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(R)) are the most frequently prescribed first-line systemic treatment for moderate-to-severe plaque psoriasis in Germany. Risankizumab (Skyrizi(R)) is a humanized IgG1 monoclonal antibody that specifically binds to the p19 subunit of interleukin 23. Objectives To compare risankizumab treatment to FAEs in patients with psoriasis. Methods This phase III randomized, active-controlled, open-label study with blinded assessment of efficacy was conducted in Germany. Patients were randomized (1 : 1) to subcutaneous risankizumab 150 mg (weeks 0, 4 and 16) or oral FAEs at increasing doses from 30 mg daily (week 0) up to 720 mg daily (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) vs. FAEs (n = 60) (P < 0 center dot 001): achievement of a >= 90% improvement in Psoriasis Area and Severity Index (PASI; primary endpoint 83 center dot 3% vs. 10 center dot 0%), >= 100% improvement in PASI (50 center dot 0% vs. 5 center dot 0%), >= 75% improvement in PASI (98 center dot 3% vs. 33 center dot 3%), >= 50% improvement in PASI (100% vs. 53 center dot 3%) and a Static Physician's Global Assessment of clear/almost clear (93 center dot 3% vs. 38 center dot 3%). The rates of gastrointestinal disorders, flushing, lymphopenia and headache were higher in the FAE group. One patient receiving risankizumab reported a serious infection (influenza, which required hospitalization). There were no malignancies, tuberculosis or opportunistic infections in either treatment arm. Conclusions Risankizumab was found to be superior to FAEs, providing earlier and greater improvement in psoriasis outcomes that persisted with continued treatment, and more favourable safety results, which is consistent with the known safety profile. No new safety signals for risankizumab or FAEs were observed.