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Drug repurposing ‘fast track’ to new medicines for obesity, diabetes
for these two conditions.
The scientists identified four pathways with known drug targets for type 2 diabetes and five with known drug targets for obesity.
Their findings suggest that:
- Palbociclib (used to treat breast cancer) and cardiac glycosides (used to treat heart failure and heart rhythm disorders) might be repurposed to treat type 2 diabetes.
- Baclofen (a muscle relaxant) and carfilzomib (a chemotherapy) could potentially be used to treat obesity.
- Fostamatinib (used to treat thrombocytopenia), sucralfate (used to treat stomach ulcers), and regorafenib (used to treat cancer) might be used to treat type 2 diabetes and obesity.
- Baclofen and sucralfate would have favorable safety profiles as repurposed treatments.
Sahar El Shair, a PhD student at the Faculty of Health and Medicine, University of Newcastle, New South Wales, Australia, presented the research during an oral session at the International Congress on Obesity, the biennial congress of the World Obesity Federation, in Melbourne.
“New treatments with higher activity and specificity are urgently needed to tackle a pandemic of chronic illness associated with type 2 diabetes and obesity,” senior coauthor Murray Cairns, PhD, said in a press release from the ICO.
“Our technology harnesses genetically informed precision medicine to identify and target new treatments for these complex disorders,” said Dr. Cairns, from the school of biomedical sciences and pharmacy at the University of Newcastle.
Matchmaking between individual, their genetic traits, and drugs
Dr. Cairns and senior coauthor William Reay, PhD, also from the school of biomedical sciences and pharmacy, have cofounded a company called PolygenRx.
The company website explains that they have developed a propriety platform termed the pharmagenic enrichment score (PES), which is “essentially a matchmaking service between patients and drugs, allowing treatment to be optimized for each individual using their unique combination of genetic risk factors.”
It is important to note the genetic risk from complex traits, such as type 2 diabetes and obesity, “are quite different [from] the rare genetic disorders caused mostly by a devastating mutation in a single gene,” Dr. Cairns explained in an email.
“Complex traits,” he noted, “are associated with thousands of [genetic] variants that are common in people and have a cumulative effect.”
For this specific research, the investigators obtained genetic data from genome-wide association studies of obesity and type 2 diabetes.
“By using very large cohorts (hundreds of thousands of individuals) and comparing the frequency of millions of genetic variants in subjects with these conditions with controls, these studies have revealed regions of the genome and genes associated with the condition,” Dr. Cairns noted.
The pharmagenic enrichment score integrates a person’s genetics with drug pharmacology to determine if a person would respond more readily to a certain drug.
“We are investigating the potential of thousands of drugs across a broad spectrum of complex traits (the list is almost endless),” Dr. Cairns explained.
From the PES score, “we have an estimate of each individual’s likelihood of a positive response to said drug,” he noted. “We all have variants that increase (and decrease) the risk of these conditions to various degrees as they are common (high frequency) genetic variants.”
With this research, “we can implement this precision medicine strategy to match the right [repurposed] drugs for individuals based on their specific burden of genetic risk” for obesity and type 2 diabetes.
“Drug repurposing can be a fast track to new medicines because there is existing knowledge about their safety and activity in humans,” he said.
Next steps: Raising funds for clinical trials
“We would like to progress some of these compounds to preclinical and clinical trials,” Dr. Cairns said, “but need to raise the funds for this expensive research. With limited government research funding opportunities, we have recently spun out a startup company to attract commercial investment in our platform and the development of new drug candidates.”
The authors have reported no relevant financial relationships. Dr. Reay and Dr. Cairns are cofounders of PolygenRx.
A version of this article first appeared on Medscape.com.
for these two conditions.
The scientists identified four pathways with known drug targets for type 2 diabetes and five with known drug targets for obesity.
Their findings suggest that:
- Palbociclib (used to treat breast cancer) and cardiac glycosides (used to treat heart failure and heart rhythm disorders) might be repurposed to treat type 2 diabetes.
- Baclofen (a muscle relaxant) and carfilzomib (a chemotherapy) could potentially be used to treat obesity.
- Fostamatinib (used to treat thrombocytopenia), sucralfate (used to treat stomach ulcers), and regorafenib (used to treat cancer) might be used to treat type 2 diabetes and obesity.
- Baclofen and sucralfate would have favorable safety profiles as repurposed treatments.
Sahar El Shair, a PhD student at the Faculty of Health and Medicine, University of Newcastle, New South Wales, Australia, presented the research during an oral session at the International Congress on Obesity, the biennial congress of the World Obesity Federation, in Melbourne.
“New treatments with higher activity and specificity are urgently needed to tackle a pandemic of chronic illness associated with type 2 diabetes and obesity,” senior coauthor Murray Cairns, PhD, said in a press release from the ICO.
“Our technology harnesses genetically informed precision medicine to identify and target new treatments for these complex disorders,” said Dr. Cairns, from the school of biomedical sciences and pharmacy at the University of Newcastle.
Matchmaking between individual, their genetic traits, and drugs
Dr. Cairns and senior coauthor William Reay, PhD, also from the school of biomedical sciences and pharmacy, have cofounded a company called PolygenRx.
The company website explains that they have developed a propriety platform termed the pharmagenic enrichment score (PES), which is “essentially a matchmaking service between patients and drugs, allowing treatment to be optimized for each individual using their unique combination of genetic risk factors.”
It is important to note the genetic risk from complex traits, such as type 2 diabetes and obesity, “are quite different [from] the rare genetic disorders caused mostly by a devastating mutation in a single gene,” Dr. Cairns explained in an email.
“Complex traits,” he noted, “are associated with thousands of [genetic] variants that are common in people and have a cumulative effect.”
For this specific research, the investigators obtained genetic data from genome-wide association studies of obesity and type 2 diabetes.
“By using very large cohorts (hundreds of thousands of individuals) and comparing the frequency of millions of genetic variants in subjects with these conditions with controls, these studies have revealed regions of the genome and genes associated with the condition,” Dr. Cairns noted.
The pharmagenic enrichment score integrates a person’s genetics with drug pharmacology to determine if a person would respond more readily to a certain drug.
“We are investigating the potential of thousands of drugs across a broad spectrum of complex traits (the list is almost endless),” Dr. Cairns explained.
From the PES score, “we have an estimate of each individual’s likelihood of a positive response to said drug,” he noted. “We all have variants that increase (and decrease) the risk of these conditions to various degrees as they are common (high frequency) genetic variants.”
With this research, “we can implement this precision medicine strategy to match the right [repurposed] drugs for individuals based on their specific burden of genetic risk” for obesity and type 2 diabetes.
“Drug repurposing can be a fast track to new medicines because there is existing knowledge about their safety and activity in humans,” he said.
Next steps: Raising funds for clinical trials
“We would like to progress some of these compounds to preclinical and clinical trials,” Dr. Cairns said, “but need to raise the funds for this expensive research. With limited government research funding opportunities, we have recently spun out a startup company to attract commercial investment in our platform and the development of new drug candidates.”
The authors have reported no relevant financial relationships. Dr. Reay and Dr. Cairns are cofounders of PolygenRx.
A version of this article first appeared on Medscape.com.
for these two conditions.
The scientists identified four pathways with known drug targets for type 2 diabetes and five with known drug targets for obesity.
Their findings suggest that:
- Palbociclib (used to treat breast cancer) and cardiac glycosides (used to treat heart failure and heart rhythm disorders) might be repurposed to treat type 2 diabetes.
- Baclofen (a muscle relaxant) and carfilzomib (a chemotherapy) could potentially be used to treat obesity.
- Fostamatinib (used to treat thrombocytopenia), sucralfate (used to treat stomach ulcers), and regorafenib (used to treat cancer) might be used to treat type 2 diabetes and obesity.
- Baclofen and sucralfate would have favorable safety profiles as repurposed treatments.
Sahar El Shair, a PhD student at the Faculty of Health and Medicine, University of Newcastle, New South Wales, Australia, presented the research during an oral session at the International Congress on Obesity, the biennial congress of the World Obesity Federation, in Melbourne.
“New treatments with higher activity and specificity are urgently needed to tackle a pandemic of chronic illness associated with type 2 diabetes and obesity,” senior coauthor Murray Cairns, PhD, said in a press release from the ICO.
“Our technology harnesses genetically informed precision medicine to identify and target new treatments for these complex disorders,” said Dr. Cairns, from the school of biomedical sciences and pharmacy at the University of Newcastle.
Matchmaking between individual, their genetic traits, and drugs
Dr. Cairns and senior coauthor William Reay, PhD, also from the school of biomedical sciences and pharmacy, have cofounded a company called PolygenRx.
The company website explains that they have developed a propriety platform termed the pharmagenic enrichment score (PES), which is “essentially a matchmaking service between patients and drugs, allowing treatment to be optimized for each individual using their unique combination of genetic risk factors.”
It is important to note the genetic risk from complex traits, such as type 2 diabetes and obesity, “are quite different [from] the rare genetic disorders caused mostly by a devastating mutation in a single gene,” Dr. Cairns explained in an email.
“Complex traits,” he noted, “are associated with thousands of [genetic] variants that are common in people and have a cumulative effect.”
For this specific research, the investigators obtained genetic data from genome-wide association studies of obesity and type 2 diabetes.
“By using very large cohorts (hundreds of thousands of individuals) and comparing the frequency of millions of genetic variants in subjects with these conditions with controls, these studies have revealed regions of the genome and genes associated with the condition,” Dr. Cairns noted.
The pharmagenic enrichment score integrates a person’s genetics with drug pharmacology to determine if a person would respond more readily to a certain drug.
“We are investigating the potential of thousands of drugs across a broad spectrum of complex traits (the list is almost endless),” Dr. Cairns explained.
From the PES score, “we have an estimate of each individual’s likelihood of a positive response to said drug,” he noted. “We all have variants that increase (and decrease) the risk of these conditions to various degrees as they are common (high frequency) genetic variants.”
With this research, “we can implement this precision medicine strategy to match the right [repurposed] drugs for individuals based on their specific burden of genetic risk” for obesity and type 2 diabetes.
“Drug repurposing can be a fast track to new medicines because there is existing knowledge about their safety and activity in humans,” he said.
Next steps: Raising funds for clinical trials
“We would like to progress some of these compounds to preclinical and clinical trials,” Dr. Cairns said, “but need to raise the funds for this expensive research. With limited government research funding opportunities, we have recently spun out a startup company to attract commercial investment in our platform and the development of new drug candidates.”
The authors have reported no relevant financial relationships. Dr. Reay and Dr. Cairns are cofounders of PolygenRx.
A version of this article first appeared on Medscape.com.
FROM ICO 2022
JAK inhibitors show no excess cardiovascular safety signal in French nationwide cohort
Janus kinase inhibitors tofacitinib (Xeljanz) and baricitinib (Olumiant) may pose no greater risk than does adalimumab (Humira and biosimilars) for major adverse cardiovascular events (MACEs) or venous thromboembolism (VTE) on the basis of a nationwide cohort study.
The French data, which included almost 16,000 patients with rheumatoid arthritis, revealed similar safety across subgroups, including older patients with at least one preexisting cardiovascular risk factor, reported lead author Léa Hoisnard, MD, of Henri Mondor Hospital, Paris, and colleagues.
These findings arrive 1 year after the U.S. Food and Drug Administration imposed class-wide boxed warnings on three Janus kinase (JAK) inhibitors, citing increased risks for both cancer and serious cardiac events detected by the open-label, randomized ORAL Surveillance postmarketing trial, which compared tofacitinib against adalimumab and etanercept.
More recently, the observational STAR-RA study, relying upon private insurance and Medicare claims in the United States, found no significant increase in cardiovascular events among patients taking tofacitinib, adding some uncertainty to the conversation.
“In this context, observational studies of unselected populations outside of North America are still needed to assess other JAK inhibitor agents,” Dr. Hoisnard and colleagues write in Annals of the Rheumatic Diseases.
Their retrospective study included 8,481 patients who received baricitinib or tofacitinib, and 7,354 patients who received adalimumab. Almost all patients in the tofacitinib group received 5 mg twice daily instead of 10 mg twice daily (99.4% vs. 0.6%), so cardiovascular safety was assessed only for the 5-mg dose. Baricitinib was prescribed at 4-mg and 2-mg doses (79.5% vs. 20.5%), allowing inclusion of both dose levels. The investigators accounted for a range of covariates, including concurrent therapy, comorbidities, and other patient characteristics.
Median follow-up durations were 440 days in the JAK inhibitor group and 344 days in the adalimumab group. The JAK inhibitor group had numerically more MACEs than did the adalimumab group, but the difference in risk was not statistically significant (54 vs. 35 MACEs; weighted hazard ratio, 1.0; 95% confidence interval, 0.7-1.5; P = .99). Similarly, more patients taking JAK inhibitors had VTEs, but relative risk was, again, not significant (75 vs. 32 VTEs; HRw, 1.1; 95% CI, 0.7-1.6; P = .63).
These findings were consistent for all subgroups, including patients aged 50 years or older and patients aged 65 years or older, although the investigators noted that statistical power was lacking for subgroup analyses.
Findings from Echo ORAL Surveillance
“I think the baricitinib data are important,” Kevin Winthrop, MD, MPH, professor of infectious diseases and epidemiology at Oregon Health & Science University, Portland, told this news organization. “There’s no difference between 2 mg and 4 mg [dose levels] in this analysis. And there doesn’t really seem to be a difference between baricitinib and tofacitinib. Most of the results are pretty consistent with ORAL Surveillance, which was a randomized, controlled trial.”
Dr. Winthrop, who has been active in JAK inhibitor clinical trials, recently coauthored an article in Nature Reviews Rheumatology encouraging clinicians to remember that the cardiovascular risks of JAK inhibitors are relative to adalimumab, and safety should be framed within the context of risk-to-benefit ratios.
He and his coauthor also called into question the FDA’s “better to be safe than sorry” approach, which resulted in boxed warnings across all JAK inhibitors, despite differences in target specificity.
“There are pros and cons of taking that approach,” Dr. Winthrop said in an interview. “The FDA might ultimately be right. Certainly, these drugs appear similar for some types of events, like herpes zoster, for example. But whether they’re similar with regard to malignancy or cardiovascular events, I don’t think we know.”
Dr. Winthrop noted that deucravacitinib was recently approved for psoriasis sans boxed warning, suggesting inconsistency in the FDA’s approach. The agent headlines as a “TYK2 inhibitor,” but TYK2 is a member of the JAK family.
“I don’t know why the FDA decided to treat them differently,” Dr. Winthrop said.
Boxed warnings encourage caution, lock treatment sequence
Michael Thakor, MD, of Arthritis & Rheumatology Clinic of Northern Colorado, Fort Collins, supports the boxed warnings because they encourage caution and transparency.
“It forces you to have that discussion with your patient, which may take some time, but it’s actually a very good thing,” Dr. Thakor said in an interview. “Some patients will say, ‘Oh my gosh, I don’t want to take that drug.’ But most patients, considering the level of risk that you’re talking about, are actually okay going ahead with the medication.”
If these risks aren’t discussed, he noted, patient trust may falter.
“They’re going to go online, and they’re going to be reading about it,” Dr. Thakor said. “And then they tend to get more spooked. They also may question your advice from then on, if you’re not telling them the possible risk.”
Reflecting on the present study, Dr. Thakor said that the findings initially appeared reassuring, but he became concerned about the lack of power and how adverse events trended higher in the JAK inhibitor group, particularly for VTEs, most of which occurred with baricitinib. This latter finding is challenging to interpret, however, because the 4-mg dose is not used in the United States, he added.
Dr. Thakor described how JAK inhibitors once seemed poised to assume a frontline role in RA until the boxed warnings came out. These safety concerns don’t take JAK inhibitors off the table, he said, but they do keep the class further down the treatment sequence, and the present data don’t alter this picture in daily practice.
