[Advances in the management of inflammatory bowel diseases]. / Nouveautés dans la prise en charge des maladies inflammatoires chroniques intestinales.

New therapeutic strategies and new molecules have been recently developed for the management of inflammatory bowel diseases. The treat-to-target strategy aims to define specific objectives based on the patient and the disease characteristics. A regular monitoring using biomarkers and imaging is required to assess the objectives' achievement. Better outcomes have been demonstrated with this approach compared to the standard of care guided by symptoms only. On top of anti-TNF, new biologics have been available for the last few years. Vedolizumab, an anti-integrine, and ustekinumab, an interleukine 12/23 inhibitor, have demonstrated their efficacy in ulcerative colitis and Crohn's disease with an excellent safety profile and a sustained efficacy over time. Small molecules like tofacitinib are available in ulcerative colitis. The delay of action of these oral molecules is short. The risk of infection is similar compared to anti-TNF. Thromboembolic events have been reported with a prolonged double dose in predisposed patients. Preferential JAK inhibitors will be shortly available with an expected better safety profile. The growing number of available molecules allows a more effective management of inflammatory bowel diseases by choosing the right treatment for the right patient.

: De nouvelles stratégies sont disponibles pour la prise en charge des maladies inflammatoires chroniques intestinales. Elles ont pour but de fixer des objectifs précis, parfois très ambitieux dans les cas les plus sévères, tout en surveillant de façon étroite les patients à l'aide de biomarqueurs ou d'imagerie. Cette stratégie a démontré une meilleure efficacité sur le moyen et le long terme qu'un traitement standard basé sur les symptômes. à côté des anti-TNF, de nouveaux biologiques comme le védolizumab, un anti-intégrine, ou l'ustékinumab, un inhibiteur des interleukines 12 et 23, sont disponibles, tous deux présentant un excellent profil de sécurité et une efficacité soutenue au fil du temps. Des petites molécules anti-JAK (Janus Kinase) comme le tofacitinib sont accessibles pour le traitement de la rectocolite ulcéro-hémorragique (RCUH). Il s'agit de traitements oraux présentant une efficacité rapide. Le risque infectieux est similaire à celui des anti-TNF. Des inhibiteurs préférentiels des JAK seront bientôt disponibles pour le traitement de la maladie de Crohn et de la RCUH, avec un meilleur profil de sécurité potentiel. Le choix thérapeutique devient de plus en plus large, mais aussi de plus en plus complexe. Il doit se baser sur le profil du patient et de la maladie et doit nécessiter un avis spécialisé dans les situations difficiles.

Comparative Risk of Incident Cancer in Patients with Inflammatory Bowel Disease with Prior Non-digestive Malignancy According to Immunomodulator: a Multicentre Cohort Study.

INTRODUCTION: Knowledge about the cancer risk when initiating a biologic in inflammatory bowel disease [IBD] patients with prior malignancy remains scarce, especially for vedolizumab. Our aim was to evaluate the rate of incident cancer in a cohort of IBD patients with prior non-digestive malignancy, according to the subsequent treatment given. METHODS: A multicentre retrospective study included consecutive IBD patients with prior non-digestive malignancy. Inclusion date corresponded to the diagnosis of index malignancy. Patients were categorized into different cohorts according to the first treatment [none, conventional immunosuppressant, anti-TNF, or vedolizumab] to which they were exposed after inclusion and before incident cancer [recurrent or new cancer]. RESULTS: Among the 538 patients {58% female; mean (standard deviation [SD]) age inclusion: 52 [15] years} analyzed, the most frequent malignancy was breast cancer [25%]. The first immunomodulator given after inclusion was a conventional immunosuppressant in 27% of patients, anti-TNF in 21%, or vedolizumab in 9%. With a median (interquartile range [IQR]) follow-up duration of 55 [23-100] months, 100 incident cancers were observed. Crude cancer incidence rates per 1000 person-years were 47.0 for patients receiving no immunomodulator, 36.6 in the anti-TNF cohort, and 33.6 in the vedolizumab cohort [p = 0.23]. Incident-cancer free survival rates were not different between patients receiving anti-TNF and those receiving vedolizumab [p = 0.56]. After adjustment, incidence rates were not different between patients receiving no immunomodulator, anti-TNF, or vedolizumab. CONCLUSIONS: In this large multicentre cohort study, there was no difference of cancer incidence in those IBD patients with prior non-digestive malignancy, treated with vedolizumab or anti-TNF.

