Efficacy and safety of ustekinumab in Russian bionaive patients with moderately to severely active ulcerative colitis: a subanalys is of global phase 3 induction and maintenance studies (UNIFI) up to 3 years
Authors: Belousova E. A. , Abdulkhakov R. A. , Bakulin I. G. , Kulyapin A. V. , Tkachev A. V. , Marano Colleen , Miao Ye 
Published: March 2023

AIM: to evaluate efficacy and safety of ustekinumab in Russian patients with ulcerative colitis in UNIFI study. PATIENTS AND METHODS: the UNIFI program (CNTO1275UCO3001) consisted of two randomized placebo-controlled trials: an 8-week induction study and a 44-week maintenance study and long-term period. This analysis included patients from 14 Russian centers.

RESULTS: the induction study of the UNIFI program enrolled 74 patients from Russia, 89.2% patients (n = 66) were bionaive. The paper presents the results of bionaive patients. Sixty-six are included in the induction phase: 18 received ustekinumab 130 mg IV, 25 received ustekinumab 6 mg/kg IV, and 23 received a placebo. At week 8 in the groups of patients treated with ustekinumab at doses of 6 mg/kg and 130 mg, clinical remission was achieved in 24.0% and 16.7%, respectively, in the placebo group, the rate was 17.4%. The proportion of patients with clinical responses at week 8 was 68.0%, 50.0% and 39.1% in the ustekinumab 6 mg/kg, 130 mg and placebo groups, respectively. Mucosal healing at week 8 was achieved in 48.0% in the ustekinumab 6 mg/kg group, in 33.3% of patients in the ustekinumab 130 mg group, and in 21.7% of patients in the placebo group. Histoendoscopic mucosal healing at week 8 developed in 27.8% of patients in the ustekinumab 130 mg group, in 24.0% of patients in the ustekinumab 6 mg/kg group, and in 21.7% of patients in the placebo group. Forty bionaive patients were re-randomized for further participation in the maintenance phase: 13 patients received ustekinumab 90 mg subcutaneously every 12 weeks, 12 received ustekinumab every 8 weeks, and 15 received a placebo. At week 44, clinical remission was achieved in 46.2% of ustekinumab every 12 weeks, 75.0% of ustekinumab every 8 weeks (p = 0.054 compared with placebo), and 33.3% of placebo. Mucosal healing achieved in 46.2% of patients in the ustekinumab once every 12 weeks group, in 75.0% of patients in the ustekinumab once every 8 weeks group (p = 0.054 compared with. placebo), and in 33.3% of patients in the placebo group. Histoendoscopic mucosal healing achieved in 46.2% of patients in the ustekinumab once every 12 weeks group, while in the ustekinumab once every 8 weeks group, the percentage of such patients was 75.0% (p = 0.021 compared with placebo) and in the placebo group — 26.7%. Symptomatic remission at week 152 developed in 83.3% in the ustekinumab every 12 weeks group, 81.8% in the ustekinumab every 8 weeks group. In the induction phase decrease of CRP and FCP median levels detected in patients treated with ustekinumab, in the maintenance phase, median levels of laboratory inflammatory markers after induction were sustained by ustekinumab treatment. The rate of steroid-free symptomatic remission at week 152 was consistent with the rate of symptomatic remission. The safety profile of ustekinumab was generally consistent with placebo during all follow up period.

CONCLUSION: subanalysis confirmed shortand long-term efficacy and safety in Russian patients with moderate to severe active ulcerative colitis. The results of subanalysis are consistent with previously obtained data in the population of patients participating in the global UNIFI program.