“If I had a patient who was over the age of 50 with at least one cardiovascular risk factor, I might have a little bit of concern, but if they need their RA treated, I would definitely discuss the possibility of using a JAK inhibitor,” Dr. Thakor said. “If the patient is comfortable with it, then I would feel comfortable going ahead.”
The investigators disclosed no outside funding or conflicts of interest. Dr. Winthrop disclosed relationships with AbbVie, AstraZeneca, Bristol-Myers Squibb, and others. Dr. Thakor disclosed no conflicts of interest.
A version of this article first appeared on Medscape.com.
Janus kinase inhibitors tofacitinib (Xeljanz) and baricitinib (Olumiant) may pose no greater risk than does adalimumab (Humira and biosimilars) for major adverse cardiovascular events (MACEs) or venous thromboembolism (VTE) on the basis of a nationwide cohort study.
The French data, which included almost 16,000 patients with rheumatoid arthritis, revealed similar safety across subgroups, including older patients with at least one preexisting cardiovascular risk factor, reported lead author Léa Hoisnard, MD, of Henri Mondor Hospital, Paris, and colleagues.
These findings arrive 1 year after the U.S. Food and Drug Administration imposed class-wide boxed warnings on three Janus kinase (JAK) inhibitors, citing increased risks for both cancer and serious cardiac events detected by the open-label, randomized ORAL Surveillance postmarketing trial, which compared tofacitinib against adalimumab and etanercept.
More recently, the observational STAR-RA study, relying upon private insurance and Medicare claims in the United States, found no significant increase in cardiovascular events among patients taking tofacitinib, adding some uncertainty to the conversation.
“In this context, observational studies of unselected populations outside of North America are still needed to assess other JAK inhibitor agents,” Dr. Hoisnard and colleagues write in Annals of the Rheumatic Diseases.
Their retrospective study included 8,481 patients who received baricitinib or tofacitinib, and 7,354 patients who received adalimumab. Almost all patients in the tofacitinib group received 5 mg twice daily instead of 10 mg twice daily (99.4% vs. 0.6%), so cardiovascular safety was assessed only for the 5-mg dose. Baricitinib was prescribed at 4-mg and 2-mg doses (79.5% vs. 20.5%), allowing inclusion of both dose levels. The investigators accounted for a range of covariates, including concurrent therapy, comorbidities, and other patient characteristics.
Median follow-up durations were 440 days in the JAK inhibitor group and 344 days in the adalimumab group. The JAK inhibitor group had numerically more MACEs than did the adalimumab group, but the difference in risk was not statistically significant (54 vs. 35 MACEs; weighted hazard ratio, 1.0; 95% confidence interval, 0.7-1.5; P = .99). Similarly, more patients taking JAK inhibitors had VTEs, but relative risk was, again, not significant (75 vs. 32 VTEs; HRw, 1.1; 95% CI, 0.7-1.6; P = .63).
These findings were consistent for all subgroups, including patients aged 50 years or older and patients aged 65 years or older, although the investigators noted that statistical power was lacking for subgroup analyses.
Findings from Echo ORAL Surveillance
“I think the baricitinib data are important,” Kevin Winthrop, MD, MPH, professor of infectious diseases and epidemiology at Oregon Health & Science University, Portland, told this news organization. “There’s no difference between 2 mg and 4 mg [dose levels] in this analysis. And there doesn’t really seem to be a difference between baricitinib and tofacitinib. Most of the results are pretty consistent with ORAL Surveillance, which was a randomized, controlled trial.”
Dr. Winthrop, who has been active in JAK inhibitor clinical trials, recently coauthored an article in Nature Reviews Rheumatology encouraging clinicians to remember that the cardiovascular risks of JAK inhibitors are relative to adalimumab, and safety should be framed within the context of risk-to-benefit ratios.
He and his coauthor also called into question the FDA’s “better to be safe than sorry” approach, which resulted in boxed warnings across all JAK inhibitors, despite differences in target specificity.
“There are pros and cons of taking that approach,” Dr. Winthrop said in an interview. “The FDA might ultimately be right. Certainly, these drugs appear similar for some types of events, like herpes zoster, for example. But whether they’re similar with regard to malignancy or cardiovascular events, I don’t think we know.”
Dr. Winthrop noted that deucravacitinib was recently approved for psoriasis sans boxed warning, suggesting inconsistency in the FDA’s approach. The agent headlines as a “TYK2 inhibitor,” but TYK2 is a member of the JAK family.
“I don’t know why the FDA decided to treat them differently,” Dr. Winthrop said.
Boxed warnings encourage caution, lock treatment sequence
Michael Thakor, MD, of Arthritis & Rheumatology Clinic of Northern Colorado, Fort Collins, supports the boxed warnings because they encourage caution and transparency.
“It forces you to have that discussion with your patient, which may take some time, but it’s actually a very good thing,” Dr. Thakor said in an interview. “Some patients will say, ‘Oh my gosh, I don’t want to take that drug.’ But most patients, considering the level of risk that you’re talking about, are actually okay going ahead with the medication.”
If these risks aren’t discussed, he noted, patient trust may falter.
“They’re going to go online, and they’re going to be reading about it,” Dr. Thakor said. “And then they tend to get more spooked. They also may question your advice from then on, if you’re not telling them the possible risk.”
Reflecting on the present study, Dr. Thakor said that the findings initially appeared reassuring, but he became concerned about the lack of power and how adverse events trended higher in the JAK inhibitor group, particularly for VTEs, most of which occurred with baricitinib. This latter finding is challenging to interpret, however, because the 4-mg dose is not used in the United States, he added.
Dr. Thakor described how JAK inhibitors once seemed poised to assume a frontline role in RA until the boxed warnings came out. These safety concerns don’t take JAK inhibitors off the table, he said, but they do keep the class further down the treatment sequence, and the present data don’t alter this picture in daily practice.
“If I had a patient who was over the age of 50 with at least one cardiovascular risk factor, I might have a little bit of concern, but if they need their RA treated, I would definitely discuss the possibility of using a JAK inhibitor,” Dr. Thakor said. “If the patient is comfortable with it, then I would feel comfortable going ahead.”
The investigators disclosed no outside funding or conflicts of interest. Dr. Winthrop disclosed relationships with AbbVie, AstraZeneca, Bristol-Myers Squibb, and others. Dr. Thakor disclosed no conflicts of interest.
A version of this article first appeared on Medscape.com.
Janus kinase inhibitors tofacitinib (Xeljanz) and baricitinib (Olumiant) may pose no greater risk than does adalimumab (Humira and biosimilars) for major adverse cardiovascular events (MACEs) or venous thromboembolism (VTE) on the basis of a nationwide cohort study.
The French data, which included almost 16,000 patients with rheumatoid arthritis, revealed similar safety across subgroups, including older patients with at least one preexisting cardiovascular risk factor, reported lead author Léa Hoisnard, MD, of Henri Mondor Hospital, Paris, and colleagues.
These findings arrive 1 year after the U.S. Food and Drug Administration imposed class-wide boxed warnings on three Janus kinase (JAK) inhibitors, citing increased risks for both cancer and serious cardiac events detected by the open-label, randomized ORAL Surveillance postmarketing trial, which compared tofacitinib against adalimumab and etanercept.
More recently, the observational STAR-RA study, relying upon private insurance and Medicare claims in the United States, found no significant increase in cardiovascular events among patients taking tofacitinib, adding some uncertainty to the conversation.
“In this context, observational studies of unselected populations outside of North America are still needed to assess other JAK inhibitor agents,” Dr. Hoisnard and colleagues write in Annals of the Rheumatic Diseases.
Their retrospective study included 8,481 patients who received baricitinib or tofacitinib, and 7,354 patients who received adalimumab. Almost all patients in the tofacitinib group received 5 mg twice daily instead of 10 mg twice daily (99.4% vs. 0.6%), so cardiovascular safety was assessed only for the 5-mg dose. Baricitinib was prescribed at 4-mg and 2-mg doses (79.5% vs. 20.5%), allowing inclusion of both dose levels. The investigators accounted for a range of covariates, including concurrent therapy, comorbidities, and other patient characteristics.
Median follow-up durations were 440 days in the JAK inhibitor group and 344 days in the adalimumab group. The JAK inhibitor group had numerically more MACEs than did the adalimumab group, but the difference in risk was not statistically significant (54 vs. 35 MACEs; weighted hazard ratio, 1.0; 95% confidence interval, 0.7-1.5; P = .99). Similarly, more patients taking JAK inhibitors had VTEs, but relative risk was, again, not significant (75 vs. 32 VTEs; HRw, 1.1; 95% CI, 0.7-1.6; P = .63).
These findings were consistent for all subgroups, including patients aged 50 years or older and patients aged 65 years or older, although the investigators noted that statistical power was lacking for subgroup analyses.
Findings from Echo ORAL Surveillance
“I think the baricitinib data are important,” Kevin Winthrop, MD, MPH, professor of infectious diseases and epidemiology at Oregon Health & Science University, Portland, told this news organization. “There’s no difference between 2 mg and 4 mg [dose levels] in this analysis. And there doesn’t really seem to be a difference between baricitinib and tofacitinib. Most of the results are pretty consistent with ORAL Surveillance, which was a randomized, controlled trial.”
Dr. Winthrop, who has been active in JAK inhibitor clinical trials, recently coauthored an article in Nature Reviews Rheumatology encouraging clinicians to remember that the cardiovascular risks of JAK inhibitors are relative to adalimumab, and safety should be framed within the context of risk-to-benefit ratios.
He and his coauthor also called into question the FDA’s “better to be safe than sorry” approach, which resulted in boxed warnings across all JAK inhibitors, despite differences in target specificity.
“There are pros and cons of taking that approach,” Dr. Winthrop said in an interview. “The FDA might ultimately be right. Certainly, these drugs appear similar for some types of events, like herpes zoster, for example. But whether they’re similar with regard to malignancy or cardiovascular events, I don’t think we know.”
Dr. Winthrop noted that deucravacitinib was recently approved for psoriasis sans boxed warning, suggesting inconsistency in the FDA’s approach. The agent headlines as a “TYK2 inhibitor,” but TYK2 is a member of the JAK family.
“I don’t know why the FDA decided to treat them differently,” Dr. Winthrop said.
Boxed warnings encourage caution, lock treatment sequence
Michael Thakor, MD, of Arthritis & Rheumatology Clinic of Northern Colorado, Fort Collins, supports the boxed warnings because they encourage caution and transparency.
“It forces you to have that discussion with your patient, which may take some time, but it’s actually a very good thing,” Dr. Thakor said in an interview. “Some patients will say, ‘Oh my gosh, I don’t want to take that drug.’ But most patients, considering the level of risk that you’re talking about, are actually okay going ahead with the medication.”
If these risks aren’t discussed, he noted, patient trust may falter.
“They’re going to go online, and they’re going to be reading about it,” Dr. Thakor said. “And then they tend to get more spooked. They also may question your advice from then on, if you’re not telling them the possible risk.”
Reflecting on the present study, Dr. Thakor said that the findings initially appeared reassuring, but he became concerned about the lack of power and how adverse events trended higher in the JAK inhibitor group, particularly for VTEs, most of which occurred with baricitinib. This latter finding is challenging to interpret, however, because the 4-mg dose is not used in the United States, he added.
Dr. Thakor described how JAK inhibitors once seemed poised to assume a frontline role in RA until the boxed warnings came out. These safety concerns don’t take JAK inhibitors off the table, he said, but they do keep the class further down the treatment sequence, and the present data don’t alter this picture in daily practice.
“If I had a patient who was over the age of 50 with at least one cardiovascular risk factor, I might have a little bit of concern, but if they need their RA treated, I would definitely discuss the possibility of using a JAK inhibitor,” Dr. Thakor said. “If the patient is comfortable with it, then I would feel comfortable going ahead.”
The investigators disclosed no outside funding or conflicts of interest. Dr. Winthrop disclosed relationships with AbbVie, AstraZeneca, Bristol-Myers Squibb, and others. Dr. Thakor disclosed no conflicts of interest.
A version of this article first appeared on Medscape.com.
FROM ANNALS OF THE RHEUMATIC DISEASES
Nonhormonal drug fezolinetant found safe for hot flashes in yearlong study
The drug fezolinetant, a selective neurokinin-3 receptor antagonist under investigation for treatment of menopausal vasomotor symptoms, showed acceptable long-term safety and tolerability during a 1-year phase 3 randomized controlled trial, according to data presented at the annual meeting of the North American Menopause Society. The study, called SKYLIGHT 4, examined fezolinetant treatment, especially in terms of endometrial health.
The findings mean that fezolinetant “may help bridge a gap in the management of vasomotor symptoms,” according to lead author Genevieve Neal-Perry, MD, PhD, chair of the department of obstetrics and gynecology at the University of North Carolina at Chapel Hill.
This study was an important step in fezolinetant’s path toward potential approval by the Food and Drug Administration for vasomotor symptoms.
”Moderate and severe vasomotor symptoms can adversely affect quality of life of those affected and result in sleep disruption as well as increased risk for heart disease and other high-risk medical problems,” Dr. Neal-Perry said. “Although menopausal hormone therapy significantly improves vasomotor symptoms, it may not be desired or it may not be safe for some women,” resulting in gaps in care and a need for targeted, nonhormonal therapies for hot flashes. A planned study will also assess the safety of the drug in patients with a diagnosis of hormone-sensitive cancer and disorders that increase the risk for blood clots.
”Fezolinetant has a low side effect profile, it is a nonhormonal option, and it is selective for the neurons that trigger and mediate hot flashes,” Dr. Neal-Perry said.
Hot flashes are caused by kisspeptin, neurokinin B, and dynorphin neurons located in the hypothalamus. Fezolinetant works by selectively blocking the neurokinin 3 receptor (NK3R), which regulates a person’s sense of temperature, Dr. Neal-Perry explained. Overactivation of NK3R, resulting from low estrogen levels, plays a role in the hot flashes and cold sweats women experience during menopause.
Drug development for hot flashes ”has been hampered by a lack of knowledge regarding the biological cause,” Dr. Neal-Perry said. “Now that we have a robust understanding of the basic biology of hot flashes, we can develop novel, highly effective, and targeted therapy.”
This safety study involved 1,830 women, ages 40-65, who were experiencing menopausal vasomotor symptoms and were randomly assigned to one of three arms for 52 weeks: 45 mg of fezolinetant, 30 mg of fezolinetant, or a placebo once daily.
The primary endpoints included the percentage of women with endometrial hyperplasia, the percentage of women with endometrial cancer, and the frequency and severity of treatment-emergent adverse events (TEAEs). To meet the primary safety endpoint, no more than 1% of participants could have hyperplasia or malignancy, with an upper confidence interval boundary not greater than 4%. Women who met prespecified criteria for their endometrial health to be assessed, underwent endometrial biopsies at baseline and at the end of the study. Three independent pathologists analyzed the tissue without knowledge of which study arm each sample came from. Among the 599 endometrial biopsy samples, 0.5% of the 203 participants taking 45 mg fezolinetant had hyperplasia while none of the women in the other two arms did. Among the 210 women taking 30 mg of fezolinetant, 0.5% had a malignancy; no malignancies occurred in the other two arms.
Overall adverse events were similar across all three arms, including rates of adverse events leading to discontinuation. The most common adverse events were headache and COVID-19. TEAEs related to the drug were 18.1% in the 45-mg arm, 15.4% in the 30-mg arm, and 17.4% in the placebo arm. Serious adverse events were similar across all three arms, and only 0.5% of participants in the 45-mg arm experienced drug-related serious adverse events, compared with none of the women in the 30-mg arm and 0.2% of women in the placebo group.
”The frequency of transaminase elevations was low, and these TEAEs were generally isolated, transient, and resolved on treatment or with discontinuation,” the authors reported.
