Long-term outcome of risankizumab in Crohn's disease: a real-world GETAID study.

INTRODUCTION: The aim of this study was to assess the long-term effectiveness and safety of risankizumab maintenance treatment in a large real-world cohort of patients with CD. PATIENTS AND METHODS: From May 2021 to August 2023, all consecutive CD patients treated with risankizumab in 25 GETAID centers have been retrospectively included. The primary endpoint was steroid-free clinical remission (Harvey Bradshaw Index (HBI) <5) at 52 weeks. RESULTS: Of the 174 patients included, 99%, 93%, and 96% had been previously exposed to anti-TNF, vedolizumab, and ustekinumab, respectively. All patients had received ≥3 biologics and 108 (62%) had previous intestinal resection. Median follow-up was 13.7 (10.0-18.1) months. The rates of steroid-free clinical remission and clinical remission at week 26 were 47% (72/152) and 52% (79/152), and 46% (58/125), and 48% (60/125) at week 52, respectively. Risankizumab persistence rates were 94%, 89%, and 79% at weeks 12, 26, and 52, respectively. At the end of follow-up, 45 (45/174, 26%) patients had discontinued risankizumab (loss of response, 42%; primary failure, 37%; intolerance, 13%). Thirty-six patients (36/174, 20.9%) were hospitalized and 22 (22/174, 12.6%) required intestinal resection. Fifty-one (29%) patients had an adverse event including 26 (15%) serious adverse events (CD flare, n=17). One death (myocardial infarction) and one cancer (papillary thyroid carcinoma) were observed. CONCLUSION: This is the first real-life study to report long-term outcomes in patients with refractory CD treated with risankizumab. Half of the patients achieved steroid-free clinical remission after one year, and the safety profile was consistent with the literature.

Adalimumab in Biologic-naïve Patients With Crohn's Disease After Resolution of an Intra-abdominal Abscess: A Prospective Study From the GETAID.

BACKGROUND & AIMS: The management of intra-abdominal abscesses complicating Crohn's disease (CD) is challenging, and surgery with delayed intestinal resection is often recommended. The aims of this study were to estimate the success rate of adalimumab (ADA) in patients with CD with an intra-abdominal abscess resolved without surgery, and to identify predictive factors for success. METHODS: A multicenter, prospective study was conducted in biologic-naïve patients with CD with resolved intra-abdominal abscess treated with ADA with a 2-year follow-up. The primary endpoint was ADA failure at week (W) 24 defined as a need for steroids after W12, intestinal resection, abscess recurrence, and clinical relapse. Secondary post-hoc endpoint was the long-term success defined as the survival without abscess relapse or intestinal resection at W104. The factors associated with ADA failure at W24 and W104 were identified using a logistic and a Cox regression, respectively. RESULTS: From April 2013 to December 2017, 190 patients from 27 GETAID centers were screened, and 117 were included in the analysis. Fifty-eight patients (50%) were male, and the median age at baseline was 28 years. At W24, 87 patients (74%; 95% confidence interval [CI], 65.5%-82.0%; n = 117) achieved ADA success. Among the 30 patients with ADA failure, 15 underwent surgery. At W104, the survival rate without abscess recurrence or surgery was 72.9% (95% CI, 62.1%-79.8%; n = 109). Abscess drainage was significantly associated with ADA failure at W24 (odds ratio, 4.18; 95% CI, 1.06-16.5; P =0 .043). Disease duration (hazard ratio [HR], 1.32; 95% CI, 1.09-1.59; P = .008), abscess drainage (HR, 5.59; 95% CI, 2.21-14.15; P = .001), and inflammatory changes in mesenteric fat (HR, 0.4; 95% CI, 0.17-0.94; P = .046) were significantly associated with ADA failure at W104. CONCLUSION: Provided that the abscess was carefully managed before initiating medical treatment, this study showed the high efficacy of ADA in the short and long term in biologic-naïve patients with CD complicated by an intra-abdominal abscess. CLINICALTRIALS: gov, Number: NCT02856763.

Risk of SARS-CoV-2 infection in healthcare workers with inflammatory bowel disease: a case-control study.

