Autologous hematopoietic stem cell transplant (AHSCT) is more effective than fingolimod and natalizumab for patients with highly active relapsing-remitting multiple sclerosis (MS), data indicate.

In a multicenter study that emulated pairwise trials, AHSCT was associated with a higher likelihood of disability improvement, compared with fingolimod (hazard ratio, 2.70).

Once the immune system is reconstituted, it can contribute to the healing process. AHSCT thus provides the possibility of improvement in MS. Disease-modifying therapies that require continued use, however, could inhibit that process.

“If you can stop the inflammation that’s driving this disease fairly early on, [patients] do have the capacity to repair,” said study author Mark Freedman, MD, a professor of neurology at the University of Ottawa. “And we start to see that especially in a treatment [like AHSCT] where you don’t maintain the hit on the immune system.”

The study was published online in JAMA Neurology.
 

Pairwise analyses

Single-arm studies and an open-label, randomized trial have suggested that AHSCT has efficacy. The regimen is associated with a 0.3%-2.0% risk for mortality, but this risk has declined with better patient selection and clinical experience, according to the researchers. Comparative studies of AHSCT and DMTs are needed, but they are difficult to carry out, which is why the current team chose a propensity-score matched case–control design, according to lead author Tomas Kalincik, MD, PhD, head of the University of Melbourne’s Clinical Outcomes Research Unit.

The researchers examined data from 4,915 patients with relapsing-remitting MS. Of this population, 3.4% received AHSCT, 52.0% received fingolimod, 30.3% received natalizumab, and 14.2% received ocrelizumab. The proportion of women in the treatment groups ranged from 65% to 70%.

The researchers used pairwise matching to simulate the randomized, controlled trials comparing AHSCT with fingolimod, natalizumab, and ocrelizumab. Patients were matched on the basis of sex, age, disability, relapse events at 12 and 24 months before baseline, time from first symptoms to baseline, the most effective previous DMT, and geographical region.

Compared with fingolimod, AHSCT was associated with fewer relapses (annualized relapse rate, 0.09 vs. 0.20; P < .001). This finding was confirmed by a reduced cumulative hazard of relapse (HR, 0.26).

Compared with natalizumab, AHSCT had only a modestly greater effect on annualized relapse rates (ARR, 0.08 vs. 0.10; P = .03), with a cumulative HR for relapses of 0.51.

There was no significant difference in the risk for relapse between treatment with AHSCT and with ocrelizumab (ARR, 0.09 vs. 0.06; P = .86), nor was the risk of cumulative relapses significantly different between these treatments.

Among patients included in the pairwise analyses who received AHSCT, 23.3% developed febrile neutropenia during mobilization, 11.3% developed serum sickness, and 8.8% were admitted to an intensive care unit. There were 82 serious adverse events among 58 patients after they were discharged post AHSCT treatment, including infections (59.8% of adverse events) that were primarily due to viral sources (41.5% of adverse events). There was one death (0.6%) due to veno-occlusive disease of the liver following busulfan exposure.

Some AHSCT protocols are stronger than others, and milder immune ablative measures are less likely to produce lasting effects. “We completely remove the old immune system and put in a brand new one,” said Dr. Freedman, referring to the practice at his center. “That’s a fairly horrendous procedure, and, not surprisingly, we’ve had a slight increase in the types of side effects, compared with other groups who don’t use that heavy-duty conditioning regimen, but we’ve had absolutely zero return of inflammatory events over 23 years that we’ve been doing this. Nobody’s had another attack, no one has even developed a single new MRI lesion.”

The so-called medium and light conditioning regimens are associated with a return of disease activity in about 25% of patients within 3 years, Dr. Freedman added. “You start to see new MRI lesions form and relapses occurring. It’s still better than any of the higher efficacy therapies, but it’s not stopped the disease.”

A key limitation of the study is that its efficacy analysis did not distinguish between different intensities of AHSCT regimens, according to the authors.
 

Encouraging results

AHSCT is highly effective at temporarily eliminating inflammation in the central nervous system, according to Jeffrey Cohen, MD, director of the Cleveland Clinic’s Mellen Center for MS Treatment and Research, and Anne Cross, MD, professor of neurology at Washington University, St. Louis, who wrote an editorial that accompanied the study. As many as 35% of patients require DMTs at some point after AHSCT.

The results of the new study are encouraging, but plenty of unanswered questions remain, Dr. Cohen said. “Many studies demonstrate AHSCT to have potent durable efficacy that appears to be greater than that of the available DMTs, but some studies – for example, this one – suggest that AHSCT may be superior to some but not all DMTs. Therefore, where to place AHSCT in the overall treatment sequence remains uncertain.” Randomized, controlled trials that are now in process “hopefully will clarify,” he added.

The study was supported by the National Health and Medical Research Council of Australia, Multiple Sclerosis Australia, and the MS Foundation of Canada. Dr. Kalincik has financial relationships with Eisai, Novartis, Biogen, Merck, Roche, Sanofi Genzyme, Teva, Celgene, Bristol-Myers Squibb, and Janssen. Dr. Freedman has financial relationships with Sanofi-Genzyme Canada, Alexion, Atara Biotherapeutics, Bayer Healthcare, Beigene, BMS (Celgene), EMD, Hoffmann-La Roche, Janssen, Merck Serono, Quanterix, Novartis, Sanofi-Genzyme, Teva Canada Innovation, Celestra Health, McKesson, and EMD Serono. Dr. Cohen has financial relationships with Biogen, Convelo, EMD Serono, Gossamer Bio, Mylan, and PSI.

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

Autologous hematopoietic stem cell transplant (AHSCT) is more effective than fingolimod and natalizumab for patients with highly active relapsing-remitting multiple sclerosis (MS), data indicate.

In a multicenter study that emulated pairwise trials, AHSCT was associated with a higher likelihood of disability improvement, compared with fingolimod (hazard ratio, 2.70).

Once the immune system is reconstituted, it can contribute to the healing process. AHSCT thus provides the possibility of improvement in MS. Disease-modifying therapies that require continued use, however, could inhibit that process.

“If you can stop the inflammation that’s driving this disease fairly early on, [patients] do have the capacity to repair,” said study author Mark Freedman, MD, a professor of neurology at the University of Ottawa. “And we start to see that especially in a treatment [like AHSCT] where you don’t maintain the hit on the immune system.”

The study was published online in JAMA Neurology.
 

Pairwise analyses

Single-arm studies and an open-label, randomized trial have suggested that AHSCT has efficacy. The regimen is associated with a 0.3%-2.0% risk for mortality, but this risk has declined with better patient selection and clinical experience, according to the researchers. Comparative studies of AHSCT and DMTs are needed, but they are difficult to carry out, which is why the current team chose a propensity-score matched case–control design, according to lead author Tomas Kalincik, MD, PhD, head of the University of Melbourne’s Clinical Outcomes Research Unit.

The researchers examined data from 4,915 patients with relapsing-remitting MS. Of this population, 3.4% received AHSCT, 52.0% received fingolimod, 30.3% received natalizumab, and 14.2% received ocrelizumab. The proportion of women in the treatment groups ranged from 65% to 70%.

The researchers used pairwise matching to simulate the randomized, controlled trials comparing AHSCT with fingolimod, natalizumab, and ocrelizumab. Patients were matched on the basis of sex, age, disability, relapse events at 12 and 24 months before baseline, time from first symptoms to baseline, the most effective previous DMT, and geographical region.

Compared with fingolimod, AHSCT was associated with fewer relapses (annualized relapse rate, 0.09 vs. 0.20; P < .001). This finding was confirmed by a reduced cumulative hazard of relapse (HR, 0.26).

Compared with natalizumab, AHSCT had only a modestly greater effect on annualized relapse rates (ARR, 0.08 vs. 0.10; P = .03), with a cumulative HR for relapses of 0.51.

There was no significant difference in the risk for relapse between treatment with AHSCT and with ocrelizumab (ARR, 0.09 vs. 0.06; P = .86), nor was the risk of cumulative relapses significantly different between these treatments.

Among patients included in the pairwise analyses who received AHSCT, 23.3% developed febrile neutropenia during mobilization, 11.3% developed serum sickness, and 8.8% were admitted to an intensive care unit. There were 82 serious adverse events among 58 patients after they were discharged post AHSCT treatment, including infections (59.8% of adverse events) that were primarily due to viral sources (41.5% of adverse events). There was one death (0.6%) due to veno-occlusive disease of the liver following busulfan exposure.

Some AHSCT protocols are stronger than others, and milder immune ablative measures are less likely to produce lasting effects. “We completely remove the old immune system and put in a brand new one,” said Dr. Freedman, referring to the practice at his center. “That’s a fairly horrendous procedure, and, not surprisingly, we’ve had a slight increase in the types of side effects, compared with other groups who don’t use that heavy-duty conditioning regimen, but we’ve had absolutely zero return of inflammatory events over 23 years that we’ve been doing this. Nobody’s had another attack, no one has even developed a single new MRI lesion.”

The so-called medium and light conditioning regimens are associated with a return of disease activity in about 25% of patients within 3 years, Dr. Freedman added. “You start to see new MRI lesions form and relapses occurring. It’s still better than any of the higher efficacy therapies, but it’s not stopped the disease.”

A key limitation of the study is that its efficacy analysis did not distinguish between different intensities of AHSCT regimens, according to the authors.
 

Encouraging results

AHSCT is highly effective at temporarily eliminating inflammation in the central nervous system, according to Jeffrey Cohen, MD, director of the Cleveland Clinic’s Mellen Center for MS Treatment and Research, and Anne Cross, MD, professor of neurology at Washington University, St. Louis, who wrote an editorial that accompanied the study. As many as 35% of patients require DMTs at some point after AHSCT.

The results of the new study are encouraging, but plenty of unanswered questions remain, Dr. Cohen said. “Many studies demonstrate AHSCT to have potent durable efficacy that appears to be greater than that of the available DMTs, but some studies – for example, this one – suggest that AHSCT may be superior to some but not all DMTs. Therefore, where to place AHSCT in the overall treatment sequence remains uncertain.” Randomized, controlled trials that are now in process “hopefully will clarify,” he added.

The study was supported by the National Health and Medical Research Council of Australia, Multiple Sclerosis Australia, and the MS Foundation of Canada. Dr. Kalincik has financial relationships with Eisai, Novartis, Biogen, Merck, Roche, Sanofi Genzyme, Teva, Celgene, Bristol-Myers Squibb, and Janssen. Dr. Freedman has financial relationships with Sanofi-Genzyme Canada, Alexion, Atara Biotherapeutics, Bayer Healthcare, Beigene, BMS (Celgene), EMD, Hoffmann-La Roche, Janssen, Merck Serono, Quanterix, Novartis, Sanofi-Genzyme, Teva Canada Innovation, Celestra Health, McKesson, and EMD Serono. Dr. Cohen has financial relationships with Biogen, Convelo, EMD Serono, Gossamer Bio, Mylan, and PSI.

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

Autologous hematopoietic stem cell transplant (AHSCT) is more effective than fingolimod and natalizumab for patients with highly active relapsing-remitting multiple sclerosis (MS), data indicate.

