Pharmacology

Use of dural-puncture epidural (DPE) shortened the onset time to surgical anesthesia by approximately 3 minutes, compared with standard epidural in patients undergoing cesarean delivery, based on data from 140 individuals.

DPE, while not new, has become more popular as an option for initiating labor analgesia, but data comparing DPE with standard epidural in conversion to surgical anesthesia for cesarean deliveries are limited, Nadir Sharawi, MD, of the University of Arkansas for Medical Sciences, Little Rock, and colleagues wrote.

courtesy University of Arkansas for Medical Sciences

DPE involves no injection of intrathecal drugs, and the potential advantages include easier translocation of epidural medications into the intrathecal space for improved analgesia, but the effects of DPE on the onset and reliability of surgical anesthesia remain unknown, they said.

In a study published in JAMA Network Open, the researchers randomized 70 women scheduled for cesarean delivery of singleton pregnancies to DPE and 70 to a standard epidural. The participants were aged 18 years and older, with a mean age of the 30.1 years; the study was conducted between April 2019 and October 2022 at a single center.

The primary outcome was the time to the loss of sharp sensation at T6, defined as “the start of epidural extension anesthesia (time zero on the stopwatch) to when the patient could no longer feel sharp sensation at T6 (assessed bilaterally at the midclavicular line),” the researchers wrote.

The onset time to surgical anesthesia was faster in the DPE group, compared with the standard group, with a median of 422 seconds versus 655 seconds.

A key secondary outcome was a composite measure of the quality of epidural anesthesia that included failure to achieve a T10 bilateral block preoperatively in the delivery room, failure to achieve a surgical block at T6 within 15 minutes of chloroprocaine administration, requirement for intraoperative analgesia, repeat neuraxial procedure, and conversion to general anesthesia. The composite rates of lower quality anesthesia were significantly less in the DPE group, compared with the standard group (15.7% vs. 36.3%; P = .007).

Additional secondary outcomes included maternal satisfaction and pain score during surgery, adverse events, opioid use in the first 24 hours, maternal vasopressor requirements, epidural block assessments, and neonatal outcomes. No significant differences in these outcomes were noted between the groups, and no instances of local anesthetic systemic toxicity or neurological complications were reported.

The findings were limited by several factors including the study population of women scheduled for cesarean delivery and not in labor, and the inability to detect less frequent complications such as post–dural-puncture headache and accidental dural puncture, the researchers noted.

In addition, the results may vary with the use of other combinations of local anesthetics and opioids. “Chloroprocaine was chosen in this study because of its ease of administration without the need for opioids and other additives along with the low risk of systemic toxic effects, which favors rapid administration for emergent cesarean delivery,” they wrote.

However, the results show an association between DPE within an hour of epidural extension for elective cesarean delivery and a faster onset of anesthesia, improved block quality, and a more favorable ratio of risks versus benefits, compared with the use of standard epidural, the researchers concluded.
 

No need for general anesthesia?

“There is controversy over whether the dural puncture epidural technique improves labor analgesia when compared to a standard epidural,” Dr. Shawari said in an interview. “However, there are limited data on whether the dural puncture epidural technique decreases the onset time to surgical anesthesia when compared to a standard epidural for cesarean delivery. This is important as a pre-existing epidural is commonly used to convert labor analgesia to surgical anesthesia in the setting of urgent cesarean delivery. A faster onset of epidural anesthesia could potentially avoid the need for general anesthesia in an emergency.”

The researchers were not surprised by the findings given their experience with performing dural puncture epidurals for labor analgesia, Dr. Shawari said. In those cases, DPE provided a faster onset when converting cesarean anesthesia, compared with a standard epidural.

The takeaway from the current study is that DPE also provided “a faster onset and improved quality of anesthesia when compared to standard epidural for elective cesarean delivery,” Dr. Shawari said. However, additional research is needed to confirm the findings for intrapartum cesarean delivery.
 

Progress in improving pain control

“Adequate pain control during cesarean delivery is incredibly important,” Catherine Albright, MD, a maternal-fetal medicine specialist at the University of Washington, Seattle, said in an interview. “Inadequate pain control leads to the need to provide additional intravenous medications or the need to be put under general anesthesia, which changes the birth experience and is more dangerous for the birthing person and the neonate.

courtesy University of Washington

“In my clinical experience, there are many times when patients do not have adequate pain control during a cesarean delivery,” said Dr. Albright, who was not involved in the current study. “I am pleased to see that there is research underway about how to best manage pain on labor and delivery, especially in the setting of conversion from labor anesthesia to cesarean anesthesia.”

The findings may have implications for clinical practice, said Dr. Albright. If the dural puncture epidural can improve cesarean anesthesia following an epidural during labor, rather than anesthesia provided for an elective cesarean), “then I believe it would reduce the number of patients who require additional pain medication, have a poor cesarean experience, and/or need to be put under general anesthesia.”

However, “as noted by the authors, additional research is needed to further determine possible risks and side effects from this technique, and also to ensure that it also works in the setting of labor, rather than for an elective cesarean,” Dr. Albright added.

The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Albright had no financial conflicts to disclose.

Use of dural-puncture epidural (DPE) shortened the onset time to surgical anesthesia by approximately 3 minutes, compared with standard epidural in patients undergoing cesarean delivery, based on data from 140 individuals.

DPE, while not new, has become more popular as an option for initiating labor analgesia, but data comparing DPE with standard epidural in conversion to surgical anesthesia for cesarean deliveries are limited, Nadir Sharawi, MD, of the University of Arkansas for Medical Sciences, Little Rock, and colleagues wrote.

courtesy University of Arkansas for Medical Sciences

DPE involves no injection of intrathecal drugs, and the potential advantages include easier translocation of epidural medications into the intrathecal space for improved analgesia, but the effects of DPE on the onset and reliability of surgical anesthesia remain unknown, they said.

In a study published in JAMA Network Open, the researchers randomized 70 women scheduled for cesarean delivery of singleton pregnancies to DPE and 70 to a standard epidural. The participants were aged 18 years and older, with a mean age of the 30.1 years; the study was conducted between April 2019 and October 2022 at a single center.

The primary outcome was the time to the loss of sharp sensation at T6, defined as “the start of epidural extension anesthesia (time zero on the stopwatch) to when the patient could no longer feel sharp sensation at T6 (assessed bilaterally at the midclavicular line),” the researchers wrote.

The onset time to surgical anesthesia was faster in the DPE group, compared with the standard group, with a median of 422 seconds versus 655 seconds.

A key secondary outcome was a composite measure of the quality of epidural anesthesia that included failure to achieve a T10 bilateral block preoperatively in the delivery room, failure to achieve a surgical block at T6 within 15 minutes of chloroprocaine administration, requirement for intraoperative analgesia, repeat neuraxial procedure, and conversion to general anesthesia. The composite rates of lower quality anesthesia were significantly less in the DPE group, compared with the standard group (15.7% vs. 36.3%; P = .007).

Additional secondary outcomes included maternal satisfaction and pain score during surgery, adverse events, opioid use in the first 24 hours, maternal vasopressor requirements, epidural block assessments, and neonatal outcomes. No significant differences in these outcomes were noted between the groups, and no instances of local anesthetic systemic toxicity or neurological complications were reported.

The findings were limited by several factors including the study population of women scheduled for cesarean delivery and not in labor, and the inability to detect less frequent complications such as post–dural-puncture headache and accidental dural puncture, the researchers noted.

In addition, the results may vary with the use of other combinations of local anesthetics and opioids. “Chloroprocaine was chosen in this study because of its ease of administration without the need for opioids and other additives along with the low risk of systemic toxic effects, which favors rapid administration for emergent cesarean delivery,” they wrote.

However, the results show an association between DPE within an hour of epidural extension for elective cesarean delivery and a faster onset of anesthesia, improved block quality, and a more favorable ratio of risks versus benefits, compared with the use of standard epidural, the researchers concluded.
 

No need for general anesthesia?

“There is controversy over whether the dural puncture epidural technique improves labor analgesia when compared to a standard epidural,” Dr. Shawari said in an interview. “However, there are limited data on whether the dural puncture epidural technique decreases the onset time to surgical anesthesia when compared to a standard epidural for cesarean delivery. This is important as a pre-existing epidural is commonly used to convert labor analgesia to surgical anesthesia in the setting of urgent cesarean delivery. A faster onset of epidural anesthesia could potentially avoid the need for general anesthesia in an emergency.”

The researchers were not surprised by the findings given their experience with performing dural puncture epidurals for labor analgesia, Dr. Shawari said. In those cases, DPE provided a faster onset when converting cesarean anesthesia, compared with a standard epidural.

The takeaway from the current study is that DPE also provided “a faster onset and improved quality of anesthesia when compared to standard epidural for elective cesarean delivery,” Dr. Shawari said. However, additional research is needed to confirm the findings for intrapartum cesarean delivery.
 

Progress in improving pain control

“Adequate pain control during cesarean delivery is incredibly important,” Catherine Albright, MD, a maternal-fetal medicine specialist at the University of Washington, Seattle, said in an interview. “Inadequate pain control leads to the need to provide additional intravenous medications or the need to be put under general anesthesia, which changes the birth experience and is more dangerous for the birthing person and the neonate.

courtesy University of Washington

“In my clinical experience, there are many times when patients do not have adequate pain control during a cesarean delivery,” said Dr. Albright, who was not involved in the current study. “I am pleased to see that there is research underway about how to best manage pain on labor and delivery, especially in the setting of conversion from labor anesthesia to cesarean anesthesia.”

The findings may have implications for clinical practice, said Dr. Albright. If the dural puncture epidural can improve cesarean anesthesia following an epidural during labor, rather than anesthesia provided for an elective cesarean), “then I believe it would reduce the number of patients who require additional pain medication, have a poor cesarean experience, and/or need to be put under general anesthesia.”

However, “as noted by the authors, additional research is needed to further determine possible risks and side effects from this technique, and also to ensure that it also works in the setting of labor, rather than for an elective cesarean,” Dr. Albright added.

The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Albright had no financial conflicts to disclose.

Use of dural-puncture epidural (DPE) shortened the onset time to surgical anesthesia by approximately 3 minutes, compared with standard epidural in patients undergoing cesarean delivery, based on data from 140 individuals.

DPE, while not new, has become more popular as an option for initiating labor analgesia, but data comparing DPE with standard epidural in conversion to surgical anesthesia for cesarean deliveries are limited, Nadir Sharawi, MD, of the University of Arkansas for Medical Sciences, Little Rock, and colleagues wrote.

courtesy University of Arkansas for Medical Sciences

DPE involves no injection of intrathecal drugs, and the potential advantages include easier translocation of epidural medications into the intrathecal space for improved analgesia, but the effects of DPE on the onset and reliability of surgical anesthesia remain unknown, they said.

In a study published in JAMA Network Open, the researchers randomized 70 women scheduled for cesarean delivery of singleton pregnancies to DPE and 70 to a standard epidural. The participants were aged 18 years and older, with a mean age of the 30.1 years; the study was conducted between April 2019 and October 2022 at a single center.

The primary outcome was the time to the loss of sharp sensation at T6, defined as “the start of epidural extension anesthesia (time zero on the stopwatch) to when the patient could no longer feel sharp sensation at T6 (assessed bilaterally at the midclavicular line),” the researchers wrote.

The onset time to surgical anesthesia was faster in the DPE group, compared with the standard group, with a median of 422 seconds versus 655 seconds.

A key secondary outcome was a composite measure of the quality of epidural anesthesia that included failure to achieve a T10 bilateral block preoperatively in the delivery room, failure to achieve a surgical block at T6 within 15 minutes of chloroprocaine administration, requirement for intraoperative analgesia, repeat neuraxial procedure, and conversion to general anesthesia. The composite rates of lower quality anesthesia were significantly less in the DPE group, compared with the standard group (15.7% vs. 36.3%; P = .007).

