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Roflumilast side effect benefits patients with psoriasis and overweight/obesity
BERLIN – .
Reporting secondary outcomes from the investigator-led trial at the annual congress of the European Academy of Dermatology and Venereology, Alexander Egeberg, MD, PhD, DMSc, noted that “clinically significant weight loss” was seen among patients who were treated with oral roflumilast, 500 mcg once daily, versus those receiving placebo.
Indeed, after 12 weeks of therapy, one in three patients treated with oral roflumilast experienced at least a 5% drop in their baseline body weight vs no patients who received placebo (35% vs. 0%; P < .05).
Additionally, a respective 17% versus 0% of patients lost 10% or more of their body weight, and 4% versus 0% lost 15% or more of their baseline body weight at 12 weeks.
After 24 weeks’ treatment, a substantial percentage of patients still had greater than or equal to 5%, greater than or equal to 10%, or greater than or equal to 15% weight loss, at 30%, 17%, and 13% for oral roflumilast, compared with 9%, 0%, and 0% for placebo, respectively.
“We saw that the higher baseline weight correlated with the proportion of weight loss, so that the more heavy patients at baseline also were the ones who experienced the greatest weight loss,” said Dr. Egeberg, who is professor of dermatology at the University of Copenhagen and a senior consultant at the department of dermatology at Bispebjerg Hospital, Copenhagen.
A beneficial side effect in psoriasis?
“You may have heard in psoriasis about topical roflumilast, but oral roflumilast is actually also shown to be effective in treating psoriasis,” said Egeberg.
Topical roflumilast is approved in the United States and Canada for treating plaque psoriasis.
Efficacy results from the PSORRO study were published earlier this year and showed a significantly greater improvement in Psoriasis Area and Severity Index (PASI) 75 with oral roflumilast vs. placebo at 12 weeks (35% vs. 0%), with a sustained effect seen at 24 weeks (44% vs. 40%).
Weight loss was among the most common side effects seen, leading Dr. Egeberg and fellow PSORRO investigators to wonder whether this may actually be a beneficial effect in patients with psoriasis.
“Oral roflumilast is actually a drug that has been on the market for quite a number of years,” Dr. Egeberg said.
Although only currently licensed for chronic obstructive pulmonary disease (COPD) in the United States, oral roflumilast, a phosphodiesterase (PDE) 4 inhibitor, is available as a generic, “which also means that it is extremely affordable,” suggested Dr. Edeberg.
Weight loss may be a problem in patients with COPD, he acknowledged; these patients tend to be underweight as a result of their poor state of health caused by the lung condition. Weight loss could be an advantage in patients with psoriasis who are overweight or living with obesity and have poor cardiometabolic parameters.
The psoriasis treatment with oral roflumilast study
The PSORRO study was a phase 2, multicenter, placebo-controlled, randomized trial performed between 2021 and 2022. A total of 46 adults with plaque psoriasis participated; half were initially treated with oral roflumilast and half with placebo.
Treatment was double-blind for the first 12 weeks, with all patients then receiving open-label treatment with roflumilast for 12 weeks.
The primary endpoint was the proportion of patients achieving at least 75% reduction from baseline PASI (PASI75). A host of secondary endpoints were studied, including weight and cardiometabolic parameters, which Dr. Egeberg reported at the EADV meeting.
Looking at the baseline characteristics of the oral roflumilast and placebo groups, the mean age was a respective 38 and 39 years, 65% and 83% were men, and the mean starting body weight was 102 kg and 105.1 kg.
After 12 weeks of treatment, body weight fell by a mean of 5.4 kg in the oral roflumilast group, with a further decrease of 1.4 kg by 24 weeks, bringing the total average weight loss to 6.8 kg. By comparison, weight loss among those in the placebo group was 0 kg at 12 weeks and around 2 kg at 24 weeks.
The majority of participants in both groups had high baseline BMIs; 70% of those who received oral roflumilast and 61% of those who received placebo had a BMI of 30 or higher.
“We wanted to investigate the impact of body weight, [so] we didn’t allow patients to be underweight when they were included,” Dr. Egeberg explained. Thus, for inclusion, patients had to have a BMI of 20 or higher.
An “extraordinary” finding was how some patients’ weight status based on their BMI changed throughout the study.
“We could see people that went from obese class 3, all the way to obese class 1. And we could see people going from being overweight to normal weight, which is really extraordinary for patients with psoriasis,” Dr. Egeberg said.
“But most importantly,” he added, “we didn’t have any patients who became underweight, suggesting that it actually is safe to use also in normal-weight patients.”
Reduced appetite behind benefit?
Trying to see why the weight loss occurred, Dr. Egeberg noted that it looked like it could be a result of a reduced appetite.
In common with other PDE-4 inhibitors, oral roflumilast treatment was associated with gastrointestinal symptoms – nausea, diarrhea, and abdominal pain – but all of these “decrease to placebo levels again, quite quickly,” he said.
“This really suggests that it’s not because of diarrhea, it’s not because of nausea and abdominal pain; it is because of a reduced appetite that patients actually lose weight when treated with roflumilast,” Dr. Egeberg said. It’s a potential bonus for the drug’s effects on the skin and could afford clinicians an opportunity to help motivate patients to eat well when they do eat, he observed.
Other cardiometabolic parameters assessed included blood pressure, glycated hemoglobin, total cholesterol and other key lipids, creatinine, alanine aminotransferase, and high-sensitivity C-reactive protein, but there were no noteworthy differences between the groups.
Roflumilast is an inexpensive drug because it is generic, Dr. Egeberg observed, but that also means that its use is likely to be off-label.
“It will be up to the treating physician to decide if this is an optimal therapy for their patients,” he suggested.
Cardiometabolic comorbidities important to target
Obesity is a cardiometabolic comorbidity that is important to consider when treating your patients with psoriasis, Paolo Gisondi, MD, of the University of Verona (Italy), said at a separate presentation at the EADV meeting.
While not directly commenting on the roflumilast study, he noted that moderate to severe psoriasis was “frequently associated” with metabolic disorders that put people at additional risk for cardiovascular and fatty liver diseases.
The PSORRO study was an investigator-initiated and investigator-led study and received no commercial funding. Research funding came from the Danish Psoriasis Foundation, Herlev and Gentofte Hospital, and several charitable and humanitarian organizations. Dr. Egeberg acknowledged acting as the principal investigator, speaker, and/or consultant to multiple pharma companies, all of which were unrelated to the study he presented. Dr. Gisondi’s comments were from a separate presentation, and he was not involved in the study.
A version of this article first appeared on Medscape.com.
BERLIN – .
Reporting secondary outcomes from the investigator-led trial at the annual congress of the European Academy of Dermatology and Venereology, Alexander Egeberg, MD, PhD, DMSc, noted that “clinically significant weight loss” was seen among patients who were treated with oral roflumilast, 500 mcg once daily, versus those receiving placebo.
Indeed, after 12 weeks of therapy, one in three patients treated with oral roflumilast experienced at least a 5% drop in their baseline body weight vs no patients who received placebo (35% vs. 0%; P < .05).
Additionally, a respective 17% versus 0% of patients lost 10% or more of their body weight, and 4% versus 0% lost 15% or more of their baseline body weight at 12 weeks.
After 24 weeks’ treatment, a substantial percentage of patients still had greater than or equal to 5%, greater than or equal to 10%, or greater than or equal to 15% weight loss, at 30%, 17%, and 13% for oral roflumilast, compared with 9%, 0%, and 0% for placebo, respectively.
“We saw that the higher baseline weight correlated with the proportion of weight loss, so that the more heavy patients at baseline also were the ones who experienced the greatest weight loss,” said Dr. Egeberg, who is professor of dermatology at the University of Copenhagen and a senior consultant at the department of dermatology at Bispebjerg Hospital, Copenhagen.
A beneficial side effect in psoriasis?
“You may have heard in psoriasis about topical roflumilast, but oral roflumilast is actually also shown to be effective in treating psoriasis,” said Egeberg.
Topical roflumilast is approved in the United States and Canada for treating plaque psoriasis.
Efficacy results from the PSORRO study were published earlier this year and showed a significantly greater improvement in Psoriasis Area and Severity Index (PASI) 75 with oral roflumilast vs. placebo at 12 weeks (35% vs. 0%), with a sustained effect seen at 24 weeks (44% vs. 40%).
Weight loss was among the most common side effects seen, leading Dr. Egeberg and fellow PSORRO investigators to wonder whether this may actually be a beneficial effect in patients with psoriasis.
“Oral roflumilast is actually a drug that has been on the market for quite a number of years,” Dr. Egeberg said.
Although only currently licensed for chronic obstructive pulmonary disease (COPD) in the United States, oral roflumilast, a phosphodiesterase (PDE) 4 inhibitor, is available as a generic, “which also means that it is extremely affordable,” suggested Dr. Edeberg.
Weight loss may be a problem in patients with COPD, he acknowledged; these patients tend to be underweight as a result of their poor state of health caused by the lung condition. Weight loss could be an advantage in patients with psoriasis who are overweight or living with obesity and have poor cardiometabolic parameters.
The psoriasis treatment with oral roflumilast study
The PSORRO study was a phase 2, multicenter, placebo-controlled, randomized trial performed between 2021 and 2022. A total of 46 adults with plaque psoriasis participated; half were initially treated with oral roflumilast and half with placebo.
Treatment was double-blind for the first 12 weeks, with all patients then receiving open-label treatment with roflumilast for 12 weeks.
The primary endpoint was the proportion of patients achieving at least 75% reduction from baseline PASI (PASI75). A host of secondary endpoints were studied, including weight and cardiometabolic parameters, which Dr. Egeberg reported at the EADV meeting.
Looking at the baseline characteristics of the oral roflumilast and placebo groups, the mean age was a respective 38 and 39 years, 65% and 83% were men, and the mean starting body weight was 102 kg and 105.1 kg.
After 12 weeks of treatment, body weight fell by a mean of 5.4 kg in the oral roflumilast group, with a further decrease of 1.4 kg by 24 weeks, bringing the total average weight loss to 6.8 kg. By comparison, weight loss among those in the placebo group was 0 kg at 12 weeks and around 2 kg at 24 weeks.
The majority of participants in both groups had high baseline BMIs; 70% of those who received oral roflumilast and 61% of those who received placebo had a BMI of 30 or higher.
“We wanted to investigate the impact of body weight, [so] we didn’t allow patients to be underweight when they were included,” Dr. Egeberg explained. Thus, for inclusion, patients had to have a BMI of 20 or higher.
An “extraordinary” finding was how some patients’ weight status based on their BMI changed throughout the study.
“We could see people that went from obese class 3, all the way to obese class 1. And we could see people going from being overweight to normal weight, which is really extraordinary for patients with psoriasis,” Dr. Egeberg said.
“But most importantly,” he added, “we didn’t have any patients who became underweight, suggesting that it actually is safe to use also in normal-weight patients.”
Reduced appetite behind benefit?
Trying to see why the weight loss occurred, Dr. Egeberg noted that it looked like it could be a result of a reduced appetite.
In common with other PDE-4 inhibitors, oral roflumilast treatment was associated with gastrointestinal symptoms – nausea, diarrhea, and abdominal pain – but all of these “decrease to placebo levels again, quite quickly,” he said.
“This really suggests that it’s not because of diarrhea, it’s not because of nausea and abdominal pain; it is because of a reduced appetite that patients actually lose weight when treated with roflumilast,” Dr. Egeberg said. It’s a potential bonus for the drug’s effects on the skin and could afford clinicians an opportunity to help motivate patients to eat well when they do eat, he observed.
Other cardiometabolic parameters assessed included blood pressure, glycated hemoglobin, total cholesterol and other key lipids, creatinine, alanine aminotransferase, and high-sensitivity C-reactive protein, but there were no noteworthy differences between the groups.
Roflumilast is an inexpensive drug because it is generic, Dr. Egeberg observed, but that also means that its use is likely to be off-label.
“It will be up to the treating physician to decide if this is an optimal therapy for their patients,” he suggested.
Cardiometabolic comorbidities important to target
Obesity is a cardiometabolic comorbidity that is important to consider when treating your patients with psoriasis, Paolo Gisondi, MD, of the University of Verona (Italy), said at a separate presentation at the EADV meeting.
While not directly commenting on the roflumilast study, he noted that moderate to severe psoriasis was “frequently associated” with metabolic disorders that put people at additional risk for cardiovascular and fatty liver diseases.
The PSORRO study was an investigator-initiated and investigator-led study and received no commercial funding. Research funding came from the Danish Psoriasis Foundation, Herlev and Gentofte Hospital, and several charitable and humanitarian organizations. Dr. Egeberg acknowledged acting as the principal investigator, speaker, and/or consultant to multiple pharma companies, all of which were unrelated to the study he presented. Dr. Gisondi’s comments were from a separate presentation, and he was not involved in the study.
A version of this article first appeared on Medscape.com.
BERLIN – .
Reporting secondary outcomes from the investigator-led trial at the annual congress of the European Academy of Dermatology and Venereology, Alexander Egeberg, MD, PhD, DMSc, noted that “clinically significant weight loss” was seen among patients who were treated with oral roflumilast, 500 mcg once daily, versus those receiving placebo.
Indeed, after 12 weeks of therapy, one in three patients treated with oral roflumilast experienced at least a 5% drop in their baseline body weight vs no patients who received placebo (35% vs. 0%; P < .05).
Additionally, a respective 17% versus 0% of patients lost 10% or more of their body weight, and 4% versus 0% lost 15% or more of their baseline body weight at 12 weeks.
After 24 weeks’ treatment, a substantial percentage of patients still had greater than or equal to 5%, greater than or equal to 10%, or greater than or equal to 15% weight loss, at 30%, 17%, and 13% for oral roflumilast, compared with 9%, 0%, and 0% for placebo, respectively.
“We saw that the higher baseline weight correlated with the proportion of weight loss, so that the more heavy patients at baseline also were the ones who experienced the greatest weight loss,” said Dr. Egeberg, who is professor of dermatology at the University of Copenhagen and a senior consultant at the department of dermatology at Bispebjerg Hospital, Copenhagen.
A beneficial side effect in psoriasis?
“You may have heard in psoriasis about topical roflumilast, but oral roflumilast is actually also shown to be effective in treating psoriasis,” said Egeberg.
Topical roflumilast is approved in the United States and Canada for treating plaque psoriasis.
Efficacy results from the PSORRO study were published earlier this year and showed a significantly greater improvement in Psoriasis Area and Severity Index (PASI) 75 with oral roflumilast vs. placebo at 12 weeks (35% vs. 0%), with a sustained effect seen at 24 weeks (44% vs. 40%).
Weight loss was among the most common side effects seen, leading Dr. Egeberg and fellow PSORRO investigators to wonder whether this may actually be a beneficial effect in patients with psoriasis.
“Oral roflumilast is actually a drug that has been on the market for quite a number of years,” Dr. Egeberg said.
Although only currently licensed for chronic obstructive pulmonary disease (COPD) in the United States, oral roflumilast, a phosphodiesterase (PDE) 4 inhibitor, is available as a generic, “which also means that it is extremely affordable,” suggested Dr. Edeberg.
Weight loss may be a problem in patients with COPD, he acknowledged; these patients tend to be underweight as a result of their poor state of health caused by the lung condition. Weight loss could be an advantage in patients with psoriasis who are overweight or living with obesity and have poor cardiometabolic parameters.
The psoriasis treatment with oral roflumilast study
The PSORRO study was a phase 2, multicenter, placebo-controlled, randomized trial performed between 2021 and 2022. A total of 46 adults with plaque psoriasis participated; half were initially treated with oral roflumilast and half with placebo.
Treatment was double-blind for the first 12 weeks, with all patients then receiving open-label treatment with roflumilast for 12 weeks.
