Commentary

It’s that time of the year, when social media is rife with many top 5 and top 10 lists. Perhaps the beginning of a new year is a good time to review how different medications can have side effects beyond the disease state they’re used to address. Among the most common complications of many medications is the potential to disrupt glycemic control. Let’s revisit some of the most commonly used medications known to increase glucose levels and look at some practical tips on overcoming these.

1. Glucocorticoids

Without a doubt, corticosteroids are at the top of the list when it comes to the potential for increasing blood glucose levels. High-dose glucocorticoid therapy is known to lead to new-onset diabetes (steroid-induced diabetes). Similarly, people with preexisting diabetes may notice significant worsening of glycemic control when they start on glucocorticoid therapy. The extent of glucose elevation depends on their glycemic status prior to initiation on steroids, the dose and duration of glucocorticoid therapy, and comorbid conditions, among other factors.

Management tip: For those with previously well-controlled diabetes or borderline diabetes, glucocorticoid-induced hyperglycemia may be managed by metformin with or without sulfonylurea therapy, especially if corticosteroid treatment is low-dose and for a shorter duration. However, for many individuals with preexisting poorly controlled diabetes or those initiated on high-dose corticosteroids, insulin therapy would perhaps be the treatment of choice. Glucocorticoid therapy generally leads to more pronounced postprandial hyperglycemia compared with fasting hyperglycemia; hence, the use of short-acting insulin therapy or perhaps NPH insulin in the morning might be a better option for many individuals. Dietary modification plays an important role in limiting the extent of postprandial hyperglycemia. Use of continuous glucose monitoring (CGM) devices may also be very helpful for understanding glycemic excursions and how to adjust insulin. In individuals for whom glucocorticoid therapy is tapered down, it is important to adjust the dose of medications with potential to cause hypoglycemia, such as insulin/sulfonylurea therapy, as the degree of hyperglycemia may decrease with decreased dose of the glucocorticoid therapy.

2. Antipsychotic Therapy

Antipsychotic medications can be obesogenic; between 15% and 72% of people who take second-generation antipsychotics experience weight gain of 7% or more. Increases in weight are not the only factor contributing to an elevated risk of developing type 2 diabetes. Antipsychotics are thought to cause downregulation of intracellular insulin signaling, leading to insulin resistance. At the same time, there seems to be a direct effect on the pancreatic beta cells. Antagonism of the dopamine D2, serotonin 5-HT2C, and muscarinic M3 receptors impairs beta-cell response to changes in blood glucose. In addition to the pharmacologic effects, cell culture experiments have shown that antipsychotics increase apoptosis of beta cells. Increased weight and concomitant development of type 2 diabetes is seen particularly in agents that exhibit high muscarinic M3 and histamine H1 receptor blockade. The effect on glucose metabolism is seen the most with agents such as clozapine, olanzapine, and haloperidol and the least with agents such as ziprasidone.

Management tip: Given the ongoing change in the understanding of increases in weight and their association with the risk of developing type 2 diabetes, a metabolically safer approach involves starting with medications that have a lower propensity for weight gain, and the partial agonists/third-generation antipsychotics as a family presently have the best overall data.

3. Thiazide Diuretics

Thiazide diuretics are commonly used for the management of hypertension and are associated with metabolic complications including hypokalemia; higher cholesterol, triglycerides, and other circulating lipids; and elevated glucose. It’s thought that the reduced potassium level occurring as a result of these medications might contribute to new-onset diabetes. The hypokalemia occurring from these medications is thought to lead to a decrease in insulin secretion and sensitivity, which is dose dependent. Studies show that the number needed to harm for chlorthalidone-induced diabetes is 29 over 1 year. There is believed to be no additional risk beyond 1 year.

Management tip: It’s important to monitor potassium levels for those initiated on thiazide diuretics. If hypokalemia occurs, it would be pertinent to correct the hypokalemia with potassium supplements to mitigate the risk for new-onset diabetes.

4. Statin Therapy

Statin therapy is thought to be associated with decreased insulin sensitivity and impairment in insulin secretion. The overall incidence of diabetes is pegged to be between 9% and 12% on statin therapy on the basis of meta-analysis studies, and higher on the basis of population-based studies. Overall, the estimated number needed to harm is: 1 out of every 255 patients on statin therapy for 4 years may develop new-onset diabetes. Compare this with the extremely strong evidence for number needed to treat being 39 for 5 years with statin therapy in patients with preexisting heart disease to prevent one occurrence of a nonfatal myocardial infarction.

Management tip: Although statins are associated with a small incident increase in the risk of developing diabetes, the potential benefits of using statin therapy for both primary and secondary prevention of cardiovascular disease significantly outweigh any of the potential risks associated with hyperglycemia. This is an important discussion to have with patients who are reluctant to use statin therapy because of the potential risk for new-onset diabetes as a side effect.

5. Beta-Blockers

Beta-blockers are another commonly used group of medications for managing hypertension, heart failure, coronary artery disease, and arrhythmia. Nonvasodilating beta-blockers such as metoprolol and atenolol are more likely to be associated with increases in A1c, mean plasma glucose, body weight, and triglycerides compared with vasodilating beta-blockers such as carvedilol, nebivolol, and labetalol (Bakris GL et al; Giugliano D et al). Similarly, studies have also shown that atenolol and metoprolol are associated with increased odds of hypoglycemia compared with carvedilol. People on beta-blockers may have masking of some of the symptoms of hypoglycemia, such as tremor, irritability, and palpitations, while other symptoms such as diaphoresis may remain unaffected on beta-blockers.

Management tip: Education on recognizing and managing hypoglycemia would be important when starting patients on beta-blockers if they are on preexisting insulin/sulfonylurea therapy. Use of CGM devices may be helpful if there is a high risk for hypoglycemia, especially as symptoms of hypoglycemia are often masked.

Honorable Mention

Several other medications — including antiretroviral therapy, tyrosine kinase inhibitors, mechanistic target of rapamycin (mTOR) inhibitors, immunosuppressants, and interferon alpha — are associated with worsening glycemic control and new-onset diabetes. Consider these agents’ effects on blood glucose, especially in people with an elevated risk of developing diabetes or those with preexisting diabetes, when prescribing.

A special mention should also be made of androgen deprivation therapy. These include treatment options like goserelin and leuprolide, which are gonadotropin-releasing hormone (GnRH) agonist therapies and are commonly used for prostate cancer management. Depending on the patient, these agents may be used for prolonged duration. Androgen deprivation therapy, by definition, decreases testosterone levels in men, thereby leading to worsening insulin resistance. Increase in fat mass and concomitant muscle wasting have been associated with the use of these medications; these, in turn, lead to peripheral insulin resistance. Nearly 1 out of every 5 men treated with long-term androgen deprivation therapy may be prone to developing worsening of A1c by 1% or more.

Management tip: Men on androgen deprivation therapy should be encouraged to participate in regular physical activity to reduce the burden of insulin resistance and to promote cardiovascular health.

Drug-induced diabetes is potentially reversible in many cases. Similarly, worsening of glycemic control due to medications in people with preexisting diabetes may also attenuate once the effect of the drug wears off. Blood glucose should be monitored on an ongoing basis so that diabetes medications can be adjusted. For some individuals, however, the worsening of glycemic status may be more chronic and may require long-term use of antihyperglycemic agents, especially if the benefits of continuation of the medication leading to hyperglycemia far exceed any potential risks.
 

Dr. Jain is Clinical Instructor, Department of Endocrinology, University of British Columbia; Endocrinologist, Fraser River Endocrinology, Vancouver, British Columbia, Canada. He disclosed ties with Abbott, Amgen, Boehringer Ingelheim, Dexcom, Eli Lilly, Janssen, Medtronic, Merck, and Novo Nordisk.

A version of this article appeared on Medscape.com.

It’s that time of the year, when social media is rife with many top 5 and top 10 lists. Perhaps the beginning of a new year is a good time to review how different medications can have side effects beyond the disease state they’re used to address. Among the most common complications of many medications is the potential to disrupt glycemic control. Let’s revisit some of the most commonly used medications known to increase glucose levels and look at some practical tips on overcoming these.

1. Glucocorticoids

Without a doubt, corticosteroids are at the top of the list when it comes to the potential for increasing blood glucose levels. High-dose glucocorticoid therapy is known to lead to new-onset diabetes (steroid-induced diabetes). Similarly, people with preexisting diabetes may notice significant worsening of glycemic control when they start on glucocorticoid therapy. The extent of glucose elevation depends on their glycemic status prior to initiation on steroids, the dose and duration of glucocorticoid therapy, and comorbid conditions, among other factors.

Management tip: For those with previously well-controlled diabetes or borderline diabetes, glucocorticoid-induced hyperglycemia may be managed by metformin with or without sulfonylurea therapy, especially if corticosteroid treatment is low-dose and for a shorter duration. However, for many individuals with preexisting poorly controlled diabetes or those initiated on high-dose corticosteroids, insulin therapy would perhaps be the treatment of choice. Glucocorticoid therapy generally leads to more pronounced postprandial hyperglycemia compared with fasting hyperglycemia; hence, the use of short-acting insulin therapy or perhaps NPH insulin in the morning might be a better option for many individuals. Dietary modification plays an important role in limiting the extent of postprandial hyperglycemia. Use of continuous glucose monitoring (CGM) devices may also be very helpful for understanding glycemic excursions and how to adjust insulin. In individuals for whom glucocorticoid therapy is tapered down, it is important to adjust the dose of medications with potential to cause hypoglycemia, such as insulin/sulfonylurea therapy, as the degree of hyperglycemia may decrease with decreased dose of the glucocorticoid therapy.

2. Antipsychotic Therapy

Antipsychotic medications can be obesogenic; between 15% and 72% of people who take second-generation antipsychotics experience weight gain of 7% or more. Increases in weight are not the only factor contributing to an elevated risk of developing type 2 diabetes. Antipsychotics are thought to cause downregulation of intracellular insulin signaling, leading to insulin resistance. At the same time, there seems to be a direct effect on the pancreatic beta cells. Antagonism of the dopamine D2, serotonin 5-HT2C, and muscarinic M3 receptors impairs beta-cell response to changes in blood glucose. In addition to the pharmacologic effects, cell culture experiments have shown that antipsychotics increase apoptosis of beta cells. Increased weight and concomitant development of type 2 diabetes is seen particularly in agents that exhibit high muscarinic M3 and histamine H1 receptor blockade. The effect on glucose metabolism is seen the most with agents such as clozapine, olanzapine, and haloperidol and the least with agents such as ziprasidone.

Management tip: Given the ongoing change in the understanding of increases in weight and their association with the risk of developing type 2 diabetes, a metabolically safer approach involves starting with medications that have a lower propensity for weight gain, and the partial agonists/third-generation antipsychotics as a family presently have the best overall data.

3. Thiazide Diuretics

Thiazide diuretics are commonly used for the management of hypertension and are associated with metabolic complications including hypokalemia; higher cholesterol, triglycerides, and other circulating lipids; and elevated glucose. It’s thought that the reduced potassium level occurring as a result of these medications might contribute to new-onset diabetes. The hypokalemia occurring from these medications is thought to lead to a decrease in insulin secretion and sensitivity, which is dose dependent. Studies show that the number needed to harm for chlorthalidone-induced diabetes is 29 over 1 year. There is believed to be no additional risk beyond 1 year.

Management tip: It’s important to monitor potassium levels for those initiated on thiazide diuretics. If hypokalemia occurs, it would be pertinent to correct the hypokalemia with potassium supplements to mitigate the risk for new-onset diabetes.

4. Statin Therapy

Statin therapy is thought to be associated with decreased insulin sensitivity and impairment in insulin secretion. The overall incidence of diabetes is pegged to be between 9% and 12% on statin therapy on the basis of meta-analysis studies, and higher on the basis of population-based studies. Overall, the estimated number needed to harm is: 1 out of every 255 patients on statin therapy for 4 years may develop new-onset diabetes. Compare this with the extremely strong evidence for number needed to treat being 39 for 5 years with statin therapy in patients with preexisting heart disease to prevent one occurrence of a nonfatal myocardial infarction.

Management tip: Although statins are associated with a small incident increase in the risk of developing diabetes, the potential benefits of using statin therapy for both primary and secondary prevention of cardiovascular disease significantly outweigh any of the potential risks associated with hyperglycemia. This is an important discussion to have with patients who are reluctant to use statin therapy because of the potential risk for new-onset diabetes as a side effect.

5. Beta-Blockers

Beta-blockers are another commonly used group of medications for managing hypertension, heart failure, coronary artery disease, and arrhythmia. Nonvasodilating beta-blockers such as metoprolol and atenolol are more likely to be associated with increases in A1c, mean plasma glucose, body weight, and triglycerides compared with vasodilating beta-blockers such as carvedilol, nebivolol, and labetalol (Bakris GL et al; Giugliano D et al). Similarly, studies have also shown that atenolol and metoprolol are associated with increased odds of hypoglycemia compared with carvedilol. People on beta-blockers may have masking of some of the symptoms of hypoglycemia, such as tremor, irritability, and palpitations, while other symptoms such as diaphoresis may remain unaffected on beta-blockers.

Management tip: Education on recognizing and managing hypoglycemia would be important when starting patients on beta-blockers if they are on preexisting insulin/sulfonylurea therapy. Use of CGM devices may be helpful if there is a high risk for hypoglycemia, especially as symptoms of hypoglycemia are often masked.

Honorable Mention

Several other medications — including antiretroviral therapy, tyrosine kinase inhibitors, mechanistic target of rapamycin (mTOR) inhibitors, immunosuppressants, and interferon alpha — are associated with worsening glycemic control and new-onset diabetes. Consider these agents’ effects on blood glucose, especially in people with an elevated risk of developing diabetes or those with preexisting diabetes, when prescribing.

A special mention should also be made of androgen deprivation therapy. These include treatment options like goserelin and leuprolide, which are gonadotropin-releasing hormone (GnRH) agonist therapies and are commonly used for prostate cancer management. Depending on the patient, these agents may be used for prolonged duration. Androgen deprivation therapy, by definition, decreases testosterone levels in men, thereby leading to worsening insulin resistance. Increase in fat mass and concomitant muscle wasting have been associated with the use of these medications; these, in turn, lead to peripheral insulin resistance. Nearly 1 out of every 5 men treated with long-term androgen deprivation therapy may be prone to developing worsening of A1c by 1% or more.

Management tip: Men on androgen deprivation therapy should be encouraged to participate in regular physical activity to reduce the burden of insulin resistance and to promote cardiovascular health.

Drug-induced diabetes is potentially reversible in many cases. Similarly, worsening of glycemic control due to medications in people with preexisting diabetes may also attenuate once the effect of the drug wears off. Blood glucose should be monitored on an ongoing basis so that diabetes medications can be adjusted. For some individuals, however, the worsening of glycemic status may be more chronic and may require long-term use of antihyperglycemic agents, especially if the benefits of continuation of the medication leading to hyperglycemia far exceed any potential risks.
 

Dr. Jain is Clinical Instructor, Department of Endocrinology, University of British Columbia; Endocrinologist, Fraser River Endocrinology, Vancouver, British Columbia, Canada. He disclosed ties with Abbott, Amgen, Boehringer Ingelheim, Dexcom, Eli Lilly, Janssen, Medtronic, Merck, and Novo Nordisk.

A version of this article appeared on Medscape.com.

It’s that time of the year, when social media is rife with many top 5 and top 10 lists. Perhaps the beginning of a new year is a good time to review how different medications can have side effects beyond the disease state they’re used to address. Among the most common complications of many medications is the potential to disrupt glycemic control. Let’s revisit some of the most commonly used medications known to increase glucose levels and look at some practical tips on overcoming these.

1. Glucocorticoids

Without a doubt, corticosteroids are at the top of the list when it comes to the potential for increasing blood glucose levels. High-dose glucocorticoid therapy is known to lead to new-onset diabetes (steroid-induced diabetes). Similarly, people with preexisting diabetes may notice significant worsening of glycemic control when they start on glucocorticoid therapy. The extent of glucose elevation depends on their glycemic status prior to initiation on steroids, the dose and duration of glucocorticoid therapy, and comorbid conditions, among other factors.

Management tip: For those with previously well-controlled diabetes or borderline diabetes, glucocorticoid-induced hyperglycemia may be managed by metformin with or without sulfonylurea therapy, especially if corticosteroid treatment is low-dose and for a shorter duration. However, for many individuals with preexisting poorly controlled diabetes or those initiated on high-dose corticosteroids, insulin therapy would perhaps be the treatment of choice. Glucocorticoid therapy generally leads to more pronounced postprandial hyperglycemia compared with fasting hyperglycemia; hence, the use of short-acting insulin therapy or perhaps NPH insulin in the morning might be a better option for many individuals. Dietary modification plays an important role in limiting the extent of postprandial hyperglycemia. Use of continuous glucose monitoring (CGM) devices may also be very helpful for understanding glycemic excursions and how to adjust insulin. In individuals for whom glucocorticoid therapy is tapered down, it is important to adjust the dose of medications with potential to cause hypoglycemia, such as insulin/sulfonylurea therapy, as the degree of hyperglycemia may decrease with decreased dose of the glucocorticoid therapy.

2. Antipsychotic Therapy

Antipsychotic medications can be obesogenic; between 15% and 72% of people who take second-generation antipsychotics experience weight gain of 7% or more. Increases in weight are not the only factor contributing to an elevated risk of developing type 2 diabetes. Antipsychotics are thought to cause downregulation of intracellular insulin signaling, leading to insulin resistance. At the same time, there seems to be a direct effect on the pancreatic beta cells. Antagonism of the dopamine D2, serotonin 5-HT2C, and muscarinic M3 receptors impairs beta-cell response to changes in blood glucose. In addition to the pharmacologic effects, cell culture experiments have shown that antipsychotics increase apoptosis of beta cells. Increased weight and concomitant development of type 2 diabetes is seen particularly in agents that exhibit high muscarinic M3 and histamine H1 receptor blockade. The effect on glucose metabolism is seen the most with agents such as clozapine, olanzapine, and haloperidol and the least with agents such as ziprasidone.

Management tip: Given the ongoing change in the understanding of increases in weight and their association with the risk of developing type 2 diabetes, a metabolically safer approach involves starting with medications that have a lower propensity for weight gain, and the partial agonists/third-generation antipsychotics as a family presently have the best overall data.

3. Thiazide Diuretics

Thiazide diuretics are commonly used for the management of hypertension and are associated with metabolic complications including hypokalemia; higher cholesterol, triglycerides, and other circulating lipids; and elevated glucose. It’s thought that the reduced potassium level occurring as a result of these medications might contribute to new-onset diabetes. The hypokalemia occurring from these medications is thought to lead to a decrease in insulin secretion and sensitivity, which is dose dependent. Studies show that the number needed to harm for chlorthalidone-induced diabetes is 29 over 1 year. There is believed to be no additional risk beyond 1 year.

Management tip: It’s important to monitor potassium levels for those initiated on thiazide diuretics. If hypokalemia occurs, it would be pertinent to correct the hypokalemia with potassium supplements to mitigate the risk for new-onset diabetes.

4. Statin Therapy

Statin therapy is thought to be associated with decreased insulin sensitivity and impairment in insulin secretion. The overall incidence of diabetes is pegged to be between 9% and 12% on statin therapy on the basis of meta-analysis studies, and higher on the basis of population-based studies. Overall, the estimated number needed to harm is: 1 out of every 255 patients on statin therapy for 4 years may develop new-onset diabetes. Compare this with the extremely strong evidence for number needed to treat being 39 for 5 years with statin therapy in patients with preexisting heart disease to prevent one occurrence of a nonfatal myocardial infarction.

Management tip: Although statins are associated with a small incident increase in the risk of developing diabetes, the potential benefits of using statin therapy for both primary and secondary prevention of cardiovascular disease significantly outweigh any of the potential risks associated with hyperglycemia. This is an important discussion to have with patients who are reluctant to use statin therapy because of the potential risk for new-onset diabetes as a side effect.

