” according to an FDA approval announcement.

Common adverse reactions, occurring in at least 20% of patients in the study, were rash, nail toxicity, stomatitis, infusion-related reaction, fatigue, edema, constipation, decreased appetite, nausea, diarrhea, and vomiting. Weight-based dosing guidance can be found in the full prescribing information.
 

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has granted new approvals for the use of amivantamab-vmjw (Rybrevant, Janssen Biotech Inc.) in certain patients with locally advanced or metastatic non-small cell lung cancer (NSCLC). 

Specifically, the FDA approved the first-line use of the agent in combination with carboplatin and pemetrexed in patients with locally advanced or metastatic NSCLC with epidermal growth factor receptor (EGFR) exon 20 insertion mutations, as detected by an FDA-approved test. 

The FDA also granted traditional approval for use in these patients after their cancer has progressed on or following platinum-based chemotherapy. The original accelerated approval for this indication occurred in 2021. At that time, the FDA also approved Guardant360^® CDx (Guardant Health, Inc.) as a companion diagnostic test for amivantamab-vmjw. 

The first-line approval, which followed priority review, was based on the randomized, open-label PAPILLON trial, which revealed a statistically significant improvement in progression-free survival (PFS) among the 153 patients who received amivantamab-vmjw plus carboplatin and pemetrexed vs the 155 who received the chemotherapy combination alone. Median PFS was 11.4 months in the amivantamab-vmjw arm vs 6.7 months in the control arm (hazard ratio, 0.40).

Data for overall survival, a key secondary endpoint of the study, were immature at the time of the latest analysis, but “no trend toward a detriment was observed,” according to an FDA approval announcement.

Common adverse reactions, occurring in at least 20% of patients in the study, were rash, nail toxicity, stomatitis, infusion-related reaction, fatigue, edema, constipation, decreased appetite, nausea, diarrhea, and vomiting. Weight-based dosing guidance can be found in the full prescribing information.
 

A version of this article appeared on Medscape.com.

Sandra Hong, MD, chair of allergy and immunology and director of the Food Allergy Center of Excellence at Cleveland Clinic, in Ohio, sees firsthand how situations that feel ordinary to most people strike fear in the hearts of her patients with food allergies. 

Not only do some experience reactions to milk when they eat a cheese pizza — they can’t be in the same room with someone enjoying a slice nearby. “That would be terrifying,” Dr. Hong said.

Omalizumab (Xolair), recently approved by the US Food and Drug Administration as monotherapy for the treatment of food allergies, may now bring peace of mind to these patients and their families by reducing their risk of dangerous allergic reactions to accidental exposure.

While the drug does not cure food allergies, a phase 3, placebo-controlled trial found that after 16 weeks of treatment, two thirds of participants were able to tolerate at least 600 mg of peanut protein — equal to about 2.5 peanuts — without experiencing moderate to severe reactions. 

An open-label extension trial also found the monoclonal antibody reduced the likelihood of serious reactions to eggs by 67%, milk by 66%, and cashews by 42%. The results of the study were published in The New England Journal of Medicine.

The treatment is approved for children as young as the age of 1 year and is the only treatment approved for multiple food allergies. It does not treat anaphylaxis or other emergency situations.

Patient Selection Key

While 8% of children and 10% of adults in the United States have a true food allergy, Brian Vickery, MD, chief of allergy and immunology and director of the Food Allergy Center at Children’s Healthcare of Atlanta, noted that a significantly higher proportion of the population restricts their diet based on perceived food intolerances.

“Most important for family doctors prior to prescribing the medication will be to be sure that the diagnosis is correct,” Kim said. “We know that allergy blood and skin testing is good but not perfect, and false positive results can occur,” said Edwin Kim, MD, chief of the Division of Pediatric Allergy and Immunology and director of the University of North Carolina Food Allergy Initiative at the University of North Carolina School of Medicine, Chapel Hill, who was a coauthor on the study in the New England Journal of Medicine. “ An allergist can conduct food challenges to confirm the diagnosis if results are unclear.”

Even for patients with confirmed IgE-mediated allergies, Dr. Hong said selecting patients who are good candidates for the therapy has “nuances.” 

Patients must be willing and able to commit to injections every 2-4 weeks. Dosing depends on body weight and the total IgE levels of each patient. Patients with IgE levels > 1850 UI/mL likely will be disqualified from treatment since the clinical trial did not enroll patients with total IgE above this level and the appropriate dose in those patients is unknown.

“My recommendation for family physicians who are counseling food-allergic patients interested in omalizumab treatment is to partner with an allergist-immunologist, if at all possible,” Dr. Vickery said. He added that patients should have a comprehensive workup before beginning treatment because starting omalizumab would reduce reactivity and alter the outcome a diagnostic oral food challenge.

