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Summary: Background and Aims: Dual blockade of BRAF and MEK kinases is a standard of care for metastatic V600E/K BRAF mutant melanoma. This study reports the first systematic description of colitis due to BRAF and MEK inhibitors. Methods: We studied consecutive patients with melanoma, treated with BRAF and MEK inhibitors, who had colitis requiring hospitalisation. Electronic files were studied; endoscopic biopsies and colectomy specimens were read centrally. Results: Between January 2021 and March 2022, nine women and one man, aged 50–90 years, were studied. Nine patients received encorafenib and binimetinib; one patient received dabrafenib and trametinib. The main symptoms were diarrhoea, haematochezia, abdominal pain and intestinal obstruction. Blood tests showed anaemia, increased CRP and low serum albumin levels in most patients. All patients had ulcerations of the right colon with (2/10) or without (8/10) stenosis of the ileocecal valve, and 4/10 patients also had ulcerations distal to the right colon. Histopathological findings were suggestive of ischaemia and mild inflammation. Nine of the 10 patients discontinued BRAF/MEK inhibitors. Drugs were reintroduced in four patients, three of whom had a severe relapse of diarrhoea. Two patients required surgery and underwent intestinal resection. One patient died of enterocolitis. Conclusion: BRAF/MEK inhibitors can induce severe colitis characterised by ulcerations of the right colon. [ABSTRACT FROM AUTHOR]

Summary: Background: Data comparing tofacitinib and vedolizumab in ulcerative colitis (UC) are lacking. Aims: To compare the effectiveness of tofacitinib and vedolizumab in patients with UC who had prior exposure to anti‐TNF therapy Methods: In this multicentre study, we included consecutive patients with UC ≥18 years old with partial Mayo score >2 and prior anti‐TNF exposure, who started tofacitinib or vedolizumab between January 2019 and June 2021. Comparisons were performed using propensity score analyses (inverse probability of treatment weighting). Results: Overall, 126 and 178 patients received tofacitinib and vedolizumab, respectively. Intensified induction (vedolizumab infusion at week 10 or tofacitinib 10 mg b.d until week 16) was performed in 28.5% and 41.5% of patients, respectively. After propensity‐score analysis, corticosteroid‐free clinical remission (partial Mayo score ≤2) was achieved at week 16 in 45.1% and 40.2% of patients receiving tofacitinib and vedolizumab, respectively (aOR = 0.82 [0.35–1.91], p = 0.64). Endoscopic improvement (corticosteroid‐free clinical remission and endoscopic Mayo score ≤1) (aOR = 0.23[0.08–0.65], p = 0.0032) and histological healing (endoscopic improvement + Nancy histological index ≤1) (13.4% vs 3.2%, aOR = 0.21[0.05–0.91], p = 0.023) were higher at week 16 in patients treated with tofacitinib. No factor was predictive of tofacitinib effectiveness. At least one primary failure to a biologic (OR = 0.46[0.22–0.99], p = 0.049), partial Mayo score >6 (OR = 0.39[0.17–0.90], p = 0.029) and CRP level > 30 mg/L at baseline (OR = 0.08[0.01–0.85], p = 0.036) were associated with vedolizumab failure. Conclusion: Tofacitinib and vedolizumab are effective in UC after failure of anti‐TNF agents. However, tofacitinib seems more effective, especially in severe disease and primary failure to biologics. [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Kim et al papers. To view these articles, visit https://doi.org/10.1111/apt.17989 and https://doi.org/10.1111/apt.18045. [ABSTRACT FROM AUTHOR]

Summary: Background: Up to 25% of patients with ulcerative colitis (UC) will require hospitalization for severe flare. In patients hospitalised for severe flare, who previously experienced multiple drug failures, including steroids and anti‐TNF agents, new quick‐acting medical options are needed. Tofacitinib is effective in refractory UC and has a rapid onset of action. Aim: To evaluate effectiveness and safety of tofacitinib as rescue therapy in patients hospitalised for UC flare. Methods: We conducted an observational and multicentre study with both retrospective and prospective collections in 14 GETAID centres. The primary objective was to assess the survival without colectomy following tofacitinib initiation in patients hospitalised for a UC flare. We determined rates of clinical response, clinical remission, and steroid‐free clinical remission at week 6 and week 14 and safety. Results: Fifty‐five patients were included (49 with prior infliximab failure and 19 previously exposed to ciclosporin). With a median follow‐up of 6.5 months (interquartile range [IQR] [3‐12.3]), rate of colectomy‐free survival was estimated at 78.9% (95 CI [68.5‐90.9]) and 73.6% (95 CI [61.9‐87.3]) at 3 and 6 months, respectively. Rates of clinical response, clinical remission and steroid‐free clinical remission were 60%, 45.5% and 37.5% at week 6 and 41.8%, 34.5% and 32.7% at week 14. Regarding safety, no death was observed, three patients withdrew tofacitinib due to adverse events. Two herpes zoster infections occurred in patients aged over 60 years old. No venous thrombotic or major adverse cardiovascular events occurred. Conclusion: Tofacitinib appears as a promising option in patients hospitalised with a UC flare but needs further validation in controlled trials. [ABSTRACT FROM AUTHOR]

