Direct Comparison of Risankizumab and Fumaric Acid Esters in Systemic-Therapy-Naive Patients With Moderate to Severe Plaque Psoriasis: A Randomized Controlled Trial.

BACKGROUND Fumaric acid esters (FAEs; Fumaderm® ) are the most frequently prescribed first-line systemic treatment for moderate-to-severe plaque psoriasis in Germany. Risankizumab (Skyrizi® ) is a humanized IgG1 monoclonal antibody that specifically binds to the p19 subunit of interleukin-23. OBJECTIVE This study compared risankizumab treatment with FAEs in psoriasis patients. METHODS This phase 3, randomized, active-controlled, open-label study with blinded assessment of efficacy was conducted in Germany. Patients were randomized (1:1) to subcutaneous risankizumab 150mg (weeks 0, 4, 16) or oral FAEs at increasing doses from 30mg/d (week 0) up to 720mg/d (weeks 8-24). Enrolled patients were adults naive to and candidates for systemic therapy, with chronic, moderate-to-severe plaque psoriasis. Phototherapy was not allowed within 14 days before or during the study. RESULTS Key efficacy endpoints were met at week 24 for risankizumab (N=60) versus FAEs (N=60) (P<.001): achievement of PASI 90 (primary endpoint; 83.3% vs 10.0%), PASI 100 (50.0% vs 5.0%), PASI 75 (98.3% vs 33.3%), PASI 50 (100% vs 53.3%), and Static Physician's Global Assessment of clear/almost clear (93.3% vs 38.3%). The rates of gastrointestinal disorders, flushing, lymphopenia, and headache were higher in the FAEs group. One risankizumab patient reported a serious infection (influenza requiring hospitalization). There were no malignancies, tuberculosis, or opportunistic infections in either treatment arm. CONCLUSIONS Risankizumab was found superior to FAEs, providing earlier and greater improvement in psoriasis outcomes that persisted with continued treatment, and more favorable safety results consistent with the known safety profile. No new safety signals for risankizumab or FAEs were observed.