Two populations Dr. Hong thinks might particularly benefit from the therapy are college students and preschoolers, who may be unable to completely avoid allergens because of poor impulse control and food sharing in group settings.

“The concerns we have about this age group are whether or not there might be other factors involved that may impede their ability to make good decisions.”

Less control of the environment in dorms or other group living situations also could increase the risk of accidental exposure to a food allergen.

For the right patients, the treatment regimen has significant advantages over oral immunotherapy treatment (OIT), including the fact that it’s not a daily medication and it has the potential to treat allergic asthma at the same time.

“The biggest pro for omalizumab is that it can treat all of your food allergies, whether you have one or many, and do it all in one medication,” Dr. Kim said. 

Managing Potential Harms

Omalizumab carries risks both primary care providers and patients must consider. First among them is that the drug carries a “black box” warning for an increased risk of anaphylaxis, Dr. Hong said. 

Although patients with multiple food allergies typically already have prescriptions for epinephrine, primary care physicians (PCPs) considering offering omalizumab must be comfortable treating severe systemic reactions and their offices capable of post-dose monitoring, Dr. Hong said. 

Anaphylaxis “can occur after the first dose or it can be delayed,” she said. “Typically, allergists will give these in our offices and we’ll actually have people wait for delayed amounts of time, for hours.”

The drug has been available since 2003 as a treatment for allergic asthma and urticaria. In addition to the warning for anaphylaxis, common reactions include joint pain and injection-site reactions. It also increases the risk for parasitic infection, and some studies show an increase in the risk for cancer.

Still, Dr. Kim said omalizumab’s safety profile is reassuring and noted it has advantages over OIT. “Since the patient is not exposing themselves to the food they are allergic to like in OIT, the safety is expected to be far better,” he said.

Lifelong Treatment 

Dr. Vickery, Dr. Hong, and Dr. Kim all cautioned that patients should understand that, while omalizumab offers protection against accidental exposure and can meaningfully improve quality of life, it won’t allow them to loosen their allergen-avoidant diets.

Further, maintaining protection requires receiving injections every 2-4 weeks for life. For those without insurance, or whose insurance does not cover the treatment, costs could reach thousands of dollars each month, Dr. Hong said.

Omalizumab “has been well covered by insurance for asthma and chronic hives, but we will have to see what it looks like for food allergy. The range of plans and out-of-pocket deductibles available to patients will also play a big role,” Dr. Kim said. 

Other novel approaches to food allergies are currently in clinical trials, and both Dr. Hong and Dr. Vickery are optimistic about potential options in the pipeline.

“We’re just on the brink of really exciting therapies coming forward in the future,” Dr. Hong said.

The study was supported by the National Institute of Allergy and Infectious Diseases and the National Center for Advancing Translational Sciences, both part of the National Institutes of Health; the Claudia and Steve Stange Family Fund; Genentech; and Novartis. Dr. Hong, Dr. Kim, and Dr. Vickery reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

Sandra Hong, MD, chair of allergy and immunology and director of the Food Allergy Center of Excellence at Cleveland Clinic, in Ohio, sees firsthand how situations that feel ordinary to most people strike fear in the hearts of her patients with food allergies. 

Not only do some experience reactions to milk when they eat a cheese pizza — they can’t be in the same room with someone enjoying a slice nearby. “That would be terrifying,” Dr. Hong said.

Omalizumab (Xolair), recently approved by the US Food and Drug Administration as monotherapy for the treatment of food allergies, may now bring peace of mind to these patients and their families by reducing their risk of dangerous allergic reactions to accidental exposure.

While the drug does not cure food allergies, a phase 3, placebo-controlled trial found that after 16 weeks of treatment, two thirds of participants were able to tolerate at least 600 mg of peanut protein — equal to about 2.5 peanuts — without experiencing moderate to severe reactions. 

An open-label extension trial also found the monoclonal antibody reduced the likelihood of serious reactions to eggs by 67%, milk by 66%, and cashews by 42%. The results of the study were published in The New England Journal of Medicine.

The treatment is approved for children as young as the age of 1 year and is the only treatment approved for multiple food allergies. It does not treat anaphylaxis or other emergency situations.

Patient Selection Key

While 8% of children and 10% of adults in the United States have a true food allergy, Brian Vickery, MD, chief of allergy and immunology and director of the Food Allergy Center at Children’s Healthcare of Atlanta, noted that a significantly higher proportion of the population restricts their diet based on perceived food intolerances.

“Most important for family doctors prior to prescribing the medication will be to be sure that the diagnosis is correct,” Kim said. “We know that allergy blood and skin testing is good but not perfect, and false positive results can occur,” said Edwin Kim, MD, chief of the Division of Pediatric Allergy and Immunology and director of the University of North Carolina Food Allergy Initiative at the University of North Carolina School of Medicine, Chapel Hill, who was a coauthor on the study in the New England Journal of Medicine. “ An allergist can conduct food challenges to confirm the diagnosis if results are unclear.”

