Introduction The approved maintenance regimens for ustekinumab in Crohn’s disease (CD) are 90 mg every 8 or 12 weeks. Some patients will partially respond to ustekinumab or will experience a secondary loss of response. It remains poorly known if these patients may benefit from shortening the interval between injections Methods All patients with active CD, as defined by Harvey-Bradshaw score ≥ 4 and one objective sign of inflammation (CRP > 5 mg/L and/or fecal calprotectin > 250 µg/g and/or radiologic and/or endoscopic evidence of disease activity) who required ustekinumab dose escalation to 90mg every 4 weeks for loss of response or incomplete response to ustekinumab 90mg every 8 weeks were included in this retrospective multicenter cohort study. Results One hundred patients, with a median age of 35 years (Interquartile Range (IQR), 28 – 49) and median disease duration of 12 (7 – 20) years were included. Dose intensification was performed after a median of 5.0 (2.8 - 9.0) months of ustekinumab treatment and was associated with corticosteroids and immunosuppressants in respectively 29% and 27% of cases. Short-term clinical response and clinical remission were observed in respectively 61% and 31% after a median of 2.4 (1.3 - 3.0) months. After a median follow-up of 8.2 (5.6-12.4) months, 61% of patients were still treated with ustekinumab, and 26% in steroid-free clinical remission. Among the 39 patients with colonoscopy during follow-up, 14 achieved endoscopic remission (no ulcers). At the end of follow-up, 27% of patients were hospitalized, and 19% underwent intestinal resection surgery. Adverse events were reported in 12% of patients, including five serious adverse events. Conclusion In this multicenter study, two-thirds of patients recaptured response following treatment intensification with ustekinumab 90 mg every 4 weeks.

Cytomegalovirus (CMV) infects approximately 40% of adults in France and persists lifelong as a latent agent in different organs, including gut. A close relationship is observed between inflammation that favors viral expression and viral replication that exacerbates inflammation. In this context, CMV colitis may impact the prognosis of patients suffering from inflammatory bowel diseases (IBDs), and notably those with ulcerative colitis (UC). In UC, the mucosal inflammation and T helper cell (TH) 2 cytokines, together with immunomodulatory drugs used for controlling flare-ups, favor viral reactivation within the gut, which, in turn, increases mucosal inflammation, impairs corticoid and immunosuppressor efficacy (the probability of steroid resistance is multiplied by more than 20 in the case of CMV colitis), and enhances the risk for colectomy. This review emphasizes the virological tools that are recommended for exploring CMV colitis during inflammatory bowel diseases (IBD) and underlines the interest of using ganciclovir for treating flare-ups associated to CMV colitis in UC patients.

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Summary The new subcutaneous (sc) formulation of the infliximab (IFX) biosimilar CT‐P13 results in homogeneous serum trough concentrations of IFX at steady state. The present study aimed to investigate in Crohn’s disease (CD) patients the intra‐individual variations of IFX drug levels at multiple time‐points during 2 consecutive cycles of maintenance therapy with CT‐P13 sc. Patients and Methods CD patients in clinico‐biological remission under maintenance therapy with intravenous (iv) IFX/CT‐P13 were switched to CT‐P13 sc 8 weeks (W) after the last infusion. They were treated with CT‐P13 sc, 120 mg every 2 W. Assessments were performed from 8 W after starting CT‐P13 sc and patients had to attend 6 visits on 2 consecutive cycles of treatment (cycles A and B). Visits were scheduled on days 4–6 (visit 1), days 7–9 (visit 2) and day 14 (visit 3) of each cycle, where days 1 and 14 were the days of sc injection of CT‐P13. At each visit, peripheral blood was collected to measure serum IFX levels and anti‐drug antibodies. Results Twenty patients underwent 120 evaluations. Large intra‐individual variations of serum drug levels of IFX were observed. When pooling the 120 evaluations, the mean drug level was 11.3 ± 4.9 μg/ml, and the median drug level was 10.9 μg/ml (IQR 7.5–15.5). During each cycle, the median drug levels were similar between visits 1 and 2 as well as between visits 1 and 3 and between visits 2 and 3. In cycle A, median drug levels were 11.1 μg/ml (7.8–14.5), 12.0 μg/ml (7.2–16.1) and 11.0 μg/ml (7.5–15.1) at V1, V2 and V3, respectively. Similar results were obtained in cycle B, where median drug levels were 11.6 μg/ml (7.9–14.9), 11.4 μg/ml (8.1–15.2) and 10.9 μg/ml (7.9–15.6) at V1, V2 and V3, respectively. In univariate analysis, we failed to identify factors predictive of low drug levels. Conclusions IFX drug levels are quite stable within 14‐day treatment cycle, without trough levels in CD patients in remission during the maintenance therapy with CT‐P13 sc. In patients with inactive CD under maintenance therapy with CT‐P13 sc, therapeutic drug monitoring of IFX can be performed at any time between two CT‐P13 sc injections.

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Based on the evidence to date, proactive TDM cannot be recommended in daily practice. However, analysis is hampered by the low level of evidence for the cutoffs used and the need for point-of-care assays. Regarding economic issues and de-escalating strategies, proactive TDM may have several future indications in IBD. Exploratory studies on proactive TDM with newly available biologic agents in IBD are also awaited.

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