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A response by L. Chouchan and colleagues to a letter to the editor about their study on the influence of age on thiopurine S-methyltransferase (TPMT) activity in inflammatory bowel disease (IBD) patients.

L'immunomonitoring des anticorps monoclonaux représente une aide pour la prise en charge des patients sous anti- Tumor Necrosis Factor-α , en particulier en gastro-entérologie. En revanche, pour les autres anticorps monoclonaux, dont le rituximab, pourtant utilisé depuis près de quinze ans en auto-immunité, les études évaluant l'intérêt de ce monitoring sont quasiment absentes. Ainsi, l'objectif de cette étude était de décrire les caractéristiques clinicobiologiques des patients pour lesquels un immunomonitoring du rituximab a été prescrit dans notre centre. Les données cliniques, biologiques et thérapeutiques disponibles pour les demandes d'immunomonitoring du rituximab (dosages de la rituximabémie et des anticorps antirituximab par une technique « sensible au médicament » LISA-TRACKER Duo Rituximab®) reçues depuis 2015 ont été analysées rétrospectivement. Les suspicions d'hypersensibilité et les non-réponses secondaires ont été incluses. Sur les 23 demandes reçues, 18 dossiers ont été inclus, impliquant plusieurs spécialités (néphrologie, hématologie, neurologie, rhumatologie, médecine interne), avec 10 suspicions d'hypersensibilité et 8 non-réponses secondaires. Les 6 patients dont la présentation clinique était évocatrice de maladie sérique, ainsi que la moitié des cas de non-réponse secondaire, étaient positifs pour les anticorps anti-rituximab. L'analyse des différentes situations cliniques présentées ici ayant conduit à une demande d'immunomonitoring du rituximab suggère que cet examen (en particulier la recherche d'anticorps antirituximab) serait intéressant en cas de suspicion de maladie sérique et/ou de non-réponse secondaire (notamment en l'absence de déplétion lymphocytaire B), et mériterait d'être étudié via des études prospectives de grande taille. Immune monitoring of monoclonal antibodies is a helpful tool in optimizing the management of patients treated with TNF blockers, especially in gastroenterology. In contrast, studies evaluating the interest of such monitoring are lacking for other monoclonal antibodies used in autoimmune diseases, including rituximab despite its widespread use in the field for almost 15 years. Hence, we conducted a study whose goal was to describe the clinical and biological characteristics of all patients who had a rituximab immune monitoring. All the clinical, biological and therapeutic data attached to the demands (from 2015 onwards) we received for immune monitoring of rituximab (measurements of rituximab serum levels and anti-rituximab antibodies using the drug-sensitive assay LISA-TRACKER Duo Rituximab®), were retrospectively reviewed. Suspected cases of hypersensitivity and secondary non-response were included. Several medical specialities (nephrology, haematology, neurology, rheumatology, internal medicine) were represented among the 18 records included in the study (out of 23 demands), 10 being suspected cases of hypersensitivity and 8 secondary non-responders. All 6 patients whose symptoms were consistent with the classical presentation of serum sickness, as well as half of the secondary non-responders, were positive for antirituximab antibodies. This detailed real world case study illustrates the potential benefits of rituximab immune monitoring (especially anti-rituximab antibodies) in autoimmune diseases, suggesting it could be helpful in suspected cases of serum sickness, as well as secondary non-response (B-cell non-depletion being an early red flag). Larger and disease-specific studies are warranted to support these findings. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article related to factors associated with relapse of inflammatory bowel disease (IBD) in the previous issue.

A letter to the editor is presented in response to the article which discusses the potential use of extracorporeal photopheresis (ECP) in the treatment for patients with steroid-dependent Crohn's disease (CD).

A letter to the editor is presented in response to the article "Acute appendicitis is characterized by local invasion with Fusobacterium nucleatum/ necrophorum" by A. Swidsinski , V. Loening-Baucke and Y. Dörffel in a 2011 issue.

A response by L. Chouchana and colleagues to a letter to the editor on their article "Review article: the benefits of pharmacogenetics for improving thiopurine therapy in inflammatory bowel disease" in the 2012 issue is presented.

A letter to the editor is presented regarding appendicectomy as a treatment for refractory ulcerative proctitis and its inverse relationship.

A letter to the editor is presented in response to the review article by Rosen et al. on the detection of the drug adalimumab in stools of patients with ulcerative colitis and Crohn's disease.

