P008 Long-Term Effectiveness and Safety of Ustekinumab for The Treatment of Crohn´s Disease: A Brazilian Multicentre Real-world Study.

Abstract

BACKGROUND: Real world data regarding long-term effectiveness and safety of ustekinumab (UST) for the treatment of Crohn’s disease (CD) is lacking in South America. We report the outcomes of a Brazilian multicentre retrospective cohort in patients with moderate-to-severe CD treated with UST in a real-world setting. METHODS: Between November 2017 and December 2019, a retrospective study was performed including patients from 12 inflammatory bowel disease (IBD) academic medical centers diagnosed with moderately to severely active CD starting on UST (weight-based single IV infusion dose followed by 90 mg subcutaneous maintenance dose administered 8 weeks after the initial intravenous dose, then every 8 weeks thereafter). The primary outcome was clinical remission (Harvey-Bradshaw index [HBI] ≤ 4) at weeks 16. Secondary outcomes included clinical remission at weeks 24 and 56, clinical response at weeks 8 and 16 (HBI decrease ≥ 3), biochemical remission at week 16 (C-reactive protein [CRP] normalization in patients with elevated CRP baseline levels), corticosteroid-free remission and drug discontinuation rates. RESULTS: Among 241 patients included (mean age 39.9 years old), 86% had been previously exposed to at least one biologic, 66 (31.9%) had been treated with only one biologic agent, and 141 (68.1%) with two or more biologics. Twenty-five percent (50/204) received combined therapy with immunomodulators. Corticosteroids were administered during induction in 97 patients (57%, 97/170). At baseline, mean HBI was 10.3 (range: 5-23) and mean CRP was 20.5 (range: 0-125). Clinical response at week 8 was observed in 66.7% of patients (144/216). In non-responder imputation (NRI) analysis, clinical remission was achieved in 60.2%, 51.4% and 24.1% at week 16, 24 and 56 respectively. Biochemical remission was achieved in 61.3% of patients (114/186). Corticosteroid-free remission was achieved in 59.6% of patients at their last follow up. A total of 39 patients (16.2%) interrupted their treatment and the main reasons for discontinuation were loss of response / disease progression (35.9%), primary failure (25.6%), lack of access / no reimbursement (17.9%), pregnancy (15.4%) and abandonment of treatment (5.1%). HBI higher than 9.5 at baseline, previous exposure to anti-TNF and penetrating disease were associated with lower rates of clinical remission. No new safety signals were observed. CONCLUSION: This is the first study to show the long-term safety and real-world effectiveness of UST in a large cohort of moderate-to-severe CD patients in Brazil. This study confirms the previous reported effectiveness and long-term maintenance of response of UST in CD patients exposed to biological therapy, especially to anti-TNF agents. UST was well tolerated, and no new safety signals were identified in this study.