Comparative Efficacy of Subcutaneous and Intravenous Infliximab and Vedolizumab for Maintenance Treatment of TNF-naive Adult Patients with Inflammatory Bowel Disease: A Systematic Literature Review and Network Meta-analysis.

BACKGROUND: Infliximab and vedolizumab are widely used to treat Crohn's disease (CD) and ulcerative colitis (UC). AIMS: This systematic review and network meta-analysis evaluated comparative efficacy of various regimens for intravenous or subcutaneous infliximab and vedolizumab during maintenance treatment in CD and UC. METHODS: Parallel-group randomized controlled trials (RCTs) were identified by a systematic literature review (CRD42022383401) and included if they evaluated therapeutics of interest for maintenance treatment of adults with moderate-to-severe luminal CD or UC and assessed clinical remission between Weeks 30 and 60. Clinical remission rates in CD or UC and mucosal healing rates in UC were analyzed in a Bayesian network meta-analysis model. Endoscopic outcomes in CD were synthesized by proportional meta-analysis. RESULTS: Overall, 13 RCTs were included in the analyses. All vedolizumab studies randomized induction responders to maintenance treatment; infliximab studies used a treat-through design. Subcutaneous infliximab 120 mg every 2 weeks had the highest odds ratio (OR) [95% credible interval] versus placebo for clinical remission during the maintenance phase (CD: 5.90 [1.90-18.2]; UC: 5.45 [1.94-15.3]), with surface under the cumulative ranking curve (SUCRA) values of 0.91 and 0.82, respectively. For mucosal healing in UC, subcutaneous infliximab 120 mg every 2 weeks showed the highest OR (4.90 [1.63-14.1]), with SUCRA value of 0.73, followed by intravenous vedolizumab 300 mg every 4 weeks (SUCRA value, 0.70). Endoscopic outcomes in CD were better with subcutaneous infliximab 120 mg every 2 weeks than intravenous infliximab 5 mg/kg every 8 weeks. CONCLUSIONS: Subcutaneous infliximab showed a favorable efficacy profile for achieving clinical remission and endoscopic outcomes during maintenance treatment in CD or UC.

Ulcerative proctitis is a frequent location of paediatric-onset UC and not a minor disease: a population-based study.

OBJECTIVE: Natural history of paediatric-onset ulcerative proctitis (UP) is poorly described. Our aim was to describe the phenotype and disease course of incident UP in a population-based study of paediatric-onset UC. PATIENTS AND METHODS: All patients with UC diagnosed <17 years from 1988 to 2004, and followed during >2 years have been extracted from a population-based registry. UC location was defined according to the Paris classification. Cumulative risks for use of immunosuppressants (IS), anti-tumour necrosis factor alpha (TNF-α) therapy, colonic extension and colectomy were described using Kaplan-Meier method. Risk factors for colonic extension were assessed using Cox proportional hazards models. RESULTS: 158 patients with paediatric-onset UC (91 females) with a median age at diagnosis of 14.5 years (Q1: 11.4-Q3: 16.1) have been identified and followed during a median of 11.4 years (8.2-15.8). Among them, 25% had UP (E1) at diagnosis and 49% of them presented a colonic extension at maximal follow-up. In these children, the cumulative risk for colonic extension was 10% at 1 year, 45% at 5 years and 52% at 10 years. No parameter at diagnosis was associated with colonic extension in the UP (E1 group). IS use was significantly lower in patients with UP than in those with E2, E3 or E4 location (p=0.049). For the UP cohort, the cumulative risk for colectomy was 3% at 1 year, 10% at 5 years, 13% at 10 years and 13% at 15 years. Risks for colonic extension, treatment with anti-TNF-α and colectomy did not differ between the E1 group and the E2-E3-E4 group. CONCLUSIONS: UP is frequent in paediatric-onset UC and should not be considered as a minor disease. Compared with more extensive UC locations, risks for colonic extension, anti-TNF-α therapy and colectomy were similar in UP, whereas the risk for use of IM was lower.

IOIBD technical review on endoscopic indices for Crohn's disease clinical trials.