A letter to the editor is presented in response to the article "Letter: mucosal healing in ulcerative colitis-higher relevance than in Crohn's disease," by M. Barreiro-de Acosta and ZJ. ZP. Gisbert that was published in the 2013 issue is presented.

Background: Since our last publication of algorithms for the management of perianal fistulas in patients with Crohn's disease, researchers have proposed a treat to target strategy systematic combotherapy for anal lesions, and indications for stem cell injection. In the absence robust publications, the Société Nationale Française de Coloproctologie (French National Society of Coloproctology [SNFCP]) wished to establish a group consensus using the Delphi method. Methods: From October 2020 to January 2021, a scientific committee and panel of gastroenterologists and surgeons established answers which were submitted to the members of the SNFCP during a national conference in November 2020. Three questions were clarified and reformulated, and then submitted during a third and final round of consultation of members of the SNFCP. Results: The target was defined as being the response obtained in every domain (symptoms, physical and radiological evaluation) which could be considered satisfactory, without the need to intensify therapeutic management. By consensus, the time required for clinical evaluation of the efficacy of treatment was 6 months. A response on magnetic resonance imaging (MRI) should include the absence of a collection of 10 mm or more in size at 6 months, and a frank decrease or complete disappearance of hyperintensity in T1 and T2 sequences of the main tract at 12 months. Systematic association of an immunosuppressant with tumor necrosis factor inhibitors did not reach the consensus level for adalimumab (50%), but just did for infliximab (70%). The majority of the respondents considered failure of one, or even two lines of different biotherapies to be potential indications for injection of stem cells. Conclusions: These findings reinforce the importance of composite targets including MRI evaluation, and underscore the need for precise timing of evaluation. Combotherapy is only recommended with infliximab. Injection of stem cells is a second- or third-line option. [ABSTRACT FROM AUTHOR]

A response from the authors of the article "Addition of an immunomodulator can reverse antibody formation and loss of response in patients treated with adalimumab" published in a 2017 issue of the periodical is presented.

Background and Aims: Contrast-enhanced ultrasonography (CEUS) is a potential interesting method for assessing accurately Crohn's disease (CD) activity. We compared the value of intestinal ultrasonography (US) coupled with contrast agent injection with that of magnetic resonance enterography (MRE) in the assessment of small bowel CD activity using surgical histopathology analysis as reference. Methods: Seventeen clinically active CD patients (14 women, mean age 33 years) requiring an ileal or ileocolonic resection were prospectively enrolled. All performed a MRE and a US coupled with contrast agent injection (CEUS) less than 8 weeks prior to surgery. Various imaging qualitative and quantitative parameters were recorded and their respective performance to detect disease activity, disease extension and presence of complications was compared to surgical histopathological analysis. Results: The median wall thickness measured by US differed significantly between patients with non-severely active CD (n = 5) and those with severely active CD (n = 12) [7.0 mm, IQR (6.5–9.5) vs 10.0 mm, IQR (8.0–12.0), respectively; p = 0.03]. A non-significant trend was found with MRE with a median wall thickness in severe active CD of 10.0 mm, IQR (8.0–13.7) compared with 8.0 mm, IQR (7.5–10.5) in non-severely active CD (p = 0.07). The area under the ROC curve (AUROC) of the wall thickness assessed by US and MRE to identify patients with or without severely active CD on surgical specimens were 0.85, 95% CI (0.64–1.04), p = 0.03 and 0.80, 95% CI (0.56–1.01), p = 0.07, respectively. Among the parameters derived from the time-intensity curve during CEUS, time to peak and rise time were the two most accurate markers [AUROC = 0.88, 95% CI (0.70–1.04), p = 0.02 and 0.86, 95% CI (0.68–1.04), p = 0.03] to detect patients with severely active CD assessed on surgical specimens. Conclusion: The accuracy of intestinal CEUS is close to that of conventional US to detect disease activity. A thickened bowel and shortened time to peak and rise time were the most accurate to identify CD patients with severe histological disease activity. [ABSTRACT FROM AUTHOR]

