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Crohn's disease (CD) is a chronic inflammatory bowel disorder that progresses to bowel damage (BD) over time. An image-based index, the Lémann index (LI), has been developed to measure cumulative BD.To characterize the long-term progression of BD in CD based on changes in the LI and to determine risk factors for long-term progression.This was a single-center longitudinal cohort study. Patients who had participated in prospective studies on the accuracy of magnetic resonance imaging using endoscopy as a gold standard and who had a follow-up of at least 5 years were re-evaluated after 5-12 years.Seventy-two patients were included. LI increased in 38 patients (52.8%), remained unchanged in 9 patients (12.5%), and decreased in 25 patients (34.7%). The small bowel score and surgery subscale significantly increased (BD, as assessed by the LI, progressed in half of the patients with CD over a period of 5-12 years. The main determinants of BD progression were ileal location, stricturing/fistulizing phenotype, and disease duration.

Background The long-term outcome of patients after antitumour necrosis factor alpha (anti-TNF) discontinuation is not well known. Aims To assess the risk of relapse in the long-term after anti-TNF discontinuation. Methods This was an extension of the evolution after anti-TNF discontinuation in patients with inflammatory bowel disease (EVODIS) study (Crohn's disease or ulcerative colitis patients treated with anti-TNFs in whom these drugs were withdrawn after achieving clinical remission) based in the same cohort of patients whose outcome was updated. Clinical remission was defined as a Harvey-Bradshaw index ≤4 points in Crohn's disease, a partial Mayo score ≤2 in ulcerative colitis and the absence of fistula drainage despite gentle finger compression in perianal disease. Results This was an observational, retrospective, multicenter study. A total of 1055 patients were included. The median follow-up time was 34 months. The incidence rate of relapse was 12% per patient-year (95% confidence interval [CI] = 11-14). The cumulative incidence of relapse was 50% (95% CI = 47-53): 19% at one year, 31% at 2 years, 38% at 3 years, 44% at 4 years and 48% at 5 years of follow-up. Of the 60% patients retreated with the same anti-TNF after relapse, 73% regained remission. Of the 75 patients who did not respond, 48% achieved remission with other therapies. Of the 190 patients who started other therapies after relapse, 62% achieved remission with the new treatment. Conclusions A significant proportion of patients who discontinued the anti-TNF remained in remission. In case of relapse, retreatment with the same anti-TNF was usually effective. Approximately half of the patients who did not respond after retreatment achieved remission with other therapies.

Background Gadolinium-enhanced sequences are not included in the simplified Magnetic Resonance Index of Activity [sMARIA], but in the derivation of this index readers had access to these sequences. The current study aimed to validate the sMARIA without gadolinium-enhanced sequences for assessing disease activity, severity, and response to treatment in patients with Crohn’s disease. Methods We prospectively included patients with active Crohn’s disease and at least one segment with severe inflammation [ulcers] at ileocolonoscopy, who required treatment with biologic drugs. Patients were evaluated by both magnetic resonance enterography [MRE] and ileocolonoscopy at baseline and 46 weeks after initiation of medical treatment. We compared the quantification of disease activity and response to treatment with sMARIA versus with ileocolonoscopy Crohn’s Disease Index of Severity [CDEIS], considered the gold standard. Results Data from both MRE and ileocolonoscopy 46 weeks after treatment initiation were available for 39 of the 50 patients. As in the derivation study, the optimal cutoffs were sMARIA ≥1 for predicting active disease (area under the curve [AUC] 0.92) and sMARIA ≥2 for predicting the presence of ulcers at ileocolonoscopy [AUC 0.93]. In evaluating the response to treatment, the sMARIA detected endoscopic ulcer healing at the segment level [sMARIA Conclusions The sMARIA is accurate and reliable in quantifying disease activity and response to treatment in luminal Crohn’s disease, without the need for gadolinium-enhanced sequences.

Methotrexate can be used to maintain remission in Crohn's disease patients who are intolerant to thiopurines. Data on its use as monotherapy in other scenarios are limited.To assess the effectiveness of methotrexate monotherapy in Crohn's disease patients after previous failure to anti-tumour necrosis factor (anti-TNFα) drugs.A retrospective, observational multicentre study of data from the Spanish ENEIDA registry. Participants were patients with active Crohn's disease and previous failure to anti-TNFα started on methotrexate monotherapy. Short-term effectiveness was assessed at 12-16 weeks based on Harvey-Bradshaw index (HBI): clinical remission as HBI ≤ 3 points and clinical response as HBI drop of ≥ 3 points over baseline. Long-term effectiveness was defined as steroid-free methotrexate persistence from 12 to 16 weeks until maximum follow up. Adverse events were recorded.Data were compiled for 110 patients treated with methotrexate after a failed response to one (39%) or two (55.6%) anti-TNFα agents. Short-term clinical response and remission rates were 60% and 30.9% respectively. Of 74 patients who continued after week 16, long-term effectiveness was achieved in 82% and 74% at 12 and 24 months respectively. In the multivariate analysis, non-remission at short term (vs remission) was associated with long-term failure (HR 2.58, 95%CI 1.95-3.68, P = 0.028). Adverse events (evaluated in 100 patients) were recorded in 44%, and in 30.4% of these patients, they led to methotrexate discontinuation.The benefits observed suggest methotrexate monotherapy could be a valid option in Crohn's disease patients with previous failure to anti-TNFα.

