Safety of Vedolizumab and Ustekinumab Compared With Anti-TNF in Pregnant Women With Inflammatory Bowel Disease.

BACKGROUND & AIMS: Limited data are available on the consequences of prenatal exposure to vedolizumab and ustekinumab. We aimed to compare the safety of vedolizumab and ustekinumab with that of anti-tumor necrosis factor (TNF) in pregnant women with inflammatory bowel diseases (IBD). METHODS: Using nationwide, comprehensive data of the EPI-MERES registry, we identified pregnancies in women with IBD in France, exposed to anti-TNF, vedolizumab, and ustekinumab between 2014 and 2021. We compared pregnancy outcomes and complications in the offspring according to treatment exposure during pregnancy. We applied a propensity score matching for maternal, IBD, and pregnancy characteristics. RESULTS: Three hundred ninety-eight pregnancies exposed to vedolizumab were compared with 1592 pregnancies exposed to anti-TNF; 464 pregnancies exposed to ustekinumab were compared with 1856 pregnancies exposed to anti-TNF. Overall, compared with anti-TNF, neither vedolizumab nor ustekinumab was associated with increased risks of abortion, caesarean section, stillbirth, preterm birth, serious infections, malignancies, or congenital abnormality in children. Women exposed to ustekinumab had an increased risk of small for gestational age births. CONCLUSIONS: Overall, the safety of vedolizumab and ustekinumab compared with anti-TNF use during pregnancy is reassuring. Further studies are needed to confirm these findings.

Long-term Outcome of Risankizumab in Crohn's Disease: a Real-world GETAID Study.

BACKGROUND & AIMS: The aim of this study was to assess the long-term effectiveness and safety of risankizumab maintenance treatment in a large real-world cohort of patients with Crohn's Disease (CD). METHODS: From May 2021 to August 2023, all consecutive patients with CD treated with risankizumab in 25 GETAID centers have been retrospectively included. The primary endpoint was steroid-free clinical remission (Harvey Bradshaw Index [HBI] <5) at 52 weeks. RESULTS: Of the 174 patients included, 99%, 93%, and 96% had been previously exposed to anti-TNF, vedolizumab, and ustekinumab, respectively. All patients had received ≥3 biologics, and 108 (62%) had previous intestinal resection. Median follow-up was 13.7 months (interquartile range, 10.0-18.1 months). The rates of steroid-free clinical remission and clinical remission at week 26 were 47% (72/152) and 52% (79/152), and 46% (58/125), and 48% (60/125) at week 52, respectively. Risankizumab persistence rates were 94%, 89%, and 79% at weeks 12, 26, and 52, respectively. At the end of follow-up, 45 (45/174; 26%) patients had discontinued risankizumab (loss of response, 42%; primary failure, 37%; intolerance, 13%). Thirty-six patients (36/174; 20.9%) were hospitalized, and 22 (22/174; 12.6%) required intestinal resection. Fifty-one patients (29%) had an adverse event, including 26 (15%) serious adverse events (CD flare, n = 17). One death (myocardial infarction) and one cancer (papillary thyroid carcinoma) were observed. CONCLUSION: This is the first real-life study to report long-term outcomes in patients with refractory CD treated with risankizumab. One-half of the patients achieved steroid-free clinical remission after 1 year, and the safety profile was consistent with the literature.

Food Processing and Risk of Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis.

BACKGROUND & AIMS: Several studies have been published on the association between food processing and risks of Crohn's disease (CD) and ulcerative colitis (UC), with some variability in results. We performed a systematic literature review and meta-analysis to study this association. METHODS: From PubMed, Medline, and Embase until October 2022, we identified cohort studies that studied the association between food processing and the risk of CD or UC. Risk of bias of the included studies was assessed by the Newcastle-Ottawa scale. We computed pooled hazard ratios (HRs) and 95% confidence intervals (CIs) using random-effects meta-analysis based on estimates and standard errors. RESULTS: A total of 1,068,425 participants were included (13,594,422 person-years) among 5 cohort studies published between 2020 and 2022. Four of the 5 included studies were scored as high quality. The average age of participants ranged from 43 to 56 years; 55%-83% were female. During follow-up, 916 participants developed CD, and 1934 developed UC. There was an increased risk for development of CD for participants with higher consumption of ultra-processed foods compared with those with lower consumption (HR, 1.71; 95% CI, 1.37-2.14; I2 = 0%) and a lower risk of CD for participants with higher consumption of unprocessed/minimally processed foods compared with those with lower consumption (HR, 0.71; 95% CI, 0.53-0.94; I2 = 11%). There was no association between risk of UC and ultra-processed foods (HR, 1.17; 95% CI, 0.86-1.61; I2 = 74%) or unprocessed/minimally processed foods (HR, 0.84; 95% CI, 0.68-1.02; I2 = 0%). CONCLUSIONS: Higher ultra-processed food and lower unprocessed/minimally processed food intakes are associated with higher risk of CD but not UC.

