Identification of the optimal medical and surgical management for patients with perianal fistulising Crohn's disease.

AIM: The aim of our study was to assess the best medical and surgical approaches for perianal Crohn's disease (PCD) in order to identify an optimal combined medical and surgical treatment. METHODS: Medical records of all patients with PCD treated with TNFα antagonists in two referral centres between 1998 and 2018 were reviewed. Predictors of long-term outcomes were identified using a Cox proportional hazard model. RESULTS: A total of 200 patients were included. Fifty-three patients (26.5%) were treated with adalimumab and 147 (73.5%) with infliximab. A combination of TNFα antagonist with an immunosuppressant and the presence of proctitis were independently associated with fistula closure. Seton was placed in 127 patients (63.5%) before starting biological therapy. Eighty patients (40%) underwent additional perineal surgery. Prior PCD surgery, seton positioning, additional perineal surgery, and additional surgery within 52 weeks of anti-TNFα treatment were associated with an increased rate of fistula closure. Finally, medical combination therapy (anti-TNFα plus immunosuppressant) along with seton placement and additional surgery within 1 year was the best management for PCD patients (p = 0.02). CONCLUSION: Combined medical and surgical management is required for the treatment of PCD patients. Medical combination therapy associated with seton placement and additional surgery within 1 year is the best management for PCD patients.

Efficacy and Safety of Infliximab Retreatment in Crohn's Disease: A Multicentre, Prospective, Observational Cohort (REGAIN) Study from the GETAID.

INTRODUCTION: The objective of this study was to describe the efficacy and safety of infliximab (IFX) reintroduction in Crohn's disease (CD) after stopping for loss of response or intolerance. METHODS: We conducted a prospective multicenter observational cohort study including adult patients with clinically (CD Activity Index >150) and objectively active luminal CD in whom IFX was reintroduced after at least 6 months of discontinuation. The reasons for the initial discontinuation could be a secondary loss of response or IFX intolerance. The reintroduction schedule included 3 IFX infusions at weeks 0, 4, and 8, after a systematic premedication. The primary end point was the efficacy of IFX retreatment at week 26 defined by a CD Activity Index of <150 in the absence of IFX discontinuation or use of corticosteroids, surgery, or other biologic. RESULTS: At week 26, 24 patients (35%) among the 69 analyzed reached the primary end point. No significant difference was observed between rates of clinical remission at week 26 in patients with prior LOR (n = 48) and those with IFX intolerance (n = 21) (35% and 33%, P = 0.87, respectively). Thirty-two acute infusion reactions were recorded in 27 patients, leading to withdrawal of IFX in 20 patients. No pharmacokinetic characteristic at baseline but detection of positive anti-drug antibodies at week 4 was predictive of IFX failure or infusion reaction at week 26. DISCUSSION: In this first prospective cohort study, IFX retreatment was safe and effective in one-third of the patients with CD, regardless the reason of prior discontinuation. Early detection of anti-drug antibodies can predict subsequent IFX reintroduction failure and infusion reactions.

Biologic Therapy for Budesonide-refractory, -dependent or -intolerant Microscopic Colitis: a Multicentre Cohort Study from the GETAID.

BACKGROUND: Budesonide remains the backbone therapy for microscopic colitis [MC]; however, relapses are frequent, and some patients are intolerant or dependent. Anti-TNF therapy is increasingly used to treat these patients, but available evidence is still limited. The aim of this study was to evaluate the effectiveness and safety of anti-TNF therapy in MC patients failing budesonide. METHODS: In a multicentre retrospective cohort study, budesonide-refractory, -dependent, or -intolerant MC patients treated with anti-TNF agents were included. Clinical remission was defined as fewer than three bowel movements per day, and clinical response was defined as an improvement in stool frequency of at least 50%. RESULTS: Fourteen patients were included. Median age was 58.5 years, median disease duration was 25 months, and median follow-up was 29.5 months. Seven patients were treated with infliximab [IFX], and seven with adalimumab. Clinical remission without steroids at 12 weeks was reached in 5/14 [35.7%] patients; all of these received IFX. Clinical response at 12 and 52 weeks, was obtained in 9/14 [64.3%] and 7/14 [50%] patients, respectively. Five patients switched to another anti-TNF agent. When considering both first- and second-line anti-TNF therapies, 7 [50%] patients were in clinical remission at Week 52. Mild to moderate adverse events were reported in six ptients. Two patients were treated with vedolizumab, of whom one had clinical response; one patient treated with ustekinumab had no response. CONCLUSIONS: This is the first multicentre cohort study showing that half of patients treated with anti-TNF therapy for MC achieved clinical remission in case of budesonide failure.

