Pharmacology

AT UEG WEEK 2023

COPENHAGEN – Risankizumab shows noninferiority for clinical remission at week 24, and superiority of endoscopic remission at week 48 when compared with ustekinumab in patients with moderately to severely active Crohn’s disease (CD) who have failed one or more anti–tumor necrosis factor (anti-TNF) therapies, according to the results of the phase 3 SEQUENCE trial.

Secondary endpoints – presented for the first time at the United European Gastroenterology Week 2023 – also showed superiority of risankizumab (Skyrizi, AbbVie), an interleulin-23 inhibitor, over ustekinumab (Stelara), an IL-12 and IL-23 inhibitor, for clinical remission at week 48 (60.8% vs. 40.8%) and a statistically significant endoscopic response also favoring risankizumab at weeks 24 and 48.

“With endoscopic remission we see that with a single agent we have doubled the endoscopic remission rate by moving from 16% to 31% with risankizumab [at week 48],” said Laurent Peyrin-Biroulet, MD, PhD, a gastroenterologist specializing in inflammatory bowel disease at Nancy University Hospital, France. “Superiority for sure was met.”

“This sort of thing happens once in your career,” noted Dr. Peyrin-Biroulet, who presented the results of the study at the meeting. “It’s totally amazing that everything you see here was in favor of risankizumab.

“Already we see the efficacy signal in the proportion of premature discontinuations at 2% vs. 13% due to lack of efficacy [in risankizumab and ustekinumab, respectively],” he said. “This is due to drug failure.”

Risankizumab is an IL-23 inhibitor that selectively blocks the cytokine IL-23, thought to be linked to a number of chronic immune-mediated diseases, by binding to its p19 subunit. It is the first IL-23 inhibitor to receive approval from the U.S. Food and Drug Administration in June 2022 for moderately to severely active CD based on data from the ADVANCE, MOTIVATE, and FORTIFY trials.

Risankizumab and ustekinumab head-to-head

The phase 3, open-label, multicenter, randomized, clinical trial evaluated risankizumab vs. ustekinumab through week 48 in patients with moderately to severely active CD.

Participants were required to have a CD Activity Index (CDAI) score of 220 to 450 at baseline, a Simple Endoscopic Score for Crohn’s Disease (SES-CD) of 6 or more for ileocolonic or colonic disease (and of 4 or more for isolated ileal disease), excluding the presence of a narrowing component, plus an average daily stool frequency of four or more and/or average daily abdominal pain score of 2 or more. They were also required to have previously failed one or more anti-TNF therapies.

Randomization was stratified by the number of anti-TNF therapies failed (one or more than one), and steroid use at baseline; steroids were then tapered from week 2. Two primary endpoints comprised clinical remission at week 24 (defined as CDAI < 150, noninferiority margin within 10% of risankizumab vs ustekinumab in 50% of participants), and also endoscopic remission (SES-CD of 4 or less, and at least a 2-point reduction vs. baseline and no subscore greater than 1 in any individual component) at week 48 demonstrating superiority of risankizumab vs ustekinumab.

Secondary endpoints included clinical remission at week 48, endoscopic response at weeks 48 and 24, steroid-free endoscopic remission at week 48, and steroid-free clinical remission at week 48 (all tested for superiority of risankizumab vs ustekinumab).

Intravenous risankizumab at 600 mg was given at weeks 0, 4 , and 8 followed by subcutaneous risankizumab at a 360-mg maintenance dose every 8 weeks through week 48 (n = 255). Participants who completed the week-48 visit continued on subcutaneous risankizumab for up to an additional 220 weeks. Ustekinumab was given as a weight-based, intravenous induction dose at week 0 followed by a 90-mg subcutaneous dose every 8 weeks, starting at week 8 through week 48 (n = 265). Participants received open-label drug administration but efficacy assessment was blinded.

Superiority of risankizumab

Both primary endpoints were met. For clinical remission at week 24, in half of the patients enrolled, rates were 58.6% (75/128) for risankizumab and 39.5% (54/137) for ustekinumab, for a difference of 18.4% [95% confidence interval, 6.6-30.3], meaning that noninferiority was met within the predefined margin of 10%. The second primary endpoint of endoscopic remission at week 48 showed rates of 31.8% (81/255) for risankizumab and 16.2% (43/265) for ustekinumab (P < .0001 for superiority).

Risankizumab was found to be superior to ustekinumab for all secondary endpoints (all with P < .0001). Steroid-free endoscopic remission at week 48 showed a 16% difference, and steroid-free clinical remission at week 48 showed a 20% difference – both in favor of risankizumab.

In addition, more participants on risankizumab completed the study (89.4%) than those on ustekinumab (74.0%), Dr. Peyrin-Biroulet reported.

Adverse event rates (events per 100 person-years) were comparable between the two drugs at 341.2 for risankizumab and 282.7 for ustekinumab. For risankizumab, no new safety risks were observed, and those recorded were consistent with the known safety profile. Serious adverse events occurred in 10% of risankizumab-treated patients, and 17% of ustekinumab-treated patients.

“We know the safety of IL-23 inhibitors is good,” said Dr. Peyrin-Biroulet. “If we look at all adverse events there was no difference across arms, and in terms of serious adverse events, it was in favor of risankizumab because a CD flare is considered a serious adverse event.”

Session comoderator, Alessandro Armuzzi, MD, head of the Inflammatory Bowel Disease Center at the IRCCS Humanitas Research Hospital in Milan, commented on the findings. “The results look in favor of risankizumab – all the endpoints were met, not only the co-endpoints but also the secondary endpoints too,” he said.

These results, showing a preference for risankizumab, have value in helping clinicians with the sequence of therapies when patients with Crohn’s disease have failed one or more TNF inhibitor, said Dr. Armuzzi.

No funding for this study was disclosed. Dr. Peyrin-Biroulet has disclosed receiving fees from Galapagos, AbbVie, Janssen, Genentech, Alimentiv, Ferring, Tillots, Celltrion, Takeda, Pfizer, Index, Sandoz, Celgene, Biogen, SamsungBioepis, Inotrem, Allergan, MSD, Roche, Arena, Gilead, Amgen, BMS, Vifor, Norgine, Mylan, Lilly, Fresenius Kabi, OSEImmunotherapeutics, Enthera, Theravance, Pandion, Gossamer, Viatris, ThermoFisher, ONOPharma, Mopac, Cytoki, Morphic, Prometheus, and Applied MolecularTransport. Dr. Armuzzi disclosed consulting/advisory board fees from AbbVie, Amgen, Arena, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Celltrion, Eli-Lilly, Ferring, Galapagos, Gilead, Janssen, Lionhealth, MSD, Nestlé, Pfizer, Protagonist Therapeutics, Roche, Samsung Bioepis, Sandoz, Takeda, and Tillots Pharma; speaker’s fees from AbbVie, Amgen, Arena, Biogen, Bristol-Myers Squibb, Eli-Lilly, Ferring, Galapagos, Gilead, Janssen, Lionhealth, MSD, Novartis, Pfizer, Roche, Samsung Bioepis, Sandoz, and Takeda; and research grants from MSD, Takeda, Pfizer, and Biogen.

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

AT UEG WEEK 2023

COPENHAGEN – Risankizumab shows noninferiority for clinical remission at week 24, and superiority of endoscopic remission at week 48 when compared with ustekinumab in patients with moderately to severely active Crohn’s disease (CD) who have failed one or more anti–tumor necrosis factor (anti-TNF) therapies, according to the results of the phase 3 SEQUENCE trial.

Secondary endpoints – presented for the first time at the United European Gastroenterology Week 2023 – also showed superiority of risankizumab (Skyrizi, AbbVie), an interleulin-23 inhibitor, over ustekinumab (Stelara), an IL-12 and IL-23 inhibitor, for clinical remission at week 48 (60.8% vs. 40.8%) and a statistically significant endoscopic response also favoring risankizumab at weeks 24 and 48.

“With endoscopic remission we see that with a single agent we have doubled the endoscopic remission rate by moving from 16% to 31% with risankizumab [at week 48],” said Laurent Peyrin-Biroulet, MD, PhD, a gastroenterologist specializing in inflammatory bowel disease at Nancy University Hospital, France. “Superiority for sure was met.”

“This sort of thing happens once in your career,” noted Dr. Peyrin-Biroulet, who presented the results of the study at the meeting. “It’s totally amazing that everything you see here was in favor of risankizumab.

“Already we see the efficacy signal in the proportion of premature discontinuations at 2% vs. 13% due to lack of efficacy [in risankizumab and ustekinumab, respectively],” he said. “This is due to drug failure.”

Risankizumab is an IL-23 inhibitor that selectively blocks the cytokine IL-23, thought to be linked to a number of chronic immune-mediated diseases, by binding to its p19 subunit. It is the first IL-23 inhibitor to receive approval from the U.S. Food and Drug Administration in June 2022 for moderately to severely active CD based on data from the ADVANCE, MOTIVATE, and FORTIFY trials.

Risankizumab and ustekinumab head-to-head

The phase 3, open-label, multicenter, randomized, clinical trial evaluated risankizumab vs. ustekinumab through week 48 in patients with moderately to severely active CD.

Participants were required to have a CD Activity Index (CDAI) score of 220 to 450 at baseline, a Simple Endoscopic Score for Crohn’s Disease (SES-CD) of 6 or more for ileocolonic or colonic disease (and of 4 or more for isolated ileal disease), excluding the presence of a narrowing component, plus an average daily stool frequency of four or more and/or average daily abdominal pain score of 2 or more. They were also required to have previously failed one or more anti-TNF therapies.

Randomization was stratified by the number of anti-TNF therapies failed (one or more than one), and steroid use at baseline; steroids were then tapered from week 2. Two primary endpoints comprised clinical remission at week 24 (defined as CDAI < 150, noninferiority margin within 10% of risankizumab vs ustekinumab in 50% of participants), and also endoscopic remission (SES-CD of 4 or less, and at least a 2-point reduction vs. baseline and no subscore greater than 1 in any individual component) at week 48 demonstrating superiority of risankizumab vs ustekinumab.

Secondary endpoints included clinical remission at week 48, endoscopic response at weeks 48 and 24, steroid-free endoscopic remission at week 48, and steroid-free clinical remission at week 48 (all tested for superiority of risankizumab vs ustekinumab).

Intravenous risankizumab at 600 mg was given at weeks 0, 4 , and 8 followed by subcutaneous risankizumab at a 360-mg maintenance dose every 8 weeks through week 48 (n = 255). Participants who completed the week-48 visit continued on subcutaneous risankizumab for up to an additional 220 weeks. Ustekinumab was given as a weight-based, intravenous induction dose at week 0 followed by a 90-mg subcutaneous dose every 8 weeks, starting at week 8 through week 48 (n = 265). Participants received open-label drug administration but efficacy assessment was blinded.

Superiority of risankizumab

Both primary endpoints were met. For clinical remission at week 24, in half of the patients enrolled, rates were 58.6% (75/128) for risankizumab and 39.5% (54/137) for ustekinumab, for a difference of 18.4% [95% confidence interval, 6.6-30.3], meaning that noninferiority was met within the predefined margin of 10%. The second primary endpoint of endoscopic remission at week 48 showed rates of 31.8% (81/255) for risankizumab and 16.2% (43/265) for ustekinumab (P < .0001 for superiority).

Risankizumab was found to be superior to ustekinumab for all secondary endpoints (all with P < .0001). Steroid-free endoscopic remission at week 48 showed a 16% difference, and steroid-free clinical remission at week 48 showed a 20% difference – both in favor of risankizumab.

In addition, more participants on risankizumab completed the study (89.4%) than those on ustekinumab (74.0%), Dr. Peyrin-Biroulet reported.

Adverse event rates (events per 100 person-years) were comparable between the two drugs at 341.2 for risankizumab and 282.7 for ustekinumab. For risankizumab, no new safety risks were observed, and those recorded were consistent with the known safety profile. Serious adverse events occurred in 10% of risankizumab-treated patients, and 17% of ustekinumab-treated patients.

“We know the safety of IL-23 inhibitors is good,” said Dr. Peyrin-Biroulet. “If we look at all adverse events there was no difference across arms, and in terms of serious adverse events, it was in favor of risankizumab because a CD flare is considered a serious adverse event.”

Session comoderator, Alessandro Armuzzi, MD, head of the Inflammatory Bowel Disease Center at the IRCCS Humanitas Research Hospital in Milan, commented on the findings. “The results look in favor of risankizumab – all the endpoints were met, not only the co-endpoints but also the secondary endpoints too,” he said.

These results, showing a preference for risankizumab, have value in helping clinicians with the sequence of therapies when patients with Crohn’s disease have failed one or more TNF inhibitor, said Dr. Armuzzi.

No funding for this study was disclosed. Dr. Peyrin-Biroulet has disclosed receiving fees from Galapagos, AbbVie, Janssen, Genentech, Alimentiv, Ferring, Tillots, Celltrion, Takeda, Pfizer, Index, Sandoz, Celgene, Biogen, SamsungBioepis, Inotrem, Allergan, MSD, Roche, Arena, Gilead, Amgen, BMS, Vifor, Norgine, Mylan, Lilly, Fresenius Kabi, OSEImmunotherapeutics, Enthera, Theravance, Pandion, Gossamer, Viatris, ThermoFisher, ONOPharma, Mopac, Cytoki, Morphic, Prometheus, and Applied MolecularTransport. Dr. Armuzzi disclosed consulting/advisory board fees from AbbVie, Amgen, Arena, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Celltrion, Eli-Lilly, Ferring, Galapagos, Gilead, Janssen, Lionhealth, MSD, Nestlé, Pfizer, Protagonist Therapeutics, Roche, Samsung Bioepis, Sandoz, Takeda, and Tillots Pharma; speaker’s fees from AbbVie, Amgen, Arena, Biogen, Bristol-Myers Squibb, Eli-Lilly, Ferring, Galapagos, Gilead, Janssen, Lionhealth, MSD, Novartis, Pfizer, Roche, Samsung Bioepis, Sandoz, and Takeda; and research grants from MSD, Takeda, Pfizer, and Biogen.

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

AT UEG WEEK 2023

COPENHAGEN – Risankizumab shows noninferiority for clinical remission at week 24, and superiority of endoscopic remission at week 48 when compared with ustekinumab in patients with moderately to severely active Crohn’s disease (CD) who have failed one or more anti–tumor necrosis factor (anti-TNF) therapies, according to the results of the phase 3 SEQUENCE trial.