In a multicenter study that emulated pairwise trials, AHSCT was associated with a higher likelihood of disability improvement, compared with fingolimod (hazard ratio, 2.70).

Once the immune system is reconstituted, it can contribute to the healing process. AHSCT thus provides the possibility of improvement in MS. Disease-modifying therapies that require continued use, however, could inhibit that process.

“If you can stop the inflammation that’s driving this disease fairly early on, [patients] do have the capacity to repair,” said study author Mark Freedman, MD, a professor of neurology at the University of Ottawa. “And we start to see that especially in a treatment [like AHSCT] where you don’t maintain the hit on the immune system.”

The study was published online in JAMA Neurology.
 

Pairwise analyses

Single-arm studies and an open-label, randomized trial have suggested that AHSCT has efficacy. The regimen is associated with a 0.3%-2.0% risk for mortality, but this risk has declined with better patient selection and clinical experience, according to the researchers. Comparative studies of AHSCT and DMTs are needed, but they are difficult to carry out, which is why the current team chose a propensity-score matched case–control design, according to lead author Tomas Kalincik, MD, PhD, head of the University of Melbourne’s Clinical Outcomes Research Unit.

The researchers examined data from 4,915 patients with relapsing-remitting MS. Of this population, 3.4% received AHSCT, 52.0% received fingolimod, 30.3% received natalizumab, and 14.2% received ocrelizumab. The proportion of women in the treatment groups ranged from 65% to 70%.

The researchers used pairwise matching to simulate the randomized, controlled trials comparing AHSCT with fingolimod, natalizumab, and ocrelizumab. Patients were matched on the basis of sex, age, disability, relapse events at 12 and 24 months before baseline, time from first symptoms to baseline, the most effective previous DMT, and geographical region.

Compared with fingolimod, AHSCT was associated with fewer relapses (annualized relapse rate, 0.09 vs. 0.20; P < .001). This finding was confirmed by a reduced cumulative hazard of relapse (HR, 0.26).

Compared with natalizumab, AHSCT had only a modestly greater effect on annualized relapse rates (ARR, 0.08 vs. 0.10; P = .03), with a cumulative HR for relapses of 0.51.

There was no significant difference in the risk for relapse between treatment with AHSCT and with ocrelizumab (ARR, 0.09 vs. 0.06; P = .86), nor was the risk of cumulative relapses significantly different between these treatments.

Among patients included in the pairwise analyses who received AHSCT, 23.3% developed febrile neutropenia during mobilization, 11.3% developed serum sickness, and 8.8% were admitted to an intensive care unit. There were 82 serious adverse events among 58 patients after they were discharged post AHSCT treatment, including infections (59.8% of adverse events) that were primarily due to viral sources (41.5% of adverse events). There was one death (0.6%) due to veno-occlusive disease of the liver following busulfan exposure.

Some AHSCT protocols are stronger than others, and milder immune ablative measures are less likely to produce lasting effects. “We completely remove the old immune system and put in a brand new one,” said Dr. Freedman, referring to the practice at his center. “That’s a fairly horrendous procedure, and, not surprisingly, we’ve had a slight increase in the types of side effects, compared with other groups who don’t use that heavy-duty conditioning regimen, but we’ve had absolutely zero return of inflammatory events over 23 years that we’ve been doing this. Nobody’s had another attack, no one has even developed a single new MRI lesion.”

The so-called medium and light conditioning regimens are associated with a return of disease activity in about 25% of patients within 3 years, Dr. Freedman added. “You start to see new MRI lesions form and relapses occurring. It’s still better than any of the higher efficacy therapies, but it’s not stopped the disease.”

A key limitation of the study is that its efficacy analysis did not distinguish between different intensities of AHSCT regimens, according to the authors.
 

Encouraging results

AHSCT is highly effective at temporarily eliminating inflammation in the central nervous system, according to Jeffrey Cohen, MD, director of the Cleveland Clinic’s Mellen Center for MS Treatment and Research, and Anne Cross, MD, professor of neurology at Washington University, St. Louis, who wrote an editorial that accompanied the study. As many as 35% of patients require DMTs at some point after AHSCT.

The results of the new study are encouraging, but plenty of unanswered questions remain, Dr. Cohen said. “Many studies demonstrate AHSCT to have potent durable efficacy that appears to be greater than that of the available DMTs, but some studies – for example, this one – suggest that AHSCT may be superior to some but not all DMTs. Therefore, where to place AHSCT in the overall treatment sequence remains uncertain.” Randomized, controlled trials that are now in process “hopefully will clarify,” he added.

The study was supported by the National Health and Medical Research Council of Australia, Multiple Sclerosis Australia, and the MS Foundation of Canada. Dr. Kalincik has financial relationships with Eisai, Novartis, Biogen, Merck, Roche, Sanofi Genzyme, Teva, Celgene, Bristol-Myers Squibb, and Janssen. Dr. Freedman has financial relationships with Sanofi-Genzyme Canada, Alexion, Atara Biotherapeutics, Bayer Healthcare, Beigene, BMS (Celgene), EMD, Hoffmann-La Roche, Janssen, Merck Serono, Quanterix, Novartis, Sanofi-Genzyme, Teva Canada Innovation, Celestra Health, McKesson, and EMD Serono. Dr. Cohen has financial relationships with Biogen, Convelo, EMD Serono, Gossamer Bio, Mylan, and PSI.

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

A new practice guideline aims to help clinicians navigate an increasingly crowded field of over-the-counter and prescription treatment options for chronic idiopathic constipation in otherwise-healthy people.

The guideline, published simultaneously in the American Journal of Gastroenterology and in Gastroenterology, was developed jointly by the American Gastroenterological Association and the American College of Gastroenterology. It marks the AGA’s first update on chronic idiopathic constipation (CIC), also called functional constipation, in a decade.

In an interview, guideline lead author Lin Chang, MD, of the University of California, Los Angeles, noted that CIC – defined as constipation lasting at least 3 months in the absence of malignancy or obstruction, a medication side effect, or inflammatory bowel disease – is common, affecting between 8% and 12% of all U.S. adults. Most will be treated by primary care physicians, not specialists, Dr. Chang said. And most will see their physicians having already tried different over-the-counter treatments.

“The criteria for CIC or functional constipation hasn’t really changed” since the last AGA guideline on it was published in 2013, Dr. Chang said, adding that the diagnostic standard currently used is the Rome IV criteria for functional constipation. “There are just more medications right now than there were 10 years ago.”

The new guideline, into which evidence from 28 studies was integrated, offers recommendations regarding different types of fiber; the osmotic laxatives polyethylene glycol, magnesium oxide, and lactulose; and the stimulant laxatives bisacodyl, sodium picosulfate, and senna. It also assesses the secretagogues lubiprostone, linaclotide, plecanatide, and the serotonin type 4 agonist prucalopride.

One commonly used agent in clinical practice, the stool softener docusate sodium, does not appear in the guideline, as there was too little data available on it to make an assessment, Dr. Chang said. Fruit-based laxatives were excluded because they were the subject of a recent evidence review. Lifestyle modifications such as exercise, surgical interventions, and probiotics were not assessed.

The guideline’s strongest recommendations are for polyethylene glycol, sodium picosulfate, linaclotide, plecanatide, and prucalopride, with conditional recommendations for fiber, lactulose, senna, magnesium oxide, and lubiprostone.

As costs of the recommended therapies vary from less than $10 a month to over $500, the authors also included price information, noting that “patient values, costs, and health equity considerations” must be factored into treatment choices. “For polyethylene glycol there’s a strong recommendation, although the certainty of evidence was moderate,” Dr. Chang said. “And with fiber, even though we made only a conditional recommendation based on the evidence, our remarks and our algorithm make clear that it should be considered as a first-line treatment.”

In general, “if someone has more mild symptoms, you should try fiber or increase their fiber intake in their diet,” Dr. Chang commented. “If that doesn’t work, try over-the-counter remedies like polyethylene glycol. Then if symptoms are more severe, or if they fail the first-line treatments, then you go to prescription agents.”

In clinical practice, “there always considerations besides scientific evidence of safety and efficacy,” Dr. Chang stressed. “You have to personalize treatment for the patient.” A patient may present having already failed with fiber, or who does not want to use magnesium or can’t afford a costlier agent.

The guidelines contain implementation advice that might guide choice of therapy or dosing. With the prescription osmotic laxative lactulose, for example, “you may not wish to use it as a first-line treatment because bloating and flatulence are very common,” Dr. Chang said. “Our implementation advice makes that clear.” For senna, a stimulant laxative derived from the leaves of the senna plant and for which quality evidence is limited, the guideline authors stressed that patients should be started on low doses to avoid cramping.

Dr. Chang said that, while the new guideline covers medication options for otherwise-healthy adults, clinicians should be mindful that patients presenting with CIC might still have a defecatory disorder. “A person could also have pelvic floor dysfunction as a primary cause or contributing factor. If someone fails fiber or polyethylene glycol, consider a digital rectal examination as part of the physical exam. If this is abnormal, consider referring them for anorectal manometry.”

Untreated constipation carries risks, Dr. Chang noted, but “sometimes people with bothersome symptoms don’t treat them because they’re worried they’ll become dependent on treatment. It’s a dependency in the sense that you have to treat any chronic condition, such as high blood pressure or diabetes, but the treatments aren’t addictive, except for some stimulant laxatives to which people can develop tolerance.”

Hemorrhoids and defecatory disorders can occur over time because of straining, Dr. Chang said. “The pelvic wall can also get very lax, and that is hard to fix. Or, one can develop a rectal prolapse. Another thing that happens when people have longstanding constipation for many years is they start losing the urge to have a bowel movement.”

For more information, see the related clinical decision support tool in Gastroenterology.

The guideline’s development was funded by the AGA and ACG, without industry support. Authors with conflicts of interest regarding a specific intervention or drug were not allowed to weigh in on those interventions.

A new practice guideline aims to help clinicians navigate an increasingly crowded field of over-the-counter and prescription treatment options for chronic idiopathic constipation in otherwise-healthy people.

The guideline, published simultaneously in the American Journal of Gastroenterology and in Gastroenterology, was developed jointly by the American Gastroenterological Association and the American College of Gastroenterology. It marks the AGA’s first update on chronic idiopathic constipation (CIC), also called functional constipation, in a decade.

In an interview, guideline lead author Lin Chang, MD, of the University of California, Los Angeles, noted that CIC – defined as constipation lasting at least 3 months in the absence of malignancy or obstruction, a medication side effect, or inflammatory bowel disease – is common, affecting between 8% and 12% of all U.S. adults. Most will be treated by primary care physicians, not specialists, Dr. Chang said. And most will see their physicians having already tried different over-the-counter treatments.

“The criteria for CIC or functional constipation hasn’t really changed” since the last AGA guideline on it was published in 2013, Dr. Chang said, adding that the diagnostic standard currently used is the Rome IV criteria for functional constipation. “There are just more medications right now than there were 10 years ago.”

The new guideline, into which evidence from 28 studies was integrated, offers recommendations regarding different types of fiber; the osmotic laxatives polyethylene glycol, magnesium oxide, and lactulose; and the stimulant laxatives bisacodyl, sodium picosulfate, and senna. It also assesses the secretagogues lubiprostone, linaclotide, plecanatide, and the serotonin type 4 agonist prucalopride.

