Rapid Symptomatic Remission in Patients With Ulcerative Colitis Treated With the Anti-MAdCAM-1 Antibody Ontamalimab: Results From TURANDOT and TURANDOT II
BACKGROUND: Treatment of ulcerative colitis (UC) aims to induce and maintain both endoscopic and symptomatic remission. While assessment of endoscopic remission is limited by timing of endoscopy, symptomatic remission can be assessed at any clinical visit, thus potentially allowing a more granular assessment of the time to onset of efficacy of a therapeutic agent. Ontamalimab (SHP647), a monoclonal IgG2 antibody against mucosal addressin cell adhesion molecule-1, can induce endoscopic remission in patients with moderate-to-severe UC after 12 weeks of treatment (1), but its effects on symptomatic remission at earlier timepoints remain unexplored. We aimed to determine rates of clinical and symptomatic remission in patients with UC during ontamalimab induction treatment.
METHODS: Two phase 2 studies (TURANDOT, NCT01620255 and TURANDOT II, NCT01771809) were conducted. Patients who completed TURANDOT, a 12-week, double-blind, placebo-controlled trial of ontamalimab (7.5, 22.5, 75 and 225 mg s.c. every 4 weeks [Q4W]), who had discontinued immunosuppressants could enter TURANDOT II, the open-label extension study. TURANDOT II consisted of two open-label periods followed by a 24-week follow-up period. At baseline (TURANDOT week 12), patients were randomized to ontamalimab 75 or 225 mg s.c. Q4W for 72 weeks. Dose escalation from 75 to 225 mg was permitted between weeks 8 and 72 in cases of clinical exacerbation or no response. Partial Mayo scores (PMS), assessed in both trials, were used to determine proportions of patients with clinical remission (PMS of ?2 with no individual subscore >1 and a rectal bleeding [RB] subscore of ?1) and symptomatic remission (an RB subscore of 0 and stool frequency subscore of ?1).
RESULTS: In total, 357 patients received placebo (n = 73) or ontamalimab (7.5 mg, n = 71; 22.5 mg, n = 72; 75 mg, n = 71; 225 mg, n = 70) in TURANDOT. At week 4, the proportions of patients with clinical remission were greater in the treated groups than the placebo group, particularly the 22.5 mg (difference vs placebo [90%CI] 11.2% [0.4, 21.9]) and 75 mg groups (10.3% [–0.5, 20.9]). The proportions with clinical remission at week 8 were 19.2%, 19.7%, 36.1%, 32.4% and 34.3%, and by week 12 were 16.4%, 23.9%, 40.3%, 36.6% and 25.7%, in the placebo, 7.5, 22.5, 75 and 225 mg groups, respectively. A total of 330 patients completed TURANDOT and were randomized and treated in TURANDOT II. All patients received open-label ontamalimab (75 mg, n = 164; 225 mg, n = 166) in TURANDOT II; 68 had previously received placebo, and 262 had received ontamalimab in TURANDOT. In patients who previously received placebo, there was a rapid increase in the proportion with clinical remission from baseline (75 mg, 24.2%; 225 mg, 11.4%) to week 4 (48.5%; 42.9%), week 8 (51.5%; 42.9%) and week 12 (63.6%; 57.1%). Similar patterns were observed in the results for symptomatic remission both in TURANDOT and TURANDOT II.
CONCLUSION(S): The ability of ontamalimab to induce clinical and symptomatic remission is rapid and robust, as shown initially in patients in TURANDOT (particularly at doses of 22.5 and 75 mg, with differences versus placebo as early as week 4) and confirmed in those who received ontamalimab for the first time in TURANDOT II.