Food Processing and Risk of Crohn's Disease and Ulcerative Colitis: A European Prospective Cohort Study.

BACKGROUND & AIMS: Industrial foods have been associated with increased risks of several chronic conditions. We investigated the relationship between the degree of food processing and risks of Crohn's disease (CD) and ulcerative colitis (UC) in the European Prospective Investigation into Cancer and Nutrition cohort. METHODS: Analyses included 413,590 participants (68.6% women; mean baseline age, 51.7 y) from 8 European countries. Dietary data were collected at baseline from validated country-specific dietary questionnaires. Associations between proportions of unprocessed/minimally processed and ultraprocessed food intake and CD and UC risks were estimated using Cox models to obtain hazard ratios (HRs) and 95% CIs. Models were stratified by center, age, and sex, and adjusted for smoking status, body mass index, physical activity, energy intake, educational level, and alcohol consumption. RESULTS: During a mean follow-up period of 13.2 years, 179 incident cases of CD and 431 incident cases of UC were identified. The risk of CD was lower in people consuming high proportions of unprocessed/minimally processed foods (adjusted HR for the highest vs lowest quartile: 0.57; 95% CI, 0.35-0.93; P trend < .01), particularly fruits and vegetables (adjusted HRs, 0.54; 95% CI, 0.34-0.87 and 0.55; 95% CI, 0.34-0.91, respectively). There was no association between unprocessed/minimally processed food intake and the risk of UC. No association was detected between ultraprocessed food consumption and CD or UC risks. CONCLUSIONS: In the European Prospective Investigation into Cancer and Nutrition cohort, consumption of unprocessed/minimally processed foods was associated with a lower risk of CD. No association between UC risk and food processing was found.

Serious immune-related upper gastrointestinal toxicity of immune checkpoint inhibitors: a multicenter case series.

BACKGROUND: Immune checkpoint inhibitors (ICI) improve the prognosis of many cancers but cause immune-related adverse events (IrAEs). Limited data are available on upper gastrointestinal (UGI) IrAEs. We describe the clinical characteristics, prognosis, and efficacy of medical therapy in patients with UGI IrAEs. METHODS: This is a retrospective, multicenter cohort study of patients with UGI symptoms and moderate to severe endoscopic UGI lesions, occurring after ICI. Efficacy of induction medical therapy and at the most recent follow-up was assessed. RESULTS: Forty patients were included; of these, 34 (85%) received anti-PD(L)1, either alone (n = 24) or combined with anti CTLA-4 (n = 10). Eighteen patients (45%) had concomitant enterocolitis. All patients had severe endoscopic lesions (erosions, ulcerations, hemorrhage, or necrotic lesions). Three patients who received an inefficient initial medical treatment had a complicated course: One patient died of enterocolitis, one had a pneumomediastinum, and one developed an ulcerated stricture of the pylorus. Thirty-five patients (88%) were treated with corticosteroids; 28 patients (80%) responded, and 20 (57%) reached clinical remission. Eight patients were treated with infliximab, and six responded (75%). After a median follow-up of 11 months, 36 patients (90%) were in corticosteroid-free clinical remission for their UGI symptoms. Endoscopic lesions persisted in 68% of patients. CONCLUSIONS: ICI cause severe UGI IrAEs, which are associated with enterocolitis in approximately half of the patients. Most patients with UGI IrAEs respond to corticosteroids or infliximab. These data support the recommendation to treat these patients without delay and in the same way as those with enterocolitis.

WallFlex® and Evolution® Duodenal Stents Have Similar Efficacy but Different Safety for Malignant Gastric Outlet Obstruction.