Relationship between clinical remission of perianal fistulas in Crohn's disease and serum adalimumab concentrations: A multi-center cross-sectional study.

BACKGROUND: Crohn's disease (CD) is complicated by perianal fistulas in approximately 20% of patients. Achieving permanent fistula closure remains a challenge for physicians. An association between serum anti-tumor necrosis factor-α concentrations and clinical outcomes in patients with CD has been demonstrated; however, little information is available on serum adalimumab (ADA) concentrations and remission of perianal fistulas in such patients. AIM: To study the relationship between serum ADA concentrations and clinical remission of CD-associated perianal fistulas. METHODS: This cross-sectional study of patients with CD-associated perianal fistulas treated with ADA was performed at four French hospitals between December 2013 and March 2018. At the time of each serum ADA concentration measurement, we collected information about the patients and their fistulas. The primary study endpoint was clinical remission of fistulas defined as the absence of drainage (in accordance with Present's criteria), with a PDAI ≤ 4, absence of a seton and assessment of the overall evaluation as favorable by the proctologist at the relevant center. We also assessed fistula healing [defined as being in clinical and radiological (magnetic resonance imaging, MRI) remission] and adverse events. RESULTS: The study cohort comprised 34 patients who underwent 56 evaluations (patients had between one and four evaluations). Fifteen patients had clinical remissions (44%), four of whom had healed fistulas on MRI. Serum ADA concentrations were significantly higher at evaluations in which clinical remission was identified than at evaluations in which it was not [14 (10-16) vs 10 (2-15) µg/mL, P = 0.01]. Serum ADA concentrations were comparable at the times of evaluation of patients with and without healed fistulas [11 (7-14) vs 10 (4-16) µg/mL, P = 0.69]. The adverse event rate did not differ between different serum ADA concentrations. CONCLUSION: We found a significant association between high serum ADA concentrations and clinical remission of CD-associated perianal fistulas.

Real-life pilot study on the impact of the telemedicine platform EasyMICI-MaMICI® on quality of life and quality of care in patients with inflammatory bowel disease.

BACKGROUND: Telemedicine has shown promising results in the follow up of patients with inflammatory bowel disease. This study compared quality of life and disease activity in patients with inflammatory bowel disease monitored using a telemedicine platform versus standard care. METHODS: In this prospective multicenter study, patients with active inflammatory bowel disease were randomized to EasyMICI-MaMICI® telemedicine platform or standard care. The main objective was to assess the efficacy of the software platform, as measured by quality of life and quality of care. Secondary outcomes were changes in the use of healthcare resources, and patient satisfaction in the MaMICI group. RESULTS: Fifty-four patients were enrolled (November 2017-June 2018); 59.3% had Crohn's disease and 40.7% ulcerative colitis. Forty-two patients received biologics at inclusion. After 12 months, a significant improvement in quality of life was observed with MaMICI versus standard care, with mean (standard deviation) changes from baseline of 14.8 (11.8) vs 6.3 (9.7) in the SIBDQ scores and 18.5 (18.7) vs 2.4 (8.3) in the EuroQol 5 D-3L questionnaire scores (both p ≤ .02). Disease activity was similar in both treatment groups. Use of MaMICI slightly reduced healthcare utilization versus controls (mean gastroenterologist consultations 2.2 vs 4.1; p = .1308). Overall satisfaction with MaMICI was high (mean score 7/10), and 46.2% of remaining patients in the MaMICI group continued to use the platform until 12 months. CONCLUSION: Significant improvement in quality of life and overall satisfaction with this telemedicine platform, indicates that further evaluation of EasyMICI-MaMICI in larger numbers of patients with inflammatory bowel disease is warranted.