5. Beta-Blockers

Beta-blockers are another commonly used group of medications for managing hypertension, heart failure, coronary artery disease, and arrhythmia. Nonvasodilating beta-blockers such as metoprolol and atenolol are more likely to be associated with increases in A1c, mean plasma glucose, body weight, and triglycerides compared with vasodilating beta-blockers such as carvedilol, nebivolol, and labetalol (Bakris GL et al; Giugliano D et al). Similarly, studies have also shown that atenolol and metoprolol are associated with increased odds of hypoglycemia compared with carvedilol. People on beta-blockers may have masking of some of the symptoms of hypoglycemia, such as tremor, irritability, and palpitations, while other symptoms such as diaphoresis may remain unaffected on beta-blockers.

Management tip: Education on recognizing and managing hypoglycemia would be important when starting patients on beta-blockers if they are on preexisting insulin/sulfonylurea therapy. Use of CGM devices may be helpful if there is a high risk for hypoglycemia, especially as symptoms of hypoglycemia are often masked.

Honorable Mention

Several other medications — including antiretroviral therapy, tyrosine kinase inhibitors, mechanistic target of rapamycin (mTOR) inhibitors, immunosuppressants, and interferon alpha — are associated with worsening glycemic control and new-onset diabetes. Consider these agents’ effects on blood glucose, especially in people with an elevated risk of developing diabetes or those with preexisting diabetes, when prescribing.

A special mention should also be made of androgen deprivation therapy. These include treatment options like goserelin and leuprolide, which are gonadotropin-releasing hormone (GnRH) agonist therapies and are commonly used for prostate cancer management. Depending on the patient, these agents may be used for prolonged duration. Androgen deprivation therapy, by definition, decreases testosterone levels in men, thereby leading to worsening insulin resistance. Increase in fat mass and concomitant muscle wasting have been associated with the use of these medications; these, in turn, lead to peripheral insulin resistance. Nearly 1 out of every 5 men treated with long-term androgen deprivation therapy may be prone to developing worsening of A1c by 1% or more.

Management tip: Men on androgen deprivation therapy should be encouraged to participate in regular physical activity to reduce the burden of insulin resistance and to promote cardiovascular health.

Drug-induced diabetes is potentially reversible in many cases. Similarly, worsening of glycemic control due to medications in people with preexisting diabetes may also attenuate once the effect of the drug wears off. Blood glucose should be monitored on an ongoing basis so that diabetes medications can be adjusted. For some individuals, however, the worsening of glycemic status may be more chronic and may require long-term use of antihyperglycemic agents, especially if the benefits of continuation of the medication leading to hyperglycemia far exceed any potential risks.
 

Dr. Jain is Clinical Instructor, Department of Endocrinology, University of British Columbia; Endocrinologist, Fraser River Endocrinology, Vancouver, British Columbia, Canada. He disclosed ties with Abbott, Amgen, Boehringer Ingelheim, Dexcom, Eli Lilly, Janssen, Medtronic, Merck, and Novo Nordisk.

A version of this article appeared on Medscape.com.

Psoriasis is a chronic inflammatory skin disease for which several lifestyle factors—smoking, alcohol use, and psychological stress—are associated with higher incidence and more severe disease.^1-3 Diet also has been implicated as a factor that can affect psoriasis,⁴ and many patients have shown interest in possible dietary interventions to help their disease.⁵

In 2018, the National Psoriasis Foundation (NPF) presented dietary recommendations for patients based on results from a systematic review. From the available literature, only dietary weight reduction with hypocaloric diets in overweight or obese patients could be strongly recommended, and it has been proven that obesity is associated with worse psoriasis severity.⁶ Other more recent studies have shown that dietary modifications such as intermittent fasting and the ketogenic diet also led to weight loss and improved psoriasis severity in overweight patients; however, it is difficult to discern if the improvement was due to weight loss alone or if the dietary patterns themselves played a role.^7,8 The paucity of well-designed studies evaluating the effects of other dietary changes has prevented further guidelines from being written. We propose that dietary patterns such as the Mediterranean diet (MeD) and vegan/vegetarian diets—even without strong data showing benefits in skin disease—may help to decrease systemic inflammation, improve gut dysbiosis, and help decrease the risk for cardiometabolic comorbidities that are associated with psoriasis.

Mediterranean Diet

The MeD is based on the dietary tendencies of inhabitants from the regions surrounding the Mediterranean Sea and is centered around nutrient-rich foods such as vegetables, olive oil, and legumes while limiting meat and dairy.⁹ The NPF recommended considering a trial of the MeD based on low-quality evidence.⁶ Observational studies have indicated that psoriasis patients are less likely to adhere to the MeD, but those who do have less severe disease.⁸ However, a search of PubMed articles indexed for MEDLINE using the terms Mediterranean diet and psoriasis yielded no prospective interventional studies. Given the association of the MeD with less severe disease, it is important to understand which specific foods in the MeD could be beneficial. Intake of omega-3 fatty acids, such as those found in fatty fish, are important for modulation of systemic inflammation.⁷ High intake of polyphenols—found in fruits and vegetables, extra-virgin olive oil, and wine—also have been implicated in improving inflammatory diseases due to potent antioxidant and anti-inflammatory properties. Individually, fruits, vegetables, whole grains, and sea fish have been associated with lowering C-reactive protein levels, which also is indicative of the benefits of these foods on systemic inflammation.⁷

Vegan/Vegetarian Diets

Although fruits, vegetables, legumes, and whole grains are a substantial component of the MeD, there are limited data on vegetarian or purely vegan plant-based diets. An observational study from the NPF found that only 48.4% (15/31) of patients on the MeD vs 69.0% (20/29) on a vegan diet reported a favorable skin response.⁵ Two case reports also have shown beneficial results of a strict vegan diet for psoriasis and psoriatic arthritis, where whole-food plant-based diets also improved joint symptoms.^10-12 As with any diet, those who pursue a plant-based diet should strive to consume a variety of foods to avoid nutrient deficiencies. A recent systematic meta-analysis of 141 studies evaluated nutrient status of vegan and vegetarian diets compared to pescovegetarians and those who consume meat. All dietary patterns showed varying degrees of low levels of different nutrients.¹³ Of note, the researchers found that vitamin B₁₂, vitamin D, iron, zinc, iodine, calcium, and docosahexaenoic acid were lower in plant-based diets. In contrast, folate; vitamins B₁, B₆, C, and E; polyunsaturated fatty acids; α-linolenic acid; and magnesium intake were higher. Those who consumed meat were at risk for inadequate intake of fiber, polyunsaturated fatty acids, α-linolenic acid, folate, vitamin E, calcium, magnesium, and vitamin D, though vitamin D intake was higher than in vegans/vegetarians.¹³ The results of this meta-analysis indicated the importance of educating patients on what constitutes a well-rounded, micronutrient-rich diet or appropriate supplementation for any diet.

Effects on Gut Microbiome

Any changes in diet can lead to alterations in the gut microbiome, which may impact skin disease, as evidence indicates a bidirectional relationship between gut and skin health.¹⁰ A metagenomic analysis of the gut microbiota in patients with untreated plaque psoriasis revealed a signature dysbiosis for which the researchers developed a psoriasis microbiota index, suggesting the gut microbiota may play a role in psoriasis pathophysiology.¹⁴ Research shows that both the MeD and vegan/vegetarian diets, which are relatively rich in fiber and omega-3 fatty acids and low in saturated fat and animal protein compared to many diets, cause increases in dietary fiber–metabolizing bacteria that produce short-chain fatty acids. These short-chain fatty acids improve gut epithelial integrity and alleviate both gut and systemic inflammation.¹⁰

The changes to the gut microbiome induced by a high-fat diet also are concerning. In contrast to the MeD or vegan/vegetarian diets, consumption of a high-fat diet induces alterations in the composition of the gut microbiota that in turn increase the release of proinflammatory cytokines and promote higher intestinal permeability.¹⁰ Similarly, high sugar consumption promotes increased intestinal permeability and shifts the gut microbiota to organisms that can rapidly utilize simple carbohydrates at the expense of other beneficial organisms, reducing bacterial diversity.¹⁵ The Western diet, which is notable for both high fat and high sugar content, is sometimes referred to as a proinflammatory diet and has been shown to worsen psoriasiformlike lesions in mice.¹⁶ Importantly, most research indicates that high fat and high sugar consumption appear to be more prevalent in psoriasis patients,⁸ but the type of fat consumed in the diet matters. The Western diet includes abundant saturated fat found in meat, dairy products, palm and coconut oils, and processed foods, as well as omega-6 fatty acids that are found in meat, poultry, and eggs. Saturated fat has been shown to promote helper T cell (T_H17) accumulation in the skin, and omega-6 fatty acids serve as precursors to various inflammatory lipid mediators.⁴ This distinction of sources of fat between the Western diet and MeD is important in understanding the diets’ different effects on psoriasis and overall health. As previously discussed, the high intake of omega-3 acids in the MeD is one of the ways it may exert its anti-inflammatory benefits.⁷

Next Steps in Advising Psoriasis Patients

A major limitation of the data for MeD and vegan/vegetarian diets is limited randomized controlled trials evaluating the impact of these diets on psoriasis. Thus, dietary recommendations for psoriasis are not as strong as for other diseases for which more conclusive data exist.⁸ Although the data on diet and psoriasis are not definitive, perhaps dermatologists should shift the question from “Does this diet definitely improve psoriasis?” to “Does this diet definitely improve my patient’s health as a whole and maybe also their psoriasis?” For instance, the MeD has been shown to reduce the risk for type 2 diabetes mellitus and cardiovascular disease as well as to slow cognitive decline.¹⁷ Vegan/vegetarian diets focusing on whole vs processed foods have been shown to be highly effective in combatting obesity, type 2 diabetes mellitus, coronary artery disease including severe atherosclerosis, and hypertension.¹⁸ Psoriasis patients are at increased risk for many of the ailments that the MeD and plant-based diets protect against, making these diets potentially even more impactful than for someone without psoriasis.¹⁹ Dietary recommendations should still be made in conjunction with continuing traditional therapies for psoriasis and in consultation with the patient’s primary care physician and/or dietitian; however, rather than waiting for more randomized controlled trials before making health-promoting recommendations, what would be the downside of starting now? At worst, the dietary change decreases their risk for several metabolic conditions, and at best they may even see an improvement in their psoriasis.

Psoriasis is a chronic inflammatory skin disease for which several lifestyle factors—smoking, alcohol use, and psychological stress—are associated with higher incidence and more severe disease.^1-3 Diet also has been implicated as a factor that can affect psoriasis,⁴ and many patients have shown interest in possible dietary interventions to help their disease.⁵

In 2018, the National Psoriasis Foundation (NPF) presented dietary recommendations for patients based on results from a systematic review. From the available literature, only dietary weight reduction with hypocaloric diets in overweight or obese patients could be strongly recommended, and it has been proven that obesity is associated with worse psoriasis severity.⁶ Other more recent studies have shown that dietary modifications such as intermittent fasting and the ketogenic diet also led to weight loss and improved psoriasis severity in overweight patients; however, it is difficult to discern if the improvement was due to weight loss alone or if the dietary patterns themselves played a role.^7,8 The paucity of well-designed studies evaluating the effects of other dietary changes has prevented further guidelines from being written. We propose that dietary patterns such as the Mediterranean diet (MeD) and vegan/vegetarian diets—even without strong data showing benefits in skin disease—may help to decrease systemic inflammation, improve gut dysbiosis, and help decrease the risk for cardiometabolic comorbidities that are associated with psoriasis.

Mediterranean Diet

The MeD is based on the dietary tendencies of inhabitants from the regions surrounding the Mediterranean Sea and is centered around nutrient-rich foods such as vegetables, olive oil, and legumes while limiting meat and dairy.⁹ The NPF recommended considering a trial of the MeD based on low-quality evidence.⁶ Observational studies have indicated that psoriasis patients are less likely to adhere to the MeD, but those who do have less severe disease.⁸ However, a search of PubMed articles indexed for MEDLINE using the terms Mediterranean diet and psoriasis yielded no prospective interventional studies. Given the association of the MeD with less severe disease, it is important to understand which specific foods in the MeD could be beneficial. Intake of omega-3 fatty acids, such as those found in fatty fish, are important for modulation of systemic inflammation.⁷ High intake of polyphenols—found in fruits and vegetables, extra-virgin olive oil, and wine—also have been implicated in improving inflammatory diseases due to potent antioxidant and anti-inflammatory properties. Individually, fruits, vegetables, whole grains, and sea fish have been associated with lowering C-reactive protein levels, which also is indicative of the benefits of these foods on systemic inflammation.⁷

Vegan/Vegetarian Diets

Although fruits, vegetables, legumes, and whole grains are a substantial component of the MeD, there are limited data on vegetarian or purely vegan plant-based diets. An observational study from the NPF found that only 48.4% (15/31) of patients on the MeD vs 69.0% (20/29) on a vegan diet reported a favorable skin response.⁵ Two case reports also have shown beneficial results of a strict vegan diet for psoriasis and psoriatic arthritis, where whole-food plant-based diets also improved joint symptoms.^10-12 As with any diet, those who pursue a plant-based diet should strive to consume a variety of foods to avoid nutrient deficiencies. A recent systematic meta-analysis of 141 studies evaluated nutrient status of vegan and vegetarian diets compared to pescovegetarians and those who consume meat. All dietary patterns showed varying degrees of low levels of different nutrients.¹³ Of note, the researchers found that vitamin B₁₂, vitamin D, iron, zinc, iodine, calcium, and docosahexaenoic acid were lower in plant-based diets. In contrast, folate; vitamins B₁, B₆, C, and E; polyunsaturated fatty acids; α-linolenic acid; and magnesium intake were higher. Those who consumed meat were at risk for inadequate intake of fiber, polyunsaturated fatty acids, α-linolenic acid, folate, vitamin E, calcium, magnesium, and vitamin D, though vitamin D intake was higher than in vegans/vegetarians.¹³ The results of this meta-analysis indicated the importance of educating patients on what constitutes a well-rounded, micronutrient-rich diet or appropriate supplementation for any diet.

Effects on Gut Microbiome

Any changes in diet can lead to alterations in the gut microbiome, which may impact skin disease, as evidence indicates a bidirectional relationship between gut and skin health.¹⁰ A metagenomic analysis of the gut microbiota in patients with untreated plaque psoriasis revealed a signature dysbiosis for which the researchers developed a psoriasis microbiota index, suggesting the gut microbiota may play a role in psoriasis pathophysiology.¹⁴ Research shows that both the MeD and vegan/vegetarian diets, which are relatively rich in fiber and omega-3 fatty acids and low in saturated fat and animal protein compared to many diets, cause increases in dietary fiber–metabolizing bacteria that produce short-chain fatty acids. These short-chain fatty acids improve gut epithelial integrity and alleviate both gut and systemic inflammation.¹⁰

The changes to the gut microbiome induced by a high-fat diet also are concerning. In contrast to the MeD or vegan/vegetarian diets, consumption of a high-fat diet induces alterations in the composition of the gut microbiota that in turn increase the release of proinflammatory cytokines and promote higher intestinal permeability.¹⁰ Similarly, high sugar consumption promotes increased intestinal permeability and shifts the gut microbiota to organisms that can rapidly utilize simple carbohydrates at the expense of other beneficial organisms, reducing bacterial diversity.¹⁵ The Western diet, which is notable for both high fat and high sugar content, is sometimes referred to as a proinflammatory diet and has been shown to worsen psoriasiformlike lesions in mice.¹⁶ Importantly, most research indicates that high fat and high sugar consumption appear to be more prevalent in psoriasis patients,⁸ but the type of fat consumed in the diet matters. The Western diet includes abundant saturated fat found in meat, dairy products, palm and coconut oils, and processed foods, as well as omega-6 fatty acids that are found in meat, poultry, and eggs. Saturated fat has been shown to promote helper T cell (T_H17) accumulation in the skin, and omega-6 fatty acids serve as precursors to various inflammatory lipid mediators.⁴ This distinction of sources of fat between the Western diet and MeD is important in understanding the diets’ different effects on psoriasis and overall health. As previously discussed, the high intake of omega-3 acids in the MeD is one of the ways it may exert its anti-inflammatory benefits.⁷

Next Steps in Advising Psoriasis Patients

A major limitation of the data for MeD and vegan/vegetarian diets is limited randomized controlled trials evaluating the impact of these diets on psoriasis. Thus, dietary recommendations for psoriasis are not as strong as for other diseases for which more conclusive data exist.⁸ Although the data on diet and psoriasis are not definitive, perhaps dermatologists should shift the question from “Does this diet definitely improve psoriasis?” to “Does this diet definitely improve my patient’s health as a whole and maybe also their psoriasis?” For instance, the MeD has been shown to reduce the risk for type 2 diabetes mellitus and cardiovascular disease as well as to slow cognitive decline.¹⁷ Vegan/vegetarian diets focusing on whole vs processed foods have been shown to be highly effective in combatting obesity, type 2 diabetes mellitus, coronary artery disease including severe atherosclerosis, and hypertension.¹⁸ Psoriasis patients are at increased risk for many of the ailments that the MeD and plant-based diets protect against, making these diets potentially even more impactful than for someone without psoriasis.¹⁹ Dietary recommendations should still be made in conjunction with continuing traditional therapies for psoriasis and in consultation with the patient’s primary care physician and/or dietitian; however, rather than waiting for more randomized controlled trials before making health-promoting recommendations, what would be the downside of starting now? At worst, the dietary change decreases their risk for several metabolic conditions, and at best they may even see an improvement in their psoriasis.

Psoriasis is a chronic inflammatory skin disease for which several lifestyle factors—smoking, alcohol use, and psychological stress—are associated with higher incidence and more severe disease.^1-3 Diet also has been implicated as a factor that can affect psoriasis,⁴ and many patients have shown interest in possible dietary interventions to help their disease.⁵

In 2018, the National Psoriasis Foundation (NPF) presented dietary recommendations for patients based on results from a systematic review. From the available literature, only dietary weight reduction with hypocaloric diets in overweight or obese patients could be strongly recommended, and it has been proven that obesity is associated with worse psoriasis severity.⁶ Other more recent studies have shown that dietary modifications such as intermittent fasting and the ketogenic diet also led to weight loss and improved psoriasis severity in overweight patients; however, it is difficult to discern if the improvement was due to weight loss alone or if the dietary patterns themselves played a role.^7,8 The paucity of well-designed studies evaluating the effects of other dietary changes has prevented further guidelines from being written. We propose that dietary patterns such as the Mediterranean diet (MeD) and vegan/vegetarian diets—even without strong data showing benefits in skin disease—may help to decrease systemic inflammation, improve gut dysbiosis, and help decrease the risk for cardiometabolic comorbidities that are associated with psoriasis.

Mediterranean Diet

The MeD is based on the dietary tendencies of inhabitants from the regions surrounding the Mediterranean Sea and is centered around nutrient-rich foods such as vegetables, olive oil, and legumes while limiting meat and dairy.⁹ The NPF recommended considering a trial of the MeD based on low-quality evidence.⁶ Observational studies have indicated that psoriasis patients are less likely to adhere to the MeD, but those who do have less severe disease.⁸ However, a search of PubMed articles indexed for MEDLINE using the terms Mediterranean diet and psoriasis yielded no prospective interventional studies. Given the association of the MeD with less severe disease, it is important to understand which specific foods in the MeD could be beneficial. Intake of omega-3 fatty acids, such as those found in fatty fish, are important for modulation of systemic inflammation.⁷ High intake of polyphenols—found in fruits and vegetables, extra-virgin olive oil, and wine—also have been implicated in improving inflammatory diseases due to potent antioxidant and anti-inflammatory properties. Individually, fruits, vegetables, whole grains, and sea fish have been associated with lowering C-reactive protein levels, which also is indicative of the benefits of these foods on systemic inflammation.⁷

Vegan/Vegetarian Diets

Although fruits, vegetables, legumes, and whole grains are a substantial component of the MeD, there are limited data on vegetarian or purely vegan plant-based diets. An observational study from the NPF found that only 48.4% (15/31) of patients on the MeD vs 69.0% (20/29) on a vegan diet reported a favorable skin response.⁵ Two case reports also have shown beneficial results of a strict vegan diet for psoriasis and psoriatic arthritis, where whole-food plant-based diets also improved joint symptoms.^10-12 As with any diet, those who pursue a plant-based diet should strive to consume a variety of foods to avoid nutrient deficiencies. A recent systematic meta-analysis of 141 studies evaluated nutrient status of vegan and vegetarian diets compared to pescovegetarians and those who consume meat. All dietary patterns showed varying degrees of low levels of different nutrients.¹³ Of note, the researchers found that vitamin B₁₂, vitamin D, iron, zinc, iodine, calcium, and docosahexaenoic acid were lower in plant-based diets. In contrast, folate; vitamins B₁, B₆, C, and E; polyunsaturated fatty acids; α-linolenic acid; and magnesium intake were higher. Those who consumed meat were at risk for inadequate intake of fiber, polyunsaturated fatty acids, α-linolenic acid, folate, vitamin E, calcium, magnesium, and vitamin D, though vitamin D intake was higher than in vegans/vegetarians.¹³ The results of this meta-analysis indicated the importance of educating patients on what constitutes a well-rounded, micronutrient-rich diet or appropriate supplementation for any diet.

