Guillaume Savoye’s research while affiliated with Unité Inserm U1077 and other places

Background In industrialized countries, the incidence of inflammatory bowel disease (IBD) appears stabilized. This study examined the incidence and phenotype of IBD in Northern France over a 30-year period. Methods Including all IBD patients recorded in the EPIMAD population-based registry from 1988 to 2017 in Northern France, we described the incidence and clinical presentation of IBD according to age, sex and time. Findings A total of 22,879 incident IBD cases were documented (59% (n = 13,445) of Crohn’s disease (CD), 38% (n = 8803) of ulcerative colitis (UC), 3% (n = 631) of IBD unclassified (IBDU)). Over the study period, incidence of IBD, CD and UC was 12.7, 7.2 and 5.1 per 10⁵ person-years, respectively. The incidence of CD increased from 5.1/10⁵ in 1988–1990 to 7.9/10⁵ in 2015–2017 (annual percent change (APC): +1.9%, p < 0.0001). The incidence of UC increased from 4.5/10⁵ to 6.1/10⁵ (APC: +1.3%, p < 0.0001). The largest increase was observed in children (+4.3% in CD, p < 0.0001; +5.4% in UC, p < 0.0001) followed by young adults aged 17–39 years (+1.9% in CD, p < 0.0001; +1.5% in UC, p < 0.0001). The increase in UC incidence was significantly higher in women than in men (+1.9% in women, +0.8% in men; p = 0.006). We estimated that in our area, by 2030, nearly 0.6% of the population will have IBD. Interpretation The persistent increase of IBD incidence among children and young adults but also in women with UC in Northern France, suggests the persistence of substantial predisposing environmental factors. Funding Santé Publique France; INSERM; Amiens, Lille and Rouen University Hospitals.

Background Acute gastrointestinal bleeding (AGIB) is common in older patients but the use of iron in this context remains understudied. Aims This study aimed to evaluate prospectively the efficacy of ferric carboxymaltose to treat anaemia in older patients after AGIB. Methods This randomised double-blinded placebo-controlled clinical trial was conducted in 10 French centres. Eligible patients were 65 years or more, had controlled upper or lower gastrointestinal bleeding and a haemoglobin level of 9–11 g/dl. Patients were randomly assigned, in a 1:1 ratio, to receive either one intravenous iron injection of ferric carboxymaltose or one injection of saline solution. The primary endpoint was the difference in haemoglobin level between day 0 and day 42. Secondary endpoints were treatment-emergent adverse events, serious adverse events, rehospitalisation and improvement of quality of life (QOL) at day 180. Results From January 2013 to January 2017, 59 patients were included. The median age of patients was 81.9 [75.8, 87.3] years. At day 42, a significant difference in haemoglobin level increase was observed (2.49 g/dl in the ferric carboxymaltose group vs. 1.56 g/dl in the placebo group, P = 0.02). At day 180, QOL, measured on European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30, improved by 10.5 points in the ferric carboxymaltose group and by 8.2 points in the placebo group (P = 0.56). Rates of adverse events and rehospitalisation were similar in the two groups. Conclusions Intravenous iron seems safe and effective to treat anaemia in older patients after AGIB and should be considered as a standard-of-care treatment. ClinicalTrials.gov (NCT01690585).

Purpose Perianal fistulae are disabling complications of Crohn’s Disease. Magnetic resonance imaging features could predict treatment response. This study aimed to determine which magnetic resonance imaging features were predictive of long-term clinical outcome in real life. Methods Consecutive patients with magnetic resonance imaging performed in a tertiary center were retrospectively analyzed. Clinical outcome was defined as a need for surgical drainage of perianal fistulae or hospitalization. Clinical data and magnetic resonance imaging features (MAGNIFI-CD and Van Assche indices, degree of fibrosis) were studied. Results Fifty-two patients were included between 2016 and 2019 with a mean follow-up of 38 months [29;48]. A higher MAGNIFI-CD index (17/25 versus 11/25; p < 0.01) was associated with an unfavorable long-term clinical outcome. The MAGNIFI-CD index showed an area under the curve of 0.74 (p = 0.006) to predict the clinical outcome of perianal Crohn’s disease, compared to 0.67 (p < 0.05) for the Van Assche index. At a threshold of 13 for the MAGNIFI-CD index, sensitivity was 75% (CI95% [59%; 86%]) and specificity was 69% (CI95% [44%; 86%]). No association was found between the degree of fibrosis and clinical outcome, but the association of a high degree of fibrosis (≥ 80%) and of a low MAGNIFI-CD index (≤ 13) was predictive of clinical outcome (p < 0.01). Conclusion The MAGNIFI-CD index could be used to predict clinical outcome in perianal Crohn’s disease. In combination with a high degree of fibrosis, a low MAGNIFI-CD index, may help to identify patients with the best prognosis.