The next steps for fezolinetant will be to assess its effect on mood and quality of life measures related to vasomotor symptoms, Dr. Neal-Perry said.
Samantha Dunham, MD, a NAMS-certified menopause practitioner and an associate professor of obstetrics and gynecology at New York University, suggested the drug’s safety in the study is encouraging.
”As a medication that treats menopausal symptoms, the study confirmed there are no issues with the endometrium, or lining of the uterus, not that one would expect issues given the mechanism of action,” Dr. Dunham, also codirector of NYU Langone’s Center for Midlife Health and Menopause, said in an interview. Dr. Dunham was not involved in the study.
”Earlier versions of medication in this class have caused liver enzyme elevation.” The trial of this medication showed that there were only transient elevations in liver enzymes, which resolved upon cessation of the medication. Dr. Dunham said. ”If the medicine proves to be safe over long periods of time in different populations, this will be a very significant medication for treating menopausal vasomotor symptoms.”
The research was funded by Astellas Pharma. Dr. Dunham had no disclosures. Dr. Neal-Perry is a scientific advisory board member for Astellas and Ferring Pharmaceuticals, and has received research funding from Merck and Overa.
The drug fezolinetant, a selective neurokinin-3 receptor antagonist under investigation for treatment of menopausal vasomotor symptoms, showed acceptable long-term safety and tolerability during a 1-year phase 3 randomized controlled trial, according to data presented at the annual meeting of the North American Menopause Society. The study, called SKYLIGHT 4, examined fezolinetant treatment, especially in terms of endometrial health.
The findings mean that fezolinetant “may help bridge a gap in the management of vasomotor symptoms,” according to lead author Genevieve Neal-Perry, MD, PhD, chair of the department of obstetrics and gynecology at the University of North Carolina at Chapel Hill.
This study was an important step in fezolinetant’s path toward potential approval by the Food and Drug Administration for vasomotor symptoms.
”Moderate and severe vasomotor symptoms can adversely affect quality of life of those affected and result in sleep disruption as well as increased risk for heart disease and other high-risk medical problems,” Dr. Neal-Perry said. “Although menopausal hormone therapy significantly improves vasomotor symptoms, it may not be desired or it may not be safe for some women,” resulting in gaps in care and a need for targeted, nonhormonal therapies for hot flashes. A planned study will also assess the safety of the drug in patients with a diagnosis of hormone-sensitive cancer and disorders that increase the risk for blood clots.
”Fezolinetant has a low side effect profile, it is a nonhormonal option, and it is selective for the neurons that trigger and mediate hot flashes,” Dr. Neal-Perry said.
Hot flashes are caused by kisspeptin, neurokinin B, and dynorphin neurons located in the hypothalamus. Fezolinetant works by selectively blocking the neurokinin 3 receptor (NK3R), which regulates a person’s sense of temperature, Dr. Neal-Perry explained. Overactivation of NK3R, resulting from low estrogen levels, plays a role in the hot flashes and cold sweats women experience during menopause.
Drug development for hot flashes ”has been hampered by a lack of knowledge regarding the biological cause,” Dr. Neal-Perry said. “Now that we have a robust understanding of the basic biology of hot flashes, we can develop novel, highly effective, and targeted therapy.”
This safety study involved 1,830 women, ages 40-65, who were experiencing menopausal vasomotor symptoms and were randomly assigned to one of three arms for 52 weeks: 45 mg of fezolinetant, 30 mg of fezolinetant, or a placebo once daily.
The primary endpoints included the percentage of women with endometrial hyperplasia, the percentage of women with endometrial cancer, and the frequency and severity of treatment-emergent adverse events (TEAEs). To meet the primary safety endpoint, no more than 1% of participants could have hyperplasia or malignancy, with an upper confidence interval boundary not greater than 4%. Women who met prespecified criteria for their endometrial health to be assessed, underwent endometrial biopsies at baseline and at the end of the study. Three independent pathologists analyzed the tissue without knowledge of which study arm each sample came from. Among the 599 endometrial biopsy samples, 0.5% of the 203 participants taking 45 mg fezolinetant had hyperplasia while none of the women in the other two arms did. Among the 210 women taking 30 mg of fezolinetant, 0.5% had a malignancy; no malignancies occurred in the other two arms.
Overall adverse events were similar across all three arms, including rates of adverse events leading to discontinuation. The most common adverse events were headache and COVID-19. TEAEs related to the drug were 18.1% in the 45-mg arm, 15.4% in the 30-mg arm, and 17.4% in the placebo arm. Serious adverse events were similar across all three arms, and only 0.5% of participants in the 45-mg arm experienced drug-related serious adverse events, compared with none of the women in the 30-mg arm and 0.2% of women in the placebo group.
”The frequency of transaminase elevations was low, and these TEAEs were generally isolated, transient, and resolved on treatment or with discontinuation,” the authors reported.
The next steps for fezolinetant will be to assess its effect on mood and quality of life measures related to vasomotor symptoms, Dr. Neal-Perry said.
Samantha Dunham, MD, a NAMS-certified menopause practitioner and an associate professor of obstetrics and gynecology at New York University, suggested the drug’s safety in the study is encouraging.
”As a medication that treats menopausal symptoms, the study confirmed there are no issues with the endometrium, or lining of the uterus, not that one would expect issues given the mechanism of action,” Dr. Dunham, also codirector of NYU Langone’s Center for Midlife Health and Menopause, said in an interview. Dr. Dunham was not involved in the study.
”Earlier versions of medication in this class have caused liver enzyme elevation.” The trial of this medication showed that there were only transient elevations in liver enzymes, which resolved upon cessation of the medication. Dr. Dunham said. ”If the medicine proves to be safe over long periods of time in different populations, this will be a very significant medication for treating menopausal vasomotor symptoms.”
The research was funded by Astellas Pharma. Dr. Dunham had no disclosures. Dr. Neal-Perry is a scientific advisory board member for Astellas and Ferring Pharmaceuticals, and has received research funding from Merck and Overa.
The drug fezolinetant, a selective neurokinin-3 receptor antagonist under investigation for treatment of menopausal vasomotor symptoms, showed acceptable long-term safety and tolerability during a 1-year phase 3 randomized controlled trial, according to data presented at the annual meeting of the North American Menopause Society. The study, called SKYLIGHT 4, examined fezolinetant treatment, especially in terms of endometrial health.
The findings mean that fezolinetant “may help bridge a gap in the management of vasomotor symptoms,” according to lead author Genevieve Neal-Perry, MD, PhD, chair of the department of obstetrics and gynecology at the University of North Carolina at Chapel Hill.
This study was an important step in fezolinetant’s path toward potential approval by the Food and Drug Administration for vasomotor symptoms.
”Moderate and severe vasomotor symptoms can adversely affect quality of life of those affected and result in sleep disruption as well as increased risk for heart disease and other high-risk medical problems,” Dr. Neal-Perry said. “Although menopausal hormone therapy significantly improves vasomotor symptoms, it may not be desired or it may not be safe for some women,” resulting in gaps in care and a need for targeted, nonhormonal therapies for hot flashes. A planned study will also assess the safety of the drug in patients with a diagnosis of hormone-sensitive cancer and disorders that increase the risk for blood clots.
”Fezolinetant has a low side effect profile, it is a nonhormonal option, and it is selective for the neurons that trigger and mediate hot flashes,” Dr. Neal-Perry said.
Hot flashes are caused by kisspeptin, neurokinin B, and dynorphin neurons located in the hypothalamus. Fezolinetant works by selectively blocking the neurokinin 3 receptor (NK3R), which regulates a person’s sense of temperature, Dr. Neal-Perry explained. Overactivation of NK3R, resulting from low estrogen levels, plays a role in the hot flashes and cold sweats women experience during menopause.
Drug development for hot flashes ”has been hampered by a lack of knowledge regarding the biological cause,” Dr. Neal-Perry said. “Now that we have a robust understanding of the basic biology of hot flashes, we can develop novel, highly effective, and targeted therapy.”
This safety study involved 1,830 women, ages 40-65, who were experiencing menopausal vasomotor symptoms and were randomly assigned to one of three arms for 52 weeks: 45 mg of fezolinetant, 30 mg of fezolinetant, or a placebo once daily.
The primary endpoints included the percentage of women with endometrial hyperplasia, the percentage of women with endometrial cancer, and the frequency and severity of treatment-emergent adverse events (TEAEs). To meet the primary safety endpoint, no more than 1% of participants could have hyperplasia or malignancy, with an upper confidence interval boundary not greater than 4%. Women who met prespecified criteria for their endometrial health to be assessed, underwent endometrial biopsies at baseline and at the end of the study. Three independent pathologists analyzed the tissue without knowledge of which study arm each sample came from. Among the 599 endometrial biopsy samples, 0.5% of the 203 participants taking 45 mg fezolinetant had hyperplasia while none of the women in the other two arms did. Among the 210 women taking 30 mg of fezolinetant, 0.5% had a malignancy; no malignancies occurred in the other two arms.
Overall adverse events were similar across all three arms, including rates of adverse events leading to discontinuation. The most common adverse events were headache and COVID-19. TEAEs related to the drug were 18.1% in the 45-mg arm, 15.4% in the 30-mg arm, and 17.4% in the placebo arm. Serious adverse events were similar across all three arms, and only 0.5% of participants in the 45-mg arm experienced drug-related serious adverse events, compared with none of the women in the 30-mg arm and 0.2% of women in the placebo group.
”The frequency of transaminase elevations was low, and these TEAEs were generally isolated, transient, and resolved on treatment or with discontinuation,” the authors reported.
The next steps for fezolinetant will be to assess its effect on mood and quality of life measures related to vasomotor symptoms, Dr. Neal-Perry said.
Samantha Dunham, MD, a NAMS-certified menopause practitioner and an associate professor of obstetrics and gynecology at New York University, suggested the drug’s safety in the study is encouraging.
”As a medication that treats menopausal symptoms, the study confirmed there are no issues with the endometrium, or lining of the uterus, not that one would expect issues given the mechanism of action,” Dr. Dunham, also codirector of NYU Langone’s Center for Midlife Health and Menopause, said in an interview. Dr. Dunham was not involved in the study.
”Earlier versions of medication in this class have caused liver enzyme elevation.” The trial of this medication showed that there were only transient elevations in liver enzymes, which resolved upon cessation of the medication. Dr. Dunham said. ”If the medicine proves to be safe over long periods of time in different populations, this will be a very significant medication for treating menopausal vasomotor symptoms.”
The research was funded by Astellas Pharma. Dr. Dunham had no disclosures. Dr. Neal-Perry is a scientific advisory board member for Astellas and Ferring Pharmaceuticals, and has received research funding from Merck and Overa.
FROM NAMS 2022
VTE prophylaxis overused in low-risk hospitalized patients
A majority of hospitalized patients at low risk for venous thromboembolism were unnecessarily treated with medication, based on data from more than 400 individuals.
Prevention of venous thromboembolism (VTE) is important, and current guidelines from the American College of Chest Physicians suggest that patients with high or moderate risk for VTE be treated with mechanical prophylaxis, and that pharmacological prophylaxis is not recommended for patients at high risk for bleeding, said Hui Chong Lau, MD, in a presentation at the annual meeting of the American College of Chest Physicians (CHEST).
However, the nature of VTE prophylaxis using a risk assessment score has not been explored, said Dr. Lau, a third-year resident in internal medicine at Crozer-Chester Medical Center, Upland, Penn.
Low-molecular-weight heparin (LWMH) and intermittent pneumatic compression are often used to reduce VTE risk during hospitalization, but for patients with low VTE risk, prophylaxis is not necessarily recommended, he said. In fact, overuse of chemical prophylaxis in low-risk patients can increase bleeding risk and contribute to patient discomfort in the form of additional needle sticks while hospitalized, Dr. Lau said in the presentation.
“We wanted to see how well physicians in the hospital used a risk assessment model to stratify patients,” and how well the patients were assigned to the correct prophylaxis, he explained.
Dr. Lau and colleagues reviewed data from 469 adult patients hospitalized at a single medical center who were hospitalized between January 2021 and June 2021. The researchers retrospectively performed risk assessment using the Padua prediction score. A score of less than 4 was considered low risk for VTE, and a score of 4 or higher was considered high risk.
In the study population, 180 patients were identified as low risk and 289 were considered high risk.
Based on the Padua score, 95% of the patients at high risk were on the correct prophylaxis, Dr. Lau said.
A total of 193 high-risk patients were on heparin. However, many of these patients had good kidney function, and could have been treated with enoxaparin instead; “this would have spared them two needle sticks per day,” Dr. Lau noted.
Of the 180 low-risk patients, 168 (93.3%) were on chemical prophylaxis, and should have been on mechanical prophylaxis, he said. Only 10 patients (5%) who were considered low risk were placed on mechanical prophylaxis.
Overall, 3.6% of all patients who received chemical VTE prophylaxis developed bleeding.
The results were limited by the retrospective design and use of data from a single center. However, the findings emphasize the need for better attention to VTE risk when considering prophylaxis, said Dr. Lau. “We have to have risk assessment every day,” during a hospital stay, and adjust treatment accordingly, he said.
he concluded.
Additional research is needed to better understand the potential consequences of overusing chemical VTE, including not only bleeding risk, but also financial costs and patient discomfort, he said.
The study received no outside funding. The researchers had no financial conflicts to disclose.
A majority of hospitalized patients at low risk for venous thromboembolism were unnecessarily treated with medication, based on data from more than 400 individuals.
Prevention of venous thromboembolism (VTE) is important, and current guidelines from the American College of Chest Physicians suggest that patients with high or moderate risk for VTE be treated with mechanical prophylaxis, and that pharmacological prophylaxis is not recommended for patients at high risk for bleeding, said Hui Chong Lau, MD, in a presentation at the annual meeting of the American College of Chest Physicians (CHEST).
However, the nature of VTE prophylaxis using a risk assessment score has not been explored, said Dr. Lau, a third-year resident in internal medicine at Crozer-Chester Medical Center, Upland, Penn.
Low-molecular-weight heparin (LWMH) and intermittent pneumatic compression are often used to reduce VTE risk during hospitalization, but for patients with low VTE risk, prophylaxis is not necessarily recommended, he said. In fact, overuse of chemical prophylaxis in low-risk patients can increase bleeding risk and contribute to patient discomfort in the form of additional needle sticks while hospitalized, Dr. Lau said in the presentation.
“We wanted to see how well physicians in the hospital used a risk assessment model to stratify patients,” and how well the patients were assigned to the correct prophylaxis, he explained.
Dr. Lau and colleagues reviewed data from 469 adult patients hospitalized at a single medical center who were hospitalized between January 2021 and June 2021. The researchers retrospectively performed risk assessment using the Padua prediction score. A score of less than 4 was considered low risk for VTE, and a score of 4 or higher was considered high risk.
In the study population, 180 patients were identified as low risk and 289 were considered high risk.
Based on the Padua score, 95% of the patients at high risk were on the correct prophylaxis, Dr. Lau said.
A total of 193 high-risk patients were on heparin. However, many of these patients had good kidney function, and could have been treated with enoxaparin instead; “this would have spared them two needle sticks per day,” Dr. Lau noted.
Of the 180 low-risk patients, 168 (93.3%) were on chemical prophylaxis, and should have been on mechanical prophylaxis, he said. Only 10 patients (5%) who were considered low risk were placed on mechanical prophylaxis.
Overall, 3.6% of all patients who received chemical VTE prophylaxis developed bleeding.
The results were limited by the retrospective design and use of data from a single center. However, the findings emphasize the need for better attention to VTE risk when considering prophylaxis, said Dr. Lau. “We have to have risk assessment every day,” during a hospital stay, and adjust treatment accordingly, he said.
he concluded.
Additional research is needed to better understand the potential consequences of overusing chemical VTE, including not only bleeding risk, but also financial costs and patient discomfort, he said.
