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Dual inhibition of IL-17A and IL-17F in psoriatic disease
Ulrich Mrowietz
Jody Quinn
Paolo Gisondi
Peter Nash
Yukari OkuboDo you know... Which of the following is the only IL-17A/IL-17F dual inhibitor approved by the FDA and EC for the treatment of adult patients with plaque psoriasis and psoriatic arthritis?
During the PsOPsA Hub Steering Committee Meeting on July 16, 2025, Peter Nash, Griffith University, Queensland, AU, chaired a discussion on dual inhibition of IL-17A and IL-17F in psoriatic disease. The discussion also featured Paolo Gisondi, Ulrich Mrowietz, Yukari Okubo, and Jody Quinn.
Dual inhibition of IL-17A and IL-17F in psoriatic disease
Dual inhibition of IL-17A and IL-17F in psoriatic disease
Presentation
Nash presented an overview of dual interleukin (IL)-17A and IL-17F inhibitors – bimekizumab, sonelokimab, and ORKA-002 – highlighting their mechanism of action and summarizing key clinical evidence in psoriatic disease.
- Differential regulation of IL-17A and IL-17F via signal transducer and activator of transcription 5 (STAT5) contributes to psoriatic disease, and dual or bispecific inhibition of IL-17A and IL-17F may provide greater efficacy than targeting IL-17A alone (Figure 1).1
- Currently, bimekizumab is the only IL-17A and IL-17F dual inhibitor approved by the U.S. Food and Drug Administration (FDA) and European Commission (EC) for the treatment of adult patients with plaque psoriasis (PsO) and psoriatic arthritis (PsA).2,3 Sonelokimab and ORKA-002 are also in development (Figure 2).
Figure 1. Role of IL-17A and IL-17F in the pathogenesis of psoriatic disease*
Figure 2. IL-17A and IL-17F dual inhibitors*
Bimekizumab
- Bimekizumab demonstrated rapid and complete skin clearance in patients with moderate-to-severe PsO in the phase II BE ABLE 1 (NCT02905006) and BE ABLE 2 (NCT03010527) trials.7, 8
- Bimekizumab showed superior efficacy compared with ustekinumab (IL-23/IL-12 inhibitor), adalimumab (tumor necrosis factor [TNF]-α inhibitor), secukinumab (IL-17A inhibitor), or placebo alone in the phase III BE VIVID (NCT03370133), BE SURE (NCT03412747), BE RADIANT (NCT03536884), and BE READY (NCT03410992) trials, respectively.9
- These findings supported the FDA approval of bimekizumab for the treatment of patients with moderate-to-severe PsO.10
- In patients with PsA, bimekizumab demonstrated efficacy across multiple disease domains, including joints, skin and nail psoriasis, dactylitis, radiographic progression, and uveitis, in those naïve to biologic DMARDs (BE OPTIMAL and open-label extension [OLE] BE VITAL) and in those with inadequate response to TNF inhibitors (BE COMPLETE and OLE BE VITAL).11–18
- Based on the findings, bimekizumab was granted FDA approval for the treatment of patients with active PsA.2
- A post-approval head-to head trial (BE BOLD; NCT06624228) of bimekizumab vs risankizumab in patients with PsA is currently ongoing.19
Sonelokimab
- Sonelokimab has demonstrated rapid and robust clinical responses compared with placebo in patients with PsO (phase IIa trial; NCT03384745)5 and PsA (phase II ARGO trial; NCT05640245).20
- Two phase III trials, IZAR-1 (NCT06641076) and IZAR-2 (NCT06641089), are currently underway to evaluate sonelokimab in patients with PsA.
ORKA-002
- ORKA-002 demonstrated around 3-fold longer half-life than bimekizumab, suggesting the potential for only 2–3 doses per year in preclinical studies.6
- A phase I first-in-human trial (NCT06944379) of ORKA-002 is currently underway.6
Discussion
- Treatment decisions in psoriatic disease are guided by both administrative and clinical factors.
- Administratively, biosimilars are recommended as first choice due to cost constraints. If treatment fails, other classes such as IL-23 (p19) or IL-17 inhibitors may be considered.
