Efficacy of ustekinumab for ulcerative colitis in patients through 3 years: Unifi long-term extension

Introduction: Ustekinumab (UST), an IL-12/23p40 antagonist, is approved for the treatment of moderate-to-severe ulcerative colitis (UC). The UNIFI long-term extension (LTE) evaluates the ongoing efficacy of UST 90 mg SC maintenance therapy. We report the efficacy data through 3 years of treatment including the subgroups based on biologic treatment history. Methods: During the maintenance phase of UNIFI, 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). Patients (pts) who completed 44 (wks) of maintenance were eligible for the LTE. 284 UST pts entered the LTE, with pts on PBO discontinued after wk44 unblinding. Pts remained in their treatment allocation initially. Beginning at wk56, randomized pts with worsening UC could adjust to q8w dosing (including sham adjustment if already receiving q8w dosing). Efficacy endpoints included symptomatic remission (Mayo stool frequency subscore of 0 or 1 and a rectal bleeding subscore of 0), biomarkers (CRP and fecal calprotectin), as well as disease-specific quality of life assessed using the Inflammatory Bowel Disease Questionnaire (IBDQ). Results: During the maintenance study, 348 pts were randomized to UST, including 174 bio naïve pts, 161 biologic failure pts, and 13 pts who were biologic-experienced but did not have documentation of biologic failure. Among all pts randomized to UST (intent-to-treat population with nonresponder imputation for missing data and treatment failure criteria), 185 pts (55.2%) were in symptomatic remission at wk152 and 96.4% (185/192) of pts in symptomatic remission at wk152 were corticosteroid-free. Among biologic naïve pts, 115 (66.1%) were in symptomatic remission at wk152 and 97.4% (112/115) of pts in symptomatic remission at wk152 were corticosteroid-free. Among biologic failure pts, 70 (43.5%) were in symptomatic remission at wk152 and 94.3% (66/70) of pts in symptomatic remission at wk152 were corticosteroid-free. Median CRP at wk152 in randomized pts treated with UST in the LTE was 1.5 mg/L. Median fecal calprotectin at wk152 was 151.0 mg/kg. Of the randomized pts treated with UST in the LTE and in IBDQ remission at maintenance baseline, 74.6% were in IBDQ remission at wk140. Conclusion: Symptomatic remission, control of inflammation as measured by CRP and fecal calprotectin levels, and improved quality of life as measured by the IBDQ were observed among pts treated with UST through 3 years.