Long-term Clinical Effectiveness of Ustekinumab in Patients with Crohn’s Disease Who Failed Biologic Therapies: A National Cohort Study

Abstract

Background Ustekinumab [UST] was recently approved in Europe for the treatment of moderate to severe Crohn’s disease [CD]. Long-term real-world data are currently scarce for CD patients previously exposed to several biologics. Methods This is an observational, national, retrospective multicentre study. Patients received intravenous UST ~6 mg/kg at baseline, with 90 mg subcutaneously thereafter every 8 weeks. Response and remission rates were assessed at Weeks 8, 16, and 52. Results Data from 152 patients were analysed. All patients were exposed to at least one anti-TNFα agent, with 69.7% were exposed to even two anti-TNFα and vedolizumab. After 1 year, 42.1% and 25.7% of patients had experienced clinical response and clinical remission, respectively, and 38.8% and 24.3% had achieved steroid-free clinical response and remission, respectively; 38.8% of patients discontinued therapy during the 12 months of follow-up. Colonic location was predictive of clinical response at 1 year, and low body mass index [BMI] at baseline was a negative predictor of clinical remission. Resolution of arthralgia was associated with clinical response over time. De novo arthralgia was reported by 17.9% of patients at Week 8 and 13.5% of patients at Week 52. No impact of UST on arthralgia was observed in patients with concomitant ankylosing spondylitis [n = 17]. Others adverse events were reported in 7.2% of patients. Conclusions This real-world cohort study confirms the effectiveness of UST in CD patients previously exposed to several biologics. Ustekinumab was well tolerated with respect to adverse events. Podcast This article has an associated podcast which can be accessed at https://academic.oup.com/ecco-jcc/pages/podcast

Short and Long-Term Effectiveness of Ustekinumab in Patients with Crohn’s Disease: Real-World Data from a German IBD Cohort

“…When comparing our results with the results of the UNITI trials [16,17] and other real-world cohorts [7,[10][11][12], differences in study design and efficacy results can be observed.…”

“…Due to its rather recent approval, most studies evaluate short-term effectiveness [7] only, are retrospective, or do not include the intravenous induction regimen [8,9]. Only a few studies provide insight into long-term effectiveness [10,11] or are prospectively conducted [12]. However, comparing this data is challenging, as the definition of remission and response is not consistent throughout the publications.…”

Editorial: real‐world short‐term effectiveness of ustekinumab in 305 patients with Crohn’s disease—results from the ENEIDA registry. Authors' reply

“…Our study has shown better outcomes than the UNITI trial, reflecting other real‐world studies . In contrast to UNITI studies, and similar to most published studies, we used HBI because the variables associated with this index are easier to collect retrospectively from the clinical history …”

“…The SES‐CD decreased in both during follow‐up. However, the proportion of endoscopic response and remission was low (20.5% and 7.1% at week 24, respectively), presumably because the evaluation was premature.…”

“…A range of studies from other European groups have analysed short‐ and long‐term effectiveness in large cohorts of CD patients . All published works include refractory CD patients with prior failure of immunosuppressant, anti‐TNF and anti‐integrin therapies.…”