Background Infliximab (IFX) demonstrated its effectiveness in perianal CD (pCD) and represents the first-line medical treatment. A subcutaneous (SC) formulation has recently been developed, however so far it has not been specifically investigated in pCD. The aim of our study was to evaluate the effectiveness and safety of SC IFX in pCD. Methods We conducted a multicentre retrospective cohort study in the French GETAID, in patients with either active (group 1) or inactive (group 2) pCD who received SC IFX. Inclusion criteria were, for group 1: active pCD in the 6 months prior to initiation of SC IFX; and for group 2: inactive pCD for > 6 months at the time of IV to SC switch, but with a history of seton drainage. The primary endpoint in group 1 was clinical remission at 6 months (absence of anal ulcers, and absence of draining fistula). Univariate and multivariable logistic regression analyses were performed to identify predictors of clinical remission. In group 2, the primary endpoint was perianal clinical recurrence during follow-up. Results A total of 192 patients were included in 24 centres. Mean age was 38.9 years, 43.2% were women, 25.1% were smokers. 66 patients were included in group 1, 117 in group 2. In 9 patients, pCD had a > 6 months persistent activity on IV IFX when switched to SC. In group 1, median follow-up was 46 (26.6-64.6) weeks, 51/66(77.3%) patients received combination therapy, surgical drainage was performed in 40(60.6%) patients. One(1.5%), 1(1.5%), 32(48.5%), 20(30.3%) and 12(18.2%) patients received 0, 1, 2, 3 and ≥ 4 IV perfusions respectively before SC switch. At M6, 27/61(44.3%) patients were in clinical remission and 53/61(86.9%) in clinical response. MRI remission or response was achieved in 19/28(68%) patients. In univariate analysis, factors inversely associated with remission were BMI, previous pCD surgery, initial seton drainage, and SC dose optimization. In multivariable analysis, prior exposure to ≥1 biologic (OR 0.248;CI95% [0.071-0.861]p= 0.0243) was predictive of clinical remission. In group 2, median follow-up was 53.6(36.7-67) weeks. The pCD recurrence rate at 6 months was 3.1%. The recurrence-free survival curve is shown in Figure1. Overall, SC IFX was discontinued in 20(10.4%) patients, 8 switched back to IV. Two cases of immunization were observed. Median IFX serum concentration was > 20(17.1- > 20) µg/l. There were 16(8.3%) cases of adverse events related to pain/injection-site reaction: 4 switched back to IV, 1 stopped IFX. There were 5 cases of infection, no case of cancer. Conclusion Our results are in line with those reported in the literature on the effectiveness of IV IFX in pCD. The SC formulation appears to be effective and safe for active pCD, and for maintaining remission in inactive pCD

Background Inflammatory bowel disease (IBD) can be associated with various disorders, including dermatological, rheumatological, or psychiatric conditions. However, little is known about the incidence of these co-morbidities in paediatric-onset IBD at the population-based level. Methods All patients diagnosed with Crohn's disease (CD) or ulcerative colitis (UC) before the age of 17 between 1988 and 2011, and included in the EPIMAD population-based registry, were followed retrospectively until 2013. In this population, we collected information on comorbidities present at diagnosis, as well as events related to the development of a new chronic condition, hospitalization, or an infectious event of interest (as pneumopathy, meningitis, or pyelonephritis) reported in the medical records during the follow-up period. Results A total of 1,344 patients were included, comprising 1,007 (74.9%) with CD and 337 (25.1%) with UC. The median age at diagnosis was 14.3 years (IQR [11.7; 16.0]). During a median follow-up of 8.3 years ([4.3-13.9]), 361 (26.9%) patients exhibited at least one comorbidity. At diagnosis, 9.4% (95% CI [7.8% - 11.0%]) of patients had at least one comorbidity. The cumulative incidence of comorbidity was 13% (95% CI [11% - 14%]) at 1 year after diagnosis and 20% (95% CI [17% - 22%]) at 5 years. No association was found between the risk of comorbidity and the clinical characteristics at IBD diagnosis. However, the cumulative incidence of comorbidity was higher in the diagnosis period 2001-2011 than in the period 1988-1993 (HR=1.7 [1.2-2.2]; p<0.001). The most frequent comorbidities were infectious (5.6%), dermatological (5.5%), and pulmonary (5.3%) (Figure 1). The most common infectious events included bacteraemia, digestive tract infection with Clostridioides difficile, and viral infection with Herpesviridae or parvovirus B19, with a cumulative incidence during follow-up of 1.2%, 1.0%, and 0.9%, respectively. During follow-up, viral infections with HBV, HCV, or HIV were observed in 0.2% of patients, and pneumopathy was diagnosed in 0.7% of patients. Eczema and asthma were the predominant dermatological and pulmonary comorbidities, affecting 2.6% and 5.1% of patients, respectively. Conclusion In this paediatric-onset IBD population-based cohort, the most common comorbidities were infectious, dermatological, and pulmonary. Bacteraemia emerged as the most prevalent severe infectious event during follow-up, affecting 1.2% of patients.