The primary endpoint was the proportion of patients achieving at least 75% reduction from baseline PASI (PASI75). A host of secondary endpoints were studied, including weight and cardiometabolic parameters, which Dr. Egeberg reported at the EADV meeting.
Looking at the baseline characteristics of the oral roflumilast and placebo groups, the mean age was a respective 38 and 39 years, 65% and 83% were men, and the mean starting body weight was 102 kg and 105.1 kg.
After 12 weeks of treatment, body weight fell by a mean of 5.4 kg in the oral roflumilast group, with a further decrease of 1.4 kg by 24 weeks, bringing the total average weight loss to 6.8 kg. By comparison, weight loss among those in the placebo group was 0 kg at 12 weeks and around 2 kg at 24 weeks.
The majority of participants in both groups had high baseline BMIs; 70% of those who received oral roflumilast and 61% of those who received placebo had a BMI of 30 or higher.
“We wanted to investigate the impact of body weight, [so] we didn’t allow patients to be underweight when they were included,” Dr. Egeberg explained. Thus, for inclusion, patients had to have a BMI of 20 or higher.
An “extraordinary” finding was how some patients’ weight status based on their BMI changed throughout the study.
“We could see people that went from obese class 3, all the way to obese class 1. And we could see people going from being overweight to normal weight, which is really extraordinary for patients with psoriasis,” Dr. Egeberg said.
“But most importantly,” he added, “we didn’t have any patients who became underweight, suggesting that it actually is safe to use also in normal-weight patients.”
Reduced appetite behind benefit?
Trying to see why the weight loss occurred, Dr. Egeberg noted that it looked like it could be a result of a reduced appetite.
In common with other PDE-4 inhibitors, oral roflumilast treatment was associated with gastrointestinal symptoms – nausea, diarrhea, and abdominal pain – but all of these “decrease to placebo levels again, quite quickly,” he said.
“This really suggests that it’s not because of diarrhea, it’s not because of nausea and abdominal pain; it is because of a reduced appetite that patients actually lose weight when treated with roflumilast,” Dr. Egeberg said. It’s a potential bonus for the drug’s effects on the skin and could afford clinicians an opportunity to help motivate patients to eat well when they do eat, he observed.
Other cardiometabolic parameters assessed included blood pressure, glycated hemoglobin, total cholesterol and other key lipids, creatinine, alanine aminotransferase, and high-sensitivity C-reactive protein, but there were no noteworthy differences between the groups.
Roflumilast is an inexpensive drug because it is generic, Dr. Egeberg observed, but that also means that its use is likely to be off-label.
“It will be up to the treating physician to decide if this is an optimal therapy for their patients,” he suggested.
Cardiometabolic comorbidities important to target
Obesity is a cardiometabolic comorbidity that is important to consider when treating your patients with psoriasis, Paolo Gisondi, MD, of the University of Verona (Italy), said at a separate presentation at the EADV meeting.
While not directly commenting on the roflumilast study, he noted that moderate to severe psoriasis was “frequently associated” with metabolic disorders that put people at additional risk for cardiovascular and fatty liver diseases.
The PSORRO study was an investigator-initiated and investigator-led study and received no commercial funding. Research funding came from the Danish Psoriasis Foundation, Herlev and Gentofte Hospital, and several charitable and humanitarian organizations. Dr. Egeberg acknowledged acting as the principal investigator, speaker, and/or consultant to multiple pharma companies, all of which were unrelated to the study he presented. Dr. Gisondi’s comments were from a separate presentation, and he was not involved in the study.
A version of this article first appeared on Medscape.com.
AT THE EADV CONGRESS
Novel triple-threat approach to acne beats placebo
TOPLINE:
A topical fixed-dose combination of three approved acne treatments significantly improves moderate to severe acne with a strong safety profile.
METHODOLOGY:
- The two multicenter studies included 363 individuals aged 9 years and older with moderate to severe acne from 30 centers, including 15 in North America.
- Moderate to severe acne was defined as having 30-100 inflammatory lesions (papules, pustules, or nodules), 35-150 noninflammatory lesions (open or closed comedones), and at least two nodules.
- Participants were randomly assigned to receive treatment with a combination gel containing phosphate 1.2%, 0.15%, and 3.1% (known as IDP-126) or a vehicle gel for once-daily application for 12 weeks.
- Treatment success was defined as a reduction of at least two grades from baseline on the Evaluator’s Global Severity Score (EGSS) and lesion counts of clear (0) or almost clear (1) at weeks 2, 4, 8, and 12.
TAKEAWAY:
- Treatment success occurred in 49.6% of the IDP-126 group, vs 24.9% of the vehicle group in study 1, and in 50.5% of the IDP-126 group, vs 20.5% of the vehicle group in study 2. Overall treatment compliance was 93.7% and 91.3% for studies 1 and 2, respectively (P < .01 for both).
- Patients in the IDP-126 groups for both studies 1 and 2 had significantly greater absolute mean reductions in both inflammatory and noninflammatory lesions from baseline to week 12 compared to the vehicle patients (P ≤ .001 for all).
- Significantly more patients in the IDP-126 group achieved a grade reduction of 2 or more in EGSS compared with those who received the vehicle, with treatment differences of approximately 32% in both studies. Changes in lesion reductions between the treatment and the vehicle groups were significantly greater as early as week 4.
- The most common treatment-related adverse events among patients treated with IDP-126 were erythema, application-site pain, dryness, irritation, and exfoliation. Discontinuation of the study drug as a result of adverse events occurred in 2.5% and 3.3% of these patients in studies 1 and 2, respectively.
IN PRACTICE:
“With its simple treatment regimen containing 3 recommended acne treatments (benzoyl peroxide, a topical retinoid, and a topical antibiotic), IDP-126 is a potential new treatment option for acne,” the researchers concluded.
SOURCE:
The study was led by Linda Stein Gold, MD, of Henry Ford Hospital, Detroit. The study was published online in the Journal of the American Academy of Dermatology.
LIMITATIONS:
In both studies, treatment duration was short, and the studies may not reflect patients’ real-world experiences. The results may be affected by interobserver bias or variation in assessment of acne severity.
DISCLOSURES:
Gold has served as investigator/consultant or speaker for Ortho Dermatologics, LEO Pharma, Dermavant, Incyte, Novartis, AbbVie, Pfizer, Sun Pharma, UCB, Arcutis, and Lilly. Other study coauthors have relationships with multiple companies, including Ortho Dermatologics, which provided medical writing support for the study.
A version of this article first appeared on Medscape.com.
TOPLINE:
A topical fixed-dose combination of three approved acne treatments significantly improves moderate to severe acne with a strong safety profile.
METHODOLOGY:
- The two multicenter studies included 363 individuals aged 9 years and older with moderate to severe acne from 30 centers, including 15 in North America.
- Moderate to severe acne was defined as having 30-100 inflammatory lesions (papules, pustules, or nodules), 35-150 noninflammatory lesions (open or closed comedones), and at least two nodules.
- Participants were randomly assigned to receive treatment with a combination gel containing phosphate 1.2%, 0.15%, and 3.1% (known as IDP-126) or a vehicle gel for once-daily application for 12 weeks.
- Treatment success was defined as a reduction of at least two grades from baseline on the Evaluator’s Global Severity Score (EGSS) and lesion counts of clear (0) or almost clear (1) at weeks 2, 4, 8, and 12.
TAKEAWAY:
- Treatment success occurred in 49.6% of the IDP-126 group, vs 24.9% of the vehicle group in study 1, and in 50.5% of the IDP-126 group, vs 20.5% of the vehicle group in study 2. Overall treatment compliance was 93.7% and 91.3% for studies 1 and 2, respectively (P < .01 for both).
- Patients in the IDP-126 groups for both studies 1 and 2 had significantly greater absolute mean reductions in both inflammatory and noninflammatory lesions from baseline to week 12 compared to the vehicle patients (P ≤ .001 for all).
- Significantly more patients in the IDP-126 group achieved a grade reduction of 2 or more in EGSS compared with those who received the vehicle, with treatment differences of approximately 32% in both studies. Changes in lesion reductions between the treatment and the vehicle groups were significantly greater as early as week 4.
- The most common treatment-related adverse events among patients treated with IDP-126 were erythema, application-site pain, dryness, irritation, and exfoliation. Discontinuation of the study drug as a result of adverse events occurred in 2.5% and 3.3% of these patients in studies 1 and 2, respectively.
IN PRACTICE:
“With its simple treatment regimen containing 3 recommended acne treatments (benzoyl peroxide, a topical retinoid, and a topical antibiotic), IDP-126 is a potential new treatment option for acne,” the researchers concluded.
SOURCE:
The study was led by Linda Stein Gold, MD, of Henry Ford Hospital, Detroit. The study was published online in the Journal of the American Academy of Dermatology.
LIMITATIONS:
In both studies, treatment duration was short, and the studies may not reflect patients’ real-world experiences. The results may be affected by interobserver bias or variation in assessment of acne severity.
DISCLOSURES:
Gold has served as investigator/consultant or speaker for Ortho Dermatologics, LEO Pharma, Dermavant, Incyte, Novartis, AbbVie, Pfizer, Sun Pharma, UCB, Arcutis, and Lilly. Other study coauthors have relationships with multiple companies, including Ortho Dermatologics, which provided medical writing support for the study.
A version of this article first appeared on Medscape.com.
TOPLINE:
A topical fixed-dose combination of three approved acne treatments significantly improves moderate to severe acne with a strong safety profile.
METHODOLOGY:
- The two multicenter studies included 363 individuals aged 9 years and older with moderate to severe acne from 30 centers, including 15 in North America.
- Moderate to severe acne was defined as having 30-100 inflammatory lesions (papules, pustules, or nodules), 35-150 noninflammatory lesions (open or closed comedones), and at least two nodules.
- Participants were randomly assigned to receive treatment with a combination gel containing phosphate 1.2%, 0.15%, and 3.1% (known as IDP-126) or a vehicle gel for once-daily application for 12 weeks.
- Treatment success was defined as a reduction of at least two grades from baseline on the Evaluator’s Global Severity Score (EGSS) and lesion counts of clear (0) or almost clear (1) at weeks 2, 4, 8, and 12.
TAKEAWAY:
- Treatment success occurred in 49.6% of the IDP-126 group, vs 24.9% of the vehicle group in study 1, and in 50.5% of the IDP-126 group, vs 20.5% of the vehicle group in study 2. Overall treatment compliance was 93.7% and 91.3% for studies 1 and 2, respectively (P < .01 for both).
- Patients in the IDP-126 groups for both studies 1 and 2 had significantly greater absolute mean reductions in both inflammatory and noninflammatory lesions from baseline to week 12 compared to the vehicle patients (P ≤ .001 for all).
- Significantly more patients in the IDP-126 group achieved a grade reduction of 2 or more in EGSS compared with those who received the vehicle, with treatment differences of approximately 32% in both studies. Changes in lesion reductions between the treatment and the vehicle groups were significantly greater as early as week 4.
- The most common treatment-related adverse events among patients treated with IDP-126 were erythema, application-site pain, dryness, irritation, and exfoliation. Discontinuation of the study drug as a result of adverse events occurred in 2.5% and 3.3% of these patients in studies 1 and 2, respectively.
IN PRACTICE:
“With its simple treatment regimen containing 3 recommended acne treatments (benzoyl peroxide, a topical retinoid, and a topical antibiotic), IDP-126 is a potential new treatment option for acne,” the researchers concluded.
SOURCE:
The study was led by Linda Stein Gold, MD, of Henry Ford Hospital, Detroit. The study was published online in the Journal of the American Academy of Dermatology.
LIMITATIONS:
In both studies, treatment duration was short, and the studies may not reflect patients’ real-world experiences. The results may be affected by interobserver bias or variation in assessment of acne severity.
DISCLOSURES:
Gold has served as investigator/consultant or speaker for Ortho Dermatologics, LEO Pharma, Dermavant, Incyte, Novartis, AbbVie, Pfizer, Sun Pharma, UCB, Arcutis, and Lilly. Other study coauthors have relationships with multiple companies, including Ortho Dermatologics, which provided medical writing support for the study.
A version of this article first appeared on Medscape.com.
FDA approves new drug for ulcerative colitis
Pfizer announced on Oct. 13.
Etrasimod is an oral sphingosine-1-phosphate (S1P) receptor that binds with high affinity to receptors 1, 4, and 5. The approved recommended dose is 2 mg once daily.
Etrasimod is the second agent in the S1P class approved for UC in the United States. The other agent, ozanimod (Zeposia, Bristol-Myers Squibb), received FDA approval for moderately to severely active UC in May 2021.
The approval of etrasimod was based on safety and efficacy data from two randomized, double-blind, placebo-controlled phase 3 trials: ELEVATE UC 52 trial and the ELEVATE UC 12 trial. The Lancet published full results from the two trials in March.
Both trials enrolled patients with UC who had previously failed or were intolerant of at least one conventional, biologic, or Janus kinase inhibitor therapy.
In ELEVATE UC 52, clinical remission at 12 weeks occurred in 27% of patients taking etrasimod versus 7% of patients taking a placebo (20% difference; P < .001). At week 52, remission rates were 32% with active treatment verus 7% with placebo (26% difference; P < .001).
In ELEVATE UC 12, clinical remission was achieved among 26% of patients who received etrasimod versus 15.0% of patients who received placebo (11% difference; P < .05).
Statistically significant improvements were also observed with etrasimod (vs. placebo) on all key secondary endpoints, including endoscopic improvement and mucosal healing at weeks 12 and 52, and corticosteroid-free remission and sustained clinical remission at week 52.
The most common side effects of etrasimod were found to be headache, elevated values on liver tests, worsening of UC, SARS-CoV-2 infection, dizziness, pyrexia, arthralgia, abdominal pain, and nausea. Full prescribing information is available online.
Etrasimod is “a proven advanced treatment with a favorable benefit-risk profile,” Michael Chiorean, MD, codirector of the IBD Center at Swedish Medical Center, Seattle, who is an investigator in the ELEVATE studies, said in a Pfizer news release.
“UC can affect patients differently and many people living with this disease struggle with ongoing symptoms. The introduction of a new treatment for UC could increase options for patients, and we look forward to seeing the impact of Velsipity for patients across the U.S.,” added Michael Osso, president and CEO of the Crohn’s & Colitis Foundation.
A version of this article first appeared on Medscape.com.
Pfizer announced on Oct. 13.
Etrasimod is an oral sphingosine-1-phosphate (S1P) receptor that binds with high affinity to receptors 1, 4, and 5. The approved recommended dose is 2 mg once daily.
Etrasimod is the second agent in the S1P class approved for UC in the United States. The other agent, ozanimod (Zeposia, Bristol-Myers Squibb), received FDA approval for moderately to severely active UC in May 2021.
The approval of etrasimod was based on safety and efficacy data from two randomized, double-blind, placebo-controlled phase 3 trials: ELEVATE UC 52 trial and the ELEVATE UC 12 trial. The Lancet published full results from the two trials in March.
Both trials enrolled patients with UC who had previously failed or were intolerant of at least one conventional, biologic, or Janus kinase inhibitor therapy.
In ELEVATE UC 52, clinical remission at 12 weeks occurred in 27% of patients taking etrasimod versus 7% of patients taking a placebo (20% difference; P < .001). At week 52, remission rates were 32% with active treatment verus 7% with placebo (26% difference; P < .001).
In ELEVATE UC 12, clinical remission was achieved among 26% of patients who received etrasimod versus 15.0% of patients who received placebo (11% difference; P < .05).
Statistically significant improvements were also observed with etrasimod (vs. placebo) on all key secondary endpoints, including endoscopic improvement and mucosal healing at weeks 12 and 52, and corticosteroid-free remission and sustained clinical remission at week 52.
The most common side effects of etrasimod were found to be headache, elevated values on liver tests, worsening of UC, SARS-CoV-2 infection, dizziness, pyrexia, arthralgia, abdominal pain, and nausea. Full prescribing information is available online.
