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.
