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

Summary Background Women with inflammatory bowel diseases (IBD) often receive biologicals during pregnancy to maintain disease remission. Data on outcome of vedolizumab‐exposed pregnancies (VDZE) are sparse. Aims To assess pregnancy and child outcomes of VDZE pregnancies and to compare these results to anti‐TNF exposed (TNFE) or both immunomodulatory and biologic unexposed (CON IBD) pregnancies. Methods A retrospective multicentre case‐control observational study was performed. Results VDZE group included 79 pregnancies in 73 IBD women. The TNFE and CON IBD group included 186 pregnancies (162 live births) in 164 IBD women and 184 pregnancies (163 live births) in 155 IBD women, respectively. At conception, cases more often had active disease ([VDZE: 36% vs TNFE: 17%, P = .002] and [VDZE: 36% vs CON IBD: 24%, P = .063]). No significant difference in miscarriage rates were found between groups (VDZE and TNFE: 16% vs 13%, P = .567; VDZE and CON IBD: 16% vs 10%, P = .216). In live‐born infants, median gestational age and birthweight were similar between groups. Median Apgar score at birth was numerically equal. Prematurity was similar in the VDZE group compared to the control groups, even when correcting for disease activity during pregnancy. The frequency of congenital anomalies was comparable between groups as were the percentages of breastfed babies. During the first year of life, no malignancies were reported and infants' infection risk did not significantly differ between groups. Conclusion No new safety signal was detected in VDZE pregnancies although larger, prospective studies are required for confirmation.

Elective switching from infliximab to adalimumab is associated with loss of tolerance and loss of efficacy within 1 year. Adherence to the first anti-TNF agent is recommended.

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Background Tofacitinib, an oral small molecule Janus kinase inhibitor, has been approved in 2018 for the treatment of moderate to severe ulcerative colitis (UC) in Europe. We report on real-world short-term efficacy and safety data from a multicenter Belgium refractory cohort of UC patients with prior exposure to both anti-TNFα and vedolizumab. Methods This is an observational, national, retrospective multicentre study including all UC active patients started on tofacitinib (10 mg BID) from 25 centres in Belgium between November 2018 and August 2019. Prospectively collected data were retrospectively analysed according to intention to treat. Primary endpoints were clinical and endoscopic response and remission rates at weeks 8 and 16. Clinical response and remission were defined as a reduction in the Modified Clinical Mayo score (rectal bleeding, stool frequency) of ≥2 and ≤1, respectively. Endoscopic response and remission were defined as a reduction in Endoscopic Mayo score of ≥1 and ≤1, respectively. Complete endoscopic remission was defined as an Endoscopic Mayo score of 0. Descriptive statistics and Wilcoxon signed-rank test were calculated using Medcal 19.1. Results Demographic and baseline data of the 70 included patients are presented in Table 1. Of note is that nearly all patients were refractory to at least one anti-TNF and vedolizumab. Median follow-up was 16 weeks (IQR 13–26). Fifty-four per cent (38/70) of patients required prolonged induction at 10mg BID. Clinical evaluation was available in all patients at week 8 and 49 patients at week 16, while endoscopic data were available in 52 patients and 42 at weeks 8 and 16, respectively. Clinical response and remission, and endoscopic response and remission at weeks 8 and 16 are presented in Figures 1 and 2. Fifty per cent (21/42) of the patients under steroids at baseline could have stopped steroids at 16 weeks. Median baseline Modified Mayo score (rectal bleeding, stool frequency and endoscopy) decreased from 7 (IQR 5–8) to 4 (IQR 2–7) after 8 weeks (n = 49) (p < 0.0001), and down to 2 (IQR 1–5) at week 16 (n = 40) (p < 0.0001). Median CRP significantly decreased from baseline (5.3 mg/l, IQR [1.9–16.8]) to 1 mg/l at week 8 (IQR 0.5–6.2) (n = 49) (p = 0.003). Tofacitinib was well tolerated with only 1 reported case of single dermatome herpes zoster and no case of venous thromboembolism. Conclusion Tofacitinib very effectively induced short-term clinical and endoscopic response and remission even in a refractory cohort of patients with UC in a real-world clinical setting. During this short-term follow-up, tofacitinib was well tolerated with respect to adverse events.

Background and Aims Dose intensification of vedolizumab (VDZ) for moderate‐to‐severe ulcerative colitis (UC) and Crohn's disease (CD) may be effective in patients losing response. We aimed to assess the clinical and pharmacokinetic effect of VDZ dose intensification. Methods We performed a multicentre open‐label prospective study from June 2017 through December 2018 in patients on VDZ losing response, defined as total Mayo score >6 (UC) or Harvey‐Bradshaw Index >4 with inflammation (CD). Blood samples and clinical scores were collected at baseline and after VDZ infusion at Weeks 4 and 8. Clinical response was defined as a decrease of partial Mayo score ≥2 points or Harvey‐Bradshaw Index ≥3 points. Biological response was defined as a decrease of C‐reactive protein to ≤5 mg/L or of >50%. Results A total of 59 patients (31 UC and 28 CD) were included. Median (IQR) trough levels (TLs) increased from 8.7 (5.1‐12.7) µg/mL (baseline) to 19.1 (12.4‐22.4) µg/mL (Week 4) and 23.1 (16.7‐28.4) µg/mL (Week 8) (all P < 0.0001). Partial Mayo score decreased with 3 points from baseline to Week 4 (P = 0.001) but stabilised to Week 8 (P = 0.16). Harvey‐Bradshaw Index decreased with 4 points from baseline to Week 4 (P = 0.001) and 1 point to Week 8 (P = 0.04). Recapture of clinical and biological response was achieved in 49% and 27% at Week 4, and 54% and 37% at Week 8 respectively. Conclusion Dose escalation to VDZ every 4 weeks after loss of response resulted in higher TLs with regain of clinical response in half of the patients.

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