Secondary endpoints – presented for the first time at the United European Gastroenterology Week 2023 – also showed superiority of risankizumab (Skyrizi, AbbVie), an interleulin-23 inhibitor, over ustekinumab (Stelara), an IL-12 and IL-23 inhibitor, for clinical remission at week 48 (60.8% vs. 40.8%) and a statistically significant endoscopic response also favoring risankizumab at weeks 24 and 48.

“With endoscopic remission we see that with a single agent we have doubled the endoscopic remission rate by moving from 16% to 31% with risankizumab [at week 48],” said Laurent Peyrin-Biroulet, MD, PhD, a gastroenterologist specializing in inflammatory bowel disease at Nancy University Hospital, France. “Superiority for sure was met.”

“This sort of thing happens once in your career,” noted Dr. Peyrin-Biroulet, who presented the results of the study at the meeting. “It’s totally amazing that everything you see here was in favor of risankizumab.

“Already we see the efficacy signal in the proportion of premature discontinuations at 2% vs. 13% due to lack of efficacy [in risankizumab and ustekinumab, respectively],” he said. “This is due to drug failure.”

Risankizumab is an IL-23 inhibitor that selectively blocks the cytokine IL-23, thought to be linked to a number of chronic immune-mediated diseases, by binding to its p19 subunit. It is the first IL-23 inhibitor to receive approval from the U.S. Food and Drug Administration in June 2022 for moderately to severely active CD based on data from the ADVANCE, MOTIVATE, and FORTIFY trials.

Risankizumab and ustekinumab head-to-head

The phase 3, open-label, multicenter, randomized, clinical trial evaluated risankizumab vs. ustekinumab through week 48 in patients with moderately to severely active CD.

Participants were required to have a CD Activity Index (CDAI) score of 220 to 450 at baseline, a Simple Endoscopic Score for Crohn’s Disease (SES-CD) of 6 or more for ileocolonic or colonic disease (and of 4 or more for isolated ileal disease), excluding the presence of a narrowing component, plus an average daily stool frequency of four or more and/or average daily abdominal pain score of 2 or more. They were also required to have previously failed one or more anti-TNF therapies.

Randomization was stratified by the number of anti-TNF therapies failed (one or more than one), and steroid use at baseline; steroids were then tapered from week 2. Two primary endpoints comprised clinical remission at week 24 (defined as CDAI < 150, noninferiority margin within 10% of risankizumab vs ustekinumab in 50% of participants), and also endoscopic remission (SES-CD of 4 or less, and at least a 2-point reduction vs. baseline and no subscore greater than 1 in any individual component) at week 48 demonstrating superiority of risankizumab vs ustekinumab.

Secondary endpoints included clinical remission at week 48, endoscopic response at weeks 48 and 24, steroid-free endoscopic remission at week 48, and steroid-free clinical remission at week 48 (all tested for superiority of risankizumab vs ustekinumab).

Intravenous risankizumab at 600 mg was given at weeks 0, 4 , and 8 followed by subcutaneous risankizumab at a 360-mg maintenance dose every 8 weeks through week 48 (n = 255). Participants who completed the week-48 visit continued on subcutaneous risankizumab for up to an additional 220 weeks. Ustekinumab was given as a weight-based, intravenous induction dose at week 0 followed by a 90-mg subcutaneous dose every 8 weeks, starting at week 8 through week 48 (n = 265). Participants received open-label drug administration but efficacy assessment was blinded.

Superiority of risankizumab

Both primary endpoints were met. For clinical remission at week 24, in half of the patients enrolled, rates were 58.6% (75/128) for risankizumab and 39.5% (54/137) for ustekinumab, for a difference of 18.4% [95% confidence interval, 6.6-30.3], meaning that noninferiority was met within the predefined margin of 10%. The second primary endpoint of endoscopic remission at week 48 showed rates of 31.8% (81/255) for risankizumab and 16.2% (43/265) for ustekinumab (P < .0001 for superiority).

Risankizumab was found to be superior to ustekinumab for all secondary endpoints (all with P < .0001). Steroid-free endoscopic remission at week 48 showed a 16% difference, and steroid-free clinical remission at week 48 showed a 20% difference – both in favor of risankizumab.

In addition, more participants on risankizumab completed the study (89.4%) than those on ustekinumab (74.0%), Dr. Peyrin-Biroulet reported.

Adverse event rates (events per 100 person-years) were comparable between the two drugs at 341.2 for risankizumab and 282.7 for ustekinumab. For risankizumab, no new safety risks were observed, and those recorded were consistent with the known safety profile. Serious adverse events occurred in 10% of risankizumab-treated patients, and 17% of ustekinumab-treated patients.

“We know the safety of IL-23 inhibitors is good,” said Dr. Peyrin-Biroulet. “If we look at all adverse events there was no difference across arms, and in terms of serious adverse events, it was in favor of risankizumab because a CD flare is considered a serious adverse event.”

Session comoderator, Alessandro Armuzzi, MD, head of the Inflammatory Bowel Disease Center at the IRCCS Humanitas Research Hospital in Milan, commented on the findings. “The results look in favor of risankizumab – all the endpoints were met, not only the co-endpoints but also the secondary endpoints too,” he said.

These results, showing a preference for risankizumab, have value in helping clinicians with the sequence of therapies when patients with Crohn’s disease have failed one or more TNF inhibitor, said Dr. Armuzzi.

No funding for this study was disclosed. Dr. Peyrin-Biroulet has disclosed receiving fees from Galapagos, AbbVie, Janssen, Genentech, Alimentiv, Ferring, Tillots, Celltrion, Takeda, Pfizer, Index, Sandoz, Celgene, Biogen, SamsungBioepis, Inotrem, Allergan, MSD, Roche, Arena, Gilead, Amgen, BMS, Vifor, Norgine, Mylan, Lilly, Fresenius Kabi, OSEImmunotherapeutics, Enthera, Theravance, Pandion, Gossamer, Viatris, ThermoFisher, ONOPharma, Mopac, Cytoki, Morphic, Prometheus, and Applied MolecularTransport. Dr. Armuzzi disclosed consulting/advisory board fees from AbbVie, Amgen, Arena, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Celltrion, Eli-Lilly, Ferring, Galapagos, Gilead, Janssen, Lionhealth, MSD, Nestlé, Pfizer, Protagonist Therapeutics, Roche, Samsung Bioepis, Sandoz, Takeda, and Tillots Pharma; speaker’s fees from AbbVie, Amgen, Arena, Biogen, Bristol-Myers Squibb, Eli-Lilly, Ferring, Galapagos, Gilead, Janssen, Lionhealth, MSD, Novartis, Pfizer, Roche, Samsung Bioepis, Sandoz, and Takeda; and research grants from MSD, Takeda, Pfizer, and Biogen.

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

For women who are obese, daily life is wrought with landmines. Whether it’s the challenges of air travel because plane seats are too small, the need to shield themselves from the world’s discriminating eyes, or the great lengths many will go to achieve better health and the promise of longevity, navigating life as an obese person requires a thick skin.

So, it’s no wonder so many are willing to pay more than $1,000 a month out of pocket to get their hands on drugs like semaglutide (Ozempic and Wegovy) or tirzepatide (Mounjaro). The benefits of these drugs, which are part of a new class called glucagonlike peptide–1 (GLP-1) receptor agonists, include significant and rapid weight loss, blood sugar control, and improved life quality; they are unprecedented in a setting where surgery has long been considered the most effective long-term option.

On the flip side, the desire for rapid weight loss and better blood sugar control also comes with an unexpected cost. Many women living with obesity who take oral contraceptives are unaware that these drugs – especially Mounjaro – can interfere with the absorption of birth control pills and how well they work, making an unintended pregnancy more likely.

Neel Shah, MD, an endocrinologist and associate professor at the University of Texas Health Science Center at Houston, said he has had several patients become pregnant without intending to. 

“It was when Mounjaro came out on the market when we started using it,” he said of the drug the Food and Drug Administration approved for type 2 diabetes in 2022. “It [the warning] was in the product insert, but clinically speaking, I don’t know if it was at the top of providers’ minds when they were prescribing Mounjaro.”

When asked if he believed that we were going to be seeing a significant increase in so-called Mounjaro babies, Dr. Shah was sure in his response. 

“Absolutely. We will because the sheer volume [of patients] will increase,” he said.
 

It’s all in the gut

One of the ways that drugs like Mounjaro work is by delaying the time that it takes for food to move from the stomach to the small intestine. Although data are still evolving, it is believed that this process – delayed gastric emptying – may affect the absorption of birth control pills. 

Dr. Shah said another theory is that vomiting, which is a common side effect of these types of drugs, also affects the pills’ ability to prevent pregnancy. 

And “there’s a prolonged period of ramping up the dose because of the GI side effects,” said Pinar Kodaman, MD, PhD, a reproductive endocrinologist and assistant professor of gynecology at Yale University in New Haven, Conn. 

“Initially, at the lowest dose, there may not be a lot of potential effect on absorption and gastric emptying. But as the dose goes up, it becomes more common, and it can cause diarrhea, which is another condition that can affect the absorption of any medication,” she said.
 

Unanticipated outcomes, extra prevention

Roughly 42% of women in the United States are obese, 40% of whom are between the ages of 20 and 39. Although these new drugs can improve fertility outcomes for women who are obese (especially those with polycystic ovary syndrome, or PCOS), only one – Mounjaro – currently carries a warning about birth control pill effectiveness on its label. Unfortunately, it appears that some doctors are unaware or not counseling patients about this risk, and the data are unclear about whether other drugs in this class, like Ozempic and Wegovy, have the same risks. 

“To date, it hasn’t been a typical thing that we counsel about,” said Dr. Kodaman. “It’s all fairly new, but when we have patients on birth control pills, we do review other medications that they are on because some can affect efficacy, and it’s something to keep in mind.”

It’s also unclear if other forms of birth control – for example, birth control patches that deliver through the skin – might carry similar pregnancy risks. Dr. Shah said some of his patients who became pregnant without intending to were using these patches. This raises even more questions, since they deliver drugs through the skin directly into the bloodstream and not through the GI system. 

What can women do to help ensure that they don’t become pregnant while using these drugs? 

“I really think that if patients want to protect themselves from an unplanned pregnancy, that as soon as they start the GLP receptor agonists, it wouldn’t be a bad idea to use condoms, because the onset of action is pretty quick,” said Dr. Kodaman, noting also that “at the lowest dose there may not be a lot of potential effect on gastric emptying. But as the dose goes up, it becomes much more common or can cause diarrhea.” 

Dr. Shah said that in his practice he’s “been telling patients to add barrier contraception” 4 weeks before they start their first dose “and at any dose adjustment.”

Zoobia Chaudhry, an obesity medicine doctor and assistant professor of medicine at Johns Hopkins University in Baltimore, recommends that “patients just make sure that the injection and medication that they take are at least 1 hour apart.”

“Most of the time, patients do take birth control before bedtime, so if the two are spaced, it should be OK,” she said.

Another option is for women to speak to their doctors about other contraceptive options like IUDs or implantable rods, where gastric absorption is not going to be an issue. 

“There’s very little research on this class of drugs,” said Emily Goodstein, a 40-year-old small-business owner in Washington, who recently switched from Ozempic to Mounjaro. “Being a person who lives in a larger body is such a horrifying experience because of the way that the world discriminates against you.”

She appreciates the feeling of being proactive that these new drugs grant. It has “opened up a bunch of opportunities for me to be seen as a full individual by the medical establishment,” she said. “I was willing to take the risk, knowing that I would be on these drugs for the rest of my life.”

In addition to being what Dr. Goodstein refers to as a guinea pig, she said she made sure that her primary care doctor was aware that she was not trying or planning to become pregnant again. (She has a 3-year-old child.) Still, her doctor mentioned only the most common side effects linked to these drugs, like nausea, vomiting, and diarrhea, and did not mention the risk of pregnancy.

“Folks are really not talking about the reproductive implications,” she said, referring to members of a Facebook group on these drugs that she belongs to. 

Like patients themselves, many doctors are just beginning to get their arms around these agents. “Awareness, education, provider involvement, and having a multidisciplinary team could help patients achieve the goals that they set out for themselves,” said Dr. Shah. 

Clear conversations are key.

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

For women who are obese, daily life is wrought with landmines. Whether it’s the challenges of air travel because plane seats are too small, the need to shield themselves from the world’s discriminating eyes, or the great lengths many will go to achieve better health and the promise of longevity, navigating life as an obese person requires a thick skin.

So, it’s no wonder so many are willing to pay more than $1,000 a month out of pocket to get their hands on drugs like semaglutide (Ozempic and Wegovy) or tirzepatide (Mounjaro). The benefits of these drugs, which are part of a new class called glucagonlike peptide–1 (GLP-1) receptor agonists, include significant and rapid weight loss, blood sugar control, and improved life quality; they are unprecedented in a setting where surgery has long been considered the most effective long-term option.

On the flip side, the desire for rapid weight loss and better blood sugar control also comes with an unexpected cost. Many women living with obesity who take oral contraceptives are unaware that these drugs – especially Mounjaro – can interfere with the absorption of birth control pills and how well they work, making an unintended pregnancy more likely.

Neel Shah, MD, an endocrinologist and associate professor at the University of Texas Health Science Center at Houston, said he has had several patients become pregnant without intending to. 

“It was when Mounjaro came out on the market when we started using it,” he said of the drug the Food and Drug Administration approved for type 2 diabetes in 2022. “It [the warning] was in the product insert, but clinically speaking, I don’t know if it was at the top of providers’ minds when they were prescribing Mounjaro.”

When asked if he believed that we were going to be seeing a significant increase in so-called Mounjaro babies, Dr. Shah was sure in his response. 

“Absolutely. We will because the sheer volume [of patients] will increase,” he said.
 

It’s all in the gut

One of the ways that drugs like Mounjaro work is by delaying the time that it takes for food to move from the stomach to the small intestine. Although data are still evolving, it is believed that this process – delayed gastric emptying – may affect the absorption of birth control pills. 

Dr. Shah said another theory is that vomiting, which is a common side effect of these types of drugs, also affects the pills’ ability to prevent pregnancy. 

And “there’s a prolonged period of ramping up the dose because of the GI side effects,” said Pinar Kodaman, MD, PhD, a reproductive endocrinologist and assistant professor of gynecology at Yale University in New Haven, Conn. 