Crohn's Disease Only Visible on Small Bowel Capsule Endoscopy: A New Entity.

BACKGROUND AND AIMS: In rare cases, the diagnosis of Crohn's disease (CD) can only be achieved using small bowel capsule endoscopy (SBCE). We investigate the characteristics of patients with CD only visible on SBCE and assess their disease course. METHODS: Data of all adult patients with confirmed CD diagnosis based on SBCE with normal endoscopic and cross-sectional imaging findings were retrospectively collected in three tertiary-level hospitals from January 2014 to March 2020. RESULTS: Thirteen patients were included. Ten patients were females, and the mean age at diagnosis was 36 years. Ileum was mostly involved (85%), while duodenum and jejunum were affected in 23% and 38% of the cases, respectively. Nine patients had one segment involved, while four subjects had two or three segments affected. All patients had inflammatory behavior. First treatment consisted of steroids in all cases, and six patients were later treated with immunosuppressant or biologics. After a mean follow-up of 27.5 months, no change in disease behavior, hospitalization, or CD-related surgery was observed. CONCLUSIONS: CD only visible at SBCE is a rare condition with a more favorable disease course compared to general CD with a lower rate of complicated behavior, hospitalization, and surgery, despite a similar use of immunosuppressant or biologics.

Setting up a Virtual Calprotectin Clinic in Inflammatory Bowel Diseases: Literature Review and Nancy Experience.

Technological progress, including virtual clinics, web or smartphone-based applications, and assessment of fecal calprotectin (FC) at home has favored the implementation of treat to target strategies for patients with inflammatory bowel diseases (IBD). Although these innovations are promising and have been associated with a significant reduction in health costs, their application in clinical practice is limited. Here, we summarize the most recent literature on virtual clinics and available FC home tests. In addition, we report the experience of IBD patients monitored through the IBDoc® test at the Nancy University Hospital, focusing on usability testing and patient's satisfaction. This pilot experience shows that a virtual calprotectin clinic doubles adherence rate to FC in IBD patients. This finding is especially clinically relevant in the post-coronavirus disease 2019 (COVID-19) pandemic era, with an increasing use of e-health.

Incidence and Patterns of COVID-19 Among Inflammatory Bowel Disease Patients From the Nancy and Milan Cohorts.

The first cases of COVID-19 infection were reported in December, 2019, in Wuhan, China. Italy (in particular Lombardy) and France (in particular Northeast) have been gravely hit. Both physicians and inflammatory bowel disease (IBD) patients are deeply concerned that immunosuppressants or biologics may increase the risk of COVID-19 infection. IOIBD has put in place an international registry, SECURE-IBD, for tracking all the cases with IBDs infected by COVID-19 (SECURE-IBD registry: http://www.covidibd.org). It will describe the outcomes of infected patients and the association between IBD-related medications and these outcomes.

Vedolizumab for perianal Crohn's disease: a multicentre cohort study in 151 patients.

BACKGROUND: The management of Crohn's disease patients with perianal lesions and anti-TNF failure is challenging. AIMS: To assess the effectiveness of vedolizumab in perianal Crohn's disease and the predictors of success in a real-life cohort. METHODS: We conducted a nationwide multicentre cohort study in patients with perianal Crohn's disease who received vedolizumab. In patients with active perianal Crohn's disease, the success of vedolizumab was defined by clinical success (no draining fistula at clinical examination and no anal ulcers for primary lesions) at 6 months without medical or surgical treatment for perianal Crohn's disease. Logistic regression analyses were performed to identify predictors of success. In patients with inactive perianal Crohn's disease, recurrence was defined by the occurrence of lesions and/or the need for medical or surgical treatments. RESULTS: One hundred and fifty-one patients were included. Among them 102 patients had active perianal disease, 33 (32.4%) males, mean age 39.8 years, mean Crohn's disease duration 14.6 years; 101 (99%) had received at least one anti-TNF. The median follow-up time was 52 weeks. Sixty-eight per cent of patients discontinued therapy after a median time of 33 weeks. Vedolizumab success was reached in 23/102 (22.5%). Among patients with setons at initiation, 9/61(15%) had a successful removal. In multivariable analysis, factors associated with success were the number of prior biologic agents (≥3, odds ratio, OR: 0.20, 95% CI 0.04-0.98) and no antibiotics at initiation (OR: 4.76, 95% CI 1.25-18.19). In 49 patients with inactive perianal Crohn's disease, perianal disease recurred in 15/49 (30.6%), 11/49 (22.4%) needed dedicated treatments. Median time to recurrence was 22 weeks. CONCLUSIONS: We identified a low rate of success of vedolizumab in patients with active perianal Crohn's disease, and nearly one third of patients with inactive perianal Crohn's disease had perianal recurrence. Further evaluation is warranted in prospective studies.

