Long-term outcome of risankizumab in Crohn's disease: a real-world GETAID study.

INTRODUCTION: The aim of this study was to assess the long-term effectiveness and safety of risankizumab maintenance treatment in a large real-world cohort of patients with CD. PATIENTS AND METHODS: From May 2021 to August 2023, all consecutive CD patients treated with risankizumab in 25 GETAID centers have been retrospectively included. The primary endpoint was steroid-free clinical remission (Harvey Bradshaw Index (HBI) <5) at 52 weeks. RESULTS: Of the 174 patients included, 99%, 93%, and 96% had been previously exposed to anti-TNF, vedolizumab, and ustekinumab, respectively. All patients had received ≥3 biologics and 108 (62%) had previous intestinal resection. Median follow-up was 13.7 (10.0-18.1) months. The rates of steroid-free clinical remission and clinical remission at week 26 were 47% (72/152) and 52% (79/152), and 46% (58/125), and 48% (60/125) at week 52, respectively. Risankizumab persistence rates were 94%, 89%, and 79% at weeks 12, 26, and 52, respectively. At the end of follow-up, 45 (45/174, 26%) patients had discontinued risankizumab (loss of response, 42%; primary failure, 37%; intolerance, 13%). Thirty-six patients (36/174, 20.9%) were hospitalized and 22 (22/174, 12.6%) required intestinal resection. Fifty-one (29%) patients had an adverse event including 26 (15%) serious adverse events (CD flare, n=17). One death (myocardial infarction) and one cancer (papillary thyroid carcinoma) were observed. CONCLUSION: This is the first real-life study to report long-term outcomes in patients with refractory CD treated with risankizumab. Half of the patients achieved steroid-free clinical remission after one year, and the safety profile was consistent with the literature.

Effectiveness and safety of risankizumab induction therapy for 100 patients with Crohn's disease: A GETAID multicentre cohort study.

BACKGROUND: Phase III trials have demonstrated the efficacy of risankizumab in moderate-to-severe Crohn's disease (CD), but no real-world data are currently available. We aimed to assess the short-term effectiveness and safety of risankizumab in patients with CD. METHODS: From May 2021 to May 2022, all patients with refractory luminal CD treated with risankizumab in 22 French GETAID centres were retrospectively included. The primary endpoint was steroid-free clinical remission at week 12 (Harvey-Bradshaw [HB] score <5). Secondary endpoints included clinical response (≥3-point decrease of HB score and/or (HB) score <5), biochemical remission (CRP ≤ 5 mg/L), need for CD-related surgery and adverse events. RESULTS: Among the 100 patients included, all have been previously exposed to anti-TNF agents, 94 to vedolizumab, 98 to ustekinumab (all exposed to at least three biologics) and 61 had a previous intestinal resection. All but three (97%) received a 600 mg risankizumab intravenous induction at weeks 0-4-8. At week 12, steroid-free clinical remission was observed in 45.8% of patients, clinical remission in 58% and clinical response in 78.5%. In subgroup analysis restricted to patients with objective signs of inflammation at baseline (n = 79), steroid-free clinical remission at week 12 was observed in 39.2% of patients. Biochemical remission was observed in 50% of patients. Six patients discontinued risankizumab before the week 12 visit due to lack of efficacy. CD-related hospitalisation was needed in six patients, and three underwent intestinal resection. In multivariable analysis, only a history of ustekinumab loss of response (vs primary failure) (odds ratio (OR), 2.80; 95% CI: 1.07-7.82; p = 0.041) was significantly associated with clinical remission at week 12. Twenty adverse events (AE) occurred in 20 patients including 7 serious AE corresponding to 6 CD exacerbation and one severe hypertension. CONCLUSION: In a cohort of highly refractory patients with luminal CD and multiple prior drug failures including ustekinumab, risankizumab induction provided a clinical response in about 3 out of 4 patients and steroid-free clinical remission in about half of patients.

Impact of thiopurines and tumour necrosis factor antagonists on primary sclerosing cholangitis outcomes in patients with inflammatory bowel disease.