Background Mucosal healing can be achieved with infliximab ( IFX). Aim To assess the impact of mucosal healing on long-term outcomes in patients with ulcerative colitis (UC) when treated with infliximab ( IFX) beyond 1 year. Methods All consecutive adult patients with refractory UC receiving maintenance treatment with IFX in five French referral centres were analysed retrospectively. Only patients who had endoscopic evaluation between 6 and 52 weeks following IFX initiation were included. According to their Mayo endoscopic sub-score, patients were categorised into mucosal healing (sub-score: 0-1) and no mucosal healing (2-3). Outcome measures were colectomy and IFX failure defined by drug withdrawal due to secondary failure among primary responders. Results Of the 63 patients (30 women; median age: 38 years), 30 (48%) achieved mucosal healing. The median follow-up duration was 27 (3-79) months. Colectomy-free survival rates at 12, 24 and 36 months were, respectively, 100%, 96% and 96% in patients with mucosal healing. The corresponding figures were, respectively, 80%, 65% and 65% in patients without mucosal healing ( P = 0.004). By multivariate analysis, mucosal healing was the only factor associated with colectomy-free survival, with an odds ratio of 18.01 (95% CI: 1.58-204.92). IFX failure-free survival rates at 12, 24 and 36 months were, respectively, 76%, 69% and 64% in patients with mucosal healing, and 44%, 25% and 21% in those without mucosal healing ( P = 0.003). Conclusion Patients with refractory UC who achieved mucosal healing after IFX initiation had better long-term outcomes, with significantly less colectomy and less IFX failure. [ABSTRACT FROM AUTHOR]

Background Although thiopurines are considered safe in humans, they are still pregnancy FDA category D drugs. Prevention of post-operative recurrence is a challenge in clinical practice in Crohn's disease. The European Crohn's and Colitis Organisation consensus states that thiopurines should be considered in high-risk patients. Aim To perform a worldwide survey for evaluating the extent to which gastroenterologists who are experts in the field of IBD are utilising thiopurines during pregnancy and in the post-operative setting in Crohn's disease. Methods This was a Web-based cross-sectional, statement-based survey, which was conducted among experts who have published at least once in the field of thiopurines in IBD. Results Between 20 December 2009 and 9 April 2010, 175 questionnaires were received. The median number of IBD patients per physician per year was 400 (IQR 25-75th, 188-600) and the total number of IBD patients followed by all responders was 82 379. In a pregnant woman with a history of severe Crohn's disease in clinical remission after 1 year on azathioprine, 89% of experts usually continue azathioprine until delivery and 9% of physicians never administrate azathioprine during pregnancy. After ileocecal resection for Crohn's disease, 39% of physicians initiate azathioprine only in highrisk patients, 28% of practitioners prescribe azathioprine according to endoscopic evaluation, 20% of gastroenterologists systematically initiate azathioprine and 13% have a different attitude. Conclusions Almost 9 of 10 physicians continue azathioprine throughout pregnancy. About 7 of 10 physicians prescribe azathioprine in the post-operative setting according to the European Crohn's and Colitis Organisation recommendations, whereas one-fifth of practitioners systematically initiate azathioprine after surgery. [ABSTRACT FROM AUTHOR]

Summary: Background: Long‐term outcome of ustekinumab in Crohn's disease (CD) has not been evaluated. Aim: To evaluate the long‐term efficacy and safety of ustekinumab and identify the predictive factors of ustekinumab failure‐free persistence in a cohort of anti‐TNF refractory CD patients. Methods: We performed a retrospective multicentre cohort study including all consecutive CD patients who began subcutaneous ustekinumab and presented a clinical response (defined as a significant improvement of CD‐related clinical symptoms assessed by the patient's physician leading to continued ustekinumab) during the first year of treatment. Primary outcome was treatment failure defined as withdrawal of treatment due to loss of response, intolerance or need for surgery. Results: Eighty‐eight of the 122 (72%) CD patients beginning ustekinumab from March 2011 to December 2014, responded to ustekinumab and were followed up until November 2016. Median time on ustekinumab was 26.6 (13.4‐34.4) months. Forty‐seven patients (54%) continued ustekinumab with a clinical response and 38 (43%) stopped treatment (32 for failure, five for remission and one for pregnancy). Endoscopic response was observed in 82% of patients with endoscopic evaluation and mucosal healing in 39%. Ustekinumab failure‐free persistence rates were 78% at 12 months, 66% at 24 months and 55% at 36 months. No predictive factor of ustekinumab failure‐free persistence was identified. One severe adverse event was observed (anal adenocarcinoma). Conclusion: In this cohort of refractory CD patients receiving long‐term ustekinumab therapy, more than 50% of patients continued ustekinumab treatment with no loss of response, intolerance or surgery and with a good safety profile. [ABSTRACT FROM AUTHOR]