“Initially, at the lowest dose, there may not be a lot of potential effect on absorption and gastric emptying. But as the dose goes up, it becomes more common, and it can cause diarrhea, which is another condition that can affect the absorption of any medication,” she said.
 

Unanticipated outcomes, extra prevention

Roughly 42% of women in the United States are obese, 40% of whom are between the ages of 20 and 39. Although these new drugs can improve fertility outcomes for women who are obese (especially those with polycystic ovary syndrome, or PCOS), only one – Mounjaro – currently carries a warning about birth control pill effectiveness on its label. Unfortunately, it appears that some doctors are unaware or not counseling patients about this risk, and the data are unclear about whether other drugs in this class, like Ozempic and Wegovy, have the same risks. 

“To date, it hasn’t been a typical thing that we counsel about,” said Dr. Kodaman. “It’s all fairly new, but when we have patients on birth control pills, we do review other medications that they are on because some can affect efficacy, and it’s something to keep in mind.”

It’s also unclear if other forms of birth control – for example, birth control patches that deliver through the skin – might carry similar pregnancy risks. Dr. Shah said some of his patients who became pregnant without intending to were using these patches. This raises even more questions, since they deliver drugs through the skin directly into the bloodstream and not through the GI system. 

What can women do to help ensure that they don’t become pregnant while using these drugs? 

“I really think that if patients want to protect themselves from an unplanned pregnancy, that as soon as they start the GLP receptor agonists, it wouldn’t be a bad idea to use condoms, because the onset of action is pretty quick,” said Dr. Kodaman, noting also that “at the lowest dose there may not be a lot of potential effect on gastric emptying. But as the dose goes up, it becomes much more common or can cause diarrhea.” 

Dr. Shah said that in his practice he’s “been telling patients to add barrier contraception” 4 weeks before they start their first dose “and at any dose adjustment.”

Zoobia Chaudhry, an obesity medicine doctor and assistant professor of medicine at Johns Hopkins University in Baltimore, recommends that “patients just make sure that the injection and medication that they take are at least 1 hour apart.”

“Most of the time, patients do take birth control before bedtime, so if the two are spaced, it should be OK,” she said.

Another option is for women to speak to their doctors about other contraceptive options like IUDs or implantable rods, where gastric absorption is not going to be an issue. 

“There’s very little research on this class of drugs,” said Emily Goodstein, a 40-year-old small-business owner in Washington, who recently switched from Ozempic to Mounjaro. “Being a person who lives in a larger body is such a horrifying experience because of the way that the world discriminates against you.”

She appreciates the feeling of being proactive that these new drugs grant. It has “opened up a bunch of opportunities for me to be seen as a full individual by the medical establishment,” she said. “I was willing to take the risk, knowing that I would be on these drugs for the rest of my life.”

In addition to being what Dr. Goodstein refers to as a guinea pig, she said she made sure that her primary care doctor was aware that she was not trying or planning to become pregnant again. (She has a 3-year-old child.) Still, her doctor mentioned only the most common side effects linked to these drugs, like nausea, vomiting, and diarrhea, and did not mention the risk of pregnancy.

“Folks are really not talking about the reproductive implications,” she said, referring to members of a Facebook group on these drugs that she belongs to. 

Like patients themselves, many doctors are just beginning to get their arms around these agents. “Awareness, education, provider involvement, and having a multidisciplinary team could help patients achieve the goals that they set out for themselves,” said Dr. Shah. 

Clear conversations are key.

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

For women who are obese, daily life is wrought with landmines. Whether it’s the challenges of air travel because plane seats are too small, the need to shield themselves from the world’s discriminating eyes, or the great lengths many will go to achieve better health and the promise of longevity, navigating life as an obese person requires a thick skin.

So, it’s no wonder so many are willing to pay more than $1,000 a month out of pocket to get their hands on drugs like semaglutide (Ozempic and Wegovy) or tirzepatide (Mounjaro). The benefits of these drugs, which are part of a new class called glucagonlike peptide–1 (GLP-1) receptor agonists, include significant and rapid weight loss, blood sugar control, and improved life quality; they are unprecedented in a setting where surgery has long been considered the most effective long-term option.

On the flip side, the desire for rapid weight loss and better blood sugar control also comes with an unexpected cost. Many women living with obesity who take oral contraceptives are unaware that these drugs – especially Mounjaro – can interfere with the absorption of birth control pills and how well they work, making an unintended pregnancy more likely.

Neel Shah, MD, an endocrinologist and associate professor at the University of Texas Health Science Center at Houston, said he has had several patients become pregnant without intending to. 

“It was when Mounjaro came out on the market when we started using it,” he said of the drug the Food and Drug Administration approved for type 2 diabetes in 2022. “It [the warning] was in the product insert, but clinically speaking, I don’t know if it was at the top of providers’ minds when they were prescribing Mounjaro.”

When asked if he believed that we were going to be seeing a significant increase in so-called Mounjaro babies, Dr. Shah was sure in his response. 

“Absolutely. We will because the sheer volume [of patients] will increase,” he said.
 

It’s all in the gut

One of the ways that drugs like Mounjaro work is by delaying the time that it takes for food to move from the stomach to the small intestine. Although data are still evolving, it is believed that this process – delayed gastric emptying – may affect the absorption of birth control pills. 

Dr. Shah said another theory is that vomiting, which is a common side effect of these types of drugs, also affects the pills’ ability to prevent pregnancy. 

And “there’s a prolonged period of ramping up the dose because of the GI side effects,” said Pinar Kodaman, MD, PhD, a reproductive endocrinologist and assistant professor of gynecology at Yale University in New Haven, Conn. 

“Initially, at the lowest dose, there may not be a lot of potential effect on absorption and gastric emptying. But as the dose goes up, it becomes more common, and it can cause diarrhea, which is another condition that can affect the absorption of any medication,” she said.
 

Unanticipated outcomes, extra prevention

Roughly 42% of women in the United States are obese, 40% of whom are between the ages of 20 and 39. Although these new drugs can improve fertility outcomes for women who are obese (especially those with polycystic ovary syndrome, or PCOS), only one – Mounjaro – currently carries a warning about birth control pill effectiveness on its label. Unfortunately, it appears that some doctors are unaware or not counseling patients about this risk, and the data are unclear about whether other drugs in this class, like Ozempic and Wegovy, have the same risks. 

“To date, it hasn’t been a typical thing that we counsel about,” said Dr. Kodaman. “It’s all fairly new, but when we have patients on birth control pills, we do review other medications that they are on because some can affect efficacy, and it’s something to keep in mind.”

It’s also unclear if other forms of birth control – for example, birth control patches that deliver through the skin – might carry similar pregnancy risks. Dr. Shah said some of his patients who became pregnant without intending to were using these patches. This raises even more questions, since they deliver drugs through the skin directly into the bloodstream and not through the GI system. 

What can women do to help ensure that they don’t become pregnant while using these drugs? 

“I really think that if patients want to protect themselves from an unplanned pregnancy, that as soon as they start the GLP receptor agonists, it wouldn’t be a bad idea to use condoms, because the onset of action is pretty quick,” said Dr. Kodaman, noting also that “at the lowest dose there may not be a lot of potential effect on gastric emptying. But as the dose goes up, it becomes much more common or can cause diarrhea.” 

Dr. Shah said that in his practice he’s “been telling patients to add barrier contraception” 4 weeks before they start their first dose “and at any dose adjustment.”

Zoobia Chaudhry, an obesity medicine doctor and assistant professor of medicine at Johns Hopkins University in Baltimore, recommends that “patients just make sure that the injection and medication that they take are at least 1 hour apart.”

“Most of the time, patients do take birth control before bedtime, so if the two are spaced, it should be OK,” she said.

Another option is for women to speak to their doctors about other contraceptive options like IUDs or implantable rods, where gastric absorption is not going to be an issue. 

“There’s very little research on this class of drugs,” said Emily Goodstein, a 40-year-old small-business owner in Washington, who recently switched from Ozempic to Mounjaro. “Being a person who lives in a larger body is such a horrifying experience because of the way that the world discriminates against you.”

She appreciates the feeling of being proactive that these new drugs grant. It has “opened up a bunch of opportunities for me to be seen as a full individual by the medical establishment,” she said. “I was willing to take the risk, knowing that I would be on these drugs for the rest of my life.”

In addition to being what Dr. Goodstein refers to as a guinea pig, she said she made sure that her primary care doctor was aware that she was not trying or planning to become pregnant again. (She has a 3-year-old child.) Still, her doctor mentioned only the most common side effects linked to these drugs, like nausea, vomiting, and diarrhea, and did not mention the risk of pregnancy.

“Folks are really not talking about the reproductive implications,” she said, referring to members of a Facebook group on these drugs that she belongs to. 

Like patients themselves, many doctors are just beginning to get their arms around these agents. “Awareness, education, provider involvement, and having a multidisciplinary team could help patients achieve the goals that they set out for themselves,” said Dr. Shah. 

Clear conversations are key.

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

The Food and Drug Administration has approved bimekizumab-bkzx (Bimzelx) for the treatment of moderate to severe plaque psoriasis in adults, the manufacturer announced in a press release.

The indication is for adults who are candidates for systemic therapy or phototherapy.

With this approval, bimekizumab becomes the only interleukin (IL)-17A and IL-17F inhibitor approved for the treatment of these patients. Psoriasis affects more than 7.5 million U.S. adults, according to the National Psoriasis Foundation.

“We have been eagerly awaiting bimekizumab,” Mark Lebwohl, MD, bimekizumab investigator and dean for clinical therapeutics at the Icahn School of Medicine at Mount Sinai, New York City, said in the press release.

Dr. Lebwohl states that bimekizumab “achieved superior levels of skin clearance at week 16 compared to placebo and three existing biologics for psoriasis, with responses being rapid and lasting up to a year. Long-term data have also shown that the majority of patients maintained high levels of clinical response through three years.”

The most common adverse reactions (occurring in at least 1% of patients) are upper respiratory infections, oral candidiasis, headache, tinea infections, gastroenteritis, herpes simplex infections, acne, folliculitis, other Candida infections, fatigue, and injection site reactions, according to the company, UCB.
 

Available in about 1 month in U.S.

Bimekizumab can be administered by a health care provider or it can be self-injected by a patient after training. It is available as a single-dose prefilled autoinjector and a single-dose prefilled syringe and will be available in the United States in about 1 month.

The recommended dosage of bimekizumab for patients with psoriasis is 320 mg (two subcutaneous injections of 160 mg each) at baseline, then on weeks 4, 8, 12, and 16, then every 8 weeks thereafter. For patients weighing at least 120 kg (about 265 lb), a dosage of 320 mg every 4 weeks after week 16 may be considered, the company states.

Three phase 3 trials

Approval was based on three phase 3 multicenter, randomized, placebo and/or active comparator-controlled trials: bimekizumab versus placebo and ustekinumab (BE VIVID); versus placebo (BE READY); and versus adalimumab (BE SURE).

“All studies met their co-primary endpoints and all ranked secondary endpoints,” the company reports. Secondary endpoints included the Psoriasis Area and Severity Index (PASI) 75 at week 4 and PASI 100 (complete skin clearance) at week 16.

Highlights from the trials include the following results, according to UCB:

• Clear or almost clear skin: More than 8 out of 10 patients achieved a 90% or greater reduction from baseline in the PASI 90 and an Investigator’s Global Assessment score of 0/1 at week 16.
• Complete skin clearance: About 60% of patients achieved PASI 100 at week 16.
• Time to response: More than 70% of patients achieved PASI 75 at week 4 following one 320-mg dose.

Safety information

The safety information includes the statement that bimekizumab may increase the risk for suicidal ideation and behavior, though a causal association has not been established. Prescribers should advise patients, caregivers, and families “to monitor for emergence or worsening of depression, suicidal ideation, or other mood changes,” according to the prescribing information.

Bimekizumab is being studied for other conditions, including hidradenitis suppurativa. In the European Union, it was approved for the treatment of psoriasis in 2021 and for the treatment of psoriatic arthritis and ankylosing spondylitis in June 2023.

Dr. Lebwohl is an investigator for UCB. He has not accepted any consulting payments from UCB.

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

The Food and Drug Administration has approved bimekizumab-bkzx (Bimzelx) for the treatment of moderate to severe plaque psoriasis in adults, the manufacturer announced in a press release.

The indication is for adults who are candidates for systemic therapy or phototherapy.

With this approval, bimekizumab becomes the only interleukin (IL)-17A and IL-17F inhibitor approved for the treatment of these patients. Psoriasis affects more than 7.5 million U.S. adults, according to the National Psoriasis Foundation.

“We have been eagerly awaiting bimekizumab,” Mark Lebwohl, MD, bimekizumab investigator and dean for clinical therapeutics at the Icahn School of Medicine at Mount Sinai, New York City, said in the press release.

Dr. Lebwohl states that bimekizumab “achieved superior levels of skin clearance at week 16 compared to placebo and three existing biologics for psoriasis, with responses being rapid and lasting up to a year. Long-term data have also shown that the majority of patients maintained high levels of clinical response through three years.”

The most common adverse reactions (occurring in at least 1% of patients) are upper respiratory infections, oral candidiasis, headache, tinea infections, gastroenteritis, herpes simplex infections, acne, folliculitis, other Candida infections, fatigue, and injection site reactions, according to the company, UCB.
 

Available in about 1 month in U.S.

Bimekizumab can be administered by a health care provider or it can be self-injected by a patient after training. It is available as a single-dose prefilled autoinjector and a single-dose prefilled syringe and will be available in the United States in about 1 month.

The recommended dosage of bimekizumab for patients with psoriasis is 320 mg (two subcutaneous injections of 160 mg each) at baseline, then on weeks 4, 8, 12, and 16, then every 8 weeks thereafter. For patients weighing at least 120 kg (about 265 lb), a dosage of 320 mg every 4 weeks after week 16 may be considered, the company states.

Three phase 3 trials

Approval was based on three phase 3 multicenter, randomized, placebo and/or active comparator-controlled trials: bimekizumab versus placebo and ustekinumab (BE VIVID); versus placebo (BE READY); and versus adalimumab (BE SURE).

“All studies met their co-primary endpoints and all ranked secondary endpoints,” the company reports. Secondary endpoints included the Psoriasis Area and Severity Index (PASI) 75 at week 4 and PASI 100 (complete skin clearance) at week 16.