BACKGROUND: Crohn's disease (CD) is a chronic disabling and progressive IBD. Only strategies looking beyond symptoms and based on tight monitoring of objective signs of inflammation such as mucosal lesions may have the potential for disease modification. Endoscopic evaluation is currently the gold standard to assess mucosal lesions and has become a major therapeutic endpoint in clinical trials. Several endoscopic indices have been proposed to evaluate disease activity; unvalidated and arbitrary definitions have been used in clinical trials for defining endoscopic response and endoscopic remission in CD. METHODS: In these recommendations from the International Organization for the Study of Inflammatory Bowel Disease, we first reviewed all technical aspects of available endoscopic scoring systems in the literature. Second, in order to achieve consensus on endoscopic definitions of remission and response in trials, a two-round vote based on a Delphi method was performed among 14 specialists in the field of IBDs. RESULTS: At the end of the voting process, the investigators ranked first a >50% decrease in Simple Endoscopic Score for Crohn's Disease (SES-CD) or Crohn's Disease Endoscopic Index of Severity for the definition of endoscopic response, and an SES-CD 0-2 for the definition of endoscopic remission in CD. All experts agreed on a Rutgeerts' score i0-i1 for the definition of endoscopic remission after surgery.

Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE): Determining Therapeutic Goals for Treat-to-Target.

OBJECTIVES: The Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) program was initiated by the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD). It examined potential treatment targets for inflammatory bowel disease (IBD) to be used for a "treat-to-target" clinical management strategy using an evidence-based expert consensus process. METHODS: A Steering Committee of 28 IBD specialists developed recommendations based on a systematic literature review and expert opinion. Consensus was gained if ≥75% of participants scored the recommendation as 7-10 on a 10-point rating scale (where 10=agree completely). RESULTS: The group agreed upon 12 recommendations for ulcerative colitis (UC) and Crohn's disease (CD). The agreed target for UC was clinical/patient-reported outcome (PRO) remission (defined as resolution of rectal bleeding and diarrhea/altered bowel habit) and endoscopic remission (defined as a Mayo endoscopic subscore of 0-1). Histological remission was considered as an adjunctive goal. Clinical/PRO remission was also agreed upon as a target for CD and defined as resolution of abdominal pain and diarrhea/altered bowel habit; and endoscopic remission, defined as resolution of ulceration at ileocolonoscopy, or resolution of findings of inflammation on cross-sectional imaging in patients who cannot be adequately assessed with ileocolonoscopy. Biomarker remission (normal C-reactive protein (CRP) and calprotectin) was considered as an adjunctive target. CONCLUSIONS: Evidence- and consensus-based recommendations for selecting the goals for treat-to-target strategies in patients with IBD are made available. Prospective studies are needed to determine how these targets will change disease course and patients' quality of life.

Development of an algorithm incorporating pharmacokinetics of adalimumab in inflammatory bowel diseases.

OBJECTIVES: Several decision algorithms based on the measurement of infliximab (IFX) trough levels and antibodies to IFX have been proposed. Whether such algorithms can be extrapolated to the pharmacokinetics of adalimumab (ADA) has yet to be determined. METHODS: A prospective study included all consecutive patients with inflammatory bowel disease (IBD) having a disease flare while being on ADA 40 mg every 2 weeks were included. All patients were primary responders to ADA therapy and were anti-tumor necrosis factor (TNF) naive. ADA trough levels and antibodies against ADA (AAA) were measured blinded to clinical data (Elisa LISA-Tracker, Theradiag). All patients were optimized with ADA 40 mg weekly. Four months later, in the absence of clinical remission (CR; Crohn's disease activity index <150 for Crohn's disease (CD), and Mayo score <2 for ulcerative colitis), patients were treated with IFX therapy. Patients were divided into three groups based on ADA trough levels and based on previous studies: group A, ADA>4.9 µg/ml; group B, ADA<4.9 µg/ml and undetectable levels of AAA (<10 ng/ml); and group C, ADA<4.9 µg/ml and AAA >10 ng/ml. RESULTS: A total of 82 patients were included (55% CD; mean age=43 years, disease duration=7.4 years, duration of ADA therapy=17 months). After optimization of ADA treatment, 29.2% of patients achieved CR in group A (N=41), 67% in group B (N=24), and 12% in group C (N=17; P<0.01 between groups A/B and B/C). C-reactive protein level at the time of relapse, disease duration, duration of ADA therapy, and IBD type was not predictive of CR after ADA optimization by univariate analysis. The response to ADA optimization was significantly more durable in group B (15 months) than in groups A and C (4 and 5 months, respectively). Fifty-two patients who failed following ADA optimization (63%) were treated with IFX, and 30.6% of them achieved CR. CR rates following IFX initiation were 6.9%, 25%, and 80% in groups A, B, and C, respectively (P<0.01 between groups C/A and between groups C/B). Duration of response to IFX was significantly higher in group C than in groups A and B (14 vs. 3 and 5 months, respectively, P<0.01). CONCLUSIONS: The presence of low ADA trough levels without AAA is strongly predictive of clinical response in 67% of cases after ADA optimization. Conversely, low ADA levels with detectable AAA are associated with ADA failure, and switching to IFX should be considered. ADA trough levels >4.9 µg/ml are associated with failure of two anti-TNF agents (ADA and IFX) in 90% of cases, and switching to another drug class should be considered.

