Safety and efficacy of ustekinumab induction therapy in patients with moderate to severe ulcerative colitis: results from the phase 3 unifi study

Introduction: The purpose of this study was to evaluate the safety and efficacy of intravenous (IV) ustekinumab (UST) induction therapy in patients with moderately to severely active ulcerative colitis (UC) who demonstrated an inadequate response to or were unable to tolerate conventional (ie, corticosteroids, immunomodulators) or biologic therapies (ie, 1 or more TNF blockers or vedolizumab). Aims and Methods: UNIFI was a Phase 3 randomized, double‐blind, placebocontrolled study in which patients were randomized 1:1:1 at Week (Wk) 0 to receive a single IV induction dose of UST 130 mg or a dose approximating UST 6mg/kg [ 6mg/kg]: 260mg [weight 55 kg], 390 mg [weight 455 kg and 85 kg], or 520 mg [weight 485 kg]) or placebo (PBO). At Wk 8, patients were evaluated for clinical remission, endoscopic healing, clinical response, change from baseline in the IBDQ score, and mucosal healing (an endpoint that includes both endoscopic healing and histologic healing). Results: Nine hundred sixty‐one patients, of which about 50% had failed biologic therapy and 16.6% had failed both anti‐TNF and vedolizumab, were randomized to treatment in the primary analysis population; 941 patients (98%) completed through Wk 8. Baseline demographics, UC disease characteristics and concomitant UC medications were generally similar among treatment groups. Significantly (p50.001) higher proportions of patients receiving UST IV 130 mg and 6mg/kg achieved clinical remission, endoscopic healing, clinical response, and mucosal healing at Wk 8 and significant improvement from baseline in IBDQ was achieved (Table 1) compared to PBO. Significant (p50.05) decreases in median levels of fecal biomarkers (calprotectin and lactoferrin) were also observed at Wk 8. Similar proportions of patients reported adverse events (41.4%, 50.0%, and 48.0%), serious adverse events (3.7%, 3.1%, and 6.6%), infections (15.9%, 15.3%, and 15.0%) and serious infections (0.6%, 0.3%, and 1.3%) in the UST IV 130mg 6mg/kg and PBO groups, respectively. No malignancies, opportunistic infections or tuberculosis were reported through Wk 8. One death from esophageal varices hemorrhage was reported for a patient with no known history of cirrhosis in the UST 6mg/kg group prior to Wk 8. Conclusion: A single IV dose of UST resulted in significant improvements in clinical, endoscopic and health‐related quality of life outcomes atWk 8 compared to PBO in patients with moderate‐severe UC who had previously failed conventional or biologic therapy. The therapy was well tolerated through induction.