How to Manage Inflammatory Bowel Disease Patients When They Withdraw Anti-Tumour Necrosis Factor [Anti-TNF] Due to Severe Anti-TNF-Induced Skin Lesions? A Multicentre Cohort Study.

BACKGROUND AND AIMS: Optimal management of patients with inflammatory bowel disease [IBD] after anti-tumour necrosis factor [TNF] discontinuation due to severe induced skin lesions is unclear. Our study aimed to describe dermatological and IBD evolution after anti-TNF discontinuation for this side effect. METHODS: We conducted a multicentre retrospective study including consecutive IBD patients who discontinued anti-TNF due to severe induced skin lesions. Our objectives were to determine factors associated with dermatological remission [complete disappearance of skin lesions] and with IBD relapse in patients with inactive disease at inclusion, notably the impact of an early switch to another biological agent within 3 months of anti-TNF discontinuation. RESULTS: Among the 181 patients [134 women, 160 Crohn's disease] included in the 13 participating centres, dermatological remission occurred in 110 [62%] patients with a median [interquartile range, IQR] interval of 8.0 [6.8-11.0] months. Scalp location was independently associated with less remission of skin lesions (hazard ratio [HR] = 0.64 [95% CI 0.43-0.94], p = 0.02) while early switch was independently associated with a higher probability of remission of skin lesions (HR = 1.64 [95% CI 1.1-2.5], p = 0.02). Among the 148 patients with inactive IBD at inclusion, disease relapse occurred in 75 [51%] patients with a median [IQR] interval of 26.0 [23.0-39.1] months. Survival rates without IBD relapse at 1 year were 85.8% [95% CI 77.5-94.9] in the early switch group and 59.3% [95% CI 48.9-71.9] in the other group [p < 0.01]. CONCLUSIONS: Early switch to a new biological is associated with a higher probability of healing of anti-TNF-induced skin lesions and significantly reduces the risk of IBD relapse.

[Clinical impact of small bowell capsule endoscopy in obscure gastrointestinal bleeding : retrospective single-center study]. / Impact clinique de la vidéocapsule endoscopique du grêle dans les saignements digestifs inexpliqués. Etude rétrospective monocentrique.

INTRODUCTION: The small-bowel capsule endoscopy (VCE) has been validated in the investigation of obscure gastrointestinal bleeding (OGIB). The aim of this study was to evaluate the clinical impact of VCE for OGIB in routine practice, in terms of subsequent management and the risk of rebleeding. METHODS: Our retrospective study analyzed the VCE at the CHU of Liège from March 2016 to December 2019 (cohort of 110 patients with OGIB). RESULTS: We found a diagnostic yield of 58 %, a change in therapeutic attitude in 39 % of patients and a recurrence rate of 22.5 % (out of 102 patients followed at 2 years). The rate of rebleeding was particularly low in patients with normal VCE and in those for whom a therapeutic modification was made. Finally, about 45 % of patients did not have any change in therapeutic attitude nor recurrence. CONCLUSION: VCE leads to a therapeutic modification in about 40 % of patients with a low risk of relapse. However, VCE could be avoided in some patients as evidenced by a subgroup representing 45 % of patients for whom there was no therapeutic modification nor recurrence.

introduction et but : La vidéocapsule endoscopique grêle (VCE) est validée dans l'exploration des saignements digestifs inexpliqués (OGIB). Le but de notre travail a été d'évaluer l'impact clinique de la réalisation d'une VCE pour OGIB en pratique courante, en termes de prise en charge ultérieure et de risque de récidive du saignement. Méthodes : Notre étude rétrospective a analysé les VCE réalisées au CHU de Liège de mars 2016 à décembre 2019. Résultats : Les VCE de 110 patients ont été rétrospectivement analysées. Nous avons observé un pouvoir diagnostique de 58 % et une modification d'attitude thérapeutique chez 39 % des patients. Le taux de récidive (pour les 102 patients dont le suivi était disponible à maximum 2 ans) était de 22,5 %. Le taux de récidive de saignement était particulièrement faible chez les patients avec VCE normale et chez ceux pour lesquels une modification thérapeutique a été faite. Enfin, environ 45 % des patients n'ont pas eu de modification de l'attitude thérapeutique ni de récidive. Conclusions : La VCE débouche sur une modification thérapeutique chez environ 40 % des patients avec, dans la foulée, un faible risque de récidive. Par contre, la VCE pourrait être évitée chez certains patients comme en témoigne un sous-groupe représentant 45 % des patients pour lesquels il n'y a eu ni modification thérapeutique ni rechute.

