UCB announced today that bimekizumab (Bimzelx) demonstrated statistically significant superiority over risankizumab (Skyrizi) in reducing psoriatic arthritis (PsA) disease activity in the BE BOLD trial, with American College of Rheumatology 50% improvement (ACR50) in joint counts and core disease activity measures as the primary endpoint at week 16.¹ The result is the first time any licensed biologic has shown superiority over an IL-23 inhibitor in a head-to-head PsA trial, and it lands at a moment when the treatment landscape is actively being reshaped by new oral and biologic entrants.¹
Bimekizumab and risankizumab are both approved, well-tolerated disease-modifying antirheumatic drugs (DMARDs) with robust placebo-controlled trial records in PsA, the former supported by data from the pivotal KEEPsAKE-1 and KEEPsAKE-2 studies and the latter by the BE OPTIMAL and BE COMPLETE studies. Notably, the KEEPsAKE studies used ACR20 as their primary end points while BE OPTIMAL and BE COMPLETE chose and succeeded at the more ambitious ACR50 end point.2,3
The announcement is significant, although full data including secondary endpoints, effect sizes, and safety through week 16 have not yet been published; UCB plans to present the complete dataset at a forthcoming international congress.¹
"Our landmark BE BOLD study provides the first head-to-head evidence of superiority versus an IL-23 inhibitor in PsA. These topline results reinforce bimekizumab's potential to deliver clinically meaningful improvements using the stringent ACR50 measure of disease activity, indicating more complete control of joint inflammation," Emmanuel Caeymaex, Executive Vice President, Head of Patient Evidence, UCB, said in a statement.1 "BE BOLD represents the fourth head-to-head study demonstrating bimekizumab superiority, supporting physicians to make informed treatment decisions and advancing our ambitions to raise the standard of care for people living with psoriatic disease."
IL-23 vs IL-17
The 2 agents work through fundamentally different pathways, which makes BE BOLD more than a commercial head-to-head — it tests a mechanistic hypothesis about where in the IL-23/IL-17 axis intervention is most effective for joint disease in PsA.
Risankizumab is a selective IL-23 inhibitor that targets the p19 subunit of IL-23, blocking the upstream cytokine signal that drives differentiation and maintenance of Th17 cells.4 Its phase 3 KEEPsAKE trials in PsA demonstrated ACR20 rates of 57.3% and 51.3% versus 33.5% and 26.5% for placebo at week 24 in people who had an inadequate respose to csDMARDs (csDMARD-IR) and bio-IR/csDMARD-IR populations respectively, with responses durable through 196 weeks.5,6
Bimekizumab takes a different approach, inhibiting both IL-17A and IL-17F — the 2 key effector cytokines downstream of IL-23 in the psoriatic inflammation cascade.² IL-17F, which is more highly expressed in psoriatic tissue than in other inflammatory conditions and increases over time in the synovium and skin, has historically been left uninhibited by first-generation IL-17A inhibitors such as secukinumab and ixekizumab.² In the pivotal BE OPTIMAL and BE COMPLETE trials, 44% and 43% of bimekizumab-treated patients achieved ACR50 at week 16, respectively, compared with 10% and 7% of placebo recipients (BE OPTIMAL: OR 7.1 [95% CI, 4.6–10.9]; P <.0001; BE COMPLETE: OR 11.1 [95% CI, 5.4–23.0], P <.0001).7,8 The dual blockade strategy positions bimekizumab as a more complete suppressor of downstream inflammatory output, particularly in skin — a domain where its approval-supporting BE OPTIMAL and BE COMPLETE trials showed substantial PASI 90 and PASI 100 rates. BE BOLD now extends that argument to joint disease.