Effects on Gut Microbiome

Any changes in diet can lead to alterations in the gut microbiome, which may impact skin disease, as evidence indicates a bidirectional relationship between gut and skin health.¹⁰ A metagenomic analysis of the gut microbiota in patients with untreated plaque psoriasis revealed a signature dysbiosis for which the researchers developed a psoriasis microbiota index, suggesting the gut microbiota may play a role in psoriasis pathophysiology.¹⁴ Research shows that both the MeD and vegan/vegetarian diets, which are relatively rich in fiber and omega-3 fatty acids and low in saturated fat and animal protein compared to many diets, cause increases in dietary fiber–metabolizing bacteria that produce short-chain fatty acids. These short-chain fatty acids improve gut epithelial integrity and alleviate both gut and systemic inflammation.¹⁰

The changes to the gut microbiome induced by a high-fat diet also are concerning. In contrast to the MeD or vegan/vegetarian diets, consumption of a high-fat diet induces alterations in the composition of the gut microbiota that in turn increase the release of proinflammatory cytokines and promote higher intestinal permeability.¹⁰ Similarly, high sugar consumption promotes increased intestinal permeability and shifts the gut microbiota to organisms that can rapidly utilize simple carbohydrates at the expense of other beneficial organisms, reducing bacterial diversity.¹⁵ The Western diet, which is notable for both high fat and high sugar content, is sometimes referred to as a proinflammatory diet and has been shown to worsen psoriasiformlike lesions in mice.¹⁶ Importantly, most research indicates that high fat and high sugar consumption appear to be more prevalent in psoriasis patients,⁸ but the type of fat consumed in the diet matters. The Western diet includes abundant saturated fat found in meat, dairy products, palm and coconut oils, and processed foods, as well as omega-6 fatty acids that are found in meat, poultry, and eggs. Saturated fat has been shown to promote helper T cell (T_H17) accumulation in the skin, and omega-6 fatty acids serve as precursors to various inflammatory lipid mediators.⁴ This distinction of sources of fat between the Western diet and MeD is important in understanding the diets’ different effects on psoriasis and overall health. As previously discussed, the high intake of omega-3 acids in the MeD is one of the ways it may exert its anti-inflammatory benefits.⁷

Next Steps in Advising Psoriasis Patients

A major limitation of the data for MeD and vegan/vegetarian diets is limited randomized controlled trials evaluating the impact of these diets on psoriasis. Thus, dietary recommendations for psoriasis are not as strong as for other diseases for which more conclusive data exist.⁸ Although the data on diet and psoriasis are not definitive, perhaps dermatologists should shift the question from “Does this diet definitely improve psoriasis?” to “Does this diet definitely improve my patient’s health as a whole and maybe also their psoriasis?” For instance, the MeD has been shown to reduce the risk for type 2 diabetes mellitus and cardiovascular disease as well as to slow cognitive decline.¹⁷ Vegan/vegetarian diets focusing on whole vs processed foods have been shown to be highly effective in combatting obesity, type 2 diabetes mellitus, coronary artery disease including severe atherosclerosis, and hypertension.¹⁸ Psoriasis patients are at increased risk for many of the ailments that the MeD and plant-based diets protect against, making these diets potentially even more impactful than for someone without psoriasis.¹⁹ Dietary recommendations should still be made in conjunction with continuing traditional therapies for psoriasis and in consultation with the patient’s primary care physician and/or dietitian; however, rather than waiting for more randomized controlled trials before making health-promoting recommendations, what would be the downside of starting now? At worst, the dietary change decreases their risk for several metabolic conditions, and at best they may even see an improvement in their psoriasis.

Psoriasis is a chronic autoimmune skin condition that affects approximately 2% to 4% of the US population and notably impacts overall quality of life.^1,2 There is no cure for this long-lasting condition. Fortunately, recent developments in research have led to more targeted therapies, paving the way for a more promising transformative landscape of psoriasis management. Herein, we explore the most up-to-date advancements and developments in the realm of psoriasis care.

Emerging Systemic Therapies

Biologics are cutting-edge treatments available for moderate to severe plaque psoriasis, as IL-17A, IL-23, and tumor necrosis factor α (TNF-α) have been recognized as key targets.³

IL-17—Bimekizumab is a unique monoclonal antibody that inhibits the activity of both IL-17A and IL-17F cytokines.³ This treatment was approved by the US Food and Drug Administration (FDA) in October 2023 for patients with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy.⁴

Bimekizumab outperformed ustekinumab in the BE VIVID phase 3 trial, with 273 of 321 patients (85%) receiving bimekizumab vs 81 of 163 patients (50%) receiving ustekinumab experiencing at least 90% improvement in psoriasis area and severity index (PASI) score at week 16.⁴ In a 2020 observational study (PSO-BIO-REAL), the efficacy rate of skin clearance after 6 months of treatment with biologics was only 25% (1/4).⁵ Aside from moderate to severe plaque psoriasis, bimekizumab demonstrated notable improvement in patients with psoriatic arthritis who had inadequate response or intolerance to TNF-α inhibitors compared to a placebo group in the BE COMPLETE phase 3 trial.⁶

IL-23—Guselkumab, risankizumab, and tildrakizumab are injectable therapies approved by the FDA in 2017 for moderate to severe plaque psoriasis.³ They inhibit IL-23 signaling by targeting the p19 subunit in addition to sparing IL-12.^3,7

A novel oral therapeutic peptide, JNJ-2113—the first oral IL-23 receptor antagonist peptide that blocks IL-23 signaling—has been developed, offering a new way to treat moderate to severe plaque psoriasis. Trial results from a phase 2 study (FRONTIER1) have supported JNJ-2113’s advancement into phase 3.^7,8 Patients who received JNJ-2113 successfully achieved PASI75 in addition to surpassing PASI90 and PASI100 at greater proportions compared to placebo at week 16.⁷

The promising early results of JNJ-2113 provide patients with greater flexibility and convenience for treatment options to address the manifestations of psoriasis. Although a considerable number of patients with moderate to severe plaque psoriasis qualify for advanced therapies, a substantial proportion remain untreated. Introducing an oral route of medication administration may help overcome barriers to therapy access due to a greater preference for pills over injections.⁹

TNF-α Inhibitors—Adalimumab is a TNF-α inhibitor that is used to treat moderate to severe chronic plaque psoriasis in adults who are candidates for systemic phototherapy.^1,10 However, one of the main barriers to initiating treatment has been cost. Biosimilars contribute to market competition, thus allowing the possibility of lower drug prices.¹⁰

There are 9 FDA-approved biosimilar products for adalimumab, with 2 having interchangeable designation. The first interchangeable biosimilar to enter the US market, adalimumab-adbm, became available in July 2023. In October 2023, adalimumab-afzb was granted interchangeable designation,¹¹ which enables pharmacists to swiftly substitute brand products for lower-cost biosimilars, providing patients with equally safe and effective alternatives without the delay of involving the prescribing clinician.¹² Pricing information indicates an initial 5% discount, which may later increase to 60%, from brand name adalimumab. Hopefully, reduced drug costs due to market competition will allow more patients to overcome barriers to therapy access.

IL-12/IL-23—Ustekinumab is a monoclonal antibody that targets IL-12 and IL-23. The FDA recently approved ustekinumab-auub as the first interchangeable ustekinumab biosimilar for the treatment of various inflammatory diseases, including moderate to severe plaque psoriasis and psoriatic arthritis.^12,13 The approval of ustekinumab-auub expands therapeutic options for the treatment of diverse inflammatory diseases. As the first interchangeable biosimilar in its category, this development underscores the importance of biosimilars in providing effective and accessible treatment.^12,14

Topical Innovations

In October 2023, the FDA approved an expanded indication for roflumilast cream 0.3% to treat children as young as 6 years for plaque psoriasis, even for use in intertriginous areas,¹⁵ which is a milestone given the lack of treatment options for the pediatric population because topical steroids, the most common treatment option for plaque psoriasis, can have safety concerns related to long-term use. With the advent of this steroid-free topical agent, pediatric patients have a safe and well-tolerated option for managing plaque psoriasis.¹⁶ This promising effort will now expand to trials in children as young as 2 years to test efficacy.¹⁶

Engel et al¹⁷ proposed a new algorithmic approach to the topical management of psoriasis with roflumilast cream and tapinarof cream as first-line treatments for mild disease due to their novelty in treating intertriginous areas, whereas traditional topical steroids in these areas would be inapt.¹⁷ The latest indication for roflumilast cream suggests that this proposed recommendation could be a promising and convenient enhancement to psoriasis management, potentially outperforming traditional topical corticosteroids.^15,17

Final Thoughts

Innovative targeted therapies ranging from new biologic agents to broader applications of topical treatments hold the potential to transform conventional psoriasis management with greater efficacy and safety, which can help create a more effective and personalized approach with greater patient satisfaction, ultimately enhancing overall quality of life. The choice of treatment is dependent not only on the severity of the disease but also on accessibility considerations such as cost. Overall, these innovative therapies add substantial value to the treatment armamentarium for psoriasis.

Psoriasis is a chronic autoimmune skin condition that affects approximately 2% to 4% of the US population and notably impacts overall quality of life.^1,2 There is no cure for this long-lasting condition. Fortunately, recent developments in research have led to more targeted therapies, paving the way for a more promising transformative landscape of psoriasis management. Herein, we explore the most up-to-date advancements and developments in the realm of psoriasis care.

Emerging Systemic Therapies

Biologics are cutting-edge treatments available for moderate to severe plaque psoriasis, as IL-17A, IL-23, and tumor necrosis factor α (TNF-α) have been recognized as key targets.³

IL-17—Bimekizumab is a unique monoclonal antibody that inhibits the activity of both IL-17A and IL-17F cytokines.³ This treatment was approved by the US Food and Drug Administration (FDA) in October 2023 for patients with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy.⁴

Bimekizumab outperformed ustekinumab in the BE VIVID phase 3 trial, with 273 of 321 patients (85%) receiving bimekizumab vs 81 of 163 patients (50%) receiving ustekinumab experiencing at least 90% improvement in psoriasis area and severity index (PASI) score at week 16.⁴ In a 2020 observational study (PSO-BIO-REAL), the efficacy rate of skin clearance after 6 months of treatment with biologics was only 25% (1/4).⁵ Aside from moderate to severe plaque psoriasis, bimekizumab demonstrated notable improvement in patients with psoriatic arthritis who had inadequate response or intolerance to TNF-α inhibitors compared to a placebo group in the BE COMPLETE phase 3 trial.⁶

IL-23—Guselkumab, risankizumab, and tildrakizumab are injectable therapies approved by the FDA in 2017 for moderate to severe plaque psoriasis.³ They inhibit IL-23 signaling by targeting the p19 subunit in addition to sparing IL-12.^3,7

A novel oral therapeutic peptide, JNJ-2113—the first oral IL-23 receptor antagonist peptide that blocks IL-23 signaling—has been developed, offering a new way to treat moderate to severe plaque psoriasis. Trial results from a phase 2 study (FRONTIER1) have supported JNJ-2113’s advancement into phase 3.^7,8 Patients who received JNJ-2113 successfully achieved PASI75 in addition to surpassing PASI90 and PASI100 at greater proportions compared to placebo at week 16.⁷

The promising early results of JNJ-2113 provide patients with greater flexibility and convenience for treatment options to address the manifestations of psoriasis. Although a considerable number of patients with moderate to severe plaque psoriasis qualify for advanced therapies, a substantial proportion remain untreated. Introducing an oral route of medication administration may help overcome barriers to therapy access due to a greater preference for pills over injections.⁹

TNF-α Inhibitors—Adalimumab is a TNF-α inhibitor that is used to treat moderate to severe chronic plaque psoriasis in adults who are candidates for systemic phototherapy.^1,10 However, one of the main barriers to initiating treatment has been cost. Biosimilars contribute to market competition, thus allowing the possibility of lower drug prices.¹⁰

There are 9 FDA-approved biosimilar products for adalimumab, with 2 having interchangeable designation. The first interchangeable biosimilar to enter the US market, adalimumab-adbm, became available in July 2023. In October 2023, adalimumab-afzb was granted interchangeable designation,¹¹ which enables pharmacists to swiftly substitute brand products for lower-cost biosimilars, providing patients with equally safe and effective alternatives without the delay of involving the prescribing clinician.¹² Pricing information indicates an initial 5% discount, which may later increase to 60%, from brand name adalimumab. Hopefully, reduced drug costs due to market competition will allow more patients to overcome barriers to therapy access.

IL-12/IL-23—Ustekinumab is a monoclonal antibody that targets IL-12 and IL-23. The FDA recently approved ustekinumab-auub as the first interchangeable ustekinumab biosimilar for the treatment of various inflammatory diseases, including moderate to severe plaque psoriasis and psoriatic arthritis.^12,13 The approval of ustekinumab-auub expands therapeutic options for the treatment of diverse inflammatory diseases. As the first interchangeable biosimilar in its category, this development underscores the importance of biosimilars in providing effective and accessible treatment.^12,14

Topical Innovations

In October 2023, the FDA approved an expanded indication for roflumilast cream 0.3% to treat children as young as 6 years for plaque psoriasis, even for use in intertriginous areas,¹⁵ which is a milestone given the lack of treatment options for the pediatric population because topical steroids, the most common treatment option for plaque psoriasis, can have safety concerns related to long-term use. With the advent of this steroid-free topical agent, pediatric patients have a safe and well-tolerated option for managing plaque psoriasis.¹⁶ This promising effort will now expand to trials in children as young as 2 years to test efficacy.¹⁶

Engel et al¹⁷ proposed a new algorithmic approach to the topical management of psoriasis with roflumilast cream and tapinarof cream as first-line treatments for mild disease due to their novelty in treating intertriginous areas, whereas traditional topical steroids in these areas would be inapt.¹⁷ The latest indication for roflumilast cream suggests that this proposed recommendation could be a promising and convenient enhancement to psoriasis management, potentially outperforming traditional topical corticosteroids.^15,17

Final Thoughts

Innovative targeted therapies ranging from new biologic agents to broader applications of topical treatments hold the potential to transform conventional psoriasis management with greater efficacy and safety, which can help create a more effective and personalized approach with greater patient satisfaction, ultimately enhancing overall quality of life. The choice of treatment is dependent not only on the severity of the disease but also on accessibility considerations such as cost. Overall, these innovative therapies add substantial value to the treatment armamentarium for psoriasis.

Psoriasis is a chronic autoimmune skin condition that affects approximately 2% to 4% of the US population and notably impacts overall quality of life.^1,2 There is no cure for this long-lasting condition. Fortunately, recent developments in research have led to more targeted therapies, paving the way for a more promising transformative landscape of psoriasis management. Herein, we explore the most up-to-date advancements and developments in the realm of psoriasis care.

Emerging Systemic Therapies

Biologics are cutting-edge treatments available for moderate to severe plaque psoriasis, as IL-17A, IL-23, and tumor necrosis factor α (TNF-α) have been recognized as key targets.³

IL-17—Bimekizumab is a unique monoclonal antibody that inhibits the activity of both IL-17A and IL-17F cytokines.³ This treatment was approved by the US Food and Drug Administration (FDA) in October 2023 for patients with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy.⁴

Bimekizumab outperformed ustekinumab in the BE VIVID phase 3 trial, with 273 of 321 patients (85%) receiving bimekizumab vs 81 of 163 patients (50%) receiving ustekinumab experiencing at least 90% improvement in psoriasis area and severity index (PASI) score at week 16.⁴ In a 2020 observational study (PSO-BIO-REAL), the efficacy rate of skin clearance after 6 months of treatment with biologics was only 25% (1/4).⁵ Aside from moderate to severe plaque psoriasis, bimekizumab demonstrated notable improvement in patients with psoriatic arthritis who had inadequate response or intolerance to TNF-α inhibitors compared to a placebo group in the BE COMPLETE phase 3 trial.⁶

IL-23—Guselkumab, risankizumab, and tildrakizumab are injectable therapies approved by the FDA in 2017 for moderate to severe plaque psoriasis.³ They inhibit IL-23 signaling by targeting the p19 subunit in addition to sparing IL-12.^3,7

A novel oral therapeutic peptide, JNJ-2113—the first oral IL-23 receptor antagonist peptide that blocks IL-23 signaling—has been developed, offering a new way to treat moderate to severe plaque psoriasis. Trial results from a phase 2 study (FRONTIER1) have supported JNJ-2113’s advancement into phase 3.^7,8 Patients who received JNJ-2113 successfully achieved PASI75 in addition to surpassing PASI90 and PASI100 at greater proportions compared to placebo at week 16.⁷

The promising early results of JNJ-2113 provide patients with greater flexibility and convenience for treatment options to address the manifestations of psoriasis. Although a considerable number of patients with moderate to severe plaque psoriasis qualify for advanced therapies, a substantial proportion remain untreated. Introducing an oral route of medication administration may help overcome barriers to therapy access due to a greater preference for pills over injections.⁹

TNF-α Inhibitors—Adalimumab is a TNF-α inhibitor that is used to treat moderate to severe chronic plaque psoriasis in adults who are candidates for systemic phototherapy.^1,10 However, one of the main barriers to initiating treatment has been cost. Biosimilars contribute to market competition, thus allowing the possibility of lower drug prices.¹⁰

There are 9 FDA-approved biosimilar products for adalimumab, with 2 having interchangeable designation. The first interchangeable biosimilar to enter the US market, adalimumab-adbm, became available in July 2023. In October 2023, adalimumab-afzb was granted interchangeable designation,¹¹ which enables pharmacists to swiftly substitute brand products for lower-cost biosimilars, providing patients with equally safe and effective alternatives without the delay of involving the prescribing clinician.¹² Pricing information indicates an initial 5% discount, which may later increase to 60%, from brand name adalimumab. Hopefully, reduced drug costs due to market competition will allow more patients to overcome barriers to therapy access.

IL-12/IL-23—Ustekinumab is a monoclonal antibody that targets IL-12 and IL-23. The FDA recently approved ustekinumab-auub as the first interchangeable ustekinumab biosimilar for the treatment of various inflammatory diseases, including moderate to severe plaque psoriasis and psoriatic arthritis.^12,13 The approval of ustekinumab-auub expands therapeutic options for the treatment of diverse inflammatory diseases. As the first interchangeable biosimilar in its category, this development underscores the importance of biosimilars in providing effective and accessible treatment.^12,14

Topical Innovations

In October 2023, the FDA approved an expanded indication for roflumilast cream 0.3% to treat children as young as 6 years for plaque psoriasis, even for use in intertriginous areas,¹⁵ which is a milestone given the lack of treatment options for the pediatric population because topical steroids, the most common treatment option for plaque psoriasis, can have safety concerns related to long-term use. With the advent of this steroid-free topical agent, pediatric patients have a safe and well-tolerated option for managing plaque psoriasis.¹⁶ This promising effort will now expand to trials in children as young as 2 years to test efficacy.¹⁶

Engel et al¹⁷ proposed a new algorithmic approach to the topical management of psoriasis with roflumilast cream and tapinarof cream as first-line treatments for mild disease due to their novelty in treating intertriginous areas, whereas traditional topical steroids in these areas would be inapt.¹⁷ The latest indication for roflumilast cream suggests that this proposed recommendation could be a promising and convenient enhancement to psoriasis management, potentially outperforming traditional topical corticosteroids.^15,17

Final Thoughts

Innovative targeted therapies ranging from new biologic agents to broader applications of topical treatments hold the potential to transform conventional psoriasis management with greater efficacy and safety, which can help create a more effective and personalized approach with greater patient satisfaction, ultimately enhancing overall quality of life. The choice of treatment is dependent not only on the severity of the disease but also on accessibility considerations such as cost. Overall, these innovative therapies add substantial value to the treatment armamentarium for psoriasis.

