Sustained Remission in Patients with Moderate to Severe Ulcerative Colitis: Results from the Phase 3 UNIFI Maintenance Study

Background:

The UNIFI randomized-withdrawal maintenance study evaluated the safety and efficacy of subcutaneous (SC) ustekinumab in patients with moderately-to-severely active ulcerative colitis (UC) who had responded to intravenous (IV) ustekinumab during induction. In this analysis, durability of remission through maintenance Week44 is described.

Methods:

At Week0 of the maintenance study, 523 patients who had responded to IV ustekinumab induction were randomized 1 : 1 : 1 to placebo SC, ustekinumab SC 90 mg q12w, or ustekinumab SC 90 mg q8w. Maintenance of clinical remission at Week44 was a major secondary endpoint; partial Mayo scores, rectal bleeding and stool frequency Mayo subscores, endoscopic healing, and Inflammatory Bowel Disease Questionnaire (IBDQ) scores were also assessed.

Results:

At baseline of the maintenance study, proportions of patients in symptomatic remission and IBDQ remission were similar among treatment groups (Tab. 1). The proportion of patients with endoscopic healing at baseline was lower in the ustekinumab q8w group (32.4%) compared with ustekinumab q12w (39.5%) and placebo groups (40.6%). Through Week 44, the proportions of patients in partial Mayo remission were sustained in the ustekinumab treatment groups, while the proportion of patients in the placebo group decreased, with consistent numerical separation from the ustekinumab q8w group by Week 8 and the q12w group by Week 16. Significantly greater proportions of patients in both ustekinumab groups compared with placebo maintained symptomatic and IBDQ remission through Week 44 and maintained endoscopic healing at Week 44 among patients who achieved each respective endpoint at maintenance baseline. Similarly, greater proportions of ustekinumab-treated patients had durable partial Mayo remission through Week44 versus placebo.

Tab. 1

	Placebo SCa	Ustekinumab SC 90 mg q12w	Ustekinumab SC 90 mg q8w
Primary efficacy analysis data set, n	175	172	176
Durable partial Mayo remission through Week 44,b n (%)	62 (35.4%)	83 (48.3%)	101 (57.4%)
p-value		0.010	< 0.001
Symptomatic remission,c n (%)
Baseline	122 (69.7%)	122 (70.9%)	119 (67.6%)
Maintenance of symptomatic remission through Week 44d	56 (45.9%)	77 (63.1%)	79 (66.4%)
p-value		0.009	0.002
Endoscopic healing,e n (%)
Baseline	71 (40.6%)	68 (39.5%)	57 (32.4%)
Maintenance of endoscopic healing at Week 44d	25 (35.2%)	41 (60.3%)	37 (64.9%)
p-value		0.002	< 0.001
IBDQ remission,f n (%)
Baseline	107 (61.1%)	109 (63.4%)	103 (58.5%)
Maintenance of IBDQ remission through Week 44d	53 (49.5%)	75 (68.8%)	68 (66.0%)
p-value		0.002	0.019
aPatients who responded to ustekinumab IV induction dosing and were randomly assigned to placebo SC upon entry into the maintenance study. bThe partial Mayo score includes stool frequency, rectal bleeding, and physician's global assessment subscores and ranges from 0 to 9. Durable partial Mayo remission (partial Mayo score ≤2) through Week 44 was defined as achieving partial Mayo remission at ≥80% of all visits (at least 9 out of 11 visits) prior to Week 44 and in partial Mayo remission at Week 44. cSymptomatic remission was defined as a Mayo stool frequency subscore of 0 or 1 and a rectal bleeding subscore of 0. Maintenance of symptomatic remission was defined as symptomatic remission at ≥80% of the visits from Week 4 to week 40 (at least 8 out of 10 visits) and at Week 44 among patients who were in symptomatic remission at maintenance baseline. dDenominator is the number of patients who had achieved this endpoint at maintenance baseline. eEndoscopic healing (also described as endoscopic improvement in the appearance of the mucosa) was defined as a Mayo endoscopy subscore of 0 or 1. Maintenance of endoscopic healing was defined as endoscopic healing at Week 44 among patients who had endoscopic healing at maintenance baseline. fInflammatory Bowel Disease Questionnaire (IBDQ) remission was defined as an IBDQ score ≥170. Maintenance of IBDQ remission was defined as IBDQ remission at both Week 20 and Week 44 among patients who were in IBDQ remission at maintenance baseline.

Conclusion:

Both doses of ustekinumab SC maintenance therapy sustained remission, measured by patient-reported symptoms and endoscopic and quality of life assessments, in patients with moderately-to-severely active UC.

Sustained remission through Week 44.