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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]

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. [ABSTRACT FROM AUTHOR]

Background Better patient knowledge on inflammatory bowel disease [IBD] could improve outcome and quality of life. The aim of this study was to assess if an education programme improves IBD patients' skills as regards their disease. Methods The GETAID group conducted a prospective multicentre randomised controlled study. IBD patients were included at diagnosis, or after a significant event in the disease course. Patients were randomised between 'educated' or control groups for 6 months. Education was performed by trained health care professionals. A psycho-pedagogic score [ECIPE] was evaluated by a 'blinded' physician at baseline and after 6 and 12 months [M6 and M12]. The primary endpoint was the increase of ECIPE score at M6 of more than 20%. Results A total of 263 patients were included in 19 centres (male:40%; median age:30.8; Crohn's disease [CD]:73%). Of these, 133 patients were randomised into the educated group and 130 into the control group. The median relative increase in ECIPE score at M6 was higher in the educated group as compared with the control group (16.7% [0–42.1%] vs 7% [0–18.8%], respectively, p = 0.0008). The primary endpoint was met in 46% vs 24% of the patients in the educated and control groups, respectively [ p = 0.0003]. A total of 92 patients met the primary endpoint. In multivariate analysis, predictors of an increase of at least 20% of the ECIPE score were randomisation in the educated group (odds ratio [OR] = 2.59) and no previous surgery [OR = 1.92]. Conclusions These findings support the set-up of education programmes in centres involved in the management of IBD patients. [ABSTRACT FROM AUTHOR]

Summary: Background: Data on combination‐biologic treatment in (IBD) are still scant. Aim: To explore outcomes of patients co‐exposed to anti‐TNF and vedolizumab. Methods: Patients starting vedolizumab having measurable anti‐TNF levels after recently stopping adalimumab/infliximab (‘VDZ‐aTNF’ group), were compared with control vedolizumab patients in a retrospective 1:2 matched case‐control study. Results: Seventy‐five patients were included (25 VDZ‐aTNF, 50 VDZ). Adverse events were experienced by 9/25 VDZ‐aTNF compared to 13/50 VDZ patients (P = 0.4, follow‐up 14 weeks in all). Week 14 clinical remission was attained in 10/25 (40%) of VDZ‐aTNF patients versus 23/50 (46%) of VDZ patients (OR = 0.8, 95% CI 0.3‐2.1, P = 0.6) and clinical response in 19/25 (76%) versus 39/50 (78%) respectively (OR = 0.9, 95% CI 0.3‐2.7, P = 0.8). Corticosteroid‐free remission and corticosteroid‐free response were experienced by 30% and 54%, respectively, of the entire cohort, and were similar between the two groups. Vedolizumab drug concentrations at week 2, 6 and 14 were similar among VDZ‐aTNF and VDZ patients (P > 0.5). Multi‐variable analysis showed independent association of some vedolizumab drug‐levels time‐points with baseline albumin and weight, but not with anti‐TNF co‐exposure. In a prospective study of a separate cohort of patients starting infliximab (n = 12), the percentage of α4β7+ memory T cells, slightly but nonsignificantly increased throughout weeks 0, 2 to 14 (26 ± 2.3%, 27.8 ± 2.9%, 29.5 ± 2.6% respectively, P = 0.06). Conclusions: Vedolizumab/anti‐TNF co‐exposure did not generate new safety signals during 14‐weeks induction, nor did it reduce efficacy or alter vedolizumab pharmacokinetics. These observations may aid the design of future co‐biologics trials and also suggest that a deliberate waiting‐interval between anti‐TNF cessation and subsequent vedolizumab initiation may not be warranted. [ABSTRACT FROM AUTHOR]

Summary: Background: The correlation between vedolizumab trough levels during induction therapy and mucosal healing remains unknown. Aim: To compare early vedolizumab trough levels in patients with and without mucosal healing within the first year after treatment initiation. Methods: We prospectively collected vedolizumab trough levels in all inflammatory bowel disease patients at weeks 2, 6 and 14 of vedolizumab treatment in three French referral centres between 1 June 2014 and 31 March 2017. Results of every patient that underwent mucosal assessment by magnetic resonance imaging and/or endoscopy in the first year after treatment initiation were analysed. Results: Median vedolizumab trough levels in the overall population (n = 82) were 27 μg/mL (interquartile range, IQR 21.2‐33.8 μg/mL) at week 2, 23 μg/mL (IQR 15‐34.5 μg/mL) at week 6 and 10.7 μg/mL (IQR 4.6‐20.4 μg/mL) at week 14. Only median vedolizumab trough levels at week 6 differed between patients with and without mucosal healing within the first year after treatment initiation (26.8 vs 15.1 μg/mL, P = 0.035). A cut‐off trough level of 18 μg/mL at week 6 predicted mucosal healing within the first year after the start of vedolizumab with an area under the receiver operating curve of 0.735 (95% confidence interval 0.531‐0.939). A vedolizumab trough level above 18 μg/mL at week 6 was the only independent variable associated with mucosal healing within the first year of treatment (odds ratio 15.7, 95% confidence interval 2.4‐173.0, P = 0.01). Conclusion: Early therapeutic drug monitoring might improve timely detection of vedolizumab‐treated patients in need for an intensified dosing regimen. [ABSTRACT FROM AUTHOR]