Risk of anti-TNF therapy on pregnancy, breastfeeding, live vaccines and related information in patients with inflammatory bowel disease: Real-world data from a nationwide study.

BACKGROUND: Anti-TNF are usually maintained during pregnancy in patients with inflammatory bowel disease (IBD) but safety is still a concern for them. AIMS: To provide data on management of anti-TNF agents during pregnancy, safety of live vaccines (BCG-MMR-rotavirus) and breastfeeding in newborns and dedicated information delivered to IBD women. METHODS: We performed an observational study in 25 centers from 2016 to 2018. We administered questionnaires to women with IBD receiving anti-TNF during pregnancy with newborn follow-up ≥ one year. RESULTS: Of 153 patients, 52 % maintained anti-TNF during the third trimester. Anti-TNF was shortly resumed in 79 % (58/73) after delivery. The rate of breastfeeding was 44 % (68/153) without any complication; 38 % of the mothers denied to breastfeed based on physician's advice. 26 % (34/129) of the newborns received live vaccines before 6 months-old (BCG:30 %; MMR:63 %; Rotavirus:8 %) and only 3 complications occurred (local BCGitis=1, fever=2). Information concerning anti-TNF during pregnancy/post-partum was delivered to 92 % of the patients, mainly by a gastroenterologist (97 %) who discussed with the obstetrician or the paediatrician in only 48 % and 25 %. CONCLUSION: In IBD patients, maintaining anti-TNF during pregnancy and breastfeeding is safe. Accidental live vaccines before 6 months did not lead to significant adverse events. The communication about these questions remains to improve.

The effect of immune therapy on surgical site infection following Crohn's Disease resection.

BACKGROUND: Patients with Crohn's disease are increasingly receiving antitumour necrosis factor α (anti-TNF-α) therapy. Whether anti-TNF-α therapy increases the risk of postoperative infectious complications in Crohn's disease is a matter of debate. METHODS: This was a retrospective study of three referral centres. The charts of patients who underwent ileocaecal or ileocolonic resection for Crohn's disease between 2000 and 2011 were reviewed. The impact of baseline characteristics and Crohn's disease-related medications on the risk of postoperative intra-abdominal infectious complications was investigated by univariable and multivariable analysis. RESULTS: A total of 217 patients were included in the study. Median age at the time of surgery was 36·8 (range 15-78) years. A postoperative intra-abdominal infection occurred in 24 (11·1 per cent) of 217 patients. No deaths were reported. On univariable analysis, age less than 25 years (P = 0·023), steroid use (P = 0·017), anti-TNF-α therapy (P = 0·043) and anti-TNF-α treatment in combination with steroids (P = 0·004) were associated with an increased risk of postoperative intra-abdominal infectious complications. On multivariable analysis, only anti-TNF-α therapy in combination with steroids significantly increased this risk (odds ratio 8·03, 95 per cent confidence interval 1·93 to 33·43; P = 0·035). CONCLUSION: Combined use of steroids and anti-TNF-α therapy was associated with an increased risk of postoperative intra-abdominal infectious complications.

ECCO Position on Harmonisation of Crohn's Disease Mucosal Histopathology.