Highlights from the trials include the following results, according to UCB:

• Clear or almost clear skin: More than 8 out of 10 patients achieved a 90% or greater reduction from baseline in the PASI 90 and an Investigator’s Global Assessment score of 0/1 at week 16.
• Complete skin clearance: About 60% of patients achieved PASI 100 at week 16.
• Time to response: More than 70% of patients achieved PASI 75 at week 4 following one 320-mg dose.

Safety information

The safety information includes the statement that bimekizumab may increase the risk for suicidal ideation and behavior, though a causal association has not been established. Prescribers should advise patients, caregivers, and families “to monitor for emergence or worsening of depression, suicidal ideation, or other mood changes,” according to the prescribing information.

Bimekizumab is being studied for other conditions, including hidradenitis suppurativa. In the European Union, it was approved for the treatment of psoriasis in 2021 and for the treatment of psoriatic arthritis and ankylosing spondylitis in June 2023.

Dr. Lebwohl is an investigator for UCB. He has not accepted any consulting payments from UCB.

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

The Food and Drug Administration has approved bimekizumab-bkzx (Bimzelx) for the treatment of moderate to severe plaque psoriasis in adults, the manufacturer announced in a press release.

The indication is for adults who are candidates for systemic therapy or phototherapy.

With this approval, bimekizumab becomes the only interleukin (IL)-17A and IL-17F inhibitor approved for the treatment of these patients. Psoriasis affects more than 7.5 million U.S. adults, according to the National Psoriasis Foundation.

“We have been eagerly awaiting bimekizumab,” Mark Lebwohl, MD, bimekizumab investigator and dean for clinical therapeutics at the Icahn School of Medicine at Mount Sinai, New York City, said in the press release.

Dr. Lebwohl states that bimekizumab “achieved superior levels of skin clearance at week 16 compared to placebo and three existing biologics for psoriasis, with responses being rapid and lasting up to a year. Long-term data have also shown that the majority of patients maintained high levels of clinical response through three years.”

The most common adverse reactions (occurring in at least 1% of patients) are upper respiratory infections, oral candidiasis, headache, tinea infections, gastroenteritis, herpes simplex infections, acne, folliculitis, other Candida infections, fatigue, and injection site reactions, according to the company, UCB.
 

Available in about 1 month in U.S.

Bimekizumab can be administered by a health care provider or it can be self-injected by a patient after training. It is available as a single-dose prefilled autoinjector and a single-dose prefilled syringe and will be available in the United States in about 1 month.

The recommended dosage of bimekizumab for patients with psoriasis is 320 mg (two subcutaneous injections of 160 mg each) at baseline, then on weeks 4, 8, 12, and 16, then every 8 weeks thereafter. For patients weighing at least 120 kg (about 265 lb), a dosage of 320 mg every 4 weeks after week 16 may be considered, the company states.

Three phase 3 trials

Approval was based on three phase 3 multicenter, randomized, placebo and/or active comparator-controlled trials: bimekizumab versus placebo and ustekinumab (BE VIVID); versus placebo (BE READY); and versus adalimumab (BE SURE).

“All studies met their co-primary endpoints and all ranked secondary endpoints,” the company reports. Secondary endpoints included the Psoriasis Area and Severity Index (PASI) 75 at week 4 and PASI 100 (complete skin clearance) at week 16.

Highlights from the trials include the following results, according to UCB:

• Clear or almost clear skin: More than 8 out of 10 patients achieved a 90% or greater reduction from baseline in the PASI 90 and an Investigator’s Global Assessment score of 0/1 at week 16.
• Complete skin clearance: About 60% of patients achieved PASI 100 at week 16.
• Time to response: More than 70% of patients achieved PASI 75 at week 4 following one 320-mg dose.

Safety information

The safety information includes the statement that bimekizumab may increase the risk for suicidal ideation and behavior, though a causal association has not been established. Prescribers should advise patients, caregivers, and families “to monitor for emergence or worsening of depression, suicidal ideation, or other mood changes,” according to the prescribing information.

Bimekizumab is being studied for other conditions, including hidradenitis suppurativa. In the European Union, it was approved for the treatment of psoriasis in 2021 and for the treatment of psoriatic arthritis and ankylosing spondylitis in June 2023.

Dr. Lebwohl is an investigator for UCB. He has not accepted any consulting payments from UCB.

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

TOPLINE:

DMT310, a novel topical treatment applied once per week, appears to be safe and effective for moderate to severe acne.

METHODOLOGY:

• Poor patient compliance with topical acne therapies is a common clinical challenge.
• In a 12-week, randomized, controlled, phase 2b trial of 181 patients 12 years of age and older, researchers investigated the safety, tolerability, and efficacy of DMT310, a powdered mixture of Spongilla lacustris for treating moderate to severe acne. (In vitro studies have found that components of S. lacustris, a freshwater sponge, have effects that include antimicrobial activity against Cutibacterium acnes and anti-inflammatory activity in human keratinocytes).
• The study’s primary efficacy endpoint was the absolute change in inflammatory lesion count from baseline to week 12.
• Endpoint success was defined as an Investigator Global Assessment (IGA) score of 0 or 1 and at least a two-grade improvement from baseline at week 12.
•  

TAKEAWAY:

• Of the 181 patients, 91 received DMT310 (applied once a week to the face and washed off after 10-15 minutes), and 90 received placebo.
• Patients in the DMT310 arm showed a significantly greater mean reduction in the number of inflammatory lesions at week 12, compared with those in the placebo arm (–15.64 vs. –10.84, respectively; P < .001).
• Similarly, patients in the DMT310 arm showed a significantly greater mean reduction in the number of noninflammatory lesions at week 12, compared with those in the placebo arm (–18.26 vs. –12.41, respectively; P < .001).
• At week 12, endpoint success based on IGA scores also significantly favored patients in the DMT310 arm, compared with those in the placebo arm (44.40% vs. 17.78%; P < .001).

IN PRACTICE:

This study is too preliminary to have practice application. The researchers concluded that the findings “support further study of DMT310 in larger, confirmatory phase 3 trials.”

SOURCE:

Lawrence F. Eichenfield, MD, professor of dermatology and pediatrics at the University of California, San Diego, led the research. The study was published online June 7 in the Journal of the American Academy of Dermatology.

LIMITATIONS:

The analysis did not include an active comparator group and it enrolled a limited number of Asian patients.

DISCLOSURES:

Dr. Eichenfield disclosed that he is a consultant to Dermata, which is developing DMT310, as were three other authors of the study. One author is a company employee. The remaining authors disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

TOPLINE:

DMT310, a novel topical treatment applied once per week, appears to be safe and effective for moderate to severe acne.

METHODOLOGY:

• Poor patient compliance with topical acne therapies is a common clinical challenge.
• In a 12-week, randomized, controlled, phase 2b trial of 181 patients 12 years of age and older, researchers investigated the safety, tolerability, and efficacy of DMT310, a powdered mixture of Spongilla lacustris for treating moderate to severe acne. (In vitro studies have found that components of S. lacustris, a freshwater sponge, have effects that include antimicrobial activity against Cutibacterium acnes and anti-inflammatory activity in human keratinocytes).
• The study’s primary efficacy endpoint was the absolute change in inflammatory lesion count from baseline to week 12.
• Endpoint success was defined as an Investigator Global Assessment (IGA) score of 0 or 1 and at least a two-grade improvement from baseline at week 12.
•  

TAKEAWAY:

• Of the 181 patients, 91 received DMT310 (applied once a week to the face and washed off after 10-15 minutes), and 90 received placebo.
• Patients in the DMT310 arm showed a significantly greater mean reduction in the number of inflammatory lesions at week 12, compared with those in the placebo arm (–15.64 vs. –10.84, respectively; P < .001).
• Similarly, patients in the DMT310 arm showed a significantly greater mean reduction in the number of noninflammatory lesions at week 12, compared with those in the placebo arm (–18.26 vs. –12.41, respectively; P < .001).
• At week 12, endpoint success based on IGA scores also significantly favored patients in the DMT310 arm, compared with those in the placebo arm (44.40% vs. 17.78%; P < .001).

IN PRACTICE:

This study is too preliminary to have practice application. The researchers concluded that the findings “support further study of DMT310 in larger, confirmatory phase 3 trials.”

SOURCE:

Lawrence F. Eichenfield, MD, professor of dermatology and pediatrics at the University of California, San Diego, led the research. The study was published online June 7 in the Journal of the American Academy of Dermatology.

LIMITATIONS:

The analysis did not include an active comparator group and it enrolled a limited number of Asian patients.

DISCLOSURES:

Dr. Eichenfield disclosed that he is a consultant to Dermata, which is developing DMT310, as were three other authors of the study. One author is a company employee. The remaining authors disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

TOPLINE:

DMT310, a novel topical treatment applied once per week, appears to be safe and effective for moderate to severe acne.

METHODOLOGY:

• Poor patient compliance with topical acne therapies is a common clinical challenge.
• In a 12-week, randomized, controlled, phase 2b trial of 181 patients 12 years of age and older, researchers investigated the safety, tolerability, and efficacy of DMT310, a powdered mixture of Spongilla lacustris for treating moderate to severe acne. (In vitro studies have found that components of S. lacustris, a freshwater sponge, have effects that include antimicrobial activity against Cutibacterium acnes and anti-inflammatory activity in human keratinocytes).
• The study’s primary efficacy endpoint was the absolute change in inflammatory lesion count from baseline to week 12.
• Endpoint success was defined as an Investigator Global Assessment (IGA) score of 0 or 1 and at least a two-grade improvement from baseline at week 12.
•  

TAKEAWAY:

• Of the 181 patients, 91 received DMT310 (applied once a week to the face and washed off after 10-15 minutes), and 90 received placebo.
• Patients in the DMT310 arm showed a significantly greater mean reduction in the number of inflammatory lesions at week 12, compared with those in the placebo arm (–15.64 vs. –10.84, respectively; P < .001).
• Similarly, patients in the DMT310 arm showed a significantly greater mean reduction in the number of noninflammatory lesions at week 12, compared with those in the placebo arm (–18.26 vs. –12.41, respectively; P < .001).
• At week 12, endpoint success based on IGA scores also significantly favored patients in the DMT310 arm, compared with those in the placebo arm (44.40% vs. 17.78%; P < .001).

IN PRACTICE:

This study is too preliminary to have practice application. The researchers concluded that the findings “support further study of DMT310 in larger, confirmatory phase 3 trials.”

SOURCE:

Lawrence F. Eichenfield, MD, professor of dermatology and pediatrics at the University of California, San Diego, led the research. The study was published online June 7 in the Journal of the American Academy of Dermatology.

LIMITATIONS:

The analysis did not include an active comparator group and it enrolled a limited number of Asian patients.

DISCLOSURES:

Dr. Eichenfield disclosed that he is a consultant to Dermata, which is developing DMT310, as were three other authors of the study. One author is a company employee. The remaining authors disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

The Food and Drug Administration has approved nivolumab (Opdivo) for the treatment of completely resected stage IIB/C melanoma for patients aged 12 years and older, expanding the melanoma indication for the programmed death receptor-1 (PD-1) inhibitor.

Nivolumab, developed by Bristol-Myers Squibb, was previously approved as a single agent or in combination with ipilimumab for patients aged 12 years and older with unresectable or metastatic melanoma and for the adjuvant treatment of those aged 12 and older with completely resected stage III or IV melanoma.

The new approval was based on findings from the phase 3 CHECKMATE-76K trial, which randomly assigned 790 patients in a 2:1 ratio to receive nivolumab 480 mg or placebo by intravenous infusion. All patients in the trial had good performance status, had undergone complete resection of the primary melanoma with negative margins, and had tested negative on sentinel lymph node assessment within 12 weeks prior to randomization. Patients received treatment every 4 weeks for up to 1 year or until disease recurrence or unacceptable toxicity occurred.

Nivolumab reduced the risk of recurrence or death by 58% compared with placebo (hazard ratio, 0.42). Recurrence-free survival at 1 year was 89% with treatment, vs 79.4% with placebo. Median recurrence-free survival at 5 years was not reached in either arm.

Adverse reactions that were reported in at least 20% of patients included fatigue, musculoskeletal pain, rash, diarrhea, and pruritus.

The recommended nivolumab dose for patients weighing 40 kg or more is 480 mg every 4 weeks or 240 mg every 2 weeks until disease recurrence or unacceptable toxicity for up to 1 year. For pediatric patients who weigh less than 40 kg, the recommended dose is 3 mg/kg every 2 weeks or 6 mg/kg every 4 weeks until disease recurrence or unacceptable toxicity for up to 1 year.

Bristol-Myers Squibb’s application for approval led to the agent’s being granted orphan drug designation, allowing expedited review.

A version of this article appeared on Medscape.com.

The Food and Drug Administration has approved nivolumab (Opdivo) for the treatment of completely resected stage IIB/C melanoma for patients aged 12 years and older, expanding the melanoma indication for the programmed death receptor-1 (PD-1) inhibitor.

Nivolumab, developed by Bristol-Myers Squibb, was previously approved as a single agent or in combination with ipilimumab for patients aged 12 years and older with unresectable or metastatic melanoma and for the adjuvant treatment of those aged 12 and older with completely resected stage III or IV melanoma.

The new approval was based on findings from the phase 3 CHECKMATE-76K trial, which randomly assigned 790 patients in a 2:1 ratio to receive nivolumab 480 mg or placebo by intravenous infusion. All patients in the trial had good performance status, had undergone complete resection of the primary melanoma with negative margins, and had tested negative on sentinel lymph node assessment within 12 weeks prior to randomization. Patients received treatment every 4 weeks for up to 1 year or until disease recurrence or unacceptable toxicity occurred.

Nivolumab reduced the risk of recurrence or death by 58% compared with placebo (hazard ratio, 0.42). Recurrence-free survival at 1 year was 89% with treatment, vs 79.4% with placebo. Median recurrence-free survival at 5 years was not reached in either arm.

Adverse reactions that were reported in at least 20% of patients included fatigue, musculoskeletal pain, rash, diarrhea, and pruritus.

The recommended nivolumab dose for patients weighing 40 kg or more is 480 mg every 4 weeks or 240 mg every 2 weeks until disease recurrence or unacceptable toxicity for up to 1 year. For pediatric patients who weigh less than 40 kg, the recommended dose is 3 mg/kg every 2 weeks or 6 mg/kg every 4 weeks until disease recurrence or unacceptable toxicity for up to 1 year.

