julilili42/papers huggingface dataset:
Faculty Opinions recommendation of Efficacy of vedolizumab induction and maintenance therapy in patients with ulcerative colitis, regardless of prior exposure to tumor necrosis factor antagonists.
2018-08-02

Read the full review for this Faculty Opinions recommended article: Efficacy of vedolizumab induction and maintenance therapy in patients with ulcerative colitis, regardless of prior exposure to tumor necrosis factor antagonists.
Faculty Opinions recommendation of Impact of thiopurines on the natural history and surgical outcome of ulcerative colitis: a cohort study.
2018-08-02

OBJECTIVE: Thiopurines are used as maintenance therapy in ulcerative colitis (UC), but whether these drugs influence the natural history of the disease is unknown. We aimed to assess the effect of thiopurines in terms of colectomy, hospital admission, progression in disease extent and anti-tumour necrosis factor (TNF) therapy within 10 years from initiation.DESIGN: Patients diagnosed with UC within the Örebro University Hospital catchment area, during 1963-2010, who initiated thiopurines (n=253) were included. To overcome the risk of confounding by indication, we compared patients who stopped treatment within 12 months because of an adverse reaction (n=76) with patients who continued therapy or discontinued due to other reasons (n=177) and assessed long-term outcomes using Cox regression with adjustment for potential confounding factors.RESULTS: The cumulative probability of colectomy within 10 years was 19.5% in tolerant patients compared with 29.0% in intolerant (adjusted HR 0.49; 95% CI 0.21 to 0.73). The probability of hospital admission was 34.0% in tolerant versus 56.2% in intolerant patients (adjusted HR 0.36; 95% CI 0.23 to 0.56). The risk for progression in disease extent was 20.4% in tolerant patients compared with 48.8% in intolerant (adjusted HR 0.47; 95% CI 0.21 to 1.06). Within 10 years, 16.1% of tolerant and 27.5% of intolerant patients received anti-TNF therapy (adjusted HR 0.49; 95% CI 0.26 to 0.92).CONCLUSION: Based on the novel approach of comparing patients tolerant and intolerant to thiopurines, we reveal that thiopurines have a profound beneficial impact of the natural history and long-term colectomy rates of UC.© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2019. All rights reserved. No commercial use is permitted unless otherwise expressly granted. PMID: 29618498
Faculty Opinions recommendation of Clinical Response to Vedolizumab in Ulcerative Colitis Patients Is Associated with Changes in Integrin Expression Profiles.
2018-08-02

BACKGROUND: Despite large clinical success, deeper insights into the immunological effects of vedolizumab therapy for inflammatory bowel diseases are scarce. In particular, the reasons for differential clinical response in individual patients, the precise impact on the equilibrium of integrin-expressing T cell subsets, and possible associations between these issues are not clear.METHODS: Blood samples from patients receiving clinical vedolizumab therapy were sequentially collected and analyzed for expression of integrins and chemokine receptors on T cells. Moreover, clinical and laboratory data from the patients were collected, and changes between homing marker expression and clinical parameters were analyzed for possible correlations.RESULTS: While no significant correlation of changes in integrin expression and changes in outcome parameters were identified in Crohn's disease (CD), increasing α4β7 levels in ulcerative colitis (UC) seemed to be associated with favorable clinical development, whereas increasing α4β1 and αEβ7 correlated with negative changes in outcome parameters. Changes in α4β1 integrin expression after 6 weeks were significantly different in responders and non-responders to vedolizumab therapy as assessed after 16 weeks with a cutoff of +4.2% yielding 100% sensitivity and 100% specificity in receiver-operator-characteristic analysis.DISCUSSION: Our data show that clinical response to vedolizumab therapy in UC but not in CD is associated with specific changes in integrin expression profiles opening novel avenues for mechanistic research and possibly prediction of response to therapy. PMID: 28717358
Faculty Opinions recommendation of Long-term outcome of patients with steroid-refractory acute severe UC treated with ciclosporin or infliximab.
2018-08-02