BACKGROUND: The WallFlex® and Evolution® stents are the most widely used duodenal stents, but no study has compared them. AIMS: We aimed to compare the efficacy and safety of WallFlex® and Evolution® stents for malignant gastric outlet obstruction. METHODS: We included all consecutive patients who were treated for malignant gastric outlet obstruction with WallFlex® or Evolution® self-expandable metal uncovered duodenal stents between 2013 and 2020. Multivariable Cox models were performed to assess duodenal stent failure, as defined by gastric outlet obstruction necessitating another duodenal stent. RESULTS: We included 129 patients: 74 received a WallFlex® stent and 55 received an Evolution® stent. The non-failure rate was of 68% (95%CI 55-84) and 65% (95%CI 50-84) at 6 months and of 48% (95%CI 32-73) and 45% (95%CI 27-74) at 1 year, with the WallFlex® and Evolution® stents, respectively. The median time to duodenal stent failure was 10.5 months in the WallFlex® group and 9.3 months in the Evolution® group. The type of duodenal stent was not associated with duodenal stent failure (p logrank = 0.43, adjusted hazard ratio 1.55; 95%CI 0.77-3.14). The overall survival was similar between the two groups (p logrank = 0.92). Three patients had complications due to Evolution® stents; it consisted in dismantled stents that led to hemorrhage in one patient. CONCLUSIONS: WallFlex® and Evolution® duodenal stents had similar efficacy for malignant gastric outlet obstruction. There were more adverse events with Evolution® stents.

Benefits and Risks Associated With Continuation of Anti-Tumor Necrosis Factor After 24 Weeks of Pregnancy in Women With Inflammatory Bowel Disease : A Nationwide Emulation Trial.

BACKGROUND: Continuation of biologics for inflammatory disorders during pregnancy is still a difficult decision. Many women with inflammatory bowel diseases (IBDs) stop anti-tumor necrosis factor (anti-TNF) treatment after 24 weeks. OBJECTIVE: To evaluate the benefits and risks of anti-TNF continuation after 24 weeks of pregnancy for mothers with IBD and their offspring. DESIGN: Target trial emulation between 2010 and 2020. SETTING: Nationwide population-based study using the Système National des Données de Santé. PATIENTS: All pregnancies with birth exposed to anti-TNF between conception and 24 weeks of pregnancy in women with IBD. INTERVENTION: Continuation of anti-TNF after 24 weeks of pregnancy. MEASUREMENTS: Occurrence of maternal IBD relapse up to 6 months after pregnancy, adverse pregnancy outcomes, and serious infections in the offspring during the first 5 years of life was compared according to anti-TNF continuation after 24 weeks of pregnancy using inverse probability-weighted marginal models. RESULTS: A total of 5293 pregnancies were included; among them, anti-TNF treatment was discontinued before 24 weeks for 2890 and continued beyond 24 weeks for 2403. Continuation of anti-TNF was associated with decreased frequencies of maternal IBD relapse (35.8% vs. 39.0%; adjusted risk ratio [aRR], 0.93 [95% CI, 0.86 to 0.99]) and prematurity (7.6% vs. 8.9%; aRR, 0.82 [CI, 0.68 to 0.99]). No difference according to anti-TNF continuation was found regarding stillbirths (0.4% vs. 0.2%; aRR, 2.16 [CI, 0.64 to 7.81]), small weight for gestational age births (13.1% vs. 12.9%; aRR, 1.01 [CI, 0.88 to 1.17]), and serious infections in the offspring (54.2 vs. 50.2 per 1000 person-years; adjusted hazard ratio, 1.08 [CI, 0.94 to 1.25]). LIMITATION: Algorithms rather than clinical data were used to identify patients with IBD, pregnancies, and serious infections. CONCLUSION: Continuation of anti-TNF after 24 weeks of pregnancy appears beneficial regarding IBD activity and prematurity, while not affecting neonatal outcomes and serious infections in the offspring. PRIMARY FUNDING SOURCE: None.

Serious Infections in Children Born to Mothers With Inflammatory Bowel Disease With In Utero Exposure to Thiopurines and Anti-Tumor Necrosis Factor.

