Effects of Glucagon-Like Peptide-1 (GLP-1)–Based Medications on Icotrokinra Efficacy, Safety, and Pharmacokinetics: Pooled Results Across ICONIC Phase 3 Studies

Introduction: In pivotal Phase 3 studies, icotrokinra (ICO) has demonstrated significant skin clearance with a favorable safety profile in patients with moderate-to-severe psoriasis (ICONIC-LEAD, ICONIC-ADVANCE 1&2) and psoriasis affecting high-impact sites (ICONIC-TOTAL). Because obesity is a common comorbidity with psoriasis and GLP-1 medication use is increasing, concomitant use with ICO may occur in clinical practice. These post-hoc analyses evaluated ICO efficacy, safety, and pharmacokinetics in ICONIC study participants who received GLP-1–based medications. Methods: Data from participants with versus without GLP-1 medication use (defined as receipt of a first dose prior to study Day 84) were pooled across studies. Efficacy (Investigator’s Global Assessment [IGA] 0/1 with ≥2-grade improvement from baseline; Psoriasis Area and Severity Index [PASI] 90) was assessed for participants randomized to once-daily ICO 200 mg or placebo (PBO) through Week (W)16 in ICONIC-LEAD and ICONIC-ADVANCE 1&2 (ICONIC-TOTAL was excluded due to different enrollment criteria/endpoints). Safety was evaluated across all 4 studies through W16. Pharmacokinetics were assessed for all participants exposed to ICO, including those who switched from PBO to ICO at W16 (all studies) and from deucravacitinib to ICO at W24 (ICONIC-ADVANCE 1&2). Results: In the pooled efficacy population, baseline characteristics were generally similar between those exposed to GLP-1 mediations (n=31) and the total population (n=2187), except participants exposed to GLP-1 medications had higher mean BMI (41.6 vs 29.5 kg/m2). Most participants started GLP-1 therapy prior to W0 (n=24; range, 10-1589 days); 7 participants started GLP-1 therapy between W0 and W12 (range, 1-75 days). At W16 in ICO-treated participants who were exposed vs not exposed to GLP-1 medications, IGA 0/1 responses were 65.0% (13/20) vs 67.5% (722/1069) (PBO, 18.2% [2/11] vs 9.0% [41/455]), and PASI 90 responses were 45.0% (9/20) vs 53.5% (572/1069) (PBO, 9.1% [1/11] vs 3.5% [16/455]), respectively. Among participants exposed to GLP-1 medications across all 4 studies, adverse events were reported through W16 for 53.3% (16/30) in the ICO group and 69.2% (9/13) in the PBO group (rates in the overall pooled population were 49.1% [636/1296] with ICO and 51.9% [295/568] with PBO). Pharmacokinetic ICO exposures (AUC) were similar in participants with (n=76) and without (n=2291) GLP-1 medication use. Conclusion: In these pooled post-hoc analyses, ICO efficacy, safety, and pharmacokinetics were generally consistent regardless of GLP-1 medication use. Interpretation is limited by small sample sizes, heterogeneity in timing and duration of GLP-1 exposure, and lack of GLP-1 medication dosing details. Supported by Johnson & Johnson.