Even for patients with confirmed IgE-mediated allergies, Dr. Hong said selecting patients who are good candidates for the therapy has “nuances.” 

Patients must be willing and able to commit to injections every 2-4 weeks. Dosing depends on body weight and the total IgE levels of each patient. Patients with IgE levels > 1850 UI/mL likely will be disqualified from treatment since the clinical trial did not enroll patients with total IgE above this level and the appropriate dose in those patients is unknown.

“My recommendation for family physicians who are counseling food-allergic patients interested in omalizumab treatment is to partner with an allergist-immunologist, if at all possible,” Dr. Vickery said. He added that patients should have a comprehensive workup before beginning treatment because starting omalizumab would reduce reactivity and alter the outcome a diagnostic oral food challenge.

Two populations Dr. Hong thinks might particularly benefit from the therapy are college students and preschoolers, who may be unable to completely avoid allergens because of poor impulse control and food sharing in group settings.

“The concerns we have about this age group are whether or not there might be other factors involved that may impede their ability to make good decisions.”

Less control of the environment in dorms or other group living situations also could increase the risk of accidental exposure to a food allergen.

For the right patients, the treatment regimen has significant advantages over oral immunotherapy treatment (OIT), including the fact that it’s not a daily medication and it has the potential to treat allergic asthma at the same time.

“The biggest pro for omalizumab is that it can treat all of your food allergies, whether you have one or many, and do it all in one medication,” Dr. Kim said. 

Managing Potential Harms

Omalizumab carries risks both primary care providers and patients must consider. First among them is that the drug carries a “black box” warning for an increased risk of anaphylaxis, Dr. Hong said. 

Although patients with multiple food allergies typically already have prescriptions for epinephrine, primary care physicians (PCPs) considering offering omalizumab must be comfortable treating severe systemic reactions and their offices capable of post-dose monitoring, Dr. Hong said. 

Anaphylaxis “can occur after the first dose or it can be delayed,” she said. “Typically, allergists will give these in our offices and we’ll actually have people wait for delayed amounts of time, for hours.”

The drug has been available since 2003 as a treatment for allergic asthma and urticaria. In addition to the warning for anaphylaxis, common reactions include joint pain and injection-site reactions. It also increases the risk for parasitic infection, and some studies show an increase in the risk for cancer.

Still, Dr. Kim said omalizumab’s safety profile is reassuring and noted it has advantages over OIT. “Since the patient is not exposing themselves to the food they are allergic to like in OIT, the safety is expected to be far better,” he said.

Lifelong Treatment 

Dr. Vickery, Dr. Hong, and Dr. Kim all cautioned that patients should understand that, while omalizumab offers protection against accidental exposure and can meaningfully improve quality of life, it won’t allow them to loosen their allergen-avoidant diets.

Further, maintaining protection requires receiving injections every 2-4 weeks for life. For those without insurance, or whose insurance does not cover the treatment, costs could reach thousands of dollars each month, Dr. Hong said.

Omalizumab “has been well covered by insurance for asthma and chronic hives, but we will have to see what it looks like for food allergy. The range of plans and out-of-pocket deductibles available to patients will also play a big role,” Dr. Kim said. 

Other novel approaches to food allergies are currently in clinical trials, and both Dr. Hong and Dr. Vickery are optimistic about potential options in the pipeline.

“We’re just on the brink of really exciting therapies coming forward in the future,” Dr. Hong said.

The study was supported by the National Institute of Allergy and Infectious Diseases and the National Center for Advancing Translational Sciences, both part of the National Institutes of Health; the Claudia and Steve Stange Family Fund; Genentech; and Novartis. Dr. Hong, Dr. Kim, and Dr. Vickery reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

Sandra Hong, MD, chair of allergy and immunology and director of the Food Allergy Center of Excellence at Cleveland Clinic, in Ohio, sees firsthand how situations that feel ordinary to most people strike fear in the hearts of her patients with food allergies. 

Not only do some experience reactions to milk when they eat a cheese pizza — they can’t be in the same room with someone enjoying a slice nearby. “That would be terrifying,” Dr. Hong said.

Omalizumab (Xolair), recently approved by the US Food and Drug Administration as monotherapy for the treatment of food allergies, may now bring peace of mind to these patients and their families by reducing their risk of dangerous allergic reactions to accidental exposure.

While the drug does not cure food allergies, a phase 3, placebo-controlled trial found that after 16 weeks of treatment, two thirds of participants were able to tolerate at least 600 mg of peanut protein — equal to about 2.5 peanuts — without experiencing moderate to severe reactions. 

An open-label extension trial also found the monoclonal antibody reduced the likelihood of serious reactions to eggs by 67%, milk by 66%, and cashews by 42%. The results of the study were published in The New England Journal of Medicine.