BACKGROUND & AIMS: We aimed to compare the risk of serious infections in children with in utero exposure to thiopurines and/or anti-tumor necrosis factor (TNF) born to mothers with inflammatory bowel disease (IBD). METHODS: Using the French national health database, which covers 99% of the French population (around 66,000,000 people), we identified live births among women with IBD in France between 2010 and 2018. The risks of serious infections in children during the first 5 years of life were compared according to treatment exposures during pregnancy using propensity score-weighted marginal Cox models. RESULTS: A total of 26,561 children were included: 3392 were exposed to thiopurine monotherapy, 3399 to anti-TNF monotherapy, 816 to combination therapy, and 18,954 were not exposed to any of these drugs. The risks of serious infections during the first year of life among children exposed to thiopurine monotherapy (adjusted hazard ratio [aHR], 0.94; 95% confidence interval [CI], 0.83-1.07) and anti-TNF monotherapy (aHR, 1.10; 95% CI, 0.95-1.27) were similar to those of unexposed children; a higher risk was observed in children exposed to combination therapy (aHR, 1.36; 95% CI, 1.04-1.79). The highest increased risks were observed for nervous system infections and viral infections. The risk of serious infections during the second to fifth years of life was not associated with IBD treatments. CONCLUSIONS: In children born to mothers with IBD, in utero exposure to thiopurine and anti-TNF monotherapies do not increase the risk of serious infections during the first 5 years of life. Combination therapy is associated with an increased risk of serious infections during the first year of life.

Comparative real-world effectiveness of vedolizumab and ustekinumab for patients with ulcerative colitis: a GETAID multicentre cohort study.

INTRODUCTION: There are currently no comparative data on the efficacy and safety of vedolizumab and ustekinumab in ulcerative colitis (UC) after anti-TNF therapy fails. METHODS: We retrieved the full datasets of two observational, multicentre, retrospective studies of patients with UC for whom anti-TNF therapy failed and the patients were then treated with either vedolizumab or ustekinumab. The outcomes included steroid-free clinical remission, clinical remission, treatment persistence, colectomy, hospitalization, and serious and infectious adverse events. Propensity scores weighted comparison was applied. RESULTS: In total, 121 patients were included in the vedolizumab group and 97 were included in the ustekinumab group. At week 14 and week 52, in the weighted cohort, no difference was found between vedolizumab and ustekinumab for steroid-free clinical remission (OR = 0.55 [0.21-1.41], p = .21 and 0.94 [0.40-2.22], p = .89, respectively). There was no difference between vedolizumab and ustekinumab for secondary outcomes such as clinical remission, hospitalization, UC-related surgery, treatment persistence and serious and infectious adverse events. CONCLUSION: In patients with UC for whom anti-TNF therapy failed, no difference was found between vedolizumab and ustekinumab after propensity scores weighted comparison. Further studies are required to determine predictive factors of the efficacy of both biological agents.

Colonoscopy in France during the COVID-19 pandemic.

PURPOSE: We hypothesized that the COVID-19 pandemic may have modified dispensing of colonoscopy preparations, a proxy for the number of colonoscopies performed. We therefore studied changes in dispensing of colonoscopy preparations during the pandemic in France. METHODS: Using the French national health data system, we identified colonoscopy preparations dispensed from 2018 to 2020. The expected 2020 dispensations were estimated from 2018 to 2019 dispensations. RESULTS: Dispensing of colonoscopy preparations decreased markedly during the eight weeks of national lockdown: 83,045 colonoscopy preparations were dispensed, i.e., 181,826 (68.6%) fewer than expected. After lockdown, dispensing of colonoscopy preparations gradually returned to expected numbers. Overall, this represents an estimated decrease of roughly 250,000 colonoscopy preparations during the six-month period following onset of the pandemic. This shortfall in the dispensing of colonoscopy preparations was of the same order of magnitude in people under or over 50 years of age, in men and women, and in those in the highest and the lowest quintiles of the deprivation index. CONCLUSION: In conclusion, roughly 250,000 fewer colonoscopy preparations were dispensed during the first six months of the COVID-19 pandemic in France. Deleterious consequences on morbidity and mortality related to gastroenterological diseases, such as colorectal cancer, are to be feared.

HSV-1 reactivation is associated with an increased risk of mortality and pneumonia in critically ill COVID-19 patients.