In April 2023, the US Preventive Services Task Force (USPSTF) issued a controversial recommendation that the current evidence is insufficient to assess the benefits vs harms of visual skin examination by clinicians for skin cancer screening in adolescents and adults who do not have signs or symptoms of skin cancer.^1,2 This recommendation by the USPSTF has not changed in a quarter century,³ but a recent study described an interesting paradox that should trigger wide evaluation and debate.

Patel et al⁴ analyzed data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results Program from January 2000 to December 2018 to identify adults with a diagnosis of first primary melanoma in situ (MIS). Overall mortality was then determined through the National Vital Statistics System, which provides cause-of-death information for all deaths in the United States. The authors found 137,872 patients who had 1—and only 1—MIS discovered over the observation period. These patients predominantly were White (96.7%), and the mean (SD) age at diagnosis was 61.9 (16.5) years. During 910,308 total person-years of follow-up (mean [SD], 6.6 [5.1] years), 893 (0.6%) patients died of melanoma and 17,327 (12.6%) died of any cause. The 15-year melanoma-specific standardized mortality rate (SMR) was 1.89 (95% CI, 1.77-2.02), yet the 15-year overall survival relative to matched population controls was 112.4% (95% CI, 112.0%-112.8%), thus all-cause SMR was significantly lower at 0.68 (95% CI, 0.67-0.7). Although MIS was associated with a small increase in cohort melanoma mortality, overall mortality was actually lower than in the general population.⁴

Patel et al⁴ did a further broader search that included an additional 18,379 patients who also experienced a second primary melanoma, of which 6751 (36.7%) were invasive and 11,628 (63.3%) were in situ, with a melanoma-specific survival of 98.2% (95% CI, 97.6%-98.5%). Yet relative all-cause survival was significantly higher at 126.7% (95% CI, 125.5%-128.0%). Even among patients in whom a second primary melanoma was invasive, melanoma-specific survival was reduced to 91.1% (95% CI, 90.0%-92.1%), but relative all-cause survival was 116.7% (95% CI, 115%-118.4%). These data in the overall cohort of 155,251 patients showed a discordance between melanoma mortality, which was 4.27-times higher than in the general population (SMR, 4.27; 95% CI, 4.07-4.48), and a lower risk for death from all causes that was approximately 27% lower than in the general population (SMR, 0.73; 95% CI, 0.72-0.74). The authors showed that their findings were not associated with socioeconomic status.⁴

The analysis by Patel et al⁴ is now the second study in the literature to show this discordant melanoma survival pattern. In an earlier Australian study of 2452 melanoma patients, Watts et al⁵ reported that melanoma detection during routine skin checks was associated with a 25% lower all-cause mortality (hazard ratio, 0.75; 95% CI, 0.63-0.90) but not melanoma-specific mortality after multivariable adjustment for a variety of factors including socioeconomic status.These analyses by 2 different groups of investigators have broad implications. Both groups suggested that the improved life span in melanoma patients may be due to health-seeking behavior, which has been defined as “any action undertaken by individuals who perceive themselves to have a health problem or to be ill for the purpose of finding an appropriate remedy.”⁶

Once treated for melanoma, it is clear that patients are likely to return at regular intervals for thorough full-body skin examinations, but this activity alone could not be responsible for improved all-cause mortality in the face of increased melanoma-specific mortality. It seems the authors are implying a broader concept of good health behavior, originally defined by MacKian⁷ as encompassing “activities undertaken to maintain good health, to prevent ill health, as well as dealing with any departure from a good state of health,” such as overt behavioral patterns, actions, and habits with the goal of maintenance, restoration, and improvement of one’s health. A variety of behaviors fall within such a definition including smoking cessation, decreased alcohol use, good diet, more physical activity, safe sexual behavior, scheduling physician visits, medication adherence, vaccination, and yes—screening examinations for health problems.⁸

The concept that individuals who are diagnosed with melanoma fall into a pattern of good health behavior is an interesting hypothesis that must remain speculative until the multiple aspects of good health behavior are rigorously studied. This concept coexists with the hypothesis of melanoma “overdiagnosis”—the idea that many melanomas are detected that will never lead to death.⁹ Both concepts deserve further analysis. Unquestionably, a randomized controlled trial could never recruit patients willing to undergo long-term untreated observation of their melanomas to test the hypothesis that their melanoma diagnosis would eventually lead to death. Furthermore, Patel et al⁴ do suggest that even MIS carries a small but measurable increased risk for death from the disease, which is not particularly supportive of the overdiagnosis hypothesis; however, analysis of the concept that improved individual health behavior is at least in part responsible for the first discovery of melanomas is certainly approachable. Here is the key question: Did the melanoma diagnosis trigger a sudden change in multiple aspects of health behavior that led to significant all-cause mortality benefits? The average age of the population studied by Patel et al⁴ was approximately 62 years. One wonders whether the consequences of a lifetime of established health behavior patterns can be rapidly ­modified—certainly possible but again remains to be proven by further studies.

Conversely, the alternative hypothesis is that discovery of MIS was the result of active pursuit of self-examination and screening procedures as part of individually ingrained good health behavior over a lifetime. Goodwin et al¹⁰ carried out a study in a sample of the Medicare population aged 69 to 90 years looking at men who had prostate cancer screening via prostate-specific antigen measurement and women who had undergone mammography in older age, compared to the contrast population who had not had these screening procedures. They tracked date of death in Medicare enrollment files. They identified 543,970 women and 362,753 men who were aged 69 to 90 years as of January 1, 2003. Patients were stratified by life expectancy based on age and comorbidity. Within each stratum, the patients with cancer screening had higher actual median survival than those who were not screened, with differences ranging from 1.7 to 2.1 years for women and 0.9 to 1.1 years for men.¹⁰ These results were not the result of lower prostate or breast cancer mortality. Rather, one surmises that other health factors yielded lower mortality in the screened cohorts.

A full-body skin examination is a time-consuming process. Patients who come to their physician for a routine annual physical don’t expect a skin examination and very few physicians have the time for a long detailed full-body skin examination. When the patient presents to a dermatologist for an examination, it often is because they have real concerns; for example, they may have had a family member who died of skin cancer, or the patient themself may have noticed a worrisome lesion. Patients, not physicians, are the drivers of skin cancer screening, a fact that often is dismissed by those who are not necessarily supportive of the practice.

In light of the findings of Patel et al,⁴ it is essential that the USPSTF reviews be reanalyzed to compare skin cancer–specific mortality, all-cause mortality, and lifespan in individuals who pursue skin cancer screening; the reanalysis also should not be exclusively limited to survival. With the advent of the immune checkpoint inhibitors, patients with metastatic melanoma are living much longer.¹¹ The burden of living with metastatic cancer must be characterized and measured to have a complete picture and a valid analysis.

After the release of the USPSTF recommendation, there have been calls for large-scale studies to prove the benefits of skin cancer screening.¹² Such studies may be valuable; however, if the hypothesis that overall healthy behavior as the major outcome determinant is substantiated, it may prove quite challenging to perform tests of association with specific interventions. It has been shown that skin cancer screening does lead to discovery of more melanomas,¹³ yet in light of the paradox described by Patel et al,⁴ it also is likely that causes of death other than melanoma impact overall mortality. Patients who pursue skin examinations may engage in multiple different health activities that are beneficial in the long term, making it difficult to analyze the specific benefit of skin cancer screening in isolation. It may prove difficult to ask patients to omit selected aspects of healthy behavior to try to prove the point. At this time, there is much more work to be done prior to offering opinions on the importance of skin cancer examination in isolation to improve overall health care. In the meantime, dermatologists owe it to our patients to continue to diligently pursue thorough and detailed skin examinations.

In April 2023, the US Preventive Services Task Force (USPSTF) issued a controversial recommendation that the current evidence is insufficient to assess the benefits vs harms of visual skin examination by clinicians for skin cancer screening in adolescents and adults who do not have signs or symptoms of skin cancer.^1,2 This recommendation by the USPSTF has not changed in a quarter century,³ but a recent study described an interesting paradox that should trigger wide evaluation and debate.

Patel et al⁴ analyzed data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results Program from January 2000 to December 2018 to identify adults with a diagnosis of first primary melanoma in situ (MIS). Overall mortality was then determined through the National Vital Statistics System, which provides cause-of-death information for all deaths in the United States. The authors found 137,872 patients who had 1—and only 1—MIS discovered over the observation period. These patients predominantly were White (96.7%), and the mean (SD) age at diagnosis was 61.9 (16.5) years. During 910,308 total person-years of follow-up (mean [SD], 6.6 [5.1] years), 893 (0.6%) patients died of melanoma and 17,327 (12.6%) died of any cause. The 15-year melanoma-specific standardized mortality rate (SMR) was 1.89 (95% CI, 1.77-2.02), yet the 15-year overall survival relative to matched population controls was 112.4% (95% CI, 112.0%-112.8%), thus all-cause SMR was significantly lower at 0.68 (95% CI, 0.67-0.7). Although MIS was associated with a small increase in cohort melanoma mortality, overall mortality was actually lower than in the general population.⁴

Patel et al⁴ did a further broader search that included an additional 18,379 patients who also experienced a second primary melanoma, of which 6751 (36.7%) were invasive and 11,628 (63.3%) were in situ, with a melanoma-specific survival of 98.2% (95% CI, 97.6%-98.5%). Yet relative all-cause survival was significantly higher at 126.7% (95% CI, 125.5%-128.0%). Even among patients in whom a second primary melanoma was invasive, melanoma-specific survival was reduced to 91.1% (95% CI, 90.0%-92.1%), but relative all-cause survival was 116.7% (95% CI, 115%-118.4%). These data in the overall cohort of 155,251 patients showed a discordance between melanoma mortality, which was 4.27-times higher than in the general population (SMR, 4.27; 95% CI, 4.07-4.48), and a lower risk for death from all causes that was approximately 27% lower than in the general population (SMR, 0.73; 95% CI, 0.72-0.74). The authors showed that their findings were not associated with socioeconomic status.⁴

The analysis by Patel et al⁴ is now the second study in the literature to show this discordant melanoma survival pattern. In an earlier Australian study of 2452 melanoma patients, Watts et al⁵ reported that melanoma detection during routine skin checks was associated with a 25% lower all-cause mortality (hazard ratio, 0.75; 95% CI, 0.63-0.90) but not melanoma-specific mortality after multivariable adjustment for a variety of factors including socioeconomic status.These analyses by 2 different groups of investigators have broad implications. Both groups suggested that the improved life span in melanoma patients may be due to health-seeking behavior, which has been defined as “any action undertaken by individuals who perceive themselves to have a health problem or to be ill for the purpose of finding an appropriate remedy.”⁶

Once treated for melanoma, it is clear that patients are likely to return at regular intervals for thorough full-body skin examinations, but this activity alone could not be responsible for improved all-cause mortality in the face of increased melanoma-specific mortality. It seems the authors are implying a broader concept of good health behavior, originally defined by MacKian⁷ as encompassing “activities undertaken to maintain good health, to prevent ill health, as well as dealing with any departure from a good state of health,” such as overt behavioral patterns, actions, and habits with the goal of maintenance, restoration, and improvement of one’s health. A variety of behaviors fall within such a definition including smoking cessation, decreased alcohol use, good diet, more physical activity, safe sexual behavior, scheduling physician visits, medication adherence, vaccination, and yes—screening examinations for health problems.⁸

The concept that individuals who are diagnosed with melanoma fall into a pattern of good health behavior is an interesting hypothesis that must remain speculative until the multiple aspects of good health behavior are rigorously studied. This concept coexists with the hypothesis of melanoma “overdiagnosis”—the idea that many melanomas are detected that will never lead to death.⁹ Both concepts deserve further analysis. Unquestionably, a randomized controlled trial could never recruit patients willing to undergo long-term untreated observation of their melanomas to test the hypothesis that their melanoma diagnosis would eventually lead to death. Furthermore, Patel et al⁴ do suggest that even MIS carries a small but measurable increased risk for death from the disease, which is not particularly supportive of the overdiagnosis hypothesis; however, analysis of the concept that improved individual health behavior is at least in part responsible for the first discovery of melanomas is certainly approachable. Here is the key question: Did the melanoma diagnosis trigger a sudden change in multiple aspects of health behavior that led to significant all-cause mortality benefits? The average age of the population studied by Patel et al⁴ was approximately 62 years. One wonders whether the consequences of a lifetime of established health behavior patterns can be rapidly ­modified—certainly possible but again remains to be proven by further studies.

Conversely, the alternative hypothesis is that discovery of MIS was the result of active pursuit of self-examination and screening procedures as part of individually ingrained good health behavior over a lifetime. Goodwin et al¹⁰ carried out a study in a sample of the Medicare population aged 69 to 90 years looking at men who had prostate cancer screening via prostate-specific antigen measurement and women who had undergone mammography in older age, compared to the contrast population who had not had these screening procedures. They tracked date of death in Medicare enrollment files. They identified 543,970 women and 362,753 men who were aged 69 to 90 years as of January 1, 2003. Patients were stratified by life expectancy based on age and comorbidity. Within each stratum, the patients with cancer screening had higher actual median survival than those who were not screened, with differences ranging from 1.7 to 2.1 years for women and 0.9 to 1.1 years for men.¹⁰ These results were not the result of lower prostate or breast cancer mortality. Rather, one surmises that other health factors yielded lower mortality in the screened cohorts.

A full-body skin examination is a time-consuming process. Patients who come to their physician for a routine annual physical don’t expect a skin examination and very few physicians have the time for a long detailed full-body skin examination. When the patient presents to a dermatologist for an examination, it often is because they have real concerns; for example, they may have had a family member who died of skin cancer, or the patient themself may have noticed a worrisome lesion. Patients, not physicians, are the drivers of skin cancer screening, a fact that often is dismissed by those who are not necessarily supportive of the practice.

In light of the findings of Patel et al,⁴ it is essential that the USPSTF reviews be reanalyzed to compare skin cancer–specific mortality, all-cause mortality, and lifespan in individuals who pursue skin cancer screening; the reanalysis also should not be exclusively limited to survival. With the advent of the immune checkpoint inhibitors, patients with metastatic melanoma are living much longer.¹¹ The burden of living with metastatic cancer must be characterized and measured to have a complete picture and a valid analysis.

After the release of the USPSTF recommendation, there have been calls for large-scale studies to prove the benefits of skin cancer screening.¹² Such studies may be valuable; however, if the hypothesis that overall healthy behavior as the major outcome determinant is substantiated, it may prove quite challenging to perform tests of association with specific interventions. It has been shown that skin cancer screening does lead to discovery of more melanomas,¹³ yet in light of the paradox described by Patel et al,⁴ it also is likely that causes of death other than melanoma impact overall mortality. Patients who pursue skin examinations may engage in multiple different health activities that are beneficial in the long term, making it difficult to analyze the specific benefit of skin cancer screening in isolation. It may prove difficult to ask patients to omit selected aspects of healthy behavior to try to prove the point. At this time, there is much more work to be done prior to offering opinions on the importance of skin cancer examination in isolation to improve overall health care. In the meantime, dermatologists owe it to our patients to continue to diligently pursue thorough and detailed skin examinations.

In April 2023, the US Preventive Services Task Force (USPSTF) issued a controversial recommendation that the current evidence is insufficient to assess the benefits vs harms of visual skin examination by clinicians for skin cancer screening in adolescents and adults who do not have signs or symptoms of skin cancer.^1,2 This recommendation by the USPSTF has not changed in a quarter century,³ but a recent study described an interesting paradox that should trigger wide evaluation and debate.

Patel et al⁴ analyzed data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results Program from January 2000 to December 2018 to identify adults with a diagnosis of first primary melanoma in situ (MIS). Overall mortality was then determined through the National Vital Statistics System, which provides cause-of-death information for all deaths in the United States. The authors found 137,872 patients who had 1—and only 1—MIS discovered over the observation period. These patients predominantly were White (96.7%), and the mean (SD) age at diagnosis was 61.9 (16.5) years. During 910,308 total person-years of follow-up (mean [SD], 6.6 [5.1] years), 893 (0.6%) patients died of melanoma and 17,327 (12.6%) died of any cause. The 15-year melanoma-specific standardized mortality rate (SMR) was 1.89 (95% CI, 1.77-2.02), yet the 15-year overall survival relative to matched population controls was 112.4% (95% CI, 112.0%-112.8%), thus all-cause SMR was significantly lower at 0.68 (95% CI, 0.67-0.7). Although MIS was associated with a small increase in cohort melanoma mortality, overall mortality was actually lower than in the general population.⁴

Patel et al⁴ did a further broader search that included an additional 18,379 patients who also experienced a second primary melanoma, of which 6751 (36.7%) were invasive and 11,628 (63.3%) were in situ, with a melanoma-specific survival of 98.2% (95% CI, 97.6%-98.5%). Yet relative all-cause survival was significantly higher at 126.7% (95% CI, 125.5%-128.0%). Even among patients in whom a second primary melanoma was invasive, melanoma-specific survival was reduced to 91.1% (95% CI, 90.0%-92.1%), but relative all-cause survival was 116.7% (95% CI, 115%-118.4%). These data in the overall cohort of 155,251 patients showed a discordance between melanoma mortality, which was 4.27-times higher than in the general population (SMR, 4.27; 95% CI, 4.07-4.48), and a lower risk for death from all causes that was approximately 27% lower than in the general population (SMR, 0.73; 95% CI, 0.72-0.74). The authors showed that their findings were not associated with socioeconomic status.⁴

The analysis by Patel et al⁴ is now the second study in the literature to show this discordant melanoma survival pattern. In an earlier Australian study of 2452 melanoma patients, Watts et al⁵ reported that melanoma detection during routine skin checks was associated with a 25% lower all-cause mortality (hazard ratio, 0.75; 95% CI, 0.63-0.90) but not melanoma-specific mortality after multivariable adjustment for a variety of factors including socioeconomic status.These analyses by 2 different groups of investigators have broad implications. Both groups suggested that the improved life span in melanoma patients may be due to health-seeking behavior, which has been defined as “any action undertaken by individuals who perceive themselves to have a health problem or to be ill for the purpose of finding an appropriate remedy.”⁶

Once treated for melanoma, it is clear that patients are likely to return at regular intervals for thorough full-body skin examinations, but this activity alone could not be responsible for improved all-cause mortality in the face of increased melanoma-specific mortality. It seems the authors are implying a broader concept of good health behavior, originally defined by MacKian⁷ as encompassing “activities undertaken to maintain good health, to prevent ill health, as well as dealing with any departure from a good state of health,” such as overt behavioral patterns, actions, and habits with the goal of maintenance, restoration, and improvement of one’s health. A variety of behaviors fall within such a definition including smoking cessation, decreased alcohol use, good diet, more physical activity, safe sexual behavior, scheduling physician visits, medication adherence, vaccination, and yes—screening examinations for health problems.⁸

The concept that individuals who are diagnosed with melanoma fall into a pattern of good health behavior is an interesting hypothesis that must remain speculative until the multiple aspects of good health behavior are rigorously studied. This concept coexists with the hypothesis of melanoma “overdiagnosis”—the idea that many melanomas are detected that will never lead to death.⁹ Both concepts deserve further analysis. Unquestionably, a randomized controlled trial could never recruit patients willing to undergo long-term untreated observation of their melanomas to test the hypothesis that their melanoma diagnosis would eventually lead to death. Furthermore, Patel et al⁴ do suggest that even MIS carries a small but measurable increased risk for death from the disease, which is not particularly supportive of the overdiagnosis hypothesis; however, analysis of the concept that improved individual health behavior is at least in part responsible for the first discovery of melanomas is certainly approachable. Here is the key question: Did the melanoma diagnosis trigger a sudden change in multiple aspects of health behavior that led to significant all-cause mortality benefits? The average age of the population studied by Patel et al⁴ was approximately 62 years. One wonders whether the consequences of a lifetime of established health behavior patterns can be rapidly ­modified—certainly possible but again remains to be proven by further studies.