Bristol-Myers Squibb’s application for approval led to the agent’s being granted orphan drug designation, allowing expedited review.

A version of this article appeared on Medscape.com.

The Food and Drug Administration has approved nivolumab (Opdivo) for the treatment of completely resected stage IIB/C melanoma for patients aged 12 years and older, expanding the melanoma indication for the programmed death receptor-1 (PD-1) inhibitor.

Nivolumab, developed by Bristol-Myers Squibb, was previously approved as a single agent or in combination with ipilimumab for patients aged 12 years and older with unresectable or metastatic melanoma and for the adjuvant treatment of those aged 12 and older with completely resected stage III or IV melanoma.

The new approval was based on findings from the phase 3 CHECKMATE-76K trial, which randomly assigned 790 patients in a 2:1 ratio to receive nivolumab 480 mg or placebo by intravenous infusion. All patients in the trial had good performance status, had undergone complete resection of the primary melanoma with negative margins, and had tested negative on sentinel lymph node assessment within 12 weeks prior to randomization. Patients received treatment every 4 weeks for up to 1 year or until disease recurrence or unacceptable toxicity occurred.

Nivolumab reduced the risk of recurrence or death by 58% compared with placebo (hazard ratio, 0.42). Recurrence-free survival at 1 year was 89% with treatment, vs 79.4% with placebo. Median recurrence-free survival at 5 years was not reached in either arm.

Adverse reactions that were reported in at least 20% of patients included fatigue, musculoskeletal pain, rash, diarrhea, and pruritus.

The recommended nivolumab dose for patients weighing 40 kg or more is 480 mg every 4 weeks or 240 mg every 2 weeks until disease recurrence or unacceptable toxicity for up to 1 year. For pediatric patients who weigh less than 40 kg, the recommended dose is 3 mg/kg every 2 weeks or 6 mg/kg every 4 weeks until disease recurrence or unacceptable toxicity for up to 1 year.

Bristol-Myers Squibb’s application for approval led to the agent’s being granted orphan drug designation, allowing expedited review.

A version of this article appeared on Medscape.com.

TOPLINE:

The prevalence of reported diagnosed arthritis in the United States is highest overall in older adults with comorbid chronic conditions.

METHODOLOGY:

• Researchers reviewed data from the National Health Interview Survey (NHIS) from 2019 to 2021 to update the prevalence of self-reported arthritis in the United States.
• The sample sizes for the 2019, 2020, and 2021 NHIS were 31,997, 21,153, and 29,482, with survey response rates of 59.1%, 48.9%, and 50.9%, respectively.
• The unadjusted and age-standardized prevalence estimates were calculated for adults aged 18 years and older and based on self-reported health and demographic data.

TAKEAWAY:

• Overall, arthritis was diagnosed in 53.2 million adults aged 18 years and older in the United States; of these, 88.3% were aged 45 years and older and 48.3% were 65 years and older.
• Age-standardized prevalence of arthritis was higher in women vs men and among veterans vs nonveterans (20.9% vs 16.3% and 24.2% vs 18.5%, respectively).
• When categorized by race, age-standardized prevalence of arthritis was higher among non-Hispanic White individuals, compared with Hispanic or Latino individuals or non-Hispanic Asian individuals (20.1%, 14.7%, and 10.3%, respectively).
• The prevalence of arthritis also was higher among individuals with self-reported diagnosis of chronic conditions including dementia, chronic obstructive pulmonary disease, stroke, heart disease, diabetes, and cancer than in those without these conditions; approximately half of adults aged 65 years and older with arthritis reported at least one of these conditions.

IN PRACTICE:

“These prevalence estimates can be used to guide public health policies and activities to increase equitable access to physical activity opportunities within the built environment and other community-based, arthritis-appropriate, evidence-based interventions,” the authors write.

SOURCE:

The study was led by Elizabeth A. Fallon, PhD, of the Centers for Disease Control and Prevention, Atlanta, Georgia. The data were published online in the CDC’s Morbidity and Mortality Weekly Report.  

LIMITATIONS:

The cross-sectional design prevented conclusions of causality between individual characteristics and arthritis diagnosis; other limitations included the reliance on self-reports, possible response bias, and the inability to calculate prevalence of arthritis subtypes. 

DISCLOSURES:

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

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

TOPLINE:

The prevalence of reported diagnosed arthritis in the United States is highest overall in older adults with comorbid chronic conditions.

METHODOLOGY:

• Researchers reviewed data from the National Health Interview Survey (NHIS) from 2019 to 2021 to update the prevalence of self-reported arthritis in the United States.
• The sample sizes for the 2019, 2020, and 2021 NHIS were 31,997, 21,153, and 29,482, with survey response rates of 59.1%, 48.9%, and 50.9%, respectively.
• The unadjusted and age-standardized prevalence estimates were calculated for adults aged 18 years and older and based on self-reported health and demographic data.

TAKEAWAY:

• Overall, arthritis was diagnosed in 53.2 million adults aged 18 years and older in the United States; of these, 88.3% were aged 45 years and older and 48.3% were 65 years and older.
• Age-standardized prevalence of arthritis was higher in women vs men and among veterans vs nonveterans (20.9% vs 16.3% and 24.2% vs 18.5%, respectively).
• When categorized by race, age-standardized prevalence of arthritis was higher among non-Hispanic White individuals, compared with Hispanic or Latino individuals or non-Hispanic Asian individuals (20.1%, 14.7%, and 10.3%, respectively).
• The prevalence of arthritis also was higher among individuals with self-reported diagnosis of chronic conditions including dementia, chronic obstructive pulmonary disease, stroke, heart disease, diabetes, and cancer than in those without these conditions; approximately half of adults aged 65 years and older with arthritis reported at least one of these conditions.

IN PRACTICE:

“These prevalence estimates can be used to guide public health policies and activities to increase equitable access to physical activity opportunities within the built environment and other community-based, arthritis-appropriate, evidence-based interventions,” the authors write.

SOURCE:

The study was led by Elizabeth A. Fallon, PhD, of the Centers for Disease Control and Prevention, Atlanta, Georgia. The data were published online in the CDC’s Morbidity and Mortality Weekly Report.  

LIMITATIONS:

The cross-sectional design prevented conclusions of causality between individual characteristics and arthritis diagnosis; other limitations included the reliance on self-reports, possible response bias, and the inability to calculate prevalence of arthritis subtypes. 

DISCLOSURES:

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

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

TOPLINE:

The prevalence of reported diagnosed arthritis in the United States is highest overall in older adults with comorbid chronic conditions.

METHODOLOGY:

• Researchers reviewed data from the National Health Interview Survey (NHIS) from 2019 to 2021 to update the prevalence of self-reported arthritis in the United States.
• The sample sizes for the 2019, 2020, and 2021 NHIS were 31,997, 21,153, and 29,482, with survey response rates of 59.1%, 48.9%, and 50.9%, respectively.
• The unadjusted and age-standardized prevalence estimates were calculated for adults aged 18 years and older and based on self-reported health and demographic data.

TAKEAWAY:

• Overall, arthritis was diagnosed in 53.2 million adults aged 18 years and older in the United States; of these, 88.3% were aged 45 years and older and 48.3% were 65 years and older.
• Age-standardized prevalence of arthritis was higher in women vs men and among veterans vs nonveterans (20.9% vs 16.3% and 24.2% vs 18.5%, respectively).
• When categorized by race, age-standardized prevalence of arthritis was higher among non-Hispanic White individuals, compared with Hispanic or Latino individuals or non-Hispanic Asian individuals (20.1%, 14.7%, and 10.3%, respectively).
• The prevalence of arthritis also was higher among individuals with self-reported diagnosis of chronic conditions including dementia, chronic obstructive pulmonary disease, stroke, heart disease, diabetes, and cancer than in those without these conditions; approximately half of adults aged 65 years and older with arthritis reported at least one of these conditions.

IN PRACTICE:

“These prevalence estimates can be used to guide public health policies and activities to increase equitable access to physical activity opportunities within the built environment and other community-based, arthritis-appropriate, evidence-based interventions,” the authors write.

SOURCE:

The study was led by Elizabeth A. Fallon, PhD, of the Centers for Disease Control and Prevention, Atlanta, Georgia. The data were published online in the CDC’s Morbidity and Mortality Weekly Report.  

LIMITATIONS:

The cross-sectional design prevented conclusions of causality between individual characteristics and arthritis diagnosis; other limitations included the reliance on self-reports, possible response bias, and the inability to calculate prevalence of arthritis subtypes. 

DISCLOSURES:

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

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

TOPLINE:

In combination with methotrexate, both abatacept (Orencia) and certolizumab pegol (Cimzia), but not tocilizumab (Actemra), showed superiority over different combinations of active conventional disease-modifying antirheumatic drugs (DMARDs) for promoting remission in patients with early, untreated rheumatoid arthritis.

METHODOLOGY:

The study population included 812 adults from sites in six European countries who had treatment-naive early RA (less than 24 months’ duration) and moderate to severe disease.

Participants were randomly assigned to open-label treatment with methotrexate plus one of four treatments:

• Active conventional therapy (oral , tapered quickly and discontinued after 9 months, or , hydroxychloroquine, and intra-articular glucocorticoid injections in swollen joints).
• Certolizumab pegol.
• Abatacept.
• Tocilizumab.

In all the biologic-treated groups, intra-articular glucocorticoid injections were allowed on demand up to week 12; thereafter, up to 40 mg were allowed every 12 weeks. In all groups, intra-articular glucocorticoids were prohibited in weeks 20-24 and weeks 44-48 to minimize their influence on week 24 and week 48 outcomes.

TAKEAWAY:

• Clinical remission rates at week 48 based on Clinical Disease Activity Index scores of 2.8 or less were 59.3% with abatacept and 52.3% with certolizumab, which were significantly greater than the rate of 39.2% seen with active conventional therapy. The 51.9% rate seen with tocilizumab was not superior to active conventional therapy.
• The co–primary outcome of change in van der Heijde-modified Sharp Score from baseline to week 48 was relatively low across all groups: 0.45 for active conventional therapy, and 0.62, 0.47, and 0.50 for abatacept, certolizumab pegol, and tocilizumab, respectively.
• No new safety signals appeared, nor did any significantly increased risk associated with glucocorticoid use; at least one adverse event was reported in 88.3%, 89.6%, 85.8%, and 96.7% of patients taking conventional therapy, certolizumab pegol, abatacept, and tocilizumab, respectively.

IN PRACTICE:

The results suggest that both abatacept and certolizumab pegol yield higher remission rates than optimized conventional therapy, and “should be considered when the management of patients with newly diagnosed RA is decided, both in clinical practice and in treatment recommendations,” the authors write.

SOURCE:

The lead author on the study was Mikkel Østergaard, MD, PhD, of the Center for Rheumatology and Spine Diseases, Rigshospitalet, Copenhagen. The study was published online in Annals of the Rheumatic Disease.  

LIMITATIONS:

The open-label study design could influence some subjective outcomes, and conventional therapy included two slightly different strategies based on national recommendations for the individual countries.

DISCLOSURES:

The study was funded by multiple public sources to centers from countries participating in the study, as well as the Icelandic Society for Rheumatology, the Swedish Rheumatism Association, and the Research Fund of University Hospital, Reykjavik, Iceland. UCB and Bristol-Myers Squibb provided certolizumab pegol and abatacept, respectively, at no cost, but were not otherwise involved in the study. Many authors, including Dr. Østergaard, report financial relationships with multiple pharmaceutical companies. The full list can be found with the original article.

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

TOPLINE:

In combination with methotrexate, both abatacept (Orencia) and certolizumab pegol (Cimzia), but not tocilizumab (Actemra), showed superiority over different combinations of active conventional disease-modifying antirheumatic drugs (DMARDs) for promoting remission in patients with early, untreated rheumatoid arthritis.

METHODOLOGY:

The study population included 812 adults from sites in six European countries who had treatment-naive early RA (less than 24 months’ duration) and moderate to severe disease.

Participants were randomly assigned to open-label treatment with methotrexate plus one of four treatments:

• Active conventional therapy (oral , tapered quickly and discontinued after 9 months, or , hydroxychloroquine, and intra-articular glucocorticoid injections in swollen joints).
• Certolizumab pegol.
• Abatacept.
• Tocilizumab.

In all the biologic-treated groups, intra-articular glucocorticoid injections were allowed on demand up to week 12; thereafter, up to 40 mg were allowed every 12 weeks. In all groups, intra-articular glucocorticoids were prohibited in weeks 20-24 and weeks 44-48 to minimize their influence on week 24 and week 48 outcomes.

TAKEAWAY:

• Clinical remission rates at week 48 based on Clinical Disease Activity Index scores of 2.8 or less were 59.3% with abatacept and 52.3% with certolizumab, which were significantly greater than the rate of 39.2% seen with active conventional therapy. The 51.9% rate seen with tocilizumab was not superior to active conventional therapy.
• The co–primary outcome of change in van der Heijde-modified Sharp Score from baseline to week 48 was relatively low across all groups: 0.45 for active conventional therapy, and 0.62, 0.47, and 0.50 for abatacept, certolizumab pegol, and tocilizumab, respectively.
• No new safety signals appeared, nor did any significantly increased risk associated with glucocorticoid use; at least one adverse event was reported in 88.3%, 89.6%, 85.8%, and 96.7% of patients taking conventional therapy, certolizumab pegol, abatacept, and tocilizumab, respectively.

IN PRACTICE:

The results suggest that both abatacept and certolizumab pegol yield higher remission rates than optimized conventional therapy, and “should be considered when the management of patients with newly diagnosed RA is decided, both in clinical practice and in treatment recommendations,” the authors write.

SOURCE:

The lead author on the study was Mikkel Østergaard, MD, PhD, of the Center for Rheumatology and Spine Diseases, Rigshospitalet, Copenhagen. The study was published online in Annals of the Rheumatic Disease.  

LIMITATIONS:

The open-label study design could influence some subjective outcomes, and conventional therapy included two slightly different strategies based on national recommendations for the individual countries.

DISCLOSURES:

The study was funded by multiple public sources to centers from countries participating in the study, as well as the Icelandic Society for Rheumatology, the Swedish Rheumatism Association, and the Research Fund of University Hospital, Reykjavik, Iceland. UCB and Bristol-Myers Squibb provided certolizumab pegol and abatacept, respectively, at no cost, but were not otherwise involved in the study. Many authors, including Dr. Østergaard, report financial relationships with multiple pharmaceutical companies. The full list can be found with the original article.