Additional secondary outcomes included maternal satisfaction and pain score during surgery, adverse events, opioid use in the first 24 hours, maternal vasopressor requirements, epidural block assessments, and neonatal outcomes. No significant differences in these outcomes were noted between the groups, and no instances of local anesthetic systemic toxicity or neurological complications were reported.

The findings were limited by several factors including the study population of women scheduled for cesarean delivery and not in labor, and the inability to detect less frequent complications such as post–dural-puncture headache and accidental dural puncture, the researchers noted.

In addition, the results may vary with the use of other combinations of local anesthetics and opioids. “Chloroprocaine was chosen in this study because of its ease of administration without the need for opioids and other additives along with the low risk of systemic toxic effects, which favors rapid administration for emergent cesarean delivery,” they wrote.

However, the results show an association between DPE within an hour of epidural extension for elective cesarean delivery and a faster onset of anesthesia, improved block quality, and a more favorable ratio of risks versus benefits, compared with the use of standard epidural, the researchers concluded.
 

No need for general anesthesia?

“There is controversy over whether the dural puncture epidural technique improves labor analgesia when compared to a standard epidural,” Dr. Shawari said in an interview. “However, there are limited data on whether the dural puncture epidural technique decreases the onset time to surgical anesthesia when compared to a standard epidural for cesarean delivery. This is important as a pre-existing epidural is commonly used to convert labor analgesia to surgical anesthesia in the setting of urgent cesarean delivery. A faster onset of epidural anesthesia could potentially avoid the need for general anesthesia in an emergency.”

The researchers were not surprised by the findings given their experience with performing dural puncture epidurals for labor analgesia, Dr. Shawari said. In those cases, DPE provided a faster onset when converting cesarean anesthesia, compared with a standard epidural.

The takeaway from the current study is that DPE also provided “a faster onset and improved quality of anesthesia when compared to standard epidural for elective cesarean delivery,” Dr. Shawari said. However, additional research is needed to confirm the findings for intrapartum cesarean delivery.
 

Progress in improving pain control

“Adequate pain control during cesarean delivery is incredibly important,” Catherine Albright, MD, a maternal-fetal medicine specialist at the University of Washington, Seattle, said in an interview. “Inadequate pain control leads to the need to provide additional intravenous medications or the need to be put under general anesthesia, which changes the birth experience and is more dangerous for the birthing person and the neonate.

courtesy University of Washington

“In my clinical experience, there are many times when patients do not have adequate pain control during a cesarean delivery,” said Dr. Albright, who was not involved in the current study. “I am pleased to see that there is research underway about how to best manage pain on labor and delivery, especially in the setting of conversion from labor anesthesia to cesarean anesthesia.”

The findings may have implications for clinical practice, said Dr. Albright. If the dural puncture epidural can improve cesarean anesthesia following an epidural during labor, rather than anesthesia provided for an elective cesarean), “then I believe it would reduce the number of patients who require additional pain medication, have a poor cesarean experience, and/or need to be put under general anesthesia.”

However, “as noted by the authors, additional research is needed to further determine possible risks and side effects from this technique, and also to ensure that it also works in the setting of labor, rather than for an elective cesarean,” Dr. Albright added.

The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Albright had no financial conflicts to disclose.

The Food and Drug Administration has approved the first oral agent specifically for postpartum depression, a condition that affects an estimated one in seven mothers in the United States.

The pill, zuranolone (Zurzuvae), is a neuroactive steroid that acts on GABAA receptors in the brain responsible for regulating mood, arousal, behavior, and cognition, according to Biogen, which, along with Sage Therapeutics, developed the product. The recommended dose for Zurzuvae is 50 mg taken once daily for 14 days, in the evening with a fatty meal, according to the FDA.

Olivier Le Moal/Getty Images

Postpartum depression often goes undiagnosed and untreated. Many mothers are hesitant to reveal their symptoms to family and clinicians, fearing they’ll be judged on their parenting. A 2017 study found that suicide accounted for roughly 5% of perinatal deaths among women in Canada, with most of those deaths occurring in the first 3 months in the year after giving birth.

“Postpartum depression is a serious and potentially life-threatening condition in which women experience sadness, guilt, worthlessness – even, in severe cases, thoughts of harming themselves or their child. And, because postpartum depression can disrupt the maternal-infant bond, it can also have consequences for the child’s physical and emotional development,” Tiffany R. Farchione, MD, director of the division of psychiatry at the FDA’s Center for Drug Evaluation and Research, said in a statement about the approval. “Having access to an oral medication will be a beneficial option for many of these women coping with extreme, and sometimes life-threatening, feelings.”

The other approved therapy for postpartum depression is the intravenous agent brexanolone (Zulresso; Sage). But the product requires prolonged infusions in hospital settings and costs $34,000.

FDA approval of Zurzuvae was based in part on data reported in a 2023 study in the American Journal of Psychiatry, which showed that the drug led to significantly greater improvement in depressive symptoms at 15 days compared with the placebo group. Improvements were observed on day 3, the earliest assessment, and were sustained at all subsequent visits during the treatment and follow-up period (through day 42).

Patients with anxiety who received the active drug experienced improvement in related symptoms compared with the patients who received a placebo.

The most common adverse events reported in the trial were somnolence and headaches. Weight gain, sexual dysfunction, withdrawal symptoms, and increased suicidal ideation or behavior were not observed.

The packaging for Zurzuvae will include a boxed warning noting that the drug can affect a user’s ability to drive and perform other potentially hazardous activities, possibly without their knowledge of the impairment, the FDA said. As a result, people who use Zurzuvae should not drive or operate heavy machinery for at least 12 hours after taking the pill.

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

The Food and Drug Administration has approved the first oral agent specifically for postpartum depression, a condition that affects an estimated one in seven mothers in the United States.

The pill, zuranolone (Zurzuvae), is a neuroactive steroid that acts on GABAA receptors in the brain responsible for regulating mood, arousal, behavior, and cognition, according to Biogen, which, along with Sage Therapeutics, developed the product. The recommended dose for Zurzuvae is 50 mg taken once daily for 14 days, in the evening with a fatty meal, according to the FDA.

Olivier Le Moal/Getty Images

Postpartum depression often goes undiagnosed and untreated. Many mothers are hesitant to reveal their symptoms to family and clinicians, fearing they’ll be judged on their parenting. A 2017 study found that suicide accounted for roughly 5% of perinatal deaths among women in Canada, with most of those deaths occurring in the first 3 months in the year after giving birth.

“Postpartum depression is a serious and potentially life-threatening condition in which women experience sadness, guilt, worthlessness – even, in severe cases, thoughts of harming themselves or their child. And, because postpartum depression can disrupt the maternal-infant bond, it can also have consequences for the child’s physical and emotional development,” Tiffany R. Farchione, MD, director of the division of psychiatry at the FDA’s Center for Drug Evaluation and Research, said in a statement about the approval. “Having access to an oral medication will be a beneficial option for many of these women coping with extreme, and sometimes life-threatening, feelings.”

The other approved therapy for postpartum depression is the intravenous agent brexanolone (Zulresso; Sage). But the product requires prolonged infusions in hospital settings and costs $34,000.

FDA approval of Zurzuvae was based in part on data reported in a 2023 study in the American Journal of Psychiatry, which showed that the drug led to significantly greater improvement in depressive symptoms at 15 days compared with the placebo group. Improvements were observed on day 3, the earliest assessment, and were sustained at all subsequent visits during the treatment and follow-up period (through day 42).

Patients with anxiety who received the active drug experienced improvement in related symptoms compared with the patients who received a placebo.

The most common adverse events reported in the trial were somnolence and headaches. Weight gain, sexual dysfunction, withdrawal symptoms, and increased suicidal ideation or behavior were not observed.

The packaging for Zurzuvae will include a boxed warning noting that the drug can affect a user’s ability to drive and perform other potentially hazardous activities, possibly without their knowledge of the impairment, the FDA said. As a result, people who use Zurzuvae should not drive or operate heavy machinery for at least 12 hours after taking the pill.

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

The Food and Drug Administration has approved the first oral agent specifically for postpartum depression, a condition that affects an estimated one in seven mothers in the United States.

The pill, zuranolone (Zurzuvae), is a neuroactive steroid that acts on GABAA receptors in the brain responsible for regulating mood, arousal, behavior, and cognition, according to Biogen, which, along with Sage Therapeutics, developed the product. The recommended dose for Zurzuvae is 50 mg taken once daily for 14 days, in the evening with a fatty meal, according to the FDA.

Olivier Le Moal/Getty Images

Postpartum depression often goes undiagnosed and untreated. Many mothers are hesitant to reveal their symptoms to family and clinicians, fearing they’ll be judged on their parenting. A 2017 study found that suicide accounted for roughly 5% of perinatal deaths among women in Canada, with most of those deaths occurring in the first 3 months in the year after giving birth.

“Postpartum depression is a serious and potentially life-threatening condition in which women experience sadness, guilt, worthlessness – even, in severe cases, thoughts of harming themselves or their child. And, because postpartum depression can disrupt the maternal-infant bond, it can also have consequences for the child’s physical and emotional development,” Tiffany R. Farchione, MD, director of the division of psychiatry at the FDA’s Center for Drug Evaluation and Research, said in a statement about the approval. “Having access to an oral medication will be a beneficial option for many of these women coping with extreme, and sometimes life-threatening, feelings.”

The other approved therapy for postpartum depression is the intravenous agent brexanolone (Zulresso; Sage). But the product requires prolonged infusions in hospital settings and costs $34,000.

FDA approval of Zurzuvae was based in part on data reported in a 2023 study in the American Journal of Psychiatry, which showed that the drug led to significantly greater improvement in depressive symptoms at 15 days compared with the placebo group. Improvements were observed on day 3, the earliest assessment, and were sustained at all subsequent visits during the treatment and follow-up period (through day 42).

Patients with anxiety who received the active drug experienced improvement in related symptoms compared with the patients who received a placebo.

The most common adverse events reported in the trial were somnolence and headaches. Weight gain, sexual dysfunction, withdrawal symptoms, and increased suicidal ideation or behavior were not observed.

The packaging for Zurzuvae will include a boxed warning noting that the drug can affect a user’s ability to drive and perform other potentially hazardous activities, possibly without their knowledge of the impairment, the FDA said. As a result, people who use Zurzuvae should not drive or operate heavy machinery for at least 12 hours after taking the pill.

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

SEATTLE – A family of blockbuster drugs for managing blood glucose – and now for promoting weight loss – has been linked to exacerbation of macular disease that frequently accompanies diabetes, new data show.

Two studies presented at the annual meeting of the American Society of Retina Specialists (ASRS) have found that use of injectable agonists of glucagonlike peptide-1 (GLP1) appears to hasten the progression of diabetic retinopathy and diabetic macular edema (DME).

Clinicians should be aware of these effects of GLP-1 inhibitors to ensure appropriate monitoring of patients for the possibility that retinopathy may accelerate, according to Ehsan Rahimy, MD, an adjunct clinical professor at Stanford (Calif.) University, and colleagues.

Dr. Rahimy presented results of a retrospective study of retinopathy progression in patients taking either GLP-1 agonists or sodium-glucose transporter-2 (SGLT-2) inhibitors, also known as gliflozins. “When we looked at the conversion to proliferative disease, you can see it was statistically higher in the GLP-1 group at all time points,” he said.

GLP-1 agonists can promote considerable weight loss in patients with and without diabetes. Moreover, the finding that gliflozins improve cardiovascular and renal function in patients with type 2 diabetes has accelerated the use of these agents for blood glucose control.

Using a repository of data from more than 13,500 people taking either of the two kinds of medication, the researchers looked for conversion of diabetic eye disease to proliferative diabetic retinopathy (PDR) or DME. Secondary outcomes were the need for intravitreal injections, panretinal photocoagulation (PRP), or pars plana vitrectomy (PPV).