Etrasimod is “a proven advanced treatment with a favorable benefit-risk profile,” Michael Chiorean, MD, codirector of the IBD Center at Swedish Medical Center, Seattle, who is an investigator in the ELEVATE studies, said in a Pfizer news release.
“UC can affect patients differently and many people living with this disease struggle with ongoing symptoms. The introduction of a new treatment for UC could increase options for patients, and we look forward to seeing the impact of Velsipity for patients across the U.S.,” added Michael Osso, president and CEO of the Crohn’s & Colitis Foundation.
A version of this article first appeared on Medscape.com.
Pfizer announced on Oct. 13.
Etrasimod is an oral sphingosine-1-phosphate (S1P) receptor that binds with high affinity to receptors 1, 4, and 5. The approved recommended dose is 2 mg once daily.
Etrasimod is the second agent in the S1P class approved for UC in the United States. The other agent, ozanimod (Zeposia, Bristol-Myers Squibb), received FDA approval for moderately to severely active UC in May 2021.
The approval of etrasimod was based on safety and efficacy data from two randomized, double-blind, placebo-controlled phase 3 trials: ELEVATE UC 52 trial and the ELEVATE UC 12 trial. The Lancet published full results from the two trials in March.
Both trials enrolled patients with UC who had previously failed or were intolerant of at least one conventional, biologic, or Janus kinase inhibitor therapy.
In ELEVATE UC 52, clinical remission at 12 weeks occurred in 27% of patients taking etrasimod versus 7% of patients taking a placebo (20% difference; P < .001). At week 52, remission rates were 32% with active treatment verus 7% with placebo (26% difference; P < .001).
In ELEVATE UC 12, clinical remission was achieved among 26% of patients who received etrasimod versus 15.0% of patients who received placebo (11% difference; P < .05).
Statistically significant improvements were also observed with etrasimod (vs. placebo) on all key secondary endpoints, including endoscopic improvement and mucosal healing at weeks 12 and 52, and corticosteroid-free remission and sustained clinical remission at week 52.
The most common side effects of etrasimod were found to be headache, elevated values on liver tests, worsening of UC, SARS-CoV-2 infection, dizziness, pyrexia, arthralgia, abdominal pain, and nausea. Full prescribing information is available online.
Etrasimod is “a proven advanced treatment with a favorable benefit-risk profile,” Michael Chiorean, MD, codirector of the IBD Center at Swedish Medical Center, Seattle, who is an investigator in the ELEVATE studies, said in a Pfizer news release.
“UC can affect patients differently and many people living with this disease struggle with ongoing symptoms. The introduction of a new treatment for UC could increase options for patients, and we look forward to seeing the impact of Velsipity for patients across the U.S.,” added Michael Osso, president and CEO of the Crohn’s & Colitis Foundation.
A version of this article first appeared on Medscape.com.
Ocrelizumab benefit confirmed in older patients with MS
MILAN – they say.
The researchers studied about 700 patients with MS aged 60 years and older from an international database, comparing outcomes with the anti-CD20 monoclonal antibody ocrelizumab versus those for interferon/glatiramer acetate (BRACE). They found ocrelizumab significantly reduced the annual rate of relapses, although after adjustments, patients overall faced a relapse rate of less than 0.1 per year. There were also no significant differences in either disability progression or improvement between the two treatments.
“We believe this study is unique in that ocrelizumab demonstrates a very clear differential treatment benefit in this age group,” said study presenter Yi Chao Foong, MD, department of neuroscience, Monash University, Melbourne. “However, this has to be balanced against the fact that overall relapse activity is extremely low in people with MS over the age of 60. We believe that this study adds valuable, real-world data for nuanced benefit versus risk DMT discussions with for older adults with MS.”
The findings were presented at the 9th Joint ECTRIMS-ACTRIMS meeting.
Lack of data in older patients
Dr. Fong explained the comparative efficacy of disease-modifying therapies (DMTs) has not been demonstrated in older people with MS, as all landmark trials to date have excluded people older than age 60 years. He underlined, however, that the inflammatory aspect of MS reduces with age, when neurodegenerative processes begin to predominate.
“This, combined with increased risk of acute infections in older adults have raised concerns over the benefit ratios of DMTs in this age group,” Dr. Fong said.
This has led to several de-escalation studies in older patients already on treatment for MS, but with “varied results.”
One study, published earlier in 2023, was unable to conclude whether DMT discontinuation was noninferior to continuation in older patients with no recent relapse or new MRI activity.
To investigate further, the Australian team used the MSBase database to study patients with a confirmed MS diagnosis who had started or switched to ocrelizumab or BRACE when older than 60 years of age.
They were also required to have undergone an Expanded Disability Status Scale (EDSS) assessment around the time of the initiation of DMT. In all, 675 patients met the inclusion criteria, of whom 248 started with ocrelizumab and 427 with BRACE.
The treatment groups were well balanced, although baseline EDSS scores were higher in patients given ocrelizumab, at 5.22 versus 3.89 with BRACE (P = .05), and they had a lower relapse rate prior in the year (P = .01) and 2 years (P = .02) prior to baseline.
Only relapse rates reduced
With more than 571 patient-years of follow-up, there were eight relapses in patients treated with ocrelizumab, compared with 182 relapses during 2238 patient-years among those given BRACE.
The team then performed propensity matching based on patient age, disease duration, sex, baseline EDSS, prior relapses, and prior DMTs.
They found that, over a median follow-up of 2.47 years for ocrelizumab and 4.48 years for BRACE, there was a lower rate of relapse with ocrelizumab, at a weighted annualized relapse rate of 0.01 versus 0.08 (P < .0001). This, they calculated, equated to an ARR ratio in favor of ocrelizumab of 0.15 (P < .01).
The time to first relapse was also longer for ocrelizumab versus BRACE, at a weighted hazard ratio for relapse of 0.11 (P < .001) and with, as Dr. Fong highlighted, separation of the curves at 5 months.
Over a follow-up duration of 3.6 years, there was, however, no significant difference in confirmed disability progression between the two treatments (P = .31), with similar results seen for confirmed disability improvement (P = .92).
Dr. Fong noted the study was limited by an inherent treatment indication bias, affecting the sensitivity analysis and weighing, while assessment of confirmed disability progression and confirmed disability improvement was hampered by the relatively short follow-up period and the lack of data on comorbidities.
He also highlighted the lack of safety data for the study population, as well as the lack of MRI.
Muddling the data
Approached for comment, Pavan Bhargava, MBBS, MD, associate professor of neurology, Johns Hopkins Precision Medicine Center of Excellence for Multiple Sclerosis, Baltimore, pointed out the study is based on retrospective data.
“The main question that we normally come up against in clinical practice, once people are older, is: What do you do with their treatment?” he asked.
This, Dr. Bhargava said, was the question that was addressed in the previous de-escalation studies.
The current study “actually answered a completely different question: If you were starting or changing a treatment after 60, which one would be better to choose?” This is a “much rarer scenario,” he said.
The results nevertheless showed what is seen in younger patients; in other words, “a more efficacious treatment is more effective at reducing relapses than a less efficacious treatment, even though overall the number of relapses is quite low,” Dr. Bhargava said.
“The other problem,” he added, is the study included “not just relapsing but also progressive patients, so that kind of muddles the data a little bit.”
Consequently, “it’s hard to really make a definitive conclusion” from the results, Dr. Bhargava concluded.
No funding was declared. Dr. Fong declares relationships with Biogen, National Health and Medical Research Council, Multiple Sclerosis Research Australia, and the Australian and New Zealand Association of Neurologists. Several coauthors also declared financial relationships with industry.
A version of this article first appeared on Medscape.com.
MILAN – they say.
The researchers studied about 700 patients with MS aged 60 years and older from an international database, comparing outcomes with the anti-CD20 monoclonal antibody ocrelizumab versus those for interferon/glatiramer acetate (BRACE). They found ocrelizumab significantly reduced the annual rate of relapses, although after adjustments, patients overall faced a relapse rate of less than 0.1 per year. There were also no significant differences in either disability progression or improvement between the two treatments.
“We believe this study is unique in that ocrelizumab demonstrates a very clear differential treatment benefit in this age group,” said study presenter Yi Chao Foong, MD, department of neuroscience, Monash University, Melbourne. “However, this has to be balanced against the fact that overall relapse activity is extremely low in people with MS over the age of 60. We believe that this study adds valuable, real-world data for nuanced benefit versus risk DMT discussions with for older adults with MS.”
The findings were presented at the 9th Joint ECTRIMS-ACTRIMS meeting.
Lack of data in older patients
Dr. Fong explained the comparative efficacy of disease-modifying therapies (DMTs) has not been demonstrated in older people with MS, as all landmark trials to date have excluded people older than age 60 years. He underlined, however, that the inflammatory aspect of MS reduces with age, when neurodegenerative processes begin to predominate.
“This, combined with increased risk of acute infections in older adults have raised concerns over the benefit ratios of DMTs in this age group,” Dr. Fong said.
This has led to several de-escalation studies in older patients already on treatment for MS, but with “varied results.”
One study, published earlier in 2023, was unable to conclude whether DMT discontinuation was noninferior to continuation in older patients with no recent relapse or new MRI activity.
To investigate further, the Australian team used the MSBase database to study patients with a confirmed MS diagnosis who had started or switched to ocrelizumab or BRACE when older than 60 years of age.
They were also required to have undergone an Expanded Disability Status Scale (EDSS) assessment around the time of the initiation of DMT. In all, 675 patients met the inclusion criteria, of whom 248 started with ocrelizumab and 427 with BRACE.
The treatment groups were well balanced, although baseline EDSS scores were higher in patients given ocrelizumab, at 5.22 versus 3.89 with BRACE (P = .05), and they had a lower relapse rate prior in the year (P = .01) and 2 years (P = .02) prior to baseline.
Only relapse rates reduced
With more than 571 patient-years of follow-up, there were eight relapses in patients treated with ocrelizumab, compared with 182 relapses during 2238 patient-years among those given BRACE.
The team then performed propensity matching based on patient age, disease duration, sex, baseline EDSS, prior relapses, and prior DMTs.
They found that, over a median follow-up of 2.47 years for ocrelizumab and 4.48 years for BRACE, there was a lower rate of relapse with ocrelizumab, at a weighted annualized relapse rate of 0.01 versus 0.08 (P < .0001). This, they calculated, equated to an ARR ratio in favor of ocrelizumab of 0.15 (P < .01).
The time to first relapse was also longer for ocrelizumab versus BRACE, at a weighted hazard ratio for relapse of 0.11 (P < .001) and with, as Dr. Fong highlighted, separation of the curves at 5 months.
Over a follow-up duration of 3.6 years, there was, however, no significant difference in confirmed disability progression between the two treatments (P = .31), with similar results seen for confirmed disability improvement (P = .92).
Dr. Fong noted the study was limited by an inherent treatment indication bias, affecting the sensitivity analysis and weighing, while assessment of confirmed disability progression and confirmed disability improvement was hampered by the relatively short follow-up period and the lack of data on comorbidities.
He also highlighted the lack of safety data for the study population, as well as the lack of MRI.
Muddling the data
Approached for comment, Pavan Bhargava, MBBS, MD, associate professor of neurology, Johns Hopkins Precision Medicine Center of Excellence for Multiple Sclerosis, Baltimore, pointed out the study is based on retrospective data.
“The main question that we normally come up against in clinical practice, once people are older, is: What do you do with their treatment?” he asked.
This, Dr. Bhargava said, was the question that was addressed in the previous de-escalation studies.
The current study “actually answered a completely different question: If you were starting or changing a treatment after 60, which one would be better to choose?” This is a “much rarer scenario,” he said.
The results nevertheless showed what is seen in younger patients; in other words, “a more efficacious treatment is more effective at reducing relapses than a less efficacious treatment, even though overall the number of relapses is quite low,” Dr. Bhargava said.
“The other problem,” he added, is the study included “not just relapsing but also progressive patients, so that kind of muddles the data a little bit.”
Consequently, “it’s hard to really make a definitive conclusion” from the results, Dr. Bhargava concluded.
No funding was declared. Dr. Fong declares relationships with Biogen, National Health and Medical Research Council, Multiple Sclerosis Research Australia, and the Australian and New Zealand Association of Neurologists. Several coauthors also declared financial relationships with industry.
A version of this article first appeared on Medscape.com.
MILAN – they say.
The researchers studied about 700 patients with MS aged 60 years and older from an international database, comparing outcomes with the anti-CD20 monoclonal antibody ocrelizumab versus those for interferon/glatiramer acetate (BRACE). They found ocrelizumab significantly reduced the annual rate of relapses, although after adjustments, patients overall faced a relapse rate of less than 0.1 per year. There were also no significant differences in either disability progression or improvement between the two treatments.
“We believe this study is unique in that ocrelizumab demonstrates a very clear differential treatment benefit in this age group,” said study presenter Yi Chao Foong, MD, department of neuroscience, Monash University, Melbourne. “However, this has to be balanced against the fact that overall relapse activity is extremely low in people with MS over the age of 60. We believe that this study adds valuable, real-world data for nuanced benefit versus risk DMT discussions with for older adults with MS.”
The findings were presented at the 9th Joint ECTRIMS-ACTRIMS meeting.
Lack of data in older patients
Dr. Fong explained the comparative efficacy of disease-modifying therapies (DMTs) has not been demonstrated in older people with MS, as all landmark trials to date have excluded people older than age 60 years. He underlined, however, that the inflammatory aspect of MS reduces with age, when neurodegenerative processes begin to predominate.
“This, combined with increased risk of acute infections in older adults have raised concerns over the benefit ratios of DMTs in this age group,” Dr. Fong said.
This has led to several de-escalation studies in older patients already on treatment for MS, but with “varied results.”
One study, published earlier in 2023, was unable to conclude whether DMT discontinuation was noninferior to continuation in older patients with no recent relapse or new MRI activity.
To investigate further, the Australian team used the MSBase database to study patients with a confirmed MS diagnosis who had started or switched to ocrelizumab or BRACE when older than 60 years of age.
They were also required to have undergone an Expanded Disability Status Scale (EDSS) assessment around the time of the initiation of DMT. In all, 675 patients met the inclusion criteria, of whom 248 started with ocrelizumab and 427 with BRACE.
The treatment groups were well balanced, although baseline EDSS scores were higher in patients given ocrelizumab, at 5.22 versus 3.89 with BRACE (P = .05), and they had a lower relapse rate prior in the year (P = .01) and 2 years (P = .02) prior to baseline.
Only relapse rates reduced
With more than 571 patient-years of follow-up, there were eight relapses in patients treated with ocrelizumab, compared with 182 relapses during 2238 patient-years among those given BRACE.
The team then performed propensity matching based on patient age, disease duration, sex, baseline EDSS, prior relapses, and prior DMTs.
They found that, over a median follow-up of 2.47 years for ocrelizumab and 4.48 years for BRACE, there was a lower rate of relapse with ocrelizumab, at a weighted annualized relapse rate of 0.01 versus 0.08 (P < .0001). This, they calculated, equated to an ARR ratio in favor of ocrelizumab of 0.15 (P < .01).
The time to first relapse was also longer for ocrelizumab versus BRACE, at a weighted hazard ratio for relapse of 0.11 (P < .001) and with, as Dr. Fong highlighted, separation of the curves at 5 months.
Over a follow-up duration of 3.6 years, there was, however, no significant difference in confirmed disability progression between the two treatments (P = .31), with similar results seen for confirmed disability improvement (P = .92).
Dr. Fong noted the study was limited by an inherent treatment indication bias, affecting the sensitivity analysis and weighing, while assessment of confirmed disability progression and confirmed disability improvement was hampered by the relatively short follow-up period and the lack of data on comorbidities.
He also highlighted the lack of safety data for the study population, as well as the lack of MRI.