Impact of a medical interview on the decision to switch from originator infliximab to its biosimilar in patients with inflammatory bowel disease.

BACKGROUND: To lighten the burden on health-care spending, switching from the infliximab originator to a biosimilar in patients with inflammatory bowel disease (IBD) is advocated. However, the uptake of biosimilars lacks initiatives aimed at educating patients. AIMS: To explore the impact of a gastroenterologist's interview on IBD patients' acceptance for switching from infliximab bio-originator Remicade® to its biosimilar CT-P13 Inflectra®. METHODS: After the interview of 138 included patients, 120 properly responded to a self-administered questionnaire to collect consent about the switch and relevant data. French national IBD patients' association (Association François Aupetit) provided an information sheet on biosimilars. RESULTS: 93 (67.0%) out of 138 and 82 (68.3%) out of 120 patients switched treatment. 114 (79.8%) had never heard about biosimilars. Paradoxically, having heard about biosimilars was associated with a poorer chance to switch (Odds Ratio OR [95% CI] = 0.13 [0.02-0.72]). On the contrary, the more satisfied about generics, the more patients accepted the switch (OR [95% CI] = 1.31 [1.01-1.69]). There were 1.47 (Relative Risk RR [95% CI] = 1.47 [1.07-2.01]) times more chance to agree to the switch if the interview modified the patient's opinion on biosimilars. CONCLUSION: This study confirms that an organized information provided to the patient is a contributive way to enhance patient's acceptance of biosimilars in IBD.

Vedolizumab Trough Levels and Histological Healing During Maintenance Therapy in Ulcerative Colitis.

BACKGROUND AND AIMS: Histological healing may be the ultimate therapeutic goal in ulcerative colitis [UC]. We investigated, for the first time, the association between vedolizumab trough levels and histological healing in UC. METHODS: This is a single-centre retrospective cohort study including all consecutive UC patients on vedolizumab maintenance therapy who had a histological evaluation blindly to clinical data and underwent therapeutic drug monitoring, between June 2014 and March 2018. Per-event analysis was performed. Histological healing was defined as a Nancy histological index ≤1. RESULTS: Thirty-five histological samples were analysed. Median [interquartile range] vedolizumab trough levels were higher in the group with histological healing (31.5 [25-49.1] µg/mL) compared with the group without histological healing (15 [9-26.6] µg/mL, p = 0.02). The higher vedolizumab trough level quartiles tended to be associated with greater rates of histological healing [p = 0.10]. A cut-off vedolizumab trough level of 25 µg/mL predicted histological healing with an accuracy of 74% and an area under the receiver operating curve of 0.62 [95% confidence interval 0.58-0.92, p = 0.004]. Bivariate analysis identified a vedolizumab trough level ≥25 µg/mL [p = 0.006], a partial Mayo score ≤1 [p = 0.008], C-reactive protein level <5 mg/L [p = 0.005] and a Mayo endoscopic subscore ≤1 [p = 0.0004] as factors associated with histological healing. CONCLUSIONS: Histological healing was associated with higher vedolizumab trough levels during maintenance therapy in UC. A vedolizumab trough level threshold of 25 µg/mL proved most optimal to predict histological healing according to the Nancy histological index. Confirmation of these data in larger, independent cohorts is needed.

Dose de-escalation to adalimumab 40 mg every three weeks in patients with inflammatory bowel disease-A multicenter, retrospective, observational study.

