Icahn School of Medicine at Mount Sinai New York, NY
Introduction: Ustekinumab (UST) is approved for moderate to severe ulcerative colitis (UC) treatment. Here we report final results of the UNIFI long-term extension (LTE) study with efficacy and safety through 4 years (yrs) of subcutaneous (SC) UST treatment.
Methods: Overall, 523 intravenous UST induction responders were randomized to SC maintenance therapy: 175 SC placebo (PBO); 172 UST 90mg every 12 weeks (q12w); 176 UST 90mg q8w. The nonrandomized population included UST induction nonresponders at week (wk) 8 who received SC UST, responded 8wks later and continued receiving UST q8w, and PBO induction responders continuing PBO. Patients (pts) completing wk44 were eligible to continue treatment in LTE. PBO pts discontinued after study unblinding. Starting at wk56, randomized pts with UC worsening could adjust to q8w. Efficacy was evaluated in UST-randomized pts (n=284) using symptomatic remission (Mayo stool frequency subscore 0/1 and rectal bleeding subscore 0). Safety was evaluated for all 588 pts treated in LTE (randomized/nonrandomized populations).
Results: Among all pts randomized to UST at maintenance baseline (intent-to-treat population with nonresponder imputation for missing data and treatment failure criteria), 55.2% were in symptomatic remission at wk200 (biologic naïve 67.2%; biologic failure 41.6%; Table 1); 53.2% achieved corticosteroid-free symptomatic remission at wk200. Overall, 42.7% of biologic failure and 18.8% of biologic naïve pts randomized to UST and treated in the LTE discontinued treatment between wks44 and 200. Among randomized pts who continued UST in the LTE, 67.6% were in symptomatic remission at wk200; 72.9% of those in clinical remission at wk44 were in symptomatic remission at wk200; and 85.1% of pts with observed data at wk200 were in symptomatic remission.
Safety events were similar between UST-treated pts and PBO throughout study. Maintenance wks0-220 included 1647.4 (UST) and 301.7 (PBO) pt yrs of follow-up. Safety events per 100 pt yrs of follow-up for UST vs PBO were adverse events (AEs): 214.45 vs 288.04, serious AEs: 7.22 vs 10.61, and serious infections: 2.00 vs 3.31. During the final yr of the LTE, no deaths or major cardiovascular events were reported in UST pts. Among UST pts, 2 cases of colorectal cancer and 1 case of cytomegalovirus were reported.
Discussion: Pts receiving SC UST generally maintained clinical benefit through 4 yrs. No new safety signals were observed.
