Efficacy and safety of ustekinumab as maintenance therapy in ulcerative colitis: week 44 results from the UNIFI study

Background and Aim: The study objective was to evaluate the safety and efficacy of subcutaneous (SC) ustekinumab (UST) as maintenance therapy in patients with ulcerative colitis (UC) who were in clinical response to a single intravenous induction dose of UST. Methods: This was a Phase III, double‐blind, randomized withdrawal study in patients with moderate‐severe active UC who failed conventional or biological therapy (including antitumor necrosis factor [TNF] and/or vedolizumab) and were in clinical response 8 weeks after receiving a single UST intravenous induction dose. The primary study population included 523 patients randomly assigned 1:1:1 to placebo (PBO) SC, UST 90 mg SC q8w or q12w at Week 0. The primary endpoint was clinical remission at Week 44 (52 weeks after intravenous induction); key secondary endpoints were maintenance of clinical response, endoscopic healing, corticosteroid‐free clinical remission, and maintenance of clinical remission among patients who achieved clinical remission at baseline. Results: Baseline (induction Week 0) demographics, UC disease characteristics, concomitant UC medications, and medication history were generally similar among treatment groups. Significantly greater proportions of UST q8w and q12w patients were in clinical remission at Week 44 (43.8% and 38.4%, respectively) compared with PBO patients (24.0%; P < 0.001 and P = 0.002, respectively). Significantly greater proportions of UST q8w and q12w patients maintained clinical response through Week 44 and achieved endoscopic healing and corticosteroid‐free clinical remission compared with PBO patients. Clinical remission through Week 44 was maintained for a significantly greater proportion of q12w patients and a numerically greater proportion of q8w versus PBO patients (Table 1). The proportions of patients with adverse events (AEs), serious AEs, infections, and serious infections in the UST groups were generally comparable to those in the PBO group. The proportions of patients who discontinued the study agent were lower with UST q8w and q12w compared with PBO. Among the primary population in the maintenance study, no deaths and two malignancies other than non‐melanoma skin cancer (NMSC) (one colon cancer, q8w; one papillary renal cell carcinoma, q12w) were reported (Table 2). One patient reported NMSC (two squamous cell carcinoma events, q12w). Conclusion: Both UST 90 mg q8w and q12w SC achieved clinical remission and maintained clinical response and were effective in achieving endoscopic healing and corticosteroid‐free remission among patients with moderate to severe UC induced into clinical response with a single intravenous dose of UST. The safety of UST in patients with UC was consistent with the known safety profile of UST in patients with Crohn's disease. (Table presented).