Background: Whether healthcare workers with inflammatory bowel disease (IBD) are at increased risk of Novel coronavirus disease (COVID-19) due to occupational exposure is unknown. Aim: To assess the risk of COVID-19 in healthcare workers with IBD. Methods: A case control study enrolled 326 healthcare workers with IBD from 17 GETAID centres and matched non-healthcare workers with IBD controls (1:1) for gender, age, disease subtype and year of diagnosis. The study period was year 2020 during the COVID-19 outbreak. Results: In total, 59 COVID-19 were recorded among cases (n = 32) and controls (n = 27), including 2 severe COVID-19 (requiring hospitalization, mechanic ventilation) but no death. No difference was observed between healthcare workers and controls regarding the overall incidence rates of COVID-19 4.9 ± 2.2 vs. 3.8 ± 1.9 per 100 patient-semesters, P = 0.34) and the overall incidence rates of severe COVID-19 (0.6 ± 7.8 vs. 0.3 ± 5.5 per 100 patient-semesters, P = 0.42). In multivariate analysis in the entire study population, COVID-19 was associated with patients with body mass index > 30 kg/m2 (HR = 2.48, 95%CI [1.13-5.44], P = 0.02). Conclusion: Healthcare workers with IBD do not have an increased risk of COVID-19 compared with other patients with IBD.

Reversible atransferrinemia in a patient with chronic enteropathy: is transferrin mandatory for iron transport?

Herein, we report the case of a 42-year-old woman, hospitalized in a French tertiary hospital for a relapse of a chronic enteropathy, who was found on admission to have no detectable serum transferrin. Surprisingly, she only exhibited mild anaemia. This atransferrinemia persisted for two months throughout her hospitalization, during which her haemoglobin concentration remained broadly stable. Based on her clinical history and evolution, we concluded to an acquired atransferrinemia secondary to chronic undernutrition, inflammation and liver failure. We discuss the investigations performed in this patient, and hypotheses regarding the relative stability of her haemoglobin concentration despite the absence of detectable transferrin.

Effectiveness and safety of risankizumab induction therapy for 100 patients with Crohn's disease: A GETAID multicentre cohort study.

BACKGROUND: Phase III trials have demonstrated the efficacy of risankizumab in moderate-to-severe Crohn's disease (CD), but no real-world data are currently available. We aimed to assess the short-term effectiveness and safety of risankizumab in patients with CD. METHODS: From May 2021 to May 2022, all patients with refractory luminal CD treated with risankizumab in 22 French GETAID centres were retrospectively included. The primary endpoint was steroid-free clinical remission at week 12 (Harvey-Bradshaw [HB] score <5). Secondary endpoints included clinical response (≥3-point decrease of HB score and/or (HB) score <5), biochemical remission (CRP ≤ 5 mg/L), need for CD-related surgery and adverse events. RESULTS: Among the 100 patients included, all have been previously exposed to anti-TNF agents, 94 to vedolizumab, 98 to ustekinumab (all exposed to at least three biologics) and 61 had a previous intestinal resection. All but three (97%) received a 600 mg risankizumab intravenous induction at weeks 0-4-8. At week 12, steroid-free clinical remission was observed in 45.8% of patients, clinical remission in 58% and clinical response in 78.5%. In subgroup analysis restricted to patients with objective signs of inflammation at baseline (n = 79), steroid-free clinical remission at week 12 was observed in 39.2% of patients. Biochemical remission was observed in 50% of patients. Six patients discontinued risankizumab before the week 12 visit due to lack of efficacy. CD-related hospitalisation was needed in six patients, and three underwent intestinal resection. In multivariable analysis, only a history of ustekinumab loss of response (vs primary failure) (odds ratio (OR), 2.80; 95% CI: 1.07-7.82; p = 0.041) was significantly associated with clinical remission at week 12. Twenty adverse events (AE) occurred in 20 patients including 7 serious AE corresponding to 6 CD exacerbation and one severe hypertension. CONCLUSION: In a cohort of highly refractory patients with luminal CD and multiple prior drug failures including ustekinumab, risankizumab induction provided a clinical response in about 3 out of 4 patients and steroid-free clinical remission in about half of patients.

Crohn-like Disease Affecting Small Bowel Due to Monogenic SLCO2A1 Mutations: First Cases of Chronic Enteropathy Associated with SLCO2A1 Gene [CEAS] in France.