In inflammatory bowel disease [IBD], mucosal healing is a major therapeutic target and a reliable predictor of clinical course. However, endoscopic mucosal healing is not synonymous with histological healing, and the additional benefits of including histological remission as a target are unclear. In Crohn´s disease [CD], there are few studies highlighting the value of histological remission as a therapeutic target. Histological activity can persist in CD patients who are in endoscopic remission, and the absence of histological activity may be associated with lower relapse rates. Therefore, standardisation of procedures to evaluate CD histological activity is desirable. Topics that would benefit from standardisation and harmonisation include biopsy procedures, biopsy processing techniques, the content of histological scores, and the definitions of histological remission, histological response, and histological activity. In line with these needs, the European Crohn's and Colitis Organisation [ECCO] assembled a consensus group with the objective of developing position statements on CD histology based on published evidence and expert consensus. There was agreement that definitions of histological remission should include absence of erosion, ulceration, and mucosal neutrophils; that the absence of neutrophilic inflammation is an appropriate histological target in CD; that CD histological scores, such as the Global Histological Disease Activity Score, lack formal validation; and that histological scoring systems for ulcerative colitis, including the Geboes Score, Robarts Histopathology Index, and Nancy Histological Index, can be used for scoring intestinal biopsies in CD patients.

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.

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.

Successive treatment with cyclosporine and infliximab in steroid-refractory ulcerative colitis.

OBJECTIVES: Rescue therapy with either cyclosporine (CYS) or infliximab (IFX) is an effective option in patients with intravenous steroid-refractory attacks of ulcerative colitis (UC). In patients who fail, colectomy is usually recommended, but a second-line rescue therapy with IFX or CYS is an alternative. The aims of this study were to investigate the efficacy and tolerance of IFX and CYS as a second-line rescue therapy in steroid-refractory UC or indeterminate colitis (IC) unsuccessfully treated with CYS or IFX. METHODS: This was a retrospective survey of patients seen during the period 2000-2008 in the GETAID centers. Inclusion criteria included a delay of <1 month between CYS withdrawal (when used first) and IFX, or a delay of <2 months between IFX (when used first) and CYS, and a follow-up of at least 3 months after inclusion. Time-to-colectomy, clinical response, and occurrence of serious adverse events were analyzed. RESULTS: A total of 86 patients (median age 34 years; 49 males; 71 UC and 15 IC) were successively treated with CYS and IFX. The median (± s.e.) follow-up time was 22.6 (7.0) months. During the study period, 49 patients failed to respond to the second-line rescue therapy and underwent a colectomy. The probability of colectomy-free survival (± s.e.) was 61.3 ± 5.3% at 3 months and 41.3 ± 5.6 % at 12 months. A case of fatal pulmonary embolism occurred at 1 day after surgery in a 45-year-old man. Also, nine infectious complications were observed during the second-line rescue therapy. CONCLUSIONS: In patients with intravenous steroid-refractory UC and who fail to respond to CYS or IFX, a second-line rescue therapy may be effective in carefully selected patients, avoiding colectomy within 2 months in two-thirds of them. The risk/benefit ratio should still be considered individually.

Defining and Assessing the Reproducibility of Crohn's Disease Endoscopic Lesions: A Delphi-like Method from the GETAID.

BACKGROUND AND AIMS: Defining and assessing the reproducibility of Crohn's disease [CD] endoscopic lesions is essential in assessing endoscopic healing. METHODS: Twelve endoscopic CD experts from the GETAID defined aphthoid erosions [AE], superficial ulcerations [SU], deep ulcerations [DU], stenosis, and fistulas according to a Delphi-like method. Thirty different GETAID physicians declared if they found acceptable each definition. Intra- and inter-observer agreements were investigated using 100 videos with one tagged specific lesion [AE, SU, DU, or sham lesion] read by 15 independent endoscopists at baseline and 1 month later in a randomised order. Video quality was determined by an external reader. According to kappa estimate [κ ±standard error], intra or inter-observer agreement was qualified as 'moderate' [0.4-0.6], 'substantial' [0.6-0.8], or 'almost perfect' [0.8-1.0]. RESULTS: Among 30 different experts, 83% to 97% found acceptable the definitions retrieved from the Delphi-like method. Intra-observer κ was 0.717 [±0.019] for SU, 0.681 [±0.027] for AE, 0.856 [±0.014] for DU, showing 'substantial' agreement. It was 0.801 [±0.016] for any ulceration [DU or SU]. There was a high variability across readers from 'moderate' to 'almost perfect' agreement. Inter-observer κ was 0.548 [±0.042] for SU, 0.554 [±0.028] for AE 0.694 [±0.041] for DU, and 0.705 [±0.042] for any ulceration. Inter-observer agreement increased when reading the 53 high-quality videos: 0.787 [±0.064] [p = 0.001], 0.607 [±0.043] [p = 0.001], and 0.782 [±0.064][p = 0.001] for DU, AE, and any ulceration, respectively. CONCLUSIONS: Despite variable intra-agreement level across readers, the GETAID definitions for CD endoscopic lesions provided 'substantial' inter-observer agreements, especially in case of high-quality videos.