The study received no outside funding. The researchers had no financial conflicts to disclose.
A majority of hospitalized patients at low risk for venous thromboembolism were unnecessarily treated with medication, based on data from more than 400 individuals.
Prevention of venous thromboembolism (VTE) is important, and current guidelines from the American College of Chest Physicians suggest that patients with high or moderate risk for VTE be treated with mechanical prophylaxis, and that pharmacological prophylaxis is not recommended for patients at high risk for bleeding, said Hui Chong Lau, MD, in a presentation at the annual meeting of the American College of Chest Physicians (CHEST).
However, the nature of VTE prophylaxis using a risk assessment score has not been explored, said Dr. Lau, a third-year resident in internal medicine at Crozer-Chester Medical Center, Upland, Penn.
Low-molecular-weight heparin (LWMH) and intermittent pneumatic compression are often used to reduce VTE risk during hospitalization, but for patients with low VTE risk, prophylaxis is not necessarily recommended, he said. In fact, overuse of chemical prophylaxis in low-risk patients can increase bleeding risk and contribute to patient discomfort in the form of additional needle sticks while hospitalized, Dr. Lau said in the presentation.
“We wanted to see how well physicians in the hospital used a risk assessment model to stratify patients,” and how well the patients were assigned to the correct prophylaxis, he explained.
Dr. Lau and colleagues reviewed data from 469 adult patients hospitalized at a single medical center who were hospitalized between January 2021 and June 2021. The researchers retrospectively performed risk assessment using the Padua prediction score. A score of less than 4 was considered low risk for VTE, and a score of 4 or higher was considered high risk.
In the study population, 180 patients were identified as low risk and 289 were considered high risk.
Based on the Padua score, 95% of the patients at high risk were on the correct prophylaxis, Dr. Lau said.
A total of 193 high-risk patients were on heparin. However, many of these patients had good kidney function, and could have been treated with enoxaparin instead; “this would have spared them two needle sticks per day,” Dr. Lau noted.
Of the 180 low-risk patients, 168 (93.3%) were on chemical prophylaxis, and should have been on mechanical prophylaxis, he said. Only 10 patients (5%) who were considered low risk were placed on mechanical prophylaxis.
Overall, 3.6% of all patients who received chemical VTE prophylaxis developed bleeding.
The results were limited by the retrospective design and use of data from a single center. However, the findings emphasize the need for better attention to VTE risk when considering prophylaxis, said Dr. Lau. “We have to have risk assessment every day,” during a hospital stay, and adjust treatment accordingly, he said.
he concluded.
Additional research is needed to better understand the potential consequences of overusing chemical VTE, including not only bleeding risk, but also financial costs and patient discomfort, he said.
The study received no outside funding. The researchers had no financial conflicts to disclose.
FROM CHEST 2022
Rapid point-of-care test could help avoid inappropriate antibiotic prescribing
The fingerstick test, FebriDx, works by detecting myxovirus resistance protein A, which the body generates in response to viral infections, and C-reactive protein (CRP), which is associated with systemic bacterial or viral infection.
In a study of 520 adults and children with symptoms of acute respiratory illness who were treated in outpatient settings, the test correctly classified bacterial infections 93.2% of the time (95% confidence interval [CI], 84.9-97.0). The negative predictive value (NPV), or probability that a person with a negative test result was truly free of a bacterial infection, was 98.7% (95% CI, 96.9-99.4).
The findings of the study, which was sponsored by the test’s manufacturer, were published in JAMA Network Open).
The ability to rule out a bacterial cause “may provide clinicians with reassurance to withhold antibiotics when supported by the clinical assessment,” the researchers wrote.
They added that the ability to identify infections that may benefit from antibiotics and confidently rule out those that will not “is essential to optimizing clinical management and addressing global antimicrobial resistance.”
FDA concerned about false negative viral infection results
FebriDx has been cleared for sale in the United Kingdom, Europe, Canada, United Arab Emirates, Brazil, and Australia, according to the manufacturer, Australia-based Lumos Diagnostics.
However, the product is not available in the United States, where the Food and Drug Administration denied marketing clearance in July. In a news release, Lumos said the FDA determined that FebriDx did not demonstrate “substantial equivalence” to a predicate device and expressed concern that false negative viral infection results could lead to missed cases of COVID-19.
In the newly published study, FebriDx identified individuals with viral infections 70.3% of the time (95% CI, 64.8-75.2). The probability that a person who tested negative for a viral infection was truly negative was 66.7% (95%CI, 60.8-72.1).
The study included patients with respiratory symptoms and recent fever who were enrolled from October 2019 to April 2021 at nine emergency departments, six urgent care clinics, and five primary care clinics in the United States. All patients were tested with FebriDx and underwent separate laboratory testing to determine a final diagnosis.
In addition, researchers recruited a control group of 120 individuals without symptoms.
Among 496 symptomatic individuals who had a final diagnosis, 73 (14.7%) were classified as having a response associated with a bacterial infection, 296 (59.7%) as having a viral-associated response, and 127 (25.6%) as negative.
FebriDx correctly ruled out a bacterial infection 88.4% of the time (95% CI, 85.0-91.1). The probability that a patient with a positive result for bacterial infection actually had a bacterial infection was 58.1% (95%CI, 49.1-66.7).
The findings bolster those of a previous study on the same test. This research included 220 patients who reported having a fever within the prior 3 days or had a measurable fever at the time of enrollment. In that study, the test correctly identified bacterial infections 85% of the time and correctly ruled out bacterial infection 93% of the time, with a NPV of 97%.
Too early to say test will be useful in practice
The idea of a test to guide the prescribing of antibiotics isn’t new, according to an expert who was not involved in FebriDx research.
Noah Ivers, MD, PhD, a family physician and associate professor at the University of Toronto who studies strategies to optimize primary care delivery, said, “many such point-of-care tests have been tried” to detect biomarkers such as CRP or procalcitonin, which is associated with bacterial infections.
Such tests have looked good in initial studies, he said, but when trialed in urgent care clinics, primary care clinics, or emergency departments, “they tend run into implementation challenges or simply lack of effects, or both.
“So, while I am happy at the news of this result, it’s too early to say with any certainty that it will prove useful in practice,” he added.
Meanwhile, Dr. Ivers said it’s “crucial that people understand that most illnesses are likely to be viral” and therefore not helped by antibiotics. When antibiotics are needed for outpatients, he said, “5 days is usually ample.”
The study was funded by Lumos Diagnostics. Among the 15 study authors, 6 had conflicts of interest disclosures, reporting ties to Inflammatix, Medical College of Wisconsin, Siemens, Technomics Research, and Lumos Diagnostics. Dr. Ivers reported no relevant financial interests.
The fingerstick test, FebriDx, works by detecting myxovirus resistance protein A, which the body generates in response to viral infections, and C-reactive protein (CRP), which is associated with systemic bacterial or viral infection.
In a study of 520 adults and children with symptoms of acute respiratory illness who were treated in outpatient settings, the test correctly classified bacterial infections 93.2% of the time (95% confidence interval [CI], 84.9-97.0). The negative predictive value (NPV), or probability that a person with a negative test result was truly free of a bacterial infection, was 98.7% (95% CI, 96.9-99.4).
The findings of the study, which was sponsored by the test’s manufacturer, were published in JAMA Network Open).
The ability to rule out a bacterial cause “may provide clinicians with reassurance to withhold antibiotics when supported by the clinical assessment,” the researchers wrote.
They added that the ability to identify infections that may benefit from antibiotics and confidently rule out those that will not “is essential to optimizing clinical management and addressing global antimicrobial resistance.”
FDA concerned about false negative viral infection results
FebriDx has been cleared for sale in the United Kingdom, Europe, Canada, United Arab Emirates, Brazil, and Australia, according to the manufacturer, Australia-based Lumos Diagnostics.
However, the product is not available in the United States, where the Food and Drug Administration denied marketing clearance in July. In a news release, Lumos said the FDA determined that FebriDx did not demonstrate “substantial equivalence” to a predicate device and expressed concern that false negative viral infection results could lead to missed cases of COVID-19.
In the newly published study, FebriDx identified individuals with viral infections 70.3% of the time (95% CI, 64.8-75.2). The probability that a person who tested negative for a viral infection was truly negative was 66.7% (95%CI, 60.8-72.1).
The study included patients with respiratory symptoms and recent fever who were enrolled from October 2019 to April 2021 at nine emergency departments, six urgent care clinics, and five primary care clinics in the United States. All patients were tested with FebriDx and underwent separate laboratory testing to determine a final diagnosis.
In addition, researchers recruited a control group of 120 individuals without symptoms.
Among 496 symptomatic individuals who had a final diagnosis, 73 (14.7%) were classified as having a response associated with a bacterial infection, 296 (59.7%) as having a viral-associated response, and 127 (25.6%) as negative.
FebriDx correctly ruled out a bacterial infection 88.4% of the time (95% CI, 85.0-91.1). The probability that a patient with a positive result for bacterial infection actually had a bacterial infection was 58.1% (95%CI, 49.1-66.7).
The findings bolster those of a previous study on the same test. This research included 220 patients who reported having a fever within the prior 3 days or had a measurable fever at the time of enrollment. In that study, the test correctly identified bacterial infections 85% of the time and correctly ruled out bacterial infection 93% of the time, with a NPV of 97%.
Too early to say test will be useful in practice
The idea of a test to guide the prescribing of antibiotics isn’t new, according to an expert who was not involved in FebriDx research.
Noah Ivers, MD, PhD, a family physician and associate professor at the University of Toronto who studies strategies to optimize primary care delivery, said, “many such point-of-care tests have been tried” to detect biomarkers such as CRP or procalcitonin, which is associated with bacterial infections.
Such tests have looked good in initial studies, he said, but when trialed in urgent care clinics, primary care clinics, or emergency departments, “they tend run into implementation challenges or simply lack of effects, or both.
“So, while I am happy at the news of this result, it’s too early to say with any certainty that it will prove useful in practice,” he added.
Meanwhile, Dr. Ivers said it’s “crucial that people understand that most illnesses are likely to be viral” and therefore not helped by antibiotics. When antibiotics are needed for outpatients, he said, “5 days is usually ample.”
The study was funded by Lumos Diagnostics. Among the 15 study authors, 6 had conflicts of interest disclosures, reporting ties to Inflammatix, Medical College of Wisconsin, Siemens, Technomics Research, and Lumos Diagnostics. Dr. Ivers reported no relevant financial interests.
The fingerstick test, FebriDx, works by detecting myxovirus resistance protein A, which the body generates in response to viral infections, and C-reactive protein (CRP), which is associated with systemic bacterial or viral infection.
In a study of 520 adults and children with symptoms of acute respiratory illness who were treated in outpatient settings, the test correctly classified bacterial infections 93.2% of the time (95% confidence interval [CI], 84.9-97.0). The negative predictive value (NPV), or probability that a person with a negative test result was truly free of a bacterial infection, was 98.7% (95% CI, 96.9-99.4).
The findings of the study, which was sponsored by the test’s manufacturer, were published in JAMA Network Open).
The ability to rule out a bacterial cause “may provide clinicians with reassurance to withhold antibiotics when supported by the clinical assessment,” the researchers wrote.
They added that the ability to identify infections that may benefit from antibiotics and confidently rule out those that will not “is essential to optimizing clinical management and addressing global antimicrobial resistance.”
FDA concerned about false negative viral infection results
FebriDx has been cleared for sale in the United Kingdom, Europe, Canada, United Arab Emirates, Brazil, and Australia, according to the manufacturer, Australia-based Lumos Diagnostics.
However, the product is not available in the United States, where the Food and Drug Administration denied marketing clearance in July. In a news release, Lumos said the FDA determined that FebriDx did not demonstrate “substantial equivalence” to a predicate device and expressed concern that false negative viral infection results could lead to missed cases of COVID-19.
In the newly published study, FebriDx identified individuals with viral infections 70.3% of the time (95% CI, 64.8-75.2). The probability that a person who tested negative for a viral infection was truly negative was 66.7% (95%CI, 60.8-72.1).
The study included patients with respiratory symptoms and recent fever who were enrolled from October 2019 to April 2021 at nine emergency departments, six urgent care clinics, and five primary care clinics in the United States. All patients were tested with FebriDx and underwent separate laboratory testing to determine a final diagnosis.
In addition, researchers recruited a control group of 120 individuals without symptoms.
Among 496 symptomatic individuals who had a final diagnosis, 73 (14.7%) were classified as having a response associated with a bacterial infection, 296 (59.7%) as having a viral-associated response, and 127 (25.6%) as negative.
FebriDx correctly ruled out a bacterial infection 88.4% of the time (95% CI, 85.0-91.1). The probability that a patient with a positive result for bacterial infection actually had a bacterial infection was 58.1% (95%CI, 49.1-66.7).
The findings bolster those of a previous study on the same test. This research included 220 patients who reported having a fever within the prior 3 days or had a measurable fever at the time of enrollment. In that study, the test correctly identified bacterial infections 85% of the time and correctly ruled out bacterial infection 93% of the time, with a NPV of 97%.
Too early to say test will be useful in practice
The idea of a test to guide the prescribing of antibiotics isn’t new, according to an expert who was not involved in FebriDx research.
Noah Ivers, MD, PhD, a family physician and associate professor at the University of Toronto who studies strategies to optimize primary care delivery, said, “many such point-of-care tests have been tried” to detect biomarkers such as CRP or procalcitonin, which is associated with bacterial infections.
Such tests have looked good in initial studies, he said, but when trialed in urgent care clinics, primary care clinics, or emergency departments, “they tend run into implementation challenges or simply lack of effects, or both.
“So, while I am happy at the news of this result, it’s too early to say with any certainty that it will prove useful in practice,” he added.
Meanwhile, Dr. Ivers said it’s “crucial that people understand that most illnesses are likely to be viral” and therefore not helped by antibiotics. When antibiotics are needed for outpatients, he said, “5 days is usually ample.”
The study was funded by Lumos Diagnostics. Among the 15 study authors, 6 had conflicts of interest disclosures, reporting ties to Inflammatix, Medical College of Wisconsin, Siemens, Technomics Research, and Lumos Diagnostics. Dr. Ivers reported no relevant financial interests.
FROM JAMA NETWORK OPEN
Apixaban outmatches rivaroxaban in patients with AFib and valvular heart disease
Compared with rivaroxaban, apixaban cut risks nearly in half, suggesting that clinicians should consider these new data when choosing an anticoagulant, reported lead author Ghadeer K. Dawwas, PhD, of the University of Pennsylvania, Philadelphia, and colleagues.
In the new retrospective study involving almost 20,000 patients, Dr. Dawwas and her colleagues “emulated a target trial” using private insurance claims from Optum’s deidentified Clinformatics Data Mart Database. The cohort was narrowed from a screened population of 58,210 patients with concurrent AFib and VHD to 9,947 new apixaban users who could be closely matched with 9,947 new rivaroxaban users. Covariates included provider specialty, type of VHD, demographic characteristics, measures of health care use, baseline use of medications, and baseline comorbidities.
The primary effectiveness outcome was a composite of systemic embolism and ischemic stroke, while the primary safety outcome was a composite of intracranial or gastrointestinal bleeding.
“Although several ongoing trials aim to compare apixaban with warfarin in patients with AFib and VHD, none of these trials will directly compare apixaban and rivaroxaban,” the investigators wrote. Their report is in Annals of Internal Medicine.
Dr. Dawwas and colleagues previously showed that direct oral anticoagulants (DOACs) were safer and more effective than warfarin in the same patient population. Comparing apixaban and rivaroxaban – the two most common DOACs – was the next logical step, Dr. Dawwas said in an interview.
Study results
Compared with rivaroxaban, patients who received apixaban had a 43% reduced risk of stroke or embolism (hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.40-0.80). Apixaban’s ability to protect against bleeding appeared even more pronounced, with a 49% reduced risk over rivaroxaban (HR, 0.51; 95% CI, 0.41-0.62).