One commonly used agent in clinical practice, the stool softener docusate sodium, does not appear in the guideline, as there was too little data available on it to make an assessment, Dr. Chang said. Fruit-based laxatives were excluded because they were the subject of a recent evidence review. Lifestyle modifications such as exercise, surgical interventions, and probiotics were not assessed.

The guideline’s strongest recommendations are for polyethylene glycol, sodium picosulfate, linaclotide, plecanatide, and prucalopride, with conditional recommendations for fiber, lactulose, senna, magnesium oxide, and lubiprostone.

As costs of the recommended therapies vary from less than $10 a month to over $500, the authors also included price information, noting that “patient values, costs, and health equity considerations” must be factored into treatment choices. “For polyethylene glycol there’s a strong recommendation, although the certainty of evidence was moderate,” Dr. Chang said. “And with fiber, even though we made only a conditional recommendation based on the evidence, our remarks and our algorithm make clear that it should be considered as a first-line treatment.”

In general, “if someone has more mild symptoms, you should try fiber or increase their fiber intake in their diet,” Dr. Chang commented. “If that doesn’t work, try over-the-counter remedies like polyethylene glycol. Then if symptoms are more severe, or if they fail the first-line treatments, then you go to prescription agents.”

In clinical practice, “there always considerations besides scientific evidence of safety and efficacy,” Dr. Chang stressed. “You have to personalize treatment for the patient.” A patient may present having already failed with fiber, or who does not want to use magnesium or can’t afford a costlier agent.

The guidelines contain implementation advice that might guide choice of therapy or dosing. With the prescription osmotic laxative lactulose, for example, “you may not wish to use it as a first-line treatment because bloating and flatulence are very common,” Dr. Chang said. “Our implementation advice makes that clear.” For senna, a stimulant laxative derived from the leaves of the senna plant and for which quality evidence is limited, the guideline authors stressed that patients should be started on low doses to avoid cramping.

Dr. Chang said that, while the new guideline covers medication options for otherwise-healthy adults, clinicians should be mindful that patients presenting with CIC might still have a defecatory disorder. “A person could also have pelvic floor dysfunction as a primary cause or contributing factor. If someone fails fiber or polyethylene glycol, consider a digital rectal examination as part of the physical exam. If this is abnormal, consider referring them for anorectal manometry.”

Untreated constipation carries risks, Dr. Chang noted, but “sometimes people with bothersome symptoms don’t treat them because they’re worried they’ll become dependent on treatment. It’s a dependency in the sense that you have to treat any chronic condition, such as high blood pressure or diabetes, but the treatments aren’t addictive, except for some stimulant laxatives to which people can develop tolerance.”

Hemorrhoids and defecatory disorders can occur over time because of straining, Dr. Chang said. “The pelvic wall can also get very lax, and that is hard to fix. Or, one can develop a rectal prolapse. Another thing that happens when people have longstanding constipation for many years is they start losing the urge to have a bowel movement.”

For more information, see the related clinical decision support tool in Gastroenterology.

The guideline’s development was funded by the AGA and ACG, without industry support. Authors with conflicts of interest regarding a specific intervention or drug were not allowed to weigh in on those interventions.

A new practice guideline aims to help clinicians navigate an increasingly crowded field of over-the-counter and prescription treatment options for chronic idiopathic constipation in otherwise-healthy people.

The guideline, published simultaneously in the American Journal of Gastroenterology and in Gastroenterology, was developed jointly by the American Gastroenterological Association and the American College of Gastroenterology. It marks the AGA’s first update on chronic idiopathic constipation (CIC), also called functional constipation, in a decade.

In an interview, guideline lead author Lin Chang, MD, of the University of California, Los Angeles, noted that CIC – defined as constipation lasting at least 3 months in the absence of malignancy or obstruction, a medication side effect, or inflammatory bowel disease – is common, affecting between 8% and 12% of all U.S. adults. Most will be treated by primary care physicians, not specialists, Dr. Chang said. And most will see their physicians having already tried different over-the-counter treatments.

“The criteria for CIC or functional constipation hasn’t really changed” since the last AGA guideline on it was published in 2013, Dr. Chang said, adding that the diagnostic standard currently used is the Rome IV criteria for functional constipation. “There are just more medications right now than there were 10 years ago.”

The new guideline, into which evidence from 28 studies was integrated, offers recommendations regarding different types of fiber; the osmotic laxatives polyethylene glycol, magnesium oxide, and lactulose; and the stimulant laxatives bisacodyl, sodium picosulfate, and senna. It also assesses the secretagogues lubiprostone, linaclotide, plecanatide, and the serotonin type 4 agonist prucalopride.

One commonly used agent in clinical practice, the stool softener docusate sodium, does not appear in the guideline, as there was too little data available on it to make an assessment, Dr. Chang said. Fruit-based laxatives were excluded because they were the subject of a recent evidence review. Lifestyle modifications such as exercise, surgical interventions, and probiotics were not assessed.

The guideline’s strongest recommendations are for polyethylene glycol, sodium picosulfate, linaclotide, plecanatide, and prucalopride, with conditional recommendations for fiber, lactulose, senna, magnesium oxide, and lubiprostone.

As costs of the recommended therapies vary from less than $10 a month to over $500, the authors also included price information, noting that “patient values, costs, and health equity considerations” must be factored into treatment choices. “For polyethylene glycol there’s a strong recommendation, although the certainty of evidence was moderate,” Dr. Chang said. “And with fiber, even though we made only a conditional recommendation based on the evidence, our remarks and our algorithm make clear that it should be considered as a first-line treatment.”

In general, “if someone has more mild symptoms, you should try fiber or increase their fiber intake in their diet,” Dr. Chang commented. “If that doesn’t work, try over-the-counter remedies like polyethylene glycol. Then if symptoms are more severe, or if they fail the first-line treatments, then you go to prescription agents.”

In clinical practice, “there always considerations besides scientific evidence of safety and efficacy,” Dr. Chang stressed. “You have to personalize treatment for the patient.” A patient may present having already failed with fiber, or who does not want to use magnesium or can’t afford a costlier agent.

The guidelines contain implementation advice that might guide choice of therapy or dosing. With the prescription osmotic laxative lactulose, for example, “you may not wish to use it as a first-line treatment because bloating and flatulence are very common,” Dr. Chang said. “Our implementation advice makes that clear.” For senna, a stimulant laxative derived from the leaves of the senna plant and for which quality evidence is limited, the guideline authors stressed that patients should be started on low doses to avoid cramping.

Dr. Chang said that, while the new guideline covers medication options for otherwise-healthy adults, clinicians should be mindful that patients presenting with CIC might still have a defecatory disorder. “A person could also have pelvic floor dysfunction as a primary cause or contributing factor. If someone fails fiber or polyethylene glycol, consider a digital rectal examination as part of the physical exam. If this is abnormal, consider referring them for anorectal manometry.”

Untreated constipation carries risks, Dr. Chang noted, but “sometimes people with bothersome symptoms don’t treat them because they’re worried they’ll become dependent on treatment. It’s a dependency in the sense that you have to treat any chronic condition, such as high blood pressure or diabetes, but the treatments aren’t addictive, except for some stimulant laxatives to which people can develop tolerance.”

Hemorrhoids and defecatory disorders can occur over time because of straining, Dr. Chang said. “The pelvic wall can also get very lax, and that is hard to fix. Or, one can develop a rectal prolapse. Another thing that happens when people have longstanding constipation for many years is they start losing the urge to have a bowel movement.”

For more information, see the related clinical decision support tool in Gastroenterology.

The guideline’s development was funded by the AGA and ACG, without industry support. Authors with conflicts of interest regarding a specific intervention or drug were not allowed to weigh in on those interventions.

The Centers for Medicare & Medicaid Services has announced that Medicare will cover drugs designed to slow Alzheimer’s disease once they receive traditional approval by the Food and Drug Administration.

The one caveat is that CMS will require physicians to participate in registries that collect evidence about how these drugs work in the real world.

Physicians will be able to submit this evidence through a nationwide, CMS-facilitated portal that will be available when any product gains traditional approval and will collect information via an easy-to-use format.

“If the FDA grants traditional approval, then Medicare will cover it in appropriate settings that also support the collection of real-world information to study the usefulness of these drugs for people with Medicare,” the CMS says in a news release.

“CMS has always been committed to helping people obtain timely access to innovative treatments that meaningfully improve care and outcomes for this disease,” added CMS Administrator Chiquita Brooks-LaSure.

“If the FDA grants traditional approval, CMS is prepared to ensure anyone with Medicare Part B who meets the criteria is covered,” Ms. Brooks-LaSure explained.

The CMS says broader Medicare coverage for an Alzheimer’s drug would begin on the same day the FDA grants traditional approval. Under CMS’ current coverage policy, if the FDA grants traditional approval to other drugs in this class, they would also be eligible for broader coverage.

Currently two drugs in this class – aducanumab (Aduhelm) and lecanemab (Leqembi) – have received accelerated approval from the FDA, but no product has received traditional approval.

Lecanemab might be the first to cross the line.

On June 9, the FDA Peripheral and Central Nervous System Drugs Advisory Committee will discuss results of a confirmatory trial of lecanemab, with a potential decision on traditional approval expected shortly thereafter.

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

The Centers for Medicare & Medicaid Services has announced that Medicare will cover drugs designed to slow Alzheimer’s disease once they receive traditional approval by the Food and Drug Administration.

The one caveat is that CMS will require physicians to participate in registries that collect evidence about how these drugs work in the real world.

Physicians will be able to submit this evidence through a nationwide, CMS-facilitated portal that will be available when any product gains traditional approval and will collect information via an easy-to-use format.

“If the FDA grants traditional approval, then Medicare will cover it in appropriate settings that also support the collection of real-world information to study the usefulness of these drugs for people with Medicare,” the CMS says in a news release.

“CMS has always been committed to helping people obtain timely access to innovative treatments that meaningfully improve care and outcomes for this disease,” added CMS Administrator Chiquita Brooks-LaSure.

“If the FDA grants traditional approval, CMS is prepared to ensure anyone with Medicare Part B who meets the criteria is covered,” Ms. Brooks-LaSure explained.

The CMS says broader Medicare coverage for an Alzheimer’s drug would begin on the same day the FDA grants traditional approval. Under CMS’ current coverage policy, if the FDA grants traditional approval to other drugs in this class, they would also be eligible for broader coverage.

Currently two drugs in this class – aducanumab (Aduhelm) and lecanemab (Leqembi) – have received accelerated approval from the FDA, but no product has received traditional approval.

Lecanemab might be the first to cross the line.

On June 9, the FDA Peripheral and Central Nervous System Drugs Advisory Committee will discuss results of a confirmatory trial of lecanemab, with a potential decision on traditional approval expected shortly thereafter.

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

The Centers for Medicare & Medicaid Services has announced that Medicare will cover drugs designed to slow Alzheimer’s disease once they receive traditional approval by the Food and Drug Administration.

The one caveat is that CMS will require physicians to participate in registries that collect evidence about how these drugs work in the real world.