Propensity score matching for age, sex, race, ethnicity, and baseline hemoglobin A1c resulted in the inclusion of 5,446 participants in each treatment group. After matching, the mean age of participants in either group was 64 years, and the mean A1c was 8.5%. Slightly more than half the participants were insulin-dependent.

Patients taking GLP-1 inhibitors had higher rates of conversion to PDR than those taking gliflozins at 3 years (6% vs. 4%; P < .01), the researchers found. Nearly 25% of those taking a GLP-1 agonist had progressed to DME after 3 years, compared with 18% of those taking a gliflozin.

People in the group taking GLP-1 inhibitors also had a greater need for interventions than those on a gliflozin; 8% vs. roughly 6%, respectively, required intravitreal injections, Dr. Rahimy reported. Similar trends were noted for need for PRP and PPV, he added, although the absolute numbers of patients were small.
 

Albiglutide the key culprit?

In other research reported at the meeting, a meta-analysis of data collected in 93 randomized clinical trials of the seven currently available GLP-1 agonists found only albiglutide was associated with diabetic retinopathy to a statistically significant degree. Compared with placebo, albiglutide more than doubled the risk for early-stage diabetic retinopathy (relative risk 2.18; 95% confidence interval, 1.01-4.67; P = .05).

Other GLP-1 agonists evaluated in the meta-analysis included semaglutide, tirzepatide, dulaglutide, exenatide, liraglutide, and lixisenatide. These findings were reported in a poster presented at the meeting by Ishani Kapoor, MD candidate, Drexel University, Philadelphia.

“The strength of these effects depends on the specific GLP-1 receptor agonist used, patient-specific clinical characteristics, and demographics,” Ms. Kapoor and coauthors reported. “Further studies are needed to clarify the patient populations that would benefit from GLP-1 receptor agonists and those at risk for [the] development of additional ocular damage.”
 

What causes progression?

Whether worsening of retinopathy stems from rapid weight loss and acute reductions in concentrations of blood glucose or is a direct effect of GLP-1 agonists on the eye is unclear.

“That rapid reduction is thought to play some role,” Dr. Rahimy said. “But if you actually look out there in the basic science literature, it’s suggested that there are direct effects of these medications on the retina too. That being said, it’s suggested that they may be protective to the retina. And I think that’s where we’ve gotten a lot of mixed signals in our community between what we’ve seen on the basic science side vs. what we’re seeing on the real-world side.”

The study was independently funded. Dr. Rahimy reports consultancies or speakerships with AbbVie, Allergan, Apellis, Carl Zeiss, Genentech, and Google, and research support from Regeneron. Ms. Kapoor reports no relevant financial relationships.

A version of this article appeared on Medscape.com.

SEATTLE – A family of blockbuster drugs for managing blood glucose – and now for promoting weight loss – has been linked to exacerbation of macular disease that frequently accompanies diabetes, new data show.

Two studies presented at the annual meeting of the American Society of Retina Specialists (ASRS) have found that use of injectable agonists of glucagonlike peptide-1 (GLP1) appears to hasten the progression of diabetic retinopathy and diabetic macular edema (DME).

Clinicians should be aware of these effects of GLP-1 inhibitors to ensure appropriate monitoring of patients for the possibility that retinopathy may accelerate, according to Ehsan Rahimy, MD, an adjunct clinical professor at Stanford (Calif.) University, and colleagues.

Dr. Rahimy presented results of a retrospective study of retinopathy progression in patients taking either GLP-1 agonists or sodium-glucose transporter-2 (SGLT-2) inhibitors, also known as gliflozins. “When we looked at the conversion to proliferative disease, you can see it was statistically higher in the GLP-1 group at all time points,” he said.

GLP-1 agonists can promote considerable weight loss in patients with and without diabetes. Moreover, the finding that gliflozins improve cardiovascular and renal function in patients with type 2 diabetes has accelerated the use of these agents for blood glucose control.

Using a repository of data from more than 13,500 people taking either of the two kinds of medication, the researchers looked for conversion of diabetic eye disease to proliferative diabetic retinopathy (PDR) or DME. Secondary outcomes were the need for intravitreal injections, panretinal photocoagulation (PRP), or pars plana vitrectomy (PPV).

Propensity score matching for age, sex, race, ethnicity, and baseline hemoglobin A1c resulted in the inclusion of 5,446 participants in each treatment group. After matching, the mean age of participants in either group was 64 years, and the mean A1c was 8.5%. Slightly more than half the participants were insulin-dependent.

Patients taking GLP-1 inhibitors had higher rates of conversion to PDR than those taking gliflozins at 3 years (6% vs. 4%; P < .01), the researchers found. Nearly 25% of those taking a GLP-1 agonist had progressed to DME after 3 years, compared with 18% of those taking a gliflozin.

People in the group taking GLP-1 inhibitors also had a greater need for interventions than those on a gliflozin; 8% vs. roughly 6%, respectively, required intravitreal injections, Dr. Rahimy reported. Similar trends were noted for need for PRP and PPV, he added, although the absolute numbers of patients were small.
 

Albiglutide the key culprit?

In other research reported at the meeting, a meta-analysis of data collected in 93 randomized clinical trials of the seven currently available GLP-1 agonists found only albiglutide was associated with diabetic retinopathy to a statistically significant degree. Compared with placebo, albiglutide more than doubled the risk for early-stage diabetic retinopathy (relative risk 2.18; 95% confidence interval, 1.01-4.67; P = .05).

Other GLP-1 agonists evaluated in the meta-analysis included semaglutide, tirzepatide, dulaglutide, exenatide, liraglutide, and lixisenatide. These findings were reported in a poster presented at the meeting by Ishani Kapoor, MD candidate, Drexel University, Philadelphia.

“The strength of these effects depends on the specific GLP-1 receptor agonist used, patient-specific clinical characteristics, and demographics,” Ms. Kapoor and coauthors reported. “Further studies are needed to clarify the patient populations that would benefit from GLP-1 receptor agonists and those at risk for [the] development of additional ocular damage.”
 

What causes progression?

Whether worsening of retinopathy stems from rapid weight loss and acute reductions in concentrations of blood glucose or is a direct effect of GLP-1 agonists on the eye is unclear.

“That rapid reduction is thought to play some role,” Dr. Rahimy said. “But if you actually look out there in the basic science literature, it’s suggested that there are direct effects of these medications on the retina too. That being said, it’s suggested that they may be protective to the retina. And I think that’s where we’ve gotten a lot of mixed signals in our community between what we’ve seen on the basic science side vs. what we’re seeing on the real-world side.”

The study was independently funded. Dr. Rahimy reports consultancies or speakerships with AbbVie, Allergan, Apellis, Carl Zeiss, Genentech, and Google, and research support from Regeneron. Ms. Kapoor reports no relevant financial relationships.

A version of this article appeared on Medscape.com.

SEATTLE – A family of blockbuster drugs for managing blood glucose – and now for promoting weight loss – has been linked to exacerbation of macular disease that frequently accompanies diabetes, new data show.

Two studies presented at the annual meeting of the American Society of Retina Specialists (ASRS) have found that use of injectable agonists of glucagonlike peptide-1 (GLP1) appears to hasten the progression of diabetic retinopathy and diabetic macular edema (DME).

Clinicians should be aware of these effects of GLP-1 inhibitors to ensure appropriate monitoring of patients for the possibility that retinopathy may accelerate, according to Ehsan Rahimy, MD, an adjunct clinical professor at Stanford (Calif.) University, and colleagues.

Dr. Rahimy presented results of a retrospective study of retinopathy progression in patients taking either GLP-1 agonists or sodium-glucose transporter-2 (SGLT-2) inhibitors, also known as gliflozins. “When we looked at the conversion to proliferative disease, you can see it was statistically higher in the GLP-1 group at all time points,” he said.

GLP-1 agonists can promote considerable weight loss in patients with and without diabetes. Moreover, the finding that gliflozins improve cardiovascular and renal function in patients with type 2 diabetes has accelerated the use of these agents for blood glucose control.

Using a repository of data from more than 13,500 people taking either of the two kinds of medication, the researchers looked for conversion of diabetic eye disease to proliferative diabetic retinopathy (PDR) or DME. Secondary outcomes were the need for intravitreal injections, panretinal photocoagulation (PRP), or pars plana vitrectomy (PPV).

Propensity score matching for age, sex, race, ethnicity, and baseline hemoglobin A1c resulted in the inclusion of 5,446 participants in each treatment group. After matching, the mean age of participants in either group was 64 years, and the mean A1c was 8.5%. Slightly more than half the participants were insulin-dependent.

Patients taking GLP-1 inhibitors had higher rates of conversion to PDR than those taking gliflozins at 3 years (6% vs. 4%; P < .01), the researchers found. Nearly 25% of those taking a GLP-1 agonist had progressed to DME after 3 years, compared with 18% of those taking a gliflozin.

People in the group taking GLP-1 inhibitors also had a greater need for interventions than those on a gliflozin; 8% vs. roughly 6%, respectively, required intravitreal injections, Dr. Rahimy reported. Similar trends were noted for need for PRP and PPV, he added, although the absolute numbers of patients were small.
 

Albiglutide the key culprit?

In other research reported at the meeting, a meta-analysis of data collected in 93 randomized clinical trials of the seven currently available GLP-1 agonists found only albiglutide was associated with diabetic retinopathy to a statistically significant degree. Compared with placebo, albiglutide more than doubled the risk for early-stage diabetic retinopathy (relative risk 2.18; 95% confidence interval, 1.01-4.67; P = .05).

Other GLP-1 agonists evaluated in the meta-analysis included semaglutide, tirzepatide, dulaglutide, exenatide, liraglutide, and lixisenatide. These findings were reported in a poster presented at the meeting by Ishani Kapoor, MD candidate, Drexel University, Philadelphia.

“The strength of these effects depends on the specific GLP-1 receptor agonist used, patient-specific clinical characteristics, and demographics,” Ms. Kapoor and coauthors reported. “Further studies are needed to clarify the patient populations that would benefit from GLP-1 receptor agonists and those at risk for [the] development of additional ocular damage.”
 

What causes progression?

Whether worsening of retinopathy stems from rapid weight loss and acute reductions in concentrations of blood glucose or is a direct effect of GLP-1 agonists on the eye is unclear.

“That rapid reduction is thought to play some role,” Dr. Rahimy said. “But if you actually look out there in the basic science literature, it’s suggested that there are direct effects of these medications on the retina too. That being said, it’s suggested that they may be protective to the retina. And I think that’s where we’ve gotten a lot of mixed signals in our community between what we’ve seen on the basic science side vs. what we’re seeing on the real-world side.”

The study was independently funded. Dr. Rahimy reports consultancies or speakerships with AbbVie, Allergan, Apellis, Carl Zeiss, Genentech, and Google, and research support from Regeneron. Ms. Kapoor reports no relevant financial relationships.

A version of this article appeared on Medscape.com.

A new lawsuit from a woman with type 2 diabetes alleges that the makers of the drugs Ozempic and Mounjaro did not provide adequate warnings for the severity of stomach problems caused by the popular medicines.

The two drugs, which are Food and Drug Administration approved to treat type 2 diabetes, have become well known for their weight loss properties. Ozempic is made by Danish drug maker Novo Nordisk, and Mounjaro is made by Indiana-based Eli Lilly and Co.

In the lawsuit, Jaclyn Bjorklund, 44, of Louisiana, asserts that she was “severely injured” after using Ozempic and Mounjaro and that the pharmaceutical companies failed to disclose the drugs’ risk of causing vomiting and diarrhea due to inflammation of the stomach lining, as well as the risk of gastroparesis.