BE BOLD
BE BOLD (NCT06624228) is a multicenter, randomized, double-blind, active-controlled, parallel-group trial enrolling 553 adults with active PsA who were either biologic-naïve or had prior exposure to one TNF inhibitor with inadequate or intolerant response.¹ Participants were randomized 1:1 to receive bimekizumab or risankizumab, with double-blinding maintained through week 24.¹ The primary endpoint was ACR50 at week 16.¹
The choice of ACR50 — rather than ACR20, which has been the primary endpoint in most PsA registration trials, including the KEEPsAKE studies — reflects both the head-to-head context and a deliberate positioning of the trial to identify clinically meaningful joint improvement rather than any measurable response.¹ UCB characterizes the result as the first head-to-head superiority demonstration by any licensed biologic against an IL-23 inhibitor in PsA, and the fourth head-to-head superiority result in the bimekizumab clinical program across psoriatic disease.¹
Key Facts
Bimekizumab (Bimzelx; UCB): dual IL-17A and IL-17F inhibitor; FDA approved for PsA since September 2024
Risankizumab (Skyrizi; AbbVie): selective IL-23 p19 subunit inhibitor; FDA approved for PsA since 2022
Trial: BE BOLD (NCT06624228); multicenter, randomized, double-blind, active-controlled; n=553
Population: Adults with active PsA; biologic-naïve or prior TNFi inadequate/intolerant response; randomized 1:1
Primary endpoint: ACR50 at week 16 — met with statistical significance favoring bimekizumab¹
Clinical significance: First superiority demonstration by a licensed biologic over an IL-23 inhibitor in PsA; fourth head-to-head superiority result in bimekizumab psoriatic disease program¹
Safety: Generally well tolerated through week 16; no new signals¹
Status: Topline data only; full results to be presented at forthcoming international congress
Safety through week 16 was described as generally well tolerated with no new signals, consistent with bimekizumab's established profile across its approved indications — plaque psoriasis, PsA, ankylosing spondylitis, non-radiographic axial spondyloarthritis, and hidradenitis suppurativa.¹˒² No specific adverse event data have been released pending the congress presentation.
It is important to note that the trial enrolled a mixed population of biologic-naïve and TNF-IR patients; how the benefit distributes across those groups may matter substantially for clinical decision-making. Furthermore, ACR50 at week 16 is an early time point — whether the difference is maintained or narrows over 52 weeks remains to be seen. Risankizumab's KEEPsAKE data show that ACR responses deepen considerably between weeks 24 and 52 in many patients, a pattern that may also apply in the head-to-head setting.6
The broader question for rheumatologists is whether the superiority signal at 16 weeks translates into meaningful differences in the outcomes patients actually care about — sustained remission, structural progression, quality of life — over the longer treatment horizon. BE BOLD was designed with a double-blind period only through week 24, and the full 52-week or longer dataset will be essential context.¹
What is already clear is that this result adds weight to the argument that dual IL-17A/IL-17F inhibition produces a more robust early joint response than upstream IL-23 blockade alone in active PsA, at least in a population enriched for biologic-naïve and single TNF-IR patients. For clinicians weighing between these 2 approved agents in a new patient, particularly 1 with high joint burden at presentation, the BE BOLD data will deserve careful attention when the full dataset is published.
REFERENCES
UCB announces U.S. FDA approvals for BIMZELX for the treatment of psoriatic arthritis, non-radiographic axial spondyloarthritis, and ankylosing spondylitis. Press release. UCB. September 23, 2024. https://www.prnewswire.com/news-releases/ucb-announces-us-fda-approvals-for-bimzelx-bimekizumab-bkzx-for-the-treatment-of-psoriatic-arthritis-non-radiographic-axial-spondyloarthritis-and-ankylosing-spondylitis-302255482.html
Östör A, Van den Bosch F, Papp K, et al. Efficacy and safety of risankizumab for active psoriatic arthritis: 24-week results from the randomised, double-blind, phase 3 KEEPsAKE 2 trial. Ann Rheum Dis. 2022;81(3):351-360. https://doi.org/10.1136/annrheumdis-2021-221048
Kristensen LE, Keiserman M, Papp K, et al. Efficacy and safety of risankizumab for active psoriatic arthritis: 52-week results from the KEEPsAKE 1 study. Rheumatology (Oxford). 2023;62(6):2113-2121. https://doi.org/10.1093/rheumatology/keac607
Östör A, et al. Efficacy and safety of risankizumab for active psoriatic arthritis: 196-week results from the KEEPsAKE 1 and KEEPsAKE 2 randomized clinical trials. Rheumatol Ther. 2025;12(6):1103-1123. https://doi.org/10.1007/s40744-025-00793-3
Merola JF, Landewé R, McInnes IB, et al. Bimekizumab in patients with active psoriatic arthritis and previous inadequate response or intolerance to tumour necrosis factor-α inhibitors: a randomised, double-blind, placebo-controlled, phase 3 trial (BE COMPLETE). The Lancet. 2023;401(10370):38-48. doi: 10.1016/s0140-6736(22)02303-0
McInnes IB, Asahina A, Coates LC, et al. Bimekizumab in patients with psoriatic arthritis, naive to biologic treatment: a randomised, double-blind, placebo-controlled, phase 3 trial (BE OPTIMAL). The Lancet. 2023;401(10370):25-37. doi: 10.1016/s0140-6736(22)02302-9