Physicians will be able to submit this evidence through a nationwide, CMS-facilitated portal that will be available when any product gains traditional approval and will collect information via an easy-to-use format.

“If the FDA grants traditional approval, then Medicare will cover it in appropriate settings that also support the collection of real-world information to study the usefulness of these drugs for people with Medicare,” the CMS says in a news release.

“CMS has always been committed to helping people obtain timely access to innovative treatments that meaningfully improve care and outcomes for this disease,” added CMS Administrator Chiquita Brooks-LaSure.

“If the FDA grants traditional approval, CMS is prepared to ensure anyone with Medicare Part B who meets the criteria is covered,” Ms. Brooks-LaSure explained.

The CMS says broader Medicare coverage for an Alzheimer’s drug would begin on the same day the FDA grants traditional approval. Under CMS’ current coverage policy, if the FDA grants traditional approval to other drugs in this class, they would also be eligible for broader coverage.

Currently two drugs in this class – aducanumab (Aduhelm) and lecanemab (Leqembi) – have received accelerated approval from the FDA, but no product has received traditional approval.

Lecanemab might be the first to cross the line.

On June 9, the FDA Peripheral and Central Nervous System Drugs Advisory Committee will discuss results of a confirmatory trial of lecanemab, with a potential decision on traditional approval expected shortly thereafter.

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

About 10% of people infected with Omicron reported having long COVID, a lower percentage than estimated for people infected with earlier strains of the coronavirus, according to a study published in JAMA. 

The research team looked at data from 8,646 adults infected with COVID-19 at different times of the pandemic and 1,118 who did not have COVID. 

“Based on a subset of 2,231 patients in this analysis who had a first COVID-19 infection on or after Dec. 1, 2021, when the Omicron variant was circulating, about 10% experienced long-term symptoms or long COVID after 6 months,” the National Institutes of Health said in a news release. 

People who were unvaccinated or got COVID before Omicron were more likely to have long COVID and had more severe cases, the NIH said.

Previous studies have come up with higher figures than 10% for people who have long COVID. 

For instance, in June 2022 the CDC said one in five Americans who had COVID reported having long COVID. And a University of Oxford study published in September 2021 found more than a third of patients had long COVID symptoms.

The scientists in the most recent study identified 12 symptoms that distinguished people who did and didn’t have COVID. The scientists developed a scoring system for the symptoms to set a threshold to identify people who had long COVID, the NIH said.

The symptoms were fatigue, brain fog, dizziness, stomach upset, heart palpitations, issues with sexual desire or capacity, loss of smell or taste, thirst, chronic coughing, chest pain, and abnormal movements. Another symptom was postexertional malaise, or worse symptoms after mental or physical exertion. 

Scientists still have many questions about long COVID, such as how many people get it and why some people get it and others don’t. 

The study was coordinated through the NIH’s RECOVER (Researching COVID to Enhance Recovery) initiative, which aims to find out how to define, detect, and treat long COVID.

“The researchers hope this study is the next step toward potential treatments for long COVID, which affects the health and wellbeing of millions of Americans,” the NIH said.

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

About 10% of people infected with Omicron reported having long COVID, a lower percentage than estimated for people infected with earlier strains of the coronavirus, according to a study published in JAMA. 

The research team looked at data from 8,646 adults infected with COVID-19 at different times of the pandemic and 1,118 who did not have COVID. 

“Based on a subset of 2,231 patients in this analysis who had a first COVID-19 infection on or after Dec. 1, 2021, when the Omicron variant was circulating, about 10% experienced long-term symptoms or long COVID after 6 months,” the National Institutes of Health said in a news release. 

People who were unvaccinated or got COVID before Omicron were more likely to have long COVID and had more severe cases, the NIH said.

Previous studies have come up with higher figures than 10% for people who have long COVID. 

For instance, in June 2022 the CDC said one in five Americans who had COVID reported having long COVID. And a University of Oxford study published in September 2021 found more than a third of patients had long COVID symptoms.

The scientists in the most recent study identified 12 symptoms that distinguished people who did and didn’t have COVID. The scientists developed a scoring system for the symptoms to set a threshold to identify people who had long COVID, the NIH said.

The symptoms were fatigue, brain fog, dizziness, stomach upset, heart palpitations, issues with sexual desire or capacity, loss of smell or taste, thirst, chronic coughing, chest pain, and abnormal movements. Another symptom was postexertional malaise, or worse symptoms after mental or physical exertion. 

Scientists still have many questions about long COVID, such as how many people get it and why some people get it and others don’t. 

The study was coordinated through the NIH’s RECOVER (Researching COVID to Enhance Recovery) initiative, which aims to find out how to define, detect, and treat long COVID.

“The researchers hope this study is the next step toward potential treatments for long COVID, which affects the health and wellbeing of millions of Americans,” the NIH said.

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

About 10% of people infected with Omicron reported having long COVID, a lower percentage than estimated for people infected with earlier strains of the coronavirus, according to a study published in JAMA. 

The research team looked at data from 8,646 adults infected with COVID-19 at different times of the pandemic and 1,118 who did not have COVID. 

“Based on a subset of 2,231 patients in this analysis who had a first COVID-19 infection on or after Dec. 1, 2021, when the Omicron variant was circulating, about 10% experienced long-term symptoms or long COVID after 6 months,” the National Institutes of Health said in a news release. 

People who were unvaccinated or got COVID before Omicron were more likely to have long COVID and had more severe cases, the NIH said.

Previous studies have come up with higher figures than 10% for people who have long COVID. 

For instance, in June 2022 the CDC said one in five Americans who had COVID reported having long COVID. And a University of Oxford study published in September 2021 found more than a third of patients had long COVID symptoms.

The scientists in the most recent study identified 12 symptoms that distinguished people who did and didn’t have COVID. The scientists developed a scoring system for the symptoms to set a threshold to identify people who had long COVID, the NIH said.

The symptoms were fatigue, brain fog, dizziness, stomach upset, heart palpitations, issues with sexual desire or capacity, loss of smell or taste, thirst, chronic coughing, chest pain, and abnormal movements. Another symptom was postexertional malaise, or worse symptoms after mental or physical exertion. 

Scientists still have many questions about long COVID, such as how many people get it and why some people get it and others don’t. 

The study was coordinated through the NIH’s RECOVER (Researching COVID to Enhance Recovery) initiative, which aims to find out how to define, detect, and treat long COVID.

“The researchers hope this study is the next step toward potential treatments for long COVID, which affects the health and wellbeing of millions of Americans,” the NIH said.

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

COVID-19 boosters are not linked to an increased chance of miscarriage, according to a new study in JAMA Network Open.

Researchers were seeking to learn whether a booster in early pregnancy, before 20 weeks, was associated with greater likelihood of spontaneous abortion.

They examined more than 100,000 pregnancies at 6-19 weeks from eight health systems in the Vaccine Safety Datalink (VSD). They found that receiving a COVID-19 booster shot in a 28-day or 42-day exposure window did not increase the chances of miscarriage.

“These findings support the safety of COVID-19 booster vaccination in early pregnancy,” they wrote.

The VSD is a collaboration between the Centers for Disease Control and Prevention’s Immunization Safety Office and large health care systems. The “observational, case-control, surveillance study” was conducted from Nov. 1, 2021, to June 12, 2022.

“COVID infection during pregnancy increases risk of poor outcomes, yet many people who are pregnant or thinking about getting pregnant are hesitant to get a booster dose because of questions about safety,” said Elyse Kharbanda, MD, senior investigator at HealthPartners Institute and lead author of the study in a press release.

The University of Minnesota reported that “previous studies have shown COIVD-19 primary vaccination is safe in pregnancy and not associated with an increased risk for miscarriage. Several studies have also shown COVID-19 can be more severe in pregnancy and lead to worse outcomes for the mother.”

The study was funded by the CDC. Five study authors reported conflicts of interest with Pfizer, Merck, GlaxoSmithKline, AbbVie, and Sanofi Pasteur.

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

COVID-19 boosters are not linked to an increased chance of miscarriage, according to a new study in JAMA Network Open.

Researchers were seeking to learn whether a booster in early pregnancy, before 20 weeks, was associated with greater likelihood of spontaneous abortion.

They examined more than 100,000 pregnancies at 6-19 weeks from eight health systems in the Vaccine Safety Datalink (VSD). They found that receiving a COVID-19 booster shot in a 28-day or 42-day exposure window did not increase the chances of miscarriage.

“These findings support the safety of COVID-19 booster vaccination in early pregnancy,” they wrote.

The VSD is a collaboration between the Centers for Disease Control and Prevention’s Immunization Safety Office and large health care systems. The “observational, case-control, surveillance study” was conducted from Nov. 1, 2021, to June 12, 2022.

“COVID infection during pregnancy increases risk of poor outcomes, yet many people who are pregnant or thinking about getting pregnant are hesitant to get a booster dose because of questions about safety,” said Elyse Kharbanda, MD, senior investigator at HealthPartners Institute and lead author of the study in a press release.

The University of Minnesota reported that “previous studies have shown COIVD-19 primary vaccination is safe in pregnancy and not associated with an increased risk for miscarriage. Several studies have also shown COVID-19 can be more severe in pregnancy and lead to worse outcomes for the mother.”

The study was funded by the CDC. Five study authors reported conflicts of interest with Pfizer, Merck, GlaxoSmithKline, AbbVie, and Sanofi Pasteur.

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

COVID-19 boosters are not linked to an increased chance of miscarriage, according to a new study in JAMA Network Open.

Researchers were seeking to learn whether a booster in early pregnancy, before 20 weeks, was associated with greater likelihood of spontaneous abortion.

They examined more than 100,000 pregnancies at 6-19 weeks from eight health systems in the Vaccine Safety Datalink (VSD). They found that receiving a COVID-19 booster shot in a 28-day or 42-day exposure window did not increase the chances of miscarriage.

“These findings support the safety of COVID-19 booster vaccination in early pregnancy,” they wrote.

The VSD is a collaboration between the Centers for Disease Control and Prevention’s Immunization Safety Office and large health care systems. The “observational, case-control, surveillance study” was conducted from Nov. 1, 2021, to June 12, 2022.

“COVID infection during pregnancy increases risk of poor outcomes, yet many people who are pregnant or thinking about getting pregnant are hesitant to get a booster dose because of questions about safety,” said Elyse Kharbanda, MD, senior investigator at HealthPartners Institute and lead author of the study in a press release.

The University of Minnesota reported that “previous studies have shown COIVD-19 primary vaccination is safe in pregnancy and not associated with an increased risk for miscarriage. Several studies have also shown COVID-19 can be more severe in pregnancy and lead to worse outcomes for the mother.”

The study was funded by the CDC. Five study authors reported conflicts of interest with Pfizer, Merck, GlaxoSmithKline, AbbVie, and Sanofi Pasteur.

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

CHICAGO – Sunscreen recommendations are most effective when a multitude of factors are considered, Susan C. Taylor, MD, said during a presentation on personal photoprotection at the inaugural Pigmentary Disorders Exchange Symposium.

Among the first factors physicians should consider before recommending sunscreen are a patient’s Fitzpatrick skin type, risks for burning or tanning, underlying skin disorders, and medications the patient is taking, Dr. Taylor, professor of dermatology at the University of Pennsylvania, Philadelphia, said at the meeting, provided by MedscapeLIVE! If patients are on hypertensives, for example, medications can make them more photosensitive.