- Clinically, treatment decisions are mainly driven by disease severity. Dual IL-17A/F inhibitors are favored for patients with severe, resistant, or diffuse psoriasis, as well as in those presenting with arthralgia – even in the absence of a confirmed PsA diagnosis – compared with adalimumab and other agents.
- In Germany, all biologics are accessible, including bimekizumab.
- IL-17 inhibitors, particularly bimekizumab and ixekizumab, are the first choice for PsA.
- Bimekizumab is also preferred after failure of other biologics or other treatments, and in severe skin disease.
- Candida infections, especially folliculitis, remain a concern, particularly during the first year of treatment. Management is further complicated by the need to avoid azole antifungals, such as fluconazole, due to CYP450-mediated drug–drug interactions.
- Despite this, bimekizumab remains a highly effective option for skin, joint, and nail involvement.
- In Japan, IL-17A or IL-23 inhibitors are typically used as first-line therapy for severe skin disease, while dual IL-17A/F inhibitors are reserved for use after treatment failure. For difficult-to-manage PsA, dual inhibitors are often preferred as first-line therapy.
- Real-world incidence of Candida appears to be reduced with consistent oral hygiene.
- Patient experience of biologics found bimekizumab to give relief from psoriatic pain, and scalp and hand psoriasis, but also suggested that treatments spaced beyond 4 weeks may be to be less effective.
This independent educational activity is supported by UCB. All content was developed independently. The funder was allowed no influence on the content of this activity.
References
Cole S, Manghera A, Burns L, et al. Differential regulation of IL-17A and IL-17F via STAT5 contributes to psoriatic disease. J Allergy Clin Immunol. 2023;152(3):783-798. DOI: 10.1016/j.jaci.2023.03.035
PR Newswire. UCB announces U.S. FDA approvals for BIMZELX® (bimekizumab-bkzx) for the treatment of psoriatic arthritis, non-radiographic axial spondyloarthritis, and ankylosing spondylitis. 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. Published Sep 23, 2024. Accessed Aug 26, 2025.
UCB Receives New European Commission Approvals for BIMZELX[®]▼(bimekizumab) for the Treatment of Psoriatic Arthritis and Axial Spondyloarthritis. https://www.ucb.com/stories-media/Press-Releases/article/UCB-Receives-New-European-Commission-Approvals-for-BIMZELXRVbimekizumab-for-the-Treatment-of-Psoriatic-Arthritis-and-Axial-Spondyloarthritis. Published Jun 7, 2023. Accessed Aug 26, 2025.
Iznardo H, Puig L. Dual inhibition of IL-17A and IL-17F in psoriatic disease. Ther Adv Chronic Dis. 2021;12:20406223211037846. DOI: 10.1177/20406223211037846
Papp KA, Weinberg MA, Morris A, et al. IL17A/F nanobody sonelokimab in patients with plaque psoriasis: A multicentre, randomised, placebo-controlled, phase 2b study. Lancet. 2021;397(10284):1564-1575. DOI: 10.1016/S0140-6736(21)00440-2
Merola J. Characterization of ORKA-002, a novel extended half-life monoclonal antibody targeting IL-17A/F for the treatment of psoriasis and other indications. Abstract #POS0016. Presented at: European Alliance of Associations for Rheumatology 2025 Congress; Jun 11–14, 2025; Barcelona, ES.
Papp KA, Merola JF, Gottlieb AB, et al. Dual neutralization of both interleukin 17A and interleukin 17F with bimekizumab in patients with psoriasis: Results from BE ABLE 1, a 12-week randomized, double-blinded, placebo-controlled phase 2b trial. J Am Acad Dermatol. 2018;79(2):277-286.e10. DOI: 10.1016/j.jaad.2018.03.037
Blauvelt A, Papp KA, Merola JF, et al. Bimekizumab for patients with moderate to severe plaque psoriasis: 60-week results from BE ABLE 2, a randomized, double-blinded, placebo-controlled, phase 2b extension study. J Am Acad Dermatol. 2020;83(5):1367-1374. DOI: 10.1016/j.jaad.2020.05.105
Freitas E, Blauvelt A, Torres T. Bimekizumab for the treatment of psoriasis. Drugs. 2021;81(15):1751-1762. DOI: 10.1007/s40265-021-01612-z
BIMZELX[®] approved by the U.S. FDA for the treatment of adults with moderate to severe plaque psoriasis. https://www.ucb.com/stories-media/Press-Releases/article/BIMZELXR-Approved-by-the-US-FDA-for-the-Treatment-of-Adults-with-Moderate-to-Severe-Plaque-Psoriasis. Published Oct 18, 2023. Accessed Aug 25, 2025.