The prescribing labels for Mounjaro and Ozempic state that each “delays gastric emptying” and warn of the risk of severe gastrointestinal adverse reactions. The prescribing labels for both drugs state that the most common side effects include vomiting, diarrhea, and stomach pain. The Ozempic label does not mention gastroparesis, and the Mounjaro label states that the drug has not been studied in people with the condition and is therefore not recommended for people who have it. 

Ms. Bjorklund has not been diagnosed with gastroparesis, but her symptoms are “indicative of” the condition, her lawyer, Paul Pennock, told NBC News.

Ms. Bjorklund used Ozempic for more than 1 year, and in July 2023 switched to Mounjaro, the lawsuit states. The document, posted on her law firm’s website, details that using the drugs resulted in “severe vomiting, stomach pain, gastrointestinal burning, being hospitalized for stomach issues on several occasions including visits to the emergency room, [and] teeth falling out due to excessive vomiting, requiring additional medications to alleviate her excessive vomiting, and throwing up whole food hours after eating.”

Novo Nordisk spokesperson Natalia Salomao told NBC News that patient safety is “of utmost importance to Novo Nordisk,” and she also noted that gastroparesis is a known risk for people with diabetes. The Food and Drug Administration declined to comment on the case, and Eli Lilly did not immediately respond to a request for comment, NBC News reported.
 

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

A new lawsuit from a woman with type 2 diabetes alleges that the makers of the drugs Ozempic and Mounjaro did not provide adequate warnings for the severity of stomach problems caused by the popular medicines.

The two drugs, which are Food and Drug Administration approved to treat type 2 diabetes, have become well known for their weight loss properties. Ozempic is made by Danish drug maker Novo Nordisk, and Mounjaro is made by Indiana-based Eli Lilly and Co.

In the lawsuit, Jaclyn Bjorklund, 44, of Louisiana, asserts that she was “severely injured” after using Ozempic and Mounjaro and that the pharmaceutical companies failed to disclose the drugs’ risk of causing vomiting and diarrhea due to inflammation of the stomach lining, as well as the risk of gastroparesis.

The prescribing labels for Mounjaro and Ozempic state that each “delays gastric emptying” and warn of the risk of severe gastrointestinal adverse reactions. The prescribing labels for both drugs state that the most common side effects include vomiting, diarrhea, and stomach pain. The Ozempic label does not mention gastroparesis, and the Mounjaro label states that the drug has not been studied in people with the condition and is therefore not recommended for people who have it. 

Ms. Bjorklund has not been diagnosed with gastroparesis, but her symptoms are “indicative of” the condition, her lawyer, Paul Pennock, told NBC News.

Ms. Bjorklund used Ozempic for more than 1 year, and in July 2023 switched to Mounjaro, the lawsuit states. The document, posted on her law firm’s website, details that using the drugs resulted in “severe vomiting, stomach pain, gastrointestinal burning, being hospitalized for stomach issues on several occasions including visits to the emergency room, [and] teeth falling out due to excessive vomiting, requiring additional medications to alleviate her excessive vomiting, and throwing up whole food hours after eating.”

Novo Nordisk spokesperson Natalia Salomao told NBC News that patient safety is “of utmost importance to Novo Nordisk,” and she also noted that gastroparesis is a known risk for people with diabetes. The Food and Drug Administration declined to comment on the case, and Eli Lilly did not immediately respond to a request for comment, NBC News reported.
 

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

A new lawsuit from a woman with type 2 diabetes alleges that the makers of the drugs Ozempic and Mounjaro did not provide adequate warnings for the severity of stomach problems caused by the popular medicines.

The two drugs, which are Food and Drug Administration approved to treat type 2 diabetes, have become well known for their weight loss properties. Ozempic is made by Danish drug maker Novo Nordisk, and Mounjaro is made by Indiana-based Eli Lilly and Co.

In the lawsuit, Jaclyn Bjorklund, 44, of Louisiana, asserts that she was “severely injured” after using Ozempic and Mounjaro and that the pharmaceutical companies failed to disclose the drugs’ risk of causing vomiting and diarrhea due to inflammation of the stomach lining, as well as the risk of gastroparesis.

The prescribing labels for Mounjaro and Ozempic state that each “delays gastric emptying” and warn of the risk of severe gastrointestinal adverse reactions. The prescribing labels for both drugs state that the most common side effects include vomiting, diarrhea, and stomach pain. The Ozempic label does not mention gastroparesis, and the Mounjaro label states that the drug has not been studied in people with the condition and is therefore not recommended for people who have it. 

Ms. Bjorklund has not been diagnosed with gastroparesis, but her symptoms are “indicative of” the condition, her lawyer, Paul Pennock, told NBC News.

Ms. Bjorklund used Ozempic for more than 1 year, and in July 2023 switched to Mounjaro, the lawsuit states. The document, posted on her law firm’s website, details that using the drugs resulted in “severe vomiting, stomach pain, gastrointestinal burning, being hospitalized for stomach issues on several occasions including visits to the emergency room, [and] teeth falling out due to excessive vomiting, requiring additional medications to alleviate her excessive vomiting, and throwing up whole food hours after eating.”

Novo Nordisk spokesperson Natalia Salomao told NBC News that patient safety is “of utmost importance to Novo Nordisk,” and she also noted that gastroparesis is a known risk for people with diabetes. The Food and Drug Administration declined to comment on the case, and Eli Lilly did not immediately respond to a request for comment, NBC News reported.
 

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

Lower doses of initial vasopressin were associated with lower mortality when used as an adjunct in patients with septic shock, according to a review of three recent studies.

“Patients with septic shock require vasoactive agents to restore adequate tissue perfusion,” writes Gretchen L. Sacha, PharmD, of the Cleveland Clinic and colleagues.

Vasopressin is an attractive alternative to norepinephrine because it avoids the adverse effects associated with catecholamines, the researchers say. Although vasopressin is the recommended second-line adjunct after norepinephrine for patients with septic shock, findings to guide its use are inconsistent and data on the timing are limited, they note.

In a review published in the journal CHEST, the researchers summarize the three large, randomized trials to date examining the use of norepinephrine and vasopressin in patients with septic shock.

In the Vasopressin in Septic Shock Trial (VASST), 382 patients with septic shock were randomized to open-label norepinephrine with blinded norepinephrine, and 382 were randomized to open-label norepinephrine with blinded adjunctive vasopressin.

After initiation of the study drug, patients randomized to vasopressin had significantly lower requirements for open-label norepinephrine (P < .001). Although no differences occurred in the primary outcome of 28-day mortality, 90-day mortality was lower in the vasopressin group.

In the Vasopressin vs Norepinephrine as Initial Therapy in Septic Shock (VANISH) trial, 204 patients with septic shock were randomized to norepinephrine and 204 to vasopressin as an initial vasoactive agent. Although no differences appeared between the groups for the two primary outcomes of 28-day mortality and days free of kidney failure, the vasopressin group had a lower frequency of the use of kidney replacement therapy (absolute difference –9.9% vs. –0.6%).

The VANISH study was limited by the fact that 85% of the patients were receiving norepinephrine when they were randomized; “therefore, this study is best described as evaluating catecholamine-adjunctive vasopressin,” the researchers say.

The third clinical trial, published only as an abstract, randomized 387 patients with septic shock who were already receiving low doses of norepinephrine to either norepinephrine with adjunctive vasopressin or norepinephrine alone. Rates of 28-day mortality were significantly lower in the vasopressin group (34.0% vs. 42.3%; P = .03).

Several meta-analyses involving multiple vasopressin receptor agonists have shown an association between reduced mortality and their use. In addition, recent observational studies have shown an association between lower mortality and the initiation of vasopressors at a lower norepinephrine-equivalent dose or lower lactate concentration.

As for clinical implications, the 2021 version of the Surviving Sepsis Campaign (SSC) guidelines included a meta-analysis of 10 randomized, controlled trials that showed improved mortality associated with vasopressin use. This version of the guidelines was the first to address the timing of vasopressin initiation.

Because of insufficient evidence, the guidance was worded as “in our practice, vasopressin is usually started when the dose of norepinephrine is in the range of 0.25-0.5 mcg/kg/min,” the researchers write. “Although this is not a recommendation by the SSC for a specific threshold of catecholamine dose where vasopressin should be initiated, this statement represents clinician interest and the need for further research on the topic,” they note.

“Future studies of vasopressin should focus on the timing of its initiation at various clinical thresholds and patient selection for receipt of vasopressin,” they conclude.

The study was supported by the National Institutes of Health, National Institute of General Medical Sciences. Dr. Sacha has disclosed consulting for Wolters Kluwer.

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

Lower doses of initial vasopressin were associated with lower mortality when used as an adjunct in patients with septic shock, according to a review of three recent studies.

“Patients with septic shock require vasoactive agents to restore adequate tissue perfusion,” writes Gretchen L. Sacha, PharmD, of the Cleveland Clinic and colleagues.

Vasopressin is an attractive alternative to norepinephrine because it avoids the adverse effects associated with catecholamines, the researchers say. Although vasopressin is the recommended second-line adjunct after norepinephrine for patients with septic shock, findings to guide its use are inconsistent and data on the timing are limited, they note.

In a review published in the journal CHEST, the researchers summarize the three large, randomized trials to date examining the use of norepinephrine and vasopressin in patients with septic shock.

In the Vasopressin in Septic Shock Trial (VASST), 382 patients with septic shock were randomized to open-label norepinephrine with blinded norepinephrine, and 382 were randomized to open-label norepinephrine with blinded adjunctive vasopressin.

After initiation of the study drug, patients randomized to vasopressin had significantly lower requirements for open-label norepinephrine (P < .001). Although no differences occurred in the primary outcome of 28-day mortality, 90-day mortality was lower in the vasopressin group.

In the Vasopressin vs Norepinephrine as Initial Therapy in Septic Shock (VANISH) trial, 204 patients with septic shock were randomized to norepinephrine and 204 to vasopressin as an initial vasoactive agent. Although no differences appeared between the groups for the two primary outcomes of 28-day mortality and days free of kidney failure, the vasopressin group had a lower frequency of the use of kidney replacement therapy (absolute difference –9.9% vs. –0.6%).

The VANISH study was limited by the fact that 85% of the patients were receiving norepinephrine when they were randomized; “therefore, this study is best described as evaluating catecholamine-adjunctive vasopressin,” the researchers say.

The third clinical trial, published only as an abstract, randomized 387 patients with septic shock who were already receiving low doses of norepinephrine to either norepinephrine with adjunctive vasopressin or norepinephrine alone. Rates of 28-day mortality were significantly lower in the vasopressin group (34.0% vs. 42.3%; P = .03).

Several meta-analyses involving multiple vasopressin receptor agonists have shown an association between reduced mortality and their use. In addition, recent observational studies have shown an association between lower mortality and the initiation of vasopressors at a lower norepinephrine-equivalent dose or lower lactate concentration.

As for clinical implications, the 2021 version of the Surviving Sepsis Campaign (SSC) guidelines included a meta-analysis of 10 randomized, controlled trials that showed improved mortality associated with vasopressin use. This version of the guidelines was the first to address the timing of vasopressin initiation.

Because of insufficient evidence, the guidance was worded as “in our practice, vasopressin is usually started when the dose of norepinephrine is in the range of 0.25-0.5 mcg/kg/min,” the researchers write. “Although this is not a recommendation by the SSC for a specific threshold of catecholamine dose where vasopressin should be initiated, this statement represents clinician interest and the need for further research on the topic,” they note.

“Future studies of vasopressin should focus on the timing of its initiation at various clinical thresholds and patient selection for receipt of vasopressin,” they conclude.

The study was supported by the National Institutes of Health, National Institute of General Medical Sciences. Dr. Sacha has disclosed consulting for Wolters Kluwer.

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

Lower doses of initial vasopressin were associated with lower mortality when used as an adjunct in patients with septic shock, according to a review of three recent studies.