MedscapeLIVE!

Consider skin type

Dr. Taylor said she was dismayed by the results of a recent study, which found that 43% of dermatologists who responded to a survey reported that they never, rarely, or only sometimes took a patient’s skin type into account when making sunscreen recommendations. The article is referenced in a 2022 expert panel consensus paper she coauthored on photoprotection “for skin of all color.” But she pointed out that considering skin type alone is inadequate.

Questions for patients in joint decision-making should include lifestyle and work choices such as whether they work inside or outside, and how much sun exposure they get in a typical day. Heat and humidity levels should also be considered as should a patient’s susceptibility to dyspigmentation. “That could be overall darkening of the skin, mottled hyperpigmentation, actinic dyspigmentation, and, of course, propensity for skin cancer,” she said.
 

Use differs by race

Dr. Taylor, who is also vice chair for diversity, equity and inclusion in the department of dermatology at the University of Pennsylvania, pointed out that sunscreen use differs considerably by race.

In study of 8,952 adults in the United States who reported that they were sun sensitive found that a subset of adults with skin of color were significantly less likely to use sunscreen when compared with non-Hispanic White adults: Non-Hispanic Black (adjusted odds ratio, 0.43); non-Hispanic Asian (aOR. 0.54); and Hispanic (aOR, 0.70) adults.

In the study, non-Hispanic Black and Hispanic adults were significantly less likely to use sunscreens with an SPF greater than 15. In addition, non-Hispanic Black, non-Hispanic Asian, and Hispanic adults were significantly more likely than non-Hispanic Whites to wear long sleeves when outside. Such differences are important to keep in mind when advising patients about sunscreens, she said.
 

Protection for lighter-colored skin

Dr. Taylor said that, for patients with lighter skin tones, “we really want to protect against ultraviolet B as well as ultraviolet A, particularly ultraviolet A2. Ultraviolet radiation is going to cause DNA damage.” Patients with Fitzpatrick skin types I, II, or III are most susceptible to the effects of UVB with sunburn inflammation, which will cause erythema and tanning, and immunosuppression.

“For those who are I, II, and III, we do want to recommend a broad-spectrum, photostable sunscreen with a critical wavelength of 370 nanometers, which is going to protect from both UVB and UVA2,” she said.

Sunscreen recommendations are meant to be paired with advice to avoid midday sun from 10 a.m. to 2 p.m., wearing protective clothing and accessories, and seeking shade, she noted.

Dr. Taylor said, for those patients with lighter skin who are more susceptible to photodamage and premature aging, physicians should recommend sunscreens that contain DNA repair enzymes such as photolyases and sunscreens that contain antioxidants that can prevent or reverse DNA damage. “The exogenous form of these lyases have been manufactured and added to sunscreens,” Dr. Taylor said. “They’re readily available in the United States. That is something to consider for patients with significant photodamage.”

Retinoids can also help alleviate or reverse photodamage, she added.
 

Protection for darker-colored skin

“Many people of color do not believe they need sunscreen,” Dr. Taylor said. But studies show that, although there may be more intrinsic protection, sunscreen is still needed.

Over 30 years ago, Halder and colleagues reported that melanin in skin of color can filter two to five times more UV radiation, and in a paper on the photoprotective role of melanin, Kaidbey and colleagues found that skin types V and VI had an intrinsic SPF of 13 when compared with those who have lighter complexions, which had an SPF of 3.

Sunburns seem to occur less frequently in people with skin of color, but that may be because erythema is less apparent in people with darker skin tones or because of differences in personal definitions of sunburn, Dr. Taylor said.

“Skin of color can and does sustain sunburns and sunscreen will help prevent that,” she said, adding that a recommendation of an SPF 30 is likely sufficient for these patients. Dr. Taylor noted that sunscreens for patients with darker skin often cost substantially more than those for lighter skin, and that should be considered in recommendations.

Tinted sunscreens

Dr. Taylor said that, while broad-spectrum photostable sunscreens protect against UVB and UVA 2, they don’t protect from visible light and UVA1. Two methods to add that protection are using inorganic tinted sunscreens that contain iron oxide or pigmentary titanium dioxide. Dr. Taylor was a coauthor of a practical guide to tinted sunscreens published in 2022.

“For iron oxide, we want a concentration of 3% or greater,” she said, adding that the percentage often is not known because if it is contained in a sunscreen, it is listed as an inactive ingredient.

Another method to address visible light and UVA1 is the use of antioxidant-containing sunscreens with vitamin E, vitamin C, or licochalcone A, Dr. Taylor said.

During the question-and-answer period following her presentation, Amit Pandya, MD, adjunct professor of dermatology at University of Texas Southwestern Medical Center, Dallas, asked why “every makeup, every sunscreen, just says iron oxide,” since it is known that visible light will cause pigmentation, especially in those with darker skin tones.

He urged pushing for a law that would require listing the percentage of iron oxide on products to assure it is sufficient, according to what the literature recommends.

Conference Chair Pearl Grimes, MD, director of the Vitiligo and Pigmentation Institute of Southern California, Los Angeles, said that she recommends tinted sunscreens almost exclusively for her patients, but those with darker skin colors struggle to match color.

Dr. Taylor referred to an analysis published in 2022 of 58 over-the counter sunscreens, which found that only 38% of tinted sunscreens was available in more than one shade, “which is a problem for many of our patients.” She said that providing samples with different hues and tactile sensations may help patients find the right product.

Dr. Taylor disclosed being on the advisory boards for AbbVie, Avita Medical, Beiersdorf, Biorez, Eli Lily, EPI Health, Evolus, Galderma, Hugel America, Johnson and Johnson, L’Oreal USA, MedScape, Pfizer, Scientis US, UCB, Vichy Laboratories. She is a consultant for Arcutis Biothermapeutics, Beiersdorf, Bristol-Myers Squibb, Cara Therapeutics, Dior, and Sanofi. She has done contracted research for Allergan Aesthetics, Concert Pharmaceuticals, Croma-Pharma, Eli Lilly, and Pfizer, and has an ownership interest in Armis Scientific, GloGetter, and Piction Health.

Medscape and this news organization are owned by the same parent company.

CHICAGO – Sunscreen recommendations are most effective when a multitude of factors are considered, Susan C. Taylor, MD, said during a presentation on personal photoprotection at the inaugural Pigmentary Disorders Exchange Symposium.

Among the first factors physicians should consider before recommending sunscreen are a patient’s Fitzpatrick skin type, risks for burning or tanning, underlying skin disorders, and medications the patient is taking, Dr. Taylor, professor of dermatology at the University of Pennsylvania, Philadelphia, said at the meeting, provided by MedscapeLIVE! If patients are on hypertensives, for example, medications can make them more photosensitive.

MedscapeLIVE!

Consider skin type

Dr. Taylor said she was dismayed by the results of a recent study, which found that 43% of dermatologists who responded to a survey reported that they never, rarely, or only sometimes took a patient’s skin type into account when making sunscreen recommendations. The article is referenced in a 2022 expert panel consensus paper she coauthored on photoprotection “for skin of all color.” But she pointed out that considering skin type alone is inadequate.

Questions for patients in joint decision-making should include lifestyle and work choices such as whether they work inside or outside, and how much sun exposure they get in a typical day. Heat and humidity levels should also be considered as should a patient’s susceptibility to dyspigmentation. “That could be overall darkening of the skin, mottled hyperpigmentation, actinic dyspigmentation, and, of course, propensity for skin cancer,” she said.
 

Use differs by race

Dr. Taylor, who is also vice chair for diversity, equity and inclusion in the department of dermatology at the University of Pennsylvania, pointed out that sunscreen use differs considerably by race.

In study of 8,952 adults in the United States who reported that they were sun sensitive found that a subset of adults with skin of color were significantly less likely to use sunscreen when compared with non-Hispanic White adults: Non-Hispanic Black (adjusted odds ratio, 0.43); non-Hispanic Asian (aOR. 0.54); and Hispanic (aOR, 0.70) adults.

In the study, non-Hispanic Black and Hispanic adults were significantly less likely to use sunscreens with an SPF greater than 15. In addition, non-Hispanic Black, non-Hispanic Asian, and Hispanic adults were significantly more likely than non-Hispanic Whites to wear long sleeves when outside. Such differences are important to keep in mind when advising patients about sunscreens, she said.
 

Protection for lighter-colored skin

Dr. Taylor said that, for patients with lighter skin tones, “we really want to protect against ultraviolet B as well as ultraviolet A, particularly ultraviolet A2. Ultraviolet radiation is going to cause DNA damage.” Patients with Fitzpatrick skin types I, II, or III are most susceptible to the effects of UVB with sunburn inflammation, which will cause erythema and tanning, and immunosuppression.

“For those who are I, II, and III, we do want to recommend a broad-spectrum, photostable sunscreen with a critical wavelength of 370 nanometers, which is going to protect from both UVB and UVA2,” she said.

Sunscreen recommendations are meant to be paired with advice to avoid midday sun from 10 a.m. to 2 p.m., wearing protective clothing and accessories, and seeking shade, she noted.

Dr. Taylor said, for those patients with lighter skin who are more susceptible to photodamage and premature aging, physicians should recommend sunscreens that contain DNA repair enzymes such as photolyases and sunscreens that contain antioxidants that can prevent or reverse DNA damage. “The exogenous form of these lyases have been manufactured and added to sunscreens,” Dr. Taylor said. “They’re readily available in the United States. That is something to consider for patients with significant photodamage.”

Retinoids can also help alleviate or reverse photodamage, she added.
 

Protection for darker-colored skin

“Many people of color do not believe they need sunscreen,” Dr. Taylor said. But studies show that, although there may be more intrinsic protection, sunscreen is still needed.

Over 30 years ago, Halder and colleagues reported that melanin in skin of color can filter two to five times more UV radiation, and in a paper on the photoprotective role of melanin, Kaidbey and colleagues found that skin types V and VI had an intrinsic SPF of 13 when compared with those who have lighter complexions, which had an SPF of 3.

Sunburns seem to occur less frequently in people with skin of color, but that may be because erythema is less apparent in people with darker skin tones or because of differences in personal definitions of sunburn, Dr. Taylor said.

“Skin of color can and does sustain sunburns and sunscreen will help prevent that,” she said, adding that a recommendation of an SPF 30 is likely sufficient for these patients. Dr. Taylor noted that sunscreens for patients with darker skin often cost substantially more than those for lighter skin, and that should be considered in recommendations.

Tinted sunscreens

Dr. Taylor said that, while broad-spectrum photostable sunscreens protect against UVB and UVA 2, they don’t protect from visible light and UVA1. Two methods to add that protection are using inorganic tinted sunscreens that contain iron oxide or pigmentary titanium dioxide. Dr. Taylor was a coauthor of a practical guide to tinted sunscreens published in 2022.

“For iron oxide, we want a concentration of 3% or greater,” she said, adding that the percentage often is not known because if it is contained in a sunscreen, it is listed as an inactive ingredient.

Another method to address visible light and UVA1 is the use of antioxidant-containing sunscreens with vitamin E, vitamin C, or licochalcone A, Dr. Taylor said.

