Biologics in psoriatic arthritis: where we are and where we are headed

Many treatments are available for psoriatic arthritis with varied efficacy across psoriatic arthritis domains. At IFPA 2024, Dr Vinod Chandran (University of Toronto, Canada) presented data on current and upcoming biologic therapies for psoriatic arthritis.

Phase 2 and 3 trials of TNF inhibitors such as adalimumab, certolizumab, etanercept, golimumab, and infliximab in psoriatic arthritis showed American College of Rheumatology 20% (ACR20) responses in 58–75%, while ACR50 and ACR70 responses are comparatively lower at 36–48% and 11–25% [1].

Responses with other biologics vary. PSUMMIT 1 showed 42–50% ACR20 and 25–28% ACR50 responses with ustekinumab, FUTURE 2 showed 63.5% ACR20 and 44% ACR50 responses with secukinumab, while SPIRIT-P1 showed approximately 60% ACR20 and 47% ACR50 responses with ixekizumab [2–4]. Comparatively, bimekizumab showed similar ACR50 responses at 44% in BE OPTIMAL, while guselkumab led to 30–35% ACR50 responses in the DISCOVER1 and DISCOVER2 trials [5–7].

In terms of therapy in clinical practice, the current guidelines recommend therapy based on psoriatic arthritis subdomain presentation (i.e. peripheral arthritis, axial disease, enthesitis, dactylitis), as well as the presence of comorbidities (e.g. psoriasis, nail disease, inflammatory bowel disease, and uveitis) [8]. These guidelines are currently being updated, and, Dr Chandran argued, should perhaps move towards a living guideline model, where small updates are posted continually [1].

Novel therapies for psoriatic arthritis on the horizon include izokibep, a small protein inhibitor of IL-17A that is being assessed in a phase 2b/3 trial in patients with active psoriatic arthritis (NCT05623345) [9]. In this trial, izokibep led to higher proportions of participants achieving ACR50 responses compared with placebo (40–43% vs 15%; P<0.0001). Another agent under investigation is sonelokimab, a humanised nanobody targeting IL-17A and IL-17F [10]. In the phase 2 ARGO trial (NCT05640245), sonelokimab showed 46% ACR50 responses compared with 20% with placebo.

Looking to the future of biologics for psoriatic arthritis, Dr Chandran argued that the goalpost should move towards remission [1]. “Dermatologists talk about PASI90 and PASI100, and we are still talking about ACR20 and ACR50. We really need to get the arthritis response out there. Is that because of the heterogeneity of the disease or our outcome measures? I think it’s a combination of both. Could we do combination therapies?” Indeed, the ongoing phase 2 AFFINITY trial (NCT05071664) of guselkumab plus golimumab versus guselkumab alone aims to answer this question.

1. 
   
   1. Chandran V. Psoriatic arthritis: Treatment advances in biologic therapies. IFPA Conference 2024, 27–29 June, Stockholm, Sweden.
   2. McInnes IB, et al. Lancet. 2013;382(9894):780-9.
   3. McInnes IB, et al. Lancet. 2015;386(9999):1137-46.
   4. Mease PJ, et al. Ann Rheum Dis. 2017;76(1):79-87.
   5. McInnes IB, et al. Lancet. 2023;401(10370):25-37.
   6. Deodhar A, et al. Lancet. 2020;395(10230):1115-1125.
   7. Mease PJ, et al. Lancet. 2020;395(10230):1126-1136.
   8. Coates LC, et al. J Rheumatol. 2022;49(6 Suppl 1):52-54.
   9. Mease PJ, et al. EULAR 2024. LBA0005, EULAR 2024 Congress, 12–15 June, Vienna, Austria.
   10. McInnes IB, et al. EULAR 2024. OP0195, EULAR 2024 Congress, 12–15 June, Vienna, Austria.

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Posted on 17 July 202417 July 2024