Background The identification of colonic stricture in patients with Crohn's disease (CD) often leads to surgery due to concerns about associated neoplasia. Nevertheless, information regarding the neoplastic risk associated to colonic stricture is still limited. The objective of this study was to assess both the incidence of colonic stricture in pediatric-onset CD and the associated neoplastic risk at the population-based level. Methods All patients diagnosed with CD before age 17 between 1988 and 2011, and included in a population-based registry, were followed until 2013. Colonic stricture was defined as a narrowing of the digestive lumen observed on endoscopic or radiological examination. Excluded were stricture in the ileocaecal valve, anal canal, or low rectum. Univariate risk factors for colonic stricture were explored using Cox proportional hazards models with time-dependent variables, and a multivariable Cox model analysis was performed. Results A total of 1,007 patients diagnosed with CD between 1988 and 2011 were included. Median age at diagnosis was 14.5 years [IQR: 12.0-16.1]. Throughout the follow-up period (median follow-up, 8.8 years [4.6-14.2]), patients were predominantly exposed to 5-aminosalicylates (88.1%), immunosuppressants (70.6%), and biologics (47.9%). Colonic stricture was diagnosed in 52 patients, including 11 at CD diagnosis. The cumulative incidence of colonic stricture in CD was 2.9% [1.8%-4.0%] at 5 years. The overall incidence rate of colonic stricture in CD was 5.4 cases/1000 person-years, 95% CI [4.1-7.1]. In multivariable analysis, an increased risk of colonic stricture was observed during periods of active disease (HR = 2.62, [1.40-4.89], p<0.01). Conversely, the absence of colonic involvement at diagnosis (HR = 0.18, [0.04, 0.80], p<0.05) or treatment with aminosalicylates (HR = 0.39, [0.19-0.79], p<0.05) was associated with a lower risk of colonic stricture. After a median follow-up of 6.4 [2.4-12.7] years, colonic stricture surgical resection was performed in 29 patients (55.8%). Colon adenocarcinoma was detected in one patient (1.9%) within 6 months after the diagnosis of colonic stricture. Conclusion In this population-based study of pediatric-onset Crohn's disease, 52 patients (5%) experienced colonic stricture, with a 2.9% incidence rate observed after 5 years of follow-up. Additionally, one patient (2%) presented with an associated adenocarcinoma.

Background Several adalimumab preparations are now available on the market for patients with inflammatory bowel disease. Comparative satisfaction and tolerability are unknown. The aim of this study was to investigate inflammatory bowel disease patient satisfaction with approved adalimumab biosimilars and their originator. Methods In this cross-sectional study, we included 941 consecutive adalimumab-treated patients with inflammatory bowel disease across 45 centres affiliated with the GETAID who completed a satisfaction questionnaire comprising four items each rated by a 10 points-scale. The differences in responses were performed using one-way analysis of variance followed by Tukey's Honest Significant Difference test. Results The most commonly used drugs at inclusion were Humira® (436/941, 46.3%), Amgevita® (177/941, 18.8%), and Hulio® (105/941, 11.2%). Mean overall satisfaction rate with adalimumab was 8.5 [standard deviation 1.8]. Overall satisfaction was significantly higher in patients treated with Humira® (8.6 [1.5]), Hulio® (8.6 [1.8]) or Amgevita® (8.5 [1.4]) (p<0.05). Satisfaction with the subcutaneous injection form was higher for patients treated with Yuflyma® (9.0 [1.4]), Humira® (8.9 [1.3]) and Hulio® (8.9 [1.7]) (p<0.05). A total of 299 patients (31.8%) described injection site reactions. Two hundred twenty-three patients (23.7%) reported that they were previously treated with another adalimumab of which (32/223, 14.3%) discontinued treatment due to side effects. Conclusion In this real-world setting, patients with inflammatory bowel disease had a high level of satisfaction with adalimumab treatment, with some differences in terms of overall satisfaction and satisfaction with the injection device.