INTRODUCTION: Multiple chronic ulcers of small intestine are mainly ascribed to Crohn's disease. Among possible differential diagnoses are chronic ulcers of small bowel caused by abnormal activation of the prostaglandin pathway either in the archetypal but uncommon non-steroidal anti-inflammatory drug [NSAID]-induced enteropathy, or in rare monogenic disorders due to PLA2G4A and SLCO2A1 mutations. SLCO2A1 variants are responsible for CEAS [chronic enteropathy associated with SLCO2A1], a syndrome which was exclusively reported in patients of Asian origin. Herein, we report the case of two French female siblings, P1 and P2, with CEAS. CASE REPORT: P1 underwent iterative bowel resections [removing 1 m of small bowel in total] for recurrent strictures and perforations. Her sister P2 had a tight duodenal stricture which required partial duodenectomy. Next-generation sequencing was performed on P1's DNA and identified two compound heterozygous variants in exon 12 in SLCO2A1, which were also present in P2. CONCLUSION: CEAS can be detected within the European population and raises the question of its incidence and recognition outside Asia. Presence of intractable recurrent ulcerations of the small intestine, mimicking Crohn's disease with concentric strictures, should motivate a genetic search for SLCO2A1 mutations, particularly in the context of family history or consanguinity.

Role of adherent and invasive Escherichia coli in Crohn's disease: lessons from the postoperative recurrence model.

OBJECTIVE: We used the postoperative recurrence model to better understand the role of adherent and invasive Escherichia coli (AIEC) bacteria in Crohn's disease (CD), taking advantage of a well-characterised postoperative cohort. DESIGN: From a prospective, multicentre cohort of operated patients with CD, AIEC identification was performed within the surgical specimen (M0) (N=181 patients) and the neoterminal ileum (n=119 patients/181) during colonoscopy performed 6 months after surgery (M6). Endoscopic postoperative recurrence was graded using Rutgeerts' index. The mucosa-associated microbiota was analysed by 16S sequencing at M0 and M6. Relative risks or ORs were adjusted on potential confounders. RESULTS: AIEC prevalence was twofold higher within the neoterminal ileum at M6 (30.3%) than within the surgical specimen (14.9%) (p<0.001). AIEC within the neoterminal ileum at M6 was associated with higher rate of early ileal lesions (i1) (41.6% vs 17.1%; aRR 3.49 (95% CI 1.01 to 12.04), p=0.048) or ileal lesions (i2b+i3) (38.2% vs 17.1%; aRR 3.45 (95% CI 1.06 to 11.30), p=0.040) compared with no lesion (i0). AIEC within the surgical specimen was predictive of higher risk of i2b-endoscopic postoperative recurrence (POR) (aOR 2.54 (95% CI 1.01 to 6.44), p=0.049) and severe endoscopic POR (aOR 3.36 (95% CI 1.25 to 9.06), p=0.017). While only 5.0% (6/119) of the patients were AIEC-positive at both M0 and M6, 43.7% (52/119), patients with history of positive test for AIEC (M0 or M6) had higher risk of ileal endoscopic POR (aOR 2.32 (95% CI 1.01 to 5.39), p=0.048)), i2b-endoscopic postoperative recurrence (aOR 2.41 (95% CI 1.01 to 5.74); p=0.048) and severe endoscopic postoperative (aOR=3.84 (95% CI 1.32 to 11.18), p=0.013). AIEC colonisation was associated with a specific microbiota signature including increased abundance of Ruminococcus gnavus. CONCLUSION: Based on the postoperative recurrence model, our data support the idea that AIEC are involved in the early steps of ileal CD. TRIAL REGISTRATION NUMBER: NCT03458195.

Screening for spondyloarthritis in patients with inflammatory bowel diseases.