Comparing the two agents on an absolute basis, apixaban reduced risk of embolism or stroke by 0.2% within the first 6 months of treatment initiation, and 1.1% within the first year of initiation. At the same time points, absolute risk reductions for bleeding were 1.2% and 1.9%, respectively.
The investigators noted that their results held consistent in an alternative analysis that considered separate types of VHD.
“Based on the results from our analysis, we showed that apixaban is effective and safe in patients with atrial fibrillation and valvular heart diseases,” Dr. Dawwas said.
Head-to-head trial needed to change practice
Christopher M. Bianco, DO, associate professor of medicine at West Virginia University Heart and Vascular Institute, Morgantown, said the findings “add to the growing body of literature,” but “a head-to-head trial would be necessary to make a definitive change to clinical practice.”
Dr. Bianco, who recently conducted a retrospective analysis of apixaban and rivaroxaban that found no difference in safety and efficacy among a different patient population, said these kinds of studies are helpful in generating hypotheses, but they can’t account for all relevant clinical factors.
“There are just so many things that go into the decision-making process of [prescribing] apixaban and rivaroxaban,” he said. “Even though [Dr. Dawwas and colleagues] used propensity matching, you’re never going to be able to sort that out with a retrospective analysis.”
Specifically, Dr. Bianco noted that the findings did not include dose data. This is a key gap, he said, considering how often real-world datasets have shown that providers underdose DOACs for a number of unaccountable reasons, and how frequently patients exhibit poor adherence.
The study also lacked detail concerning the degree of renal dysfunction, which can determine drug eligibility, Dr. Bianco said. Furthermore, attempts to stratify patients based on thrombosis and bleeding risk were likely “insufficient,” he added.
Dr. Bianco also cautioned that the investigators defined valvular heart disease as any valve-related disease of any severity. In contrast, previous studies have generally restricted valvular heart disease to patients with mitral stenosis or prosthetic valves.
“This is definitely not the traditional definition of valvular heart disease, so the title is a little bit misleading in that sense, although they certainly do disclose that in the methods,” Dr. Bianco said.
On a more positive note, he highlighted the size of the patient population, and the real-world data, which included many patients who would be excluded from clinical trials.
More broadly, the study helps drive research forward, Dr. Bianco concluded; namely, by attracting financial support for a more powerful head-to-head trial that drug makers are unlikely to fund due to inherent market risk.
This study was supported by the National Institutes of Health. The investigators disclosed additional relationships with Takeda, Spark, Sanofi, and others. Dr. Bianco disclosed no conflicts of interest.
Compared with rivaroxaban, apixaban cut risks nearly in half, suggesting that clinicians should consider these new data when choosing an anticoagulant, reported lead author Ghadeer K. Dawwas, PhD, of the University of Pennsylvania, Philadelphia, and colleagues.
In the new retrospective study involving almost 20,000 patients, Dr. Dawwas and her colleagues “emulated a target trial” using private insurance claims from Optum’s deidentified Clinformatics Data Mart Database. The cohort was narrowed from a screened population of 58,210 patients with concurrent AFib and VHD to 9,947 new apixaban users who could be closely matched with 9,947 new rivaroxaban users. Covariates included provider specialty, type of VHD, demographic characteristics, measures of health care use, baseline use of medications, and baseline comorbidities.
The primary effectiveness outcome was a composite of systemic embolism and ischemic stroke, while the primary safety outcome was a composite of intracranial or gastrointestinal bleeding.
“Although several ongoing trials aim to compare apixaban with warfarin in patients with AFib and VHD, none of these trials will directly compare apixaban and rivaroxaban,” the investigators wrote. Their report is in Annals of Internal Medicine.
Dr. Dawwas and colleagues previously showed that direct oral anticoagulants (DOACs) were safer and more effective than warfarin in the same patient population. Comparing apixaban and rivaroxaban – the two most common DOACs – was the next logical step, Dr. Dawwas said in an interview.
Study results
Compared with rivaroxaban, patients who received apixaban had a 43% reduced risk of stroke or embolism (hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.40-0.80). Apixaban’s ability to protect against bleeding appeared even more pronounced, with a 49% reduced risk over rivaroxaban (HR, 0.51; 95% CI, 0.41-0.62).
Comparing the two agents on an absolute basis, apixaban reduced risk of embolism or stroke by 0.2% within the first 6 months of treatment initiation, and 1.1% within the first year of initiation. At the same time points, absolute risk reductions for bleeding were 1.2% and 1.9%, respectively.
The investigators noted that their results held consistent in an alternative analysis that considered separate types of VHD.
“Based on the results from our analysis, we showed that apixaban is effective and safe in patients with atrial fibrillation and valvular heart diseases,” Dr. Dawwas said.
Head-to-head trial needed to change practice
Christopher M. Bianco, DO, associate professor of medicine at West Virginia University Heart and Vascular Institute, Morgantown, said the findings “add to the growing body of literature,” but “a head-to-head trial would be necessary to make a definitive change to clinical practice.”
Dr. Bianco, who recently conducted a retrospective analysis of apixaban and rivaroxaban that found no difference in safety and efficacy among a different patient population, said these kinds of studies are helpful in generating hypotheses, but they can’t account for all relevant clinical factors.
“There are just so many things that go into the decision-making process of [prescribing] apixaban and rivaroxaban,” he said. “Even though [Dr. Dawwas and colleagues] used propensity matching, you’re never going to be able to sort that out with a retrospective analysis.”
Specifically, Dr. Bianco noted that the findings did not include dose data. This is a key gap, he said, considering how often real-world datasets have shown that providers underdose DOACs for a number of unaccountable reasons, and how frequently patients exhibit poor adherence.
The study also lacked detail concerning the degree of renal dysfunction, which can determine drug eligibility, Dr. Bianco said. Furthermore, attempts to stratify patients based on thrombosis and bleeding risk were likely “insufficient,” he added.
Dr. Bianco also cautioned that the investigators defined valvular heart disease as any valve-related disease of any severity. In contrast, previous studies have generally restricted valvular heart disease to patients with mitral stenosis or prosthetic valves.
“This is definitely not the traditional definition of valvular heart disease, so the title is a little bit misleading in that sense, although they certainly do disclose that in the methods,” Dr. Bianco said.
On a more positive note, he highlighted the size of the patient population, and the real-world data, which included many patients who would be excluded from clinical trials.
More broadly, the study helps drive research forward, Dr. Bianco concluded; namely, by attracting financial support for a more powerful head-to-head trial that drug makers are unlikely to fund due to inherent market risk.
This study was supported by the National Institutes of Health. The investigators disclosed additional relationships with Takeda, Spark, Sanofi, and others. Dr. Bianco disclosed no conflicts of interest.
Compared with rivaroxaban, apixaban cut risks nearly in half, suggesting that clinicians should consider these new data when choosing an anticoagulant, reported lead author Ghadeer K. Dawwas, PhD, of the University of Pennsylvania, Philadelphia, and colleagues.
In the new retrospective study involving almost 20,000 patients, Dr. Dawwas and her colleagues “emulated a target trial” using private insurance claims from Optum’s deidentified Clinformatics Data Mart Database. The cohort was narrowed from a screened population of 58,210 patients with concurrent AFib and VHD to 9,947 new apixaban users who could be closely matched with 9,947 new rivaroxaban users. Covariates included provider specialty, type of VHD, demographic characteristics, measures of health care use, baseline use of medications, and baseline comorbidities.
The primary effectiveness outcome was a composite of systemic embolism and ischemic stroke, while the primary safety outcome was a composite of intracranial or gastrointestinal bleeding.
“Although several ongoing trials aim to compare apixaban with warfarin in patients with AFib and VHD, none of these trials will directly compare apixaban and rivaroxaban,” the investigators wrote. Their report is in Annals of Internal Medicine.
Dr. Dawwas and colleagues previously showed that direct oral anticoagulants (DOACs) were safer and more effective than warfarin in the same patient population. Comparing apixaban and rivaroxaban – the two most common DOACs – was the next logical step, Dr. Dawwas said in an interview.
Study results
Compared with rivaroxaban, patients who received apixaban had a 43% reduced risk of stroke or embolism (hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.40-0.80). Apixaban’s ability to protect against bleeding appeared even more pronounced, with a 49% reduced risk over rivaroxaban (HR, 0.51; 95% CI, 0.41-0.62).
Comparing the two agents on an absolute basis, apixaban reduced risk of embolism or stroke by 0.2% within the first 6 months of treatment initiation, and 1.1% within the first year of initiation. At the same time points, absolute risk reductions for bleeding were 1.2% and 1.9%, respectively.
The investigators noted that their results held consistent in an alternative analysis that considered separate types of VHD.
“Based on the results from our analysis, we showed that apixaban is effective and safe in patients with atrial fibrillation and valvular heart diseases,” Dr. Dawwas said.
Head-to-head trial needed to change practice
Christopher M. Bianco, DO, associate professor of medicine at West Virginia University Heart and Vascular Institute, Morgantown, said the findings “add to the growing body of literature,” but “a head-to-head trial would be necessary to make a definitive change to clinical practice.”
Dr. Bianco, who recently conducted a retrospective analysis of apixaban and rivaroxaban that found no difference in safety and efficacy among a different patient population, said these kinds of studies are helpful in generating hypotheses, but they can’t account for all relevant clinical factors.
“There are just so many things that go into the decision-making process of [prescribing] apixaban and rivaroxaban,” he said. “Even though [Dr. Dawwas and colleagues] used propensity matching, you’re never going to be able to sort that out with a retrospective analysis.”
Specifically, Dr. Bianco noted that the findings did not include dose data. This is a key gap, he said, considering how often real-world datasets have shown that providers underdose DOACs for a number of unaccountable reasons, and how frequently patients exhibit poor adherence.
The study also lacked detail concerning the degree of renal dysfunction, which can determine drug eligibility, Dr. Bianco said. Furthermore, attempts to stratify patients based on thrombosis and bleeding risk were likely “insufficient,” he added.
Dr. Bianco also cautioned that the investigators defined valvular heart disease as any valve-related disease of any severity. In contrast, previous studies have generally restricted valvular heart disease to patients with mitral stenosis or prosthetic valves.
“This is definitely not the traditional definition of valvular heart disease, so the title is a little bit misleading in that sense, although they certainly do disclose that in the methods,” Dr. Bianco said.
On a more positive note, he highlighted the size of the patient population, and the real-world data, which included many patients who would be excluded from clinical trials.
More broadly, the study helps drive research forward, Dr. Bianco concluded; namely, by attracting financial support for a more powerful head-to-head trial that drug makers are unlikely to fund due to inherent market risk.
This study was supported by the National Institutes of Health. The investigators disclosed additional relationships with Takeda, Spark, Sanofi, and others. Dr. Bianco disclosed no conflicts of interest.
FROM ANNALS OF INTERNAL MEDICINE
Self-worth training boosts ketamine’s effects in severe depression
The double-blind, randomized clinical trial is the first to assess combining ketamine with a low-cost protective learning program, researchers note.
They add that the findings are an important step toward long-lasting depression treatment for millions of patients whose depression does not improve following first-line therapies.
“One of the biggest challenges in psychiatry and psychology is seeing evidence of longer-term benefits and longer-term compliance,” lead investigator Rebecca B. Price, PhD, associate professor of psychiatry and psychology, University of Pittsburgh, told this news organization.
“Anything that can get somebody well quickly and keep them well for some length of time is really exciting – and a whole paradigm shift for how things have been done up to now,” Dr. Price said.
The findings were published online in the American Journal of Psychiatry.
Promoting self-worth
About one-third of patients with depression remain treatment-resistant even after trying different medications at different doses and at different combinations, the investigators note.
Ketamine and esketamine, a nasal spray formulation of the drug, have been shown previously to improve symptoms in patients with TRD. While the benefits are evident within a few hours of treatment, the effects often wane after just a few weeks.
Ketamine and esketamine must be administered in a clinical setting and patients must be monitored for at least 2 hours after treatment. Repeat dosing is costly, both in time and expense, so clinical researchers have been studying ways to extend the drug’s effects without additional treatments.
The new study combined ketamine treatment with a computer-based active automated self-association training (ASAT) program that the researchers developed. It uses positive words and imagery to promote positive self-image and self-worth.
The trial included 154 adults with treatment-resistant unipolar depression whose symptoms persisted after therapy with at least two medications. Participants received an IV infusion of ketamine 0.5 mg/kg plus active ASAT (n = 53), saline plus active ASAT (n = 51), or ketamine plus sham ASAT (n = 50).
The active program used words like “sweet,” “lovable,” and “worthy” that appeared on the screen interspersed with images of people smiling and the patient’s own photo. Participants were also asked to complete certain mouse-tracking tasks during the session.
The sham ASAT was similar but included neutral words and images. ASAT and sham ASAT were delivered twice daily over 4 consecutive days for 20 minutes.
Clear benefit
Results showed that ketamine rapidly and significantly reduced depression scores within 24 hours of treatment (group-by-time interaction: standardized beta, –1.30; 95% confidence interval, –1.89 to –0.70).
Depression scores in the ketamine-plus-ASAT group remained low and stable over a 30-day period, compared with the saline-plus-ASAT group (standardized beta, –0.61; 95% CI, –0.95 to –0.28).
Participants who received ketamine plus sham ASAT saw initial improvement in symptoms immediately following infusion, but depression symptoms returned after a few weeks.
While researchers hoped to see positive effects from ASAT, “I certainly did not expect to see something so clear to jump right out,” Dr. Price said.
The investigators are now examining whether the computer program can be administered effectively remotely and whether its effects are equally beneficial following treatment with esketamine.
Greatest unmet need
Gerard Sanacora, MD, PhD, professor of psychiatry, and director, Yale Depression Research Program, Yale University, New Haven, Conn., said that extending the effects of ketamine or esketamine without additional dosing is “probably the greatest unmet need in relation to treatments with ketamine and esketamine.”
He added that there are large economic, time, and access burdens associated with the treatment of ketamine.
“Anything we can do to reduce the number of treatments needed or increase the sustainability or the duration of effect would be a tremendous benefit,” said Dr. Sanacora, who was not involved with the research.
Adding an easily accessible, nonpharmacological therapeutic approach to ketamine treatment could be valuable, he said – but more research is needed.
“I’m not sure that this specific associated positive thinking is really the critical component. I think we still have some work to do there. But it does demonstrate that we can use ancillary or augmenting nonpharmacological treatments to extend the effect,” Dr. Sanacora said.
The study was funded by the National Institute of Mental Health and Clinical and Translational Science Institute at the University of Pittsburgh. Dr. Price is the named inventor on a University of Pittsburgh–owned provisional patent filing related to the combination intervention described in this report. Dr. Sanacora reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The double-blind, randomized clinical trial is the first to assess combining ketamine with a low-cost protective learning program, researchers note.
They add that the findings are an important step toward long-lasting depression treatment for millions of patients whose depression does not improve following first-line therapies.
“One of the biggest challenges in psychiatry and psychology is seeing evidence of longer-term benefits and longer-term compliance,” lead investigator Rebecca B. Price, PhD, associate professor of psychiatry and psychology, University of Pittsburgh, told this news organization.
“Anything that can get somebody well quickly and keep them well for some length of time is really exciting – and a whole paradigm shift for how things have been done up to now,” Dr. Price said.
The findings were published online in the American Journal of Psychiatry.
Promoting self-worth
About one-third of patients with depression remain treatment-resistant even after trying different medications at different doses and at different combinations, the investigators note.
Ketamine and esketamine, a nasal spray formulation of the drug, have been shown previously to improve symptoms in patients with TRD. While the benefits are evident within a few hours of treatment, the effects often wane after just a few weeks.
Ketamine and esketamine must be administered in a clinical setting and patients must be monitored for at least 2 hours after treatment. Repeat dosing is costly, both in time and expense, so clinical researchers have been studying ways to extend the drug’s effects without additional treatments.