BACKGROUND: Data about the outcomes after adalimumab dose de-escalation in inflammatory bowel disease (IBD) are scarce. OBJECTIVES: To assess the outcomes after adalimumab dose de-escalation, and to identify potential factors associated with failure. METHODS: Retrospective, observational study including all IBD patients who had undergone adalimumab dose de-escalation to 40 mg every three weeks across seven GETAID centers, between June 2011 and September 2017. Failure of adalimumab dose de-escalation was defined as the need for treatment re-escalation, discontinuation of adalimumab, or clinical, biochemical and/or morphologic disease relapse. RESULTS: Fifty-six patients were identified (n = 46 Crohn's disease, n = 10 ulcerative colitis). Median (IQR) duration of follow-up after adalimumab dose de-escalation was 15.9 (7.9-30.6) months. Adalimumab dose de-escalation was a failure in 21/56 (37.5%) patients and successful in 35/56 (62.5%) patients. Median (IQR) time until failure was 8.9 (4.6-15.6) months. At multivariate analysis, inactive disease at magnetic resonance imaging and/or endoscopy in the year before adalimumab dose de-escalation decreased the risk of failure with a factor five (P = 0.02). CONCLUSIONS: Adalimumab dose de-escalation to 40 mg every three weeks is possible in almost two thirds of IBD patients. Objective morphologic signs of active disease should be ruled out before considering a de-escalation strategy with adalimumab.

Accuracy of Diffusion-weighted Magnetic Resonance Colonography in Assessing Mucosal Healing and the Treatment Response in Patients with Ulcerative Colitis.

BACKGROUND AND AIMS: Using sigmoidoscopy as the gold standard, we assessed the accuracy, and the responsiveness to change, of diffusion-weighted magnetic resonance colonography in ulcerative colitis, using the Nancy score. METHODS: A total of 29 ulcerative colitis patients, having undergone at least two diffusion-weighted magnetic resonance colonographies, were included. Disease activity was evaluated using the Mayo endoscopic subscore and the Nancy score. We determined the accuracy of the Nancy score in the diagnosis of mucosal healing. We also assessed its responsiveness to change in 17 patients with a Mayo endoscopic subscore of 2 or 3 at treatment initiation. RESULTS: A total Nancy score < 7 had a sensitivity of 0.75 and a specificity of 0.67 (area under the curve: 0.72; 95% confidence interval: [0.56-0.88]; p = 0.0063) in the diagnosis of mucosal healing. The total Nancy score was sensitive to change in ulcerative colitis [Guyatt's responsiveness index: 1.8; standardised effect size ratio: 1.36]. The Nancy score was reliable [intra-class correlation coefficient: 0.63; p = 0.01]. The mean Mayo endoscopic subscore and the mean Nancy score both fell significantly in patients who achieved mucosal healing (mean ± standard deviation [SD] Mayo endoscopic subscore: 2.4 ± 0.55 at baseline and 0.6 ± 0.55 at reassessment, p = 0.02; mean Nancy score: 18.2 ± 9.1 at baseline and 3 ± 1.6 at reassessment, p = 0.006). No significant changes in Nancy score were observed in active patients at reassessment. CONCLUSIONS: The Nancy score is a highly responsive, reliable tool for assessing treatment response in patients with ulcerative colitis. The Nancy score accurately detects mucosal healing.

Prevalence of Bowel Damage Assessed by Cross-Sectional Imaging in Early Crohn's Disease and its Impact on Disease Outcome.

BACKGROUND AND AIMS: Bowel damage in Crohn's disease [CD] is defined as the presence of intestinal strictures, fistulas or abscesses. Early disease may represent a window of opportunity for timely intervention. We evaluated disease activity and severity by the Lémann Index [LI] and the Magnetic Resonance Index of Activity [MaRIA] score, and their prognostic value in early CD. METHODS: All consecutive patients diagnosed with CD in two referral centres, assessed by magnetic resonance imaging or computerized tomography, were prospectively included. Disease activity and bowel damage in early CD, the correlation between the LI and the MaRIA score, and the value of cross-sectional imaging findings in predicting disease progression were assessed. Statistical analyses employed time-to-event methods. RESULTS: We included 142 consecutive CD patients. Median time from diagnosis to baseline imaging was 0.3 years; median follow-up time was 4.9 years. At diagnosis, 39.4% of CD patients had bowel damage. At multivariable analysis, bowel damage and the LI were independent prognostic factors for intestinal surgery (hazards ratio [HR]: 3.21 and 1.11, respectively, p<0.001), and of CD-related hospitalization during patient follow-up [HR: 1.88, p=0.002, and 1.08, p<0.001, respectively]. Disease activity as expressed by the MaRIA score did not predict the disease course. The correlation between the LI and MaRIA score was weak [rho: +0.32; p<0.001]. CONCLUSION: Four out of ten CD patients have bowel damage at the time of the first imaging study. The presence of bowel damage, and not the MaRIA score, in early CD is associated with a worse outcome, with increased risks of surgery and hospitalization.