Inflammatory bowel diseases (IBDs) can be associated with various musculoskeletal (IBD-MSK) manifestations that could be difficult to classify for gastroenterologists. We aimed to evaluate the characteristics of patients with IBD-MSK and the prevalence of spondyloarthritis (SpA). In this observational cross-sectional study, we included patients with IBD-MSK complaints (peripheral or back pain). All patients underwent a standardized rheumatology evaluation including clinical, biological and imaging evaluations (MRI of spine and sacroiliac joints and ultrasonography of enthesis). We included 183 IBD patients (60.7% women; median [interquartile range] age 45 [36-56] years); 159 (87%) had joint pain. In 43 (23.5%) and 25/175 (14.3%) patients, enthesis abnormalities were found on ultrasonography and sacroiliitis on MRI, respectively. SpA was diagnosed in 54 (29.5%) patients. IBD-related arthralgia and degenerative spine disease were diagnosed in 105 (57.4%) and 72 (39.3%) patients. Sixteen (29.6%) SpA patients initiated a new conventional synthetic disease modifying anti-rheumatic drug (DMARD). A biologic DMARD was initiated in 10 patients or changed in 3. More than half of IBD-MSK patients had IBD-related arthralgia, and about one-third had definite SpA. Ultrasonography of enthesis and systematic MRI of sacroiliac joints seem useful for SpA classification and differential diagnosis in these patients who often have musculoskeletal pain complaints. Therapeutics were changed in most patients, which highlights the need for a multidisciplinary approach for managing IBD with extra-intestinal symptoms.

Intra-abdominal abscesses in CD - When to treat with biologics?

Management of intra-abdominal abscesses complicating Crohn's disease (CD) is challenging. After initial drainage and antibiotherapy treatment, surgery with delayed intestinal resection is often recommended but new data suggests efficacy of biotherapies in this context. This review aims to summarize new data regarding efficacy and safety of anti-TNF in the management of intra-abdominal abscesses complicating CD. We performed a review of the literature on medical management of intra-abdominal abscesses complicating CD. After effective drainage of abscess, treatment with anti-TNF can allow resolving of abscess. In some patients and at a specific timing, the use of biotherapies could avoid delayed surgery and long-term abscess recurrence.

Bariatric Surgery in Patients With Inflammatory Bowel Disease: A Case-Control Study from the GETAID.

BACKGROUND: The prevalence of obesity and the number of bariatric surgeries in both the general population and in patients with inflammatory bowel disease (IBD) have increased significantly in recent years. Due to small sample sizes and the lack of adequate controls, no definite conclusions can be drawn from the available studies on the safety and efficacy of bariatric surgery (BS) in patients with IBD. Our aim was to assess safety, weight loss, and deficiencies in patients with IBD and obesity who underwent BS and compare findings to a control group. METHODS: Patients with IBD and a history of BS were retrospectively recruited to centers belonging to the Groupe d'Etude Thérapeutique des Affections Inflammatoires du Tube Digestif (GETAID). Patients were matched 1:2 for age, sex, body mass index (BMI), hospital of surgery, and type of BS with non-IBD patients who underwent BS. Complications, rehospitalizations, weight, and deficiencies after BS were collected in cases and controls. RESULTS: We included 88 procedures in 85 patients (64 Crohn's disease, 20 ulcerative colitis, 1 unclassified IBD) with a mean BMI of 41.6 ± 5.9 kg/m2. Bariatric surgery included Roux-en-Y gastric bypass (n = 3), sleeve gastrectomy (n = 73), and gastric banding (n = 12). Eight (9%) complications were reported, including 4 (5%) requiring surgery. At a mean follow-up of 34 months, mean weight was 88.6 ± 22.4 kg. No difference was observed between cases and controls for postoperative complications (P = .31), proportion of weight loss (P = .27), or postoperative deficiencies (P = .99). CONCLUSIONS: Bariatric surgery is a safe and effective procedure in patients with IBD and obesity; outcomes in this patient group were similar to those observed in a control population.

Kidney function monitoring in inflammatory bowel disease: The MONITORED consensus.

BACKGROUND AND AIMS: Patients with inflammatory bowel diseases (IBD) are exposed to drug-related nephrotoxicity and kidney-related extra-intestinal manifestations (EIMs). Patients should be monitored but guidance is lacking in current international recommendations. The objective of the Kidney Function Monitoring in Inflammatory Bowel Disease (MONITORED) initiative was to achieve an expert consensus about monitoring kidney function in IBD. METHODS: A literature review was first conducted. Then, an expert consensus meeting, involving 28 attendees representing French-speaking gastroenterologists and nephrologists, was held as part of an academic initiative on May 28, 2021. An anonymous Delphi process was used to discuss and vote on statements. Agreement was defined as at least 75% of participants voting for any one statement. RESULTS: Experts reached consensus on 11 criteria for referral to the nephrologist. Concerning kidney function monitoring, participants unanimously validated the use of serum creatinine with estimation of the glomerular filtration rate via the MDRD or CKD-EPI equations. A blood ionogram and a urine sample with measurement of a protein-to-creatinine ratio were also broadly agreed validated. Experts recommended performing this monitoring at IBD diagnosis, prior introducing a new treatment, and annually for EIMs screening and evaluation of treatment tolerance. An evaluation 3 months after starting mesalamine and then every 6 months was felt necessary, while for biologics an annually monitoring was deemed sufficient. CONCLUSION: The MONITORED consensus proposed guidelines on how to monitor kidney function in IBD. These recommendations should be considered in clinical practice to preserve kidney function and ensure the best approach to our patients.