Conversely, the alternative hypothesis is that discovery of MIS was the result of active pursuit of self-examination and screening procedures as part of individually ingrained good health behavior over a lifetime. Goodwin et al¹⁰ carried out a study in a sample of the Medicare population aged 69 to 90 years looking at men who had prostate cancer screening via prostate-specific antigen measurement and women who had undergone mammography in older age, compared to the contrast population who had not had these screening procedures. They tracked date of death in Medicare enrollment files. They identified 543,970 women and 362,753 men who were aged 69 to 90 years as of January 1, 2003. Patients were stratified by life expectancy based on age and comorbidity. Within each stratum, the patients with cancer screening had higher actual median survival than those who were not screened, with differences ranging from 1.7 to 2.1 years for women and 0.9 to 1.1 years for men.¹⁰ These results were not the result of lower prostate or breast cancer mortality. Rather, one surmises that other health factors yielded lower mortality in the screened cohorts.

A full-body skin examination is a time-consuming process. Patients who come to their physician for a routine annual physical don’t expect a skin examination and very few physicians have the time for a long detailed full-body skin examination. When the patient presents to a dermatologist for an examination, it often is because they have real concerns; for example, they may have had a family member who died of skin cancer, or the patient themself may have noticed a worrisome lesion. Patients, not physicians, are the drivers of skin cancer screening, a fact that often is dismissed by those who are not necessarily supportive of the practice.

In light of the findings of Patel et al,⁴ it is essential that the USPSTF reviews be reanalyzed to compare skin cancer–specific mortality, all-cause mortality, and lifespan in individuals who pursue skin cancer screening; the reanalysis also should not be exclusively limited to survival. With the advent of the immune checkpoint inhibitors, patients with metastatic melanoma are living much longer.¹¹ The burden of living with metastatic cancer must be characterized and measured to have a complete picture and a valid analysis.

After the release of the USPSTF recommendation, there have been calls for large-scale studies to prove the benefits of skin cancer screening.¹² Such studies may be valuable; however, if the hypothesis that overall healthy behavior as the major outcome determinant is substantiated, it may prove quite challenging to perform tests of association with specific interventions. It has been shown that skin cancer screening does lead to discovery of more melanomas,¹³ yet in light of the paradox described by Patel et al,⁴ it also is likely that causes of death other than melanoma impact overall mortality. Patients who pursue skin examinations may engage in multiple different health activities that are beneficial in the long term, making it difficult to analyze the specific benefit of skin cancer screening in isolation. It may prove difficult to ask patients to omit selected aspects of healthy behavior to try to prove the point. At this time, there is much more work to be done prior to offering opinions on the importance of skin cancer examination in isolation to improve overall health care. In the meantime, dermatologists owe it to our patients to continue to diligently pursue thorough and detailed skin examinations.

A pair of dueling editorials in the journal Hypertension debate whether our focus should be on sodium or its often neglected partner, potassium.

Should we cut sodium from our diet or eat more potassium to lower blood pressure? The answer requires an intricate understanding of renal physiology that is fascinating. To nephrologists. A meta-analysis of 85 trials showed a consistent and linear. It may also depend on where you live and whether your concern is treating individuals or implementing effective food policy.

The Case for Sodium Restriction

Stephen Juraschek, MD, PhD, of the Beth Israel Deaconess Medical Center, Boston, Massachusetts, co-author of one editorial, told me in a zoom interview that he believes his side of the debate clearly has the stronger argument. Of the two cations in question, there has been infinitely more ink spilled about sodium.

Studies such as INTERSALT, the DASH diet, and TOHP may be the most well-known, but there are many, many intervention studies of sodium restriction’s effect on blood pressure. A meta-analysis of 85 trials of showed a consistent and linear relationship between sodium reduction and blood pressure. In contrast, the evidence base for potassium is more limited and less consistent. There are half as many trials with potassium, and its ability to lower blood pressure may depend on how much sodium is present in the diet.

An outlier in the sodium restriction evidence base is the PURE study, which suggested that extreme sodium restriction could increase cardiovascular mortality, but the trial suffered from two potential issues. First, it used a single spot urine specimen to measure sodium rather than the generally accepted more accurate 24-hour urine collection. A reanalysis of the TOHP study using a spot urine rather than a 24-hour urine collection changed the relationship between sodium intake and mortality and possibly explained the U-shaped association observed in PURE. Second, PURE was an observational cohort and was prone to confounding, or in this case, reverse causation. Why did people who consumed very little salt have an increased risk for cardiovascular disease? It is very possible that people with a high risk for cardiovascular disease were told to consume less salt to begin with. Hence B led to A rather than A leading to B.

The debate on sodium restriction has been bitter at times. Opposing camps formed, and people took sides in the “salt wars.” A group of researchers, termed the Jackson 6, met and decided to end the controversy by running a randomized trial in US prisons (having discounted the options of long-term care homes and military bases). They detailed their plan in an editorial in Hypertension. The study never came to fruition for two reasons: the obvious ethical problems of experimenting on prisoners and the revelation of undisclosed salt industry funding.

More recent studies have mercifully been more conventional. The SSaSS study, a randomized controlled trial of a salt substitute, provided the cardiovascular outcomes data that many were waiting for. And CARDIA-SSBP, a cross-over randomized trial recently presented at the American Heart Association meeting, showed that reducing dietary sodium was on par with medication when it came to lowering blood pressure.

For Dr. Juraschek, the evidence is clear: “If you were going to choose one, I would say the weight of the evidence is still really heavily on the sodium side.”

The Case for Potassium Supplementation

The evidence for salt restriction notwithstanding, Swapnil Hiremath, MD, MPH, from the University of Ottawa, Ontario, Canada, argued in his editorial that potassium supplementation has gotten short shrift. Though he admits the studies for potassium supplementation have been smaller and sometimes rely on observational evidence, the evidence is there. In the distal convoluted tubule, the sodium chloride cotransporter (NCC), aka the potassium switch, is turned on by low potassium levels and leads to sodium reabsorption by the kidney even in settings of high sodium intake (Figure). To nonnephrologists, renal physiology may be a black box. But if you quickly brush up on the mechanism of action of thiazide diuretics, the preceding descriptor will make more sense.

Medscape

Realistic Diets and Taste Issues

“We know that increasing potassium, decreasing sodium is useful. The question is how do we do that?” says Dr. Hiremath. Should we encourage fruit and vegetable consumption in a healthy diet, give potassium supplements, or encourage the use of low-sodium salt substitutes?

Recommending a healthier diet with more fruits and vegetables is a no-brainer. But getting people to do it is hard. In a world where fruit is more expensive than junk food is, economic realities may drive food choice regardless of our best efforts. The 4700 mg of potassium in the DASH eating plan is the equivalent of eleven bananas daily; although not impossible, it would require a substantive shift in eating patterns for most people.

Given that we prescribe iron, vitamin B12, calcium, and vitamin D to patients who need them, why not potassium tablets to help with blood pressure? Granted, there are concerns about inducing hyperkalemia. Also, why not just prescribe a proven anti-hypertensive, such as ramipril, which has the added benefit of helping with renal protection or cardiac remodeling? Dr. Hiremath points out that patients are far less reluctant to take dietary supplements. Medication is something you take when sick. A supplement is seen as “natural” and “healthy” and might be more attractive to people resistant to prescription meds.

Another drawback of oral potassium supplementation is taste. In a Consumer Reports taste test, potassium chloride fared poorly. It was bitter and had a metallic aftertaste. At least one tester wouldn’t ever consume it again. Potassium citrate is slightly more palpable.

Salt substitutes, like the 75:25 ratio of sodium to potassium used in SSaSS, may be as high as you can go for potassium in any low-sodium salt alternative. If you go any higher than that, the taste will just turn people off, suggests Dr. Hiremath.

But SsaSS, which was done in China, may not be relevant to North America. In China, most sodium is added during cooking at home, and the consumption of processed foods is low. For the typical North American, roughly three quarters of the sodium eaten is added to their food by someone else; only about 15% is added during cooking at home or at the dinner table. If you aren’t someone who cooks, buying a salt substitute is probably not going to have much impact.

Given that reality, Dr. Juraschek thinks we need to target the sodium in processed foods. “There’s just so much sodium in so many products,” he says. “When you think about public policy, it’s most expeditious for there to be more regulation about how much is added to our food supply vs trying to get people to consume eight to 12 servings of fruit.”

No Salt War Here

Despite their different editorial takes, Dr. Hiremath and Dr. Juraschek largely agree on the broad strokes of the problem. This isn’t X (or Twitter) after all. Potassium supplementation may be useful in some parts of the world but may not address the underlying problem in countries where processed foods are the source of most dietary sodium.

The CARDIA-SSBP trial showed that a very low–sodium diet had the same blood pressure–lowering effect as a first-line antihypertensive, but most people will not be able to limit themselves to 500 mg of dietary sodium per day. In CARDIA-SSBP, just as in DASH, participants were provided with meals from study kitchens. They were not just told to eat less salt, which would almost certainly have failed.

“We should aim for stuff that is practical and doable rather than aim for stuff that cannot be done,” according to Dr. Hiremath. Whether that should be salt substitutes or policy change may depend on which part of the planet you live on.

One recent positive change may herald the beginning of a policy change, at least in the United States. In March 2023, the US Food and Drug Administration proposed a rule change to allow salt substitutes to be labeled as salt. This would make it easier for food manufacturers to swap out sodium chloride for a low-sodium alternative and reduce the amount of sodium in the US diet without having a large impact on taste and consumer uptake. Both Dr. Hiremath and Dr. Juraschek agree that it may not be enough on its own but that it’s a start.

Christopher Labos is a cardiologist with a degree in epidemiology. He spends most of his time doing things that he doesn’t get paid for, like research, teaching, and podcasting. Occasionally, he finds time to practice cardiology to pay the rent. He realizes that half of his research findings will be disproved in 5 years; he just doesn’t know which half. He is a regular contributor to the Montreal Gazette, CJAD radio, and CTV television in Montreal, and is host of the award-winning podcast The Body of Evidence.

A version of this article appeared on Medscape.com.

A pair of dueling editorials in the journal Hypertension debate whether our focus should be on sodium or its often neglected partner, potassium.

Should we cut sodium from our diet or eat more potassium to lower blood pressure? The answer requires an intricate understanding of renal physiology that is fascinating. To nephrologists. A meta-analysis of 85 trials showed a consistent and linear. It may also depend on where you live and whether your concern is treating individuals or implementing effective food policy.

The Case for Sodium Restriction

Stephen Juraschek, MD, PhD, of the Beth Israel Deaconess Medical Center, Boston, Massachusetts, co-author of one editorial, told me in a zoom interview that he believes his side of the debate clearly has the stronger argument. Of the two cations in question, there has been infinitely more ink spilled about sodium.

Studies such as INTERSALT, the DASH diet, and TOHP may be the most well-known, but there are many, many intervention studies of sodium restriction’s effect on blood pressure. A meta-analysis of 85 trials of showed a consistent and linear relationship between sodium reduction and blood pressure. In contrast, the evidence base for potassium is more limited and less consistent. There are half as many trials with potassium, and its ability to lower blood pressure may depend on how much sodium is present in the diet.

An outlier in the sodium restriction evidence base is the PURE study, which suggested that extreme sodium restriction could increase cardiovascular mortality, but the trial suffered from two potential issues. First, it used a single spot urine specimen to measure sodium rather than the generally accepted more accurate 24-hour urine collection. A reanalysis of the TOHP study using a spot urine rather than a 24-hour urine collection changed the relationship between sodium intake and mortality and possibly explained the U-shaped association observed in PURE. Second, PURE was an observational cohort and was prone to confounding, or in this case, reverse causation. Why did people who consumed very little salt have an increased risk for cardiovascular disease? It is very possible that people with a high risk for cardiovascular disease were told to consume less salt to begin with. Hence B led to A rather than A leading to B.

The debate on sodium restriction has been bitter at times. Opposing camps formed, and people took sides in the “salt wars.” A group of researchers, termed the Jackson 6, met and decided to end the controversy by running a randomized trial in US prisons (having discounted the options of long-term care homes and military bases). They detailed their plan in an editorial in Hypertension. The study never came to fruition for two reasons: the obvious ethical problems of experimenting on prisoners and the revelation of undisclosed salt industry funding.

More recent studies have mercifully been more conventional. The SSaSS study, a randomized controlled trial of a salt substitute, provided the cardiovascular outcomes data that many were waiting for. And CARDIA-SSBP, a cross-over randomized trial recently presented at the American Heart Association meeting, showed that reducing dietary sodium was on par with medication when it came to lowering blood pressure.

For Dr. Juraschek, the evidence is clear: “If you were going to choose one, I would say the weight of the evidence is still really heavily on the sodium side.”

The Case for Potassium Supplementation

The evidence for salt restriction notwithstanding, Swapnil Hiremath, MD, MPH, from the University of Ottawa, Ontario, Canada, argued in his editorial that potassium supplementation has gotten short shrift. Though he admits the studies for potassium supplementation have been smaller and sometimes rely on observational evidence, the evidence is there. In the distal convoluted tubule, the sodium chloride cotransporter (NCC), aka the potassium switch, is turned on by low potassium levels and leads to sodium reabsorption by the kidney even in settings of high sodium intake (Figure). To nonnephrologists, renal physiology may be a black box. But if you quickly brush up on the mechanism of action of thiazide diuretics, the preceding descriptor will make more sense.

Medscape

Realistic Diets and Taste Issues

“We know that increasing potassium, decreasing sodium is useful. The question is how do we do that?” says Dr. Hiremath. Should we encourage fruit and vegetable consumption in a healthy diet, give potassium supplements, or encourage the use of low-sodium salt substitutes?

Recommending a healthier diet with more fruits and vegetables is a no-brainer. But getting people to do it is hard. In a world where fruit is more expensive than junk food is, economic realities may drive food choice regardless of our best efforts. The 4700 mg of potassium in the DASH eating plan is the equivalent of eleven bananas daily; although not impossible, it would require a substantive shift in eating patterns for most people.

Given that we prescribe iron, vitamin B12, calcium, and vitamin D to patients who need them, why not potassium tablets to help with blood pressure? Granted, there are concerns about inducing hyperkalemia. Also, why not just prescribe a proven anti-hypertensive, such as ramipril, which has the added benefit of helping with renal protection or cardiac remodeling? Dr. Hiremath points out that patients are far less reluctant to take dietary supplements. Medication is something you take when sick. A supplement is seen as “natural” and “healthy” and might be more attractive to people resistant to prescription meds.

Another drawback of oral potassium supplementation is taste. In a Consumer Reports taste test, potassium chloride fared poorly. It was bitter and had a metallic aftertaste. At least one tester wouldn’t ever consume it again. Potassium citrate is slightly more palpable.

Salt substitutes, like the 75:25 ratio of sodium to potassium used in SSaSS, may be as high as you can go for potassium in any low-sodium salt alternative. If you go any higher than that, the taste will just turn people off, suggests Dr. Hiremath.

But SsaSS, which was done in China, may not be relevant to North America. In China, most sodium is added during cooking at home, and the consumption of processed foods is low. For the typical North American, roughly three quarters of the sodium eaten is added to their food by someone else; only about 15% is added during cooking at home or at the dinner table. If you aren’t someone who cooks, buying a salt substitute is probably not going to have much impact.

Given that reality, Dr. Juraschek thinks we need to target the sodium in processed foods. “There’s just so much sodium in so many products,” he says. “When you think about public policy, it’s most expeditious for there to be more regulation about how much is added to our food supply vs trying to get people to consume eight to 12 servings of fruit.”

No Salt War Here

Despite their different editorial takes, Dr. Hiremath and Dr. Juraschek largely agree on the broad strokes of the problem. This isn’t X (or Twitter) after all. Potassium supplementation may be useful in some parts of the world but may not address the underlying problem in countries where processed foods are the source of most dietary sodium.

The CARDIA-SSBP trial showed that a very low–sodium diet had the same blood pressure–lowering effect as a first-line antihypertensive, but most people will not be able to limit themselves to 500 mg of dietary sodium per day. In CARDIA-SSBP, just as in DASH, participants were provided with meals from study kitchens. They were not just told to eat less salt, which would almost certainly have failed.

“We should aim for stuff that is practical and doable rather than aim for stuff that cannot be done,” according to Dr. Hiremath. Whether that should be salt substitutes or policy change may depend on which part of the planet you live on.

One recent positive change may herald the beginning of a policy change, at least in the United States. In March 2023, the US Food and Drug Administration proposed a rule change to allow salt substitutes to be labeled as salt. This would make it easier for food manufacturers to swap out sodium chloride for a low-sodium alternative and reduce the amount of sodium in the US diet without having a large impact on taste and consumer uptake. Both Dr. Hiremath and Dr. Juraschek agree that it may not be enough on its own but that it’s a start.

Christopher Labos is a cardiologist with a degree in epidemiology. He spends most of his time doing things that he doesn’t get paid for, like research, teaching, and podcasting. Occasionally, he finds time to practice cardiology to pay the rent. He realizes that half of his research findings will be disproved in 5 years; he just doesn’t know which half. He is a regular contributor to the Montreal Gazette, CJAD radio, and CTV television in Montreal, and is host of the award-winning podcast The Body of Evidence.

A version of this article appeared on Medscape.com.

A pair of dueling editorials in the journal Hypertension debate whether our focus should be on sodium or its often neglected partner, potassium.

Should we cut sodium from our diet or eat more potassium to lower blood pressure? The answer requires an intricate understanding of renal physiology that is fascinating. To nephrologists. A meta-analysis of 85 trials showed a consistent and linear. It may also depend on where you live and whether your concern is treating individuals or implementing effective food policy.

The Case for Sodium Restriction

Stephen Juraschek, MD, PhD, of the Beth Israel Deaconess Medical Center, Boston, Massachusetts, co-author of one editorial, told me in a zoom interview that he believes his side of the debate clearly has the stronger argument. Of the two cations in question, there has been infinitely more ink spilled about sodium.

Studies such as INTERSALT, the DASH diet, and TOHP may be the most well-known, but there are many, many intervention studies of sodium restriction’s effect on blood pressure. A meta-analysis of 85 trials of showed a consistent and linear relationship between sodium reduction and blood pressure. In contrast, the evidence base for potassium is more limited and less consistent. There are half as many trials with potassium, and its ability to lower blood pressure may depend on how much sodium is present in the diet.

An outlier in the sodium restriction evidence base is the PURE study, which suggested that extreme sodium restriction could increase cardiovascular mortality, but the trial suffered from two potential issues. First, it used a single spot urine specimen to measure sodium rather than the generally accepted more accurate 24-hour urine collection. A reanalysis of the TOHP study using a spot urine rather than a 24-hour urine collection changed the relationship between sodium intake and mortality and possibly explained the U-shaped association observed in PURE. Second, PURE was an observational cohort and was prone to confounding, or in this case, reverse causation. Why did people who consumed very little salt have an increased risk for cardiovascular disease? It is very possible that people with a high risk for cardiovascular disease were told to consume less salt to begin with. Hence B led to A rather than A leading to B.