Background Tacrolimus is a calcineurin inhibitor commonly used for prophylaxis of rejection in renal and liver transplantation. There are limited but favourable data regarding its possible use in patients with inflammatory bowel disease (IBD). Aims To evaluate the efficacy and safety of tacrolimus in patients with IBD in clinical practice. Methods We performed a retrospective, multicentre study in 22 centres in Spain. All adult patients who received oral tacrolimus for luminal or perianal IBD were included. Clinical response was assessed by Harvey-Bradshaw index and partial Mayo score after 3 months. Perianal disease was evaluated by fistula drainage assessment. Results One hundred and forty-three patients were included (mean age 38 years; 51% male; median disease duration 110 months). In ulcerative colitis (UC) (n = 58), the partial Mayo score decreased after 3 months from median 6 to 3 (P = 0.0001), whereas in Crohn's disease (CD) (n = 85), the Harvey-Bradshaw index decreased after 3 months from median 9 to 7 (P = 0.011). In CD patients, blood tacrolimus concentrations during induction (>10 ng/mL vs

New generations of small molecules are being developed for the treatment of ulcerative colitis. Among them, tofatinib (a Janus kinase (JAK) inhibitor) has demonstrated efficacy for inducing and maintaining remission and achieving mucosal healing with a reasonable safety profile. Oral administration is attractive for patients and lack of immunogenicity represents an advantage over biologic drugs. Areas covered: This review discusses the molecular aspects of the JAK-STAT pathway; the mechanism of action of tofacitinib pertinent to ulcerative colitis and the evidence on the efficacy of tofacitinib for achieving clinically relevant outcomes, including clinical remission, mucosal healing, and normalization of quality of life, as well as safety aspects with special attention to adverse events related to the mode of action of the drug. Expert commentary: Tofacitinib will be the first drug on the class of JAK inhibitors to be available for treatment of ulcerative colitis. The efficacy of the drug, with a rapid onset of action even in cases of severe colitis, oral administration, and possibility to use the drug intermittently without generating immunogenicity, will bring about a redesign of current treatment paradigms for ulcerative colitis.

Background It has been suggested that biologic therapy may increase the risk of postoperative complications in inflammatory bowel disease (IBD), but the evidence is scarce. Our aim was to evaluate whether the treatment with anti-TNF agents, ustekinumab or vedolizumab increase the risk of complications after surgery. Methods IBD patients undergoing intra-abdominal surgery between 1st January 2009 and 31st December of 2019 were retrospectively selected. Data collection included clinical characteristic of IBD, biochemical parameters and surgical aspects. Postoperative complications (PC) were defined as those occurring within 30 days after surgery. Exposed cohort (EC): Patients who received the last dose of the biologic within 3 months before surgery. Non-exposed cohort (NEC): Patients who did not receive biologic treatment within 3 moths prior to surgery. Predictive factors for PC and for infections were identified by logistic regression analyses. A genetic matching score was performed to balance the clinical characteristics of both groups. Results A total of 1,535 surgeries performed in 37 centres were included: 81% in Crohn’s disease, 18% in ulcerative colitis and 1% in unclassified-IBD patients. A total of 711 surgeries (46.3%) had been exposed to biologics (583 under anti-TNF therapy, 58 under vedolizumab and 69 under ustekinumab) and 824 surgeries (53.7%) the NEC. PC were reported in 38% (n=267) of patients in the exposed cohort and in 34% (n=280) of patients in the non-exposed one (p=0.15), including dehiscence, infection, obstruction, ileus, bleeding, thrombosis, fistula and evisceration. The most frequent complications were infections (48% of all the cases). A 30-day hospital readmission was needed in 7% (n=110) of the patients, and 2% (n=29) required a new surgery with no differences (p>0.05). Multivariate analysis for PC and infections is presented in table 1. The frequencies of PC for each biologic in the univariate analysis are represented in figure 1. No specific treatment was associated to PC or infections in multivariate analysis. Conclusion Preoperative administration of biological therapy does not seem to be a risk factor for overall PC, although it may be for postoperative infections.