Tofacitinib as salvage therapy for 55 patients hospitalised with refractory severe ulcerative colitis: A GETAID cohort.

BACKGROUND: Up to 25% of patients with ulcerative colitis (UC) will require hospitalization for severe flare. In patients hospitalised for severe flare, who previously experienced multiple drug failures, including steroids and anti-TNF agents, new quick-acting medical options are needed. Tofacitinib is effective in refractory UC and has a rapid onset of action. AIM: To evaluate effectiveness and safety of tofacitinib as rescue therapy in patients hospitalised for UC flare. METHODS: We conducted an observational and multicentre study with both retrospective and prospective collections in 14 GETAID centres. The primary objective was to assess the survival without colectomy following tofacitinib initiation in patients hospitalised for a UC flare. We determined rates of clinical response, clinical remission, and steroid-free clinical remission at week 6 and week 14 and safety. RESULTS: Fifty-five patients were included (49 with prior infliximab failure and 19 previously exposed to ciclosporin). With a median follow-up of 6.5 months (interquartile range [IQR] [3-12.3]), rate of colectomy-free survival was estimated at 78.9% (95 CI [68.5-90.9]) and 73.6% (95 CI [61.9-87.3]) at 3 and 6 months, respectively. Rates of clinical response, clinical remission and steroid-free clinical remission were 60%, 45.5% and 37.5% at week 6 and 41.8%, 34.5% and 32.7% at week 14. Regarding safety, no death was observed, three patients withdrew tofacitinib due to adverse events. Two herpes zoster infections occurred in patients aged over 60 years old. No venous thrombotic or major adverse cardiovascular events occurred. CONCLUSION: Tofacitinib appears as a promising option in patients hospitalised with a UC flare but needs further validation in controlled trials.

Safety of ustekinumab or vedolizumab in pregnant inflammatory bowel disease patients: a multicentre cohort study.

BACKGROUND: The prevalence of inflammatory bowel diseases (IBD) is high in women of childbearing age. Achieving clinical remission from conception to delivery using current medications is a major issue in IBD. AIMS: To assess maternal and neonatal complications and management of vedolizumab or ustekinumab) in pregnant women with IBD receiving these agents. METHODS: We performed a retrospective cohort study among GETAID centres including women with IBD who received ustekinumab or vedolizumab during pregnancy or within the 2 months before conception and compared outcomes to women exposed to anti-TNF treatment during pregnancy. RESULTS: Seventy-three pregnancies in 68 women with IBD were analysed: 29 on ustekinumab resulting in 26 (90%) live births, two (7%) spontaneous abortions and one (3%) elective termination; 44 on vedolizumab resulting in 38 (86%) live births, five (11%) spontaneous abortions and one (3%) medical interruption. The control group included 88 pregnancies exposed to anti-TNF in 76 women with IBD. The median age at conception, the proportion of women who smoked or in clinical activity at conception was comparable between groups. Only the proportion of patients exposed to >2 anti-TNF agents was significantly increased among the ustekinumab and vedolizumab groups compared to control group (22% and 10% vs 3%, P < 0.005). Rates of prematurity, spontaneous abortion, congenital malformations and maternal complications were comparable between groups. CONCLUSION: We report 73 pregnancies in patients receiving vedolizumab or ustekinumab without a negative signal on maternal or neonatal outcomes. Further prospective studies are needed on the outcomes of pregnancies with new biologic drugs.

Long-term outcome of Crohn's disease patients with upper gastrointestinal stricture: A GETAID study.