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

TOPLINE:

In combination with methotrexate, both abatacept (Orencia) and certolizumab pegol (Cimzia), but not tocilizumab (Actemra), showed superiority over different combinations of active conventional disease-modifying antirheumatic drugs (DMARDs) for promoting remission in patients with early, untreated rheumatoid arthritis.

METHODOLOGY:

The study population included 812 adults from sites in six European countries who had treatment-naive early RA (less than 24 months’ duration) and moderate to severe disease.

Participants were randomly assigned to open-label treatment with methotrexate plus one of four treatments:

• Active conventional therapy (oral , tapered quickly and discontinued after 9 months, or , hydroxychloroquine, and intra-articular glucocorticoid injections in swollen joints).
• Certolizumab pegol.
• Abatacept.
• Tocilizumab.

In all the biologic-treated groups, intra-articular glucocorticoid injections were allowed on demand up to week 12; thereafter, up to 40 mg were allowed every 12 weeks. In all groups, intra-articular glucocorticoids were prohibited in weeks 20-24 and weeks 44-48 to minimize their influence on week 24 and week 48 outcomes.

TAKEAWAY:

• Clinical remission rates at week 48 based on Clinical Disease Activity Index scores of 2.8 or less were 59.3% with abatacept and 52.3% with certolizumab, which were significantly greater than the rate of 39.2% seen with active conventional therapy. The 51.9% rate seen with tocilizumab was not superior to active conventional therapy.
• The co–primary outcome of change in van der Heijde-modified Sharp Score from baseline to week 48 was relatively low across all groups: 0.45 for active conventional therapy, and 0.62, 0.47, and 0.50 for abatacept, certolizumab pegol, and tocilizumab, respectively.
• No new safety signals appeared, nor did any significantly increased risk associated with glucocorticoid use; at least one adverse event was reported in 88.3%, 89.6%, 85.8%, and 96.7% of patients taking conventional therapy, certolizumab pegol, abatacept, and tocilizumab, respectively.

IN PRACTICE:

The results suggest that both abatacept and certolizumab pegol yield higher remission rates than optimized conventional therapy, and “should be considered when the management of patients with newly diagnosed RA is decided, both in clinical practice and in treatment recommendations,” the authors write.

SOURCE:

The lead author on the study was Mikkel Østergaard, MD, PhD, of the Center for Rheumatology and Spine Diseases, Rigshospitalet, Copenhagen. The study was published online in Annals of the Rheumatic Disease.  

LIMITATIONS:

The open-label study design could influence some subjective outcomes, and conventional therapy included two slightly different strategies based on national recommendations for the individual countries.

DISCLOSURES:

The study was funded by multiple public sources to centers from countries participating in the study, as well as the Icelandic Society for Rheumatology, the Swedish Rheumatism Association, and the Research Fund of University Hospital, Reykjavik, Iceland. UCB and Bristol-Myers Squibb provided certolizumab pegol and abatacept, respectively, at no cost, but were not otherwise involved in the study. Many authors, including Dr. Østergaard, report financial relationships with multiple pharmaceutical companies. The full list can be found with the original article.

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

TOPLINE:

Solriamfetol – a medication approved for excessive daytime sleepiness caused by narcolepsy or obstructive sleep apnea – significantly improved symptoms of attention-deficit/hyperactivity disorder (ADHD) and clinical impression of ADHD severity in a pilot study of adults with ADHD.

METHODOLOGY:

• Solriamfetol is a dopamine and norepinephrine reuptake inhibitor that shares some of the properties of current ADHD medications.
• Researchers conducted a randomized, double-blind, placebo-controlled, dose-optimization trial of 75- or 150-mg solriamfetol in 60 adults with ADHD. For nearly all of the individuals who received solriamfetol, doses increased to 150 mg after the first week.
• The primary outcome was change in scores on the Adult ADHD Investigator Symptom Rating Scale (AISRS).
• Secondary outcomes included scores on the Clinical Global Impressions (CGI) scale and standard measures of executive function, behavior, and sleep.

TAKEAWAY:

• By week 6, total AISRS score improved 25% for 52% of individuals to took solriamfetol, vs. 17% of those who received placebo. Total AISRS score improved 50% by week 6 in 28% of those who took solriamfetol, vs. 3.4% of those who received placebo.
• By week 6, CGI ratings of “much improved” or “very much improved” occurred in significantly more individuals who received solriamfetol than those who took placebo (45% vs. 7%).
• Significantly more individuals who received solriamfetol than placebo self-reported improvements in executive function (69% vs. 34%). Improvement in wakefulness was noted with solriamfetol, but that did not moderate the change in ADHD symptom burden.
• Solriamfetol was well tolerated, with no significant effect on sleep quality or blood pressure. Adverse effects that occurred at a higher rate in the treatment group than in the placebo group were typical for solriamfetol and sympathomimetic agents used for ADHD.

IN PRACTICE:

Massachusetts General Hospital

“Solriamfetol may be a safe and effective treatment for ADHD in adults. Larger studies replicating these findings could confirm the strong evidence of benefit and the tolerability of this agent as a treatment,” lead author Craig B.H. Surman, MD, director of the clinical and research program in adult ADHD, Massachusetts General Hospital, Boston, said in a statement.

SOURCE:

The study was published online in The Journal of Clinical Psychiatry.

LIMITATIONS:

Limitations include the small sample size and short 6-week duration. More women than men received solriamfetol; it’s unclear how this could have affected the results.

DISCLOSURES:

The study was an investigator-initiated trial supported by Jazz Pharmaceuticals and Axsome Therapeutics. Dr. Surman has received consultant fees, research support, and royalties from multiple companies.

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

TOPLINE:

Solriamfetol – a medication approved for excessive daytime sleepiness caused by narcolepsy or obstructive sleep apnea – significantly improved symptoms of attention-deficit/hyperactivity disorder (ADHD) and clinical impression of ADHD severity in a pilot study of adults with ADHD.

METHODOLOGY:

• Solriamfetol is a dopamine and norepinephrine reuptake inhibitor that shares some of the properties of current ADHD medications.
• Researchers conducted a randomized, double-blind, placebo-controlled, dose-optimization trial of 75- or 150-mg solriamfetol in 60 adults with ADHD. For nearly all of the individuals who received solriamfetol, doses increased to 150 mg after the first week.
• The primary outcome was change in scores on the Adult ADHD Investigator Symptom Rating Scale (AISRS).
• Secondary outcomes included scores on the Clinical Global Impressions (CGI) scale and standard measures of executive function, behavior, and sleep.

TAKEAWAY:

• By week 6, total AISRS score improved 25% for 52% of individuals to took solriamfetol, vs. 17% of those who received placebo. Total AISRS score improved 50% by week 6 in 28% of those who took solriamfetol, vs. 3.4% of those who received placebo.
• By week 6, CGI ratings of “much improved” or “very much improved” occurred in significantly more individuals who received solriamfetol than those who took placebo (45% vs. 7%).
• Significantly more individuals who received solriamfetol than placebo self-reported improvements in executive function (69% vs. 34%). Improvement in wakefulness was noted with solriamfetol, but that did not moderate the change in ADHD symptom burden.
• Solriamfetol was well tolerated, with no significant effect on sleep quality or blood pressure. Adverse effects that occurred at a higher rate in the treatment group than in the placebo group were typical for solriamfetol and sympathomimetic agents used for ADHD.

IN PRACTICE:

Massachusetts General Hospital

“Solriamfetol may be a safe and effective treatment for ADHD in adults. Larger studies replicating these findings could confirm the strong evidence of benefit and the tolerability of this agent as a treatment,” lead author Craig B.H. Surman, MD, director of the clinical and research program in adult ADHD, Massachusetts General Hospital, Boston, said in a statement.

SOURCE:

The study was published online in The Journal of Clinical Psychiatry.

LIMITATIONS:

Limitations include the small sample size and short 6-week duration. More women than men received solriamfetol; it’s unclear how this could have affected the results.

DISCLOSURES:

The study was an investigator-initiated trial supported by Jazz Pharmaceuticals and Axsome Therapeutics. Dr. Surman has received consultant fees, research support, and royalties from multiple companies.

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

TOPLINE:

Solriamfetol – a medication approved for excessive daytime sleepiness caused by narcolepsy or obstructive sleep apnea – significantly improved symptoms of attention-deficit/hyperactivity disorder (ADHD) and clinical impression of ADHD severity in a pilot study of adults with ADHD.

METHODOLOGY:

• Solriamfetol is a dopamine and norepinephrine reuptake inhibitor that shares some of the properties of current ADHD medications.
• Researchers conducted a randomized, double-blind, placebo-controlled, dose-optimization trial of 75- or 150-mg solriamfetol in 60 adults with ADHD. For nearly all of the individuals who received solriamfetol, doses increased to 150 mg after the first week.
• The primary outcome was change in scores on the Adult ADHD Investigator Symptom Rating Scale (AISRS).
• Secondary outcomes included scores on the Clinical Global Impressions (CGI) scale and standard measures of executive function, behavior, and sleep.

TAKEAWAY:

• By week 6, total AISRS score improved 25% for 52% of individuals to took solriamfetol, vs. 17% of those who received placebo. Total AISRS score improved 50% by week 6 in 28% of those who took solriamfetol, vs. 3.4% of those who received placebo.
• By week 6, CGI ratings of “much improved” or “very much improved” occurred in significantly more individuals who received solriamfetol than those who took placebo (45% vs. 7%).
• Significantly more individuals who received solriamfetol than placebo self-reported improvements in executive function (69% vs. 34%). Improvement in wakefulness was noted with solriamfetol, but that did not moderate the change in ADHD symptom burden.
• Solriamfetol was well tolerated, with no significant effect on sleep quality or blood pressure. Adverse effects that occurred at a higher rate in the treatment group than in the placebo group were typical for solriamfetol and sympathomimetic agents used for ADHD.

IN PRACTICE:

Massachusetts General Hospital

“Solriamfetol may be a safe and effective treatment for ADHD in adults. Larger studies replicating these findings could confirm the strong evidence of benefit and the tolerability of this agent as a treatment,” lead author Craig B.H. Surman, MD, director of the clinical and research program in adult ADHD, Massachusetts General Hospital, Boston, said in a statement.

SOURCE:

The study was published online in The Journal of Clinical Psychiatry.

LIMITATIONS:

Limitations include the small sample size and short 6-week duration. More women than men received solriamfetol; it’s unclear how this could have affected the results.

DISCLOSURES:

The study was an investigator-initiated trial supported by Jazz Pharmaceuticals and Axsome Therapeutics. Dr. Surman has received consultant fees, research support, and royalties from multiple companies.

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

VANCOUVER – A highly controlled retrospective analysis suggests that denosumab (Prolia) leads to greater reduction in fracture risk than does zoledronic acid (Reclast) among treatment-naive postmenopausal women with osteoporosis.

A previous head-to-head comparison showed that denosumab increased bone mineral density at key skeletal sites compared with zoledronic acid, but only a single, small observational study has examined fracture risk, and it found no difference.

The new study, presented at the annual meeting of the American Society for Bone and Mineral Research, used a relatively new method of real-world comparative effectiveness analysis called negative control outcome (NCO) to analyze Medicare fee-for-service data.

NCO analysis takes extra pains to remove bias through data that might be linked to potential confounders but could not reasonably be attributed to a drug. For example, people who have greater contact with the health care system may be more likely to get one drug or another. The researchers used the frequency of receiving a flu or pneumonia vaccine as a proxy for this. If the two comparison groups had a significant difference in a proxy, it suggested a hidden bias and forced the researchers to abandon those groupings. Another example used car accidents as a proxy for cognitive impairment.

“If you find meaningful differences between the two groups, and you can say there’s no way a bone drug could account for these differences, then we shouldn’t do this analysis because these groups just aren’t comparable. They probably differ by that confounding factor we couldn’t measure,” said Jeffrey Curtis, MD, who presented the study. He is a professor of medicine in the division of clinical immunology and rheumatology at the University of Alabama at Birmingham.

The study strongly suggests superiority for denosumab. “There was a significant difference in multiple different groupings of fractures – beginning at year 2, extending to year 3 and even out to year 5 – that showed that there is a significant reduction in fracture risk if you get treated with denosumab [that was greater] than if you get treated with zoledronic acid,” Dr. Curtis said.

The researchers weighed 118 covariates and ultimately identified a population of 90,805 women taking denosumab and 37,328 taking zoledronic acid that was equally balanced in all patient characteristics. The mean age was about 75 years in the denosumab group and 74 in the zoledronic acid group.

The researchers found a 34% lower risk for hip fracture in the denosumab group by 5 years (relative risk, 0.66; 95% confidence interval, 0.43-0.90).

Similar patterns in fracture risk reduction were observed at 5 years for nonvertebral fracture (RR, 0.67; 95% CI, 0.52-0.82), nonhip nonvertebral fracture (RR, 0.69; 95% CI, 0.50-0.88), and major osteoporotic fracture (RR, 0.74; 95% CI, 0.59-0.89).

During the Q&A session after the talk, one audience member commented that the study was limited because the researchers only followed patients who received zoledronic acid for 60 days, which could have missed potential long-term benefits of the drug, especially since bisphosphonates have a lengthy skeletal retention time. Dr. Curtis acknowledged the point but said, “Usually, that’s not something we do, but these are different enough mechanisms of action that it may be warranted at least as a sensitivity analysis,” he said.

The study and its methodology were impressive, according to Yumie Rhee, MD, who comoderated the session where the study was presented. “I think they did a really good job by doing the negative control analysis. We’re not going to have a head-to-head clinical trial, so we don’t know the real fracture reduction differences [between denosumab and zoledronic acid]. [The NCO analysis] is more than the propensity matching score that we do usually,” said Dr. Rhee, who is a professor of endocrinology at Yonsei University College of Medicine in Seoul, South Korea.

In particular, the study showed a significantly greater reduction in hip fractures with denosumab. “Even in the RCTs, it was really hard to see the reduction in hip fracture, so I think this is showing much stronger data for denosumab. Especially in patients who have more [general fracture] risk and patients with higher hip fracture risk, I would go with denosumab,” Dr. Rhee said.

Her comoderator, Maria Zanchetta, MD, agreed. “It can have clinical implication, because we think denosumab is better than [zoledronic acid] for higher-risk patients, but we didn’t have the evidence. So at least we have a new [study] to look at, and I think it’s very important for our practice,” said Dr. Zanchetta, who is a professor of osteology at the Institute of Diagnostics and Metabolic Research, Universidad del Salvador, Buenos Aires.