Summary: Background: The prevalence of inflammatory bowel diseases (IBD) is high in women of childbearing age. Achieving clinical remission from conception to delivery using current medications is a major issue in IBD. Aims: To assess maternal and neonatal complications and management of vedolizumab or ustekinumab) in pregnant women with IBD receiving these agents. Methods: We performed a retrospective cohort study among GETAID centres including women with IBD who received ustekinumab or vedolizumab during pregnancy or within the 2 months before conception and compared outcomes to women exposed to anti‐TNF treatment during pregnancy. Results: Seventy‐three pregnancies in 68 women with IBD were analysed: 29 on ustekinumab resulting in 26 (90%) live births, two (7%) spontaneous abortions and one (3%) elective termination; 44 on vedolizumab resulting in 38 (86%) live births, five (11%) spontaneous abortions and one (3%) medical interruption. The control group included 88 pregnancies exposed to anti‐TNF in 76 women with IBD. The median age at conception, the proportion of women who smoked or in clinical activity at conception was comparable between groups. Only the proportion of patients exposed to >2 anti‐TNF agents was significantly increased among the ustekinumab and vedolizumab groups compared to control group (22% and 10% vs 3%, P < 0.005). Rates of prematurity, spontaneous abortion, congenital malformations and maternal complications were comparable between groups. Conclusion: We report 73 pregnancies in patients receiving vedolizumab or ustekinumab without a negative signal on maternal or neonatal outcomes. Further prospective studies are needed on the outcomes of pregnancies with new biologic drugs. [ABSTRACT FROM AUTHOR]

Summary: Background: Abdominal or pelvic radiotherapy in inflammatory bowel disease (IBD) patients raises concerns regarding the risk of worsening of underlying disease. Aim: To assess the impact of radiotherapy on IBD course. Methods: A retrospective multicentre study including IBD patients exposed to abdominal or pelvic irradiation was conducted, retrieving IBD activity by semester (6‐month periods) before (from S‐4 to S‐1) and after (from S + 1 to S + 6) radiotherapy and IBD flare during follow‐up. Results: Sixty‐one patients (32 women, mean age 59 years), with 467 patient semesters of follow‐up, treated for digestive (n = 31), urinary tract (n = 23) and gynaecological cancers (n = 7) were included. Rates of IBD activity per semester were, respectively, 21% (95% CI: 16‐27) from S‐4 to S‐1; 12% (7‐19) from S + 1 to S + 3 (P = 0.15 vs S‐4 to S‐1) and 16% (10‐25) from S + 4 to S + 6 (P = 0.45 vs S‐4 to S‐1). With a median follow‐up of 156 weeks (interquartile range: 82‐365), rates of survival without IBD flare at 1 and 3 years after radiotherapy were 82.5% (73.2‐93.0) and 70.6% (58.8‐84.7). Moderate‐to‐severe acute radiotherapy‐induced gut toxicity and the absence of concomitant chemotherapy were independently associated with an increased risk of flare. Conclusion: Most patients with non‐active IBD can be safely treated with abdominal or pelvic radiotherapy. Patients having acute gut toxicity and those without concomitant chemotherapy should be more closely monitored in the post‐radiotherapy period. [ABSTRACT FROM AUTHOR]

LINKED CONTENT This article is linked to Taxonera et al and Taxonera & Alba papers. To view these articles, visit https://doi.org/10.1111/apt.15804 and https://doi.org/10.1111/apt.16055 [ABSTRACT FROM AUTHOR]

Summary: Background: Phase III trials have demonstrated the efficacy and safety of ustekinumab in moderate‐to‐severe ulcerative colitis (UC), but few real‐world data are currently available. Aim: To assess short‐term effectiveness and safety of ustekinumab in patients with UC. Methods: From January to September 2019, all patients with UC treated with ustekinumab in 20 French GETAID centres were retrospectively included. The primary outcome was steroid‐free clinical remission (partial Mayo Clinic score ≤2) at weeks 12‐16 without a rectal bleeding subscore >1. Results: Among the 103 patients included, 70% had been previously exposed to ≥2 anti‐TNF agents and 85% to vedolizumab. At weeks 12‐16, steroid‐free clinical remission and clinical remission rates were 35.0% and 39.8% respectively; the absence of rectal bleeding with normal stool frequency was noted in 19.4% of patients. Two patients discontinued ustekinumab before the week 12‐16 visit and underwent surgery. In multivariable analysis, a partial Mayo Clinic score >6 at inclusion (18.6% vs 46.7%, P = 0.003) and a history of both exposure to anti‐TNF and vedolizumab therapies (27.3% vs 80.0%, P = 0.001) were negatively associated with steroid‐free clinical remission at weeks 12‐16. Adverse events occurred in 7.8% of patients and serious adverse events in 3.9% of patients. Conclusion: In a cohort of highly refractory patients with UC with multiple prior drug failures, ustekinumab provided steroid‐free clinical remission in one‐third of cases at weeks 12‐16. Clinical severity and previous use of anti‐TNF and vedolizumab therapies were associated with ustekinumab failure at weeks 12‐16. [ABSTRACT FROM AUTHOR]