Under current therapeutic algorithms, half of the patients with moderate-severe ulcerative colitis or Crohn’s disease fail in achieving a sustained remission. New drugs with different mechanisms of action are needed. After two decades of new drug avenues in inflammatory bowel disease dominated by the development of monoclonal antibodies, in recent years we are witnessing promising developments of small molecules for these conditions. Their intrinsic characteristics make them attractive compared to the monoclonal antibodies based on their oral administration, short plasma half-life, lack of immunogenicity and predictable pharmacokinetics. Among them, Janus kinase (JAK) inhibitors are a promising new class that have demonstrated efficacy with a favorable safety profile in clinical trials. Tofacitinib has been the first JAK inhibitor approved for the treatment of ulcerative colitis. This review discusses the molecular aspects of the JAK-STAT pathway, its role in the pathogenesis of inflammatory bowel disease, and the rational use of JAK inhibitors in these conditions. The different compounds with JAK inhibitory activity tested are reviewed and we provide an overview of recent evidence from clinical trials. Finally, we consider the positioning of these drugs in the treatment of inflammatory bowel diseases.

Significant unmet needs remain in patients with Crohn's disease and perianal fistulas. Mesenchymal stromal cells have potent immunomodulatory actions. The Phase II studies reported efficacy of local injection of mesenchymal stromal cells to achieve closure of fistulas. A Phase III trial demonstrated that in patients with Crohn's disease and refractory complex perianal fistulas, a single injection of 120 × 106 cells was superior to local injection of placebo associated with the same surgical procedure, in obtaining closure of the fistula tracts together with absence of abscesses >2 cm, 24 weeks after the injection, a stringent combined primary end point. The benefit over placebo was sustained 52 weeks after the single injection. The therapy is safe with adverse events limited to local pain.

The magnetic resonance index of activity (MARIA) for Crohn's disease (CD) is used to assess the activity of luminal CD. However, it has a number of practical limitations. We aimed to develop and validate a simplified MARIA to more easily and quickly assess CD activity and response to therapy.We performed a retrospective analysis of magnetic resonance imaging data from 98 participants in 2 studies. We used logistic regression analysis to identify magnetic resonance imaging parameters independently associated with CD endoscopic index of severity (CDEIS) scores (the reference standard). We validated the responsiveness and reliability of the simplified MARIA in an independent cohort of 37 patients who underwent magnetic resonance imaging and endoscopy before and after a therapeutic intervention.Logistic regression analysis showed that dichotomous qualitative assessment of wall thickening (3 mm), presence of mural edema, perienteric fat stranding, and ulcers were independently associated with CDEIS scores; we used these factors to create a simplified MARIA. Simplified MARIA scores greater than 1 identified segments with active CD with 90% sensitivity and 81% specificity (area under the curve 0.91; 95% confidence interval 0.88-0.94). Simplified MARIA scores of 2 or more detected severe lesions (ulcers) with 85% sensitivity and 92% specificity (area under the curve 0.94; 95% confidence interval 0.91-0.96). For each patient, there was a high level of correlation between simplified MARIA scores and CDEIS scores (r = 0.83) and simplified MARIA scores and original MARIA scores (and r = 0.93) (P.001). The simplified MARIA score accurately detected changes in lesion severity in response to therapy and was as reliable as endoscopy for the assessment of mucosal healing.We developed and validated a simplified MARIA for easier and faster assessment of CD activity and severity. This index identifies patients with a response to therapy with a high level of accuracy. These findings require confirmation in independent, multireader studies.

In Crohn's disease, it is essential to distinguish between persistent damage and abnormalities that can heal with anti-inflammatory therapy.To assess magnetic resonance enterography (MRE) lesions that persist in patients in long-standing endoscopic remission, analyse their relationship with baseline characteristics, and determine their prognostic implications.We systematically reviewed pre- and post-treatment MRE findings in patients with Crohn's disease and severe inflammation (segmental CDEIS ≥ 7 or ulcers in at least one segment) who achieved endoscopic remission (CDEIS 2) after 1 year of treatment with TNF-inhibitors or autologous haematopoietic stem-cell transplantation. Logistic regression analysis was used to identify predictors of persistent abnormalities.Endoscopic remission was achieved in 73 intestinal segments in 28 patients (69% females; 9.95 years disease duration, 67.9% inflammatory phenotype; 39.3% ileal location). Creeping fat and intestinal wall fat deposits were unchanged on pre- and post-treatment MRE despite the endoscopic remission. Luminal strictures persisted in 6 out of the 8 segments with baseline strictures, and wall thickening in 23 out of the 72 of segments with thickening at baseline. Predictors of persistent mural thickening were pre-treatment wall thickness 5.9 mm (OR = 4.38, P = 0.027) and refractory disease prior to baseline (OR = 2.35, P = 0.001). Creeping fat was the only predictor for persistence of creeping fat (OR = 36.43, P 0.001). Persistence of strictures at MRE is associated with earlier recurrence (P = 0.014).Persistent MRE abnormalities are frequent in patients with Crohn's disease despite achieving endoscopic remission. Significant wall thickening, intestinal fat deposition, strictures, and creeping fat at baseline MRE are signs of established damage.