The new study combined ketamine treatment with a computer-based active automated self-association training (ASAT) program that the researchers developed. It uses positive words and imagery to promote positive self-image and self-worth.
The trial included 154 adults with treatment-resistant unipolar depression whose symptoms persisted after therapy with at least two medications. Participants received an IV infusion of ketamine 0.5 mg/kg plus active ASAT (n = 53), saline plus active ASAT (n = 51), or ketamine plus sham ASAT (n = 50).
The active program used words like “sweet,” “lovable,” and “worthy” that appeared on the screen interspersed with images of people smiling and the patient’s own photo. Participants were also asked to complete certain mouse-tracking tasks during the session.
The sham ASAT was similar but included neutral words and images. ASAT and sham ASAT were delivered twice daily over 4 consecutive days for 20 minutes.
Clear benefit
Results showed that ketamine rapidly and significantly reduced depression scores within 24 hours of treatment (group-by-time interaction: standardized beta, –1.30; 95% confidence interval, –1.89 to –0.70).
Depression scores in the ketamine-plus-ASAT group remained low and stable over a 30-day period, compared with the saline-plus-ASAT group (standardized beta, –0.61; 95% CI, –0.95 to –0.28).
Participants who received ketamine plus sham ASAT saw initial improvement in symptoms immediately following infusion, but depression symptoms returned after a few weeks.
While researchers hoped to see positive effects from ASAT, “I certainly did not expect to see something so clear to jump right out,” Dr. Price said.
The investigators are now examining whether the computer program can be administered effectively remotely and whether its effects are equally beneficial following treatment with esketamine.
Greatest unmet need
Gerard Sanacora, MD, PhD, professor of psychiatry, and director, Yale Depression Research Program, Yale University, New Haven, Conn., said that extending the effects of ketamine or esketamine without additional dosing is “probably the greatest unmet need in relation to treatments with ketamine and esketamine.”
He added that there are large economic, time, and access burdens associated with the treatment of ketamine.
“Anything we can do to reduce the number of treatments needed or increase the sustainability or the duration of effect would be a tremendous benefit,” said Dr. Sanacora, who was not involved with the research.
Adding an easily accessible, nonpharmacological therapeutic approach to ketamine treatment could be valuable, he said – but more research is needed.
“I’m not sure that this specific associated positive thinking is really the critical component. I think we still have some work to do there. But it does demonstrate that we can use ancillary or augmenting nonpharmacological treatments to extend the effect,” Dr. Sanacora said.
The study was funded by the National Institute of Mental Health and Clinical and Translational Science Institute at the University of Pittsburgh. Dr. Price is the named inventor on a University of Pittsburgh–owned provisional patent filing related to the combination intervention described in this report. Dr. Sanacora reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The double-blind, randomized clinical trial is the first to assess combining ketamine with a low-cost protective learning program, researchers note.
They add that the findings are an important step toward long-lasting depression treatment for millions of patients whose depression does not improve following first-line therapies.
“One of the biggest challenges in psychiatry and psychology is seeing evidence of longer-term benefits and longer-term compliance,” lead investigator Rebecca B. Price, PhD, associate professor of psychiatry and psychology, University of Pittsburgh, told this news organization.
“Anything that can get somebody well quickly and keep them well for some length of time is really exciting – and a whole paradigm shift for how things have been done up to now,” Dr. Price said.
The findings were published online in the American Journal of Psychiatry.
Promoting self-worth
About one-third of patients with depression remain treatment-resistant even after trying different medications at different doses and at different combinations, the investigators note.
Ketamine and esketamine, a nasal spray formulation of the drug, have been shown previously to improve symptoms in patients with TRD. While the benefits are evident within a few hours of treatment, the effects often wane after just a few weeks.
Ketamine and esketamine must be administered in a clinical setting and patients must be monitored for at least 2 hours after treatment. Repeat dosing is costly, both in time and expense, so clinical researchers have been studying ways to extend the drug’s effects without additional treatments.
The new study combined ketamine treatment with a computer-based active automated self-association training (ASAT) program that the researchers developed. It uses positive words and imagery to promote positive self-image and self-worth.
The trial included 154 adults with treatment-resistant unipolar depression whose symptoms persisted after therapy with at least two medications. Participants received an IV infusion of ketamine 0.5 mg/kg plus active ASAT (n = 53), saline plus active ASAT (n = 51), or ketamine plus sham ASAT (n = 50).
The active program used words like “sweet,” “lovable,” and “worthy” that appeared on the screen interspersed with images of people smiling and the patient’s own photo. Participants were also asked to complete certain mouse-tracking tasks during the session.
The sham ASAT was similar but included neutral words and images. ASAT and sham ASAT were delivered twice daily over 4 consecutive days for 20 minutes.
Clear benefit
Results showed that ketamine rapidly and significantly reduced depression scores within 24 hours of treatment (group-by-time interaction: standardized beta, –1.30; 95% confidence interval, –1.89 to –0.70).
Depression scores in the ketamine-plus-ASAT group remained low and stable over a 30-day period, compared with the saline-plus-ASAT group (standardized beta, –0.61; 95% CI, –0.95 to –0.28).
Participants who received ketamine plus sham ASAT saw initial improvement in symptoms immediately following infusion, but depression symptoms returned after a few weeks.
While researchers hoped to see positive effects from ASAT, “I certainly did not expect to see something so clear to jump right out,” Dr. Price said.
The investigators are now examining whether the computer program can be administered effectively remotely and whether its effects are equally beneficial following treatment with esketamine.
Greatest unmet need
Gerard Sanacora, MD, PhD, professor of psychiatry, and director, Yale Depression Research Program, Yale University, New Haven, Conn., said that extending the effects of ketamine or esketamine without additional dosing is “probably the greatest unmet need in relation to treatments with ketamine and esketamine.”
He added that there are large economic, time, and access burdens associated with the treatment of ketamine.
“Anything we can do to reduce the number of treatments needed or increase the sustainability or the duration of effect would be a tremendous benefit,” said Dr. Sanacora, who was not involved with the research.
Adding an easily accessible, nonpharmacological therapeutic approach to ketamine treatment could be valuable, he said – but more research is needed.
“I’m not sure that this specific associated positive thinking is really the critical component. I think we still have some work to do there. But it does demonstrate that we can use ancillary or augmenting nonpharmacological treatments to extend the effect,” Dr. Sanacora said.
The study was funded by the National Institute of Mental Health and Clinical and Translational Science Institute at the University of Pittsburgh. Dr. Price is the named inventor on a University of Pittsburgh–owned provisional patent filing related to the combination intervention described in this report. Dr. Sanacora reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM AMERICAN JOURNAL OF PSYCHIATRY
New deep dive into Paxlovid interactions with CVD meds
Nirmatrelvir/ritonavir (Paxlovid) has been a game changer for high-risk patients with early COVID-19 symptoms but has significant interactions with commonly used cardiovascular medications, a new paper cautions.
COVID-19 patients with cardiovascular disease (CVD) or risk factors such as diabetes, hypertension, and chronic kidney disease are at high risk of severe disease and account for the lion’s share of those receiving Paxlovid. Data from the initial EPIC-HR trial and recent real-world data also suggest they’re among the most likely to benefit from the oral antiviral, regardless of their COVID-19 vaccination status.
“But at the same time, it unfortunately interacts with many very commonly prescribed cardiovascular medications and with many of them in a very clinically meaningful way, which may lead to serious adverse consequences,” senior author Sarju Ganatra, MD, said in an interview. “So, while it’s being prescribed with a good intention to help these people, we may actually end up doing more harm than good.
“We don’t want to deter people from getting their necessary COVID-19 treatment, which is excellent for the most part these days as an outpatient,” he added. “So, we felt the need to make a comprehensive list of cardiac medications and level of interactions with Paxlovid and also to help the clinicians and prescribers at the point of care to make the clinical decision of what modifications they may need to do.”
The paper, published online in the Journal of the American College of Cardiology, details drug-drug interactions with some 80 CV medications including statins, antihypertensive agents, heart failure therapies, and antiplatelet/anticoagulants.
It also includes a color-coded figure denoting whether a drug is safe to coadminister with Paxlovid, may potentially interact and require a dose adjustment or temporary discontinuation, or is contraindicated.
Among the commonly used blood thinners, for example, the paper notes that Paxlovid significantly increases drug levels of the direct oral anticoagulants (DOACs) apixaban, rivaroxaban, edoxaban, and dabigatran and, thus, increases the risk of bleeding.
“It can still be administered, if it’s necessary, but the dose of the DOAC either needs to be reduced or held depending on what they are getting it for, whether they’re getting it for pulmonary embolism or atrial fibrillation, and we adjust for all those things in the table in the paper,” said Dr. Ganatra, from Lahey Hospital and Medical Center, Burlington, Mass.
When the DOAC can’t be interrupted or dose adjusted, however, Paxlovid should not be given, the experts said. The antiviral is safe to use with enoxaparin, a low-molecular-weight heparin, but can increase or decrease levels of warfarin and should be used with close international normalized ratio monitoring.
For patients on antiplatelet agents, clinicians are advised to avoid prescribing nirmatrelvir/ritonavir to those on ticagrelor or clopidogrel unless the agents can be replaced by prasugrel.
Ritonavir – an inhibitor of cytochrome P 450 enzymes, particularly CYP3A4 – poses an increased risk of bleeding when given with ticagrelor, a CYP3A4 substrate, and decreases the active metabolite of clopidogrel, cutting its platelet inhibition by 20%. Although there’s a twofold decrease in the maximum concentration of prasugrel in patients on ritonavir, this does not affect its antiplatelet activity, the paper explains.
Among the lipid-lowering agents, experts suggested temporarily withholding atorvastatin, rosuvastatin, simvastatin, and lovastatin because of an increased risk for myopathy and liver toxicity but say that other statins, fibrates, ezetimibe, and the proprotein convertase subtilisin/kexin type 9 inhibitors evolocumab and alirocumab are safe to coadminister with Paxlovid.
While statins typically leave the body within hours, most of the antiarrhythmic drugs, except for sotalol, are not safe to give with Paxlovid, Dr. Ganatra said. It’s technically not feasible to hold these drugs because most have long half-lives, reaching about 100 days, for example, for amiodarone.
“It’s going to hang around in your system for a long time, so you don’t want to be falsely reassured that you’re holding the drug and it’s going to be fine to go back slowly,” he said. “You need to look for alternative therapies in those scenarios for COVID-19 treatment, which could be other antivirals, or a monoclonal antibody individualized to the patient’s risk.”
Although there’s limited clinical information regarding interaction-related adverse events with Paxlovid, the team used pharmacokinetics and pharmacodynamics data to provide the guidance. Serious adverse events are also well documented for ritonavir, which has been prescribed for years to treat HIV, Dr. Ganatra noted.
The Infectious Disease Society of America also published guidance on the management of potential drug interactions with Paxlovid in May and, earlier in October, the Food and Drug Administration updated its Paxlovid patient eligibility screening checklist.
Still, most prescribers are actually primary care physicians and even pharmacists, who may not be completely attuned, said Dr. Ganatra, who noted that some centers have started programs to help connect primary care physicians with their cardiology colleagues to check on CV drugs in their COVID-19 patients.
“We need to be thinking more broadly and at a system level where the hospital or health care system leverages the electronic health record systems,” he said. “Most of them are sophisticated enough to incorporate simple drug-drug interaction information, so if you try to prescribe someone Paxlovid and it’s a heart transplant patient who is on immunosuppressive therapy or a patient on a blood thinner, then it should give you a warning ... or at least give them a link to our paper or other valuable resources.
“If someone is on a blood thinner and the blood thinner level goes up by ninefold, we can only imagine what we would be dealing with,” Dr. Ganatra said. “So, these interactions should be taken very seriously and I think it’s worth the time and investment.”
The authors reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Nirmatrelvir/ritonavir (Paxlovid) has been a game changer for high-risk patients with early COVID-19 symptoms but has significant interactions with commonly used cardiovascular medications, a new paper cautions.
COVID-19 patients with cardiovascular disease (CVD) or risk factors such as diabetes, hypertension, and chronic kidney disease are at high risk of severe disease and account for the lion’s share of those receiving Paxlovid. Data from the initial EPIC-HR trial and recent real-world data also suggest they’re among the most likely to benefit from the oral antiviral, regardless of their COVID-19 vaccination status.
“But at the same time, it unfortunately interacts with many very commonly prescribed cardiovascular medications and with many of them in a very clinically meaningful way, which may lead to serious adverse consequences,” senior author Sarju Ganatra, MD, said in an interview. “So, while it’s being prescribed with a good intention to help these people, we may actually end up doing more harm than good.
“We don’t want to deter people from getting their necessary COVID-19 treatment, which is excellent for the most part these days as an outpatient,” he added. “So, we felt the need to make a comprehensive list of cardiac medications and level of interactions with Paxlovid and also to help the clinicians and prescribers at the point of care to make the clinical decision of what modifications they may need to do.”
The paper, published online in the Journal of the American College of Cardiology, details drug-drug interactions with some 80 CV medications including statins, antihypertensive agents, heart failure therapies, and antiplatelet/anticoagulants.
It also includes a color-coded figure denoting whether a drug is safe to coadminister with Paxlovid, may potentially interact and require a dose adjustment or temporary discontinuation, or is contraindicated.
Among the commonly used blood thinners, for example, the paper notes that Paxlovid significantly increases drug levels of the direct oral anticoagulants (DOACs) apixaban, rivaroxaban, edoxaban, and dabigatran and, thus, increases the risk of bleeding.
“It can still be administered, if it’s necessary, but the dose of the DOAC either needs to be reduced or held depending on what they are getting it for, whether they’re getting it for pulmonary embolism or atrial fibrillation, and we adjust for all those things in the table in the paper,” said Dr. Ganatra, from Lahey Hospital and Medical Center, Burlington, Mass.
When the DOAC can’t be interrupted or dose adjusted, however, Paxlovid should not be given, the experts said. The antiviral is safe to use with enoxaparin, a low-molecular-weight heparin, but can increase or decrease levels of warfarin and should be used with close international normalized ratio monitoring.
For patients on antiplatelet agents, clinicians are advised to avoid prescribing nirmatrelvir/ritonavir to those on ticagrelor or clopidogrel unless the agents can be replaced by prasugrel.
Ritonavir – an inhibitor of cytochrome P 450 enzymes, particularly CYP3A4 – poses an increased risk of bleeding when given with ticagrelor, a CYP3A4 substrate, and decreases the active metabolite of clopidogrel, cutting its platelet inhibition by 20%. Although there’s a twofold decrease in the maximum concentration of prasugrel in patients on ritonavir, this does not affect its antiplatelet activity, the paper explains.
Among the lipid-lowering agents, experts suggested temporarily withholding atorvastatin, rosuvastatin, simvastatin, and lovastatin because of an increased risk for myopathy and liver toxicity but say that other statins, fibrates, ezetimibe, and the proprotein convertase subtilisin/kexin type 9 inhibitors evolocumab and alirocumab are safe to coadminister with Paxlovid.
While statins typically leave the body within hours, most of the antiarrhythmic drugs, except for sotalol, are not safe to give with Paxlovid, Dr. Ganatra said. It’s technically not feasible to hold these drugs because most have long half-lives, reaching about 100 days, for example, for amiodarone.
“It’s going to hang around in your system for a long time, so you don’t want to be falsely reassured that you’re holding the drug and it’s going to be fine to go back slowly,” he said. “You need to look for alternative therapies in those scenarios for COVID-19 treatment, which could be other antivirals, or a monoclonal antibody individualized to the patient’s risk.”
Although there’s limited clinical information regarding interaction-related adverse events with Paxlovid, the team used pharmacokinetics and pharmacodynamics data to provide the guidance. Serious adverse events are also well documented for ritonavir, which has been prescribed for years to treat HIV, Dr. Ganatra noted.
