Picankibart

Evaluate guselkumab efficacy, an anti-interleukin-23p19-subunit antibody, in patients with active psoriatic arthritis (PsA) and inadequate response to 1 or 2 tumour necrosis factor inhibitors (TNFi-IR), utilizing composite indices assessing disease activity across disease domains.

In the Phase IIIb COSMOS trial, 285 adults with TNFi-IR PsA were randomized (2:1) to receive guselkumab 100 mg or placebo at Week (W)0, W4, then every 8 weeks through W44. Patients receiving placebo crossed over to guselkumab at W24. In this post hoc analysis, composite indices evaluated included the Disease Activity Index for Psoriatic Arthritis (DAPSA), Disease Activity Score 28 (DAS28), Psoriatic Arthritis Response Criteria (PsARC), Psoriatic Arthritis Disease Activity Score (PASDAS), GRAPPA Composite score (GRACE), modified Composite Psoriatic Disease Activity Index (mCPDAI), minimal disease activity (MDA), and very low disease activity (VLDA). Through W24, treatment failure rules were applied. Through W48, non-responder imputation was used for missing data.

Greater proportions of guselkumab- than placebo-randomized patients achieved composite index endpoints relating to low disease activity (LDA; 14.8–52.4% vs 3.1–28.1%) or remission (3.7–5.3% vs 0.0–2.1%) at W24. Among guselkumab-randomized patients, LDA rates increased to W48 (DAPSA, 44.4%; DAS28, 47.8%; PASDAS, 34.4%; GRACE, 33.3%; mCPDAI, 40.2%), and 27.0% and 64.0% achieved MDA and a PsARC response, respectively. In the placebo→guselkumab crossover group, W48 response rates were similar to the guselkumab-randomized group.

Guselkumab treatment provided substantial benefits across multiple disease domains, with increasing proportions of patients achieving LDA/remission over 1 year, highlighting the effectiveness of guselkumab despite previous inadequate response to TNFi.

Mirikizumab is a humanized anti‐interleukin‐23p19 monoclonal antibody being developed for ulcerative colitis (UC) and Crohn's disease. We characterized the relationship of mirikizumab systemic exposure with efficacy and safety end points in patients with UC using phase II (NCT02589665) and III (NCT03518086, NCT03524092) trial data. Exposure–response models were developed for clinical remission, clinical response, endoscopic remission, and change in modified Mayo score following induction (50–1,000 mg i.v. every 4 weeks) and maintenance (200 mg s.c. every 4 or 12 weeks) treatment. These models evaluated observed and pharmacokinetic model‐predicted mirikizumab exposures as the exposure measure. Key safety event rates were compared across mirikizumab exposure quartiles in the phase III trial. Mirikizumab efficacy in patients with UC showed an apparent positive association with systemic exposure following both induction and maintenance. However, further analysis found this relationship to be overstated by the presence of confounding factors that were not among the tested patient covariates. While prior biologic experience and baseline disease severity showed statistically significant influences on estimated placebo effect, no patient factors affected the mirikizumab effect parameters in any of the phase III exposure–response models. There was no apparent mirikizumab concentration relationship with any adverse event of special interest. When the phase II and III data and confounding are considered together, efficacy was unlikely to be strongly affected by variation in exposures across individual patients at the phase III dose. Together with the previously demonstrated mirikizumab exposure insensitivity to patient factors, these findings indicate that mirikizumab dose adjustment to patient characteristics is not required.