BACKGROUND: Data in the literature about HSV reactivation in COVID-19 patients are scarce, and the association between HSV-1 reactivation and mortality remains to be determined. Our objectives were to evaluate the impact of Herpes simplex virus (HSV) reactivation in patients with severe SARS-CoV-2 infections primarily on mortality, and secondarily on hospital-acquired pneumonia/ventilator-associated pneumonia (HAP/VAP) and intensive care unit-bloodstream infection (ICU-BSI). METHODS: We conducted an observational study using prospectively collected data and HSV-1 blood and respiratory samples from all critically ill COVID-19 patients in a large reference center who underwent HSV tests. Using multivariable Cox and cause-specific (cs) models, we investigated the association between HSV reactivation and mortality or healthcare-associated infections. RESULTS: Of the 153 COVID-19 patients admitted for ≥ 48 h from Feb-2020 to Feb-2021, 40/153 (26.1%) patients had confirmed HSV-1 reactivation (19/61 (31.1%) with HSV-positive respiratory samples, and 36/146 (24.7%) with HSV-positive blood samples. Day-60 mortality was higher in patients with HSV-1 reactivation (57.5%) versus without (33.6%, p = 0.001). After adjustment for mortality risk factors, HSV-1 reactivation was associated with an increased mortality risk (hazard risk [HR] 2.05; 95% CI 1.16-3.62; p = 0.01). HAP/VAP occurred in 67/153 (43.8%) and ICU-BSI in 42/153 (27.5%) patients. In patients with HSV-1 reactivation, multivariable cause-specific models showed an increased risk of HAP/VAP (csHR 2.38, 95% CI 1.06-5.39, p = 0.037), but not of ICU-BSI. CONCLUSIONS: HSV-1 reactivation in critically ill COVID-19 patients was associated with an increased risk of day-60 mortality and HAP/VAP.

Effectiveness and Safety of Reference Infliximab and Biosimilar in Crohn Disease: A French Equivalence Study.

Background: CT-P13 is a biosimilar of the reference product (RP) infliximab, with demonstrated efficacy and safety for some inflammatory arthritides. It was approved for the treatment of Crohn disease (CD) on that basis, without specific studies examining its effects in CD. Objective: To compare the effectiveness and safety of CT-P13 and RP in infliximab-naive patients with CD. Design: Comparative equivalence cohort study. Setting: Système National des Données de Santé (SNDS), a French nationwide health administrative database (1 March 2015 to 30 June 2017). Patients: 5050 infliximab-naive patients with CD who were older than 15 years, had started treatment with RP (n = 2551) or CT-P13 (n = 2499), and had no other indications for infliximab. Measurements: The primary outcome was a composite end point of death, CD-related surgery, all-cause hospitalization, and reimbursement of another biologic therapy. Equivalence was defined as a 95% CI of the hazard ratio (HR) of CT-P13 versus RP in a multivariable marginal Cox model situated within prespecified margins (0.80 to 1.25). Results: Overall, 1147 patients in the RP group and 952 patients in the CT-P13 group met the composite end point (including 838 and 719 hospitalizations, respectively). In multivariable analysis of the primary outcome, CT-P13 was equivalent to RP (HR, 0.92 [95% CI, 0.85 to 0.99]). No differences in safety outcomes were observed between the 2 groups: serious infections (HR, 0.82 [CI, 0.61 to 1.11]), tuberculosis (HR, 1.10 [CI, 0.36 to 3.34]), and solid or hematologic cancer (HR, 0.66 [CI, 0.33 to 1.32]). Limitation: The SNDS does not contain all relevant clinical data (for example, disease activity). Conclusion: This analysis of real-world data indicates that the effectiveness of CT-P13 is equivalent to that of RP for infliximab-naive patients with CD. No difference was observed for safety outcomes. Primary Funding Source: Caisse Nationale de l'Assurance Maladie.

Chronic gastrointestinal immune-related adverse events in patients exposed to immune checkpoint inhibitors.