Muddling the data
Approached for comment, Pavan Bhargava, MBBS, MD, associate professor of neurology, Johns Hopkins Precision Medicine Center of Excellence for Multiple Sclerosis, Baltimore, pointed out the study is based on retrospective data.
“The main question that we normally come up against in clinical practice, once people are older, is: What do you do with their treatment?” he asked.
This, Dr. Bhargava said, was the question that was addressed in the previous de-escalation studies.
The current study “actually answered a completely different question: If you were starting or changing a treatment after 60, which one would be better to choose?” This is a “much rarer scenario,” he said.
The results nevertheless showed what is seen in younger patients; in other words, “a more efficacious treatment is more effective at reducing relapses than a less efficacious treatment, even though overall the number of relapses is quite low,” Dr. Bhargava said.
“The other problem,” he added, is the study included “not just relapsing but also progressive patients, so that kind of muddles the data a little bit.”
Consequently, “it’s hard to really make a definitive conclusion” from the results, Dr. Bhargava concluded.
No funding was declared. Dr. Fong declares relationships with Biogen, National Health and Medical Research Council, Multiple Sclerosis Research Australia, and the Australian and New Zealand Association of Neurologists. Several coauthors also declared financial relationships with industry.
A version of this article first appeared on Medscape.com.
AT ECTRIMS 2023
GLP-1 agonists linked to higher risk for rare but serious GI complications
Patients taking either of these glucagonlike peptide-1 (GLP-1) receptor agonists had a 9-fold elevation in risk for pancreatitis. They were also 4 times more likely to develop bowel obstruction and over 3.5 times more likely to experience gastroparesis.
The research letter was published online in JAMA.
Investigators say their findings are not about scaring people off the weight-loss drugs, but instead about increasing awareness that these potential adverse outcomes can happen.
“Given the wide use of these drugs, these adverse events, although rare, must be considered by patients thinking about using them for weight loss,” said lead author Mohit Sodhi, MSc, in a news release about the study. Mr. Sodhi is a graduate of the experimental medicine program at the University of British Columbia in Vancouver, and also a 4th-year medical student at UBC.
People taking a GLP-1 agonist to treat diabetes might be more willing to accept the risks, given their potential advantages, especially that of lowering the risk for heart problems, said Mahyar Etminan, PharmD, MSc, the study’s senior author and an expert in drug safety and pharmacoepidemiology at UBC. “But those who are otherwise healthy and just taking them for weight loss might want to be more careful in weighing the risk–benefit equation.”
People taking these drugs for weight loss have an approximately 1%-2% chance of experiencing these events, including a 1% risk for gastroparesis, Dr. Etminan said.
Key findings
The study included 4,144 people taking liraglutide, 613 taking semaglutide, and 654 taking naltrexone/bupropion based on medical records between 2006 and 2020.
They included patients with a recent history of obesity but excluded those with diabetes or who had been prescribed another diabetes medication.
The use of GLP-1 agonists, compared with naltrexone/bupropion, was associated with an increased risk for pancreatitis (adjusted hazard ratio, 9.09; 95% confidence interval, 1.25-66.00), bowel obstruction (HR, 4.22; 95% CI, 1.02-17.40), and gastroparesis (HR, 3.67; 95% CI, 1.15-11.90).
The study also found a higher incidence of biliary disease, but the difference was not statistically significant (HR, 1.50; 95% CI, 0.89-2.53). The incidence of biliary disease (per 1,000 person-years) was 11.7 for semaglutide, 18.6 for liraglutide, and 12.6 for naltrexone/bupropion.
Not the first report of GI issues
“This important paper confirms the safety signals hinted at in previous randomized controlled trials,” said Carel Le Roux, MBChB, PhD, professor of metabolic medicine, Ulster University, Coleraine, Ireland, and professor of experimental pathology at University College Dublin.
“The limitations of the paper are acknowledged but do not detract from the value of the robust data,” Dr. Le Roux said. “Patients should be informed of the low risk of serious complications, such as pancreatitis, gastroparesis, and bowel obstruction, before they start semaglutide or liraglutide.”
This is not the first report of GI issues associated with GLP-1 agonists, but it’s one of the largest. Most reports have been anecdotal. The U.S. Food and Drug Administration announced on Sept. 28 that it would require manufacturers to include a warning about gastrointestinal ileus on the Ozempic (semaglutide) label.
“The results from this study highlight how important it is that patients access these drugs only through trusted medical professionals, and only with ongoing support and monitoring,” noted Simon Cork, PhD, senior lecturer in physiology, Anglia Ruskin University in Cambridge, England.
Dr. Cork added that “it’s important to look at this in the proper context.” Obesity significantly increases the risk for developing cardiovascular disease, type 2 diabetes, cancer, gallbladder disease, and stroke, risks that fall dramatically with clinically meaningful and sustained weight loss, he said.
“For the overwhelming majority of patients for whom these drugs are targeted (those with the most severe forms of obesity), the benefits of weight loss far outweigh the risks,” Dr. Cork said.
The study was independently supported. Mr. Sodhi, Dr. Etminan, and Dr. Cork report no relevant financial relationships. Dr. Le Roux is a consultant and has received research funding and reimbursement of travel expenses from Novo Nordisk.
A version of this article first appeared on Medscape.com.
Patients taking either of these glucagonlike peptide-1 (GLP-1) receptor agonists had a 9-fold elevation in risk for pancreatitis. They were also 4 times more likely to develop bowel obstruction and over 3.5 times more likely to experience gastroparesis.
The research letter was published online in JAMA.
Investigators say their findings are not about scaring people off the weight-loss drugs, but instead about increasing awareness that these potential adverse outcomes can happen.
“Given the wide use of these drugs, these adverse events, although rare, must be considered by patients thinking about using them for weight loss,” said lead author Mohit Sodhi, MSc, in a news release about the study. Mr. Sodhi is a graduate of the experimental medicine program at the University of British Columbia in Vancouver, and also a 4th-year medical student at UBC.
People taking a GLP-1 agonist to treat diabetes might be more willing to accept the risks, given their potential advantages, especially that of lowering the risk for heart problems, said Mahyar Etminan, PharmD, MSc, the study’s senior author and an expert in drug safety and pharmacoepidemiology at UBC. “But those who are otherwise healthy and just taking them for weight loss might want to be more careful in weighing the risk–benefit equation.”
People taking these drugs for weight loss have an approximately 1%-2% chance of experiencing these events, including a 1% risk for gastroparesis, Dr. Etminan said.
Key findings
The study included 4,144 people taking liraglutide, 613 taking semaglutide, and 654 taking naltrexone/bupropion based on medical records between 2006 and 2020.
They included patients with a recent history of obesity but excluded those with diabetes or who had been prescribed another diabetes medication.
The use of GLP-1 agonists, compared with naltrexone/bupropion, was associated with an increased risk for pancreatitis (adjusted hazard ratio, 9.09; 95% confidence interval, 1.25-66.00), bowel obstruction (HR, 4.22; 95% CI, 1.02-17.40), and gastroparesis (HR, 3.67; 95% CI, 1.15-11.90).
The study also found a higher incidence of biliary disease, but the difference was not statistically significant (HR, 1.50; 95% CI, 0.89-2.53). The incidence of biliary disease (per 1,000 person-years) was 11.7 for semaglutide, 18.6 for liraglutide, and 12.6 for naltrexone/bupropion.
Not the first report of GI issues
“This important paper confirms the safety signals hinted at in previous randomized controlled trials,” said Carel Le Roux, MBChB, PhD, professor of metabolic medicine, Ulster University, Coleraine, Ireland, and professor of experimental pathology at University College Dublin.
“The limitations of the paper are acknowledged but do not detract from the value of the robust data,” Dr. Le Roux said. “Patients should be informed of the low risk of serious complications, such as pancreatitis, gastroparesis, and bowel obstruction, before they start semaglutide or liraglutide.”
This is not the first report of GI issues associated with GLP-1 agonists, but it’s one of the largest. Most reports have been anecdotal. The U.S. Food and Drug Administration announced on Sept. 28 that it would require manufacturers to include a warning about gastrointestinal ileus on the Ozempic (semaglutide) label.
“The results from this study highlight how important it is that patients access these drugs only through trusted medical professionals, and only with ongoing support and monitoring,” noted Simon Cork, PhD, senior lecturer in physiology, Anglia Ruskin University in Cambridge, England.
Dr. Cork added that “it’s important to look at this in the proper context.” Obesity significantly increases the risk for developing cardiovascular disease, type 2 diabetes, cancer, gallbladder disease, and stroke, risks that fall dramatically with clinically meaningful and sustained weight loss, he said.
“For the overwhelming majority of patients for whom these drugs are targeted (those with the most severe forms of obesity), the benefits of weight loss far outweigh the risks,” Dr. Cork said.
The study was independently supported. Mr. Sodhi, Dr. Etminan, and Dr. Cork report no relevant financial relationships. Dr. Le Roux is a consultant and has received research funding and reimbursement of travel expenses from Novo Nordisk.
A version of this article first appeared on Medscape.com.
Patients taking either of these glucagonlike peptide-1 (GLP-1) receptor agonists had a 9-fold elevation in risk for pancreatitis. They were also 4 times more likely to develop bowel obstruction and over 3.5 times more likely to experience gastroparesis.
The research letter was published online in JAMA.
Investigators say their findings are not about scaring people off the weight-loss drugs, but instead about increasing awareness that these potential adverse outcomes can happen.
“Given the wide use of these drugs, these adverse events, although rare, must be considered by patients thinking about using them for weight loss,” said lead author Mohit Sodhi, MSc, in a news release about the study. Mr. Sodhi is a graduate of the experimental medicine program at the University of British Columbia in Vancouver, and also a 4th-year medical student at UBC.
People taking a GLP-1 agonist to treat diabetes might be more willing to accept the risks, given their potential advantages, especially that of lowering the risk for heart problems, said Mahyar Etminan, PharmD, MSc, the study’s senior author and an expert in drug safety and pharmacoepidemiology at UBC. “But those who are otherwise healthy and just taking them for weight loss might want to be more careful in weighing the risk–benefit equation.”
People taking these drugs for weight loss have an approximately 1%-2% chance of experiencing these events, including a 1% risk for gastroparesis, Dr. Etminan said.
Key findings
The study included 4,144 people taking liraglutide, 613 taking semaglutide, and 654 taking naltrexone/bupropion based on medical records between 2006 and 2020.
They included patients with a recent history of obesity but excluded those with diabetes or who had been prescribed another diabetes medication.
The use of GLP-1 agonists, compared with naltrexone/bupropion, was associated with an increased risk for pancreatitis (adjusted hazard ratio, 9.09; 95% confidence interval, 1.25-66.00), bowel obstruction (HR, 4.22; 95% CI, 1.02-17.40), and gastroparesis (HR, 3.67; 95% CI, 1.15-11.90).
The study also found a higher incidence of biliary disease, but the difference was not statistically significant (HR, 1.50; 95% CI, 0.89-2.53). The incidence of biliary disease (per 1,000 person-years) was 11.7 for semaglutide, 18.6 for liraglutide, and 12.6 for naltrexone/bupropion.
Not the first report of GI issues
“This important paper confirms the safety signals hinted at in previous randomized controlled trials,” said Carel Le Roux, MBChB, PhD, professor of metabolic medicine, Ulster University, Coleraine, Ireland, and professor of experimental pathology at University College Dublin.
“The limitations of the paper are acknowledged but do not detract from the value of the robust data,” Dr. Le Roux said. “Patients should be informed of the low risk of serious complications, such as pancreatitis, gastroparesis, and bowel obstruction, before they start semaglutide or liraglutide.”
This is not the first report of GI issues associated with GLP-1 agonists, but it’s one of the largest. Most reports have been anecdotal. The U.S. Food and Drug Administration announced on Sept. 28 that it would require manufacturers to include a warning about gastrointestinal ileus on the Ozempic (semaglutide) label.
“The results from this study highlight how important it is that patients access these drugs only through trusted medical professionals, and only with ongoing support and monitoring,” noted Simon Cork, PhD, senior lecturer in physiology, Anglia Ruskin University in Cambridge, England.
Dr. Cork added that “it’s important to look at this in the proper context.” Obesity significantly increases the risk for developing cardiovascular disease, type 2 diabetes, cancer, gallbladder disease, and stroke, risks that fall dramatically with clinically meaningful and sustained weight loss, he said.
“For the overwhelming majority of patients for whom these drugs are targeted (those with the most severe forms of obesity), the benefits of weight loss far outweigh the risks,” Dr. Cork said.
The study was independently supported. Mr. Sodhi, Dr. Etminan, and Dr. Cork report no relevant financial relationships. Dr. Le Roux is a consultant and has received research funding and reimbursement of travel expenses from Novo Nordisk.
A version of this article first appeared on Medscape.com.
FROM JAMA
Confirmed: Intermittent use of benzodiazepines is the safest option
BARCELONA – results of a large-scale study show.
Investigators matched more than 57,000 chronic benzodiazepine users with nearly 114,000 intermittent users and found that, at 1 year, chronic users had an 8% increased risk for emergency department visits and/or hospitalizations for falls.
Chronic users also had a 25% increased risk for hip fracture, a 4% raised risk for ED visits and/or hospitalizations for any reason, and a 23% increased risk for death.
Study investigator Simon J.C. Davies, MD, PhD, MSc, Centre for Addiction & Mental Health, Toronto, said that the research shows that, where possible, patients older than 65 years with anxiety or insomnia who are taking benzodiazepines should not stay on these medications continuously.
However, he acknowledged that, “in practical terms, there will be some who can’t change or do not want to change” their treatment.
The findings were presented at the annual meeting of the European College of Neuropsychopharmacology.
Wide range of adverse outcomes
The authors noted that benzodiazepines are used to treat anxiety and insomnia but are associated with a range of adverse outcomes, including falls, fractures, cognitive impairment, and mortality as well as tolerance and dose escalation.
“These risks are especially relevant in older adults,” they added, noting that some guidelines recommend avoiding the drugs in this population, whereas other suggest short-term benzodiazepine use for a maximum of 4 weeks.
Despite this, “benzodiazepines are widely prescribed in older adults.” One study showed that almost 15% of adults aged 65 years or older received at least one benzodiazepine prescription.
Moreover, chronic use is more common in older versus younger patients.
Benzodiazepine use among older adults “used to be higher,” Dr. Davies said in an interview, at around 20%, but the “numbers have come down,” partly because of the introduction of benzodiazepine-like sleep medications but also because of educational efforts.
“There are certainly campaigns in Ontario to educate physicians,” Dr. Davies said, “but I think more broadly people are aware of the activity of these drugs, and the tolerance and other issues.”
To compare the risk associated with chronic versus intermittent use of benzodiazepines in older adults, the team performed a population-based cohort study using linked health care databases in Ontario.
They focused on adults aged 65 years or older with a first benzodiazepine prescription after at least 1 year without taking the drugs.
Chronic benzodiazepine use was defined as 120 days of prescriptions over the first 180 days after the index prescription. Patients who met these criteria were matched with intermittent users in a 2:1 ratio by age and sex.
Patients were then propensity matched using 24 variables, including health system use in the year prior to the index prescription, clinical diagnoses, prior psychiatric health system use, falls, and income level.
The team identified 57,072 chronic benzodiazepine users and 312,468 intermittent users, of whom, 57,041 and 113,839, respectively, were propensity matched.
As expected, chronic users were prescribed benzodiazepines for more days than were the intermittent users over both the initial 180-day exposure period, at 141 days versus 33 days, and again during a further 180-day follow-up period, at 181 days versus 19 days.
Over the follow-up period, the daily lorazepam dose-equivalents of chronic users four times that of intermittent users.
Hospitalizations and/or ED visits for falls were higher among patients in the chronic benzodiazepine group, at 4.6% versus 3.2% in those who took the drugs intermittently.