“Patients with septic shock require vasoactive agents to restore adequate tissue perfusion,” writes Gretchen L. Sacha, PharmD, of the Cleveland Clinic and colleagues.

Vasopressin is an attractive alternative to norepinephrine because it avoids the adverse effects associated with catecholamines, the researchers say. Although vasopressin is the recommended second-line adjunct after norepinephrine for patients with septic shock, findings to guide its use are inconsistent and data on the timing are limited, they note.

In a review published in the journal CHEST, the researchers summarize the three large, randomized trials to date examining the use of norepinephrine and vasopressin in patients with septic shock.

In the Vasopressin in Septic Shock Trial (VASST), 382 patients with septic shock were randomized to open-label norepinephrine with blinded norepinephrine, and 382 were randomized to open-label norepinephrine with blinded adjunctive vasopressin.

After initiation of the study drug, patients randomized to vasopressin had significantly lower requirements for open-label norepinephrine (P < .001). Although no differences occurred in the primary outcome of 28-day mortality, 90-day mortality was lower in the vasopressin group.

In the Vasopressin vs Norepinephrine as Initial Therapy in Septic Shock (VANISH) trial, 204 patients with septic shock were randomized to norepinephrine and 204 to vasopressin as an initial vasoactive agent. Although no differences appeared between the groups for the two primary outcomes of 28-day mortality and days free of kidney failure, the vasopressin group had a lower frequency of the use of kidney replacement therapy (absolute difference –9.9% vs. –0.6%).

The VANISH study was limited by the fact that 85% of the patients were receiving norepinephrine when they were randomized; “therefore, this study is best described as evaluating catecholamine-adjunctive vasopressin,” the researchers say.

The third clinical trial, published only as an abstract, randomized 387 patients with septic shock who were already receiving low doses of norepinephrine to either norepinephrine with adjunctive vasopressin or norepinephrine alone. Rates of 28-day mortality were significantly lower in the vasopressin group (34.0% vs. 42.3%; P = .03).

Several meta-analyses involving multiple vasopressin receptor agonists have shown an association between reduced mortality and their use. In addition, recent observational studies have shown an association between lower mortality and the initiation of vasopressors at a lower norepinephrine-equivalent dose or lower lactate concentration.

As for clinical implications, the 2021 version of the Surviving Sepsis Campaign (SSC) guidelines included a meta-analysis of 10 randomized, controlled trials that showed improved mortality associated with vasopressin use. This version of the guidelines was the first to address the timing of vasopressin initiation.

Because of insufficient evidence, the guidance was worded as “in our practice, vasopressin is usually started when the dose of norepinephrine is in the range of 0.25-0.5 mcg/kg/min,” the researchers write. “Although this is not a recommendation by the SSC for a specific threshold of catecholamine dose where vasopressin should be initiated, this statement represents clinician interest and the need for further research on the topic,” they note.

“Future studies of vasopressin should focus on the timing of its initiation at various clinical thresholds and patient selection for receipt of vasopressin,” they conclude.

The study was supported by the National Institutes of Health, National Institute of General Medical Sciences. Dr. Sacha has disclosed consulting for Wolters Kluwer.

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

In patients aged 2-11 years, roflumilast cream was well tolerated and improved signs and symptoms of psoriasis over 4 weeks, according to results from a pair of phase two studies.

“Limited topical treatments are approved for children younger than 12 years old with psoriasis,” researchers led by Adelaide A. Hebert, MD, wrote in their abstract. The results were presented during a poster session at the annual meeting of the Society for Pediatric Dermatology.

Roflumilast cream 0.3% (Zoryve) is a once-daily, topical nonsteroidal treatment from Arcutis Biotherapeutics. A phosphodiesterase-4 inhibitor, it was approved by the Food and Drug Administration in 2022 for mild, moderate and severe psoriasis in individuals aged 12 and older, including intertriginous psoriasis.

For the analysis, Dr. Hebert, chief of pediatric dermatology at the University of Texas, Houston, and colleagues conducted two 4-week, phase 2, open-label safety studies of roflumilast cream 0.3%.

One, study 216, enrolled 10 children aged 2-5, and all but one were Black. The other, study 215, enrolled 20 children aged 6-11, and half were Black and nearly half were White. At baseline, patients had 2% or greater body surface area (BSA) involvement and an Investigator Global Assessment (IGA) score of at least mild.

Caregivers applied roflumilast cream to all affected areas once daily for 28 days. The researchers collected pharmacokinetic samples at week 2 and week 4. The primary endpoints were pharmacokinetic, safety, and tolerability.

Efficacy was evaluated as exploratory endpoints: An IGA of clear or almost clear plus a 2-grade or more improvement from baseline, a 50% or greater improvement and a 75% or greater improvement on the Psoriasis Area and Severity Index (PASI-50 and PASI-75), a 4-point or greater reduction in the Worst Itch–Numeric Rating Scale (WI-NRS) in patients with a baseline score of 4 or greater, a mean change from baseline in BSA, and improvement in the Children’s Dermatology Life Quality Index (CDLQI).

At baseline, the mean BSA was similar for patients enrolled in studies 216 and 215 (9.6% and 8.8%, respectively), and 80% of all patients had baseline IGA of moderate. By week 2, the mean roflumilast and N-oxide predose plasma concentrations among patients in the younger group were 2.15 and 22.4 ng/mL, compared with 3.15 and 28.9 ng/mL among those in the older group. At week 4, the mean roflumilast and N-oxide predose concentrations were 2.04 and 15.8 ng/mL in the younger group (study 216), compared with 1.68 and 15.7 ng/mL in the older group (study 215).

As for efficacy, 90% and 40% of patients in studies 216 and 215 achieved IGA success at week 4, respectively, while 90% and 50% achieved PASI-75, 90% and 40% achieved WI-NRS success, and the mean BSA reductions at week 4 were 79.1% and 44.4%. Meanwhile, one younger patient in study 216 reported a treatment-emergent adverse event (TEAE) of headache, which was considered mild, while four older patients in study 215 reported 8 TEAEs, which were considered mild and ranged from back pain to nasal congestion.

“The rapid onset of action was surprising but exceedingly rewarding for the subjects enrolled in the study,” Dr. Hebert told this news organization after the meeting. “The PASI scores and itch scores were markedly improved at the end of the 4-week clinical trial. Patient and parents alike were pleased to use a steroid-free option with once-daily application and rapid onset of action to help control plaque psoriasis.”

In the poster abstract, she and her coauthors concluded that “under maximal use conditions in children aged 2-11 years, roflumilast cream 0.3% was well tolerated and improved signs and symptoms of psoriasis with measured improvements in IGA score, PASI score, BSA involvement, CDLQI, and WI-NRS. Overall, pharmacokinetics, safety, tolerability, and efficacy in patients aged 2-11 years were consistent with prior results in adults and adolescents.”

The study was funded by Arcutis Biotherapeutics. Dr. Hebert reported that she is an investigator for Arcutis. About half the coauthors are employees of Arcutis, and the other half disclosed grants, research funding and/or honoraria from the company. Research grants from the company for this study were paid to the McGovern Medical School at the University of Texas.

In patients aged 2-11 years, roflumilast cream was well tolerated and improved signs and symptoms of psoriasis over 4 weeks, according to results from a pair of phase two studies.

“Limited topical treatments are approved for children younger than 12 years old with psoriasis,” researchers led by Adelaide A. Hebert, MD, wrote in their abstract. The results were presented during a poster session at the annual meeting of the Society for Pediatric Dermatology.

Roflumilast cream 0.3% (Zoryve) is a once-daily, topical nonsteroidal treatment from Arcutis Biotherapeutics. A phosphodiesterase-4 inhibitor, it was approved by the Food and Drug Administration in 2022 for mild, moderate and severe psoriasis in individuals aged 12 and older, including intertriginous psoriasis.

For the analysis, Dr. Hebert, chief of pediatric dermatology at the University of Texas, Houston, and colleagues conducted two 4-week, phase 2, open-label safety studies of roflumilast cream 0.3%.

One, study 216, enrolled 10 children aged 2-5, and all but one were Black. The other, study 215, enrolled 20 children aged 6-11, and half were Black and nearly half were White. At baseline, patients had 2% or greater body surface area (BSA) involvement and an Investigator Global Assessment (IGA) score of at least mild.

Caregivers applied roflumilast cream to all affected areas once daily for 28 days. The researchers collected pharmacokinetic samples at week 2 and week 4. The primary endpoints were pharmacokinetic, safety, and tolerability.

Efficacy was evaluated as exploratory endpoints: An IGA of clear or almost clear plus a 2-grade or more improvement from baseline, a 50% or greater improvement and a 75% or greater improvement on the Psoriasis Area and Severity Index (PASI-50 and PASI-75), a 4-point or greater reduction in the Worst Itch–Numeric Rating Scale (WI-NRS) in patients with a baseline score of 4 or greater, a mean change from baseline in BSA, and improvement in the Children’s Dermatology Life Quality Index (CDLQI).

At baseline, the mean BSA was similar for patients enrolled in studies 216 and 215 (9.6% and 8.8%, respectively), and 80% of all patients had baseline IGA of moderate. By week 2, the mean roflumilast and N-oxide predose plasma concentrations among patients in the younger group were 2.15 and 22.4 ng/mL, compared with 3.15 and 28.9 ng/mL among those in the older group. At week 4, the mean roflumilast and N-oxide predose concentrations were 2.04 and 15.8 ng/mL in the younger group (study 216), compared with 1.68 and 15.7 ng/mL in the older group (study 215).

As for efficacy, 90% and 40% of patients in studies 216 and 215 achieved IGA success at week 4, respectively, while 90% and 50% achieved PASI-75, 90% and 40% achieved WI-NRS success, and the mean BSA reductions at week 4 were 79.1% and 44.4%. Meanwhile, one younger patient in study 216 reported a treatment-emergent adverse event (TEAE) of headache, which was considered mild, while four older patients in study 215 reported 8 TEAEs, which were considered mild and ranged from back pain to nasal congestion.

“The rapid onset of action was surprising but exceedingly rewarding for the subjects enrolled in the study,” Dr. Hebert told this news organization after the meeting. “The PASI scores and itch scores were markedly improved at the end of the 4-week clinical trial. Patient and parents alike were pleased to use a steroid-free option with once-daily application and rapid onset of action to help control plaque psoriasis.”

In the poster abstract, she and her coauthors concluded that “under maximal use conditions in children aged 2-11 years, roflumilast cream 0.3% was well tolerated and improved signs and symptoms of psoriasis with measured improvements in IGA score, PASI score, BSA involvement, CDLQI, and WI-NRS. Overall, pharmacokinetics, safety, tolerability, and efficacy in patients aged 2-11 years were consistent with prior results in adults and adolescents.”

The study was funded by Arcutis Biotherapeutics. Dr. Hebert reported that she is an investigator for Arcutis. About half the coauthors are employees of Arcutis, and the other half disclosed grants, research funding and/or honoraria from the company. Research grants from the company for this study were paid to the McGovern Medical School at the University of Texas.

In patients aged 2-11 years, roflumilast cream was well tolerated and improved signs and symptoms of psoriasis over 4 weeks, according to results from a pair of phase two studies.

“Limited topical treatments are approved for children younger than 12 years old with psoriasis,” researchers led by Adelaide A. Hebert, MD, wrote in their abstract. The results were presented during a poster session at the annual meeting of the Society for Pediatric Dermatology.

Roflumilast cream 0.3% (Zoryve) is a once-daily, topical nonsteroidal treatment from Arcutis Biotherapeutics. A phosphodiesterase-4 inhibitor, it was approved by the Food and Drug Administration in 2022 for mild, moderate and severe psoriasis in individuals aged 12 and older, including intertriginous psoriasis.