During the question-and-answer period following her presentation, Amit Pandya, MD, adjunct professor of dermatology at University of Texas Southwestern Medical Center, Dallas, asked why “every makeup, every sunscreen, just says iron oxide,” since it is known that visible light will cause pigmentation, especially in those with darker skin tones.

He urged pushing for a law that would require listing the percentage of iron oxide on products to assure it is sufficient, according to what the literature recommends.

Conference Chair Pearl Grimes, MD, director of the Vitiligo and Pigmentation Institute of Southern California, Los Angeles, said that she recommends tinted sunscreens almost exclusively for her patients, but those with darker skin colors struggle to match color.

Dr. Taylor referred to an analysis published in 2022 of 58 over-the counter sunscreens, which found that only 38% of tinted sunscreens was available in more than one shade, “which is a problem for many of our patients.” She said that providing samples with different hues and tactile sensations may help patients find the right product.

Dr. Taylor disclosed being on the advisory boards for AbbVie, Avita Medical, Beiersdorf, Biorez, Eli Lily, EPI Health, Evolus, Galderma, Hugel America, Johnson and Johnson, L’Oreal USA, MedScape, Pfizer, Scientis US, UCB, Vichy Laboratories. She is a consultant for Arcutis Biothermapeutics, Beiersdorf, Bristol-Myers Squibb, Cara Therapeutics, Dior, and Sanofi. She has done contracted research for Allergan Aesthetics, Concert Pharmaceuticals, Croma-Pharma, Eli Lilly, and Pfizer, and has an ownership interest in Armis Scientific, GloGetter, and Piction Health.

Medscape and this news organization are owned by the same parent company.

CHICAGO – Sunscreen recommendations are most effective when a multitude of factors are considered, Susan C. Taylor, MD, said during a presentation on personal photoprotection at the inaugural Pigmentary Disorders Exchange Symposium.

Among the first factors physicians should consider before recommending sunscreen are a patient’s Fitzpatrick skin type, risks for burning or tanning, underlying skin disorders, and medications the patient is taking, Dr. Taylor, professor of dermatology at the University of Pennsylvania, Philadelphia, said at the meeting, provided by MedscapeLIVE! If patients are on hypertensives, for example, medications can make them more photosensitive.

MedscapeLIVE!

Consider skin type

Dr. Taylor said she was dismayed by the results of a recent study, which found that 43% of dermatologists who responded to a survey reported that they never, rarely, or only sometimes took a patient’s skin type into account when making sunscreen recommendations. The article is referenced in a 2022 expert panel consensus paper she coauthored on photoprotection “for skin of all color.” But she pointed out that considering skin type alone is inadequate.

Questions for patients in joint decision-making should include lifestyle and work choices such as whether they work inside or outside, and how much sun exposure they get in a typical day. Heat and humidity levels should also be considered as should a patient’s susceptibility to dyspigmentation. “That could be overall darkening of the skin, mottled hyperpigmentation, actinic dyspigmentation, and, of course, propensity for skin cancer,” she said.
 

Use differs by race

Dr. Taylor, who is also vice chair for diversity, equity and inclusion in the department of dermatology at the University of Pennsylvania, pointed out that sunscreen use differs considerably by race.

In study of 8,952 adults in the United States who reported that they were sun sensitive found that a subset of adults with skin of color were significantly less likely to use sunscreen when compared with non-Hispanic White adults: Non-Hispanic Black (adjusted odds ratio, 0.43); non-Hispanic Asian (aOR. 0.54); and Hispanic (aOR, 0.70) adults.

In the study, non-Hispanic Black and Hispanic adults were significantly less likely to use sunscreens with an SPF greater than 15. In addition, non-Hispanic Black, non-Hispanic Asian, and Hispanic adults were significantly more likely than non-Hispanic Whites to wear long sleeves when outside. Such differences are important to keep in mind when advising patients about sunscreens, she said.
 

Protection for lighter-colored skin

Dr. Taylor said that, for patients with lighter skin tones, “we really want to protect against ultraviolet B as well as ultraviolet A, particularly ultraviolet A2. Ultraviolet radiation is going to cause DNA damage.” Patients with Fitzpatrick skin types I, II, or III are most susceptible to the effects of UVB with sunburn inflammation, which will cause erythema and tanning, and immunosuppression.

“For those who are I, II, and III, we do want to recommend a broad-spectrum, photostable sunscreen with a critical wavelength of 370 nanometers, which is going to protect from both UVB and UVA2,” she said.

Sunscreen recommendations are meant to be paired with advice to avoid midday sun from 10 a.m. to 2 p.m., wearing protective clothing and accessories, and seeking shade, she noted.

Dr. Taylor said, for those patients with lighter skin who are more susceptible to photodamage and premature aging, physicians should recommend sunscreens that contain DNA repair enzymes such as photolyases and sunscreens that contain antioxidants that can prevent or reverse DNA damage. “The exogenous form of these lyases have been manufactured and added to sunscreens,” Dr. Taylor said. “They’re readily available in the United States. That is something to consider for patients with significant photodamage.”

Retinoids can also help alleviate or reverse photodamage, she added.
 

Protection for darker-colored skin

“Many people of color do not believe they need sunscreen,” Dr. Taylor said. But studies show that, although there may be more intrinsic protection, sunscreen is still needed.

Over 30 years ago, Halder and colleagues reported that melanin in skin of color can filter two to five times more UV radiation, and in a paper on the photoprotective role of melanin, Kaidbey and colleagues found that skin types V and VI had an intrinsic SPF of 13 when compared with those who have lighter complexions, which had an SPF of 3.

Sunburns seem to occur less frequently in people with skin of color, but that may be because erythema is less apparent in people with darker skin tones or because of differences in personal definitions of sunburn, Dr. Taylor said.

“Skin of color can and does sustain sunburns and sunscreen will help prevent that,” she said, adding that a recommendation of an SPF 30 is likely sufficient for these patients. Dr. Taylor noted that sunscreens for patients with darker skin often cost substantially more than those for lighter skin, and that should be considered in recommendations.

Tinted sunscreens

Dr. Taylor said that, while broad-spectrum photostable sunscreens protect against UVB and UVA 2, they don’t protect from visible light and UVA1. Two methods to add that protection are using inorganic tinted sunscreens that contain iron oxide or pigmentary titanium dioxide. Dr. Taylor was a coauthor of a practical guide to tinted sunscreens published in 2022.

“For iron oxide, we want a concentration of 3% or greater,” she said, adding that the percentage often is not known because if it is contained in a sunscreen, it is listed as an inactive ingredient.

Another method to address visible light and UVA1 is the use of antioxidant-containing sunscreens with vitamin E, vitamin C, or licochalcone A, Dr. Taylor said.

During the question-and-answer period following her presentation, Amit Pandya, MD, adjunct professor of dermatology at University of Texas Southwestern Medical Center, Dallas, asked why “every makeup, every sunscreen, just says iron oxide,” since it is known that visible light will cause pigmentation, especially in those with darker skin tones.

He urged pushing for a law that would require listing the percentage of iron oxide on products to assure it is sufficient, according to what the literature recommends.

Conference Chair Pearl Grimes, MD, director of the Vitiligo and Pigmentation Institute of Southern California, Los Angeles, said that she recommends tinted sunscreens almost exclusively for her patients, but those with darker skin colors struggle to match color.

Dr. Taylor referred to an analysis published in 2022 of 58 over-the counter sunscreens, which found that only 38% of tinted sunscreens was available in more than one shade, “which is a problem for many of our patients.” She said that providing samples with different hues and tactile sensations may help patients find the right product.

Dr. Taylor disclosed being on the advisory boards for AbbVie, Avita Medical, Beiersdorf, Biorez, Eli Lily, EPI Health, Evolus, Galderma, Hugel America, Johnson and Johnson, L’Oreal USA, MedScape, Pfizer, Scientis US, UCB, Vichy Laboratories. She is a consultant for Arcutis Biothermapeutics, Beiersdorf, Bristol-Myers Squibb, Cara Therapeutics, Dior, and Sanofi. She has done contracted research for Allergan Aesthetics, Concert Pharmaceuticals, Croma-Pharma, Eli Lilly, and Pfizer, and has an ownership interest in Armis Scientific, GloGetter, and Piction Health.

Medscape and this news organization are owned by the same parent company.

The Food and Drug Administration is warning people to avoid using compounded medicines as substitutes for the popular weight loss and diabetes drugs Ozempic, Rybelsus, and Wegovy.

Compounded medicines are not FDA approved but are allowed to be made during an official drug shortage. Ozempic and Wegovy are currently on the FDA’s shortage list, but the federal agency warned that it has received reports of people experiencing “adverse events” after using compounded versions of the drugs. (The FDA did not provide details of those events or where the drugs involved were compounded.)

Agency officials are concerned that the compounded versions may contain ingredients that sound like the brand name drugs’ active ingredient, semaglutide, but are different because the ingredients are in salt form.

“Patients should be aware that some products sold as ‘semaglutide’ may not contain the same active ingredient as FDA-approved semaglutide products and may be the salt formulations,” the FDA warning stated. “Products containing these salts, such as semaglutide sodium and semaglutide acetate, have not been shown to be safe and effective.”

The agency said salt forms don’t meet the criteria for compounding during a shortage and sent a letter to the National Association of Boards of Pharmacy expressing “concerns with use of the salt forms in compounded products.”

Patients and health care providers should be aware that “compounded drugs are not FDA approved, and the agency does not verify the safety or effectiveness of compounded drugs,” the FDA explained in its statement.

The Alliance for Pharmacy Compounding’s board of directors said in a statement that some compounders’ arguments for the suitability of semaglutide sodium are “worthy of discussion,” but the board did not endorse those arguments.

For people who use an online pharmacy, the FDA recommends checking the FDA’s website BeSafeRx to check its credentials.

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

The Food and Drug Administration is warning people to avoid using compounded medicines as substitutes for the popular weight loss and diabetes drugs Ozempic, Rybelsus, and Wegovy.

Compounded medicines are not FDA approved but are allowed to be made during an official drug shortage. Ozempic and Wegovy are currently on the FDA’s shortage list, but the federal agency warned that it has received reports of people experiencing “adverse events” after using compounded versions of the drugs. (The FDA did not provide details of those events or where the drugs involved were compounded.)

Agency officials are concerned that the compounded versions may contain ingredients that sound like the brand name drugs’ active ingredient, semaglutide, but are different because the ingredients are in salt form.

“Patients should be aware that some products sold as ‘semaglutide’ may not contain the same active ingredient as FDA-approved semaglutide products and may be the salt formulations,” the FDA warning stated. “Products containing these salts, such as semaglutide sodium and semaglutide acetate, have not been shown to be safe and effective.”

The agency said salt forms don’t meet the criteria for compounding during a shortage and sent a letter to the National Association of Boards of Pharmacy expressing “concerns with use of the salt forms in compounded products.”

Patients and health care providers should be aware that “compounded drugs are not FDA approved, and the agency does not verify the safety or effectiveness of compounded drugs,” the FDA explained in its statement.