BACKGROUND: There are few data concerning patients with Crohn's disease (CD) complicated by a stricture of the upper gastrointestinal tract (UGT). AIMS: We evaluated the outcome and management of CD patients complicated by a stricture of the UGT. METHODS: We performed a retrospective multicenter study including all CD patients with a non-passable symptomatic UGT stricture on endoscopy. Primary outcome measure was surgery-free survival from diagnosis of stricture. Efficacy of medical, endoscopic, and surgical treatments, and identification of predictors of surgery were also evaluated. RESULTS: 60 CD patients with an UGT stricture were included. 60% of the strictures were located in the duodenum. With a median follow-up of 5.5 (IQR: 3.0-12.0) years since stricture diagnosis, surgical-free survival was 75% and 64% at 1 and 5 years, respectively. At the end of the follow up, 27 (45%) patients underwent surgery. 77 endoscopic procedures were performed in 30 patients with an immediate success of 81% and a clinical benefit in 84% of the procedures. In multivariate analysis, anti-TNF treatment initiation was associated with a reduced risk of surgery. CONCLUSION: CD UGT strictures are mainly located in the duodenum. Medical and endoscopic treatments allow to avoid surgery in half of the patients.

Surgery for Crohn's disease during pregnancy: A nationwide survey.

BACKGROUND AND AIMS: Crohn's disease (CD) frequently affects young women and may require surgery during pregnancy. Data regarding operation for CD in expectant mothers are scare. MATERIALS AND METHODS: This was a retrospective nationwide survey from the GETAID Chirurgie. Any woman with CD undergoing surgery during pregnancy was eligible. RESULTS: A total of 15 cases were collected between 1992 and 2015. Most operations were performed due to penetrating or stricturing complications. Mean gestational age at delivery was 34 weeks, with a mean birth weight of 2507 g. Maternal post-operative complications occurred in two-thirds of cases. Maternal mortality rate was 6.7% and neonatal mortality rate 9.1%. CONCLUSIONS: This is the largest case series of surgery for CD during pregnancy. This operation may have significant morbidity and mortality for mother, fetus, and newborn. Indication needs to be tailored to maternal status, disease severity, and gestational age. Surgery should be managed by experienced gynecologists, physicians, and surgeons. Active CD may be associated with a greater risk to the fetus than the surgical procedure itself.

Prominence of ileal mucosa-associated microbiota to predict postoperative endoscopic recurrence in Crohn's disease.

OBJECTIVE: Following ileal resection for Crohn's disease (CD), recurrence is very frequent. Although several clinical risk factors of recurrence have been identified, predicting relapse remains challenging. Performing an ileocolonoscopy within the first year after surgery is currently recommended to assess endoscopic recurrence and to adjust the treatment. We took advantage of a large prospective multicentric cohort to investigate the role of the ileal mucosa-associated microbiota in postoperative endoscopic recurrence. PATIENTS AND METHODS: Ileal mucosa-associated microbiota was analysed by 16S sequencing at the time of surgery and/or of endoscopic evaluation in 201 patients (288 samples in total) prospectively recruited in France. RESULTS: Ileal mucosa-associated microbiota exhibits profound changes following surgery in CD. Compared with non-recurrence setting, endoscopic recurrence is associated with strong changes in ileal mucosa-associated microbiota that are highly reminiscent of those observed generally in ileal CD compared with healthy subjects with a reduction in alpha diversity, an increase in several members of the Proteobacteria phylum and a decrease in several members of the Lachnospiraceae and the Ruminococcaceae families within the Firmicutes phylum. At the time of surgery, we identified several bacterial taxa associated with endoscopic recurrence and that can better predict relapse than usual clinical risk factors. CONCLUSION: Surgery has an important impact on ileal mucosa-associated microbiota. Postoperative endoscopic recurrence is associated with changes in microbiota composition and alpha diversity. The gut microbiota has the potential to predict postoperative evolution and recurrence.

Real-world evidence of tofacitinib effectiveness and safety in patients with refractory ulcerative colitis.

