Efficacy and Safety of Ustekinumab in Patients With Crohn`s disease: Data From a Real World Study in Brazil
BACKGROUND: Ustekinumab (UST)is a fully human monoclonal antibody against IL-12/23 approved in Brazil for the treatment of moderate-to-severe Crohn’s disease (CD) in November 2017. UST has demonstrated its efficacy in induction and maintenance therapy for patients with CD. Real world data regarding the efficacy and safety of UST in this population is lacking in our country. We hereby report our experience with UST in patients with moderate to severe CD. METHODS: A retrospective chart review and a prospective study were performed including patients from eleven IBD referral centers with moderately to severely active CD starting on UST (IV infusions followed by scheduled subcutaneous [SC] injections) between November 2017 and April 2019. We accessed clinical response and remission (based on Harvey-Bradshaw index [HBI]), and C-reactive protein (CRP) levels. Clinical response and clinical remission were defined by HBI decrease; 3 and HBI; 3, respectively. Clinical remission was accessed in weeks 0, 8, 16, 24 and 48. CRP was evaluated in weeks 0, 8 and 48. Statistical analysis was performed and the data is presented as observed. The study was approved by Ethical Committee (no 3.335.068/2019). RESULTS: One-hundred and sixty-one patients were treated with UST during the study period. The mean age was 38.2 years, disease duration 10.3 years, 58.4% had previous surgeries, 46.6% had perianal disease, 55.5% had anaemia, 55.3% were female, 16.2% were smokers. The majority of patients were treated with 90mg every 8 weeks (97.4%) during maintenance. The majority of patients were previously exposed to biological therapy (85.7%) and 23 patients were naive. Forty-four patients were previously exposed to one biologic, 78 exposed to two biologics and 16 exposed to three biologics. Mean HBI at baseline was 10.1 and 38.5% have or had previously presented extra intestinal manifestations. At baseline mean CRP was 21.3 mg/L. At week 8, 76.9% of patients achieved clinical response and 38.9% achieved clinical remission. Clinical remission was observed in 53.1% (week 16), in 53.9% (week 24) and in 62.5% (week 48) of patients. CRP decreased to 14.4mg/L at week 8, followed by a significant decrease until week 48 (7.7 mg/L). Adverse events occurred in 28.6% of patients. Inflammatory behavior, naive or previously exposure to one biological, disease duration lower than two years were associated to better outcomes in statistical analysis. Twenty-four patients stopped UST, thirteen due to surgery and/or lack of response, three due to pregnancy, seven due to lack of access of the drug and one due to depression. No new safety signals were observed. CONCLUSION(S): UST therapy was successful for inducing and maintenance of clinical remission and improving laboratory biomarkers of disease activity in patients with moderate to severe CD and who were refractory to anti-TNF therapy. Both UST induction and maintenance regimens until week 48 were overall well tolerated. These results support a favorable safety and efficacy profile.
