P0735Safety and Efficacy of Ustekinumab in Indian Patients with Moderate to Severe Crohn’s Disease: A Multicentre, Interventional, Phase IV study

Abstract Background Ustekinumab (UST), a monoclonal antibody targeting the p40 subunit of interleukin (IL)-12/23, has been approved globally. It has shown to be well tolerated and effective for the treatment of moderate to severe Crohn’s disease (CD). However, data on UST use in the Indian population is presently lacking. Therefore, this health-authority mandated real-world study aimed to evaluate the safety and efficacy of UST in Indian patients (pts) with CD. Methods This open-label, multicentre (10 sites), study enrolled consented adult pts with CD (CD Activity Index CDAI score 220-450) for ≥3 months and those who had failed or were intolerant to standard treatments. After 1-week (wk) of screening, pts received a body weight-based intravenous induction dose of UST at Wk 0 (260-520 mg), then 90 mg subcutaneous maintenance doses every 8 wks (Wk 8 to 24) and an end-of-study (EOS) visit at Wk 38. Primary objective was evaluation of safety and primary endpoint was assessing number and percentage of adverse events (AEs) or serious AEs. Secondary objectives and endpoints included percentage of pts achieving clinical remission (CDAI 150) and clinical response (≥100 decrease in CDAI/ total CDAI score 150) at Wks 8, 16, and 24. Exploratory endpoints included C-reactive protein (CRP) and fecal calprotectin (FCP) levels measured at baseline, Wk 8, and Wk 24. Results A total of 80 pts were enrolled in the study. At baseline, mean (SD) age of pts was 35.3 (14.4) years, with a median disease duration of 2.6 years. Mean (SD) baseline CDAI was 296.2 (52.5); 48.8% of pts had CDAI 300. About 66 pts (82.5%) had received one or more prior CD medications, while 14 (17.5%) were bio-naïve. Clinical remission and clinical response were achieved in 12.8%, 33.3%, 38.5% and 69.2%, 50.0%, 69.2% of pts at Wk 8, 16, and 24, respectively. Mean change in CRP and FCP levels from baseline (12.8 30.47 mg/L and 717.5 1216 mg/kg) was -5.5 (26.86) mg/L and -184 (1345.68) mg/kg at Wk 8 and -1.2 (30.22) mg/L and -266.7 (1239.65) mg/kg, at Wk 24, respectively. Overall, 29 (36.3%) pts experienced ≥1 AEs (Table). Most common ≥5% AEs (≥5% observed were anaemia (16 pts, 20%) and pyrexia (6 pts, 7.5%). Serious treatment-emergent (TE)AEs in 2 (2.5%), TEAEs related to discontinuation of therapy in 1 (1.3%) and TE infections in 4 (5%) pts were observed. One death was reported in the study. No cases of tuberculosis were detected during the study. Conclusion The study findings showed that UST was well tolerated and effective in Indian pts with moderate to severe CD, consistent with the existing global evidence. No new safety signals, including tuberculosis, were identified Conflict of interest: Banerjee, Rupa: RB has received grants/research support from Asian Healthcare Foundation, and the Leona M and Harry B Helmsley Charitable Trust Advisory board fees from Abbott, AstraZeneca, Abbvie, Cadila, Cipla, Dr Reddy Labs, Eli Lilly, Emcure, Ferring Pharma, Hetero Drugs, Janssen, MSN Labs, Mankind Pharma, Menarini, Micro Labs, Pfizer, Sun Pharmaceuticals, Takeda Pharmaceuticals, Torrent, Waterley, and Zydus. Ahuja, Vineet: No conflict of interest Choudhuri, Gourdas: No conflict of interest Dalal, Ashok: No conflict of interest Kalla, Mukesh: No conflict of interest Mehta, Rajiv: No conflict of interest Midha, Vandana: No conflict of interest Behl, Nitin: No conflict of interest Kumar, Ravi Kant: No conflict of interest Panchal, Sagar: Employee of Johnson & Johnson Private Limited, India, and may own stock or stock options in Johnson & Johnson. Shah, Nishita: Employee of Johnson & Johnson Private Limited, India, and may own stock or stock options in Johnson & Johnson. Dr. Kulkarni, Utkarsha: Employee of Johnson & Johnson Private Limited, India, and may own stock or stock options in Johnson & Johnson. Rege, Milind: Employee of Johnson & Johnson Private Limited, India, and may own stock or stock options in Johnson & Johnson.