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.

Summary Background Ustekinumab is effective in Crohn's disease. However, a substantial proportion of patients will not respond or lose response to ustekinumab. The current evidence to support the effectiveness of dose‐optimisation for ustekinumab nonresponse is limited. Aim To assess the effectiveness of dose escalation of ustekinumab. Methods This was a multicentre retrospective cohort study. We included active Crohn's disease patients who received a standard‐dose intravenous induction and at least one subcutaneous ustekinumab 90 mg dose. All enrolled patients received dose escalation by either shortening the interval between the doses to every 4 or 6 weeks, intravenous reinduction or a combination of strategies. The primary outcome of the study was clinical response at week 16 after dose escalation. Results A total of 142 patients (22 centres/14 countries) were included. The patients were dose‐escalated after a median treatment duration of 30 weeks. At week 16 from escalation, 73/142 (51.4%) responded to treatment, including 55/142 (38.7%) in clinical remission. Corticosteroid‐free remission was achieved in 6/34 (17.6%) patients on corticosteroids at the time of escalation; 118/142 (83%) continued treatment beyond week 16. Follow‐up data beyond week 16 were available for 74/118 (62.7%) patients. On the last follow‐up, 51/98 (52%) patients with available data responded to treatment, including 41/98 (42%) in clinical remission. Conclusions Intensification of ustekinumab maintenance dosage was effective in over 50% of the patients. This strategy should be considered in patients who are nonresponsive to every 8 weeks ustekinumab maintenance dosing.

Background: Despite many publications regarding the role of faecal calprotectin (FC) in inflammatory bowel disease (IBD), clear recommendations for its use in clinical practice are currently lacking in the literature. Aim: The aim of this article is to provide practical guidance for clinicians for the use of FC in the detection and management of patients with IBD. Methods: All relevant publications were analysed and practical statements were proposed based on a Delphi consensus approach. Results: Different commercial assays have been developed but international standardisation is lacking. FC can help in the diagnosis process of IBD. In IBD, FC can predict response to therapy, detect subclinical inflammation and help to drive treatment decisions to achieve better endoscopic and clinical outcomes. After Crohn's surgery FC can identify patients with early endoscopic recurrence. Conclusion: Although major therapeutic changes should not be based on FC alone, FC is a valuable tool to optimise the care for IBD patients.

Background Vedolizumab (VDZ) is effective as an induction and maintenance treatment for Crohn's disease and ulcerative colitis, but, as observed with antitumour necrosis factor-α (anti-TNFα) agents, some patients are nonetheless experiencing loss of response.Objective The aim of this study was to investigate the impact of the pharmacokinetics of VDZ during induction on long-term treatment response. Patients and methods This study focused on a single cohort of 103 inflammatory bowel disease patients treated with VDZ. VDZ trough levels (TLs) were measured by enzyme-linked immunosorbent assay (n = 536 samples), and thereafter correlated to clinical, biological, endoscopic and serological data. For patients exposed previously to infliximab, antibodies to infliximab were measured at baseline. On the basis of the outcome at the end of follow-up, patients were then categorized into long-term response, optimized and treatment failure groups. Results During VDZ induction, at week 6, inflammatory bowel disease patients with long-term response had higher TLs compared with patients in the treatment failure group (33 vs. 24 µg/ml, P = 0.02). A cut-off TL of 28 µg/ml predicted a sustained response in the follow-up with an area under curve of 0.723 (95% confidence interval = 0.567-0.878, P = 0.02). Patients with mucosal healing in maintenance had higher TLs at week 6 (41.65 µg/ml) compared with patients with mild (26 µg/ml) or severe endoscopic activity (20.8 µg/ml), P = 0.009. Positive perinuclear antineutrophil cytoplasmic antibody serology was associated with lower TLs. Patients previously exposed to anti-TNFα had lower TLs than naive patients (22.5 vs. 36 µg/ml, P = 0.03) without any impact of detectable antibodies to infliximab. Finally, the presence of an immunomodulator at induction did not impact on VDZ TLs at induction. Conclusion We confirmed that a drug exposure-efficacy association was found early on at induction. This study emphasizes that previous exposure to anti-TNFα and positive perinuclear antineutrophil cytoplasmic antibody serology are important factors influencing VDZ TLs at induction. Eur J Gastroenterol Hepatol 31:478-485

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.