The interleukin-17A (IL-17A) and IL-17F blocker has also racked up significant wins against ustekinumab and secukinumab, other standard biologic options for adults with moderate to severe plaque psoriasis, and is currently under review for the indication by the US Food and Drug Administration and European Medicines Agency.
In the adalimumab trial, dubbed BE SURE, bimekizumab had higher clinical response rates than the tumor necrosis factor (TNF) blocker over the 24-week head-to-head phase of the 478-patient trial, with substantial improvements in both PASI 90 response and Investigator’s Global Assessment (IGA) scores of 0 or 1, which signifies clear or almost clear skin.
The results were published in the New England Journal of Medicine and are scheduled to be presented at the American Academy of Dermatology Virtual Meeting Experience on April 24.
“The data look good,” said psoriasis specialist Steven Feldman, MD, PhD, professor of dermatology at Wake Forest School of Medicine in Winston-Salem, North Carolina, when asked for comment.
Bimekizumab “appears more effective than current options. The big question is safety. The 10-20% rate of oral candidiasis is much higher than other treatments but should be entirely manageable, as long as there are no unknown worse candida issues.” In addition, there were no cases of inflammatory bowel disease in BE SURE, which “is very encouraging, as that is one of the limitations for existing IL-17 blockers,” he said.
The trial was launched after previous reports suggested that IL-17A inhibition may be better than TNF blockade in controlling psoriasis, said investigators led by Richard Warren, MBChB, PhD, a dermatology professor at the University of Manchester in England.
Patients were assigned evenly to one of three regimens: subcutaneous bimekizumab at a dose of 320 mg every 4 weeks for 56 weeks; bimekizumab at 320 mg every 4 weeks for 16 weeks, then every 8 weeks out to 56 weeks; or subcutaneous adalimumab at a dose of 40 mg every 2 weeks for 24 weeks, followed by bimekizumab at a dose of 320 mg every 4 weeks to week 56.
At week 16, 86.2% of those in the bimekizumab group but just 47.2% in the adalimumab group had a PASI 90 response (P < .001), and 85.3% of the bimekizumab vs 57.2% in the adalimumab group had an IGA score of 0 or 1 (P < .001).
About 52% of the adalimumab group had a PASI 90 response at week 24, when they were switched to bimekizumab. By week 56, their PASI 90 response rate rose to 81.8%. Skin clearance was maintained through week 56 whether subjects were dosed every 4 or every 8 weeks with the interleukin blocker.
The incidence of oral candidiasis (9.5% – 17.4% vs 0% with adalimumab alone) was similar to other trials and likely due to the short circuiting of IL-17, which plays a role protecting against candida. Most cases were mild to moderate.
The increased risk of oral thrush with bimekizumab “may not be particularly clinically meaningful, especially if” it can be managed by an occasional fluconazole pill. It’s “reassuring…if that’s the biggest problem with the drug, or we may wonder if in real-life use more severe, perhaps esophageal or systemic fungal infection may be observed,” Feldman said in a recent editorial.
“Not knowing the future may make some physicians reticent about using the drug when other options are available, at least until data are available on much larger numbers of exposed patients treated for longer periods of time,” he and his colleague William Huang, MD, also a dermatologist at Wake Forest, said.
One of the limits of the trial was that the head-to-head portion was only 24 weeks, “which was too brief for a comparison of safety between bimekizumab and adalimumab in a lifelong disease,” the investigators noted.
The mean age of the patients was 44.9 years, and the mean baseline PASI score was 19.8.
Although the initial dose of adalimumab in the study was 40 mg, labeling recommends an initial dose of 80 mg for the TNF blocker.
The study was funded by UCB Pharma. The investigators had numerous disclosures, including Warren who reported grants and personal fees from the company. Feldman reported research, speaking, and/or consulting support from UCB and other companies.
N Engl J Med. Published online April 23, 2021. Abstract
M. Alexander Otto is a physician assistant with a master’s degree in medical science and a Newhouse journalism degree from Syracuse University. He is an award-winning medical journalist who worked for McClatchy and Bloomberg before joining Medscape, and also an MIT Knight Science Journalism fellow. Email: [email protected]