The debate on sodium restriction has been bitter at times. Opposing camps formed, and people took sides in the “salt wars.” A group of researchers, termed the Jackson 6, met and decided to end the controversy by running a randomized trial in US prisons (having discounted the options of long-term care homes and military bases). They detailed their plan in an editorial in Hypertension. The study never came to fruition for two reasons: the obvious ethical problems of experimenting on prisoners and the revelation of undisclosed salt industry funding.

More recent studies have mercifully been more conventional. The SSaSS study, a randomized controlled trial of a salt substitute, provided the cardiovascular outcomes data that many were waiting for. And CARDIA-SSBP, a cross-over randomized trial recently presented at the American Heart Association meeting, showed that reducing dietary sodium was on par with medication when it came to lowering blood pressure.

For Dr. Juraschek, the evidence is clear: “If you were going to choose one, I would say the weight of the evidence is still really heavily on the sodium side.”

The Case for Potassium Supplementation

The evidence for salt restriction notwithstanding, Swapnil Hiremath, MD, MPH, from the University of Ottawa, Ontario, Canada, argued in his editorial that potassium supplementation has gotten short shrift. Though he admits the studies for potassium supplementation have been smaller and sometimes rely on observational evidence, the evidence is there. In the distal convoluted tubule, the sodium chloride cotransporter (NCC), aka the potassium switch, is turned on by low potassium levels and leads to sodium reabsorption by the kidney even in settings of high sodium intake (Figure). To nonnephrologists, renal physiology may be a black box. But if you quickly brush up on the mechanism of action of thiazide diuretics, the preceding descriptor will make more sense.

Medscape

Realistic Diets and Taste Issues

“We know that increasing potassium, decreasing sodium is useful. The question is how do we do that?” says Dr. Hiremath. Should we encourage fruit and vegetable consumption in a healthy diet, give potassium supplements, or encourage the use of low-sodium salt substitutes?

Recommending a healthier diet with more fruits and vegetables is a no-brainer. But getting people to do it is hard. In a world where fruit is more expensive than junk food is, economic realities may drive food choice regardless of our best efforts. The 4700 mg of potassium in the DASH eating plan is the equivalent of eleven bananas daily; although not impossible, it would require a substantive shift in eating patterns for most people.

Given that we prescribe iron, vitamin B12, calcium, and vitamin D to patients who need them, why not potassium tablets to help with blood pressure? Granted, there are concerns about inducing hyperkalemia. Also, why not just prescribe a proven anti-hypertensive, such as ramipril, which has the added benefit of helping with renal protection or cardiac remodeling? Dr. Hiremath points out that patients are far less reluctant to take dietary supplements. Medication is something you take when sick. A supplement is seen as “natural” and “healthy” and might be more attractive to people resistant to prescription meds.

Another drawback of oral potassium supplementation is taste. In a Consumer Reports taste test, potassium chloride fared poorly. It was bitter and had a metallic aftertaste. At least one tester wouldn’t ever consume it again. Potassium citrate is slightly more palpable.

Salt substitutes, like the 75:25 ratio of sodium to potassium used in SSaSS, may be as high as you can go for potassium in any low-sodium salt alternative. If you go any higher than that, the taste will just turn people off, suggests Dr. Hiremath.

But SsaSS, which was done in China, may not be relevant to North America. In China, most sodium is added during cooking at home, and the consumption of processed foods is low. For the typical North American, roughly three quarters of the sodium eaten is added to their food by someone else; only about 15% is added during cooking at home or at the dinner table. If you aren’t someone who cooks, buying a salt substitute is probably not going to have much impact.

Given that reality, Dr. Juraschek thinks we need to target the sodium in processed foods. “There’s just so much sodium in so many products,” he says. “When you think about public policy, it’s most expeditious for there to be more regulation about how much is added to our food supply vs trying to get people to consume eight to 12 servings of fruit.”

No Salt War Here

Despite their different editorial takes, Dr. Hiremath and Dr. Juraschek largely agree on the broad strokes of the problem. This isn’t X (or Twitter) after all. Potassium supplementation may be useful in some parts of the world but may not address the underlying problem in countries where processed foods are the source of most dietary sodium.

The CARDIA-SSBP trial showed that a very low–sodium diet had the same blood pressure–lowering effect as a first-line antihypertensive, but most people will not be able to limit themselves to 500 mg of dietary sodium per day. In CARDIA-SSBP, just as in DASH, participants were provided with meals from study kitchens. They were not just told to eat less salt, which would almost certainly have failed.

“We should aim for stuff that is practical and doable rather than aim for stuff that cannot be done,” according to Dr. Hiremath. Whether that should be salt substitutes or policy change may depend on which part of the planet you live on.

One recent positive change may herald the beginning of a policy change, at least in the United States. In March 2023, the US Food and Drug Administration proposed a rule change to allow salt substitutes to be labeled as salt. This would make it easier for food manufacturers to swap out sodium chloride for a low-sodium alternative and reduce the amount of sodium in the US diet without having a large impact on taste and consumer uptake. Both Dr. Hiremath and Dr. Juraschek agree that it may not be enough on its own but that it’s a start.

Christopher Labos is a cardiologist with a degree in epidemiology. He spends most of his time doing things that he doesn’t get paid for, like research, teaching, and podcasting. Occasionally, he finds time to practice cardiology to pay the rent. He realizes that half of his research findings will be disproved in 5 years; he just doesn’t know which half. He is a regular contributor to the Montreal Gazette, CJAD radio, and CTV television in Montreal, and is host of the award-winning podcast The Body of Evidence.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

From the year 2000 until around 2016, the incidence of breast cancer among young women — those under age 50 — rose steadily, if slowly.

JAMA Network Open

JAMA Network Open

JAMA Network Open

Dr. F. Perry Wilson is associate professor of medicine and public health and director of the Clinical and Translational Research Accelerator at Yale University, New Haven, Conn. He has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

From the year 2000 until around 2016, the incidence of breast cancer among young women — those under age 50 — rose steadily, if slowly.

JAMA Network Open

JAMA Network Open

JAMA Network Open

Dr. F. Perry Wilson is associate professor of medicine and public health and director of the Clinical and Translational Research Accelerator at Yale University, New Haven, Conn. He has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

From the year 2000 until around 2016, the incidence of breast cancer among young women — those under age 50 — rose steadily, if slowly.

JAMA Network Open

JAMA Network Open

JAMA Network Open

Dr. F. Perry Wilson is associate professor of medicine and public health and director of the Clinical and Translational Research Accelerator at Yale University, New Haven, Conn. He has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Neha Pathak, MD: Hello. Today, we’re talking to Dr. Daniel Clauw, a professor at the University of Michigan in Ann Arbor, who is running a major trial on treatments for chronic back pain. We’re talking today about managing back pain in the post-opioid world. Thank you so much, Dr. Clauw, for taking the time to be our resident pain consultant today. Managing chronic pain can lead to a large amount of burnout and helplessness in the clinic setting. That’s the reality with some of the modalities that patients are requesting; there is still confusion about what is optimal for a particular type of patient, this feeling that we’re not really helping people get better, and whenever patients come in, that’s always still their chief complaint.

How would you advise providers to think about that and to settle into their role as communicators about better strategies without the burnout?

Daniel Clauw, MD: The first thing is to broaden the number of other providers that you get involved in these individuals’ care as the evidence base for all of these nonpharmacologic therapies being effective in chronic pain increases and increases. As third-party payers begin to reimburse for more and more of these therapies, it’s really difficult to manage chronic pain patients if you’re trying to do it alone on an island.

If you can, identify the good physical therapists in your community that are going to really work with people to give them an exercise program that they can use at home; find a pain psychologist that can offer some cognitive-behavioral therapy (CBT) for insomnia and some CBT for pain; and in the subset of patients with trauma, give them the emotional awareness of the neural reprocessing therapy for that specific subset.

As you start to identify more and more of these nonpharmacologic therapies that you want your patients to try, each of those has a set of providers and they can be incredibly helpful so that you, as the primary care provider (PCP), don’t really feel overwhelmed that you’re it, that you’re the only one.

Many of these individuals have more time to spend, and they have more one-on-one in-person time than you do as a primary care physician in the current healthcare system. Many of those providers have become really good at doing amateur CBT, goal-setting, and some of the other things that you need to do when you manage chronic pain patients. Try to find that other group of people that you can send your patients to that are going to be offering some of these nonpharmacologic therapies, and they’ll really help you manage these individuals.

Dr. Pathak: I think a couple of things come up for me. One is that we have to maybe broaden thinking about pain management, not only as multimodal strategies but also as multidisciplinary strategies. To your point, I think that’s really important. I also worry and wonder about health equity concerns, because just as overburdened as many PCPs are, we’re seeing it’s very difficult to get into physical therapy or to get into a setting where you’d be able to receive CBT for your pain. Any thoughts on those types of considerations?

Dr. Clauw: That’s a huge problem. Our group and many other groups in the pain space are developing websites, smartphone apps, and things like that to try to get some of these things directly to individuals with pain, not only for the reasons that you stated but also so that persons with pain don’t have to become patients. Our healthcare systems often make pain worse rather than better.

There were some great articles in The Lancet about 5 years ago talking about low back pain and that in different countries, the healthcare systems, for different reasons, have a tendency to actually make low back pain worse because they do too much surgery, immobilize people, or things like that rather than just not make them better. I think we’ve overmedicalized chronic pain in some settings, and much of what we’re trying to lead people to are things that are parts of wellness programs. The NIH National Center for Complementary and Integrative Health director talks about whole person health often.

I think that these interdisciplinary, integrative approaches are what we have to be using for chronic pain patients. I tell pain patients that, among acupuncture, acupressure, mindfulness, five different forms of CBT, yoga, and tai chi, I don’t know which of those is going to work, but I know that about 1 in 3 individuals that tries each of those therapies gets a benefit. What I really should be doing most is incentivizing people and motivating people to keep trying some of those nonpharmacologic approaches that they haven’t yet tried, because when they find one that works for them, then they will integrate it into their day-to-day life.

The other trick I would use for primary care physicians or anyone managing chronic pain patients is, don’t try to incentivize a pain patient to go try a new nonpharmacologic therapy or start an exercise program because you want their pain score to go from a 6 to a 3. Incentivize them by asking them, what are two or three things that you’re not able to do now because you have chronic pain that you’d really like to be able to do?

You’d like to play nine holes of golf; you’d like to be able to hug your grandchild; or you’d like to be able to do something else. Use those functional goals that are patient0driven to motivate your patients to do these things, because that will work much better. Again, any of us are inherently more likely to take the time and the effort to do some of these nonpharmacologic therapies if it’s for a reason that internally motivates us.

Dr. Pathak: I think that’s great. I’m very privileged to work within the Veterans Affairs (VA) healthcare system. I think that there’s been a huge shift within VA healthcare to provide these ancillary services, whether it’s yoga, tai chi, or acupuncture, as an adjunct to the pain management strategy.

Also, what comes up for me, as you’re saying, is grounding the point that instead of relying on a pain score — which can be objective and different from patient to patient and even within a patient — we should choose a smart goal that is almost more objective when it’s functional. Your goal is to walk two blocks to the mailbox. Can we achieve that as part of your pain control strategy?

I so appreciate your taking the time to be our pain consultant today. I really appreciate our discussion, and I’d like to hand it over to you for any final thoughts.

Dr. Clauw: I’d add that when you’re seeing chronic pain patients, many of them are going to have comorbid sleep problems. They’re going to have comorbid problems with fatigue and memory problems, especially the central nervous system–driven forms of pain that we now call nociplastic pain. Look at those as therapeutic targets.

If you’re befuddled because you’ve tried many different things for pain in this individual you’ve been seeing for a while, focus on their sleep and focus on getting them more active. Don’t use the word exercise — because that scares chronic pain patients — but focus on getting them more active.

There are many different tactics and strategies that you can use to motivate the patients to try some of these new nonpharmacologic approaches as the evidence base continues to increase.

Dr. Pathak: Thank you so much, again, to Dr. Clauw for joining us and being our pain consultant, really helping us to think about managing back pain in the postopioid world.
 

Dr. Pathak is Chief Physician Editor, Health and Lifestyle Medicine, WebMD. She has disclosed no relevant financial relationships. Dr. Clauw is Director, Chronic Pain and Fatigue Research Center, Department of Anesthesia, University of Michigan, Ann Arbor. He disclosed ties with Tonix and Viatris.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Neha Pathak, MD: Hello. Today, we’re talking to Dr. Daniel Clauw, a professor at the University of Michigan in Ann Arbor, who is running a major trial on treatments for chronic back pain. We’re talking today about managing back pain in the post-opioid world. Thank you so much, Dr. Clauw, for taking the time to be our resident pain consultant today. Managing chronic pain can lead to a large amount of burnout and helplessness in the clinic setting. That’s the reality with some of the modalities that patients are requesting; there is still confusion about what is optimal for a particular type of patient, this feeling that we’re not really helping people get better, and whenever patients come in, that’s always still their chief complaint.

How would you advise providers to think about that and to settle into their role as communicators about better strategies without the burnout?

Daniel Clauw, MD: The first thing is to broaden the number of other providers that you get involved in these individuals’ care as the evidence base for all of these nonpharmacologic therapies being effective in chronic pain increases and increases. As third-party payers begin to reimburse for more and more of these therapies, it’s really difficult to manage chronic pain patients if you’re trying to do it alone on an island.

If you can, identify the good physical therapists in your community that are going to really work with people to give them an exercise program that they can use at home; find a pain psychologist that can offer some cognitive-behavioral therapy (CBT) for insomnia and some CBT for pain; and in the subset of patients with trauma, give them the emotional awareness of the neural reprocessing therapy for that specific subset.

As you start to identify more and more of these nonpharmacologic therapies that you want your patients to try, each of those has a set of providers and they can be incredibly helpful so that you, as the primary care provider (PCP), don’t really feel overwhelmed that you’re it, that you’re the only one.

Many of these individuals have more time to spend, and they have more one-on-one in-person time than you do as a primary care physician in the current healthcare system. Many of those providers have become really good at doing amateur CBT, goal-setting, and some of the other things that you need to do when you manage chronic pain patients. Try to find that other group of people that you can send your patients to that are going to be offering some of these nonpharmacologic therapies, and they’ll really help you manage these individuals.

Dr. Pathak: I think a couple of things come up for me. One is that we have to maybe broaden thinking about pain management, not only as multimodal strategies but also as multidisciplinary strategies. To your point, I think that’s really important. I also worry and wonder about health equity concerns, because just as overburdened as many PCPs are, we’re seeing it’s very difficult to get into physical therapy or to get into a setting where you’d be able to receive CBT for your pain. Any thoughts on those types of considerations?

Dr. Clauw: That’s a huge problem. Our group and many other groups in the pain space are developing websites, smartphone apps, and things like that to try to get some of these things directly to individuals with pain, not only for the reasons that you stated but also so that persons with pain don’t have to become patients. Our healthcare systems often make pain worse rather than better.

There were some great articles in The Lancet about 5 years ago talking about low back pain and that in different countries, the healthcare systems, for different reasons, have a tendency to actually make low back pain worse because they do too much surgery, immobilize people, or things like that rather than just not make them better. I think we’ve overmedicalized chronic pain in some settings, and much of what we’re trying to lead people to are things that are parts of wellness programs. The NIH National Center for Complementary and Integrative Health director talks about whole person health often.

I think that these interdisciplinary, integrative approaches are what we have to be using for chronic pain patients. I tell pain patients that, among acupuncture, acupressure, mindfulness, five different forms of CBT, yoga, and tai chi, I don’t know which of those is going to work, but I know that about 1 in 3 individuals that tries each of those therapies gets a benefit. What I really should be doing most is incentivizing people and motivating people to keep trying some of those nonpharmacologic approaches that they haven’t yet tried, because when they find one that works for them, then they will integrate it into their day-to-day life.

The other trick I would use for primary care physicians or anyone managing chronic pain patients is, don’t try to incentivize a pain patient to go try a new nonpharmacologic therapy or start an exercise program because you want their pain score to go from a 6 to a 3. Incentivize them by asking them, what are two or three things that you’re not able to do now because you have chronic pain that you’d really like to be able to do?

You’d like to play nine holes of golf; you’d like to be able to hug your grandchild; or you’d like to be able to do something else. Use those functional goals that are patient0driven to motivate your patients to do these things, because that will work much better. Again, any of us are inherently more likely to take the time and the effort to do some of these nonpharmacologic therapies if it’s for a reason that internally motivates us.

Dr. Pathak: I think that’s great. I’m very privileged to work within the Veterans Affairs (VA) healthcare system. I think that there’s been a huge shift within VA healthcare to provide these ancillary services, whether it’s yoga, tai chi, or acupuncture, as an adjunct to the pain management strategy.

Also, what comes up for me, as you’re saying, is grounding the point that instead of relying on a pain score — which can be objective and different from patient to patient and even within a patient — we should choose a smart goal that is almost more objective when it’s functional. Your goal is to walk two blocks to the mailbox. Can we achieve that as part of your pain control strategy?

I so appreciate your taking the time to be our pain consultant today. I really appreciate our discussion, and I’d like to hand it over to you for any final thoughts.

Dr. Clauw: I’d add that when you’re seeing chronic pain patients, many of them are going to have comorbid sleep problems. They’re going to have comorbid problems with fatigue and memory problems, especially the central nervous system–driven forms of pain that we now call nociplastic pain. Look at those as therapeutic targets.

If you’re befuddled because you’ve tried many different things for pain in this individual you’ve been seeing for a while, focus on their sleep and focus on getting them more active. Don’t use the word exercise — because that scares chronic pain patients — but focus on getting them more active.

There are many different tactics and strategies that you can use to motivate the patients to try some of these new nonpharmacologic approaches as the evidence base continues to increase.

Dr. Pathak: Thank you so much, again, to Dr. Clauw for joining us and being our pain consultant, really helping us to think about managing back pain in the postopioid world.
 

Dr. Pathak is Chief Physician Editor, Health and Lifestyle Medicine, WebMD. She has disclosed no relevant financial relationships. Dr. Clauw is Director, Chronic Pain and Fatigue Research Center, Department of Anesthesia, University of Michigan, Ann Arbor. He disclosed ties with Tonix and Viatris.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Neha Pathak, MD: Hello. Today, we’re talking to Dr. Daniel Clauw, a professor at the University of Michigan in Ann Arbor, who is running a major trial on treatments for chronic back pain. We’re talking today about managing back pain in the post-opioid world. Thank you so much, Dr. Clauw, for taking the time to be our resident pain consultant today. Managing chronic pain can lead to a large amount of burnout and helplessness in the clinic setting. That’s the reality with some of the modalities that patients are requesting; there is still confusion about what is optimal for a particular type of patient, this feeling that we’re not really helping people get better, and whenever patients come in, that’s always still their chief complaint.

How would you advise providers to think about that and to settle into their role as communicators about better strategies without the burnout?

Daniel Clauw, MD: The first thing is to broaden the number of other providers that you get involved in these individuals’ care as the evidence base for all of these nonpharmacologic therapies being effective in chronic pain increases and increases. As third-party payers begin to reimburse for more and more of these therapies, it’s really difficult to manage chronic pain patients if you’re trying to do it alone on an island.

If you can, identify the good physical therapists in your community that are going to really work with people to give them an exercise program that they can use at home; find a pain psychologist that can offer some cognitive-behavioral therapy (CBT) for insomnia and some CBT for pain; and in the subset of patients with trauma, give them the emotional awareness of the neural reprocessing therapy for that specific subset.

As you start to identify more and more of these nonpharmacologic therapies that you want your patients to try, each of those has a set of providers and they can be incredibly helpful so that you, as the primary care provider (PCP), don’t really feel overwhelmed that you’re it, that you’re the only one.

Many of these individuals have more time to spend, and they have more one-on-one in-person time than you do as a primary care physician in the current healthcare system. Many of those providers have become really good at doing amateur CBT, goal-setting, and some of the other things that you need to do when you manage chronic pain patients. Try to find that other group of people that you can send your patients to that are going to be offering some of these nonpharmacologic therapies, and they’ll really help you manage these individuals.