The Alliance for Pharmacy Compounding’s board of directors said in a statement that some compounders’ arguments for the suitability of semaglutide sodium are “worthy of discussion,” but the board did not endorse those arguments.

For people who use an online pharmacy, the FDA recommends checking the FDA’s website BeSafeRx to check its credentials.

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

The Food and Drug Administration is warning people to avoid using compounded medicines as substitutes for the popular weight loss and diabetes drugs Ozempic, Rybelsus, and Wegovy.

Compounded medicines are not FDA approved but are allowed to be made during an official drug shortage. Ozempic and Wegovy are currently on the FDA’s shortage list, but the federal agency warned that it has received reports of people experiencing “adverse events” after using compounded versions of the drugs. (The FDA did not provide details of those events or where the drugs involved were compounded.)

Agency officials are concerned that the compounded versions may contain ingredients that sound like the brand name drugs’ active ingredient, semaglutide, but are different because the ingredients are in salt form.

“Patients should be aware that some products sold as ‘semaglutide’ may not contain the same active ingredient as FDA-approved semaglutide products and may be the salt formulations,” the FDA warning stated. “Products containing these salts, such as semaglutide sodium and semaglutide acetate, have not been shown to be safe and effective.”

The agency said salt forms don’t meet the criteria for compounding during a shortage and sent a letter to the National Association of Boards of Pharmacy expressing “concerns with use of the salt forms in compounded products.”

Patients and health care providers should be aware that “compounded drugs are not FDA approved, and the agency does not verify the safety or effectiveness of compounded drugs,” the FDA explained in its statement.

The Alliance for Pharmacy Compounding’s board of directors said in a statement that some compounders’ arguments for the suitability of semaglutide sodium are “worthy of discussion,” but the board did not endorse those arguments.

For people who use an online pharmacy, the FDA recommends checking the FDA’s website BeSafeRx to check its credentials.

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

A new study reveals health concerns about the sugar substitute sucralose so alarming that researchers said people should stop eating it and the government should regulate it more.

Sucralose is sold under the brand name Splenda and is also used as an ingredient in packaged foods and beverages.

The findings were published in the Journal of Toxicology and Environmental Health, Part B. The researchers conducted a series of laboratory experiments exposing human blood cells and gut tissue to sucralose-6-acetate. The findings build on previous research that linked sucralose to gut health problems.

The researchers found that sucralose causes DNA to break apart, putting people at risk for disease. They also linked sucralose to leaky gut syndrome, which means the lining of the intestines are worn down and become permeable. Symptoms are a burning sensation, painful digestion, diarrhea, gas, and bloating.

When a substance damages DNA, it is called genotoxic. Researchers have found that eating sucralose results in the body producing a substance called sucralose-6-acetate, which the new study now shows is genotoxic. The researchers also found sucralose-6-acetate in trace amounts in off-the-shelf products that are so high, they would exceed the safety levels currently allowed in Europe.

“It’s time to revisit the safety and regulatory status of sucralose because the evidence is mounting that it carries significant risks. If nothing else, I encourage people to avoid products containing sucralose,” researcher Susan Schiffman, PhD, adjunct professor of biomedical engineering at North Carolina State University, Raleigh, said in a statement. “It’s something you should not be eating.”

The FDA says sucralose is safe, describing it as 600 times sweeter than table sugar and used in “baked goods, beverages, chewing gum, gelatins, and frozen dairy desserts.”

“To determine the safety of sucralose, the FDA reviewed more than 110 studies designed to identify possible toxic effects, including studies on the reproductive and nervous systems, carcinogenicity, and metabolism,” the agency explained on its website. “The FDA also reviewed human clinical trials to address metabolism and effects on patients with diabetes.”

The study authors reported that they had no conflicts of interest.A version of this article first appeared on WebMD.com.

A new study reveals health concerns about the sugar substitute sucralose so alarming that researchers said people should stop eating it and the government should regulate it more.

Sucralose is sold under the brand name Splenda and is also used as an ingredient in packaged foods and beverages.

The findings were published in the Journal of Toxicology and Environmental Health, Part B. The researchers conducted a series of laboratory experiments exposing human blood cells and gut tissue to sucralose-6-acetate. The findings build on previous research that linked sucralose to gut health problems.

The researchers found that sucralose causes DNA to break apart, putting people at risk for disease. They also linked sucralose to leaky gut syndrome, which means the lining of the intestines are worn down and become permeable. Symptoms are a burning sensation, painful digestion, diarrhea, gas, and bloating.

When a substance damages DNA, it is called genotoxic. Researchers have found that eating sucralose results in the body producing a substance called sucralose-6-acetate, which the new study now shows is genotoxic. The researchers also found sucralose-6-acetate in trace amounts in off-the-shelf products that are so high, they would exceed the safety levels currently allowed in Europe.

“It’s time to revisit the safety and regulatory status of sucralose because the evidence is mounting that it carries significant risks. If nothing else, I encourage people to avoid products containing sucralose,” researcher Susan Schiffman, PhD, adjunct professor of biomedical engineering at North Carolina State University, Raleigh, said in a statement. “It’s something you should not be eating.”

The FDA says sucralose is safe, describing it as 600 times sweeter than table sugar and used in “baked goods, beverages, chewing gum, gelatins, and frozen dairy desserts.”

“To determine the safety of sucralose, the FDA reviewed more than 110 studies designed to identify possible toxic effects, including studies on the reproductive and nervous systems, carcinogenicity, and metabolism,” the agency explained on its website. “The FDA also reviewed human clinical trials to address metabolism and effects on patients with diabetes.”

The study authors reported that they had no conflicts of interest.A version of this article first appeared on WebMD.com.

A new study reveals health concerns about the sugar substitute sucralose so alarming that researchers said people should stop eating it and the government should regulate it more.

Sucralose is sold under the brand name Splenda and is also used as an ingredient in packaged foods and beverages.

The findings were published in the Journal of Toxicology and Environmental Health, Part B. The researchers conducted a series of laboratory experiments exposing human blood cells and gut tissue to sucralose-6-acetate. The findings build on previous research that linked sucralose to gut health problems.

The researchers found that sucralose causes DNA to break apart, putting people at risk for disease. They also linked sucralose to leaky gut syndrome, which means the lining of the intestines are worn down and become permeable. Symptoms are a burning sensation, painful digestion, diarrhea, gas, and bloating.

When a substance damages DNA, it is called genotoxic. Researchers have found that eating sucralose results in the body producing a substance called sucralose-6-acetate, which the new study now shows is genotoxic. The researchers also found sucralose-6-acetate in trace amounts in off-the-shelf products that are so high, they would exceed the safety levels currently allowed in Europe.

“It’s time to revisit the safety and regulatory status of sucralose because the evidence is mounting that it carries significant risks. If nothing else, I encourage people to avoid products containing sucralose,” researcher Susan Schiffman, PhD, adjunct professor of biomedical engineering at North Carolina State University, Raleigh, said in a statement. “It’s something you should not be eating.”

The FDA says sucralose is safe, describing it as 600 times sweeter than table sugar and used in “baked goods, beverages, chewing gum, gelatins, and frozen dairy desserts.”

“To determine the safety of sucralose, the FDA reviewed more than 110 studies designed to identify possible toxic effects, including studies on the reproductive and nervous systems, carcinogenicity, and metabolism,” the agency explained on its website. “The FDA also reviewed human clinical trials to address metabolism and effects on patients with diabetes.”

The study authors reported that they had no conflicts of interest.A version of this article first appeared on WebMD.com.

Myopia affects roughly one-third of the population worldwide - a figure that is projected to reach 50% by 2050. Low-dose atropine, which helps curb the condition, currently is available in the United States only through compounding pharmacies. The products contain preservatives – raising questions about potential toxicities to the eye – and may not be of pharmaceutical grade. In a new study published in JAMA Ophthalmology, a preservative-free eyedrop containing 0.01% atropine led to significant improvements in several markers of myopia in children who received the experimental therapy.

Methodology

• The CHAMP study was a double-masked, placebo-controlled, randomized, phase 3 trial conducted between Nov. 20, 2017, and Aug. 22, 2022, that involved children at 26 sites in North America and 5 centers in Europe.
• Children received either 0.01% or 0.02% atropine drops once per day.
• Patients were aged 3-16 years. They demonstrated a spherical equivalent refractive error (SER) of −0.50 diopter (D) to −6.00 D astigmatism no worse than −1.50 D.
• Of these patients, 573 were included in a safety analysis, and 489 were included in a modified intention-to-treat analysis.

Takeaways

• After 36 months, the 0.01% dose of atropine was associated with a significantly lower responder proportion (odds ratio, 4.54) and slower progression of SER and axial elongation.
• The effect of the 0.02% dose on responder proportion and SER progression was not statistically significant, but the treatment was associated with slower axial elongation.
• The researchers observed no serious ocular adverse events and few serious nonocular events, none of which was determined to be associated with the treatment.

In practice: According to the researchers, “from a risk/benefit perspective, the efficacy and safety observed suggests that low-dose atropine may provide a treatment option for children aged 3-17 years with myopia progression, which may lead to less frequent or delayed change in glasses, progression to less severe correction, and potentially reduce long-term sequelae, which could lead to vision loss later in life, such as myopic maculopathy.”

Study details: The CHAMP study was led by Karla Zadnik, OD, PhD, of Ohio State University, Columbus, and was funded by Vylulma.

Limitations: The researchers said the trial was potentially limited by the fact that patients switched from the study drug to confounding treatments. In addition, patients at the low and high age ranges were not well represented.

Disclosures: Dr. Zadnik received consultant fees from Vyluma during the study.

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

Myopia affects roughly one-third of the population worldwide - a figure that is projected to reach 50% by 2050. Low-dose atropine, which helps curb the condition, currently is available in the United States only through compounding pharmacies. The products contain preservatives – raising questions about potential toxicities to the eye – and may not be of pharmaceutical grade. In a new study published in JAMA Ophthalmology, a preservative-free eyedrop containing 0.01% atropine led to significant improvements in several markers of myopia in children who received the experimental therapy.

Methodology

• The CHAMP study was a double-masked, placebo-controlled, randomized, phase 3 trial conducted between Nov. 20, 2017, and Aug. 22, 2022, that involved children at 26 sites in North America and 5 centers in Europe.
• Children received either 0.01% or 0.02% atropine drops once per day.
• Patients were aged 3-16 years. They demonstrated a spherical equivalent refractive error (SER) of −0.50 diopter (D) to −6.00 D astigmatism no worse than −1.50 D.
• Of these patients, 573 were included in a safety analysis, and 489 were included in a modified intention-to-treat analysis.

Takeaways

• After 36 months, the 0.01% dose of atropine was associated with a significantly lower responder proportion (odds ratio, 4.54) and slower progression of SER and axial elongation.
• The effect of the 0.02% dose on responder proportion and SER progression was not statistically significant, but the treatment was associated with slower axial elongation.
• The researchers observed no serious ocular adverse events and few serious nonocular events, none of which was determined to be associated with the treatment.

In practice: According to the researchers, “from a risk/benefit perspective, the efficacy and safety observed suggests that low-dose atropine may provide a treatment option for children aged 3-17 years with myopia progression, which may lead to less frequent or delayed change in glasses, progression to less severe correction, and potentially reduce long-term sequelae, which could lead to vision loss later in life, such as myopic maculopathy.”