After adjusting for benzodiazepine dose, the team found that chronic benzodiazepine use was associated with a significant increase in the risk for falls leading to hospital presentation over the 360-day study period, compared with intermittent use (hazard ratio, 1.08; P = .0124).
Sex differences
In addition, chronic use was linked to a significantly increased risk for hip fracture (HR, 1.25; P = .0095), and long-term care admission (HR, 1.32; P < .0001).
There was also a significant increase in ED visits and/or hospitalizations for any reason with chronic benzodiazepine use versus intermittent use (HR, 1.04; P = .0007), and an increase in the risk for death (HR, 1.23; P < .0001).
A nonsignificant increased risk for wrist fracture was also associated with chronic use of benzodiazepines (HR, 1.02; P = .8683).
Further analysis revealed some sex differences. For instance, men had a marked increase in the risk for hip fracture with chronic use (HR, 1.50; P = .0154), whereas the risk was not significant in women (HR, 1.16; P = .1332). In addition, mortality risk associated with chronic use was higher in men than in women (HR, 1.39; P < .0001 vs. HR, 1.10; P = .2245).
The decision to discontinue chronic benzodiazepine use can be challenging, said Dr. Davies. “If you’re advising people to stop, what happens to the treatment of their anxiety?”
He said that there are many other treatment options for anxiety that don’t come with tolerance or risk for addiction.
“My position would be that intermittent use is perfectly acceptable while you bide your time to explore other treatments. They may be pharmacological; they may, of course, be lifestyle changes, psychotherapies, and so on,” said Dr. Davies.
If, however, patients feel that chronic benzodiazepine use is their only option, this research informs that decision by quantifying the risks.
“We’ve always known that there was a problem, but there haven’t been high-quality epidemiological studies like this that allowed us to say what the numbers are,” said Dr. Davies.
Confirmatory research
In a comment, Christoph U. Correll, MD, professor of psychiatry at Hofstra University, Hempstead, N.Y., noted that the risk associated with benzodiazepine use, especially in older people, has been demonstrated repeatedly.
“In that context, it is not surprising that less continuous exposure to an established risk factor attenuates the risk for these adverse outcomes,” he said.
Dr. Correll, who was not involved in the study pointed out there is nevertheless a “risk of residual confounding by indication.”
In other words, “people with intermittent benzodiazepine use may have less severe underlying illness and better healthy lifestyle behaviors than those requiring chronic benzodiazepine administration.”
Also commenting on the research, Christian Vinkers, MD, PhD, psychiatrist and professor of stress and resilience, Amsterdam University Medical Centre, said that it confirms “once again that long-term benzodiazepine use should not be encouraged.”
“The risk of falls, as well as cognitive side effects and impaired driving skills, with the risk of road accidents, make chronic overuse of benzodiazepines a public health issue. Of course, there is a small group of patients who should have access to long-term use, but it is reasonable to assume that this group is currently too large,” he added.
The study was funded through a grant from the University of Toronto Department of Psychiatry Excellence Funds. No relevant financial relationships were declared.
A version of this article first appeared on Medscape.com.
BARCELONA – results of a large-scale study show.
Investigators matched more than 57,000 chronic benzodiazepine users with nearly 114,000 intermittent users and found that, at 1 year, chronic users had an 8% increased risk for emergency department visits and/or hospitalizations for falls.
Chronic users also had a 25% increased risk for hip fracture, a 4% raised risk for ED visits and/or hospitalizations for any reason, and a 23% increased risk for death.
Study investigator Simon J.C. Davies, MD, PhD, MSc, Centre for Addiction & Mental Health, Toronto, said that the research shows that, where possible, patients older than 65 years with anxiety or insomnia who are taking benzodiazepines should not stay on these medications continuously.
However, he acknowledged that, “in practical terms, there will be some who can’t change or do not want to change” their treatment.
The findings were presented at the annual meeting of the European College of Neuropsychopharmacology.
Wide range of adverse outcomes
The authors noted that benzodiazepines are used to treat anxiety and insomnia but are associated with a range of adverse outcomes, including falls, fractures, cognitive impairment, and mortality as well as tolerance and dose escalation.
“These risks are especially relevant in older adults,” they added, noting that some guidelines recommend avoiding the drugs in this population, whereas other suggest short-term benzodiazepine use for a maximum of 4 weeks.
Despite this, “benzodiazepines are widely prescribed in older adults.” One study showed that almost 15% of adults aged 65 years or older received at least one benzodiazepine prescription.
Moreover, chronic use is more common in older versus younger patients.
Benzodiazepine use among older adults “used to be higher,” Dr. Davies said in an interview, at around 20%, but the “numbers have come down,” partly because of the introduction of benzodiazepine-like sleep medications but also because of educational efforts.
“There are certainly campaigns in Ontario to educate physicians,” Dr. Davies said, “but I think more broadly people are aware of the activity of these drugs, and the tolerance and other issues.”
To compare the risk associated with chronic versus intermittent use of benzodiazepines in older adults, the team performed a population-based cohort study using linked health care databases in Ontario.
They focused on adults aged 65 years or older with a first benzodiazepine prescription after at least 1 year without taking the drugs.
Chronic benzodiazepine use was defined as 120 days of prescriptions over the first 180 days after the index prescription. Patients who met these criteria were matched with intermittent users in a 2:1 ratio by age and sex.
Patients were then propensity matched using 24 variables, including health system use in the year prior to the index prescription, clinical diagnoses, prior psychiatric health system use, falls, and income level.
The team identified 57,072 chronic benzodiazepine users and 312,468 intermittent users, of whom, 57,041 and 113,839, respectively, were propensity matched.
As expected, chronic users were prescribed benzodiazepines for more days than were the intermittent users over both the initial 180-day exposure period, at 141 days versus 33 days, and again during a further 180-day follow-up period, at 181 days versus 19 days.
Over the follow-up period, the daily lorazepam dose-equivalents of chronic users four times that of intermittent users.
Hospitalizations and/or ED visits for falls were higher among patients in the chronic benzodiazepine group, at 4.6% versus 3.2% in those who took the drugs intermittently.
After adjusting for benzodiazepine dose, the team found that chronic benzodiazepine use was associated with a significant increase in the risk for falls leading to hospital presentation over the 360-day study period, compared with intermittent use (hazard ratio, 1.08; P = .0124).
Sex differences
In addition, chronic use was linked to a significantly increased risk for hip fracture (HR, 1.25; P = .0095), and long-term care admission (HR, 1.32; P < .0001).
There was also a significant increase in ED visits and/or hospitalizations for any reason with chronic benzodiazepine use versus intermittent use (HR, 1.04; P = .0007), and an increase in the risk for death (HR, 1.23; P < .0001).
A nonsignificant increased risk for wrist fracture was also associated with chronic use of benzodiazepines (HR, 1.02; P = .8683).
Further analysis revealed some sex differences. For instance, men had a marked increase in the risk for hip fracture with chronic use (HR, 1.50; P = .0154), whereas the risk was not significant in women (HR, 1.16; P = .1332). In addition, mortality risk associated with chronic use was higher in men than in women (HR, 1.39; P < .0001 vs. HR, 1.10; P = .2245).
The decision to discontinue chronic benzodiazepine use can be challenging, said Dr. Davies. “If you’re advising people to stop, what happens to the treatment of their anxiety?”
He said that there are many other treatment options for anxiety that don’t come with tolerance or risk for addiction.
“My position would be that intermittent use is perfectly acceptable while you bide your time to explore other treatments. They may be pharmacological; they may, of course, be lifestyle changes, psychotherapies, and so on,” said Dr. Davies.
If, however, patients feel that chronic benzodiazepine use is their only option, this research informs that decision by quantifying the risks.
“We’ve always known that there was a problem, but there haven’t been high-quality epidemiological studies like this that allowed us to say what the numbers are,” said Dr. Davies.
Confirmatory research
In a comment, Christoph U. Correll, MD, professor of psychiatry at Hofstra University, Hempstead, N.Y., noted that the risk associated with benzodiazepine use, especially in older people, has been demonstrated repeatedly.
“In that context, it is not surprising that less continuous exposure to an established risk factor attenuates the risk for these adverse outcomes,” he said.
Dr. Correll, who was not involved in the study pointed out there is nevertheless a “risk of residual confounding by indication.”
In other words, “people with intermittent benzodiazepine use may have less severe underlying illness and better healthy lifestyle behaviors than those requiring chronic benzodiazepine administration.”
Also commenting on the research, Christian Vinkers, MD, PhD, psychiatrist and professor of stress and resilience, Amsterdam University Medical Centre, said that it confirms “once again that long-term benzodiazepine use should not be encouraged.”
“The risk of falls, as well as cognitive side effects and impaired driving skills, with the risk of road accidents, make chronic overuse of benzodiazepines a public health issue. Of course, there is a small group of patients who should have access to long-term use, but it is reasonable to assume that this group is currently too large,” he added.
The study was funded through a grant from the University of Toronto Department of Psychiatry Excellence Funds. No relevant financial relationships were declared.
A version of this article first appeared on Medscape.com.
BARCELONA – results of a large-scale study show.
Investigators matched more than 57,000 chronic benzodiazepine users with nearly 114,000 intermittent users and found that, at 1 year, chronic users had an 8% increased risk for emergency department visits and/or hospitalizations for falls.
Chronic users also had a 25% increased risk for hip fracture, a 4% raised risk for ED visits and/or hospitalizations for any reason, and a 23% increased risk for death.
Study investigator Simon J.C. Davies, MD, PhD, MSc, Centre for Addiction & Mental Health, Toronto, said that the research shows that, where possible, patients older than 65 years with anxiety or insomnia who are taking benzodiazepines should not stay on these medications continuously.
However, he acknowledged that, “in practical terms, there will be some who can’t change or do not want to change” their treatment.
The findings were presented at the annual meeting of the European College of Neuropsychopharmacology.
Wide range of adverse outcomes
The authors noted that benzodiazepines are used to treat anxiety and insomnia but are associated with a range of adverse outcomes, including falls, fractures, cognitive impairment, and mortality as well as tolerance and dose escalation.
“These risks are especially relevant in older adults,” they added, noting that some guidelines recommend avoiding the drugs in this population, whereas other suggest short-term benzodiazepine use for a maximum of 4 weeks.
Despite this, “benzodiazepines are widely prescribed in older adults.” One study showed that almost 15% of adults aged 65 years or older received at least one benzodiazepine prescription.
Moreover, chronic use is more common in older versus younger patients.
Benzodiazepine use among older adults “used to be higher,” Dr. Davies said in an interview, at around 20%, but the “numbers have come down,” partly because of the introduction of benzodiazepine-like sleep medications but also because of educational efforts.
“There are certainly campaigns in Ontario to educate physicians,” Dr. Davies said, “but I think more broadly people are aware of the activity of these drugs, and the tolerance and other issues.”
To compare the risk associated with chronic versus intermittent use of benzodiazepines in older adults, the team performed a population-based cohort study using linked health care databases in Ontario.
They focused on adults aged 65 years or older with a first benzodiazepine prescription after at least 1 year without taking the drugs.
Chronic benzodiazepine use was defined as 120 days of prescriptions over the first 180 days after the index prescription. Patients who met these criteria were matched with intermittent users in a 2:1 ratio by age and sex.
Patients were then propensity matched using 24 variables, including health system use in the year prior to the index prescription, clinical diagnoses, prior psychiatric health system use, falls, and income level.
The team identified 57,072 chronic benzodiazepine users and 312,468 intermittent users, of whom, 57,041 and 113,839, respectively, were propensity matched.
As expected, chronic users were prescribed benzodiazepines for more days than were the intermittent users over both the initial 180-day exposure period, at 141 days versus 33 days, and again during a further 180-day follow-up period, at 181 days versus 19 days.
Over the follow-up period, the daily lorazepam dose-equivalents of chronic users four times that of intermittent users.
Hospitalizations and/or ED visits for falls were higher among patients in the chronic benzodiazepine group, at 4.6% versus 3.2% in those who took the drugs intermittently.
After adjusting for benzodiazepine dose, the team found that chronic benzodiazepine use was associated with a significant increase in the risk for falls leading to hospital presentation over the 360-day study period, compared with intermittent use (hazard ratio, 1.08; P = .0124).
Sex differences
In addition, chronic use was linked to a significantly increased risk for hip fracture (HR, 1.25; P = .0095), and long-term care admission (HR, 1.32; P < .0001).
There was also a significant increase in ED visits and/or hospitalizations for any reason with chronic benzodiazepine use versus intermittent use (HR, 1.04; P = .0007), and an increase in the risk for death (HR, 1.23; P < .0001).
A nonsignificant increased risk for wrist fracture was also associated with chronic use of benzodiazepines (HR, 1.02; P = .8683).
Further analysis revealed some sex differences. For instance, men had a marked increase in the risk for hip fracture with chronic use (HR, 1.50; P = .0154), whereas the risk was not significant in women (HR, 1.16; P = .1332). In addition, mortality risk associated with chronic use was higher in men than in women (HR, 1.39; P < .0001 vs. HR, 1.10; P = .2245).
The decision to discontinue chronic benzodiazepine use can be challenging, said Dr. Davies. “If you’re advising people to stop, what happens to the treatment of their anxiety?”
He said that there are many other treatment options for anxiety that don’t come with tolerance or risk for addiction.
“My position would be that intermittent use is perfectly acceptable while you bide your time to explore other treatments. They may be pharmacological; they may, of course, be lifestyle changes, psychotherapies, and so on,” said Dr. Davies.
If, however, patients feel that chronic benzodiazepine use is their only option, this research informs that decision by quantifying the risks.
“We’ve always known that there was a problem, but there haven’t been high-quality epidemiological studies like this that allowed us to say what the numbers are,” said Dr. Davies.
Confirmatory research
In a comment, Christoph U. Correll, MD, professor of psychiatry at Hofstra University, Hempstead, N.Y., noted that the risk associated with benzodiazepine use, especially in older people, has been demonstrated repeatedly.
“In that context, it is not surprising that less continuous exposure to an established risk factor attenuates the risk for these adverse outcomes,” he said.
Dr. Correll, who was not involved in the study pointed out there is nevertheless a “risk of residual confounding by indication.”
In other words, “people with intermittent benzodiazepine use may have less severe underlying illness and better healthy lifestyle behaviors than those requiring chronic benzodiazepine administration.”
Also commenting on the research, Christian Vinkers, MD, PhD, psychiatrist and professor of stress and resilience, Amsterdam University Medical Centre, said that it confirms “once again that long-term benzodiazepine use should not be encouraged.”
“The risk of falls, as well as cognitive side effects and impaired driving skills, with the risk of road accidents, make chronic overuse of benzodiazepines a public health issue. Of course, there is a small group of patients who should have access to long-term use, but it is reasonable to assume that this group is currently too large,” he added.
The study was funded through a grant from the University of Toronto Department of Psychiatry Excellence Funds. No relevant financial relationships were declared.
A version of this article first appeared on Medscape.com.
AT ECNP 2023
Esketamine bests quetiapine for severe depression in head-to-head trial
BARCELONA – (TRD), results of a large, multicenter, head-to-head phase 3 trial show.
Results from the ESCAPE-TRD study, which included 675 participants with TRD, show that esketamine was associated with significantly increased rates of both depression and functional remission, compared with quetiapine.
More than 675 patients were randomly assigned to receive one of the two drugs along with ongoing treatment with an SSRI or a serotonin-norepinephrine reuptake inhibitor (SNRI).
Esketamine increased remission rates at 2 and 8 months over quetiapine by 72% and raised functional remission rates at 8 months by 88% while decreasing adverse event rates.
The findings were presented at the annual meeting of the European College of Neuropsychopharmacology and were published online in the New England Journal of Medicine.
