Loading ...

LONDON — When managing joint involvement in people with psoriatic arthritis (PsA), dual inhibition of interleukin (IL)-17A and IL-17F with bimekizumab (Bimzelx) proved to be superior to inhibition of IL-23 with risankizumab (Skyrizi) in the BE BOLD trial.

The primary endpoint of a 50% reduction in the American College of Rheumatology response criteria (ACR50) at week 16 was met by 49.1% of 277 people treated with bimekizumab and 38.0% of the 276 treated with risankizumab. The 11.1% difference was highly significant (P = .0058).

The difference in achieving ACR50 between the two arms was apparent as early as 4 weeks (19.9% vs 7.2%, respectively; P < .0001) and continued to the end of the 24-week treatment period (54.9% vs 43.8%). 

“I think this is relevant to us clinically, insofar as we make our clinical decisions as early as 12 weeks in many patients,” Joseph Merola, MD, MMSc, professor and chair of the Department of Dermatology and professor of internal medicine in the Division of Rheumatic Diseases at UT Southwestern Medical Center, Dallas, said at the European Alliance of Associations for Rheumatology (EULAR) 2026 Annual Meeting.

“We've [also] talked for many years about how time matters to patients with this disease, both with regard to symptoms but also functional damage over time,” he added.

BE BOLD Study Design 

BE BOLD was a phase 3b study with a standard design consisting of a 24-week treatment period with a 12-week follow-up for safety evaluation. 

Adults with active PsA were recruited if they had three or more tender or swollen joints and an inadequate response or intolerance to a TNF inhibitor (TNFi) or if they were naïve to treatment with a TNFi. 

Participants were randomly allocated to receive bimekizumab or risankizumab for 24 weeks. Those in the bimekizumab arm with no or moderate psoriasis (n = 248) were given 160 mg every 4 weeks for the full treatment period, and those with moderate to severe psoriasis (about 11% of the population in both arms) were treated with a higher dose of 320 mg every 4 weeks for the first 16 weeks, and then every 8 weeks until the end of treatment. Participants in the risankizumab arm were given 150 mg at baseline, at week 4, and then every 12 weeks, as per its label. 

Baseline characteristics were well matched. Mean age was 51 years, and 51% were men who had been diagnosed a mean of 6 years ago. About one fifth had received prior TNFi therapy, and 70% had been administered any conventional synthetic disease-modifying antirheumatic drug. 

Starting tender and swollen joint counts were a respective 17.3 and 10.1 in the bimekizumab group and 16.6 and 9.5 in the risankizumab group.

First Head-to-Head Trial in PsA

Both bimekizumab and risankizumab are approved to treat plaque psoriasis and PsA, but this is the first time they have been directly compared for improvement of a joint-focused outcome in PsA, “which is why I think it's so incredibly exciting,” Merola said. “We haven't had such high-quality data to date in this space; these [data] will be important for treatment guidelines, and I think it will inform our management of psoriatic arthritis.”

Topline results at 16 weeks have already been released. Merola reported some of the 24-week results during a late-breaking abstract presentation.

Disease Activity, Joint and Skin Improvements 

Among the new findings were continued improvement with bimekizumab vs risankizumab in most secondary endpoints at week 24. These were exploratory results, however, because hierarchical statistical testing had been used and only a numerical advantage had been seen for the first secondary endpoint tested, the proportion of patients achieving minimal disease activity (MDA).

An MDA response at weeks 4, 16, and 24 was achieved in a respective 13.7%, 43.3%, and 49.1% of bimekizumab-treated participants and in 6.5%, 39.9%, and 42.4% in the risankizumab group.

ACR50 and completely clear skin, as indicated by a Psoriasis Area and Severity Index (PASI) of 100, occurred in 3.4% vs 1.1% of the bimekizumab and risankizumab group, respectively, at 4 weeks; in 33.5% vs 24.4% at 16 weeks; and in 39.2% vs 34.1% at 24 weeks. 

Among participants who had at least 3% body surface area affected by psoriasis at baseline, PASI 100 rates were numerically higher in the bimekizumab group than in the risankizumab group at week 4 (12.5% vs 3.4%) and week 16 (53.4% vs 46.6%), but not at week 24 (59.7% vs 59.1%). 

Treatment with bimekizumab led to numerically higher rates of patients who met criteria for either low disease activity or remission on the Disease Activity Index for Psoriatic Arthritis compared to risankizumab across all time points: 29.6% vs 21.7% at week 4, 65.3% vs 55.1% at week 16, and 68.2% vs 62.3% at week 24. 

Comparable Safety

Early safety findings suggested the two treatments were comparable, and there were no new safety signals, Merola said. 

Treatment-emergent adverse events (TEAEs) occurred in a respective 58.1% and 55.3% of bimekizumab- and risankizumab-treated participants. Serious TEAEs occurred in 1.8% and 3.3.% of participants, respectively, and severe TEAEs in 1.8% and 1.8%; discontinuation as a result of TEAEs was 1.4% and 1.1%.

The rates of specific side effects were not reported to preserve blinding in the ongoing study, so only limited data could be presented, Merola said. However, rates of serious infections, inflammatory bowel disease, malignancy, neutropenia, hypersensitivity, and hepatic or cardiovascular events were low across both treatment arms, he noted.

Candida infections were more frequent in bimekizumab-treated than in risankizumab-treated participants, but none were considered serious, systemic, or a reason to discontinue the study.

One patient with a history of coronary artery disease, hypertension, and dyslipidemia died from a myocardial infarction, but their treatment group was not reported, and the death was deemed unrelated to study medications. 

“It's important to show dual IL-17 inhibition is superior to IL-23 inhibition, which helps to direct choice of appropriate therapy to patients with psoriatic arthritis,” Jonathan Kay, MD, the Timothy S. and Elaine L. Peterson Chair in Rheumatology and professor of medicine at the University of Massachusetts School of Medicine, Worcester, told Medscape Medical News. Kay was not involved in the study.

The study was funded by UCB. Merola has disclosed acting as a consultant and/or investigator for AbbVie, Amgen, AstraZeneca, Biogen, Bristol Myers Squibb, Boehringer Ingelheim, Eli Lilly, Galderma, Janssen, MoonLake Immunotherapeutics, Novartis, Oruka Therapeutics, Pfizer, Regeneron, Sanofi, Sun Pharma, and UCB. Kay acknowledged receiving research support paid to his institution from Biogen and Galapagos NV in the past 12 months, and acting as a consultant to Artiva Biotherapeutics, AstraZeneca, Cue Biopharma, Immunovant, Immunitas Therapeutics, Organon, Samsung Bioepis, and Spyre Therapeutics. 

Sara Freeman, BSc, MSc, is a freelance medical journalist based in London, UK. She has been reporting for specialist healthcare news organizations for more than 20 years.