Impact of immunosuppressive therapy on hepatitis B vaccination in inflammatory bowel diseases.

BACKGROUND AND AIMS: The vaccination rate against hepatitis B virus (HBV) is low in inflammatory bowel disease (IBD) patients. The Consensus from the European Crohn's and Colitis Organisation on opportunistic infections recommends testing all IBD patients for HBV at diagnosis and vaccinating all HBV-negative patients. We compared the efficacy of HBV vaccine between IBD patients and healthy controls and investigated the impact of immunosuppressive therapy on vaccine response in IBD patients. MATERIALS AND METHODS: IBD patients and healthy adult workers were vaccinated against HBV following a standard protocol (at 0, 1, and 6 months; Engerix B). The efficacy of vaccination was evaluated at 8 months by a titer of antibodies against hepatitis B surface antigen (anti-HBs). RESULTS: Among 164 participants (96 with IBD and 68 healthy workers), the level of anti-HBs was greater than 10 IU/l in 80.2 and 94.1% (P=0.0115) of IBD patients and healthy controls, respectively, and anti-HBs levels greater than 100 IU/l were seen in 45.8 versus 77.9% (P<0.0001) of IBD patients and healthy controls, respectively. The median level of anti-HBs was significantly higher in healthy controls (497.0±386.2) than in IBD patients (253.9±34.5) (P<0.0001). None of the baseline characteristics of IBD patients, including immunomodulators and antitumor necrosis factor therapy, influenced the vaccine response. In the multivariate analysis, ileal disease was the only factor associated with a lower response to the vaccine (odds ratio=3.2; 95% confidence interval=1.0-9.7; P=0.049). CONCLUSION: The response rate to HBV vaccination is significantly lower in IBD patients than in the general population. Immunosuppressive therapy for IBD did not influence the vaccine response.

Self-insertion of a nasogastric tube for home enteral nutrition: a pilot study.

BACKGROUND: Enteral tube feeding can be a source of discomfort and reluctance from patients. We evaluated for the first time the tolerability of self-insertion of a nasogastric (NG) tube for home enteral nutrition (EN). MATERIALS AND METHODS: All patients requiring enteral tube feeding for chronic diseases were enrolled in a therapeutic patient education (TPE) program at Nancy University Hospital. RESULTS: In our department, between November 2008 and August 2012, 66 patients received EN with an NG tube. Twenty-nine of 66 had self-insertion of the NG tube (median age, 44 years), 17 had an anatomical contraindication, and 20 were excluded because of cognitive disability or language barrier or refusal. Twenty-eight of 29 patients completed the TPE program. One patient died of pancreatic cancer in palliative care during the study. Median follow-up was 20 months (interquartile range [IQR], 4-31). Median gain weight was 3.1 kg (IQR, 1.8-6.0) (P = .0002). Median duration of self-insertion of the NG tube was 3 months (IQR, 2-5), and it was well tolerated by all 29 patients. Two patients described minor adverse events: abdominal pain and nausea for 1 patient and epistaxis leading to temporary discontinuation of EN for another patient. A group of 10 consecutive patients previously had a long-term NG tube for EN. If they had the choice between a self-inserted NG tube and a long-term NG tube, all 10 patients reported they would prefer to start again with the self-inserted NG tube. CONCLUSION: This pilot study suggests that self-insertion of an NG tube may be efficacious and well tolerated in patients receiving EN for chronic conditions.