Efficacy and Safety of Ustekinumab as Maintenance Therapy in Ulcerative Colitis: Week 44 Results from UNIFI

Background:

Study objective was to evaluate safety and efficacy of SC ustekinumab (UST) as maintenance therapy in UC patients who were in clinical response to a single IV induction dose of UST.

Methods:

This was a Phase3, double-blind, randomized withdrawal study in patients with moderate-severe UC who failed conventional or biologic therapy (including anti-TNF and/or vedolizumab) and were in clinical response 8 wks after receiving a single UST IV induction dose. Study population included 523 patients randomized 1: 1: 1 to PBO SC, UST90 mg SC q8w or q12w. Primary endpoint was clinical remission at Wk44; key secondary endpoints were maintenance of clinical response, endoscopic healing, corticosteroid-free clinical remission, and maintenance of clinical remission among patients who achieved clinical remission at baseline.

Results:

Baseline demographics, disease characteristics, concomitant UC medications &medication history were similar among treatments. Significantly greater proportions of UST q8w and q12w patients were in clinical remission at Wk44 (43.8% and 38.4%, respectively) vs. PBO patients (24.0%). Significantly greater proportions of USTq8w and q12w patients maintained clinical response through Wk44 and achieved endoscopic healing and corticosteroid-free clinical remission vs. PBO patients. Clinical remission through Wk44 was maintained for a significantly greater proportion of q12w patients and a numerically greater proportion of q8w vs. PBO patients (Tab. 1). The proportions of patients with AEs, serious AEs, infections, and serious infections with UST were generally comparable to PBO (Tab. 2).

Tab. 1:

Primary and Key Secondary Endpoints and Safety data

	PBO SCa	UST 90 mg SC q12w	UST 90 mg SC q8w
Number of randomized patients	175	172	176
Patients in clinical remission at Week 44b	42 (24.0%)	66 (38.4%) p = 0.002	77 (43.8%) p < 0.001
Patients maintained clinical response through Week 44c	78 (44.6%)	117 (68.0%) p < 0.001	125 (71.0%) p < 0.001
Patients achieved endoscopic healing at Week 44d	50 (28.6%)	75 (43.6%) p = 0.002	90 (51.1%) p < 0.001
Patients in clinical remission and not receiving corticosteroids at Week 44b	41 (23.4%)	65 (37.8%) p = 0.002	74 (42.0%) p < 0.001
Patients who maintained clinical remission through Week 44 among patients in remission at maintenance baselineb	17/45 (37.8%)	26/40 (65.0%) p = 0.011	22/38 (57.9%) p = 0.069
Average duration of follow-up (weeks)	42.3	41.8	42.2
Average exposure (number of administrations)	7.1	7.3	7.4
Patients who died	0	0	0
Patients with 1 or more
Adverse events	138 (78.9%)	119 (69.2%)	136 (77.3%)
Serious adverse events	17 (9.7%)	13 (7.6%)	15 (8.5%)
Infections	81 (46.3%)	58 (33.7%)	86 (48.9%)
Serious infections	4 (2.3%)	6 (3.5%)	3 (1.7%)
AEs leading to DC of study agent	20 (11.4%)	9 (5.2%)	5 (2.8%)
Malignancies (excluding NMSC)	0	1 (0.6%)	1 (0.6%)
a Patients who were in clinical response to ustekinumab IV induction dosing and were randomised to placebo SC on entry into this maintenance study. b Mayo score ≤2 points, with no individual subscore > 1. c Decrease from induction baseline in the Mayo score by ≥30% and ≥3 points, with either a decrease from induction baseline in the rectal bleeding subscore ≥1 or a rectal bleeding subscore = 0 or 1. d Also described as endoscopic improvement in the appearance of the mucosa and defined as a Mayo endoscopy subscore = 0 or 1.

Conclusion:

Both UST90 mg q8w and q12w SC achieved clinical remission and maintained clinical response and were effective in achieving endoscopic healing and corticosteroid-free remission among patients with moderate-to-severe UC induced into clinical response with single IV dose of UST. The safety for UST in UC patients was consistent with the known safety profile of UST.