The study was funded by Amgen, which markets denosumab. Dr. Curtis has consulted for Amgen. Dr. Rhee and Dr. Zanchetta report no relevant financial relationships.

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

VANCOUVER – A highly controlled retrospective analysis suggests that denosumab (Prolia) leads to greater reduction in fracture risk than does zoledronic acid (Reclast) among treatment-naive postmenopausal women with osteoporosis.

A previous head-to-head comparison showed that denosumab increased bone mineral density at key skeletal sites compared with zoledronic acid, but only a single, small observational study has examined fracture risk, and it found no difference.

The new study, presented at the annual meeting of the American Society for Bone and Mineral Research, used a relatively new method of real-world comparative effectiveness analysis called negative control outcome (NCO) to analyze Medicare fee-for-service data.

NCO analysis takes extra pains to remove bias through data that might be linked to potential confounders but could not reasonably be attributed to a drug. For example, people who have greater contact with the health care system may be more likely to get one drug or another. The researchers used the frequency of receiving a flu or pneumonia vaccine as a proxy for this. If the two comparison groups had a significant difference in a proxy, it suggested a hidden bias and forced the researchers to abandon those groupings. Another example used car accidents as a proxy for cognitive impairment.

“If you find meaningful differences between the two groups, and you can say there’s no way a bone drug could account for these differences, then we shouldn’t do this analysis because these groups just aren’t comparable. They probably differ by that confounding factor we couldn’t measure,” said Jeffrey Curtis, MD, who presented the study. He is a professor of medicine in the division of clinical immunology and rheumatology at the University of Alabama at Birmingham.

The study strongly suggests superiority for denosumab. “There was a significant difference in multiple different groupings of fractures – beginning at year 2, extending to year 3 and even out to year 5 – that showed that there is a significant reduction in fracture risk if you get treated with denosumab [that was greater] than if you get treated with zoledronic acid,” Dr. Curtis said.

The researchers weighed 118 covariates and ultimately identified a population of 90,805 women taking denosumab and 37,328 taking zoledronic acid that was equally balanced in all patient characteristics. The mean age was about 75 years in the denosumab group and 74 in the zoledronic acid group.

The researchers found a 34% lower risk for hip fracture in the denosumab group by 5 years (relative risk, 0.66; 95% confidence interval, 0.43-0.90).

Similar patterns in fracture risk reduction were observed at 5 years for nonvertebral fracture (RR, 0.67; 95% CI, 0.52-0.82), nonhip nonvertebral fracture (RR, 0.69; 95% CI, 0.50-0.88), and major osteoporotic fracture (RR, 0.74; 95% CI, 0.59-0.89).

During the Q&A session after the talk, one audience member commented that the study was limited because the researchers only followed patients who received zoledronic acid for 60 days, which could have missed potential long-term benefits of the drug, especially since bisphosphonates have a lengthy skeletal retention time. Dr. Curtis acknowledged the point but said, “Usually, that’s not something we do, but these are different enough mechanisms of action that it may be warranted at least as a sensitivity analysis,” he said.

The study and its methodology were impressive, according to Yumie Rhee, MD, who comoderated the session where the study was presented. “I think they did a really good job by doing the negative control analysis. We’re not going to have a head-to-head clinical trial, so we don’t know the real fracture reduction differences [between denosumab and zoledronic acid]. [The NCO analysis] is more than the propensity matching score that we do usually,” said Dr. Rhee, who is a professor of endocrinology at Yonsei University College of Medicine in Seoul, South Korea.

In particular, the study showed a significantly greater reduction in hip fractures with denosumab. “Even in the RCTs, it was really hard to see the reduction in hip fracture, so I think this is showing much stronger data for denosumab. Especially in patients who have more [general fracture] risk and patients with higher hip fracture risk, I would go with denosumab,” Dr. Rhee said.

Her comoderator, Maria Zanchetta, MD, agreed. “It can have clinical implication, because we think denosumab is better than [zoledronic acid] for higher-risk patients, but we didn’t have the evidence. So at least we have a new [study] to look at, and I think it’s very important for our practice,” said Dr. Zanchetta, who is a professor of osteology at the Institute of Diagnostics and Metabolic Research, Universidad del Salvador, Buenos Aires.

The study was funded by Amgen, which markets denosumab. Dr. Curtis has consulted for Amgen. Dr. Rhee and Dr. Zanchetta report no relevant financial relationships.

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

VANCOUVER – A highly controlled retrospective analysis suggests that denosumab (Prolia) leads to greater reduction in fracture risk than does zoledronic acid (Reclast) among treatment-naive postmenopausal women with osteoporosis.

A previous head-to-head comparison showed that denosumab increased bone mineral density at key skeletal sites compared with zoledronic acid, but only a single, small observational study has examined fracture risk, and it found no difference.

The new study, presented at the annual meeting of the American Society for Bone and Mineral Research, used a relatively new method of real-world comparative effectiveness analysis called negative control outcome (NCO) to analyze Medicare fee-for-service data.

NCO analysis takes extra pains to remove bias through data that might be linked to potential confounders but could not reasonably be attributed to a drug. For example, people who have greater contact with the health care system may be more likely to get one drug or another. The researchers used the frequency of receiving a flu or pneumonia vaccine as a proxy for this. If the two comparison groups had a significant difference in a proxy, it suggested a hidden bias and forced the researchers to abandon those groupings. Another example used car accidents as a proxy for cognitive impairment.

“If you find meaningful differences between the two groups, and you can say there’s no way a bone drug could account for these differences, then we shouldn’t do this analysis because these groups just aren’t comparable. They probably differ by that confounding factor we couldn’t measure,” said Jeffrey Curtis, MD, who presented the study. He is a professor of medicine in the division of clinical immunology and rheumatology at the University of Alabama at Birmingham.

The study strongly suggests superiority for denosumab. “There was a significant difference in multiple different groupings of fractures – beginning at year 2, extending to year 3 and even out to year 5 – that showed that there is a significant reduction in fracture risk if you get treated with denosumab [that was greater] than if you get treated with zoledronic acid,” Dr. Curtis said.

The researchers weighed 118 covariates and ultimately identified a population of 90,805 women taking denosumab and 37,328 taking zoledronic acid that was equally balanced in all patient characteristics. The mean age was about 75 years in the denosumab group and 74 in the zoledronic acid group.

The researchers found a 34% lower risk for hip fracture in the denosumab group by 5 years (relative risk, 0.66; 95% confidence interval, 0.43-0.90).

Similar patterns in fracture risk reduction were observed at 5 years for nonvertebral fracture (RR, 0.67; 95% CI, 0.52-0.82), nonhip nonvertebral fracture (RR, 0.69; 95% CI, 0.50-0.88), and major osteoporotic fracture (RR, 0.74; 95% CI, 0.59-0.89).

During the Q&A session after the talk, one audience member commented that the study was limited because the researchers only followed patients who received zoledronic acid for 60 days, which could have missed potential long-term benefits of the drug, especially since bisphosphonates have a lengthy skeletal retention time. Dr. Curtis acknowledged the point but said, “Usually, that’s not something we do, but these are different enough mechanisms of action that it may be warranted at least as a sensitivity analysis,” he said.

The study and its methodology were impressive, according to Yumie Rhee, MD, who comoderated the session where the study was presented. “I think they did a really good job by doing the negative control analysis. We’re not going to have a head-to-head clinical trial, so we don’t know the real fracture reduction differences [between denosumab and zoledronic acid]. [The NCO analysis] is more than the propensity matching score that we do usually,” said Dr. Rhee, who is a professor of endocrinology at Yonsei University College of Medicine in Seoul, South Korea.

In particular, the study showed a significantly greater reduction in hip fractures with denosumab. “Even in the RCTs, it was really hard to see the reduction in hip fracture, so I think this is showing much stronger data for denosumab. Especially in patients who have more [general fracture] risk and patients with higher hip fracture risk, I would go with denosumab,” Dr. Rhee said.

Her comoderator, Maria Zanchetta, MD, agreed. “It can have clinical implication, because we think denosumab is better than [zoledronic acid] for higher-risk patients, but we didn’t have the evidence. So at least we have a new [study] to look at, and I think it’s very important for our practice,” said Dr. Zanchetta, who is a professor of osteology at the Institute of Diagnostics and Metabolic Research, Universidad del Salvador, Buenos Aires.

The study was funded by Amgen, which markets denosumab. Dr. Curtis has consulted for Amgen. Dr. Rhee and Dr. Zanchetta report no relevant financial relationships.

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

HAMBURG, GERMANY – The investigational incretin receptor agonist pemvidutide produced significant weight loss and other cardiometabolic benefits in a phase 2 randomized trial, adding a different type of “twincretin” to a growing mix of incretin-based weight-loss drugs in development that also offer additional benefits.

Pemvidutide (Altimmune Inc) is a long-acting “balanced” dual agonist of both glucagon-like peptide 1 (GLP-1) and glucagon that is in development for the treatment of obesity and nonalcoholic steatohepatitis (NASH) but not type 2 diabetes, as its effect on glucose is neutral. Phase 1 data for pemvidutide’s liver effect were presented in 2022.

In contrast, the dual GLP-1-glucose-dependent insulinotropic polypeptide (GIP) agonist tirzepatide (Mounjaro, Lilly) has been approved for the treatment of type 2 diabetes. It awaits an indication for obesity.

“When you look [at] the results for any given agent, think about obesity as a series of problems. Some overlap, and some don’t. While about 20%-25% of people with obesity also have type 2 diabetes, not everybody does. So the compounds that don’t lower glucose ... those will be great for others who have [fatty liver disease] or hyperlipidemia. ... It’s not going to be one compound for everybody,” said Louis J. Aronne, MD, director of the center for weight management and metabolic clinical research, Weill Cornell Medicine, New York.

Results of a new 24-week interim analysis of data from the phase 2 pemvidutide trial, called MOMENTUM, were presented at the annual meeting of the European Association for the Study of Diabetes by Dr. Aronne.

Included in that session were encore presentations of data for another GLP-1-glucagon dual agonist, survodutide, as well as data for Eli Lilly’s GLP-1-GIP-glucagon “triagonist,” retatrutide. Retatrutide is in development to induce weight loss, while survodutide (Boehringer Ingelheim and Zealand Pharma), like pemvidutide, is in development to induce weight loss and treat fatty liver disease.

Added Dr. Aronne, “As good as [the triple agonist] retatrutide looks, I doubt that every single person with obesity in the world will be treated with it. ... Think about this as a field, the way you treat diabetes and every other chronic illness.”

Asked to comment, session moderator Rajna Golubic, PhD, of the Oxford (England) Centre for Diabetes, Endocrinology and Metabolism, told this news organization, “We need to think in terms of treating beyond weight loss. ... We need to look at the person holistically and at other aspects of cardiometabolic health and treat in a personalized way and choose treatments according to the comorbidities people have.”

Regarding the dual GLP-1-glucagon agonists, including pemvidutide, Dr. Golubic pointed out that the glucagon agonism does the opposite of glucose-lowering agents but that the compound is “balanced for greater affinity for the GLP-1 receptor vs. glucagon, so that the beneficial effects outweigh the effect for glucose but it still harnesses the benefits of glucagon on liver with a decrease in liver fat, with positive effects on heart, positive effects on kidneys, and other beneficial metabolic effects.”
 

Pemvidutide lowers weight, LDL cholesterol, triglycerides, and blood pressure

Dr. Aronne began his presentation by noting that dyslipidemia, fatty liver disease, and hypertension are the most significant comorbidities of obesity, occurring in 66%-70%, 58%-75%, and 45%-55% of patients, respectively, while type 2 diabetes is less common, at 19%-23%.

Pemvidutide’s GLP-1 receptor agonism reduces appetite, inflammation, and gastric emptying, while glucagon agonism increases lipolysis, mobilizes fat, and increases energy expenditure, Dr. Aronne explained.

The 48-week phase 2 MOMENTUM trial randomly assigned 320 participants with overweight or obesity and at least one obesity-related comorbidity but not diabetes to receive weekly doses of 1.2 mg, 1.8 mg, or 2.4 mg of pemvidutide or placebo. The two lower pemvidutide doses were initiated immediately without titration, while the 2.4-mg dose was titrated rapidly over 4 weeks.

In a prespecified interim analysis of 160 participants, the percent body weight loss at 24 weeks was 10.7%, 9.4%, and 7.3% with the 2.4-mg, 1.8-mg, and 1.2-mg doses, respectively (P < .001). All weight loss values were significant; weight loss with placebo was a nonsignificant 1%.

The proportions of patients who lost at least 5% of their body weight were 84.6%, 66.7%, and 66.7%, respectively, vs. 25% with placebo. Half of the patients who received the 2.4-mg and 1.8-mg doses lost at least 10% of their body weight. Reductions in waist circumference followed suit; the patients who received the 2.4-mg dose lost an average of 10.2 cm, or “in the U.S., about 4 inches or 4 belt loops. That’s pretty good, you need a new belt,” Dr. Aronne commented.

Significant reductions in total cholesterol and triglyceride levels were also seen at week 24 by 16.5% and 25.0%, respectively, with the 2.4-mg dose. Low-density lipoprotein cholesterol levels also dropped, although not significantly; high-density lipoprotein levels dropped significantly.

Systolic blood pressure dropped by 5.5 mm Hg, and diastolic blood pressure dropped by 1.8 mm Hg in the 2.4-mg group and by lesser degrees among the patients who received lower doses. There were no significant changes in heart rate, Dr. Aronne noted.

Glucose homeostasis was preserved in all groups throughout the 24 weeks.

As with all drugs in the incretin class, gastrointestinal adverse events were common. Severe vomiting occurred in one person in the 1.8-mg group and in four with 2.4 mg. Efforts will be made to reduce that in subsequent trials, Dr. Aronne said.

“We have learned over time that going more gradually in titrating up these agents is a better strategy, allowing dose reduction may be a better strategy, and allowing antiemetics temporarily as we increase the dose is a lesson that many have learned doing these trials and of course in our clinical practices,” he commented.

Dr. Golubic told this news organization that the recent emergence of potent incretin-based weight loss drugs is “a huge paradigm shift. The prevalence of obesity will be 35% or higher by 2035. Bariatric surgery isn’t feasible for everyone, and it’s very expensive, so we need drugs to provide benefits in terms of lowering weight, glucose, and other cardiometabolic risk factors.”