Impact of an Education Programme on IBD Patients' Skills: Results of a Randomised Controlled Multicentre Study [ECIPE].

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.

Anti-TNF therapy in inflammatory bowel diseases: a huge review.

Anti-tumour necrosis factor-alpha (TNF-a) agents have changed the way of treating inflammatory bowel diseases (IBD) refractory to conventional medications (corticosteroids, immu-nomodulators). Infliximab, adalimumab, and certolizumab are more effective than placebo for induction and maintenance of remission in luminal Crohn's disease. Infliximab and adalimumab are also effective for maintenance of fistula closure in Crohn's disease. Only infliximab is Food and Drug Administration (FDA)-approved for ulcerative colitis. Only adalimumab has demonstrated its efficacy in a randomized controlled trial to induce remission after infliximab failure in Crohn's disease. Anti-TNF therapy leads to mucosal healing, reduces hospitalizations and surgeries, and improves patients' quality of life. Safety data indicate that serious infections occur in 2-4% of patients treated with anti-TNF therapy, with no statistical difference when compared to controls. The risk of rare events such as malignancies and lymphoma, in IBD patients treated with anti-TNF agents, will require a longer duration of follow-up. Currently, the risk-benefit ratio of anti-TNF therapy supports its use in IBD. Several questions remain to be answered: can an indiscriminate use of anti-TNF agents modify the natural course of the disease, should mucosal healing be used in clinical practice, and should anti-TNF therapy be used alone or in combination with immunomodulators in the long-term?

Toll-like receptor 2 is critical for induction of Reg3 beta expression and intestinal clearance of Yersinia pseudotuberculosis.

OBJECTIVE: Yersinia pseudotuberculosis causes ileitis and mesenteric lymphadenitis by mainly invading the Peyer's patches that are positioned in the terminal ileum. Whereas toll-like-receptor 2 (TLR2) controls mucosal inflammation by detecting certain microbiota-derived signals, its exact role in protecting Peyer's patches against bacterial invasion has not been defined. DESIGN: Wild-type, Tlr2-, Nod2- and MyD88-deficient animals were challenged by Y pseudotuberculosis via the oral or systemic route. The role of microbiota in conditioning Peyer's patches against Yersinia through TLR2 was assessed by delivering, ad libitum, exogenous TLR2 agonists in drinking water to germ-free and streptomycin-treated animals. Bacterial eradication from Peyer's patches was measured by using a colony-forming unit assay. Expression of cryptdins and the c-type lectin Reg3 beta was quantified by quantitative reverse transcriptase polymerase chain reaction analysis. RESULTS: Our data demonstrated that Tlr2-deficient mice failed to limit Yersinia dissemination from the Peyer's patches and succumbed to sepsis independently of nucleotide-binding and oligomerisation domain 2 (NOD2). Recognition of both microbiota-derived and myeloid differentiation factor 88 (MyD88)-mediated elicitors was found to be critically involved in gut protection against Yersinia-induced lethality, while TLR2 was dispensable to systemic Yersinia infection. Gene expression analyses revealed that optimal epithelial transcript level of the anti-infective Reg3 beta requires TLR2 activation. Consistently, Yersinia infection triggered TLR2-dependent Reg3 beta expression in Peyer's patches. Importantly, oral treatment with exogenous TLR2 agonists in germ-free animals was able to further enhance Yersinia-induced expression of Reg3 beta and to restore intestinal resistance to Yersinia. Lastly, genetic ablation of Reg3 beta resulted in impaired clearance of the bacterial load in Peyer's patches. CONCLUSIONS: TLR2/REG3 beta is thus an essential component in conditioning epithelial defence signalling pathways against bacterial invasion.

Safety of Drugs During Previous and Current Coronavirus Pandemics: Lessons for Inflammatory Bowel Disease.