The treatment is approved for children as young as the age of 1 year and is the only treatment approved for multiple food allergies. It does not treat anaphylaxis or other emergency situations.

Patient Selection Key

While 8% of children and 10% of adults in the United States have a true food allergy, Brian Vickery, MD, chief of allergy and immunology and director of the Food Allergy Center at Children’s Healthcare of Atlanta, noted that a significantly higher proportion of the population restricts their diet based on perceived food intolerances.

“Most important for family doctors prior to prescribing the medication will be to be sure that the diagnosis is correct,” Kim said. “We know that allergy blood and skin testing is good but not perfect, and false positive results can occur,” said Edwin Kim, MD, chief of the Division of Pediatric Allergy and Immunology and director of the University of North Carolina Food Allergy Initiative at the University of North Carolina School of Medicine, Chapel Hill, who was a coauthor on the study in the New England Journal of Medicine. “ An allergist can conduct food challenges to confirm the diagnosis if results are unclear.”

Even for patients with confirmed IgE-mediated allergies, Dr. Hong said selecting patients who are good candidates for the therapy has “nuances.” 

Patients must be willing and able to commit to injections every 2-4 weeks. Dosing depends on body weight and the total IgE levels of each patient. Patients with IgE levels > 1850 UI/mL likely will be disqualified from treatment since the clinical trial did not enroll patients with total IgE above this level and the appropriate dose in those patients is unknown.

“My recommendation for family physicians who are counseling food-allergic patients interested in omalizumab treatment is to partner with an allergist-immunologist, if at all possible,” Dr. Vickery said. He added that patients should have a comprehensive workup before beginning treatment because starting omalizumab would reduce reactivity and alter the outcome a diagnostic oral food challenge.

Two populations Dr. Hong thinks might particularly benefit from the therapy are college students and preschoolers, who may be unable to completely avoid allergens because of poor impulse control and food sharing in group settings.

“The concerns we have about this age group are whether or not there might be other factors involved that may impede their ability to make good decisions.”

Less control of the environment in dorms or other group living situations also could increase the risk of accidental exposure to a food allergen.

For the right patients, the treatment regimen has significant advantages over oral immunotherapy treatment (OIT), including the fact that it’s not a daily medication and it has the potential to treat allergic asthma at the same time.

“The biggest pro for omalizumab is that it can treat all of your food allergies, whether you have one or many, and do it all in one medication,” Dr. Kim said. 

Managing Potential Harms

Omalizumab carries risks both primary care providers and patients must consider. First among them is that the drug carries a “black box” warning for an increased risk of anaphylaxis, Dr. Hong said. 

Although patients with multiple food allergies typically already have prescriptions for epinephrine, primary care physicians (PCPs) considering offering omalizumab must be comfortable treating severe systemic reactions and their offices capable of post-dose monitoring, Dr. Hong said. 

Anaphylaxis “can occur after the first dose or it can be delayed,” she said. “Typically, allergists will give these in our offices and we’ll actually have people wait for delayed amounts of time, for hours.”

The drug has been available since 2003 as a treatment for allergic asthma and urticaria. In addition to the warning for anaphylaxis, common reactions include joint pain and injection-site reactions. It also increases the risk for parasitic infection, and some studies show an increase in the risk for cancer.

Still, Dr. Kim said omalizumab’s safety profile is reassuring and noted it has advantages over OIT. “Since the patient is not exposing themselves to the food they are allergic to like in OIT, the safety is expected to be far better,” he said.

Lifelong Treatment 

Dr. Vickery, Dr. Hong, and Dr. Kim all cautioned that patients should understand that, while omalizumab offers protection against accidental exposure and can meaningfully improve quality of life, it won’t allow them to loosen their allergen-avoidant diets.

Further, maintaining protection requires receiving injections every 2-4 weeks for life. For those without insurance, or whose insurance does not cover the treatment, costs could reach thousands of dollars each month, Dr. Hong said.

Omalizumab “has been well covered by insurance for asthma and chronic hives, but we will have to see what it looks like for food allergy. The range of plans and out-of-pocket deductibles available to patients will also play a big role,” Dr. Kim said. 

Other novel approaches to food allergies are currently in clinical trials, and both Dr. Hong and Dr. Vickery are optimistic about potential options in the pipeline.

“We’re just on the brink of really exciting therapies coming forward in the future,” Dr. Hong said.

The study was supported by the National Institute of Allergy and Infectious Diseases and the National Center for Advancing Translational Sciences, both part of the National Institutes of Health; the Claudia and Steve Stange Family Fund; Genentech; and Novartis. Dr. Hong, Dr. Kim, and Dr. Vickery reported no relevant financial relationships.

A version of this article appeared on Medscape.com.