Background We recently showed that vedolizumab is effective in patients with Crohn's disease (CD) and ulcerative colitis (UC) with prior anti-TNF failure in a multicentre compassionate early-access programme before marketing authorisation was granted to vedolizumab. Aims To assess effectiveness and safety of vedolizumab at week 54 in patients UC and CD. Methods Between June and December 2014, 173 patients with Crohn's disease (CD) and 121 with ulcerative colitis (UC) were treated with vedolizumab induction therapy. Among those 294 patients, 272 completed the induction period and were evaluated at the week 14 visit (161 patients with CD and 111 with UC). Disease activity was assessed using the Harvey-Bradshaw Index for CD and the partial Mayo Clinic score for UC. The primary outcome was steroid-free clinical remission at week 54. Results At week 54, steroid-free clinical remission rates at week 54 were 27.2% and 40.5% in patients with CD and UC respectively. In addition, the sustained steroid-free clinical remission (from week 14 to week 54) rates were 8.1% and 19.0% respectively. No deaths were observed. Severe adverse events occurred in 17 (7.2%) patients, including six (2.5%) leading to vedolizumab discontinuation. Conclusion Vedolizumab is able to maintain steroid-free clinical remission in up to one-third of patients with UC and CD at week 54 with a reasonable safety profile. A significant number of patients experienced loss of response during the first year of treatment, particularly in patients with CD. [ABSTRACT FROM AUTHOR]

Background Infliximab ( IFX) combined with azathioprine ( AZA) is more effective than IFX monotherapy in inflammatory bowel disease ( IBD). Aim To identify the AZA optimal dose that is required for efficacy when receiving combination therapy. Methods Patients with IBD in durable remission on combination therapy were enrolled in a 1-year, open-label, prospective trial after randomisation into three groups: AZA steady (2-2.5 mg/kg/day, n=28) vs AZA down (dose was halved 1-1.25 mg/kg/day, n=27) vs AZA stopped (n=26). Primary endpoint was failure defined as occurrence of a clinical relapse and/or any change in IBD therapy. Results Eighty-one patients were included. Five (17.9%), 3 (11.1%), and 8 (30.8%) patients experienced failure at 1 year in groups AZA steady, AZA down and AZA stopped, respectively ( P=.1 across the groups). The median trough levels of IFX at inclusion were close to those measured at the end of follow-up in group AZA steady (3.65 vs 3.45 μg/ mL, P=.9) and in group AZA down (3.95 vs 3.60 μg/ mL, P=.5), whereas these levels dropped from 4.25 to 2.15 μg/ mL ( P=.02) in group AZA stopped. Four (14.3%), four (14.8%) and 11 (42.3%) patients experienced an unfavourable evolution of IFX pharmacokinetics in groups AZA steady, AZA down and AZA stopped, respectively. A threshold of 6- TGN <105 pmoles/8.108 RBC was associated with an unfavourable evolution of IFX pharmacokinetics. Conclusions Under combination therapy, AZA dose reduction, but not withdrawal, appears to be as effective as continuation of AZA at full dose. [ABSTRACT FROM AUTHOR]

Background: Ustekinumab is a fully human monoclonal antibody against the p40 subunit of interleukin (IL) 12 and 23 which is involved in the pathogenesis of several inflammatory diseases. Ustekinumab is approved for psoriasis and psoriatic arthritis treatment and has been successfully evaluated in phase II and III trials for patients with Crohn's disease (CD).Case Presentation: We report here the case of a patient who became pregnant during treatment with ustekinumab for a refractory CD and which ended in miscarriage.Conclusion: Ustekinumab is a relatively new pharmacotherapy and in addition to this clinical case, we reviewed the published literature concerning the use of this treatment during pregnancy and its consequences on pregnancy and fetus outcome. [ABSTRACT FROM AUTHOR]

Background: Antibodies to infliximab [ATI] and trough levels to infliximab [TRI] are associated with loss of response in inflammatory bowel diseases [IBD]. The best way to predict loss of response [LOR] to infliximab [IFX] is unknown. Methods: We conducted a prospective observational cohort study enrolling all IBD patients who were in clinical remission at Week 14 after IFX treatment initiation. TRI, ATI and C-reactive protein [CRP] level were measured at Week 22 [T1] and thereafter at every other IFX infusion. Loss of clinical response was defined by a flare requiring therapeutic change [IFX dose intensification, initiation of another drug class, and/or surgery]. Results: A total of 93 patients [59 Crohn's disease, mean duration of follow-up 17.2 months] were included; 32 patients [34.4%] lost clinical response during follow-up. Cumulative probability of LOR was 50% at 20 months. Mean TRI at T1 was significantly lower in IBD patients with stable ATI as compared with those with transient ATI or without ATI [0.052, 3.34,and 4.29 µg/ml, respectively; p = 0.001 between no ATI vs stable ATI, and p = 0.005 between stable and transient ATI] [p = 0.0001]. Three independent factors were predictive of LOR after Cox proportional hazards modelling: TRI > 5.5 µg/ml (hazard ratio [HR]: 0.21; 95% confidence interval [CI]: 0.05- 0.89;p = 0.034) at T1, CRP > 5mg/l [HR: 2.5; 95% CI: 1.16-5.26; p = 0.019] at T1, and stable ATI defined by two consecutive ATI > 20ng/ml [HR: 3.77; 95% CI: 1.45-10.0; p = 0.007]. Transient ATI did not influence LOR. Conclusions: LOR can be predicted based on a combination of CRP, TRI and stable ATI with a high degree of accuracy. [ABSTRACT FROM AUTHOR]