The coronavirus 2019 [COVID-19] pandemic has posed challenges in the routine care of patients with inflammatory bowel disease [IBD]. One of the key challenges is quantification of the risks of immunosuppressive and biological therapies in IBD patients during the pandemic. The similarities and differences between previous coronavirus outbreaks and the pathobiology of the infections can give useful information in understanding the risks, and perhaps potential beneficial aspects of drugs used in IBD. Although clinical, immunological and pharmacological data from the experience with previous coronavirus outbreaks cannot be automatically translated to predict the safety of IBD therapies during the COVID-19 pandemic, the signals so far from these outbreaks on IBD patients who are on immunomodulators and biologics are reassuring to patients and clinicians alike.

Inflammatory Bowel Disease Management During the COVID-19 Outbreak: The Ten Do's and Don'ts from the ECCO-COVID Taskforce.

Our knowledge of COVID-19 is changing and evolving rapidly, with novel insights and recommendations, almost on a daily basis. It behooves the medical community to provide updated information on a regular basis, on best practice to facilitate optimal care of infected patients and on appropriate advice for the general population. This is particularly important in the case of patients with chronic conditions, such as inflammatory bowel disease [IBD]. In this review, we have compiled existing evidence on the impact of COVID-19 in IBD patients and provide guidance on the most appropriate care to adopt during the pandemic. Our review highlights that IBD, per se, is not a risk factor for COVID-19. However, all IBD patients with symptoms should be tested for SARS-CoV-2 and the procedures for disease management should be carefully adapted: [i] in SARS-CoV-2-positive IBD patients, medical treatments should be re-evaluated [with a particular focus on corticosteroids] always with the purpose of treating active disease and maintaining remission; [ii] non-urgent surgeries and endoscopic procedures should be postponed for all patients; [iii] online consultancy should be implemented; and [iv] hospitalization and surgery should be limited to life-threatening situations.

TNF antagonists in the treatment of inflammatory bowel disease: results of a survey of gastroenterologists in the French region of Lorraine.

BACKGROUND AND OBJECTIVE: We conducted a survey of nonacademic gastroenterologists to evaluate the use of tumor necrosis factor (TNF) antagonists in inflammatory bowel disease (IBD). METHODS: A total of 100 questionnaires were sent by mail to a representative sample of gastroenterologists practicing in the French region of Lorraine. RESULTS: Forty-six practitioners responded to the survey, of whom 95.5% prescribed scheduled infliximab treatment. After 6 months of infliximab in combination with azathioprine, 55% then prescribed infliximab as monotherapy. A complete pretherapeutic assessment was performed by only one fourth of the gastroenterologists. When the PPD skin test measured 7 mm, nearly half of the physicians introduced anti-TNF therapy without chemoprophylaxis (versus only 2.4% when the diameter was 11 mm). In the event of quiescent Crohn's disease (CD) after 1 year of anti-TNF treatment, 35.7% stopped the drug. In refractory CD, 72.7% prescribed infliximab as the first-line therapy (versus 27.3% who used adalimumab). In patients with urinary tract infection, 44.2% initiated antibiotics and delayed anti-TNF treatment, while 46.5% initiated anti-TNF therapy along with antibiotic therapy. CONCLUSION: This study is the first survey upon the use of TNF antagonists by nonacademic gastroenterologists, and the findings suggest that physicians using these drugs may require more information about the pretherapeutic assessment and management of the infectious risk.

Inflammatory bowel disease and hepatitis B and C.

The risk of viral B and C hepatitis has long been considered to be increased in patients with inflammatory bowel disease (IBD). Blood transfusion and surgery have been identified as the two main risk factors, suggesting nosocomial transmission could be involved. However, recent epidemiologic surveys have found that prevalence in IBD patients is similar to or even lower than that in the general population. Part of the explanation of these recent data may lie in the application of protective measures against viral infection (hepatitis B virus [HBV] vaccination and hepatitis C virus [HCV]-free blood transfusions). Sometimes fatal viral reactivations have been reported in patients on immunosuppressive therapy. Two periods can be distinguished: a) during therapy, a rise in viremia associated with a decrease of immune-mediated hepatic lesions; b) after cessation of therapy, an immune rebound with a destruction of virus-infected hepatocytes. For HBV, preemptive strategy consisting of an antiviral analog is efficient in chronic HBs antigen carriers. For HCV, the impact of immunosuppressive drugs on the natural history is unclear. Most studies report improved comfort although no biopsies were performed before and after immunosuppressive treatment. Physicians managing IBD patients should be aware of the need for screening and institute preventive measures against B and C hepatitis.