The Infectious Disease Society of America also published guidance on the management of potential drug interactions with Paxlovid in May and, earlier in October, the Food and Drug Administration updated its Paxlovid patient eligibility screening checklist.
Still, most prescribers are actually primary care physicians and even pharmacists, who may not be completely attuned, said Dr. Ganatra, who noted that some centers have started programs to help connect primary care physicians with their cardiology colleagues to check on CV drugs in their COVID-19 patients.
“We need to be thinking more broadly and at a system level where the hospital or health care system leverages the electronic health record systems,” he said. “Most of them are sophisticated enough to incorporate simple drug-drug interaction information, so if you try to prescribe someone Paxlovid and it’s a heart transplant patient who is on immunosuppressive therapy or a patient on a blood thinner, then it should give you a warning ... or at least give them a link to our paper or other valuable resources.
“If someone is on a blood thinner and the blood thinner level goes up by ninefold, we can only imagine what we would be dealing with,” Dr. Ganatra said. “So, these interactions should be taken very seriously and I think it’s worth the time and investment.”
The authors reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Nirmatrelvir/ritonavir (Paxlovid) has been a game changer for high-risk patients with early COVID-19 symptoms but has significant interactions with commonly used cardiovascular medications, a new paper cautions.
COVID-19 patients with cardiovascular disease (CVD) or risk factors such as diabetes, hypertension, and chronic kidney disease are at high risk of severe disease and account for the lion’s share of those receiving Paxlovid. Data from the initial EPIC-HR trial and recent real-world data also suggest they’re among the most likely to benefit from the oral antiviral, regardless of their COVID-19 vaccination status.
“But at the same time, it unfortunately interacts with many very commonly prescribed cardiovascular medications and with many of them in a very clinically meaningful way, which may lead to serious adverse consequences,” senior author Sarju Ganatra, MD, said in an interview. “So, while it’s being prescribed with a good intention to help these people, we may actually end up doing more harm than good.
“We don’t want to deter people from getting their necessary COVID-19 treatment, which is excellent for the most part these days as an outpatient,” he added. “So, we felt the need to make a comprehensive list of cardiac medications and level of interactions with Paxlovid and also to help the clinicians and prescribers at the point of care to make the clinical decision of what modifications they may need to do.”
The paper, published online in the Journal of the American College of Cardiology, details drug-drug interactions with some 80 CV medications including statins, antihypertensive agents, heart failure therapies, and antiplatelet/anticoagulants.
It also includes a color-coded figure denoting whether a drug is safe to coadminister with Paxlovid, may potentially interact and require a dose adjustment or temporary discontinuation, or is contraindicated.
Among the commonly used blood thinners, for example, the paper notes that Paxlovid significantly increases drug levels of the direct oral anticoagulants (DOACs) apixaban, rivaroxaban, edoxaban, and dabigatran and, thus, increases the risk of bleeding.
“It can still be administered, if it’s necessary, but the dose of the DOAC either needs to be reduced or held depending on what they are getting it for, whether they’re getting it for pulmonary embolism or atrial fibrillation, and we adjust for all those things in the table in the paper,” said Dr. Ganatra, from Lahey Hospital and Medical Center, Burlington, Mass.
When the DOAC can’t be interrupted or dose adjusted, however, Paxlovid should not be given, the experts said. The antiviral is safe to use with enoxaparin, a low-molecular-weight heparin, but can increase or decrease levels of warfarin and should be used with close international normalized ratio monitoring.
For patients on antiplatelet agents, clinicians are advised to avoid prescribing nirmatrelvir/ritonavir to those on ticagrelor or clopidogrel unless the agents can be replaced by prasugrel.
Ritonavir – an inhibitor of cytochrome P 450 enzymes, particularly CYP3A4 – poses an increased risk of bleeding when given with ticagrelor, a CYP3A4 substrate, and decreases the active metabolite of clopidogrel, cutting its platelet inhibition by 20%. Although there’s a twofold decrease in the maximum concentration of prasugrel in patients on ritonavir, this does not affect its antiplatelet activity, the paper explains.
Among the lipid-lowering agents, experts suggested temporarily withholding atorvastatin, rosuvastatin, simvastatin, and lovastatin because of an increased risk for myopathy and liver toxicity but say that other statins, fibrates, ezetimibe, and the proprotein convertase subtilisin/kexin type 9 inhibitors evolocumab and alirocumab are safe to coadminister with Paxlovid.
While statins typically leave the body within hours, most of the antiarrhythmic drugs, except for sotalol, are not safe to give with Paxlovid, Dr. Ganatra said. It’s technically not feasible to hold these drugs because most have long half-lives, reaching about 100 days, for example, for amiodarone.
“It’s going to hang around in your system for a long time, so you don’t want to be falsely reassured that you’re holding the drug and it’s going to be fine to go back slowly,” he said. “You need to look for alternative therapies in those scenarios for COVID-19 treatment, which could be other antivirals, or a monoclonal antibody individualized to the patient’s risk.”
Although there’s limited clinical information regarding interaction-related adverse events with Paxlovid, the team used pharmacokinetics and pharmacodynamics data to provide the guidance. Serious adverse events are also well documented for ritonavir, which has been prescribed for years to treat HIV, Dr. Ganatra noted.
The Infectious Disease Society of America also published guidance on the management of potential drug interactions with Paxlovid in May and, earlier in October, the Food and Drug Administration updated its Paxlovid patient eligibility screening checklist.
Still, most prescribers are actually primary care physicians and even pharmacists, who may not be completely attuned, said Dr. Ganatra, who noted that some centers have started programs to help connect primary care physicians with their cardiology colleagues to check on CV drugs in their COVID-19 patients.
“We need to be thinking more broadly and at a system level where the hospital or health care system leverages the electronic health record systems,” he said. “Most of them are sophisticated enough to incorporate simple drug-drug interaction information, so if you try to prescribe someone Paxlovid and it’s a heart transplant patient who is on immunosuppressive therapy or a patient on a blood thinner, then it should give you a warning ... or at least give them a link to our paper or other valuable resources.
“If someone is on a blood thinner and the blood thinner level goes up by ninefold, we can only imagine what we would be dealing with,” Dr. Ganatra said. “So, these interactions should be taken very seriously and I think it’s worth the time and investment.”
The authors reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM THE JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
FDA confirms nationwide Adderall shortage
The U.S. Food and Drug Administration which are approved for treating attention deficit hyperactivity disorder and narcolepsy.
The FDA announcement follows weeks of reports of a shortage of the drug by pharmacy chains and Adderall users.
The agency said it is in “frequent” contact with all manufacturers of Adderall – and reported that one of those companies, Teva, is experiencing ongoing intermittent manufacturing delays.
Other manufacturers continue to produce amphetamine mixed salts, but there is not enough supply to continue to meet U.S. market demand through those producers, the FDA noted.
“Until supply is restored, there are alternative therapies, including the extended-release version of amphetamine mixed salts, available to health care professionals and their patients for amphetamine mixed salts’ approved indications,” the agency said.
Patients should work with their health care provider to determine their best treatment option, it added.
The organization is continuing to monitor the supply of Adderall and to help manufacturers resolve the shortage.
Its Drug Shortage webpage has additional information about the situation and is updated regularly.
“We continue to use all the tools we have available to help keep supply available for patients and will provide public updates regarding the Adderall shortage,” the FDA said.
A version of this article first appeared on Medscape.com.
The U.S. Food and Drug Administration which are approved for treating attention deficit hyperactivity disorder and narcolepsy.
The FDA announcement follows weeks of reports of a shortage of the drug by pharmacy chains and Adderall users.
The agency said it is in “frequent” contact with all manufacturers of Adderall – and reported that one of those companies, Teva, is experiencing ongoing intermittent manufacturing delays.
Other manufacturers continue to produce amphetamine mixed salts, but there is not enough supply to continue to meet U.S. market demand through those producers, the FDA noted.
“Until supply is restored, there are alternative therapies, including the extended-release version of amphetamine mixed salts, available to health care professionals and their patients for amphetamine mixed salts’ approved indications,” the agency said.
Patients should work with their health care provider to determine their best treatment option, it added.
The organization is continuing to monitor the supply of Adderall and to help manufacturers resolve the shortage.
Its Drug Shortage webpage has additional information about the situation and is updated regularly.
“We continue to use all the tools we have available to help keep supply available for patients and will provide public updates regarding the Adderall shortage,” the FDA said.
A version of this article first appeared on Medscape.com.
The U.S. Food and Drug Administration which are approved for treating attention deficit hyperactivity disorder and narcolepsy.
The FDA announcement follows weeks of reports of a shortage of the drug by pharmacy chains and Adderall users.
The agency said it is in “frequent” contact with all manufacturers of Adderall – and reported that one of those companies, Teva, is experiencing ongoing intermittent manufacturing delays.
Other manufacturers continue to produce amphetamine mixed salts, but there is not enough supply to continue to meet U.S. market demand through those producers, the FDA noted.
“Until supply is restored, there are alternative therapies, including the extended-release version of amphetamine mixed salts, available to health care professionals and their patients for amphetamine mixed salts’ approved indications,” the agency said.
Patients should work with their health care provider to determine their best treatment option, it added.
The organization is continuing to monitor the supply of Adderall and to help manufacturers resolve the shortage.
Its Drug Shortage webpage has additional information about the situation and is updated regularly.
“We continue to use all the tools we have available to help keep supply available for patients and will provide public updates regarding the Adderall shortage,” the FDA said.
A version of this article first appeared on Medscape.com.
Dermatologists fear effects of Dobbs decision for patients on isotretinoin, methotrexate
More than 3 months after the Dobbs decision by the U.S. Supreme Court overturned Roe v. Wade and revoked the constitutional right to an abortion, Some have beefed up their already stringent instructions and lengthy conversations about avoiding pregnancy while on the medication.
The major fear is that a patient who is taking contraceptive precautions, in accordance with the isotretinoin risk-management program, iPLEDGE, but still becomes pregnant while on isotretinoin may find out about the pregnancy too late to undergo an abortion in her own state and may not be able to travel to another state – or the patient may live in a state where abortions are entirely prohibited and is unable to travel to another state.
Isotretinoin is marketed as Absorica, Absorica LD, Claravis, Amnesteem, Myorisan, and Zenatane; its former brand name was Accutane.
As of Oct. 7, a total of 14 states have banned most abortions, while 4 others have bans at 6, 15, 18, or 20 weeks. Attempts to restrict abortion on several other states are underway.
“To date, we don’t know of any specific effects of the Dobbs decision on isotretinoin prescribing, but with abortion access banned in many states, we anticipate that this could be a very real issue for individuals who accidentally become pregnant while taking isotretinoin,” said Ilona Frieden, MD, professor of dermatology and pediatrics at the University of California, San Francisco, and chair of the American Academy of Dermatology Association’s iPLEDGE Workgroup.
The iPLEDGE REMS (Risk Evaluation and Mitigation Strategy) is the Food and Drug Administration–required safety program that is in place to manage the risk of isotretinoin teratogenicity and minimize fetal exposure. The work group meets with the FDA and isotretinoin manufacturers to keep the program safe and operating smoothly. The iPLEDGE workgroup has not yet issued any specific statements on the implications of the Dobbs decision on prescribing isotretinoin.
But work on the issue is ongoing by the American Academy of Dermatology. In a statement issued in September, Mark D. Kaufmann, MD, president of the AAD, said that the academy “is continuing to work with its Patient Guidance for State Regulations Regarding Reproductive Health Task Force to help dermatologists best navigate state laws about how care should be implemented for patients who are or might become pregnant, and have been exposed to teratogenic medications.”
The task force, working with the academy, is “in the process of developing resources to help members better assist patients and have a productive and caring dialogue with them,” according to the statement. No specific timeline was given for when those resources might be available.
Methotrexate prescriptions
Also of concern are prescriptions for methotrexate, which is prescribed for psoriasis, atopic dermatitis, and other skin diseases. Soon after the Dobbs decision was announced on June 24, pharmacies began to require pharmacists in states that banned abortions to verify that a prescription for methotrexate was not intended for an abortion, since methotrexate is used in combination with misoprostol for termination of an early pregnancy.
The action was taken, spokespersons for several major pharmacies said, to comply with state laws. According to Kara Page, a CVS spokesperson: “Pharmacists are caught in the middle on this issue.” Laws in some states, she told this news organization, “restrict the dispensing of medications for the purpose of inducing an abortion. These laws, some of which include criminal penalties, have forced us to require pharmacists in these states to validate that the intended indication is not to terminate a pregnancy before they can fill a prescription for methotrexate.”
“New laws in various states require additional steps for dispensing certain prescriptions and apply to all pharmacies, including Walgreens,” Fraser Engerman, a spokesperson for Walgreens, told this news organization. “In these states, our pharmacists work closely with prescribers as needed, to fill lawful, clinically appropriate prescriptions. We provide ongoing training and information to help our pharmacists understand the latest requirements in their area, and with these supports, the expectation is they are empowered to fill these prescriptions.”
The iPLEDGE program has numerous requirements before a patient can begin isotretinoin treatment. Patients capable of becoming pregnant must agree to use two effective forms of birth control during the entire treatment period, which typically lasts 4 or 5 months, as well as 1 month before and 1 month after treatment, or commit to total abstinence during that time.
Perspective: A Georgia dermatologist
Howa Yeung, MD, MSc, assistant professor of dermatology at Emory University, Atlanta, who sees patients regularly, practices in Georgia, where abortion is now banned at about 6 weeks of pregnancy. Dr. Yeung worries that some dermatologists in Georgia and elsewhere may not even want to take the risk of prescribing isotretinoin, although the results in treating resistant acne are well documented.
That isn’t his only concern. “Some may not want to prescribe it to a patient who reports they are abstinent and instead require them to go on two forms [of contraception].” Or some women who are not sexually active with anyone who can get them pregnant may also be asked to go on contraception, he said. Abstinence is an alternative option in iPLEDGE.
In the past, he said, well before the Dobbs decision, some doctors have argued that iPLEDGE should not include abstinence as an option. That 2020 report was challenged by others who pointed out that removing the abstinence option would pose ethical issues and may disproportionately affect minorities and others.
Before the Dobbs decision, Dr. Yeung noted, dermatologists prescribing isotretinoin focused on pregnancy prevention but knew that if pregnancy accidentally occurred, abortion was available as an option. “The reality after the decision is, it may or may not be available to all our patients.”
Of the 14 states banning most abortions, 10 are clustered within the South and Southeast. A woman living in Arkansas, which bans most abortions, for example, is surrounded by 6 other states that do the same.
Perspective: An Arizona dermatologist
Christina Kranc, MD, is a general dermatologist in Phoenix and Scottsdale. Arizona now bans most abortions. However, this has not changed her practice much when prescribing isotretinoin, she told this news organization, because when selecting appropriate candidates for the medication, she is strict on the contraceptive requirement, and only very rarely agrees to a patient relying on abstinence.
And if a patient capable of becoming pregnant was only having sex with another patient capable of becoming pregnant? Dr. Kranc said she would still require contraception unless it was impossible for pregnancy to occur.
Among the many scenarios a dermatologist might have to consider are a lesbian cisgender woman who is having, or has only had, sexual activity with another cisgender women.
Perspective: A Connecticut dermatologist
The concern is not only about isotretinoin but all teratogenic drugs, according to Jane M. Grant-Kels, MD, vice chair of dermatology and professor of dermatology, pathology, and pediatrics at the University of Connecticut, Farmington. She often prescribes methotrexate, which is also teratogenic.
Her advice for colleagues: “Whether you believe in abortion or not is irrelevant; it’s something you discuss with your patients.” She, too, fears that doctors in states banning abortions will stop prescribing these medications, “and that is very sad.”