New hope
The results provide “some hope for our patients suffering from TRD, which, given the data, is somewhat of a misnomer,” said study investigator Andreas Reif, MD, professor of psychiatry, psychosomatic medicine, and psychotherapy, University Hospital Frankfurt–Goethe University, Frankfurt am Main, Germany, and president-elect of the ECNP.
“These patients are not resistant, they just have resistance to monoaminergic drugs,” he added. Esketamine, he said, is a “new weapon in our armamentarium.”
Dr. Reif said TRD is a serious condition that affects approximately 20%-30% of those with major depressive disorder and has “substantial impact” on patients’ lives, including quality of life and level of functioning.
“We know that esketamine nasal spray is effective in TRD. However, up to now, there were only placebo-controlled trials in addition to ongoing antidepressant treatment,” Dr. Reif noted. Consequently, he added, a head-to-head comparison with an active agent with proven efficacy was “urgently needed.”
For the trial, patients from 171 sites in 24 countries with TRD, defined as a less than 25% improvement in symptoms with two or more consecutive treatments of adequate dosage and duration, were randomly assigned to receive esketamine nasal spray (n = 336) or quetiapine (n = 340) extended release together with ongoing SSRI or SNRI therapy.
Both esketamine and quetiapine were flexibly dosed. The primary endpoint was rates of remission at week 8 on the Montgomery-Åsberg Depression Rating Scale (MADRS). After week 8, patients entered a maintenance phase that lasted to week 32.
Dr. Reif said the study population was representative of a typical TRD population.
The average duration of the current depression episode was more than 5 years, and the average MADRS score was above 30.
Key findings
Results showed that those who received esketamine in combination with an SSRI or SNRI experienced a significantly higher rate of remission at week 8, compared with those treated with quetiapine (27.1% vs. 17.6%; P = .003). This equated to an adjusted odds ratio for remission of 1.74 (P = .003).
Use of esketamine was also associated with a higher rate of remission at week 8, and patients remained relapse free at week 32 (21.7% vs. 14.1% with quetiapine; odds ratio, 1.72; P = .008).
At every time point through the study, the proportion of patients experiencing remission was significantly greater with esketamine than with quetiapine. The absolute rate of remission at week 32 was 55.0%, versus 37.0% (P < .001).
Dr. Reif noted that the definition of remission used in the study was a MADRS score of less than or equal to 10, but if the “more lenient” definition of less than or equal to 12, which has been used previously, were to be applied, the absolute remission rates would rise to 65.1%, versus 46.7%.
Dr. Reif also presented results on functional remission rates beyond 32 weeks – data that were not included in the study as published in NEJM.
While remission rates increased over time in both study arms, the functional remission rate at week 32 was, again, significantly higher with esketamine than with quetiapine (38.1% vs. 25.0%; OR, 1.88; P < .001).
The safety data revealed no new signals, Dr. Reif said. Use of esketamine was associated with a lower rate of treatment-emergent adverse events that led to treatment discontinuation, at 4.2% vs. 11.0% with quetiapine.
Among patients given the ketamine-derived drug, there were lower rates of nervous system disorders, and there were no incidences of weight gain, fatigue, or hangover.
Dr. Reif said the results show that esketamine nasal spray was superior to quetiapine in achieving remission over time and that it “greatly improves patients’ functional impairment” while achieving “generally lower” adverse event rates.
He added that they are currently running a significant number of secondary analyses “to give us a better grasp of which patient benefits most” from esketamine therapy over quetiapine. The results may potentially be used to guide patient selection.
‘Tremendous advance’
Session co-chair Mark Weiser, MD, chairman at the department of psychiatry, Tel Aviv (Israel) University, said in an interview that the results are “very exciting” and offer “further proof of a tremendous advance in our field.”
Dr. Weiser, who was not involved in the study, added that demonstrating functional improvement with esketamine was key.
“It’s great to improve symptoms,” he said, “but to have patients show an improvement in their functionality is really the bottom line of this. Not only do you feel better, but you function better, and that’s of extreme importance and makes us feel very optimistic about the future.”
Josep Antoni Ramos-Quiroga, MD, PhD, head of psychiatry, Vall Hebron University Hospital and Autonomous University of Barcelona, welcomed the findings.
“The results of this study show the superior response and safety of esketamine nasal spray when compared with quetiapine,” he said in a release. “This gives people with treatment-resistant depression more safe treatment options.”
The study was funded by Janssen EMEA. Dr. Reif has relationships with Boehringer Ingelheim, COMPASS, Janssen Pharmaceuticals, LivaNova USA, Medice, Saga Therapeutics, and Shire. Other authors have disclosed numerous relationships with industry.
A version of this article first appeared on Medscape.com.
BARCELONA – (TRD), results of a large, multicenter, head-to-head phase 3 trial show.
Results from the ESCAPE-TRD study, which included 675 participants with TRD, show that esketamine was associated with significantly increased rates of both depression and functional remission, compared with quetiapine.
More than 675 patients were randomly assigned to receive one of the two drugs along with ongoing treatment with an SSRI or a serotonin-norepinephrine reuptake inhibitor (SNRI).
Esketamine increased remission rates at 2 and 8 months over quetiapine by 72% and raised functional remission rates at 8 months by 88% while decreasing adverse event rates.
The findings were presented at the annual meeting of the European College of Neuropsychopharmacology and were published online in the New England Journal of Medicine.
New hope
The results provide “some hope for our patients suffering from TRD, which, given the data, is somewhat of a misnomer,” said study investigator Andreas Reif, MD, professor of psychiatry, psychosomatic medicine, and psychotherapy, University Hospital Frankfurt–Goethe University, Frankfurt am Main, Germany, and president-elect of the ECNP.
“These patients are not resistant, they just have resistance to monoaminergic drugs,” he added. Esketamine, he said, is a “new weapon in our armamentarium.”
Dr. Reif said TRD is a serious condition that affects approximately 20%-30% of those with major depressive disorder and has “substantial impact” on patients’ lives, including quality of life and level of functioning.
“We know that esketamine nasal spray is effective in TRD. However, up to now, there were only placebo-controlled trials in addition to ongoing antidepressant treatment,” Dr. Reif noted. Consequently, he added, a head-to-head comparison with an active agent with proven efficacy was “urgently needed.”
For the trial, patients from 171 sites in 24 countries with TRD, defined as a less than 25% improvement in symptoms with two or more consecutive treatments of adequate dosage and duration, were randomly assigned to receive esketamine nasal spray (n = 336) or quetiapine (n = 340) extended release together with ongoing SSRI or SNRI therapy.
Both esketamine and quetiapine were flexibly dosed. The primary endpoint was rates of remission at week 8 on the Montgomery-Åsberg Depression Rating Scale (MADRS). After week 8, patients entered a maintenance phase that lasted to week 32.
Dr. Reif said the study population was representative of a typical TRD population.
The average duration of the current depression episode was more than 5 years, and the average MADRS score was above 30.
Key findings
Results showed that those who received esketamine in combination with an SSRI or SNRI experienced a significantly higher rate of remission at week 8, compared with those treated with quetiapine (27.1% vs. 17.6%; P = .003). This equated to an adjusted odds ratio for remission of 1.74 (P = .003).
Use of esketamine was also associated with a higher rate of remission at week 8, and patients remained relapse free at week 32 (21.7% vs. 14.1% with quetiapine; odds ratio, 1.72; P = .008).
At every time point through the study, the proportion of patients experiencing remission was significantly greater with esketamine than with quetiapine. The absolute rate of remission at week 32 was 55.0%, versus 37.0% (P < .001).
Dr. Reif noted that the definition of remission used in the study was a MADRS score of less than or equal to 10, but if the “more lenient” definition of less than or equal to 12, which has been used previously, were to be applied, the absolute remission rates would rise to 65.1%, versus 46.7%.
Dr. Reif also presented results on functional remission rates beyond 32 weeks – data that were not included in the study as published in NEJM.
While remission rates increased over time in both study arms, the functional remission rate at week 32 was, again, significantly higher with esketamine than with quetiapine (38.1% vs. 25.0%; OR, 1.88; P < .001).
The safety data revealed no new signals, Dr. Reif said. Use of esketamine was associated with a lower rate of treatment-emergent adverse events that led to treatment discontinuation, at 4.2% vs. 11.0% with quetiapine.
Among patients given the ketamine-derived drug, there were lower rates of nervous system disorders, and there were no incidences of weight gain, fatigue, or hangover.
Dr. Reif said the results show that esketamine nasal spray was superior to quetiapine in achieving remission over time and that it “greatly improves patients’ functional impairment” while achieving “generally lower” adverse event rates.
He added that they are currently running a significant number of secondary analyses “to give us a better grasp of which patient benefits most” from esketamine therapy over quetiapine. The results may potentially be used to guide patient selection.
‘Tremendous advance’
Session co-chair Mark Weiser, MD, chairman at the department of psychiatry, Tel Aviv (Israel) University, said in an interview that the results are “very exciting” and offer “further proof of a tremendous advance in our field.”
Dr. Weiser, who was not involved in the study, added that demonstrating functional improvement with esketamine was key.
“It’s great to improve symptoms,” he said, “but to have patients show an improvement in their functionality is really the bottom line of this. Not only do you feel better, but you function better, and that’s of extreme importance and makes us feel very optimistic about the future.”
Josep Antoni Ramos-Quiroga, MD, PhD, head of psychiatry, Vall Hebron University Hospital and Autonomous University of Barcelona, welcomed the findings.
“The results of this study show the superior response and safety of esketamine nasal spray when compared with quetiapine,” he said in a release. “This gives people with treatment-resistant depression more safe treatment options.”
The study was funded by Janssen EMEA. Dr. Reif has relationships with Boehringer Ingelheim, COMPASS, Janssen Pharmaceuticals, LivaNova USA, Medice, Saga Therapeutics, and Shire. Other authors have disclosed numerous relationships with industry.
A version of this article first appeared on Medscape.com.
BARCELONA – (TRD), results of a large, multicenter, head-to-head phase 3 trial show.
Results from the ESCAPE-TRD study, which included 675 participants with TRD, show that esketamine was associated with significantly increased rates of both depression and functional remission, compared with quetiapine.
More than 675 patients were randomly assigned to receive one of the two drugs along with ongoing treatment with an SSRI or a serotonin-norepinephrine reuptake inhibitor (SNRI).
Esketamine increased remission rates at 2 and 8 months over quetiapine by 72% and raised functional remission rates at 8 months by 88% while decreasing adverse event rates.
The findings were presented at the annual meeting of the European College of Neuropsychopharmacology and were published online in the New England Journal of Medicine.
New hope
The results provide “some hope for our patients suffering from TRD, which, given the data, is somewhat of a misnomer,” said study investigator Andreas Reif, MD, professor of psychiatry, psychosomatic medicine, and psychotherapy, University Hospital Frankfurt–Goethe University, Frankfurt am Main, Germany, and president-elect of the ECNP.
“These patients are not resistant, they just have resistance to monoaminergic drugs,” he added. Esketamine, he said, is a “new weapon in our armamentarium.”
Dr. Reif said TRD is a serious condition that affects approximately 20%-30% of those with major depressive disorder and has “substantial impact” on patients’ lives, including quality of life and level of functioning.
“We know that esketamine nasal spray is effective in TRD. However, up to now, there were only placebo-controlled trials in addition to ongoing antidepressant treatment,” Dr. Reif noted. Consequently, he added, a head-to-head comparison with an active agent with proven efficacy was “urgently needed.”
For the trial, patients from 171 sites in 24 countries with TRD, defined as a less than 25% improvement in symptoms with two or more consecutive treatments of adequate dosage and duration, were randomly assigned to receive esketamine nasal spray (n = 336) or quetiapine (n = 340) extended release together with ongoing SSRI or SNRI therapy.
Both esketamine and quetiapine were flexibly dosed. The primary endpoint was rates of remission at week 8 on the Montgomery-Åsberg Depression Rating Scale (MADRS). After week 8, patients entered a maintenance phase that lasted to week 32.
Dr. Reif said the study population was representative of a typical TRD population.
The average duration of the current depression episode was more than 5 years, and the average MADRS score was above 30.
Key findings
Results showed that those who received esketamine in combination with an SSRI or SNRI experienced a significantly higher rate of remission at week 8, compared with those treated with quetiapine (27.1% vs. 17.6%; P = .003). This equated to an adjusted odds ratio for remission of 1.74 (P = .003).
Use of esketamine was also associated with a higher rate of remission at week 8, and patients remained relapse free at week 32 (21.7% vs. 14.1% with quetiapine; odds ratio, 1.72; P = .008).
At every time point through the study, the proportion of patients experiencing remission was significantly greater with esketamine than with quetiapine. The absolute rate of remission at week 32 was 55.0%, versus 37.0% (P < .001).
Dr. Reif noted that the definition of remission used in the study was a MADRS score of less than or equal to 10, but if the “more lenient” definition of less than or equal to 12, which has been used previously, were to be applied, the absolute remission rates would rise to 65.1%, versus 46.7%.
Dr. Reif also presented results on functional remission rates beyond 32 weeks – data that were not included in the study as published in NEJM.
While remission rates increased over time in both study arms, the functional remission rate at week 32 was, again, significantly higher with esketamine than with quetiapine (38.1% vs. 25.0%; OR, 1.88; P < .001).
The safety data revealed no new signals, Dr. Reif said. Use of esketamine was associated with a lower rate of treatment-emergent adverse events that led to treatment discontinuation, at 4.2% vs. 11.0% with quetiapine.
Among patients given the ketamine-derived drug, there were lower rates of nervous system disorders, and there were no incidences of weight gain, fatigue, or hangover.
Dr. Reif said the results show that esketamine nasal spray was superior to quetiapine in achieving remission over time and that it “greatly improves patients’ functional impairment” while achieving “generally lower” adverse event rates.
He added that they are currently running a significant number of secondary analyses “to give us a better grasp of which patient benefits most” from esketamine therapy over quetiapine. The results may potentially be used to guide patient selection.
‘Tremendous advance’
Session co-chair Mark Weiser, MD, chairman at the department of psychiatry, Tel Aviv (Israel) University, said in an interview that the results are “very exciting” and offer “further proof of a tremendous advance in our field.”
Dr. Weiser, who was not involved in the study, added that demonstrating functional improvement with esketamine was key.
“It’s great to improve symptoms,” he said, “but to have patients show an improvement in their functionality is really the bottom line of this. Not only do you feel better, but you function better, and that’s of extreme importance and makes us feel very optimistic about the future.”
Josep Antoni Ramos-Quiroga, MD, PhD, head of psychiatry, Vall Hebron University Hospital and Autonomous University of Barcelona, welcomed the findings.
“The results of this study show the superior response and safety of esketamine nasal spray when compared with quetiapine,” he said in a release. “This gives people with treatment-resistant depression more safe treatment options.”
The study was funded by Janssen EMEA. Dr. Reif has relationships with Boehringer Ingelheim, COMPASS, Janssen Pharmaceuticals, LivaNova USA, Medice, Saga Therapeutics, and Shire. Other authors have disclosed numerous relationships with industry.
A version of this article first appeared on Medscape.com.
AT ECNP 2023
Proton pump inhibitors linked to increased dementia risk
TOPLINE:
and was highest among those diagnosed before age 70 years regardless of when PPI treatment was initiated.
METHODOLOGY:
- Researchers used four Danish registries to collect data on dementia diagnoses and prescription PPI use among 1,983,785 individuals aged 60-75 years between 2000 and 2018.
- The median follow-up time was 10.3 years.
TAKEAWAY:
- There were 99,384 (5.0%) cases of all-cause dementia during follow-up, with a median age of diagnosis of 79 years.
- Twenty-one-point-two percent of dementia cases and 18.9% of controls reported a history of PPI use.
