Risankizumab (SKYRIZI®): A Comprehensive Monograph on its Pharmacology, Clinical Efficacy, and Therapeutic Role in Immune-Mediated Inflammatory Diseases

Executive Summary

Risankizumab, marketed as SKYRIZI®, is a humanized immunoglobulin G1 (IgG1) monoclonal antibody that represents a significant advancement in the targeted treatment of several immune-mediated inflammatory diseases. By selectively binding to the p19 subunit of interleukin-23 (IL-23), risankizumab inhibits a key cytokine pathway implicated in the pathophysiology of plaque psoriasis, psoriatic arthritis, Crohn's disease, and ulcerative colitis. This targeted mechanism of action has translated into a robust clinical profile characterized by high levels of efficacy, durable responses, and a generally favorable long-term safety profile.

Clinical development has consistently demonstrated risankizumab's superiority over placebo and key active comparators. In moderate-to-severe plaque psoriasis, pivotal Phase 3 trials showed significantly higher rates of skin clearance compared to both ustekinumab and adalimumab. For psoriatic arthritis, risankizumab has proven effective in patients with an inadequate response to both conventional synthetic and biologic disease-modifying antirheumatic drugs. In gastroenterology, its approval for Crohn's disease was bolstered by the head-to-head SEQUENCE trial, which established its superiority over ustekinumab in achieving endoscopic remission, a critical treatment goal. Most recently, its approval for ulcerative colitis further expands its therapeutic reach within inflammatory bowel disease. Conversely, the drug's development for atopic dermatitis was discontinued after failing to meet its primary endpoint in a Phase 2 study, a result that underscores the distinct immunopathology of that condition and validates the specificity of the IL-23 pathway as risankizumab's target.