BACKGROUND: Patients with primary sclerosing cholangitis (PSC) and inflammatory bowel disease (IBD) are at risk of biliary tract cancer and liver damage (possibly leading to liver transplantation), and are often treated for IBD with thiopurines and/or tumour necrosis factor antagonists (anti-TNF) on a long-term basis. AIMS: To assess the risk of biliary tract cancer and liver transplantation in patients exposed to thiopurines and/or anti TNF agents in a French nationwide cohort. METHODS: We performed a population-based study of patients aged 18 years or older with PSC and IBD in the French national health insurance database. Patients were followed from 1 January 2009 to 31 December 2018. The risks of biliary tract cancer and liver transplantation associated with thiopurines and anti-TNF exposure were assessed with marginal structural Cox proportional hazard models, adjusting for baseline demographics and comorbidities, and time-varying medications and PSC activity. RESULTS: Among the 1929 patients with PSC and IBD included, 37 biliary tract cancers and 83 liver transplantations occurred. Compared with patients not exposed to thiopurines or anti-TNF agents, patients exposed to thiopurines (hazard ratio [HR], 1.05; 95% confidence interval [CI], 0.39-2.82) or anti-TNF agents (HR, 0.59; 95% CI, 0.13-2.80) had no excess risk of biliary tract cancer. Similarly, patients exposed to thiopurines (HR, 0.67; 95% CI, 0.30-1.48) or anti-TNF agents (HR, 0.68; CI, 0.22-2.09) had no excess risk of liver transplantation. CONCLUSIONS: Patients with PSC and IBD who are exposed to thiopurines or anti-TNF agents are not at excess risk of biliary tract cancer or liver transplantation.

Diagnosis of postoperative recurrence of Crohn disease with MR-enterography: Value of diffusion-weighted imaging.

PURPOSE: To compare the diagnostic capabilities of MR enterography (MRE) using contrast-enhanced (CE) sequences with those of MRE using diffusion-weighted (DW) imaging for the diagnosis of postoperative recurrence at the neo-terminal ileum and/or anastomosis after ileocolonic resection in patients with Crohn disease (CD), and to clarify the role of additional DW imaging to CE-MRE in this context. MATERIAL AND METHODS: Forty patients who underwent ileal resection for CD, and both endoscopy and MRE within the first year after surgery were included. There were 21 men and 19 women, with a mean age of 38 years±12 (SD) years (range: 18-67 years). MRE examinations were blindly analyzed independently by one senior (R1) and one junior (R2) radiologist for the presence of small bowel postoperative recurrence at the anastomotic site. During a first reading session, T2-, steady-state- and DW-MRE were reviewed (DW-MRE or set 1). During a separate distant session, T2-, steady-state- and CE-MRE were reviewed (CE-MRE or set 2). Lastly, all sequences were analyzed altogether (set 3). Performances of each reader for the diagnosis of postoperative recurrence were evaluated using endoscopic findings as the standard of reference (Rutgeerts score≥i2b). RESULTS: Fifteen patients out of 40 (37.5%) had endoscopic postoperative recurrence at the anastomotic site. Sensitivity for the diagnosis of postoperative recurrence was 73% (95% CI: 51-96%) for R1 and 67% (95% CI: 43-91%) for R2 using set 1, and 80% (95% CI: 60-100%) for both readers using set 2. There was no significant differences in sensitivity between reading set 1 and reading set 2, for either R1 or R2 (R1, P> 0.99; R2, P=0.48). Specificity was 96% (95% CI: 88-100%) for both readers using set 1 or using set 2. Reading set 3 yielded an area under the ROC curve (AUC) of 0.93 (95% CI: 0.84-1) versus 0.89 (95% CI: 0.75-1) with set 1 (P=0.18) and versus 0.89 (95% CI: 0.78-1) with set 2 (P=0.21). No significant differences in AUC were found between set 1 or 2 and set 3 (P=0.18), nor between set 1 and 2 (P=0.76). Accuracies were 88% (95% CI: 74-95%) and 85% (95% CI: 71-93%) for DW-MRE for R1 and R2, respectively; 90% (95% CI: 77-96%) for CE-MRE for both readers; and 93% (95% CI: 80-97%) and 88% (95% CI: 74-95%) for R1 and R2 with set 3, respectively. CONCLUSION: DW-MRE has diagnostic capabilities similar to those of CE-MRE for the diagnosis of postoperative recurrence of CD at the anastomotic site.