For the analysis, Dr. Hebert, chief of pediatric dermatology at the University of Texas, Houston, and colleagues conducted two 4-week, phase 2, open-label safety studies of roflumilast cream 0.3%.

One, study 216, enrolled 10 children aged 2-5, and all but one were Black. The other, study 215, enrolled 20 children aged 6-11, and half were Black and nearly half were White. At baseline, patients had 2% or greater body surface area (BSA) involvement and an Investigator Global Assessment (IGA) score of at least mild.

Caregivers applied roflumilast cream to all affected areas once daily for 28 days. The researchers collected pharmacokinetic samples at week 2 and week 4. The primary endpoints were pharmacokinetic, safety, and tolerability.

Efficacy was evaluated as exploratory endpoints: An IGA of clear or almost clear plus a 2-grade or more improvement from baseline, a 50% or greater improvement and a 75% or greater improvement on the Psoriasis Area and Severity Index (PASI-50 and PASI-75), a 4-point or greater reduction in the Worst Itch–Numeric Rating Scale (WI-NRS) in patients with a baseline score of 4 or greater, a mean change from baseline in BSA, and improvement in the Children’s Dermatology Life Quality Index (CDLQI).

At baseline, the mean BSA was similar for patients enrolled in studies 216 and 215 (9.6% and 8.8%, respectively), and 80% of all patients had baseline IGA of moderate. By week 2, the mean roflumilast and N-oxide predose plasma concentrations among patients in the younger group were 2.15 and 22.4 ng/mL, compared with 3.15 and 28.9 ng/mL among those in the older group. At week 4, the mean roflumilast and N-oxide predose concentrations were 2.04 and 15.8 ng/mL in the younger group (study 216), compared with 1.68 and 15.7 ng/mL in the older group (study 215).

As for efficacy, 90% and 40% of patients in studies 216 and 215 achieved IGA success at week 4, respectively, while 90% and 50% achieved PASI-75, 90% and 40% achieved WI-NRS success, and the mean BSA reductions at week 4 were 79.1% and 44.4%. Meanwhile, one younger patient in study 216 reported a treatment-emergent adverse event (TEAE) of headache, which was considered mild, while four older patients in study 215 reported 8 TEAEs, which were considered mild and ranged from back pain to nasal congestion.

“The rapid onset of action was surprising but exceedingly rewarding for the subjects enrolled in the study,” Dr. Hebert told this news organization after the meeting. “The PASI scores and itch scores were markedly improved at the end of the 4-week clinical trial. Patient and parents alike were pleased to use a steroid-free option with once-daily application and rapid onset of action to help control plaque psoriasis.”

In the poster abstract, she and her coauthors concluded that “under maximal use conditions in children aged 2-11 years, roflumilast cream 0.3% was well tolerated and improved signs and symptoms of psoriasis with measured improvements in IGA score, PASI score, BSA involvement, CDLQI, and WI-NRS. Overall, pharmacokinetics, safety, tolerability, and efficacy in patients aged 2-11 years were consistent with prior results in adults and adolescents.”

The study was funded by Arcutis Biotherapeutics. Dr. Hebert reported that she is an investigator for Arcutis. About half the coauthors are employees of Arcutis, and the other half disclosed grants, research funding and/or honoraria from the company. Research grants from the company for this study were paid to the McGovern Medical School at the University of Texas.

The U.S. Food and Drug Administration has approved dostarlimab-gxly (Jemperli, GlaxoSmithKline) with carboplatin and paclitaxel, followed by single-agent dostarlimab, for primary advanced or recurrent endometrial cancer that is mismatch repair–deficient (dMMR), as determined by an FDA-approved test or microsatellite instability–high (MSI-H).

The approval was based on GSK’s RUBY trial. Across 122 patients with dMMR/MSI-H primary advanced or recurrent endometrial cancer, progression-free survival was 30.3 months in women randomly assigned to dostarlimab on a background of carboplatin and paclitaxel, followed by dostarlimab monotherapy, vs. 7.7 months among women randomly assigned to placebo (hazard ratio, 0.29; P < .0001), according to the FDA’s press release.

MMR/MSI tumor status was determined by local testing or by the Ventana MMR RxDx Panel when local testing was unavailable.

“Until now, chemotherapy alone has been the standard of care with many patients experiencing disease progression,” GSK executive Hesham Abdullah said in the company’s press release. The trial results “and today’s approval underscore our belief in the potential for Jemperli to transform cancer treatment as a backbone immuno-oncology therapy.”

Dostarlimab was already approved in the United States as monotherapy for adults with dMMR recurrent or advanced endometrial cancer that has progressed on or following a platinum-containing chemotherapy and is not a candidate for curative surgery or radiation. The latest approval means that the agent “is now indicated earlier in treatment in combination with chemotherapy,” GSK said.

Dostarlimab also carries an indication for dMMR recurrent or advanced solid tumors that have progressed on or following prior treatment when there are no satisfactory alternative treatment options.

Immune-mediated adverse reactions with dostarlimab include pneumonitis, colitis, hepatitis, endocrinopathies such as hypothyroidism, nephritis with renal dysfunction, and skin adverse reactions. The most common adverse reactions (≥ 20%) with carboplatin and paclitaxel in the Ruby trial were rash, diarrhea, hypothyroidism, and hypertension.

The recommended dostarlimab dose is 500 mg every 3 weeks for 6 doses with carboplatin and paclitaxel, followed by 1,000 mg monotherapy every 6 weeks until disease progression or unacceptable toxicity, or up to 3 years.

Drugs.com lists dostarlimab’s price at $11,712.66 for 500 mg/10 mL intravenous solution.

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

The U.S. Food and Drug Administration has approved dostarlimab-gxly (Jemperli, GlaxoSmithKline) with carboplatin and paclitaxel, followed by single-agent dostarlimab, for primary advanced or recurrent endometrial cancer that is mismatch repair–deficient (dMMR), as determined by an FDA-approved test or microsatellite instability–high (MSI-H).

The approval was based on GSK’s RUBY trial. Across 122 patients with dMMR/MSI-H primary advanced or recurrent endometrial cancer, progression-free survival was 30.3 months in women randomly assigned to dostarlimab on a background of carboplatin and paclitaxel, followed by dostarlimab monotherapy, vs. 7.7 months among women randomly assigned to placebo (hazard ratio, 0.29; P < .0001), according to the FDA’s press release.

MMR/MSI tumor status was determined by local testing or by the Ventana MMR RxDx Panel when local testing was unavailable.

“Until now, chemotherapy alone has been the standard of care with many patients experiencing disease progression,” GSK executive Hesham Abdullah said in the company’s press release. The trial results “and today’s approval underscore our belief in the potential for Jemperli to transform cancer treatment as a backbone immuno-oncology therapy.”

Dostarlimab was already approved in the United States as monotherapy for adults with dMMR recurrent or advanced endometrial cancer that has progressed on or following a platinum-containing chemotherapy and is not a candidate for curative surgery or radiation. The latest approval means that the agent “is now indicated earlier in treatment in combination with chemotherapy,” GSK said.

Dostarlimab also carries an indication for dMMR recurrent or advanced solid tumors that have progressed on or following prior treatment when there are no satisfactory alternative treatment options.

Immune-mediated adverse reactions with dostarlimab include pneumonitis, colitis, hepatitis, endocrinopathies such as hypothyroidism, nephritis with renal dysfunction, and skin adverse reactions. The most common adverse reactions (≥ 20%) with carboplatin and paclitaxel in the Ruby trial were rash, diarrhea, hypothyroidism, and hypertension.

The recommended dostarlimab dose is 500 mg every 3 weeks for 6 doses with carboplatin and paclitaxel, followed by 1,000 mg monotherapy every 6 weeks until disease progression or unacceptable toxicity, or up to 3 years.

Drugs.com lists dostarlimab’s price at $11,712.66 for 500 mg/10 mL intravenous solution.

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

The U.S. Food and Drug Administration has approved dostarlimab-gxly (Jemperli, GlaxoSmithKline) with carboplatin and paclitaxel, followed by single-agent dostarlimab, for primary advanced or recurrent endometrial cancer that is mismatch repair–deficient (dMMR), as determined by an FDA-approved test or microsatellite instability–high (MSI-H).

The approval was based on GSK’s RUBY trial. Across 122 patients with dMMR/MSI-H primary advanced or recurrent endometrial cancer, progression-free survival was 30.3 months in women randomly assigned to dostarlimab on a background of carboplatin and paclitaxel, followed by dostarlimab monotherapy, vs. 7.7 months among women randomly assigned to placebo (hazard ratio, 0.29; P < .0001), according to the FDA’s press release.

MMR/MSI tumor status was determined by local testing or by the Ventana MMR RxDx Panel when local testing was unavailable.

“Until now, chemotherapy alone has been the standard of care with many patients experiencing disease progression,” GSK executive Hesham Abdullah said in the company’s press release. The trial results “and today’s approval underscore our belief in the potential for Jemperli to transform cancer treatment as a backbone immuno-oncology therapy.”

Dostarlimab was already approved in the United States as monotherapy for adults with dMMR recurrent or advanced endometrial cancer that has progressed on or following a platinum-containing chemotherapy and is not a candidate for curative surgery or radiation. The latest approval means that the agent “is now indicated earlier in treatment in combination with chemotherapy,” GSK said.

Dostarlimab also carries an indication for dMMR recurrent or advanced solid tumors that have progressed on or following prior treatment when there are no satisfactory alternative treatment options.

Immune-mediated adverse reactions with dostarlimab include pneumonitis, colitis, hepatitis, endocrinopathies such as hypothyroidism, nephritis with renal dysfunction, and skin adverse reactions. The most common adverse reactions (≥ 20%) with carboplatin and paclitaxel in the Ruby trial were rash, diarrhea, hypothyroidism, and hypertension.

The recommended dostarlimab dose is 500 mg every 3 weeks for 6 doses with carboplatin and paclitaxel, followed by 1,000 mg monotherapy every 6 weeks until disease progression or unacceptable toxicity, or up to 3 years.

Drugs.com lists dostarlimab’s price at $11,712.66 for 500 mg/10 mL intravenous solution.

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

AUSTIN, TEX. – Treatment with the anticalcitonin gene-related peptide (anti-CGRP) fremanezumab (Ajovy, Teva Pharmaceuticals) reduces depressive symptoms in patients with migraine and comorbid major depressive disorder, new research shows.

Patients with both conditions who were randomly assigned to receive fremanezumab showed a statistically significant reduction in both the 17-item Hamilton Depression Rating Scale (HAMD-17) and the nine-criteria Patient Health Questionnaire (PHQ-9) scores, compared with matched controls who received placebo.

The results from the UNITE trial were presented at the annual meeting of the American Headache Society.
 

Long-standing questions

“It’s been well known for a long time that migraine is comorbid with a number of illnesses, and one of the most common is depression,” said study investigator Richard B. Lipton, a professor of neurology at Albert Einstein College of Medicine and the director of the Montefiore Headache Center, New York.

“Do you treat the depression? Do you treat the migraine? Do you independently treat both? Those have been long-standing questions for clinicians,” Dr. Lipton said.

Investigators randomly assigned 330 adults with migraine who were diagnosed with moderate-to-severe MDD (defined as a PHQ-9 score of 10 or greater) to receive 225 mg subcutaneous monthly fremanezumab (n = 164) or placebo (n = 166) for 12 weeks.

The trial continued as an open-label trial for another 12 weeks.

During the double-blind phase of the study, the mean change from baseline in the HAMD-17 score with placebo was –4.6 at week 8 and –5.4 at week 12, compared with –6.0 with fremanezumab at week 8 (P = .0205) and –6.7 at week 12 (P = .0228).

The change from baseline in PHQ-9 total score at week 8 was –5.8 for placebo and –7.1 for fremanezumab (P = .0283). At week 12, the change was –6.3 for placebo versus –7.8 for fremanezumab (P = .0108). These reductions were maintained throughout the open-label period of the trial.