Summary: Background: A clinical decision support tool (CDST) has been validated for predicting treatment effectiveness of vedolizumab (VDZ) in Crohn's disease. Aim: To assess the utility of this CDST for predicting exposure‐efficacy and disease outcomes. Methods: Using data from three independent datasets (GEMINI, GETAID and VICTORY), we assessed clinical remission rates and measured VDZ exposure, rapidity of onset of action, response to dose optimisation and progression to surgery by CDST‐defined response groups (low, intermediate and high). Results: A linear relationship existed between CDST‐defined groups, measured VDZ exposure, rapidity of onset of action and efficacy in GEMINI through week 52 (P < 0.001 at all time points across three CDST‐defined groups). In GETAID, CDST predicted differences in clinical remission at week 14 (AUC = 0.68) and rapidity of onset of action (P = 0.04) between probability groups. The high‐probability patients did not benefit from shortening of infusion intervals, and differences in onset of action between the high‐intermediate and low‐probability groups within GETAID were no longer significant when including low‐probability patients who received a week 10 infusion. CDST predicted a twofold increase in surgery risk over 12 months of VDZ therapy among low‐ to intermediate‐probability vs high‐probability patients (adjusted HR 2.06, 95% CI 1.33‐3.21). Conclusions: We further extended the clinical utility of a previously validated VDZ CDST, which accurately predicts at baseline exposure‐efficacy relationships and rapidity of onset of action and could be used to help identify patients who would most benefit from interval shortening and those most likely to require surgery while on active therapy. [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Avni‐Biron et al papers. To view these articles, visit https://doi.org/10.1111/apt.17224 and https://doi.org/10.1111/apt.17282 [ABSTRACT FROM AUTHOR]

Summary: Background: Whether healthcare workers with inflammatory bowel disease (IBD) are at increased risk of severe infection due to daily pathogen exposure is controversial. Aim: To assess the risk of severe infection in healthcare workers with IBD in a large multicentre case‐control study. Methods: The study population comprised 482 healthcare workers with IBD from 17 centres who were matched for gender, age, disease subtype and year of diagnosis to 482 controls (non‐healthcare workers with IBD). The study period was between the date of diagnosis of IBD and June 2016. Severe infection was defined as any community‐acquired infection that required hospitalisation. Results: With a median follow‐up of 9.3 years, 139 severe infections were recorded among cases and controls, including 30 Clostridium difficile infections, 33 severe viral infections, nine tuberculosis infections, 21 community‐acquired pneumonia and 46 others. No difference was observed between healthcare workers and controls regarding the overall incidence rates of severe infection. An increased risk of tuberculosis was noted in healthcare workers. In multivariate analysis in the entire study population, severe infection was associated with current exposure to corticosteroids (OR = 3.05, 95% CI [2.06‐4.52], P < 0.001), immunosuppressants (OR = 1.98, 95% CI [1.38‐2.84], P < 0.001) and anti‐TNF agents (OR = 2.93, 95% CI [2.02‐4.27], P < 0.001) and reduced with Crohn's disease (OR = 0.63, 95% CI [0.43‐0.91], P = 0.01). Conclusions: Healthcare workers with IBD do not have an increased risk of severe infection compared with other patients with IBD, except for tuberculosis. Screening for tuberculosis exposure should be assessed in this high‐risk population when treated with anti‐TNF agents. [ABSTRACT FROM AUTHOR]

Background We recently showed that vedolizumab is effective in patients with Crohn's disease (CD) and ulcerative colitis (UC) with prior anti-TNF failure in a multicentre compassionate early-access programme before marketing authorisation was granted to vedolizumab. Aims To assess effectiveness and safety of vedolizumab at week 54 in patients UC and CD. Methods Between June and December 2014, 173 patients with Crohn's disease (CD) and 121 with ulcerative colitis (UC) were treated with vedolizumab induction therapy. Among those 294 patients, 272 completed the induction period and were evaluated at the week 14 visit (161 patients with CD and 111 with UC). Disease activity was assessed using the Harvey-Bradshaw Index for CD and the partial Mayo Clinic score for UC. The primary outcome was steroid-free clinical remission at week 54. Results At week 54, steroid-free clinical remission rates at week 54 were 27.2% and 40.5% in patients with CD and UC respectively. In addition, the sustained steroid-free clinical remission (from week 14 to week 54) rates were 8.1% and 19.0% respectively. No deaths were observed. Severe adverse events occurred in 17 (7.2%) patients, including six (2.5%) leading to vedolizumab discontinuation. Conclusion Vedolizumab is able to maintain steroid-free clinical remission in up to one-third of patients with UC and CD at week 54 with a reasonable safety profile. A significant number of patients experienced loss of response during the first year of treatment, particularly in patients with CD. [ABSTRACT FROM AUTHOR]