Ustekinumab is effective and safe for ulcerative colitis through 2 years of maintenance therapy

Abstract

Background: The ongoing UNIFI long-term extension evaluates subcutaneous ustekinumab for moderate-to-severe ulcerative colitis (UC) from weeks 44 through 220.

Aims: To assess efficacy (through week 92) and safety (through week 96) during the long-term extension METHODS: Overall, 399 responders to intravenous ustekinumab induction and who were randomised to maintenance therapy were treated in the long-term extension (115 received subcutaneous placebo, 141 received ustekinumab 90 mg every 12 weeks [q12w], and 143 received ustekinumab 90 mg q8w). Placebo treatment was discontinued at unblinding after week 44. Partial Mayo scores were collected every 12 weeks and at each dosing visit after unblinding. Safety was evaluated throughout.

Results: Among all patients randomised in maintenance, symptomatic remission rates (stool frequency = 0/1; rectal bleeding = 0) at week 92 were, 64.5% and 67.6% in the ustekinumab q12w and q8w groups, respectively. Among randomised patients treated in the long-term extension, 78.7% and 83.2% of patients receiving q12w and q8w, respectively, attained symptomatic remission at week 92; >95% of patients in symptomatic remission at week 92 were corticosteroid-free. Both ustekinumab groups maintained efficacy through week 92. From weeks 44 to 96, adverse events (AEs) per hundred patient-years (PY) of follow-up for combined ustekinumab vs placebo were: 255.68 vs 267.93; serious AEs, 9.34 vs 12.69; malignancies (including non-melanoma skin cancers), 0.93 vs 1.49; and serious infections, 2.33 vs 2.99. One patient with multiple comorbidities who received one ustekinumab dose after dose adjusting from placebo experienced a fatal cardiac arrest.

Conclusions: The efficacy of ustekinumab in patients with UC was sustained through 92 weeks. No new safety signals were observed (ClinicalTrials.gov number, NCT02407236).

Figure 1:

UNIFI maintenance and long-term extension study design: randomised (A) and non-randomised (B) patients

Figure 2:

Nonresponder imputation analysis of all patients randomized in maintenance study (intent-to-treat population) for symptomatic remission^{†, ‡, §, ¶, ††, ‡‡} through Week 92 (A) and by biologic treatment history subgroup (B)

Figure 3:

Nonresponder imputation analysis of corticosteroid-free symptomatic remission through Week 92^{†, ‡, §, ¶, ††, ‡‡} for all patients randomized to ustekinumab in the maintenance study (intent-to-treat population)

Figure 4:

Nonresponder imputation analysis of symptomatic remission^{†, ‡, §, ¶} from Week 44 through Week 92 for all patients randomized to ustekinumab in the maintenance study and treated in the long-term extension (A) and by biologic treatment history subgroup (B)

Figure 5:

Nonresponder imputation analysis of symptomatic remission and corticosteroid-free symptomatic remission^{†, ‡, §, ¶} at Week 92; patients randomized to ustekinumab in the maintenance study and treated in the long-term extension

Figure 6:

All adverse events (A) and key safety events (B) during ustekinumab exposure^{†, ‡,§, ¶,††} †. Number of treatment-emergent adverse events per 100 patient-years of follow-up and 95% confidence interval (rates by each year of follow-up) in the pooled ustekinumab ulcerative colitis safety cohort. Confidence intervals based on an exact method assuming that the observed number of events follows a Poisson distribution. ‡. Infection as assessed by the investigator. §. Placebo (First Year) includes 1) Patients who were in clinical response to ustekinumab IV induction dosing and were randomized to placebo SC on entry into this maintenance study and were followed after Week 8; and 2) Patients who were in clinical response to placebo IV induction dosing and received placebo SC on entry into this maintenance study. Only includes data from Week 8 onward for patients who were in clinical response to ustekinumab IV induction dosing and were randomized to placebo SC on entry into this maintenance study. ¶. All Ustekinumab (First Year) includes 1) patients who received ustekinumab SC (q8w or q12w) in this maintenance study; and 2) patients who were in clinical response to ustekinumab IV induction dosing and received placebo SC on entry into this maintenance study; 2)data from Week 0 to Week 8 for patients who were in clinical response to ustekinumab IV induction dosing and were randomized to placebo SC on entry into this maintenance study. ††. All Ustekinumab-treated in the LTE (Second Year) includes: 1) Patients who were in clinical response to ustekinumab IV induction dosing and were randomized to receive ustekinumab 90 mg SC q12w or q8w on entry into the maintenance study, with data from Week 44 through Week 96; 2) Patients who were in clinical response to ustekinumab IV induction dosing, randomized to receive placebo SC on entry into the maintenance study, and had a dose adjustment to ustekinumab 90 mg SC q8w, with data from the time of dose adjustment onward; 3) Patients who were not in clinical response to ustekinumab at I-8 but were in clinical response at I-16 after a SC administration of ustekinumab at I-8 and received ustekinumab 90 mg SC q8w on entry into the maintenance study with data from Week 44 through Week 96. Key: CI, confidence interval; IV, intravenous; NMSC, nonmelanoma skin cancer; q8w, every 8 weeks; 12w, every 12 weeks; SC, subcutaneous