Background and Aims: The usefulness of anti-glycan antibodies alone or combined with anti-Saccharomyces cerevisiae [ASCA] or perinuclear antineutrophil cytoplasmic [pANCA] antibodies for diagnosis of inflammatory bowel disease [IBD], differentiation between Crohn's disease [CD] and ulcerative colitis [UC], disease stratification including IBD phenotype, and also for determination of the course of the disease, remain unclear. Methods: A large panel of serological anti-glycan carbohydrate antibodies, including antimannobioside IgG antibodies [AMCA], anti-chitobioside IgA [ACCA], anti-laminaribioside IgG antibodies [ALCA], anti-laminarin [anti-L] and anti-chitine [anti-C] were measured in the serum from a cohort of 195 patients with IBD] [107 CD and 88 UC]. The respective accuracy of isolated or combined markers for diagnosis, disease differentiation, stratification disease phenotype, and severity of the disease course, defined by a wide panel of criteria obtained from the past medical history, was assessed. Results: The positivity of at least one anti-glycan antibody was detected in a significant higher proportion of CD and UC compared with healthy controls [p < 0.0001 and p < 0.0007, respectively]. Whereas ASCA and ANCA antibody status had the highest efficacy to be associated with CD in comparison with UC (area under receiver operating characteristic curve [AUROC] = 0.70 for each], the adjunction of anti-laminarin antibody substantially improved the differentiation between CD and UC [AUROC = 0.77]. Titres of ACCA [> 51 U/ml] and anti-laminarin [> 31 U/ml] were significantly linked with a higher association with steroid dependency (odds ratio [OR] =2.0 [1.0-4.0], p = 0.03 and OR = 2.4 [1.1-5.2], p = 0.02, respectively]. We further defined the respective performance of anti-glycan antibodies to discriminate between patients with severe or not severe CD and UC course and determined the associated optimal cut-off values: severe CD course was significantly more likely in case of AMCA > 77 U/ml [OR = 4.3; p = 0.002], ASCA > 63 U/ ml [OR = 3.5; p < 0.009] and at a lesser degree ACCA > 50 U/ml [OR = 2.8; p < 0.02] and severe UC course was significantly associated with AMCA > 52 U/ml [OR = 3.4; p = 0.04] and ACCA > 25 U/ ml [OR = 3.0; p < 0.04]. Conclusions: Anti-glycan antibodies are valuable serological markers, especially AMCA antibodies that may help clinicians to promptly classify patients into high risk for severe disease. [ABSTRACT FROM AUTHOR]

Background and Aims: Long-term benefits of combination therapy (combotherapy) with infliximab (IFX) and azathioprine (AZA) have been less studied in ulcerative colitis (UC) than in Crohn's disease. The aim of the present study was to determine UC disease activity in patients who received at least 6 months of combotherapy, and whether cotreatment for more than 6 months was useful in these patients. Methods: A retrospective multicenter study was conducted in seven French academic centers from January 2010 to September 2012, including all UC patients having received at least 6 months of combotherapy in prolonged remission off steroids. During the follow-up period, which was divided into trimesters, scheduled IFX was continued as maintenance and AZA could be withdrawn. Assessment of UC activity by trimester was based on the following events: disease relapse defined by clinical relapse requiring a change of treatment, IFX failure, and colectomy. Results: Eighty-two patients were included (mean age 38 years; male:female ratio 1:1) and followed up for a median of 22.3 ± 14.0 months. Comparing 393 trimesters of combotherapy with 282 trimesters of IFX alone, fewer clinical relapses were observed with combotherapy (p = 0.049). Similar results were observed for IFX failure (p = 0.048). No difference was observed for colectomy. Duration of combotherapy longer than 9 months was inversely associated with clinical relapse (hazard ratio = 0.32 [95% confidence interval 0.15-0.70]). Conclusions: UC patients treated with combotherapy should maintain IFX and AZA for at least 9 months. Further studies are required to determine the optimal duration of combotherapy before stopping AZA in this situation. [ABSTRACT FROM AUTHOR]

The article discusses research on association of permanent antibodies against infiximab (ATI) with poor outcomes in inflammatory bowel disease (IBD) patients. Topics discussed include investigate the kinetics of antibodies against adalimumab (AAA) in IBD patients and its correlation with clinical outcomes, measurement of adalimumab level by enzyme-linked immunosorbent assay (ELISA), and characteristics of IBD patients.