BACKGROUND AND AIMS: Immune checkpoint inhibitors (ICI) cause acute gastrointestinal (GI) immune-related adverse events (IrAEs). We aimed to report and describe chronic GI IrAEs. METHODS: We included consecutive patients addressed to a single center between October 2010 and March 2022 for endoscopic and/or histological GI inflammation persisting at least six months after the last dose of ICI. RESULTS: Among a total of 178 patients addressed for GI IrAE, 14 met the inclusion criteria (8 %). The median follow-up was 13 months after discontinuation of ICI. The most common symptom was watery diarrhea (54 %). Ten (77 %) patients had colonic involvement and three patients (21 %) had ileal involvement. Ten patients (77 %) had inflammatory lesions, two patients (15 %) had fistulas and one patient had (8 %) a stricture. All patients had lymphoplasmacytic infiltrate and basal plasmacytosis, and seven (54 %) had crypt distortions. Nine patients (69 %) received medical therapy, including five patients treated with vedolizumab, two patients (15 %) underwent intestinal resection. At the last follow-up, seven of the 13 patients were receiving maintenance therapy. Endoscopic lesions persisted one year after discontinuing ICI in 4/6 patients, and two years after discontinuation in 3/4 patients. CONCLUSIONS: Chronic GI IrAEs exist after ICI use.

Risk of Gastrointestinal Perforation in Patients With Rheumatic Diseases Exposed to Janus Kinase Inhibitors Versus Adalimumab: A Nationwide Cohort Study.

OBJECTIVE: To compare the risk of gastrointestinal perforation (GIP), a rare but serious adverse event, in patients who a JAK inhibitor (JAKi; tofacitinib, baricitinib, upadacitinib, or filgotinib) versus adalimumab (tumor necrosis factor inhibitor) among a comprehensive real-world population of patients with rheumatic diseases. METHODS: We conducted a nationwide population-based cohort study of the French national health data system, the exposed group that received a JAKi and the comparison group adalimumab. We included all individuals with a rheumatic disease who had their first dispensation of these treatments from July 2017 to December 2021. The primary endpoint was the occurrence of GIP (end of follow-up May 2022). Weighted hazard ratios (wHRs) were estimated with the inverse probability of treatment weighting method to account for confounding factors. Concomitant administration of systemic glucocorticoids, nonsteroidal anti-inflammatory drugs, and proton-pump inhibitors were time-varying variables. RESULTS: The cohort included 39,758 patients: 12,335 and 27,423 in the groups that received a JAKi and adalimumab (mean age 58.2 and 47.3 years; female 76% and 58%; rheumatoid arthritis 85.3% and 27.3%, and psoriatic arthritis/axial spondyloarthritis 14.7% and 72.7%), respectively. During follow-up, 38 and 42 GIPs occurred in the groups that received a JAKi and adalimumab groups; incidence rates were 2.1 (95% confidence interval [CI] 1.5-2.8) and 1.1 (95% CI 0.8-1.5) per 1,000 person-years, respectively. Rates of GIP did not differ between the groups that received a JAKi and adalimumab: wHR 1.1 (95% CI 0.7-1.9; P = 0.65). Despite the lack of power in some subgroup analyses, results were consistent whatever the subgroup of a type of JAKi received or subgroup with a type of rheumatic disease. CONCLUSION: In this nationwide cohort study, the rates of GIPs did not differ between groups of patients who received JAKi and adalimumab treatment. These results need to be confirmed in other observational studies.

Targeted surgery combined with postoperative medical therapy for residual disease for severe and multifocal Crohn disease.

BACKGROUND: In patients with multifocal intestinal Crohn disease requiring surgery for complication or uncontrolled disease, resection of all the lesions may lead to diarrhea and malnutrition. METHODS: This is a single-center retrospective review of all patients undergoing targeted surgery for multifocal Crohn disease with at least one residual Crohn disease location left behind. The primary endpoint was the rate of insufficient control of residual Crohn disease lesions requiring redo-surgery targeting these lesions. The rate of clinical remission defined by Harvey-Bradshaw index <4 was studied over time. RESULTS: From January 2012 to August 2022, among 320 patients undergoing surgery for intestinal Crohn disease, 30 met all criteria. Before surgery, patients had received a mean of 3 medical treatment lines; 83% (n = 25) had a clinically active Crohn disease (Harvey-Bradshaw index ≥4). Surgery consisted in ileocolonic (n = 14;47%), small bowel (n = 5;17%) or colonic resection (n = 12;40%) and strictureplasty (n = 4;13%). Operative mortality was nil. Overall postoperative and severe morbidity rates were 15 of 30 (50%) and 3 of 30. Residual lesions were in the small bowel (n = 15;50%), the colon (n = 16;53%), and/or the rectum (n = 16;53%). Twenty-five patients (83%) had postoperative medical therapy. Median follow-up was 65. Six patients (20%) required reoperation for insufficient control of residual lesions at index surgery after a mean of 98 ± 8 months. The clinical remission rate increased from 17% before surgery to 59% at 6-12 months and 71% at 24 months. CONCLUSION: In patients with multifocal Crohn disease, surgery targeted to severe and complicated lesions combined with postoperative medical treatment is a safe and effective strategy.

