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

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

Parra Rogerio1, Chebli Julio2, Chebli Liliana2, Bertges Erika3, Ambrogini Junior Orlando4, Schiavetti Bianca5, Alves Júnior Antonio José6, Flores Cristina7, Lubini Marcio8, Gasparetti Jr Newton9, Bafutto Mauro10, Azevedo Matheus11, Damião Adérson11, Queiroz Natália11, Steinwurz Flavio12, Carvalho Nayara13, Boratto Sandra14, Vilela Eduardo15, Rocha José Joaquim1, Féres Omar1
1 Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil, 2 Federal University of Juiz de Fora, Juiz de Fora, Brazil, 3 UFJF, Juiz de Fora, Brazil, 4 UNIFESP, São Paulo, Brazil, 5 Universidade Federal de São Paulo, Vila Clementino, Brazil, 6 Pontifícia Universidade Católica de Campinas - PUCCAMP, Campinas, Brazil, 7 Hospital de Clinicas de Porto Alegre, R. Ramiro Barcelos, Porto Alegre, Brazil, 8 University of Passo Fundo, Passo Fundo, Brazil, 9 Hospital Vivalle Rede D'Or, Jacareí, Brazil, 10 Instituto Goiano de Gastroenterologia, Goiania, Brazil, 11 University of Sao Paulo, São Paulo, Brazil, 12 Santa Casa de Sao Paulo / Hospital Israelita Albert Einstein, São Paulo, Brazil, 13 University Federal de Sao Paulo/ Hospital Israelita Albert Einstein, São Paulo, Brazil, 14 Faculdade de Medicina do ABC, Santo André, Brazil, 15 Universidade Federal de Minas Gerais, UFMG, Belo Horizonte, Brazil

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(S): 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.