Study details: The CHAMP study was led by Karla Zadnik, OD, PhD, of Ohio State University, Columbus, and was funded by Vylulma.

Limitations: The researchers said the trial was potentially limited by the fact that patients switched from the study drug to confounding treatments. In addition, patients at the low and high age ranges were not well represented.

Disclosures: Dr. Zadnik received consultant fees from Vyluma during the study.

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

Myopia affects roughly one-third of the population worldwide - a figure that is projected to reach 50% by 2050. Low-dose atropine, which helps curb the condition, currently is available in the United States only through compounding pharmacies. The products contain preservatives – raising questions about potential toxicities to the eye – and may not be of pharmaceutical grade. In a new study published in JAMA Ophthalmology, a preservative-free eyedrop containing 0.01% atropine led to significant improvements in several markers of myopia in children who received the experimental therapy.

Methodology

• The CHAMP study was a double-masked, placebo-controlled, randomized, phase 3 trial conducted between Nov. 20, 2017, and Aug. 22, 2022, that involved children at 26 sites in North America and 5 centers in Europe.
• Children received either 0.01% or 0.02% atropine drops once per day.
• Patients were aged 3-16 years. They demonstrated a spherical equivalent refractive error (SER) of −0.50 diopter (D) to −6.00 D astigmatism no worse than −1.50 D.
• Of these patients, 573 were included in a safety analysis, and 489 were included in a modified intention-to-treat analysis.

Takeaways

• After 36 months, the 0.01% dose of atropine was associated with a significantly lower responder proportion (odds ratio, 4.54) and slower progression of SER and axial elongation.
• The effect of the 0.02% dose on responder proportion and SER progression was not statistically significant, but the treatment was associated with slower axial elongation.
• The researchers observed no serious ocular adverse events and few serious nonocular events, none of which was determined to be associated with the treatment.

In practice: According to the researchers, “from a risk/benefit perspective, the efficacy and safety observed suggests that low-dose atropine may provide a treatment option for children aged 3-17 years with myopia progression, which may lead to less frequent or delayed change in glasses, progression to less severe correction, and potentially reduce long-term sequelae, which could lead to vision loss later in life, such as myopic maculopathy.”

Study details: The CHAMP study was led by Karla Zadnik, OD, PhD, of Ohio State University, Columbus, and was funded by Vylulma.

Limitations: The researchers said the trial was potentially limited by the fact that patients switched from the study drug to confounding treatments. In addition, patients at the low and high age ranges were not well represented.

Disclosures: Dr. Zadnik received consultant fees from Vyluma during the study.

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

Dual orexin receptor antagonists (DORAs), a class of drugs approved to treat insomnia, may also be effective for rapid eye movement sleep behavior disorder (RBD), a study suggests.

About 3 million people in the United States have RBD, which is often a precursor to Parkinson’s disease. People with the disorder act out their dreams by talking, flailing their arms and legs, punching, kicking, and exhibiting other behaviors while asleep.

Researchers used an animal model for the study, which they say is the first to identify a new form of treatment for RBD.

“REM behavior disorder is difficult to treat, and the treatments are mostly limited to clonazepam and melatonin,” which may have side effects, senior investigator Andrew Varga, MD, PhD, associate professor of pulmonary, critical care, and sleep medicine at the Icahn School of Medicine at Mount Sinai, New York, told this news organization. “We’re using something completely different, which raises the possibility this might be something useful for REM behavior disorders.”

The findings, with Mount Sinai assistant professor Korey Kam, PhD, as lead author, were published online in the Journal of Neuroscience.
 

A new model for RBD?

RBD can signal risk for synucleinopathies, a group of neurological conditions such as Parkinson’s disease that involve the formation of clumps of alpha-synuclein protein in the brain.

Prior research on RBD was done in synucleinopathy mouse models. For this study, however, researchers used a tauopathy mouse model to investigate how the abnormal accumulation of tau protein might affect RBD.

Researchers collected data on biophysical properties when the mice were awake and in REM and non-REM sleep. They examined length of sleep, transitions from waking to sleep, and how some factors are related to age.

Nearly a third of the older animals showed behaviors similar to REM sleep behavior disorder in humans, including chewing and limb extension.

But after researchers administered a DORA medication twice during a 24-hour period, they noted that the medication not only helped the animals fall asleep faster and for longer, it also reduced levels of dream enactment that are a hallmark of RBD.
 

The ‘bigger highlight’

Finding RBD behaviors in a tauopathy animal model was surprising, Dr. Varga said, because RBD has been previously linked to synucleinopathies. There was no known correlation between RBD and abnormal accumulation of tau.

Another unexpected finding was the detection of RBD in some of the younger animals, who had not yet shown evidence of tau accumulation.

“It appears to be a biomarker or a signature of something that’s going on that predicts the impending tauopathy at a time where there is very little, or no, tau pathology going on in the brain,” Dr. Varga said.

If RBD is an early predictor of future tau accumulation, the model could guide future prevention and treatment. However, the more important finding is the potential new treatment for the condition.

“The bigger highlight here is less about what’s causing the RBD [than about] what you can do to make it better,” he said.

The next step in the work is to study whether the effect of DORAs on RBD seen in this tauopathy mouse model is evidenced in other animals and whether it is effective in humans with RBD, Dr. Varga said.

The study was funded by the Alzheimer’s Association and Merck Investigator Studies Program. Dr. Kam, Dr. Varga, and coauthors report no relevant financial relationships.

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

Dual orexin receptor antagonists (DORAs), a class of drugs approved to treat insomnia, may also be effective for rapid eye movement sleep behavior disorder (RBD), a study suggests.

About 3 million people in the United States have RBD, which is often a precursor to Parkinson’s disease. People with the disorder act out their dreams by talking, flailing their arms and legs, punching, kicking, and exhibiting other behaviors while asleep.

Researchers used an animal model for the study, which they say is the first to identify a new form of treatment for RBD.

“REM behavior disorder is difficult to treat, and the treatments are mostly limited to clonazepam and melatonin,” which may have side effects, senior investigator Andrew Varga, MD, PhD, associate professor of pulmonary, critical care, and sleep medicine at the Icahn School of Medicine at Mount Sinai, New York, told this news organization. “We’re using something completely different, which raises the possibility this might be something useful for REM behavior disorders.”

The findings, with Mount Sinai assistant professor Korey Kam, PhD, as lead author, were published online in the Journal of Neuroscience.
 

A new model for RBD?

RBD can signal risk for synucleinopathies, a group of neurological conditions such as Parkinson’s disease that involve the formation of clumps of alpha-synuclein protein in the brain.

Prior research on RBD was done in synucleinopathy mouse models. For this study, however, researchers used a tauopathy mouse model to investigate how the abnormal accumulation of tau protein might affect RBD.

Researchers collected data on biophysical properties when the mice were awake and in REM and non-REM sleep. They examined length of sleep, transitions from waking to sleep, and how some factors are related to age.

Nearly a third of the older animals showed behaviors similar to REM sleep behavior disorder in humans, including chewing and limb extension.

But after researchers administered a DORA medication twice during a 24-hour period, they noted that the medication not only helped the animals fall asleep faster and for longer, it also reduced levels of dream enactment that are a hallmark of RBD.
 

The ‘bigger highlight’

Finding RBD behaviors in a tauopathy animal model was surprising, Dr. Varga said, because RBD has been previously linked to synucleinopathies. There was no known correlation between RBD and abnormal accumulation of tau.

Another unexpected finding was the detection of RBD in some of the younger animals, who had not yet shown evidence of tau accumulation.

“It appears to be a biomarker or a signature of something that’s going on that predicts the impending tauopathy at a time where there is very little, or no, tau pathology going on in the brain,” Dr. Varga said.

If RBD is an early predictor of future tau accumulation, the model could guide future prevention and treatment. However, the more important finding is the potential new treatment for the condition.

“The bigger highlight here is less about what’s causing the RBD [than about] what you can do to make it better,” he said.

The next step in the work is to study whether the effect of DORAs on RBD seen in this tauopathy mouse model is evidenced in other animals and whether it is effective in humans with RBD, Dr. Varga said.

The study was funded by the Alzheimer’s Association and Merck Investigator Studies Program. Dr. Kam, Dr. Varga, and coauthors report no relevant financial relationships.

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

Dual orexin receptor antagonists (DORAs), a class of drugs approved to treat insomnia, may also be effective for rapid eye movement sleep behavior disorder (RBD), a study suggests.

About 3 million people in the United States have RBD, which is often a precursor to Parkinson’s disease. People with the disorder act out their dreams by talking, flailing their arms and legs, punching, kicking, and exhibiting other behaviors while asleep.

Researchers used an animal model for the study, which they say is the first to identify a new form of treatment for RBD.

“REM behavior disorder is difficult to treat, and the treatments are mostly limited to clonazepam and melatonin,” which may have side effects, senior investigator Andrew Varga, MD, PhD, associate professor of pulmonary, critical care, and sleep medicine at the Icahn School of Medicine at Mount Sinai, New York, told this news organization. “We’re using something completely different, which raises the possibility this might be something useful for REM behavior disorders.”

The findings, with Mount Sinai assistant professor Korey Kam, PhD, as lead author, were published online in the Journal of Neuroscience.
 

A new model for RBD?

RBD can signal risk for synucleinopathies, a group of neurological conditions such as Parkinson’s disease that involve the formation of clumps of alpha-synuclein protein in the brain.

Prior research on RBD was done in synucleinopathy mouse models. For this study, however, researchers used a tauopathy mouse model to investigate how the abnormal accumulation of tau protein might affect RBD.

Researchers collected data on biophysical properties when the mice were awake and in REM and non-REM sleep. They examined length of sleep, transitions from waking to sleep, and how some factors are related to age.

Nearly a third of the older animals showed behaviors similar to REM sleep behavior disorder in humans, including chewing and limb extension.

But after researchers administered a DORA medication twice during a 24-hour period, they noted that the medication not only helped the animals fall asleep faster and for longer, it also reduced levels of dream enactment that are a hallmark of RBD.
 

The ‘bigger highlight’

Finding RBD behaviors in a tauopathy animal model was surprising, Dr. Varga said, because RBD has been previously linked to synucleinopathies. There was no known correlation between RBD and abnormal accumulation of tau.

Another unexpected finding was the detection of RBD in some of the younger animals, who had not yet shown evidence of tau accumulation.

“It appears to be a biomarker or a signature of something that’s going on that predicts the impending tauopathy at a time where there is very little, or no, tau pathology going on in the brain,” Dr. Varga said.

If RBD is an early predictor of future tau accumulation, the model could guide future prevention and treatment. However, the more important finding is the potential new treatment for the condition.

“The bigger highlight here is less about what’s causing the RBD [than about] what you can do to make it better,” he said.

The next step in the work is to study whether the effect of DORAs on RBD seen in this tauopathy mouse model is evidenced in other animals and whether it is effective in humans with RBD, Dr. Varga said.

The study was funded by the Alzheimer’s Association and Merck Investigator Studies Program. Dr. Kam, Dr. Varga, and coauthors report no relevant financial relationships.

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