- Risk for all-cause dementia before age 90 years was 36% higher with PPI use in people aged 60-69 years at baseline (adjusted incidence rate ratio, 1.36; 95% confidence interval, 1.29-1.43) and 6% higher in those who were age 80-89 years at baseline (aIRR, 1.06; 95% CI, 1.03-1.09).
- Investigators found significant increased dementia risk before age 90 years with PPI use regardless of when PPI treatment began and found no link between PPI use and dementia diagnoses after age 90 years.
IN PRACTICE:
“The association between PPI use and dementia was unambiguously largest among the youngest cases of dementia, potentially suggestive of a critical window of exposure where midlife PPI use affects dementia risk to a larger degree compared to late-life use,” the authors wrote. “Further, the finding could signify a declining impact of individual risk factors with advancing age owing to lengthy ongoing neuropathological processes.”
SOURCE:
Lead author of the study was Nelsan Pourhadi, MD, Danish Dementia Research Centre, department of neurology, Copenhagen University Hospital–Rigshospitalet. It was published online in Alzheimer’s and Dementia.
LIMITATIONS:
The study did not include data on PPI prescriptions before 1995, over-the-counter PPI use, and in-hospital intravenous use of PPI during the study period.
DISCLOSURES:
The study was funded by the Danish Ministry of Health. The authors reported no relevant conflicts.
A version of this article first appeared on Medscape.com.
TOPLINE:
and was highest among those diagnosed before age 70 years regardless of when PPI treatment was initiated.
METHODOLOGY:
- Researchers used four Danish registries to collect data on dementia diagnoses and prescription PPI use among 1,983,785 individuals aged 60-75 years between 2000 and 2018.
- The median follow-up time was 10.3 years.
TAKEAWAY:
- There were 99,384 (5.0%) cases of all-cause dementia during follow-up, with a median age of diagnosis of 79 years.
- Twenty-one-point-two percent of dementia cases and 18.9% of controls reported a history of PPI use.
- Risk for all-cause dementia before age 90 years was 36% higher with PPI use in people aged 60-69 years at baseline (adjusted incidence rate ratio, 1.36; 95% confidence interval, 1.29-1.43) and 6% higher in those who were age 80-89 years at baseline (aIRR, 1.06; 95% CI, 1.03-1.09).
- Investigators found significant increased dementia risk before age 90 years with PPI use regardless of when PPI treatment began and found no link between PPI use and dementia diagnoses after age 90 years.
IN PRACTICE:
“The association between PPI use and dementia was unambiguously largest among the youngest cases of dementia, potentially suggestive of a critical window of exposure where midlife PPI use affects dementia risk to a larger degree compared to late-life use,” the authors wrote. “Further, the finding could signify a declining impact of individual risk factors with advancing age owing to lengthy ongoing neuropathological processes.”
SOURCE:
Lead author of the study was Nelsan Pourhadi, MD, Danish Dementia Research Centre, department of neurology, Copenhagen University Hospital–Rigshospitalet. It was published online in Alzheimer’s and Dementia.
LIMITATIONS:
The study did not include data on PPI prescriptions before 1995, over-the-counter PPI use, and in-hospital intravenous use of PPI during the study period.
DISCLOSURES:
The study was funded by the Danish Ministry of Health. The authors reported no relevant conflicts.
A version of this article first appeared on Medscape.com.
TOPLINE:
and was highest among those diagnosed before age 70 years regardless of when PPI treatment was initiated.
METHODOLOGY:
- Researchers used four Danish registries to collect data on dementia diagnoses and prescription PPI use among 1,983,785 individuals aged 60-75 years between 2000 and 2018.
- The median follow-up time was 10.3 years.
TAKEAWAY:
- There were 99,384 (5.0%) cases of all-cause dementia during follow-up, with a median age of diagnosis of 79 years.
- Twenty-one-point-two percent of dementia cases and 18.9% of controls reported a history of PPI use.
- Risk for all-cause dementia before age 90 years was 36% higher with PPI use in people aged 60-69 years at baseline (adjusted incidence rate ratio, 1.36; 95% confidence interval, 1.29-1.43) and 6% higher in those who were age 80-89 years at baseline (aIRR, 1.06; 95% CI, 1.03-1.09).
- Investigators found significant increased dementia risk before age 90 years with PPI use regardless of when PPI treatment began and found no link between PPI use and dementia diagnoses after age 90 years.
IN PRACTICE:
“The association between PPI use and dementia was unambiguously largest among the youngest cases of dementia, potentially suggestive of a critical window of exposure where midlife PPI use affects dementia risk to a larger degree compared to late-life use,” the authors wrote. “Further, the finding could signify a declining impact of individual risk factors with advancing age owing to lengthy ongoing neuropathological processes.”
SOURCE:
Lead author of the study was Nelsan Pourhadi, MD, Danish Dementia Research Centre, department of neurology, Copenhagen University Hospital–Rigshospitalet. It was published online in Alzheimer’s and Dementia.
LIMITATIONS:
The study did not include data on PPI prescriptions before 1995, over-the-counter PPI use, and in-hospital intravenous use of PPI during the study period.
DISCLOSURES:
The study was funded by the Danish Ministry of Health. The authors reported no relevant conflicts.
A version of this article first appeared on Medscape.com.
Tirzepatide with insulin glargine improves type 2 diabetes
HAMBURG, GERMANY – Once-weekly tirzepatide (Mounjaro, Lilly) added to insulin glargine resulted in greater reductions in hemoglobin A1c along with more weight loss and less hypoglycemia, compared with prandial insulin lispro (Humalog, Sanofi), for patients with inadequately controlled type 2 diabetes, show data from the SURPASS-6 randomized clinical trial.
It also resulted in a higher percentage of participants meeting an A1c target of less than 7.0%, wrote the researchers, whose study was presented at the annual meeting of the European Association for the Study of Diabetes and was published simultaneously in JAMA.
Also, daily insulin glargine use was substantially lower among participants who received tirzepatide, compared with insulin lispro. Insulin glargine was administered at a dosage 13 IU/day; insulin lispro was administered at a dosage of 62 IU/day. “At the highest dose, some patients stopped their insulin [glargine] in the tirzepatide arm,” said Juan Pablo Frias, MD, medical director and principal investigator of Velocity Clinical Research, Los Angeles, who presented the findings. “We demonstrated clinically meaningful and superior glycemic and body weight control with tirzepatide compared with insulin lispro, while tirzepatide was also associated with less clinically significant hypoglycemia.”
Weight improved for participants who received tirzepatide compared with those who received insulin lispro, at –10 kg and +4 kg respectively. The rate of clinically significant hypoglycemia (blood glucose < 54 mg/dL) or severe hypoglycemia was tenfold lower with tirzepatide, compared with insulin lispro.
The session dedicated to tirzepatide was comoderated by Apostolos Tsapas, MD, professor of medicine and diabetes, Aristotle University, Thessaloniki, Greece, and Konstantinos Toulis, MD, consultant in endocrinology and diabetes, General Military Hospital, Thessaloniki, Greece. Dr. Toulis remarked that, in the chronic disease setting, management and treatment intensification are challenging to integrate, and there are barriers to adoption in routine practice. “This is particularly true when it adds complexity, as in the case of multiple prandial insulin injections on top of basal insulin in suboptimally treated individuals with type 2 diabetes.
“Demonstrating superiority over insulin lispro in terms of the so-called trio of A1c, weight loss, and hypoglycemic events, tirzepatide offers both a simpler to adhere to and a more efficacious treatment intensification option.” He noted that, while long-term safety data are awaited, “this seems to be a definite step forward from any viewpoint, with the possible exception of the taxpayer’s perspective.”
Dr. Tsapas added: “These data further support the very high dual glucose and weight efficacy of tirzepatide and the primary role of incretin-related therapies amongst the injectables for the treatment of type 2 diabetes.”
Tirzepatide 5, 10, 15 mg vs. insulin lispro in addition to insulin glargine
The researchers aimed to assess the efficacy and safety of adding once-weekly tirzepatide, compared with thrice-daily prandial insulin lispro, as an adjunctive therapy to insulin glargine for patients with type 2 diabetes that was inadequately controlled with basal insulin.
Tirzepatide activates the body’s receptors for glucose-dependent insulinotropic polypeptide and glucagonlike peptide–1 (GLP-1). The study authors noted that “recent guidelines support adding an injectable incretin-related therapy such as GLP-1 receptor agonist for glycemic control, rather than basal insulin, when oral medications are inadequate.”
The open-label, phase 3b clinical trial drew data from 135 sites across 15 countries and included 1,428 adults with type 2 diabetes who were taking basal insulin. Participants were randomly assigned in a 1:1:1:3 ratio to receive once-weekly subcutaneous injections of tirzepatide (5 mg [n = 243], 10 mg [n = 238], or 15 mg [n = 236]) or prandial thrice-daily insulin lispro (n = 708).
Both arms were well matched. The average age was 60 years, and 60% of participants were women. The average amount of time patients had type 2 diabetes was 14 years; 85% of participants continued taking metformin. The average A1c level was 8.8% at baseline. Patients were categorized as having obesity (average body mass index, 33 kg/m2). The average insulin glargine dose was 46 units, or 0.5 units/kg.
Outcomes included noninferiority of tirzepatide (pooled cohort) compared with insulin lispro, both in addition to insulin glargine; and A1c change from baseline to week 52 (noninferiority margin, 0.3%). Key secondary endpoints included change in body weight and percentage of participants who achieved an A1c target of less than 7.0%.
About 90% of participants who received the study drug completed the study, said Dr. Frias. “Only 0.5% of tirzepatide patients needed rescue therapy, while only 2% of the insulin lispro did.”
Prior to optimization, the average insulin glargine dose was 42 IU/kg; during optimization, it rose to an average of 46 IU/kg. “At 52 weeks, those on basal-bolus insulin found their insulin glargine dose stayed flat while insulin lispro was 62 units,” reported Dr. Frias. “The three tirzepatide doses show a reduction in insulin glargine, such that the pooled dose reached an average of 11 units, while 20% actually came off their basal insulin altogether [pooled tirzepatide].”
Tirzepatide (pooled) led to the recommended A1c target of less than 7.0% for 68% of patients versus 36% of patients in the insulin lispro group.
About 68% of the patients who received tirzepatide (pooled) achieved the recommended A1c target of less than 7.0% versus 36% of patients in the insulin lispro group.
“Individual tirzepatide doses and pooled doses showed significant reduction in A1c and up to a 2.5% reduction,” Dr. Frias added. “Normoglycemia was obtained by a greater proportion of patients on tirzepatide doses versus basal-bolus insulin – one-third in the 15-mg tirzepatide dose.”
Body weight reduction of 10% or more with tirzepatide
Further, at week 52, weight loss of 5% or more was achieved by 75.4% of participants in the pooled tirzepatide group, compared with 6.3% in the prandial lispro group. The weight loss was accompanied by clinically relevant improvements in cardiometabolic parameters.
In an exploratory analysis, weight loss of 10% or more was achieved by a mean of 48.9% of pooled tirzepatide-treated participants at week 52, compared with 2% of those taking insulin lispro, said Dr. Frias.
“It is possible that the body weight loss induced by tirzepatide therapy and its reported effect in reducing liver fat content may have led to an improvement in insulin sensitivity and decreased insulin requirements,” wrote the researchers in their article.
Hypoglycemia risk and the weight gain observed with complex insulin regimens that include prandial insulin have been main limitations to optimally up-titrate insulin therapy in clinical practice, wrote the authors.
Dr. Frias noted that, in this study, 48% of patients who received insulin lispro experienced clinically significant hypoglycemia, while only 10% of patients in the tirzepatide arms did. “This was 0.4 episodes per patient-year versus 4.4 in tirzepatide and insulin lispro respectively.”
There were more reports of adverse events among the tirzepatide groups than the insulin lispro group. “Typically, with tirzepatide, the commonest adverse events were GI in origin and were mild to moderate.” Rates were 14%-26% for nausea, 11%-15% for diarrhea, and 5%-13% for vomiting.
The study was sponsored by Eli Lilly. Dr. Frias has received grants from Eli Lilly paid to his institution during the conduct of the study and grants, personal fees, or nonfinancial support from Boehringer Ingelheim, Pfizer, Merck, Altimmune, 89BIO, Akero, Carmot Therapeutics, Intercept, Janssen, Madrigal, Novartis, Eli Lilly, Sanofi, and Novo Nordisk outside the submitted work. Dr. Toulis and Dr. Tsapas declared no relevant disclosures.
A version of this article first appeared on Medscape.com.
HAMBURG, GERMANY – Once-weekly tirzepatide (Mounjaro, Lilly) added to insulin glargine resulted in greater reductions in hemoglobin A1c along with more weight loss and less hypoglycemia, compared with prandial insulin lispro (Humalog, Sanofi), for patients with inadequately controlled type 2 diabetes, show data from the SURPASS-6 randomized clinical trial.
It also resulted in a higher percentage of participants meeting an A1c target of less than 7.0%, wrote the researchers, whose study was presented at the annual meeting of the European Association for the Study of Diabetes and was published simultaneously in JAMA.
Also, daily insulin glargine use was substantially lower among participants who received tirzepatide, compared with insulin lispro. Insulin glargine was administered at a dosage 13 IU/day; insulin lispro was administered at a dosage of 62 IU/day. “At the highest dose, some patients stopped their insulin [glargine] in the tirzepatide arm,” said Juan Pablo Frias, MD, medical director and principal investigator of Velocity Clinical Research, Los Angeles, who presented the findings. “We demonstrated clinically meaningful and superior glycemic and body weight control with tirzepatide compared with insulin lispro, while tirzepatide was also associated with less clinically significant hypoglycemia.”
Weight improved for participants who received tirzepatide compared with those who received insulin lispro, at –10 kg and +4 kg respectively. The rate of clinically significant hypoglycemia (blood glucose < 54 mg/dL) or severe hypoglycemia was tenfold lower with tirzepatide, compared with insulin lispro.
The session dedicated to tirzepatide was comoderated by Apostolos Tsapas, MD, professor of medicine and diabetes, Aristotle University, Thessaloniki, Greece, and Konstantinos Toulis, MD, consultant in endocrinology and diabetes, General Military Hospital, Thessaloniki, Greece. Dr. Toulis remarked that, in the chronic disease setting, management and treatment intensification are challenging to integrate, and there are barriers to adoption in routine practice. “This is particularly true when it adds complexity, as in the case of multiple prandial insulin injections on top of basal insulin in suboptimally treated individuals with type 2 diabetes.
“Demonstrating superiority over insulin lispro in terms of the so-called trio of A1c, weight loss, and hypoglycemic events, tirzepatide offers both a simpler to adhere to and a more efficacious treatment intensification option.” He noted that, while long-term safety data are awaited, “this seems to be a definite step forward from any viewpoint, with the possible exception of the taxpayer’s perspective.”
Dr. Tsapas added: “These data further support the very high dual glucose and weight efficacy of tirzepatide and the primary role of incretin-related therapies amongst the injectables for the treatment of type 2 diabetes.”
Tirzepatide 5, 10, 15 mg vs. insulin lispro in addition to insulin glargine
The researchers aimed to assess the efficacy and safety of adding once-weekly tirzepatide, compared with thrice-daily prandial insulin lispro, as an adjunctive therapy to insulin glargine for patients with type 2 diabetes that was inadequately controlled with basal insulin.
Tirzepatide activates the body’s receptors for glucose-dependent insulinotropic polypeptide and glucagonlike peptide–1 (GLP-1). The study authors noted that “recent guidelines support adding an injectable incretin-related therapy such as GLP-1 receptor agonist for glycemic control, rather than basal insulin, when oral medications are inadequate.”
The open-label, phase 3b clinical trial drew data from 135 sites across 15 countries and included 1,428 adults with type 2 diabetes who were taking basal insulin. Participants were randomly assigned in a 1:1:1:3 ratio to receive once-weekly subcutaneous injections of tirzepatide (5 mg [n = 243], 10 mg [n = 238], or 15 mg [n = 236]) or prandial thrice-daily insulin lispro (n = 708).
