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Contains fulltext : 290620.pdf (Publisher’s version ) (Open Access) BACKGROUND: Tofacitinib is an oral Janus kinase (JAK) inhibitor and is registered for the treatment of ulcerative colitis (UC). The effectiveness of tofacitinib has been evaluated up to 12 months of treatment. AIM: The aim of this study was to assess the effectiveness and safety of 24 months of tofacitinib use in UC patients in the Netherlands. METHODS: Patients initiating tofacitinib treatment were included in the ICC Registry, a nationwide, observational registry. Patients were prospectively evaluated for up to 24 months. The primary outcome was corticosteroid-free clinical remission (CSFR, Simple Clinical Colitis Activity Index [SCCAI] ≤2) at week 104. Secondary outcomes included biochemical remission (C-reactive protein (CRP) ≤5 mg/L and faecal calprotectin (FC) ≤250 μg/g), safety, and discontinuation rate. RESULTS: We included 110 patients of whom 104 (94.5%) were anti-TNF experienced. After 104 weeks of tofacitinib, 31.8% (34/107) were in CSFR, 23.4% (25/107) in biochemical remission and 18.7% (20/107) in combined clinical and biochemical remission. Of the patients in CSFR at week 52, 76.5% (26/34) remained so after 104 weeks of treatment. Sixty-one patients (55.5%) discontinued tofacitinib after a median duration of 13 weeks (IQR 7-34). The main reasons for discontinuation were non-response (59%), loss of response (14.8%), and adverse events (18%). There were 33.9 possible tofacitinib-related adverse events per 100 patient-years during follow-up. Adverse events most probably related to tofacitinib were skin reactions and headaches. There were 6.4 herpes zoster infections per 100 patient-years. CONCLUSION: Tofacitinib was effective in 31.8% of patients after 24 months of treatment. 01 januari 2023

Aliment Pharmacol Ther 31, 1322–1329 Summary Background Several reports suggest an increased rate of adverse reactions to azathioprine in patients with Crohn’s disease. Aim To compare the incidence of thiopurine-induced acute pancreatitis in patients with inflammatory bowel disease (IBD) with that in patients with vasculitis. Methods This retrospective analysis was performed using data collected in three databases by two university hospitals (241 patients with IBD and 108 patients with vasculitis) and one general district hospital (72 patients with IBD). Results The cumulative incidence of thiopurine-induced acute pancreatitis in Crohn’s disease equalled that of ulcerative colitis (UC) (2.6% vs. 3.7%) and this did not differ from vasculitis patients (2.6% vs.1.9%). In addition, the cumulative incidence of thiopurine-induced acute pancreatitis in UC patients was not different from that in vasculitis patients. In the IBD group, 100% of thiopurine-induced acute pancreatitis patients were women, whereas in the vasculitis group the two observed thiopurine-induced acute pancreatitis cases (n = 2 of 2) concerned were men (P = 0.012). Conclusions In this study, the alleged higher cumulative incidence of thiopurine-induced acute pancreatitis in Crohn’s disease compared with vasculitis or UC patients was not confirmed. Female gender appears to be a risk factor for developing thiopurine-induced acute pancreatitis in IBD patients.

SUMMARY Background The amino acid citrulline is mainly produced by enterocytes from conversion of glutamine. As fasting plasma citrulline proved disappointing as a biomarker for enterocyte dysfunction in clinical practice, we propose a citrulline generation test (CGT) to assess enterocyte function. Aim To assess the feasibility of a CGT in healthy subjects and patients with decreased enterocyte mass. Methods Nineteen healthy subjects, 16 patients with intestinal villous atrophy and nine patients with short bowel syndrome (SBS) were given an oral bolus of 20 g of the dipeptide alanine–glutamine. Subsequent changes in plasma citrulline and other amino acid concentrations were determined using reverse-phase high-performance liquid chromatography. Results Following the oral bolus of alanine–glutamine, plasma citrulline concentrations showed a time dependent rise in healthy subjects of 44 13% (38–55 lmol ⁄ L, P < 0.0001). The slope from baseline plasma citrulline to peak concentrations was 0.22 0.08, 0.13 0.04 and 0.09 0.04 lmol ⁄ L ⁄ min in healthy subjects, patients with coeliac disease (CeD) and refractory CeD, respectively (healthy subjects vs. CeD P < 0.05, healthy subjects vs. refractory CeD P < 0.001). In patients with SBS, the CGT was able to distinguish between non-adapted and adapted SBS by means of the incremental area under the CGT curve till 90 min (iAUC T90). The iAUC T90 was 447 179 and 1039 178 lmol ⁄ L ⁄ min in nonadapted and adapted SBS, respectively (P = 0.04).