Funding and conclusions of network meta-analyses on targeted therapies in inflammatory diseases: an overview.

OBJECTIVES: To explore the association between industry funding and network meta-analyses' (NMAs) conclusion, and the use in Clinical Practice Guidelines (CPGs) of NMAs. STUDY DESIGN AND SETTING: This was an overview of NMAs and CPGs. We searched PubMed/MEDLINE, Epistemonikos, and several guideline databases up to February 18th 2023. We included CPGs from the last 5 years and NMAs of randomized controlled trials that evaluated targeted therapies in immune-mediated inflammatory diseases. Data extraction and outcome assessments were done in duplicate by independent authors. RESULTS: We included 216 NMAs and 99 CPGs. 31% (67/216) were industry-funded. The proportion of industry-funded NMAs that cited one treatment as being best was 44% (25/57) compared to 26% (30/116) for nonindustry-funded (OR = 2.24 [1.15-4.39]; aOR = 1.76 [0.81-3.81]). The abstract's conclusion of 39/67 (58%) industry-funded and 69/149 (46%) nonindustry-funded NMAs were considered unsupported by the results (OR = 1.61 [0.90-2.89]; aOR = 1.40 [0.71-2.78]). All industry-funded NMAs that cited one treatment as best cited their own sponsored drug. 59/99 (60%) CPGs included at least one NMA, with 23/59 (39%) of them citing industry-funded NMAs. CONCLUSIONS: We did not find evidence that industry-funded NMAs were more likely to have unsupported conclusions or to cite only one treatment as being best in their conclusions compared to non-industry-funded NMAs. However, almost all industry-funded NMAs favored their own treatments. Even though 40% of the CPGs did not rely on NMA, over a third of those who did used industry-funded NMAs. Limitations include the possible misclassification due to undisclosed funding and potential confounders that have not been accounted for.

Dietary index based on the Food Standards Agency nutrient profiling system and risk of Crohn's disease and ulcerative colitis.

BACKGROUND: Nutri-score is now widely available in food packages in Europe. AIM: To study the overall nutritional quality of the diet in relation to risks of Crohn's disease (CD) and ulcerative colitis (UC), in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort METHODS: We collected dietary data at baseline from validated food frequency questionnaires. We used a dietary index based on the UK Food Standards Agency modified nutrient profiling system (FSAm-NPS-DI) underlying the Nutri-Score label, to measure the nutritional quality of the diet. We estimated the association between FSAm-NPS-DI score, and CD and UC risks using Cox models stratified by centre, sex and age; and adjusted for smoking status, BMI, physical activity, energy intake, educational level and alcohol intake. RESULTS: We included 394,255 participants (68.1% women; mean age at recruitment 52.1 years). After a mean follow-up of 13.6 years, there were 184 incident cases of CD and 459 incident cases of UC. Risk of CD was higher in those with a lower nutritional quality, that is higher FSAm-NPS-DI Score (fourth vs. first quartile: aHR: 2.04, 95% CI: 1.24-3.36; p-trend: <0.01). Among items of the FSAm-NPS-DI Score, low intakes of dietary fibre and fruits/vegetables/legumes/nuts were associated with higher risk of CD. Nutritional quality was not associated with risk of UC (fourth vs. first quartile of the FSAm-NPS-DI Score: aHR: 0.91, 95% CI: 0.69-1.21; p-trend: 0.76). CONCLUSIONS: A diet with low nutritional quality as measured by the FSAm-NPS-DI Score is associated with a higher risk of CD but not UC.

Severe colitis in patients with melanoma treated with BRAF/MEK inhibitors.

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.