Ustekinumab in bio-naïve and bio-failure Crohn's disease patients: Results from a « real-life ¼ monocentric cohort.

BACKGROUND: The pivotal clinical trials have largely demonstrated the efficacy and safety of ustekinumab in Crohn's disease. Real-life cohorts published so far only include very few bio-naïve patients. This study assesses effectiveness and safety of ustekinumab in bio-naïve and bio-failure patients treated with ustekinumab in routine practice and look for predictors of response. METHODS: We performed a retrospective monocentric study. Initial response was assessed by maintenance therapy beyond week 16. Sustained response was assessed by the continuation or cessation of therapy over time for another reason than stopping in sustained remission. Treatment persistence was assessed by Kaplan Meier curves and predictors of treatment persistence were studied by univariate and multivariate Cox model. RESULTS: Out of 156 recorded patients, three patients were still in their induction phase at time of analysis and 5 patients were lost to follow-up, leaving 148 patients for clinical effectiveness analyses, including 35 bio-naïve when starting ustekinumab. A maintenance therapy was initiated in 79.7%. At one year, the probability to be still treated with ustekinumab was 73.8%. Treatment cessation increased with smoking in multivariate analysis. Previous biologic failure (as a whole), CRP and fecal calprotectin baseline levels did not influence initial response and treatment persistence. CONCLUSION: A large proportion of CD patients initially respond to ustekinumab and continue this treatment beyond one year. Treatment persistence is as high in bio-failure as in bio-naïve patients.

Effectiveness and persistence of Vedolizumab in patients with inflammatory bowel disease : results from the Belgian REal-LIfe study with VEdolizumab (Be-RELIVE).

BACKGROUND AND STUDY AIMS: Vedolizumab (VDZ) is a gutselective integrin inhibitor used to treat Crohn's disease (CD) and ulcerative colitis (UC). This retrospective study assessed effectiveness and treatment persistence of VDZ in a Belgian reallife cohort of CD and UC patients. PATIENTS AND METHODS: CD and UC patients from 15 Belgian centers, who started VDZ between 01/09/2015 and 31/06/2016 and attended ≥1 visit after the first VDZ infusion, were included. Data were collected before first infusion, at week (W)10, W14 (CD patients only), month (M)6 and last follow-up. Treatment response and remission rates (changes in disease activity scores) and treatment persistence (Kaplan-Meier analysis) were assessed. RESULTS: Of the 348 patients receiving at least one dose of VDZ, 325 (202 CD, 45 biologic-naïve; and 123 UC, 42 biologic-naïve) patients were included in data analyses. At M6, 87.6% (176/201) of CD and 86.1% (105/122) of UC patients were still on VDZ treatment, 75.6% (34/45) and 83.9% (26/31) achieved clinical response, and 66.7% (44/66) and 42.9% (15/35) were in remission. At M6 remission rates was significantly higher while response rates tended to be higher among biologic-naïve versus biologic-failure CD patients. CONCLUSIONS: VDZ offers an effective treatment option in real-life settings and treatment effectiveness appears higher in biologic-naïve versus biologic-failure CD patients. (Acta gastroenterol. belg., 2020, 83, 15-23).

[How I explore Crohn's disease by various imaging modalities]. / Comment j'explore la maladie de Crohn par imagerie.

Crohn's disease is a chronic inflammatory condition characterized by recurrent and/or chronic lesions, leading to cumulative structural bowel damage. It is established that the correlation between symptoms and intestinal lesions is weak. Therefore, monitoring by frequent cross-sectional imaging is proposed to assess the disease activity. There is no consensus about the preferred imaging option. Priority is given to non-radiating modalities, such as ultrasonography and MRI. Tomodensitometry will be reserved for emergency cases. Ultrasonography can be useful, in emergency as well as for the monitoring of lesions of known topography. Entero-MRI is henceforth considered the standard imaging technique for the diagnosis and follow-up of Crohn's disease. Its high contrast resolution allows an accurate assessment of disease activity, therapeutic efficacy, cumulative structural bowel damage and complications.

