Dual inhibition of IL-17A and IL-17F achieved superiority in key psoriatic arthritis outcomes in first head-to-head with IL-23p19 inhibition.
Prescribing bimekizumab yields significantly better joint outcomes and faster symptom relief for psoriatic arthritis (PsA) patients than risankizumab, according to findings from the first direct head-to-head trial comparing the two mechanisms for joint-focused outcomes.
Data from the phase 3b BE BOLD trial, presented at the European Alliance of Associations for Rheumatology (EULAR) 2026 Annual Meeting in London, showed that bimekizumab met its primary endpoint, achieving a significantly higher 16-week ACR50 response rate than its IL-23 competitor.
The trial results indicate that targeting both IL-17A and IL-17F provides a distinct advantage in managing peripheral joint inflammation, according to presenter Professor Joseph Merola, chair of dermatology and a professor of internal medicine at UT Southwestern Medical Centre in Dallas.
Rapid separation in joint efficacy
The randomised, phase 3b study evaluated adults with active PsA who had three or more tender or swollen joints and were either biologic-naïve or had experienced an inadequate response or intolerance to a TNF inhibitor.
Participants were allocated to receive either bimekizumab (160mg every 4 weeks, increased to 320mg for those with moderate-to-severe skin involvement) or risankizumab (150mg at baseline, week 4, and every 12 weeks thereafter) for a 24-week treatment block.
Baseline demographics were well matched between the arms; cohorts had a mean age of 51 years and an average disease duration of six years, with heavy joint disease burdens at baseline (mean tender joint counts of around 17 and swollen joint counts of around 10).
At the 16-week primary endpoint, 49.1% of the 277 patients in the bimekizumab arm achieved an ACR50 response (a 50% improvement in standard joint criteria), compared with 38.0% of the 276 patients treated with risankizumab. This 11.1% therapeutic gap was highly significant (P = .0058).
By week four, nearly three times as many bimekizumab patients achieved an ACR50 response compared to those on risankizumab (19.9% vs 7.2%; P < .0001). This numerical advantage persisted through the end of the 24 weeks, ending at 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,” Professor Merola said.
“Time matters to patients with this disease, both about symptoms but also functional damage over time.”
Tracking disease activity and skin outcomes
Secondary exploratory outcomes also favoured dual IL-17A/F inhibition, particularly when assessing minimal disease activity (MDA).
At week four, bimekizumab patients hit MDA targets at more than double the rate of the risankizumab group (13.7% versus 6.5%). This outperformance continued through the mid-study mark, with 43.3% of bimekizumab patients reaching MDA at week 16 compared to 39.9% on risankizumab.
By the end of the 24-week treatment window, the bimekizumab arm maintained its lead, with 49.1% achieving MDA compared with 42.4% in the risankizumab cohort.
Parallel benefits were noted when tracking composite joint-and-skin targets. The stringent combined goal of achieving an ACR50 response with completely clear skin (PASI 100) was met by 39.2% of the bimekizumab group at week 24, compared with 34.1% of risankizumab patients.
For the subgroup entering the trial with at least 3% body surface area affected by psoriasis, bimekizumab led to much faster initial skin clearance at week four (12.5% vs 3.4% PASI 100 rates). However, the IL-23 arm effectively caught up by the 24-week mark, with both medications achieving identical absolute skin clearance rates of approximately 59%.
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Parallel safety profiles
The overall safety profiles of the two biologics were highly comparable over 24 weeks, with no unexpected safety signals.
Treatment-emergent adverse events (TEAEs) occurred in 58.1% of the bimekizumab cohort and 55.3% of the risankizumab cohort, with serious complications remaining low in both arms (1.8% vs 3.3%, respectively). Discontinuations due to adverse events occurred in fewer than 1.5% of patients across the board.
While specific side effect breakdowns were withheld to preserve blinding during the ongoing follow-up phase, rates of major cardiovascular events, malignancies, and severe infections were uniformly low. As anticipated from its mechanism of action, localised Candida infections were more frequent in the bimekizumab group; however, all cases were non-systemic, mild-to-moderate, and did not prompt treatment discontinuations.
Dr Subhashis Banerjee, a rheumatologist and chief medical officer at Artiva Biotherapeutics in San Diego, California, told Rheumatology Republic that the comparable adverse event rates provide reassuring clinical boundaries.
“While the elevated rate of localised Candida infections is an expected consequence of blocking IL-17F alongside IL-17A, the lack of systemic complications or treatment dropouts indicates this is a highly manageable side effect in clinical practice, rather than a deterrent,” he said.