Dr. Pathak: I think a couple of things come up for me. One is that we have to maybe broaden thinking about pain management, not only as multimodal strategies but also as multidisciplinary strategies. To your point, I think that’s really important. I also worry and wonder about health equity concerns, because just as overburdened as many PCPs are, we’re seeing it’s very difficult to get into physical therapy or to get into a setting where you’d be able to receive CBT for your pain. Any thoughts on those types of considerations?

Dr. Clauw: That’s a huge problem. Our group and many other groups in the pain space are developing websites, smartphone apps, and things like that to try to get some of these things directly to individuals with pain, not only for the reasons that you stated but also so that persons with pain don’t have to become patients. Our healthcare systems often make pain worse rather than better.

There were some great articles in The Lancet about 5 years ago talking about low back pain and that in different countries, the healthcare systems, for different reasons, have a tendency to actually make low back pain worse because they do too much surgery, immobilize people, or things like that rather than just not make them better. I think we’ve overmedicalized chronic pain in some settings, and much of what we’re trying to lead people to are things that are parts of wellness programs. The NIH National Center for Complementary and Integrative Health director talks about whole person health often.

I think that these interdisciplinary, integrative approaches are what we have to be using for chronic pain patients. I tell pain patients that, among acupuncture, acupressure, mindfulness, five different forms of CBT, yoga, and tai chi, I don’t know which of those is going to work, but I know that about 1 in 3 individuals that tries each of those therapies gets a benefit. What I really should be doing most is incentivizing people and motivating people to keep trying some of those nonpharmacologic approaches that they haven’t yet tried, because when they find one that works for them, then they will integrate it into their day-to-day life.

The other trick I would use for primary care physicians or anyone managing chronic pain patients is, don’t try to incentivize a pain patient to go try a new nonpharmacologic therapy or start an exercise program because you want their pain score to go from a 6 to a 3. Incentivize them by asking them, what are two or three things that you’re not able to do now because you have chronic pain that you’d really like to be able to do?

You’d like to play nine holes of golf; you’d like to be able to hug your grandchild; or you’d like to be able to do something else. Use those functional goals that are patient0driven to motivate your patients to do these things, because that will work much better. Again, any of us are inherently more likely to take the time and the effort to do some of these nonpharmacologic therapies if it’s for a reason that internally motivates us.

Dr. Pathak: I think that’s great. I’m very privileged to work within the Veterans Affairs (VA) healthcare system. I think that there’s been a huge shift within VA healthcare to provide these ancillary services, whether it’s yoga, tai chi, or acupuncture, as an adjunct to the pain management strategy.

Also, what comes up for me, as you’re saying, is grounding the point that instead of relying on a pain score — which can be objective and different from patient to patient and even within a patient — we should choose a smart goal that is almost more objective when it’s functional. Your goal is to walk two blocks to the mailbox. Can we achieve that as part of your pain control strategy?

I so appreciate your taking the time to be our pain consultant today. I really appreciate our discussion, and I’d like to hand it over to you for any final thoughts.

Dr. Clauw: I’d add that when you’re seeing chronic pain patients, many of them are going to have comorbid sleep problems. They’re going to have comorbid problems with fatigue and memory problems, especially the central nervous system–driven forms of pain that we now call nociplastic pain. Look at those as therapeutic targets.

If you’re befuddled because you’ve tried many different things for pain in this individual you’ve been seeing for a while, focus on their sleep and focus on getting them more active. Don’t use the word exercise — because that scares chronic pain patients — but focus on getting them more active.

There are many different tactics and strategies that you can use to motivate the patients to try some of these new nonpharmacologic approaches as the evidence base continues to increase.

Dr. Pathak: Thank you so much, again, to Dr. Clauw for joining us and being our pain consultant, really helping us to think about managing back pain in the postopioid world.
 

Dr. Pathak is Chief Physician Editor, Health and Lifestyle Medicine, WebMD. She has disclosed no relevant financial relationships. Dr. Clauw is Director, Chronic Pain and Fatigue Research Center, Department of Anesthesia, University of Michigan, Ann Arbor. He disclosed ties with Tonix and Viatris.

A version of this article appeared on Medscape.com.

Veterans Administration (VA) hospitals are a stepchild in the bizarre mishmash of the U.S. healthcare system. They’re best known (often justifiably so) for rather cantankerous patients, rigid rules, and other oddities (such as patients being able to go on leave and come back).

The majority of American doctors, including myself, did at least part of our training at a VA and have no shortage of stories about them. One I worked at (Omaha VA) was powered by its own nuclear reactor in the basement (no, really, it was, though sadly it’s since been taken out).

VA hospitals, in general, are no-frills — linoleum floors, no piano player in the lobby, very few private rooms, and occasionally in the news for scandals like the one at my hometown Carl T. Hayden VA hospital (I trained there, too).

Yet, a recent study found VA hospitals to be surprisingly efficient compared with the private sector. Their focus on patient care, rather than profits, allows them to run with 8% fewer administrative staff since they generally don’t have to deal with insurance billings, denials, and other paperwork (they also don’t have to deal with shareholders and investor demands or ridiculous CEO salaries, though the study didn’t address that).

On a national scale, this would mean roughly 900,000 fewer administrative jobs in the private sector. Granted, that also would mean those people would have to find other jobs, but let’s look at the patient side. If you had 900,000 fewer desk workers, you’d have the money to hire more nurses, respiratory techs, therapists, and other people directly involved in patient care. You’d also need a lot less office space, which further brings down overhead.

Part of the problem is that a lot of the current medical business is in marketing — how many ads do you see each day for different hospitals in your area? — and upcoding to extract more money from each billing. Neither of these has any clinical value on the patient side of things.

You don’t have to look back too far (2020) for the study that found U.S. healthcare spent four times as much money ($812 billion) per capita than our northern neighbors.

And, for all the jokes we make about the VA (myself included), a study last year found its care was on par (or even better than) most hospitals .

I’m not saying the VA is perfect. All of us who worked there can think of times it wasn’t. But we also remember plenty of issues we’ve had at other places we’ve practiced, too.

Maybe it’s time to stop laughing at the VA and realize they’re doing something right — and learn from it to make healthcare better at the other 6,000 or so hospitals in the U.S.
 

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

Veterans Administration (VA) hospitals are a stepchild in the bizarre mishmash of the U.S. healthcare system. They’re best known (often justifiably so) for rather cantankerous patients, rigid rules, and other oddities (such as patients being able to go on leave and come back).

The majority of American doctors, including myself, did at least part of our training at a VA and have no shortage of stories about them. One I worked at (Omaha VA) was powered by its own nuclear reactor in the basement (no, really, it was, though sadly it’s since been taken out).

VA hospitals, in general, are no-frills — linoleum floors, no piano player in the lobby, very few private rooms, and occasionally in the news for scandals like the one at my hometown Carl T. Hayden VA hospital (I trained there, too).

Yet, a recent study found VA hospitals to be surprisingly efficient compared with the private sector. Their focus on patient care, rather than profits, allows them to run with 8% fewer administrative staff since they generally don’t have to deal with insurance billings, denials, and other paperwork (they also don’t have to deal with shareholders and investor demands or ridiculous CEO salaries, though the study didn’t address that).

On a national scale, this would mean roughly 900,000 fewer administrative jobs in the private sector. Granted, that also would mean those people would have to find other jobs, but let’s look at the patient side. If you had 900,000 fewer desk workers, you’d have the money to hire more nurses, respiratory techs, therapists, and other people directly involved in patient care. You’d also need a lot less office space, which further brings down overhead.

Part of the problem is that a lot of the current medical business is in marketing — how many ads do you see each day for different hospitals in your area? — and upcoding to extract more money from each billing. Neither of these has any clinical value on the patient side of things.

You don’t have to look back too far (2020) for the study that found U.S. healthcare spent four times as much money ($812 billion) per capita than our northern neighbors.

And, for all the jokes we make about the VA (myself included), a study last year found its care was on par (or even better than) most hospitals .

I’m not saying the VA is perfect. All of us who worked there can think of times it wasn’t. But we also remember plenty of issues we’ve had at other places we’ve practiced, too.

Maybe it’s time to stop laughing at the VA and realize they’re doing something right — and learn from it to make healthcare better at the other 6,000 or so hospitals in the U.S.
 

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

Veterans Administration (VA) hospitals are a stepchild in the bizarre mishmash of the U.S. healthcare system. They’re best known (often justifiably so) for rather cantankerous patients, rigid rules, and other oddities (such as patients being able to go on leave and come back).

The majority of American doctors, including myself, did at least part of our training at a VA and have no shortage of stories about them. One I worked at (Omaha VA) was powered by its own nuclear reactor in the basement (no, really, it was, though sadly it’s since been taken out).

VA hospitals, in general, are no-frills — linoleum floors, no piano player in the lobby, very few private rooms, and occasionally in the news for scandals like the one at my hometown Carl T. Hayden VA hospital (I trained there, too).

Yet, a recent study found VA hospitals to be surprisingly efficient compared with the private sector. Their focus on patient care, rather than profits, allows them to run with 8% fewer administrative staff since they generally don’t have to deal with insurance billings, denials, and other paperwork (they also don’t have to deal with shareholders and investor demands or ridiculous CEO salaries, though the study didn’t address that).

On a national scale, this would mean roughly 900,000 fewer administrative jobs in the private sector. Granted, that also would mean those people would have to find other jobs, but let’s look at the patient side. If you had 900,000 fewer desk workers, you’d have the money to hire more nurses, respiratory techs, therapists, and other people directly involved in patient care. You’d also need a lot less office space, which further brings down overhead.

Part of the problem is that a lot of the current medical business is in marketing — how many ads do you see each day for different hospitals in your area? — and upcoding to extract more money from each billing. Neither of these has any clinical value on the patient side of things.

You don’t have to look back too far (2020) for the study that found U.S. healthcare spent four times as much money ($812 billion) per capita than our northern neighbors.

And, for all the jokes we make about the VA (myself included), a study last year found its care was on par (or even better than) most hospitals .

I’m not saying the VA is perfect. All of us who worked there can think of times it wasn’t. But we also remember plenty of issues we’ve had at other places we’ve practiced, too.

Maybe it’s time to stop laughing at the VA and realize they’re doing something right — and learn from it to make healthcare better at the other 6,000 or so hospitals in the U.S.
 

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

This transcript has been edited for clarity.

Hi. I’m Art Caplan. I’m at the Division of Medical Ethics at the NYU Grossman School of Medicine. There has been an explosion of interest recently in bills that propose to extend medical assistance in dying to more Americans as states begin to contemplate legalization.

Right now, there are 10 states and the District of Columbia that have had some version of medical assistance in dying approved and on the books. That basically means that about 20% of Americans have access where they live to a physician who can prescribe a lethal dose of medication to them if they’re terminally ill and can ingest the medication themselves. That leaves many Americans not covered by this kind of access to this kind of service.

Many of you watching this may live in states where it is legal, like Oregon, Washington, New Jersey, Colorado, and Hawaii. I know many doctors say, “I’m not going to do that.” It’s not something that anyone is compelling a doctor to do. For some Americans, access is not just about where they live but whether there is a doctor willing to participate with them in bringing about their accelerated death, knowing that they’re inevitably going to die.

There’s not much we can do about that. It’s up to the conscience of each physician as to what they’re comfortable with. Certainly, there are other things that can be done to extend the possibility of having this available.

One thing that’s taking place is that, after lawsuits were filed, Vermont and Oregon have given up on their residency requirement, so you don’t have to be there 6 months or a year in order to use this opportunity. It’s legal now to move to the state or visit the state, and as soon as you get there, sign up for this kind of end-of-life intervention.

New Jersey is also being sued. I’ll predict that every state that has a residency requirement, when sued in court, is going to lose because we’ve long recognized the right of Americans to seek out healthcare in the United States, wherever they want to go.

If some states have made this a legitimate medical procedure, courts are going to say you can’t restrict it only to state residents. If someone wants to use a service, they’re entitled to show up from another state or another place and use it. I’m not sure about foreign nationals, but I’m very sure that Americans can go state to state in search of legitimate medical procedures.

The other bills that are out there, however, are basically saying they want to emulate Oregon, Washington, and the other states and say that the terminally ill, with severe restrictions, are going to be able to get this service without going anywhere.

The restrictions include a diagnosis of terminal illness and that you have to be deemed mentally competent. You can’t use this if you have Alzheimer’s or severe depression. You have to make a request twice with a week or two in between to make sure that your request is authentic. And obviously, everyone is on board to make sure that you’re not being coerced or pushed somehow into requesting a somewhat earlier death than you would have experienced without having the availability of the pills.

You also have to take the pills yourself or be able to pull a switch so that you could use a feeding tube–type administration. If you can’t do that, say due to ALS, you’re not eligible to use medical aid in dying. It’s a pretty restricted intervention.

Many people who get pills after going through these restrictions in the states that permit it don’t use it. As many as one third say they like having it there as a safety valve or a parachute, but once they know they could end their life sooner, then they’re going to stick it out.

Should states make this legal? New York, Massachusetts, Florida, and many other states have bills that are moving through. I’m going to say yes. We’ve had Oregon and Washington since the late 1990s with medical aid in dying on the books. There doesn’t seem to be any evidence of pushing people to use this, of bias against the disabled, or bigotry against particular ethnic or racial groups being used to encourage people to end their life sooner.

I think it is an option that Americans want. I think it’s an option that makes some sense. I’m well aware that we also have to make sure that people know about hospice. In some of these states, medical aid in dying is offered as a part of hospice — not all, but a few. Not everybody wants hospice once they realize that they’re dying and that it is coming relatively soon. They may want to leave with family present, with a ceremony, or with a quality of life that they desire.

Past experience says let’s continue to expand availability in each state. Let’s also realize that we have to keep the restrictions in place on how it’s used because they have protected us against abuse. Let’s understand that every doctor has an option to do this or not do this. It’s a matter of conscience and a matter of comfort.

I think legalization is the direction we’re going to be going in. Getting rid of the residency requirements that have been around, as I think courts are going to overturn them, also gives a push to the idea that once the service is in this many states, it’s something that should be available if there are doctors willing to do it.

I’m Art Caplan at the Division of Medical Ethics at NYU Grossman School of Medicine. New York, NY. Thank you for watching.

Arthur L. Caplan, PhD, has disclosed the following relevant financial relationships:

• Served as a director, officer, partner, employee, advisor, consultant, or trustee for: Johnson & Johnson’s Panel for Compassionate Drug Use (unpaid position)
• Serves as a contributing author and adviser for: Medscape

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Hi. I’m Art Caplan. I’m at the Division of Medical Ethics at the NYU Grossman School of Medicine. There has been an explosion of interest recently in bills that propose to extend medical assistance in dying to more Americans as states begin to contemplate legalization.

Right now, there are 10 states and the District of Columbia that have had some version of medical assistance in dying approved and on the books. That basically means that about 20% of Americans have access where they live to a physician who can prescribe a lethal dose of medication to them if they’re terminally ill and can ingest the medication themselves. That leaves many Americans not covered by this kind of access to this kind of service.

Many of you watching this may live in states where it is legal, like Oregon, Washington, New Jersey, Colorado, and Hawaii. I know many doctors say, “I’m not going to do that.” It’s not something that anyone is compelling a doctor to do. For some Americans, access is not just about where they live but whether there is a doctor willing to participate with them in bringing about their accelerated death, knowing that they’re inevitably going to die.

There’s not much we can do about that. It’s up to the conscience of each physician as to what they’re comfortable with. Certainly, there are other things that can be done to extend the possibility of having this available.

One thing that’s taking place is that, after lawsuits were filed, Vermont and Oregon have given up on their residency requirement, so you don’t have to be there 6 months or a year in order to use this opportunity. It’s legal now to move to the state or visit the state, and as soon as you get there, sign up for this kind of end-of-life intervention.

New Jersey is also being sued. I’ll predict that every state that has a residency requirement, when sued in court, is going to lose because we’ve long recognized the right of Americans to seek out healthcare in the United States, wherever they want to go.

If some states have made this a legitimate medical procedure, courts are going to say you can’t restrict it only to state residents. If someone wants to use a service, they’re entitled to show up from another state or another place and use it. I’m not sure about foreign nationals, but I’m very sure that Americans can go state to state in search of legitimate medical procedures.

The other bills that are out there, however, are basically saying they want to emulate Oregon, Washington, and the other states and say that the terminally ill, with severe restrictions, are going to be able to get this service without going anywhere.

The restrictions include a diagnosis of terminal illness and that you have to be deemed mentally competent. You can’t use this if you have Alzheimer’s or severe depression. You have to make a request twice with a week or two in between to make sure that your request is authentic. And obviously, everyone is on board to make sure that you’re not being coerced or pushed somehow into requesting a somewhat earlier death than you would have experienced without having the availability of the pills.

You also have to take the pills yourself or be able to pull a switch so that you could use a feeding tube–type administration. If you can’t do that, say due to ALS, you’re not eligible to use medical aid in dying. It’s a pretty restricted intervention.

Many people who get pills after going through these restrictions in the states that permit it don’t use it. As many as one third say they like having it there as a safety valve or a parachute, but once they know they could end their life sooner, then they’re going to stick it out.

Should states make this legal? New York, Massachusetts, Florida, and many other states have bills that are moving through. I’m going to say yes. We’ve had Oregon and Washington since the late 1990s with medical aid in dying on the books. There doesn’t seem to be any evidence of pushing people to use this, of bias against the disabled, or bigotry against particular ethnic or racial groups being used to encourage people to end their life sooner.

I think it is an option that Americans want. I think it’s an option that makes some sense. I’m well aware that we also have to make sure that people know about hospice. In some of these states, medical aid in dying is offered as a part of hospice — not all, but a few. Not everybody wants hospice once they realize that they’re dying and that it is coming relatively soon. They may want to leave with family present, with a ceremony, or with a quality of life that they desire.

Past experience says let’s continue to expand availability in each state. Let’s also realize that we have to keep the restrictions in place on how it’s used because they have protected us against abuse. Let’s understand that every doctor has an option to do this or not do this. It’s a matter of conscience and a matter of comfort.

I think legalization is the direction we’re going to be going in. Getting rid of the residency requirements that have been around, as I think courts are going to overturn them, also gives a push to the idea that once the service is in this many states, it’s something that should be available if there are doctors willing to do it.

I’m Art Caplan at the Division of Medical Ethics at NYU Grossman School of Medicine. New York, NY. Thank you for watching.

Arthur L. Caplan, PhD, has disclosed the following relevant financial relationships:

• Served as a director, officer, partner, employee, advisor, consultant, or trustee for: Johnson & Johnson’s Panel for Compassionate Drug Use (unpaid position)
• Serves as a contributing author and adviser for: Medscape

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Hi. I’m Art Caplan. I’m at the Division of Medical Ethics at the NYU Grossman School of Medicine. There has been an explosion of interest recently in bills that propose to extend medical assistance in dying to more Americans as states begin to contemplate legalization.

Right now, there are 10 states and the District of Columbia that have had some version of medical assistance in dying approved and on the books. That basically means that about 20% of Americans have access where they live to a physician who can prescribe a lethal dose of medication to them if they’re terminally ill and can ingest the medication themselves. That leaves many Americans not covered by this kind of access to this kind of service.

Many of you watching this may live in states where it is legal, like Oregon, Washington, New Jersey, Colorado, and Hawaii. I know many doctors say, “I’m not going to do that.” It’s not something that anyone is compelling a doctor to do. For some Americans, access is not just about where they live but whether there is a doctor willing to participate with them in bringing about their accelerated death, knowing that they’re inevitably going to die.

There’s not much we can do about that. It’s up to the conscience of each physician as to what they’re comfortable with. Certainly, there are other things that can be done to extend the possibility of having this available.

One thing that’s taking place is that, after lawsuits were filed, Vermont and Oregon have given up on their residency requirement, so you don’t have to be there 6 months or a year in order to use this opportunity. It’s legal now to move to the state or visit the state, and as soon as you get there, sign up for this kind of end-of-life intervention.

New Jersey is also being sued. I’ll predict that every state that has a residency requirement, when sued in court, is going to lose because we’ve long recognized the right of Americans to seek out healthcare in the United States, wherever they want to go.