BACKGROUND: Phase III trials demonstrated effectiveness of tofacitinib, an oral Janus kinase inhibitor, to induce and maintain remission in patients with moderate-to-severe active ulcerative colitis (UC). AIMS: We report the real-world effectiveness and safety of tofacitinib in patients with UC in France. METHODS: From February 2017 to December 2018, we performed a national French cohort study, which included all consecutive patients with an active UC refractory to anti-TNF and vedolizumab, who received tofacitinib. Outcomes were survival without colectomy, survival without tofacitinib discontinuation and steroid-free clinical remission at weeks 14, 24 and 48. RESULTS: Thirty-eight patients were included, with a median follow-up of 41.5 (18.5-56.8) weeks. Survival without colectomy was 77% [95% confidence interval (95%CI): 59.3-87.9] at week 24 and 70% (95%CI: 50.9-82.8) at week 48. Survival without treatment discontinuation was 70% (95%CI: 52.6-82.3) at week 24. Steroid-free clinical remission was observed in 13 (34%) patients at week 48. Adverse events occurred in 14 (37%) patients, including 6 severe adverse events and three herpes zoster infections. CONCLUSION: In a highly refractory UC population, one third of patients treated with tofacitinib achieved steroid-free clinical remission at week 14 and 70% of patients avoided colectomy at one year, with an acceptable safety profile. These data confirm tofacitinib effectiveness in UC, especially after multiple biologic failures.

Three-year effectiveness and safety of vedolizumab therapy for inflammatory bowel disease: a prospective multi-centre cohort study.

BACKGROUND: Cohort studies have described the short-term effectiveness and safety of vedolizumab in treating patients with Crohn's disease (CD) and ulcerative colitis (UC), but data beyond 1 year are lacking. AIM: To assess the effectiveness and safety of vedolizumab after 162 weeks in patients with UC and CD. METHODS: Between June and December 2014, 294 patients including 173 patients with CD and 121 with UC were treated with vedolizumab induction therapy. Among them, 149 continued to be treated with vedolizumab beyond week 54 (78 patients with CD and 71 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 162, computed for the whole population included at week 0. RESULTS: Steroid-free clinical remission rates at week 162 were 19.9% and 36.1% in patients with CD and UC respectively. Vedolizumab dose optimisation to 300 mg every 4 weeks instead of 300 mg every 8 weeks was at investigator's discretion and occurred in 58.7% and 52.1% of patients with CD and UC respectively. The 1-, 2- and 3-year persistence rates of vedolizumab were 48.5%, 31.4% and 26.3% respectively, in patients with CD and 61.0%, 49.9% and 42.9% respectively, in patients with UC. No new safety signal was identified. CONCLUSION: Vedolizumab is able to maintain steroid-free clinical remission in patients with UC and CD up to week 162. Loss of response resulting in discontinuation of vedolizumab occurred in 10% of patients per year.

T cell clonal expansions in ileal Crohn's disease are associated with smoking behaviour and postoperative recurrence.

T cell clonal expansions are present in the inflamed mucosa of patients with Crohn's disease (CD) and may be implicated in postoperative recurrence after ileocolonic resection. METHODS: T cell receptor (TCR) analysis was performed in 57 patients included in a prospective multicentre cohort. Endoscopic recurrence was defined by a Rutgeerts score >i0. DNA and mRNA were extracted from biopsies collected from the surgical specimen and endoscopy, and analysed by high throughput sequencing and microarray, respectively. RESULTS: TCR repertoire in the mucosa of patients with CD displayed diverse clonal expansions. Active smokers at time of surgery had a significantly increased proportion of clonal expansions as compared with non-smokers (25.9%vs17.9%, p=0.02). The percentage of high frequency clones in the surgical specimen was significantly higher in patients with recurrence and correlated with postoperative endoscopic recurrence (area under the curve (AUC) 0.69, 95% CI 0.54 to 0.83). All patients with clonality above 26.8% (18/57) had an endoscopic recurrence. These patients with a high clonality were more frequently smokers than patients with a low clonality (61% vs 23%, p=0.005). The persistence of a similar TCR repertoire at postoperative endoscopy was associated with smoking and disease recurrence. Patients with high clonality showed increased expression of genes associated with CD8 T cells and reduced expression of inflammation-related genes. Expanded clones were found predominantly in the CD8 T cell compartment. CONCLUSION: Clonal T cell expansions are implicated in postoperative endoscopic recurrence. CD patients with increased proportion of clonal T cell expansions in the ileal mucosa represent a subgroup associated with smoking and where pathogenesis appears as T cell driven. TRIAL REGISTRATION NUMBER: NCT03458195.