Both arms were well matched. The average age was 60 years, and 60% of participants were women. The average amount of time patients had type 2 diabetes was 14 years; 85% of participants continued taking metformin. The average A1c level was 8.8% at baseline. Patients were categorized as having obesity (average body mass index, 33 kg/m2). The average insulin glargine dose was 46 units, or 0.5 units/kg.
Outcomes included noninferiority of tirzepatide (pooled cohort) compared with insulin lispro, both in addition to insulin glargine; and A1c change from baseline to week 52 (noninferiority margin, 0.3%). Key secondary endpoints included change in body weight and percentage of participants who achieved an A1c target of less than 7.0%.
About 90% of participants who received the study drug completed the study, said Dr. Frias. “Only 0.5% of tirzepatide patients needed rescue therapy, while only 2% of the insulin lispro did.”
Prior to optimization, the average insulin glargine dose was 42 IU/kg; during optimization, it rose to an average of 46 IU/kg. “At 52 weeks, those on basal-bolus insulin found their insulin glargine dose stayed flat while insulin lispro was 62 units,” reported Dr. Frias. “The three tirzepatide doses show a reduction in insulin glargine, such that the pooled dose reached an average of 11 units, while 20% actually came off their basal insulin altogether [pooled tirzepatide].”
Tirzepatide (pooled) led to the recommended A1c target of less than 7.0% for 68% of patients versus 36% of patients in the insulin lispro group.
About 68% of the patients who received tirzepatide (pooled) achieved the recommended A1c target of less than 7.0% versus 36% of patients in the insulin lispro group.
“Individual tirzepatide doses and pooled doses showed significant reduction in A1c and up to a 2.5% reduction,” Dr. Frias added. “Normoglycemia was obtained by a greater proportion of patients on tirzepatide doses versus basal-bolus insulin – one-third in the 15-mg tirzepatide dose.”
Body weight reduction of 10% or more with tirzepatide
Further, at week 52, weight loss of 5% or more was achieved by 75.4% of participants in the pooled tirzepatide group, compared with 6.3% in the prandial lispro group. The weight loss was accompanied by clinically relevant improvements in cardiometabolic parameters.
In an exploratory analysis, weight loss of 10% or more was achieved by a mean of 48.9% of pooled tirzepatide-treated participants at week 52, compared with 2% of those taking insulin lispro, said Dr. Frias.
“It is possible that the body weight loss induced by tirzepatide therapy and its reported effect in reducing liver fat content may have led to an improvement in insulin sensitivity and decreased insulin requirements,” wrote the researchers in their article.
Hypoglycemia risk and the weight gain observed with complex insulin regimens that include prandial insulin have been main limitations to optimally up-titrate insulin therapy in clinical practice, wrote the authors.
Dr. Frias noted that, in this study, 48% of patients who received insulin lispro experienced clinically significant hypoglycemia, while only 10% of patients in the tirzepatide arms did. “This was 0.4 episodes per patient-year versus 4.4 in tirzepatide and insulin lispro respectively.”
There were more reports of adverse events among the tirzepatide groups than the insulin lispro group. “Typically, with tirzepatide, the commonest adverse events were GI in origin and were mild to moderate.” Rates were 14%-26% for nausea, 11%-15% for diarrhea, and 5%-13% for vomiting.
The study was sponsored by Eli Lilly. Dr. Frias has received grants from Eli Lilly paid to his institution during the conduct of the study and grants, personal fees, or nonfinancial support from Boehringer Ingelheim, Pfizer, Merck, Altimmune, 89BIO, Akero, Carmot Therapeutics, Intercept, Janssen, Madrigal, Novartis, Eli Lilly, Sanofi, and Novo Nordisk outside the submitted work. Dr. Toulis and Dr. Tsapas declared no relevant disclosures.
A version of this article first appeared on Medscape.com.
HAMBURG, GERMANY – Once-weekly tirzepatide (Mounjaro, Lilly) added to insulin glargine resulted in greater reductions in hemoglobin A1c along with more weight loss and less hypoglycemia, compared with prandial insulin lispro (Humalog, Sanofi), for patients with inadequately controlled type 2 diabetes, show data from the SURPASS-6 randomized clinical trial.
It also resulted in a higher percentage of participants meeting an A1c target of less than 7.0%, wrote the researchers, whose study was presented at the annual meeting of the European Association for the Study of Diabetes and was published simultaneously in JAMA.
Also, daily insulin glargine use was substantially lower among participants who received tirzepatide, compared with insulin lispro. Insulin glargine was administered at a dosage 13 IU/day; insulin lispro was administered at a dosage of 62 IU/day. “At the highest dose, some patients stopped their insulin [glargine] in the tirzepatide arm,” said Juan Pablo Frias, MD, medical director and principal investigator of Velocity Clinical Research, Los Angeles, who presented the findings. “We demonstrated clinically meaningful and superior glycemic and body weight control with tirzepatide compared with insulin lispro, while tirzepatide was also associated with less clinically significant hypoglycemia.”
Weight improved for participants who received tirzepatide compared with those who received insulin lispro, at –10 kg and +4 kg respectively. The rate of clinically significant hypoglycemia (blood glucose < 54 mg/dL) or severe hypoglycemia was tenfold lower with tirzepatide, compared with insulin lispro.
The session dedicated to tirzepatide was comoderated by Apostolos Tsapas, MD, professor of medicine and diabetes, Aristotle University, Thessaloniki, Greece, and Konstantinos Toulis, MD, consultant in endocrinology and diabetes, General Military Hospital, Thessaloniki, Greece. Dr. Toulis remarked that, in the chronic disease setting, management and treatment intensification are challenging to integrate, and there are barriers to adoption in routine practice. “This is particularly true when it adds complexity, as in the case of multiple prandial insulin injections on top of basal insulin in suboptimally treated individuals with type 2 diabetes.
“Demonstrating superiority over insulin lispro in terms of the so-called trio of A1c, weight loss, and hypoglycemic events, tirzepatide offers both a simpler to adhere to and a more efficacious treatment intensification option.” He noted that, while long-term safety data are awaited, “this seems to be a definite step forward from any viewpoint, with the possible exception of the taxpayer’s perspective.”
Dr. Tsapas added: “These data further support the very high dual glucose and weight efficacy of tirzepatide and the primary role of incretin-related therapies amongst the injectables for the treatment of type 2 diabetes.”
Tirzepatide 5, 10, 15 mg vs. insulin lispro in addition to insulin glargine
The researchers aimed to assess the efficacy and safety of adding once-weekly tirzepatide, compared with thrice-daily prandial insulin lispro, as an adjunctive therapy to insulin glargine for patients with type 2 diabetes that was inadequately controlled with basal insulin.
Tirzepatide activates the body’s receptors for glucose-dependent insulinotropic polypeptide and glucagonlike peptide–1 (GLP-1). The study authors noted that “recent guidelines support adding an injectable incretin-related therapy such as GLP-1 receptor agonist for glycemic control, rather than basal insulin, when oral medications are inadequate.”
The open-label, phase 3b clinical trial drew data from 135 sites across 15 countries and included 1,428 adults with type 2 diabetes who were taking basal insulin. Participants were randomly assigned in a 1:1:1:3 ratio to receive once-weekly subcutaneous injections of tirzepatide (5 mg [n = 243], 10 mg [n = 238], or 15 mg [n = 236]) or prandial thrice-daily insulin lispro (n = 708).
Both arms were well matched. The average age was 60 years, and 60% of participants were women. The average amount of time patients had type 2 diabetes was 14 years; 85% of participants continued taking metformin. The average A1c level was 8.8% at baseline. Patients were categorized as having obesity (average body mass index, 33 kg/m2). The average insulin glargine dose was 46 units, or 0.5 units/kg.
Outcomes included noninferiority of tirzepatide (pooled cohort) compared with insulin lispro, both in addition to insulin glargine; and A1c change from baseline to week 52 (noninferiority margin, 0.3%). Key secondary endpoints included change in body weight and percentage of participants who achieved an A1c target of less than 7.0%.
About 90% of participants who received the study drug completed the study, said Dr. Frias. “Only 0.5% of tirzepatide patients needed rescue therapy, while only 2% of the insulin lispro did.”
Prior to optimization, the average insulin glargine dose was 42 IU/kg; during optimization, it rose to an average of 46 IU/kg. “At 52 weeks, those on basal-bolus insulin found their insulin glargine dose stayed flat while insulin lispro was 62 units,” reported Dr. Frias. “The three tirzepatide doses show a reduction in insulin glargine, such that the pooled dose reached an average of 11 units, while 20% actually came off their basal insulin altogether [pooled tirzepatide].”
Tirzepatide (pooled) led to the recommended A1c target of less than 7.0% for 68% of patients versus 36% of patients in the insulin lispro group.
About 68% of the patients who received tirzepatide (pooled) achieved the recommended A1c target of less than 7.0% versus 36% of patients in the insulin lispro group.
“Individual tirzepatide doses and pooled doses showed significant reduction in A1c and up to a 2.5% reduction,” Dr. Frias added. “Normoglycemia was obtained by a greater proportion of patients on tirzepatide doses versus basal-bolus insulin – one-third in the 15-mg tirzepatide dose.”
Body weight reduction of 10% or more with tirzepatide
Further, at week 52, weight loss of 5% or more was achieved by 75.4% of participants in the pooled tirzepatide group, compared with 6.3% in the prandial lispro group. The weight loss was accompanied by clinically relevant improvements in cardiometabolic parameters.
In an exploratory analysis, weight loss of 10% or more was achieved by a mean of 48.9% of pooled tirzepatide-treated participants at week 52, compared with 2% of those taking insulin lispro, said Dr. Frias.
“It is possible that the body weight loss induced by tirzepatide therapy and its reported effect in reducing liver fat content may have led to an improvement in insulin sensitivity and decreased insulin requirements,” wrote the researchers in their article.
Hypoglycemia risk and the weight gain observed with complex insulin regimens that include prandial insulin have been main limitations to optimally up-titrate insulin therapy in clinical practice, wrote the authors.
Dr. Frias noted that, in this study, 48% of patients who received insulin lispro experienced clinically significant hypoglycemia, while only 10% of patients in the tirzepatide arms did. “This was 0.4 episodes per patient-year versus 4.4 in tirzepatide and insulin lispro respectively.”
There were more reports of adverse events among the tirzepatide groups than the insulin lispro group. “Typically, with tirzepatide, the commonest adverse events were GI in origin and were mild to moderate.” Rates were 14%-26% for nausea, 11%-15% for diarrhea, and 5%-13% for vomiting.
The study was sponsored by Eli Lilly. Dr. Frias has received grants from Eli Lilly paid to his institution during the conduct of the study and grants, personal fees, or nonfinancial support from Boehringer Ingelheim, Pfizer, Merck, Altimmune, 89BIO, Akero, Carmot Therapeutics, Intercept, Janssen, Madrigal, Novartis, Eli Lilly, Sanofi, and Novo Nordisk outside the submitted work. Dr. Toulis and Dr. Tsapas declared no relevant disclosures.
A version of this article first appeared on Medscape.com.
AT EASD 2023
FDA approves first tocilizumab biosimilar
The Food and Drug Administration has approved the biosimilar tocilizumab-bavi (Tofidence), Biogen, the drug’s manufacturer, announced on Sept. 29.
It is the first tocilizumab biosimilar approved by the FDA. The reference product, Actemra (Genentech), was first approved by the agency in 2010.
“The approval of Tofidence in the U.S. marks another positive step toward helping more people with chronic autoimmune conditions gain access to leading therapies,” Ian Henshaw, global head of biosimilars at Biogen, said in a statement. “With the increasing numbers of approved biosimilars, we expect increased savings and sustainability for health care systems and an increase in physician choice and patient access to biologics.”
Biogen’s pricing for tocilizumab-bavi will be available closer to the product’s launch date, which has yet to be determined, a company spokesman said. The U.S. average monthly cost of Actemra for rheumatoid arthritis, administered intravenously, is $2,134-$4,268 depending on dosage, according to a Genentech spokesperson.
Tocilizumab-bavi is an intravenous formulation (20 mg/mL) indicated for treatment of moderately to severely active RA, polyarticular juvenile idiopathic arthritis (PJIA), and systemic juvenile idiopathic arthritis (SJIA). The medication is administered every 4 weeks in RA and PJIA and every 8 weeks in SJIA as a single intravenous drip infusion over 1 hour.
The European Commission approved its first tocilizumab biosimilar, Tyenne (Fresenius Kabi), earlier in 2023 in both subcutaneous and intravenous formulations. Biogen did not comment on whether the company is working on a subcutaneous formulation for tocilizumab-bavi.
A version of this article appeared on Medscape.com.
The Food and Drug Administration has approved the biosimilar tocilizumab-bavi (Tofidence), Biogen, the drug’s manufacturer, announced on Sept. 29.
It is the first tocilizumab biosimilar approved by the FDA. The reference product, Actemra (Genentech), was first approved by the agency in 2010.
“The approval of Tofidence in the U.S. marks another positive step toward helping more people with chronic autoimmune conditions gain access to leading therapies,” Ian Henshaw, global head of biosimilars at Biogen, said in a statement. “With the increasing numbers of approved biosimilars, we expect increased savings and sustainability for health care systems and an increase in physician choice and patient access to biologics.”
Biogen’s pricing for tocilizumab-bavi will be available closer to the product’s launch date, which has yet to be determined, a company spokesman said. The U.S. average monthly cost of Actemra for rheumatoid arthritis, administered intravenously, is $2,134-$4,268 depending on dosage, according to a Genentech spokesperson.
Tocilizumab-bavi is an intravenous formulation (20 mg/mL) indicated for treatment of moderately to severely active RA, polyarticular juvenile idiopathic arthritis (PJIA), and systemic juvenile idiopathic arthritis (SJIA). The medication is administered every 4 weeks in RA and PJIA and every 8 weeks in SJIA as a single intravenous drip infusion over 1 hour.
The European Commission approved its first tocilizumab biosimilar, Tyenne (Fresenius Kabi), earlier in 2023 in both subcutaneous and intravenous formulations. Biogen did not comment on whether the company is working on a subcutaneous formulation for tocilizumab-bavi.
A version of this article appeared on Medscape.com.
The Food and Drug Administration has approved the biosimilar tocilizumab-bavi (Tofidence), Biogen, the drug’s manufacturer, announced on Sept. 29.
It is the first tocilizumab biosimilar approved by the FDA. The reference product, Actemra (Genentech), was first approved by the agency in 2010.
“The approval of Tofidence in the U.S. marks another positive step toward helping more people with chronic autoimmune conditions gain access to leading therapies,” Ian Henshaw, global head of biosimilars at Biogen, said in a statement. “With the increasing numbers of approved biosimilars, we expect increased savings and sustainability for health care systems and an increase in physician choice and patient access to biologics.”
Biogen’s pricing for tocilizumab-bavi will be available closer to the product’s launch date, which has yet to be determined, a company spokesman said. The U.S. average monthly cost of Actemra for rheumatoid arthritis, administered intravenously, is $2,134-$4,268 depending on dosage, according to a Genentech spokesperson.
Tocilizumab-bavi is an intravenous formulation (20 mg/mL) indicated for treatment of moderately to severely active RA, polyarticular juvenile idiopathic arthritis (PJIA), and systemic juvenile idiopathic arthritis (SJIA). The medication is administered every 4 weeks in RA and PJIA and every 8 weeks in SJIA as a single intravenous drip infusion over 1 hour.
The European Commission approved its first tocilizumab biosimilar, Tyenne (Fresenius Kabi), earlier in 2023 in both subcutaneous and intravenous formulations. Biogen did not comment on whether the company is working on a subcutaneous formulation for tocilizumab-bavi.
A version of this article appeared on Medscape.com.