For those practicing in states limiting or banning abortions, Dr. Grant-Kels said, “They need to have an even longer discussion with their patients about how serious this is.” Those doctors need to talk about not only two or three types of birth control, but also discuss with the patient about the potential need for travel, should pregnancy occur and abortion be the chosen option.
Although the newer biologics are an option for psoriasis, they are expensive. And, she said, many insurers require a step-therapy approach, and “want you to start with cheaper medications,” such as methotrexate. As a result, “in some states you won’t have access to the targeted therapies unless a patient fails something like methotrexate.”
Dr. Grant-Kels worries in particular about low-income women who may not have the means to travel to get an abortion.
Need for EC education
In a recent survey of 57 pediatric dermatologists who prescribe isotretinoin, only a third said they felt confident in their understanding of emergency contraception.
The authors of the study noted that the most common reasons for pregnancies during isotretinoin therapy reported to the FDA from 2011 to 2017 “included ineffective or inconsistent use” of contraceptives and “unsuccessful abstinence,” and recommended that physicians who prescribe isotretinoin update and increase their understanding of emergency contraception.
Dr. Yeung, Dr. Kranc, Dr. Grant-Kels, and Dr. Frieden reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
More than 3 months after the Dobbs decision by the U.S. Supreme Court overturned Roe v. Wade and revoked the constitutional right to an abortion, Some have beefed up their already stringent instructions and lengthy conversations about avoiding pregnancy while on the medication.
The major fear is that a patient who is taking contraceptive precautions, in accordance with the isotretinoin risk-management program, iPLEDGE, but still becomes pregnant while on isotretinoin may find out about the pregnancy too late to undergo an abortion in her own state and may not be able to travel to another state – or the patient may live in a state where abortions are entirely prohibited and is unable to travel to another state.
Isotretinoin is marketed as Absorica, Absorica LD, Claravis, Amnesteem, Myorisan, and Zenatane; its former brand name was Accutane.
As of Oct. 7, a total of 14 states have banned most abortions, while 4 others have bans at 6, 15, 18, or 20 weeks. Attempts to restrict abortion on several other states are underway.
“To date, we don’t know of any specific effects of the Dobbs decision on isotretinoin prescribing, but with abortion access banned in many states, we anticipate that this could be a very real issue for individuals who accidentally become pregnant while taking isotretinoin,” said Ilona Frieden, MD, professor of dermatology and pediatrics at the University of California, San Francisco, and chair of the American Academy of Dermatology Association’s iPLEDGE Workgroup.
The iPLEDGE REMS (Risk Evaluation and Mitigation Strategy) is the Food and Drug Administration–required safety program that is in place to manage the risk of isotretinoin teratogenicity and minimize fetal exposure. The work group meets with the FDA and isotretinoin manufacturers to keep the program safe and operating smoothly. The iPLEDGE workgroup has not yet issued any specific statements on the implications of the Dobbs decision on prescribing isotretinoin.
But work on the issue is ongoing by the American Academy of Dermatology. In a statement issued in September, Mark D. Kaufmann, MD, president of the AAD, said that the academy “is continuing to work with its Patient Guidance for State Regulations Regarding Reproductive Health Task Force to help dermatologists best navigate state laws about how care should be implemented for patients who are or might become pregnant, and have been exposed to teratogenic medications.”
The task force, working with the academy, is “in the process of developing resources to help members better assist patients and have a productive and caring dialogue with them,” according to the statement. No specific timeline was given for when those resources might be available.
Methotrexate prescriptions
Also of concern are prescriptions for methotrexate, which is prescribed for psoriasis, atopic dermatitis, and other skin diseases. Soon after the Dobbs decision was announced on June 24, pharmacies began to require pharmacists in states that banned abortions to verify that a prescription for methotrexate was not intended for an abortion, since methotrexate is used in combination with misoprostol for termination of an early pregnancy.
The action was taken, spokespersons for several major pharmacies said, to comply with state laws. According to Kara Page, a CVS spokesperson: “Pharmacists are caught in the middle on this issue.” Laws in some states, she told this news organization, “restrict the dispensing of medications for the purpose of inducing an abortion. These laws, some of which include criminal penalties, have forced us to require pharmacists in these states to validate that the intended indication is not to terminate a pregnancy before they can fill a prescription for methotrexate.”
“New laws in various states require additional steps for dispensing certain prescriptions and apply to all pharmacies, including Walgreens,” Fraser Engerman, a spokesperson for Walgreens, told this news organization. “In these states, our pharmacists work closely with prescribers as needed, to fill lawful, clinically appropriate prescriptions. We provide ongoing training and information to help our pharmacists understand the latest requirements in their area, and with these supports, the expectation is they are empowered to fill these prescriptions.”
The iPLEDGE program has numerous requirements before a patient can begin isotretinoin treatment. Patients capable of becoming pregnant must agree to use two effective forms of birth control during the entire treatment period, which typically lasts 4 or 5 months, as well as 1 month before and 1 month after treatment, or commit to total abstinence during that time.
Perspective: A Georgia dermatologist
Howa Yeung, MD, MSc, assistant professor of dermatology at Emory University, Atlanta, who sees patients regularly, practices in Georgia, where abortion is now banned at about 6 weeks of pregnancy. Dr. Yeung worries that some dermatologists in Georgia and elsewhere may not even want to take the risk of prescribing isotretinoin, although the results in treating resistant acne are well documented.
That isn’t his only concern. “Some may not want to prescribe it to a patient who reports they are abstinent and instead require them to go on two forms [of contraception].” Or some women who are not sexually active with anyone who can get them pregnant may also be asked to go on contraception, he said. Abstinence is an alternative option in iPLEDGE.
In the past, he said, well before the Dobbs decision, some doctors have argued that iPLEDGE should not include abstinence as an option. That 2020 report was challenged by others who pointed out that removing the abstinence option would pose ethical issues and may disproportionately affect minorities and others.
Before the Dobbs decision, Dr. Yeung noted, dermatologists prescribing isotretinoin focused on pregnancy prevention but knew that if pregnancy accidentally occurred, abortion was available as an option. “The reality after the decision is, it may or may not be available to all our patients.”
Of the 14 states banning most abortions, 10 are clustered within the South and Southeast. A woman living in Arkansas, which bans most abortions, for example, is surrounded by 6 other states that do the same.
Perspective: An Arizona dermatologist
Christina Kranc, MD, is a general dermatologist in Phoenix and Scottsdale. Arizona now bans most abortions. However, this has not changed her practice much when prescribing isotretinoin, she told this news organization, because when selecting appropriate candidates for the medication, she is strict on the contraceptive requirement, and only very rarely agrees to a patient relying on abstinence.
And if a patient capable of becoming pregnant was only having sex with another patient capable of becoming pregnant? Dr. Kranc said she would still require contraception unless it was impossible for pregnancy to occur.
Among the many scenarios a dermatologist might have to consider are a lesbian cisgender woman who is having, or has only had, sexual activity with another cisgender women.
Perspective: A Connecticut dermatologist
The concern is not only about isotretinoin but all teratogenic drugs, according to Jane M. Grant-Kels, MD, vice chair of dermatology and professor of dermatology, pathology, and pediatrics at the University of Connecticut, Farmington. She often prescribes methotrexate, which is also teratogenic.
Her advice for colleagues: “Whether you believe in abortion or not is irrelevant; it’s something you discuss with your patients.” She, too, fears that doctors in states banning abortions will stop prescribing these medications, “and that is very sad.”
For those practicing in states limiting or banning abortions, Dr. Grant-Kels said, “They need to have an even longer discussion with their patients about how serious this is.” Those doctors need to talk about not only two or three types of birth control, but also discuss with the patient about the potential need for travel, should pregnancy occur and abortion be the chosen option.
Although the newer biologics are an option for psoriasis, they are expensive. And, she said, many insurers require a step-therapy approach, and “want you to start with cheaper medications,” such as methotrexate. As a result, “in some states you won’t have access to the targeted therapies unless a patient fails something like methotrexate.”
Dr. Grant-Kels worries in particular about low-income women who may not have the means to travel to get an abortion.
Need for EC education
In a recent survey of 57 pediatric dermatologists who prescribe isotretinoin, only a third said they felt confident in their understanding of emergency contraception.
The authors of the study noted that the most common reasons for pregnancies during isotretinoin therapy reported to the FDA from 2011 to 2017 “included ineffective or inconsistent use” of contraceptives and “unsuccessful abstinence,” and recommended that physicians who prescribe isotretinoin update and increase their understanding of emergency contraception.
Dr. Yeung, Dr. Kranc, Dr. Grant-Kels, and Dr. Frieden reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
More than 3 months after the Dobbs decision by the U.S. Supreme Court overturned Roe v. Wade and revoked the constitutional right to an abortion, Some have beefed up their already stringent instructions and lengthy conversations about avoiding pregnancy while on the medication.
The major fear is that a patient who is taking contraceptive precautions, in accordance with the isotretinoin risk-management program, iPLEDGE, but still becomes pregnant while on isotretinoin may find out about the pregnancy too late to undergo an abortion in her own state and may not be able to travel to another state – or the patient may live in a state where abortions are entirely prohibited and is unable to travel to another state.
Isotretinoin is marketed as Absorica, Absorica LD, Claravis, Amnesteem, Myorisan, and Zenatane; its former brand name was Accutane.
As of Oct. 7, a total of 14 states have banned most abortions, while 4 others have bans at 6, 15, 18, or 20 weeks. Attempts to restrict abortion on several other states are underway.
“To date, we don’t know of any specific effects of the Dobbs decision on isotretinoin prescribing, but with abortion access banned in many states, we anticipate that this could be a very real issue for individuals who accidentally become pregnant while taking isotretinoin,” said Ilona Frieden, MD, professor of dermatology and pediatrics at the University of California, San Francisco, and chair of the American Academy of Dermatology Association’s iPLEDGE Workgroup.
The iPLEDGE REMS (Risk Evaluation and Mitigation Strategy) is the Food and Drug Administration–required safety program that is in place to manage the risk of isotretinoin teratogenicity and minimize fetal exposure. The work group meets with the FDA and isotretinoin manufacturers to keep the program safe and operating smoothly. The iPLEDGE workgroup has not yet issued any specific statements on the implications of the Dobbs decision on prescribing isotretinoin.
But work on the issue is ongoing by the American Academy of Dermatology. In a statement issued in September, Mark D. Kaufmann, MD, president of the AAD, said that the academy “is continuing to work with its Patient Guidance for State Regulations Regarding Reproductive Health Task Force to help dermatologists best navigate state laws about how care should be implemented for patients who are or might become pregnant, and have been exposed to teratogenic medications.”
The task force, working with the academy, is “in the process of developing resources to help members better assist patients and have a productive and caring dialogue with them,” according to the statement. No specific timeline was given for when those resources might be available.
Methotrexate prescriptions
Also of concern are prescriptions for methotrexate, which is prescribed for psoriasis, atopic dermatitis, and other skin diseases. Soon after the Dobbs decision was announced on June 24, pharmacies began to require pharmacists in states that banned abortions to verify that a prescription for methotrexate was not intended for an abortion, since methotrexate is used in combination with misoprostol for termination of an early pregnancy.
The action was taken, spokespersons for several major pharmacies said, to comply with state laws. According to Kara Page, a CVS spokesperson: “Pharmacists are caught in the middle on this issue.” Laws in some states, she told this news organization, “restrict the dispensing of medications for the purpose of inducing an abortion. These laws, some of which include criminal penalties, have forced us to require pharmacists in these states to validate that the intended indication is not to terminate a pregnancy before they can fill a prescription for methotrexate.”
“New laws in various states require additional steps for dispensing certain prescriptions and apply to all pharmacies, including Walgreens,” Fraser Engerman, a spokesperson for Walgreens, told this news organization. “In these states, our pharmacists work closely with prescribers as needed, to fill lawful, clinically appropriate prescriptions. We provide ongoing training and information to help our pharmacists understand the latest requirements in their area, and with these supports, the expectation is they are empowered to fill these prescriptions.”
The iPLEDGE program has numerous requirements before a patient can begin isotretinoin treatment. Patients capable of becoming pregnant must agree to use two effective forms of birth control during the entire treatment period, which typically lasts 4 or 5 months, as well as 1 month before and 1 month after treatment, or commit to total abstinence during that time.
Perspective: A Georgia dermatologist
Howa Yeung, MD, MSc, assistant professor of dermatology at Emory University, Atlanta, who sees patients regularly, practices in Georgia, where abortion is now banned at about 6 weeks of pregnancy. Dr. Yeung worries that some dermatologists in Georgia and elsewhere may not even want to take the risk of prescribing isotretinoin, although the results in treating resistant acne are well documented.
That isn’t his only concern. “Some may not want to prescribe it to a patient who reports they are abstinent and instead require them to go on two forms [of contraception].” Or some women who are not sexually active with anyone who can get them pregnant may also be asked to go on contraception, he said. Abstinence is an alternative option in iPLEDGE.
In the past, he said, well before the Dobbs decision, some doctors have argued that iPLEDGE should not include abstinence as an option. That 2020 report was challenged by others who pointed out that removing the abstinence option would pose ethical issues and may disproportionately affect minorities and others.
Before the Dobbs decision, Dr. Yeung noted, dermatologists prescribing isotretinoin focused on pregnancy prevention but knew that if pregnancy accidentally occurred, abortion was available as an option. “The reality after the decision is, it may or may not be available to all our patients.”
Of the 14 states banning most abortions, 10 are clustered within the South and Southeast. A woman living in Arkansas, which bans most abortions, for example, is surrounded by 6 other states that do the same.
Perspective: An Arizona dermatologist
Christina Kranc, MD, is a general dermatologist in Phoenix and Scottsdale. Arizona now bans most abortions. However, this has not changed her practice much when prescribing isotretinoin, she told this news organization, because when selecting appropriate candidates for the medication, she is strict on the contraceptive requirement, and only very rarely agrees to a patient relying on abstinence.
And if a patient capable of becoming pregnant was only having sex with another patient capable of becoming pregnant? Dr. Kranc said she would still require contraception unless it was impossible for pregnancy to occur.
Among the many scenarios a dermatologist might have to consider are a lesbian cisgender woman who is having, or has only had, sexual activity with another cisgender women.
Perspective: A Connecticut dermatologist
The concern is not only about isotretinoin but all teratogenic drugs, according to Jane M. Grant-Kels, MD, vice chair of dermatology and professor of dermatology, pathology, and pediatrics at the University of Connecticut, Farmington. She often prescribes methotrexate, which is also teratogenic.
Her advice for colleagues: “Whether you believe in abortion or not is irrelevant; it’s something you discuss with your patients.” She, too, fears that doctors in states banning abortions will stop prescribing these medications, “and that is very sad.”
For those practicing in states limiting or banning abortions, Dr. Grant-Kels said, “They need to have an even longer discussion with their patients about how serious this is.” Those doctors need to talk about not only two or three types of birth control, but also discuss with the patient about the potential need for travel, should pregnancy occur and abortion be the chosen option.
Although the newer biologics are an option for psoriasis, they are expensive. And, she said, many insurers require a step-therapy approach, and “want you to start with cheaper medications,” such as methotrexate. As a result, “in some states you won’t have access to the targeted therapies unless a patient fails something like methotrexate.”
Dr. Grant-Kels worries in particular about low-income women who may not have the means to travel to get an abortion.
Need for EC education
In a recent survey of 57 pediatric dermatologists who prescribe isotretinoin, only a third said they felt confident in their understanding of emergency contraception.
The authors of the study noted that the most common reasons for pregnancies during isotretinoin therapy reported to the FDA from 2011 to 2017 “included ineffective or inconsistent use” of contraceptives and “unsuccessful abstinence,” and recommended that physicians who prescribe isotretinoin update and increase their understanding of emergency contraception.
Dr. Yeung, Dr. Kranc, Dr. Grant-Kels, and Dr. Frieden reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.