Ritchlin CT, Coates LC, McInnes IB, et al. Bimekizumab treatment in biologic DMARD-naïve patients with active psoriatic arthritis: 52-week efficacy and safety results from the phase III, randomised, placebo-controlled, active reference BE OPTIMAL study. Ann Rheum Dis. 2023;82(11):1404-1414. DOI: 10.1136/ard-2023-224431
Coates LC, Landewé R, McInnes IB, et al. Bimekizumab treatment in patients with active psoriatic arthritis and prior inadequate response to tumour necrosis factor inhibitors: 52-week safety and efficacy from the phase III BE COMPLETE study and its open-label extension BE VITAL. RMD Open. 2024;10(1):e003855. DOI: 10.1136/rmdopen-2023-003855
McInnes IB. Dual inhibition of IL-17A and IL-17F with bimekizumab demonstrated long-term safety and efficacy in patients with active psoriatic arthritis and prior inadequate response to tumour necrosis factor inhibitors: final 3-year results from the phase 3 be complete study and its open-label extension. Abstract #POS0105. Presented at: European Alliance of Associations for Rheumatology 2025 Congress; Jun 11–14, 2025; Barcelona, ES.
McInnes I, et al. Bimekizumab efficacy and safety in biologic DMARD-naïve patients with psoriatic arthritis was consistent with or without methotrexate: 52-week results from the phase 3 active‑reference study BE OPTIMAL. Ann Rheum Dis. 2023;82:1133-1134.
Gossec L. Bimekizumab, a dual inhibitor of IL-17A and IL-17F, demonstrated long-term safety and efficacy in biologic DMARD-naïve patients with active psoriatic arthritis: Final 3-year results from the phase 3 be optimal study and its open-label extension. Abstract #POS1294. Presented at: European Alliance of Associations for Rheumatology 2025 Congress; Jun 11–14, 2025; Barcelona, ES.
Baraliakos X, Deodhar A, van der Heijde D, et al. Bimekizumab treatment in patients with active axial spondyloarthritis: 52-week efficacy and safety from the randomised parallel phase 3 BE MOBILE 1 and BE MOBILE 2 studies. Ann Rheum Dis. 2024;83(2):199-213. DOI: 10.1136/ard-2023-224803
van der Heijde D, Deodhar A, Baraliakos X, et al. Efficacy and safety of bimekizumab in axial spondyloarthritis: Results of two parallel phase 3 randomised controlled trials. Ann Rheum Dis. 2023;82(4):515-526. DOI: 10.1136/ard-2022-223595.
Coates LC. Inhibition of radiographic progression with bimekizumab treatment observed in bDMARD naïve patients with active psoriatic arthritis at 2 years: Results from a phase 3 study and its open-label extension. Abstract #POS1257. Presented at: European Alliance of Associations for Rheumatology 2025 Congress; Jun 11–14, 2025; Barcelona, ES.
ClinicalTrials.gov. A study to evaluate the efficacy and safety of bimekizumab in adult study participants with active psoriatic arthritis. https://www.clinicaltrials.gov/study/NCT06624228?intr=NCT06624228&rank=1. Updated Aug 15, 2025. Accessed Aug 26, 2025.
McInnes IB. Efficacy and safety of sonelokimab, a novel IL-17A- and IL-17F-inhibiting Nanobody®, in patients with active psoriatic arthritis (PsA): Results from the global, randomized, double-blind, placebo-controlled Phase 2 ARGO trial. Abstract #OP0195. Presented at: European Alliance of Associations for Rheumatology 2024 Congress; Jun 12–15, 2024; Vienna, AT.
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