PsA: Are new IL-23 agents impactful in today’s treatment landscape? Save

IL-23 therapies are among the most efficacious and safest treatment options for patients with skin psoriasis (PsO). The enthusiasm for IL-23 agents for PsA is perhaps more tempered; while efficacy has been demonstrated for peripheral joint disease, there is concern that these agents are not effective in patients with axial disease. Furthermore, there is ongoing debate about the comparative efficacy of IL-23 medications for peripheral joint disease versus other drug classes like TNFi and IL-17 inhibitors. 

Abstract 2804 being presented this ACR advances this concern: when treatment with IL-23 inhibitor risankizumab (RIS) was compared to IL-17 A/F inhibitor bimekizumab (BIM), PsA patients receiving BIM had significantly greater ACR50 response at both early (week 4) and late (week 24) timepoints.1 In the ACR abstracts discussed below, two novel IL-23 targeted agents are studied as potential options for PsA treatment. 

Can this new data make a compelling argument for their use in PsA against existing options? Let’s explore. 

Tildrakizumab: an IL-23 p19 antibody subcutaneous agent 

What about the introduction of a unique, subcutaneous IL-23 agent that has efficacy in PsO? Abstract 2313 by Mease et al., reports the pooled, 24 week results of INSPIRE 1 and 2: two trials evaluating tildrakizumab (TIL), an IL-23 p19 antibody, in patients with prior TNFi use and in TNFi naïve patients respectively. In total, 806 patients with active joint and skin disease who had not been treated with prior IL-17, 23, or 12/23 agents were randomized to tildrakizumab 100mg vs. placebo (PBO).2 Compared to PBO, a higher number of TIL treated patients achieved an ACR20 response by week 24 (38.8% vs. 24.4%, p=0.00002), as well as secondary outcomes ACR50 (21.5% vs. 12.5%, p=0.0001) and ACR70 (8.6% vs. 3.5%, p=0.006). HAQ-DI scores were not significantly different between groups. Safety was reportedly comparable though not presented in the abstract. 

While direct comparison to RCTs of guselkumab (GUS) and risankizumab (RIS) is limited due to methodologic and patient population differences, it is noteworthy that the ACR20 response rates of tildrakizumab are lower. This seems to mirror comparisons of skin responses which were lower with TIL compared to RIS and GUS in a recent Cochrane meta-analysis.3 Unless the finalized results of INSPIRE 1 and 2 report a longer-term benefit or an advantage in safety or other disease subdomain (ie enthesitis) compared to existing IL-23 agents, it seems there would be limited bandwidth for TIL to shift the current therapeutic landscape.

Icotrokinra: an IL-23 targeted oral peptide 

One approach to encouraging use of IL-23 agents in PsA, despite results from studies like BE-BOLD, might be through the introduction of an oral modality. In LB12, Kishimoto et al. report the 24 week results of ICONIC-PsA1: an investigation of icotrokinra (ICO), an IL-23 targeted oral peptide, in the treatment of biologic-naïve PsA patients.4 Patients with active, DMARD-refractory PsA were randomized to receive ICO (200mg or 400mg daily), placebo or subQ ustekinumab (safety comparator, no statistical comparisons planned). Placebo patients were re-randomized to an ICO dose group at week 16.  In total, 552 patients, with a mean swollen joint count of 9 and mean tender joint count of 15.2, were randomized. Higher proportions of patients receiving ICO 200mg (58% vs. 41%, p=0.002) and ICO 400mg (52% vs. 41%, p=0.052) achieved ACR 20 response compared to placebo. Statistically significant improvements in ACR50 and ACR70 were seen in the ICO 200mg group (29% vs. 16% ACR50, 13% vs. 5% ACR70), but not in the ICO 400mg group (23% ACR 50, 10% ACR 70). Adverse events were similar across groups without new safety signals. 

These early findings of efficacy and safety of ICO are encouraging. In comparison to other oral options, ICO may have the potential to outperform Otezla and Sotyktu, while retaining ability to be used first-line compared to JAK inhibitors. The placebo arm performance in the trial was fairly high, which does provide important context for the raw efficacy numbers we are seeing.

Ultimately, we will have to wait for the full, finalized trial data for both of these drugs to fully understand their utility, but these abstracts facilitate interesting insight into the potential future agents. 

References:

1. McInnes I, Gossec L, Gottlieb A et al. Bimekizumab Efficacy & Safety Versus Risankizumab in Patients with Active Psoriatic Arthritis: 24-Week Results from a Head-To-Head, Multicenter, Randomized, Phase 3b Study [abstract]. Arthritis Rheumatol. 2026; 78 (suppl 9). https://acrabstracts.org/abstract/bimekizumab-efficacy-safety-versus-ri….
2. Mease P, Nishandar T, Mehta S et al. Tildrakizumab for the treatment of prior anti-tumor necrosis factor-experienced or -naïve participants with active psoriatic arthritis: pooled Week 24 results of two Phase 3, randomized, double-blind, placebo-controlled studies, INSPIRE 1 and INSPIRE 2 [abstract]. Arthritis Rheumatol. 2026; 78 (suppl 9). https://acrabstracts.org/abstract/tildrakizumab-for-the-treatment-of-pr….
3. Sbidian E, Chaimani A, Guelimi R et al. Systemic pharmacological treatments for chronic plaque psoriasis: a network meta‐analysis. Cochrane Database of Systematic Reviews 2025, Issue 8. Art. No.: CD011535. DOI: 10.1002/14651858.CD011535.pub7.
4. Kishimoto M, Nash P, Mease P et al. Icotrokinra, an IL-23 Receptor Targeted Oral Peptide, in Biologic-Naïve Participants With Active Psoriatic Arthritis: Results Through Week 24 of a Phase 3, Randomized, Double-Blind, Placebo-Controlled Study [abstract]. Arthritis Rheumatol. 2026; 78 (suppl 9). https://acrabstracts.org/abstract/icotrokinra-an-il-23-receptor-targete…