The full 48-week data for MOMENTUM will be announced in the fourth quarter of 2023.

Dr. Aronne has received consulting fees from and serves on advisory boards for Allurion, Altimmune, Atria, Gelesis, Jamieson Wellness, Janssen Pharmaceuticals, Jazz Pharmaceuticals, Novo Nordisk, Pfizer, Optum, Eli Lilly, Senda Biosciences, and Versanis; has received research funding from Allurion, AstraZeneca, Gelesis, Janssen Pharmaceuticals, Novo Nordisk, and Eli Lilly; has equity interests in Allurion, ERX Pharmaceuticals, Gelesis, Intellihealth, Jamieson Wellness, and Myos Corp; and serves on a board of directors for ERX Pharmaceuticals, Intellihealth, and Jamieson Wellness. Dr. Golubic has received research support from AstraZeneca.

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

HAMBURG, GERMANY – The investigational incretin receptor agonist pemvidutide produced significant weight loss and other cardiometabolic benefits in a phase 2 randomized trial, adding a different type of “twincretin” to a growing mix of incretin-based weight-loss drugs in development that also offer additional benefits.

Pemvidutide (Altimmune Inc) is a long-acting “balanced” dual agonist of both glucagon-like peptide 1 (GLP-1) and glucagon that is in development for the treatment of obesity and nonalcoholic steatohepatitis (NASH) but not type 2 diabetes, as its effect on glucose is neutral. Phase 1 data for pemvidutide’s liver effect were presented in 2022.

In contrast, the dual GLP-1-glucose-dependent insulinotropic polypeptide (GIP) agonist tirzepatide (Mounjaro, Lilly) has been approved for the treatment of type 2 diabetes. It awaits an indication for obesity.

“When you look [at] the results for any given agent, think about obesity as a series of problems. Some overlap, and some don’t. While about 20%-25% of people with obesity also have type 2 diabetes, not everybody does. So the compounds that don’t lower glucose ... those will be great for others who have [fatty liver disease] or hyperlipidemia. ... It’s not going to be one compound for everybody,” said Louis J. Aronne, MD, director of the center for weight management and metabolic clinical research, Weill Cornell Medicine, New York.

Results of a new 24-week interim analysis of data from the phase 2 pemvidutide trial, called MOMENTUM, were presented at the annual meeting of the European Association for the Study of Diabetes by Dr. Aronne.

Included in that session were encore presentations of data for another GLP-1-glucagon dual agonist, survodutide, as well as data for Eli Lilly’s GLP-1-GIP-glucagon “triagonist,” retatrutide. Retatrutide is in development to induce weight loss, while survodutide (Boehringer Ingelheim and Zealand Pharma), like pemvidutide, is in development to induce weight loss and treat fatty liver disease.

Added Dr. Aronne, “As good as [the triple agonist] retatrutide looks, I doubt that every single person with obesity in the world will be treated with it. ... Think about this as a field, the way you treat diabetes and every other chronic illness.”

Asked to comment, session moderator Rajna Golubic, PhD, of the Oxford (England) Centre for Diabetes, Endocrinology and Metabolism, told this news organization, “We need to think in terms of treating beyond weight loss. ... We need to look at the person holistically and at other aspects of cardiometabolic health and treat in a personalized way and choose treatments according to the comorbidities people have.”

Regarding the dual GLP-1-glucagon agonists, including pemvidutide, Dr. Golubic pointed out that the glucagon agonism does the opposite of glucose-lowering agents but that the compound is “balanced for greater affinity for the GLP-1 receptor vs. glucagon, so that the beneficial effects outweigh the effect for glucose but it still harnesses the benefits of glucagon on liver with a decrease in liver fat, with positive effects on heart, positive effects on kidneys, and other beneficial metabolic effects.”
 

Pemvidutide lowers weight, LDL cholesterol, triglycerides, and blood pressure

Dr. Aronne began his presentation by noting that dyslipidemia, fatty liver disease, and hypertension are the most significant comorbidities of obesity, occurring in 66%-70%, 58%-75%, and 45%-55% of patients, respectively, while type 2 diabetes is less common, at 19%-23%.

Pemvidutide’s GLP-1 receptor agonism reduces appetite, inflammation, and gastric emptying, while glucagon agonism increases lipolysis, mobilizes fat, and increases energy expenditure, Dr. Aronne explained.

The 48-week phase 2 MOMENTUM trial randomly assigned 320 participants with overweight or obesity and at least one obesity-related comorbidity but not diabetes to receive weekly doses of 1.2 mg, 1.8 mg, or 2.4 mg of pemvidutide or placebo. The two lower pemvidutide doses were initiated immediately without titration, while the 2.4-mg dose was titrated rapidly over 4 weeks.

In a prespecified interim analysis of 160 participants, the percent body weight loss at 24 weeks was 10.7%, 9.4%, and 7.3% with the 2.4-mg, 1.8-mg, and 1.2-mg doses, respectively (P < .001). All weight loss values were significant; weight loss with placebo was a nonsignificant 1%.

The proportions of patients who lost at least 5% of their body weight were 84.6%, 66.7%, and 66.7%, respectively, vs. 25% with placebo. Half of the patients who received the 2.4-mg and 1.8-mg doses lost at least 10% of their body weight. Reductions in waist circumference followed suit; the patients who received the 2.4-mg dose lost an average of 10.2 cm, or “in the U.S., about 4 inches or 4 belt loops. That’s pretty good, you need a new belt,” Dr. Aronne commented.

Significant reductions in total cholesterol and triglyceride levels were also seen at week 24 by 16.5% and 25.0%, respectively, with the 2.4-mg dose. Low-density lipoprotein cholesterol levels also dropped, although not significantly; high-density lipoprotein levels dropped significantly.

Systolic blood pressure dropped by 5.5 mm Hg, and diastolic blood pressure dropped by 1.8 mm Hg in the 2.4-mg group and by lesser degrees among the patients who received lower doses. There were no significant changes in heart rate, Dr. Aronne noted.

Glucose homeostasis was preserved in all groups throughout the 24 weeks.

As with all drugs in the incretin class, gastrointestinal adverse events were common. Severe vomiting occurred in one person in the 1.8-mg group and in four with 2.4 mg. Efforts will be made to reduce that in subsequent trials, Dr. Aronne said.

“We have learned over time that going more gradually in titrating up these agents is a better strategy, allowing dose reduction may be a better strategy, and allowing antiemetics temporarily as we increase the dose is a lesson that many have learned doing these trials and of course in our clinical practices,” he commented.

Dr. Golubic told this news organization that the recent emergence of potent incretin-based weight loss drugs is “a huge paradigm shift. The prevalence of obesity will be 35% or higher by 2035. Bariatric surgery isn’t feasible for everyone, and it’s very expensive, so we need drugs to provide benefits in terms of lowering weight, glucose, and other cardiometabolic risk factors.”

The full 48-week data for MOMENTUM will be announced in the fourth quarter of 2023.

Dr. Aronne has received consulting fees from and serves on advisory boards for Allurion, Altimmune, Atria, Gelesis, Jamieson Wellness, Janssen Pharmaceuticals, Jazz Pharmaceuticals, Novo Nordisk, Pfizer, Optum, Eli Lilly, Senda Biosciences, and Versanis; has received research funding from Allurion, AstraZeneca, Gelesis, Janssen Pharmaceuticals, Novo Nordisk, and Eli Lilly; has equity interests in Allurion, ERX Pharmaceuticals, Gelesis, Intellihealth, Jamieson Wellness, and Myos Corp; and serves on a board of directors for ERX Pharmaceuticals, Intellihealth, and Jamieson Wellness. Dr. Golubic has received research support from AstraZeneca.

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

HAMBURG, GERMANY – The investigational incretin receptor agonist pemvidutide produced significant weight loss and other cardiometabolic benefits in a phase 2 randomized trial, adding a different type of “twincretin” to a growing mix of incretin-based weight-loss drugs in development that also offer additional benefits.

Pemvidutide (Altimmune Inc) is a long-acting “balanced” dual agonist of both glucagon-like peptide 1 (GLP-1) and glucagon that is in development for the treatment of obesity and nonalcoholic steatohepatitis (NASH) but not type 2 diabetes, as its effect on glucose is neutral. Phase 1 data for pemvidutide’s liver effect were presented in 2022.

In contrast, the dual GLP-1-glucose-dependent insulinotropic polypeptide (GIP) agonist tirzepatide (Mounjaro, Lilly) has been approved for the treatment of type 2 diabetes. It awaits an indication for obesity.

“When you look [at] the results for any given agent, think about obesity as a series of problems. Some overlap, and some don’t. While about 20%-25% of people with obesity also have type 2 diabetes, not everybody does. So the compounds that don’t lower glucose ... those will be great for others who have [fatty liver disease] or hyperlipidemia. ... It’s not going to be one compound for everybody,” said Louis J. Aronne, MD, director of the center for weight management and metabolic clinical research, Weill Cornell Medicine, New York.

Results of a new 24-week interim analysis of data from the phase 2 pemvidutide trial, called MOMENTUM, were presented at the annual meeting of the European Association for the Study of Diabetes by Dr. Aronne.

Included in that session were encore presentations of data for another GLP-1-glucagon dual agonist, survodutide, as well as data for Eli Lilly’s GLP-1-GIP-glucagon “triagonist,” retatrutide. Retatrutide is in development to induce weight loss, while survodutide (Boehringer Ingelheim and Zealand Pharma), like pemvidutide, is in development to induce weight loss and treat fatty liver disease.

Added Dr. Aronne, “As good as [the triple agonist] retatrutide looks, I doubt that every single person with obesity in the world will be treated with it. ... Think about this as a field, the way you treat diabetes and every other chronic illness.”

Asked to comment, session moderator Rajna Golubic, PhD, of the Oxford (England) Centre for Diabetes, Endocrinology and Metabolism, told this news organization, “We need to think in terms of treating beyond weight loss. ... We need to look at the person holistically and at other aspects of cardiometabolic health and treat in a personalized way and choose treatments according to the comorbidities people have.”

Regarding the dual GLP-1-glucagon agonists, including pemvidutide, Dr. Golubic pointed out that the glucagon agonism does the opposite of glucose-lowering agents but that the compound is “balanced for greater affinity for the GLP-1 receptor vs. glucagon, so that the beneficial effects outweigh the effect for glucose but it still harnesses the benefits of glucagon on liver with a decrease in liver fat, with positive effects on heart, positive effects on kidneys, and other beneficial metabolic effects.”
 

Pemvidutide lowers weight, LDL cholesterol, triglycerides, and blood pressure

Dr. Aronne began his presentation by noting that dyslipidemia, fatty liver disease, and hypertension are the most significant comorbidities of obesity, occurring in 66%-70%, 58%-75%, and 45%-55% of patients, respectively, while type 2 diabetes is less common, at 19%-23%.

Pemvidutide’s GLP-1 receptor agonism reduces appetite, inflammation, and gastric emptying, while glucagon agonism increases lipolysis, mobilizes fat, and increases energy expenditure, Dr. Aronne explained.

The 48-week phase 2 MOMENTUM trial randomly assigned 320 participants with overweight or obesity and at least one obesity-related comorbidity but not diabetes to receive weekly doses of 1.2 mg, 1.8 mg, or 2.4 mg of pemvidutide or placebo. The two lower pemvidutide doses were initiated immediately without titration, while the 2.4-mg dose was titrated rapidly over 4 weeks.

In a prespecified interim analysis of 160 participants, the percent body weight loss at 24 weeks was 10.7%, 9.4%, and 7.3% with the 2.4-mg, 1.8-mg, and 1.2-mg doses, respectively (P < .001). All weight loss values were significant; weight loss with placebo was a nonsignificant 1%.

The proportions of patients who lost at least 5% of their body weight were 84.6%, 66.7%, and 66.7%, respectively, vs. 25% with placebo. Half of the patients who received the 2.4-mg and 1.8-mg doses lost at least 10% of their body weight. Reductions in waist circumference followed suit; the patients who received the 2.4-mg dose lost an average of 10.2 cm, or “in the U.S., about 4 inches or 4 belt loops. That’s pretty good, you need a new belt,” Dr. Aronne commented.

Significant reductions in total cholesterol and triglyceride levels were also seen at week 24 by 16.5% and 25.0%, respectively, with the 2.4-mg dose. Low-density lipoprotein cholesterol levels also dropped, although not significantly; high-density lipoprotein levels dropped significantly.

Systolic blood pressure dropped by 5.5 mm Hg, and diastolic blood pressure dropped by 1.8 mm Hg in the 2.4-mg group and by lesser degrees among the patients who received lower doses. There were no significant changes in heart rate, Dr. Aronne noted.

Glucose homeostasis was preserved in all groups throughout the 24 weeks.

As with all drugs in the incretin class, gastrointestinal adverse events were common. Severe vomiting occurred in one person in the 1.8-mg group and in four with 2.4 mg. Efforts will be made to reduce that in subsequent trials, Dr. Aronne said.

“We have learned over time that going more gradually in titrating up these agents is a better strategy, allowing dose reduction may be a better strategy, and allowing antiemetics temporarily as we increase the dose is a lesson that many have learned doing these trials and of course in our clinical practices,” he commented.

Dr. Golubic told this news organization that the recent emergence of potent incretin-based weight loss drugs is “a huge paradigm shift. The prevalence of obesity will be 35% or higher by 2035. Bariatric surgery isn’t feasible for everyone, and it’s very expensive, so we need drugs to provide benefits in terms of lowering weight, glucose, and other cardiometabolic risk factors.”

The full 48-week data for MOMENTUM will be announced in the fourth quarter of 2023.

Dr. Aronne has received consulting fees from and serves on advisory boards for Allurion, Altimmune, Atria, Gelesis, Jamieson Wellness, Janssen Pharmaceuticals, Jazz Pharmaceuticals, Novo Nordisk, Pfizer, Optum, Eli Lilly, Senda Biosciences, and Versanis; has received research funding from Allurion, AstraZeneca, Gelesis, Janssen Pharmaceuticals, Novo Nordisk, and Eli Lilly; has equity interests in Allurion, ERX Pharmaceuticals, Gelesis, Intellihealth, Jamieson Wellness, and Myos Corp; and serves on a board of directors for ERX Pharmaceuticals, Intellihealth, and Jamieson Wellness. Dr. Golubic has received research support from AstraZeneca.

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