La maladie de Crohn est une maladie inflammatoire intestinale dont les manifestations récurrentes ou chroniques entraînent des dommages tissulaires cumulatifs. Il est avéré que la corrélation entre la symptomatologie clinique et les lésions intestinales est faible. Par conséquent, des examens d'imagerie fréquents sont nécessaires pour déterminer l'activité de la maladie. Il n'existe pas de consensus quant à l'utilisation de l'une ou l'autre technique. La priorité sera donnée à des examens peu irradiants comme l'échographie et l'IRM. La tomodensitométrie sera réservée aux situations d'urgence ou en cas de contre-indication à l'IRM. L'échographie est un outil à ne pas négliger, tant en urgence que pour le suivi de lésions de topographie connue. L'entéro-IRM est dorénavant l'examen de choix pour le diagnostic et le suivi de la maladie de Crohn. Son excellente résolution en contraste permet d'évaluer l'activité de la maladie, l'efficacité thérapeutique, les dommages tissulaires cumulés et la présence de complications.

Long-term evolution and predictive factors of mild inflammatory bowel disease.

BACKGROUND: Crohn's disease (CD) and ulcerative colitis (UC) are potentially progressive diseases. Few data are available on the prevalence and the factors associated with mild inflammatory bowel diseases (IBD). AIM: Our aim was to assess the natural history of mild CD and mild UC and to identify predictive factors of mild evolution over the long term. METHODS: Retrospective study of IBD patients registered in the database of the university hospital CHU of Liège, Belgium. Mild CD was defined as an inflammatory luminal disease (no stricture, abdominal or perianal fistulae) requiring no immunomodulator (IM), anti-TNF and no surgery. Mild UC was defined as no requirement for IM, anti-TNF and no colectomy. RESULTS: Four hundred and seventy-three CD and 189 UC were included (median follow-up: 13 and 11 years respectively). At 1 year, 147 patients had mild CD. At 5 years and the maximum follow-up, 56% and 13% patients still had mild CD, respectively. At 1 year, 142 patients had mild UC. At 5 years and the maximum follow-up, 72% and 44% still had a mild UC, respectively. Factors associated with long-term mild CD and UC were older age at diagnosis and absence of corticosteroids in the first year. In UC proctitis location was associated with mild UC. CONCLUSIONS: In this cohort, 90% of CD patients and 3/4 of UC with mild disease at 1 year lost their mild disease status over time. An old age at diagnosis was predictive of the persistence of a mild CD and UC.

Persisting signs of disease activity at Magnetic Resonance Enterocolonography predict clinical relapse and disease progression in quiescent Crohn's disease.

INTRODUCTION: Deep remission including clinical remission and tissue healing has been advocated as the therapeutic target in Crohn's disease. Yet, the definition of deep remission remains unclear. The aim of this study was to assess the persisting lesions at magnetic resonance enterocolonography (MREC) in clinically quiescent Crohn's disease as well as their relapse predictive value. METHODS: we performed a prospective monocentre cohort study. We included patients with clinical remission. At baseline, these patients had blood tests, the measurement of fecal calprotectin and underwent a MREC. They were then followed up clinically for a minimum of 1 year. A relapse was defined by a HBI > 4 with an increase of at least 3 points. Correlations between clinical, demographic, biological parameters and MREC signs were assessed as well as the time-to-relapse predictive value of the studied variables. RESULTS: Twenty seven patients were recruited. Fourteen out of 27 had persisting disease activity at MREC. MREC signs only partly correlated with biomarkers. Ten out of 27 patients relapsed over a median follow up of 25 months. In univariate analysis, relative contrast enhancement of the most affected segment (HR: 2.56; P = 0.046), ulcers (HR: 12.5; P = 0.039), fistulas (HR: 14.1; P = 0.009) and target sign (HR: 3.63; P = 0.049) were associated with relapse. In multivariate analysis, fistula was the only one. CONCLUSIONS: Half of the patients with clinically quiescent Crohn's disease had persisting signs of disease activity at MREC. These signs predicted time-to-relapse.

[FROM EVIDENCE-BASED MEDICINE TO PERSONALIZED MEDICINE IN CROHN'S DISEASE]. / DE L'"EVIDENCE-BASED MEDICINE" À LA MÉDECINE PERSONNALISÉE DANS LA MALADIE DE CROHN.

The therapeutic armamentarium in Crohn's disease includes mesalazine, steroids (including topical drugs), anti-metabolites (purines, methotrexate), anti-TNFα antibodies and, more recently, selective inhibitors of lymphocytes homing (vedolizumab). The efficacy of these drugs has been shown in pivotal phase 3 placebo-controlled trials and meta-analyses. However, the use of these drugs in routine practice still remains ill-defined. Those are rather the cohort studies, natural history data and therapeutic strategy trials that help the clinician to determine, for each individual patient, the treatment leading to an optimal benefit/risk profile, aiming at moving from evidence-based medicine towards personalized medicine.