The beneficial effect on depression and migraine demonstrated in the study is interesting on several levels, Dr. Lipton said.

“One, it tells us that if the patient has migraine and depression and you treat with fremanezumab, both disorders get better to a statistically significant degree. That’s critically important,” he said.

“The other thing, and this is actually what I find most interesting about this study, is that fremanezumab doesn’t get into the brain. There are many antimigraine therapies that do, so you can treat a patient with migraine and depression with a tricyclic antidepressant.”

“It may make the migraine better and the depression better, but you don’t know if the benefit in depression comes from the improvement in migraine, because of course the antidepressant works for both conditions. Maybe there are people who would disagree with this, but my interpretation [of the trial results] is that the depression got better because the migraine got better,” he added.

The link between migraine and depression is well established, Dr. Lipton added. Longitudinal studies have shown that people with depression but without migraine develop migraine at increased rates, compared with people with no depression. Conversely, people with migraine but no depression develop depression at increased rates.

“Both disorders may have a common substrate, but I also think many forms of chronic pain lead to depression, and that’s the part we’re making better,” he said.

If fremanezumab has this dual effect on migraine and depression, it is possible that other anti-CGRP drugs will have a similar effect, Dr. Lipton said.

“Honestly, my hope is that other companies that make effective drugs will do similar studies to see if other monoclonal antibodies that target CGRP have the same effect. My guess is that all of them work but until the studies are done, I’m going to use fremanezumab, the one that has been studied, in my patients.”

He added that depression is an important comorbidity of migraine and represents a huge challenge for clinicians. “A lot of headache patients want to know what to do about comorbid anxiety or comorbid depression. I run a headache center in a specialty practice, and when people come in with migraine, they almost always come in with migraine and depression or anxiety or another pain disorder, or something else, and one of the great challenges in the practice is managing these comorbidities,” he said.
 

A bidirectional relationship

The overlap between migraine and depression and anxiety has been known for quite a while, agreed Elizabeth W. Loder, MD, MPH, vice chair of academic affairs, department of neurology, Brigham and Women’s Hospital, and professor of neurology at Harvard Medical School, both in Boston.

“I think the relationship is generally viewed as bidirectional and causality is uncertain. I still do not think I would assume that any drug that reduces migraine would reduce depression,” said Dr. Loder.

However, she added, the fremanezumab study data are interesting. “The effects of any drug on depression could be due to improvement of migraine or it could be due to some other effect of the treatment on depression. That is what makes these results so intriguing. If the findings are borne out by other studies, it could mean that these treatments would be preferred to those older ones in patients with depression,” Dr. Loder said.

Also commenting on the findings, Huma Sheikh, MD, CEO of NY Neurology Medicine PC, said the study is important because it confirms the strong association between migraine and depression. “Both conditions have similar underlying neurobiological pathophysiologies, and if you are impacting one area in the brain with the CGRP inhibitors, you might also be targeting some of the receptors or pathways that are involved in depression,” Dr. Sheikh said.

The study was funded by Teva Pharmaceuticals. Dr. Lipton reported financial relationships with Teva and multiple other pharmaceutical companies. Dr. Loder and Dr. Sheikh have disclosed no relevant financial relationships.

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

AUSTIN, TEX. – Treatment with the anticalcitonin gene-related peptide (anti-CGRP) fremanezumab (Ajovy, Teva Pharmaceuticals) reduces depressive symptoms in patients with migraine and comorbid major depressive disorder, new research shows.

Patients with both conditions who were randomly assigned to receive fremanezumab showed a statistically significant reduction in both the 17-item Hamilton Depression Rating Scale (HAMD-17) and the nine-criteria Patient Health Questionnaire (PHQ-9) scores, compared with matched controls who received placebo.

The results from the UNITE trial were presented at the annual meeting of the American Headache Society.
 

Long-standing questions

“It’s been well known for a long time that migraine is comorbid with a number of illnesses, and one of the most common is depression,” said study investigator Richard B. Lipton, a professor of neurology at Albert Einstein College of Medicine and the director of the Montefiore Headache Center, New York.

“Do you treat the depression? Do you treat the migraine? Do you independently treat both? Those have been long-standing questions for clinicians,” Dr. Lipton said.

Investigators randomly assigned 330 adults with migraine who were diagnosed with moderate-to-severe MDD (defined as a PHQ-9 score of 10 or greater) to receive 225 mg subcutaneous monthly fremanezumab (n = 164) or placebo (n = 166) for 12 weeks.

The trial continued as an open-label trial for another 12 weeks.

During the double-blind phase of the study, the mean change from baseline in the HAMD-17 score with placebo was –4.6 at week 8 and –5.4 at week 12, compared with –6.0 with fremanezumab at week 8 (P = .0205) and –6.7 at week 12 (P = .0228).

The change from baseline in PHQ-9 total score at week 8 was –5.8 for placebo and –7.1 for fremanezumab (P = .0283). At week 12, the change was –6.3 for placebo versus –7.8 for fremanezumab (P = .0108). These reductions were maintained throughout the open-label period of the trial.

The beneficial effect on depression and migraine demonstrated in the study is interesting on several levels, Dr. Lipton said.

“One, it tells us that if the patient has migraine and depression and you treat with fremanezumab, both disorders get better to a statistically significant degree. That’s critically important,” he said.

“The other thing, and this is actually what I find most interesting about this study, is that fremanezumab doesn’t get into the brain. There are many antimigraine therapies that do, so you can treat a patient with migraine and depression with a tricyclic antidepressant.”

“It may make the migraine better and the depression better, but you don’t know if the benefit in depression comes from the improvement in migraine, because of course the antidepressant works for both conditions. Maybe there are people who would disagree with this, but my interpretation [of the trial results] is that the depression got better because the migraine got better,” he added.

The link between migraine and depression is well established, Dr. Lipton added. Longitudinal studies have shown that people with depression but without migraine develop migraine at increased rates, compared with people with no depression. Conversely, people with migraine but no depression develop depression at increased rates.

“Both disorders may have a common substrate, but I also think many forms of chronic pain lead to depression, and that’s the part we’re making better,” he said.

If fremanezumab has this dual effect on migraine and depression, it is possible that other anti-CGRP drugs will have a similar effect, Dr. Lipton said.

“Honestly, my hope is that other companies that make effective drugs will do similar studies to see if other monoclonal antibodies that target CGRP have the same effect. My guess is that all of them work but until the studies are done, I’m going to use fremanezumab, the one that has been studied, in my patients.”

He added that depression is an important comorbidity of migraine and represents a huge challenge for clinicians. “A lot of headache patients want to know what to do about comorbid anxiety or comorbid depression. I run a headache center in a specialty practice, and when people come in with migraine, they almost always come in with migraine and depression or anxiety or another pain disorder, or something else, and one of the great challenges in the practice is managing these comorbidities,” he said.
 

A bidirectional relationship

The overlap between migraine and depression and anxiety has been known for quite a while, agreed Elizabeth W. Loder, MD, MPH, vice chair of academic affairs, department of neurology, Brigham and Women’s Hospital, and professor of neurology at Harvard Medical School, both in Boston.

“I think the relationship is generally viewed as bidirectional and causality is uncertain. I still do not think I would assume that any drug that reduces migraine would reduce depression,” said Dr. Loder.

However, she added, the fremanezumab study data are interesting. “The effects of any drug on depression could be due to improvement of migraine or it could be due to some other effect of the treatment on depression. That is what makes these results so intriguing. If the findings are borne out by other studies, it could mean that these treatments would be preferred to those older ones in patients with depression,” Dr. Loder said.

Also commenting on the findings, Huma Sheikh, MD, CEO of NY Neurology Medicine PC, said the study is important because it confirms the strong association between migraine and depression. “Both conditions have similar underlying neurobiological pathophysiologies, and if you are impacting one area in the brain with the CGRP inhibitors, you might also be targeting some of the receptors or pathways that are involved in depression,” Dr. Sheikh said.

The study was funded by Teva Pharmaceuticals. Dr. Lipton reported financial relationships with Teva and multiple other pharmaceutical companies. Dr. Loder and Dr. Sheikh have disclosed no relevant financial relationships.

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

AUSTIN, TEX. – Treatment with the anticalcitonin gene-related peptide (anti-CGRP) fremanezumab (Ajovy, Teva Pharmaceuticals) reduces depressive symptoms in patients with migraine and comorbid major depressive disorder, new research shows.

Patients with both conditions who were randomly assigned to receive fremanezumab showed a statistically significant reduction in both the 17-item Hamilton Depression Rating Scale (HAMD-17) and the nine-criteria Patient Health Questionnaire (PHQ-9) scores, compared with matched controls who received placebo.

The results from the UNITE trial were presented at the annual meeting of the American Headache Society.
 

Long-standing questions

“It’s been well known for a long time that migraine is comorbid with a number of illnesses, and one of the most common is depression,” said study investigator Richard B. Lipton, a professor of neurology at Albert Einstein College of Medicine and the director of the Montefiore Headache Center, New York.

“Do you treat the depression? Do you treat the migraine? Do you independently treat both? Those have been long-standing questions for clinicians,” Dr. Lipton said.

Investigators randomly assigned 330 adults with migraine who were diagnosed with moderate-to-severe MDD (defined as a PHQ-9 score of 10 or greater) to receive 225 mg subcutaneous monthly fremanezumab (n = 164) or placebo (n = 166) for 12 weeks.

The trial continued as an open-label trial for another 12 weeks.

During the double-blind phase of the study, the mean change from baseline in the HAMD-17 score with placebo was –4.6 at week 8 and –5.4 at week 12, compared with –6.0 with fremanezumab at week 8 (P = .0205) and –6.7 at week 12 (P = .0228).

The change from baseline in PHQ-9 total score at week 8 was –5.8 for placebo and –7.1 for fremanezumab (P = .0283). At week 12, the change was –6.3 for placebo versus –7.8 for fremanezumab (P = .0108). These reductions were maintained throughout the open-label period of the trial.

The beneficial effect on depression and migraine demonstrated in the study is interesting on several levels, Dr. Lipton said.

“One, it tells us that if the patient has migraine and depression and you treat with fremanezumab, both disorders get better to a statistically significant degree. That’s critically important,” he said.

“The other thing, and this is actually what I find most interesting about this study, is that fremanezumab doesn’t get into the brain. There are many antimigraine therapies that do, so you can treat a patient with migraine and depression with a tricyclic antidepressant.”

“It may make the migraine better and the depression better, but you don’t know if the benefit in depression comes from the improvement in migraine, because of course the antidepressant works for both conditions. Maybe there are people who would disagree with this, but my interpretation [of the trial results] is that the depression got better because the migraine got better,” he added.

The link between migraine and depression is well established, Dr. Lipton added. Longitudinal studies have shown that people with depression but without migraine develop migraine at increased rates, compared with people with no depression. Conversely, people with migraine but no depression develop depression at increased rates.

“Both disorders may have a common substrate, but I also think many forms of chronic pain lead to depression, and that’s the part we’re making better,” he said.

If fremanezumab has this dual effect on migraine and depression, it is possible that other anti-CGRP drugs will have a similar effect, Dr. Lipton said.

“Honestly, my hope is that other companies that make effective drugs will do similar studies to see if other monoclonal antibodies that target CGRP have the same effect. My guess is that all of them work but until the studies are done, I’m going to use fremanezumab, the one that has been studied, in my patients.”

He added that depression is an important comorbidity of migraine and represents a huge challenge for clinicians. “A lot of headache patients want to know what to do about comorbid anxiety or comorbid depression. I run a headache center in a specialty practice, and when people come in with migraine, they almost always come in with migraine and depression or anxiety or another pain disorder, or something else, and one of the great challenges in the practice is managing these comorbidities,” he said.
 