If some states have made this a legitimate medical procedure, courts are going to say you can’t restrict it only to state residents. If someone wants to use a service, they’re entitled to show up from another state or another place and use it. I’m not sure about foreign nationals, but I’m very sure that Americans can go state to state in search of legitimate medical procedures.

The other bills that are out there, however, are basically saying they want to emulate Oregon, Washington, and the other states and say that the terminally ill, with severe restrictions, are going to be able to get this service without going anywhere.

The restrictions include a diagnosis of terminal illness and that you have to be deemed mentally competent. You can’t use this if you have Alzheimer’s or severe depression. You have to make a request twice with a week or two in between to make sure that your request is authentic. And obviously, everyone is on board to make sure that you’re not being coerced or pushed somehow into requesting a somewhat earlier death than you would have experienced without having the availability of the pills.

You also have to take the pills yourself or be able to pull a switch so that you could use a feeding tube–type administration. If you can’t do that, say due to ALS, you’re not eligible to use medical aid in dying. It’s a pretty restricted intervention.

Many people who get pills after going through these restrictions in the states that permit it don’t use it. As many as one third say they like having it there as a safety valve or a parachute, but once they know they could end their life sooner, then they’re going to stick it out.

Should states make this legal? New York, Massachusetts, Florida, and many other states have bills that are moving through. I’m going to say yes. We’ve had Oregon and Washington since the late 1990s with medical aid in dying on the books. There doesn’t seem to be any evidence of pushing people to use this, of bias against the disabled, or bigotry against particular ethnic or racial groups being used to encourage people to end their life sooner.

I think it is an option that Americans want. I think it’s an option that makes some sense. I’m well aware that we also have to make sure that people know about hospice. In some of these states, medical aid in dying is offered as a part of hospice — not all, but a few. Not everybody wants hospice once they realize that they’re dying and that it is coming relatively soon. They may want to leave with family present, with a ceremony, or with a quality of life that they desire.

Past experience says let’s continue to expand availability in each state. Let’s also realize that we have to keep the restrictions in place on how it’s used because they have protected us against abuse. Let’s understand that every doctor has an option to do this or not do this. It’s a matter of conscience and a matter of comfort.

I think legalization is the direction we’re going to be going in. Getting rid of the residency requirements that have been around, as I think courts are going to overturn them, also gives a push to the idea that once the service is in this many states, it’s something that should be available if there are doctors willing to do it.

I’m Art Caplan at the Division of Medical Ethics at NYU Grossman School of Medicine. New York, NY. Thank you for watching.

Arthur L. Caplan, PhD, has disclosed the following relevant financial relationships:

• Served as a director, officer, partner, employee, advisor, consultant, or trustee for: Johnson & Johnson’s Panel for Compassionate Drug Use (unpaid position)
• Serves as a contributing author and adviser for: Medscape

A version of this article appeared on Medscape.com.

Prior to 2013, the backbone of hepatitis C virus (HCV) therapy was pegylated interferon (PEG) in combination with ribavirin (RBV). This year-long therapy was associated with significant side effects and abysmal cure rates. Although efficacy improved with the addition of first-generation protease inhibitors, cure rates remained suboptimal and treatment side effects continued to be significant.

Clinicians and patients needed better options and looked to the drug pipeline with hope. However, even among the most optimistic, the idea that HCV therapy could evolve into an all-oral option seemed a relative pipe dream.

The Sofosbuvir Revolution Begins

The Liver Meeting held in 2013 changed everything.

Several presentations featured compelling data with sofosbuvir, a new polymerase inhibitor that, when combined with RBV, offered an all-oral option to patients with genotypes 2 and 3, as well as improved efficacy for patients with genotypes 1, 4, 5, and 6 when it was combined with 12 weeks of PEG/RBV.

However, the glass ceiling of HCV care was truly shattered with the randomized COSMOS trial, a late-breaker abstract that revealed 12-week functional cure rates in patients receiving sofosbuvir in combination with the protease inhibitor simeprevir.

This phase 2a trial in treatment-naive and -experienced genotype 1 patients with and without cirrhosis showed that an all-oral option was not only viable for the most common strain of HCV but was also safe and efficacious, even in difficult-to-treat populations.

On December 6, 2013, the US Food and Drug Administration (FDA) approved sofosbuvir for the treatment of HCV, ushering in a new era of therapy.

Guidelines quickly changed to advocate for both expansive HCV screening and generous treatment. Yet, as this more permissive approach was being recommended, the high price tag and large anticipated volume of those seeking prescriptions were setting off alarms. The drug cost triggered extensive restrictions based on degree of fibrosis, sobriety, and provider type in an effort to prevent immediate healthcare expenditures.

Given its high cost, rules restricting a patient to only one course of sofosbuvir-based therapy also surfaced. Although treatment with first-generation protease inhibitors carried a hefty price of $161,813.49 per sustained virologic response (SVR), compared with $66,000-$100,000 for 12 weeks of all-oral therapy, its uptake was low and limited by side effects and comorbid conditions. All-oral treatment appeared to have few medical barriers, leading payers to find ways to slow utilization. These restrictions are now gradually being eliminated.

Because of high SVR rates and few contraindications to therapy, most patients who gained access to treatment achieved cure. This included patients who had previously not responded to treatment and prioritized those with more advanced disease.

This quickly led to a significant shift in the population in need of treatment. Prior to 2013, many patients with HCV had advanced disease and did not respond to prior treatment options. After uptake of all-oral therapy, individuals in need were typically treatment naive without advanced disease.

This shift also added new psychosocial dimensions, as many of the newly infected individuals were struggling with active substance abuse. HCV treatment providers needed to change, with increasing recruitment of advanced practice providers, primary care physicians, and addiction medication specialists.

Progress, but Far From Reaching Targets

Fast-forward to 2023.

Ten years after FDA approval, 13.2 million individuals infected with HCV have been treated globally, 82% with sofosbuvir-based regimens and most in lower-middle-income countries. This is absolutely cause for celebration, but not complacency.

In 2016, the World Health Assembly adopted a resolution of elimination of viral hepatitis by 2030. The World Health Organization (WHO) defined elimination of HCV as 90% reduction in new cases of infection, 90% diagnosis of those infected, 80% of eligible individuals treated, and 65% reduction of deaths by 2030.

Despite all the success thus far, the CDA Foundation estimates that the WHO elimination targets will not be achieved until after the year 2050. They also note that in 2020, over 50 million individuals were infected with HCV, of which only 20% were diagnosed and 1% annually treated.

The HCV care cascade, by which the patient journeys from screening to cure, is complicated, and a one-size-fits-all solution is not possible. Reflex testing (an automatic transition to HCV polymerase chain reaction [PCR] testing in the lab for those who are HCV antibody positive) has significantly improved diagnosis. However, communicating these results and linking a patient to curative therapy remain significant obstacles.

Models and real-life experience show that multiple strategies can be successful. They include leveraging the electronic medical record, simplified treatment algorithms, test-and-treat strategies (screening high-risk populations with a point-of-care test that allows treatment initiation at the same visit), and co-localizing HCV screening and treatment with addiction services and relinkage programs (finding those who are already diagnosed and linking them to treatment).

In addition, focusing on populations at high risk for HCV infection — such as people who inject drugs, men who have sex with men, and incarcerated individuals — allows for better resource utilization.

Though daunting, HCV elimination is not impossible. There are several examples of success, including in the countries of Georgia and Iceland. Although, comparatively, the United States remains behind the curve, the White House has asked Congress for $11 billion to fund HCV elimination domestically.

As we await action at the national level, clinicians are reminded that there are several things we can do in caring for patients with HCV:

• A one-time HCV screening is recommended in all individuals aged 18 or older, including pregnant people with each pregnancy.
• HCV antibody testing with reflex to PCR should be used as the screening test.
• Pan-genotypic all-oral therapy is recommended for patients with HCV. Cure rates are greater than 95%, and there are few contraindications to treatment.
• Most people are eligible for simplified treatment algorithms that allow minimal on-treatment monitoring.

Without increased screening and linkage to curative therapy, we will not meet the WHO goals for HCV elimination.

Dr. Reau is chief of the hepatology section at Rush University Medical Center in Chicago and a regular contributor to this news organization. She serves as editor of Clinical Liver Disease, a multimedia review journal, and recently as a member of HCVGuidelines.org, a web-based resource from the American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America, as well as educational chair of the AASLD hepatitis C special interest group. She continues to have an active role in the hepatology interest group of the World Gastroenterology Organisation and the American Liver Foundation at the regional and national levels. She disclosed ties with AbbVie, Gilead, Arbutus, Intercept, and Salix.

A version of this article appeared on Medscape.com.

Prior to 2013, the backbone of hepatitis C virus (HCV) therapy was pegylated interferon (PEG) in combination with ribavirin (RBV). This year-long therapy was associated with significant side effects and abysmal cure rates. Although efficacy improved with the addition of first-generation protease inhibitors, cure rates remained suboptimal and treatment side effects continued to be significant.

Clinicians and patients needed better options and looked to the drug pipeline with hope. However, even among the most optimistic, the idea that HCV therapy could evolve into an all-oral option seemed a relative pipe dream.

The Sofosbuvir Revolution Begins

The Liver Meeting held in 2013 changed everything.

Several presentations featured compelling data with sofosbuvir, a new polymerase inhibitor that, when combined with RBV, offered an all-oral option to patients with genotypes 2 and 3, as well as improved efficacy for patients with genotypes 1, 4, 5, and 6 when it was combined with 12 weeks of PEG/RBV.

However, the glass ceiling of HCV care was truly shattered with the randomized COSMOS trial, a late-breaker abstract that revealed 12-week functional cure rates in patients receiving sofosbuvir in combination with the protease inhibitor simeprevir.

This phase 2a trial in treatment-naive and -experienced genotype 1 patients with and without cirrhosis showed that an all-oral option was not only viable for the most common strain of HCV but was also safe and efficacious, even in difficult-to-treat populations.

On December 6, 2013, the US Food and Drug Administration (FDA) approved sofosbuvir for the treatment of HCV, ushering in a new era of therapy.

Guidelines quickly changed to advocate for both expansive HCV screening and generous treatment. Yet, as this more permissive approach was being recommended, the high price tag and large anticipated volume of those seeking prescriptions were setting off alarms. The drug cost triggered extensive restrictions based on degree of fibrosis, sobriety, and provider type in an effort to prevent immediate healthcare expenditures.

Given its high cost, rules restricting a patient to only one course of sofosbuvir-based therapy also surfaced. Although treatment with first-generation protease inhibitors carried a hefty price of $161,813.49 per sustained virologic response (SVR), compared with $66,000-$100,000 for 12 weeks of all-oral therapy, its uptake was low and limited by side effects and comorbid conditions. All-oral treatment appeared to have few medical barriers, leading payers to find ways to slow utilization. These restrictions are now gradually being eliminated.

Because of high SVR rates and few contraindications to therapy, most patients who gained access to treatment achieved cure. This included patients who had previously not responded to treatment and prioritized those with more advanced disease.

This quickly led to a significant shift in the population in need of treatment. Prior to 2013, many patients with HCV had advanced disease and did not respond to prior treatment options. After uptake of all-oral therapy, individuals in need were typically treatment naive without advanced disease.

This shift also added new psychosocial dimensions, as many of the newly infected individuals were struggling with active substance abuse. HCV treatment providers needed to change, with increasing recruitment of advanced practice providers, primary care physicians, and addiction medication specialists.

Progress, but Far From Reaching Targets

Fast-forward to 2023.

Ten years after FDA approval, 13.2 million individuals infected with HCV have been treated globally, 82% with sofosbuvir-based regimens and most in lower-middle-income countries. This is absolutely cause for celebration, but not complacency.

In 2016, the World Health Assembly adopted a resolution of elimination of viral hepatitis by 2030. The World Health Organization (WHO) defined elimination of HCV as 90% reduction in new cases of infection, 90% diagnosis of those infected, 80% of eligible individuals treated, and 65% reduction of deaths by 2030.

Despite all the success thus far, the CDA Foundation estimates that the WHO elimination targets will not be achieved until after the year 2050. They also note that in 2020, over 50 million individuals were infected with HCV, of which only 20% were diagnosed and 1% annually treated.

The HCV care cascade, by which the patient journeys from screening to cure, is complicated, and a one-size-fits-all solution is not possible. Reflex testing (an automatic transition to HCV polymerase chain reaction [PCR] testing in the lab for those who are HCV antibody positive) has significantly improved diagnosis. However, communicating these results and linking a patient to curative therapy remain significant obstacles.

Models and real-life experience show that multiple strategies can be successful. They include leveraging the electronic medical record, simplified treatment algorithms, test-and-treat strategies (screening high-risk populations with a point-of-care test that allows treatment initiation at the same visit), and co-localizing HCV screening and treatment with addiction services and relinkage programs (finding those who are already diagnosed and linking them to treatment).

In addition, focusing on populations at high risk for HCV infection — such as people who inject drugs, men who have sex with men, and incarcerated individuals — allows for better resource utilization.

Though daunting, HCV elimination is not impossible. There are several examples of success, including in the countries of Georgia and Iceland. Although, comparatively, the United States remains behind the curve, the White House has asked Congress for $11 billion to fund HCV elimination domestically.

As we await action at the national level, clinicians are reminded that there are several things we can do in caring for patients with HCV:

• A one-time HCV screening is recommended in all individuals aged 18 or older, including pregnant people with each pregnancy.
• HCV antibody testing with reflex to PCR should be used as the screening test.
• Pan-genotypic all-oral therapy is recommended for patients with HCV. Cure rates are greater than 95%, and there are few contraindications to treatment.
• Most people are eligible for simplified treatment algorithms that allow minimal on-treatment monitoring.

Without increased screening and linkage to curative therapy, we will not meet the WHO goals for HCV elimination.

Dr. Reau is chief of the hepatology section at Rush University Medical Center in Chicago and a regular contributor to this news organization. She serves as editor of Clinical Liver Disease, a multimedia review journal, and recently as a member of HCVGuidelines.org, a web-based resource from the American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America, as well as educational chair of the AASLD hepatitis C special interest group. She continues to have an active role in the hepatology interest group of the World Gastroenterology Organisation and the American Liver Foundation at the regional and national levels. She disclosed ties with AbbVie, Gilead, Arbutus, Intercept, and Salix.

A version of this article appeared on Medscape.com.

Prior to 2013, the backbone of hepatitis C virus (HCV) therapy was pegylated interferon (PEG) in combination with ribavirin (RBV). This year-long therapy was associated with significant side effects and abysmal cure rates. Although efficacy improved with the addition of first-generation protease inhibitors, cure rates remained suboptimal and treatment side effects continued to be significant.

Clinicians and patients needed better options and looked to the drug pipeline with hope. However, even among the most optimistic, the idea that HCV therapy could evolve into an all-oral option seemed a relative pipe dream.

The Sofosbuvir Revolution Begins

The Liver Meeting held in 2013 changed everything.

Several presentations featured compelling data with sofosbuvir, a new polymerase inhibitor that, when combined with RBV, offered an all-oral option to patients with genotypes 2 and 3, as well as improved efficacy for patients with genotypes 1, 4, 5, and 6 when it was combined with 12 weeks of PEG/RBV.

However, the glass ceiling of HCV care was truly shattered with the randomized COSMOS trial, a late-breaker abstract that revealed 12-week functional cure rates in patients receiving sofosbuvir in combination with the protease inhibitor simeprevir.

This phase 2a trial in treatment-naive and -experienced genotype 1 patients with and without cirrhosis showed that an all-oral option was not only viable for the most common strain of HCV but was also safe and efficacious, even in difficult-to-treat populations.

On December 6, 2013, the US Food and Drug Administration (FDA) approved sofosbuvir for the treatment of HCV, ushering in a new era of therapy.

Guidelines quickly changed to advocate for both expansive HCV screening and generous treatment. Yet, as this more permissive approach was being recommended, the high price tag and large anticipated volume of those seeking prescriptions were setting off alarms. The drug cost triggered extensive restrictions based on degree of fibrosis, sobriety, and provider type in an effort to prevent immediate healthcare expenditures.

Given its high cost, rules restricting a patient to only one course of sofosbuvir-based therapy also surfaced. Although treatment with first-generation protease inhibitors carried a hefty price of $161,813.49 per sustained virologic response (SVR), compared with $66,000-$100,000 for 12 weeks of all-oral therapy, its uptake was low and limited by side effects and comorbid conditions. All-oral treatment appeared to have few medical barriers, leading payers to find ways to slow utilization. These restrictions are now gradually being eliminated.

Because of high SVR rates and few contraindications to therapy, most patients who gained access to treatment achieved cure. This included patients who had previously not responded to treatment and prioritized those with more advanced disease.

This quickly led to a significant shift in the population in need of treatment. Prior to 2013, many patients with HCV had advanced disease and did not respond to prior treatment options. After uptake of all-oral therapy, individuals in need were typically treatment naive without advanced disease.

This shift also added new psychosocial dimensions, as many of the newly infected individuals were struggling with active substance abuse. HCV treatment providers needed to change, with increasing recruitment of advanced practice providers, primary care physicians, and addiction medication specialists.

Progress, but Far From Reaching Targets

Fast-forward to 2023.

Ten years after FDA approval, 13.2 million individuals infected with HCV have been treated globally, 82% with sofosbuvir-based regimens and most in lower-middle-income countries. This is absolutely cause for celebration, but not complacency.

In 2016, the World Health Assembly adopted a resolution of elimination of viral hepatitis by 2030. The World Health Organization (WHO) defined elimination of HCV as 90% reduction in new cases of infection, 90% diagnosis of those infected, 80% of eligible individuals treated, and 65% reduction of deaths by 2030.

Despite all the success thus far, the CDA Foundation estimates that the WHO elimination targets will not be achieved until after the year 2050. They also note that in 2020, over 50 million individuals were infected with HCV, of which only 20% were diagnosed and 1% annually treated.

The HCV care cascade, by which the patient journeys from screening to cure, is complicated, and a one-size-fits-all solution is not possible. Reflex testing (an automatic transition to HCV polymerase chain reaction [PCR] testing in the lab for those who are HCV antibody positive) has significantly improved diagnosis. However, communicating these results and linking a patient to curative therapy remain significant obstacles.

Models and real-life experience show that multiple strategies can be successful. They include leveraging the electronic medical record, simplified treatment algorithms, test-and-treat strategies (screening high-risk populations with a point-of-care test that allows treatment initiation at the same visit), and co-localizing HCV screening and treatment with addiction services and relinkage programs (finding those who are already diagnosed and linking them to treatment).

In addition, focusing on populations at high risk for HCV infection — such as people who inject drugs, men who have sex with men, and incarcerated individuals — allows for better resource utilization.

Though daunting, HCV elimination is not impossible. There are several examples of success, including in the countries of Georgia and Iceland. Although, comparatively, the United States remains behind the curve, the White House has asked Congress for $11 billion to fund HCV elimination domestically.

As we await action at the national level, clinicians are reminded that there are several things we can do in caring for patients with HCV:

• A one-time HCV screening is recommended in all individuals aged 18 or older, including pregnant people with each pregnancy.
• HCV antibody testing with reflex to PCR should be used as the screening test.
• Pan-genotypic all-oral therapy is recommended for patients with HCV. Cure rates are greater than 95%, and there are few contraindications to treatment.
• Most people are eligible for simplified treatment algorithms that allow minimal on-treatment monitoring.

Without increased screening and linkage to curative therapy, we will not meet the WHO goals for HCV elimination.

Dr. Reau is chief of the hepatology section at Rush University Medical Center in Chicago and a regular contributor to this news organization. She serves as editor of Clinical Liver Disease, a multimedia review journal, and recently as a member of HCVGuidelines.org, a web-based resource from the American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America, as well as educational chair of the AASLD hepatitis C special interest group. She continues to have an active role in the hepatology interest group of the World Gastroenterology Organisation and the American Liver Foundation at the regional and national levels. She disclosed ties with AbbVie, Gilead, Arbutus, Intercept, and Salix.

A version of this article appeared on Medscape.com.