Effects of ustekinumab maintenance therapy on endoscopic improvement and histologic improvement in the UNIFI phase 3 study in ulcerative colitis

INTRODUCTION:

Ustekinumab (UST) is an effective therapy for moderate-to-severe ulcerative colitis (UC), but its effects on mucosal healing (endoscopic improvement 1 histologic improvement) during maintenance treatment are unknown.

METHODS:

We evaluated the effects of maintenance UST on histologic and endoscopic activity in the UNIFI Phase 3 study of UST in moderate-to-severe UC (n = 961). Pts in response 8 weeks after receiving intravenous UST were randomized to receive maintenance treatment with subcutaneous (SC) placebo or UST 90 mg every 8 (q8w) or 12 weeks (q12w). Two colonic biopsies were collected from the distal colon at screening and Weeks 0 and 44 of maintenance. Endoscopic improvement (EI) was defined as a Mayo endoscopy subscore <1; histologic improvement (HI) comprised the following Geboes score-based criteria: absence of erosions or ulcerations, absence of crypt destruction, and <5% of crypts with neutrophil infiltration. To encompass both macroand microscopic scales, histo-endoscopic mucosal healing (MH) was defined as achieving both EI and HI.

RESULTS:

At maintenance Week 44, EI was achieved in 28.6%, 43.6%, and 51.1% of pts treated with placebo, UST q12w (P = 0.002 vs placebo), and UST q8w (P < 0.001), respectively. HI was achieved at Week 44 in 32.9%, 54.0%, and 59.3% of pts treated with placebo, UST q12w, and UST q8w, respectively (P < 0.001 for both q12w and q8w). MH was achieved at Week 44 in 24.1%, 38.8%, and 45.9% of pts treated with placebo, UST q12w (P = 0.002), and UST q8w (P 0.001), respectively. HI at Week 44 (irrespective of maintenance treatment) was significantly associated with EI and MH (P < 0.001) and with both lower absolute levels and larger post-treatment changes in total Mayo score, partial Mayo score, and Mayo symptom sub-scores for stool frequency and rectal bleeding at Week 44. Both EI and HI following 8 weeks of UST treatment were associated with clinical remission and steroid-free clinical remission at Week 44 (P < 0.05), as well as remission through Week 44 (i.e., at both Week 8 and Week 44). For example, 26% of pts with induction HI were in clinical remission through Week 44, versus 4% of pts without induction HI. Induction MH was similarly associated with positive outcomes at maintenance Week 44.

CONCLUSION:

Among pts with moderately-to-severely active UC, those receiving SC UST maintenance had higher rates of EI, HI, and MH than those receiving placebo. Both EI and HI are associated with subsequent clinical remission and steroid-free clinical remission. (Figure Presented).