A bidirectional relationship

The overlap between migraine and depression and anxiety has been known for quite a while, agreed Elizabeth W. Loder, MD, MPH, vice chair of academic affairs, department of neurology, Brigham and Women’s Hospital, and professor of neurology at Harvard Medical School, both in Boston.

“I think the relationship is generally viewed as bidirectional and causality is uncertain. I still do not think I would assume that any drug that reduces migraine would reduce depression,” said Dr. Loder.

However, she added, the fremanezumab study data are interesting. “The effects of any drug on depression could be due to improvement of migraine or it could be due to some other effect of the treatment on depression. That is what makes these results so intriguing. If the findings are borne out by other studies, it could mean that these treatments would be preferred to those older ones in patients with depression,” Dr. Loder said.

Also commenting on the findings, Huma Sheikh, MD, CEO of NY Neurology Medicine PC, said the study is important because it confirms the strong association between migraine and depression. “Both conditions have similar underlying neurobiological pathophysiologies, and if you are impacting one area in the brain with the CGRP inhibitors, you might also be targeting some of the receptors or pathways that are involved in depression,” Dr. Sheikh said.

The study was funded by Teva Pharmaceuticals. Dr. Lipton reported financial relationships with Teva and multiple other pharmaceutical companies. Dr. Loder and Dr. Sheikh have disclosed no relevant financial relationships.

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

The U.S. Food and Drug Administration has approved rozanolixizumab (Rystiggo) to treat adults with generalized myasthenia gravis (gMG) who are positive for anti-acetylcholine receptor (AChR) or anti–muscle-specific tyrosine kinase (MuSK) antibody, the drug’s manufacturer, UCB, has announced.

Olivier Le Moal/Getty Images

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

The U.S. Food and Drug Administration has approved rozanolixizumab (Rystiggo) to treat adults with generalized myasthenia gravis (gMG) who are positive for anti-acetylcholine receptor (AChR) or anti–muscle-specific tyrosine kinase (MuSK) antibody, the drug’s manufacturer, UCB, has announced.

Olivier Le Moal/Getty Images

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

The U.S. Food and Drug Administration has approved rozanolixizumab (Rystiggo) to treat adults with generalized myasthenia gravis (gMG) who are positive for anti-acetylcholine receptor (AChR) or anti–muscle-specific tyrosine kinase (MuSK) antibody, the drug’s manufacturer, UCB, has announced.

Olivier Le Moal/Getty Images

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

The Food and Drug Administration approved ritlecitinib on June 23 for the treatment of severe alopecia areata in people ages 12 and older, the manufacturer announced.

Taken as a once-daily pill, ritlecitinib is a dual inhibitor of the TEC family of tyrosine kinases and of Janus kinase 3 (JAK3). The recommended dose of ritlecitinib, which will be marketed as Litfulo, is 50 mg once a day, according to the statement announcing the approval from Pfizer.

Olivier Le Moal/Getty Images

It is the second JAK inhibitor approved for treating alopecia areata, following approval of baricitinib (Olumiant) in June 2022 for AA in adults. Ritlecitinib is the first JAK inhibitor approved for children ages 12 and older with AA.  

The European Medicines Agency has also accepted the Marketing Authorization Application for ritlecitinib in the same population and a decision is expected in the fourth quarter of this year.
 

Approval based on ALLEGRO trials

Approval was based on  previously announced results from trials, including the phase 2b/3 ALLEGRO study of ritlecitinib in 718 patients aged 12 years and older with alopecia areata, with 50% of more scalp hair loss, as measured by the Severity of Alopecia Tool (SALT), including patients with alopecia totalis (complete scalp hair loss) and alopecia universalis (complete scalp, face, and body hair loss).

Patients in the trial were experiencing a current episode of alopecia areata that had lasted between 6 months and 10 years. They were randomized to receive once-daily ritlecitinib at doses of 30 mg or 50 mg (with or without 1 month of initial treatment with once-daily ritlecitinib 200 mg), ritlecitinib 10 mg, or placebo.

Statistically significantly higher proportions of patients treated with ritlecitinib 30 mg and 50 mg (with or without the loading dose) had 80% or more scalp hair coverage, as measured by a SALT score of 20 or less after 6 months of treatment versus placebo. After 6 months of treatment, among those on the 50-mg dose, 23% had achieved a SALT score of 20 or less, compared with 2% of those on placebo. The results were published in The Lancet.

According to the company release, efficacy and safety of ritlecitinib was consistent between those ages 12-17 and adults, and the most common adverse events reported in the study, in at least 4% of patients treated with ritlecitinib, were headache (10.8%), diarrhea (10%), acne (6.2%), rash (5.4%), and urticaria (4.6%). 

Ritlecitinib labeling includes the boxed warning about the risk for serious infections, mortality, malignancy, major adverse cardiovascular events, and thrombosis, which is included in the labels for other JAK inhibitors.
 

Ritlecitinib evaluated for other diseases

In addition to alopecia areata, ritlecitinib has shown efficacy and acceptable safety in treating ulcerative colitis and is being evaluated for treating vitiligo, Crohn’s disease, and rheumatoid arthritis.

In the statement, the company says that ritlecitinib will be available “in the coming weeks.” The manufacturer says it also has completed regulatory submissions for ritlecitinib in the United Kingdom, China, and Japan, and expects decisions this year.

Alopecia areata affects about 6.8 million people in the United States and 147 million globally.

In a statement, Nicole Friedland, president and CEO of the National Alopecia Areata Foundation, said that NAAF “is thrilled to have a second FDA-approved treatment for alopecia areata, which is the first approved for adolescents.”

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

The Food and Drug Administration approved ritlecitinib on June 23 for the treatment of severe alopecia areata in people ages 12 and older, the manufacturer announced.

Taken as a once-daily pill, ritlecitinib is a dual inhibitor of the TEC family of tyrosine kinases and of Janus kinase 3 (JAK3). The recommended dose of ritlecitinib, which will be marketed as Litfulo, is 50 mg once a day, according to the statement announcing the approval from Pfizer.

Olivier Le Moal/Getty Images

It is the second JAK inhibitor approved for treating alopecia areata, following approval of baricitinib (Olumiant) in June 2022 for AA in adults. Ritlecitinib is the first JAK inhibitor approved for children ages 12 and older with AA.  

The European Medicines Agency has also accepted the Marketing Authorization Application for ritlecitinib in the same population and a decision is expected in the fourth quarter of this year.
 

Approval based on ALLEGRO trials

Approval was based on  previously announced results from trials, including the phase 2b/3 ALLEGRO study of ritlecitinib in 718 patients aged 12 years and older with alopecia areata, with 50% of more scalp hair loss, as measured by the Severity of Alopecia Tool (SALT), including patients with alopecia totalis (complete scalp hair loss) and alopecia universalis (complete scalp, face, and body hair loss).

Patients in the trial were experiencing a current episode of alopecia areata that had lasted between 6 months and 10 years. They were randomized to receive once-daily ritlecitinib at doses of 30 mg or 50 mg (with or without 1 month of initial treatment with once-daily ritlecitinib 200 mg), ritlecitinib 10 mg, or placebo.

Statistically significantly higher proportions of patients treated with ritlecitinib 30 mg and 50 mg (with or without the loading dose) had 80% or more scalp hair coverage, as measured by a SALT score of 20 or less after 6 months of treatment versus placebo. After 6 months of treatment, among those on the 50-mg dose, 23% had achieved a SALT score of 20 or less, compared with 2% of those on placebo. The results were published in The Lancet.

According to the company release, efficacy and safety of ritlecitinib was consistent between those ages 12-17 and adults, and the most common adverse events reported in the study, in at least 4% of patients treated with ritlecitinib, were headache (10.8%), diarrhea (10%), acne (6.2%), rash (5.4%), and urticaria (4.6%). 

Ritlecitinib labeling includes the boxed warning about the risk for serious infections, mortality, malignancy, major adverse cardiovascular events, and thrombosis, which is included in the labels for other JAK inhibitors.
 

Ritlecitinib evaluated for other diseases

In addition to alopecia areata, ritlecitinib has shown efficacy and acceptable safety in treating ulcerative colitis and is being evaluated for treating vitiligo, Crohn’s disease, and rheumatoid arthritis.

In the statement, the company says that ritlecitinib will be available “in the coming weeks.” The manufacturer says it also has completed regulatory submissions for ritlecitinib in the United Kingdom, China, and Japan, and expects decisions this year.

Alopecia areata affects about 6.8 million people in the United States and 147 million globally.

In a statement, Nicole Friedland, president and CEO of the National Alopecia Areata Foundation, said that NAAF “is thrilled to have a second FDA-approved treatment for alopecia areata, which is the first approved for adolescents.”

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

The Food and Drug Administration approved ritlecitinib on June 23 for the treatment of severe alopecia areata in people ages 12 and older, the manufacturer announced.

Taken as a once-daily pill, ritlecitinib is a dual inhibitor of the TEC family of tyrosine kinases and of Janus kinase 3 (JAK3). The recommended dose of ritlecitinib, which will be marketed as Litfulo, is 50 mg once a day, according to the statement announcing the approval from Pfizer.

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It is the second JAK inhibitor approved for treating alopecia areata, following approval of baricitinib (Olumiant) in June 2022 for AA in adults. Ritlecitinib is the first JAK inhibitor approved for children ages 12 and older with AA.  

The European Medicines Agency has also accepted the Marketing Authorization Application for ritlecitinib in the same population and a decision is expected in the fourth quarter of this year.
 

Approval based on ALLEGRO trials

Approval was based on  previously announced results from trials, including the phase 2b/3 ALLEGRO study of ritlecitinib in 718 patients aged 12 years and older with alopecia areata, with 50% of more scalp hair loss, as measured by the Severity of Alopecia Tool (SALT), including patients with alopecia totalis (complete scalp hair loss) and alopecia universalis (complete scalp, face, and body hair loss).

Patients in the trial were experiencing a current episode of alopecia areata that had lasted between 6 months and 10 years. They were randomized to receive once-daily ritlecitinib at doses of 30 mg or 50 mg (with or without 1 month of initial treatment with once-daily ritlecitinib 200 mg), ritlecitinib 10 mg, or placebo.

Statistically significantly higher proportions of patients treated with ritlecitinib 30 mg and 50 mg (with or without the loading dose) had 80% or more scalp hair coverage, as measured by a SALT score of 20 or less after 6 months of treatment versus placebo. After 6 months of treatment, among those on the 50-mg dose, 23% had achieved a SALT score of 20 or less, compared with 2% of those on placebo. The results were published in The Lancet.

According to the company release, efficacy and safety of ritlecitinib was consistent between those ages 12-17 and adults, and the most common adverse events reported in the study, in at least 4% of patients treated with ritlecitinib, were headache (10.8%), diarrhea (10%), acne (6.2%), rash (5.4%), and urticaria (4.6%). 

Ritlecitinib labeling includes the boxed warning about the risk for serious infections, mortality, malignancy, major adverse cardiovascular events, and thrombosis, which is included in the labels for other JAK inhibitors.
 

Ritlecitinib evaluated for other diseases

In addition to alopecia areata, ritlecitinib has shown efficacy and acceptable safety in treating ulcerative colitis and is being evaluated for treating vitiligo, Crohn’s disease, and rheumatoid arthritis.

In the statement, the company says that ritlecitinib will be available “in the coming weeks.” The manufacturer says it also has completed regulatory submissions for ritlecitinib in the United Kingdom, China, and Japan, and expects decisions this year.

Alopecia areata affects about 6.8 million people in the United States and 147 million globally.

In a statement, Nicole Friedland, president and CEO of the National Alopecia Areata Foundation, said that NAAF “is thrilled to have a second FDA-approved treatment for alopecia areata, which is the first approved for adolescents.”

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