OBJECTIVE: Ciclosporin and infliximab have demonstrated short-term similar efficacy as second-line therapies in patients with acute severe UC (ASUC) refractory to intravenous steroids. The aim of this study was to assess long-term outcome of patients included in a randomised trial comparing ciclosporin and infliximab.DESIGN: Between 2007 and 2010, 115 patients with steroid-refractory ASUC were randomised in 29 European centres to receive ciclosporin or infliximab in association with azathioprine. Patients were followed until death or last news up to January 2015. Colectomy-free survival rates at 1 and 5 years and changes in therapy were estimated through Kaplan-Meier method and compared between initial treatment groups through log-rank test.RESULTS: After a median follow-up of 5.4 years, colectomy-free survival rates (95% CI) at 1 and 5 years were, respectively, 70.9% (59.2% to 82.6%) and 61.5% (48.7% to 74.2%) in patients who received ciclosporin and 69.1% (56.9% to 81.3%) and 65.1% (52.4% to 77.8%) in those who received infliximab (p=0.97). Cumulative incidence of first infliximab use at 1 and 5 years in patients initially treated with ciclosporin was, respectively, 45.7% (32.6% to 57.9%) and 57.1% (43.0% to 69.0%). Only four patients from the infliximab group were subsequently switched to ciclosporin. Three patients died during the follow-up, none directly related to UC or its treatment.CONCLUSIONS: In this cohort of patients with steroid-refractory ASUC initially treated by ciclosporin or infliximab, long-term colectomy-free survival was independent from initial treatment. These long-term results further confirm a similar efficacy and good safety profiles of both drugs and do not favour one drug over the other.TRIAL REGISTRATION NUMBER: EudraCT: 2006-005299-42; ClinicalTrials.gouv number: NCT00542152; post-results.Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/. PMID: 28053054
Faculty Opinions recommendation of Limited uptake of ulcerative colitis "treat-to-target" recommendations in real-world practice.
2018-08-02

BACKGROUND AND AIMS: A "treat-to-target" approach has been proposed for ulcerative colitis (UC), with a target of combined clinical and endoscopic remission. The aim of the study was to evaluate the extent to which proposed targets are achieved in real-world care, along with clinician perceptions and potential challenges.METHODS: A multicentre, retrospective, cross-sectional review of patients with UC attending outpatient services in South Australia was conducted. Clinical and objective assessment of disease activity (endoscopy, histology, and/or biomarkers) was recorded. A survey evaluated gastroenterologists' perceptions of treat to target in UC. Statistical analysis included logistic regression and Fisher's exact tests.RESULTS: Of 246 patients with UC, 61% were in clinical remission (normal bowel habit and no rectal bleeding), 35% in clinical and endoscopic remission (Mayo endoscopic sub-score ≤ 1), and 16% in concordant clinical, endoscopic, and histological (Truelove and Richards' Index) remission. Rather than disease-related factors (extent/activity), clinician-related factors dominated outcome. Hospital location and the choice of therapy predicted combined clinical and endoscopic remission (OR 3.6, 95% CI 1.6-8.7, P < 0.001; OR 3.3, 95% CI 1.1-12.5, P = 0.04, respectively). Clinicians used C-reactive protein more often than endoscopy as a biomarker for disease activity (75% vs 47%, P < 0.001). In the survey, 45/61 gastroenterologists responded, with significant disparity between clinician estimates of targets achieved in practice and real-world data (P < 0.001 for clinical and endoscopic remission).CONCLUSIONS: Most patients with UC do not achieve composite clinical and endoscopic remission in "real-world" practice. Clinician uptake of proposed treat-to-target guidelines is a challenge to their implementation.© 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd. PMID: 28806471
Faculty Opinions recommendation of Tofacitinib as induction and maintenance therapy for ulcerative colitis.
2018-08-02

BACKGROUND: Tofacitinib, an oral, small-molecule Janus kinase inhibitor, was shown to have potential efficacy as induction therapy for ulcerative colitis in a phase 2 trial. We further evaluated the efficacy of tofacitinib as induction and maintenance therapy.METHODS: We conducted three phase 3, randomized, double-blind, placebo-controlled trials of tofacitinib therapy in adults with ulcerative colitis. In the OCTAVE Induction 1 and 2 trials, 598 and 541 patients, respectively, who had moderately to severely active ulcerative colitis despite previous conventional therapy or therapy with a tumor necrosis factor antagonist were randomly assigned to receive induction therapy with tofacitinib (10 mg twice daily) or placebo for 8 weeks. The primary end point was remission at 8 weeks. In the OCTAVE Sustain trial, 593 patients who had a clinical response to induction therapy were randomly assigned to receive maintenance therapy with tofacitinib (either 5 mg or 10 mg twice daily) or placebo for 52 weeks. The primary end point was remission at 52 weeks.RESULTS: In the OCTAVE Induction 1 trial, remission at 8 weeks occurred in 18.5% of the patients in the tofacitinib group versus 8.2% in the placebo group (P=0.007); in the OCTAVE Induction 2 trial, remission occurred in 16.6% versus 3.6% (P< 0.001). In the OCTAVE Sustain trial, remission at 52 weeks occurred in 34.3% of the patients in the 5-mg tofacitinib group and 40.6% in the 10-mg tofacitinib group versus 11.1% in the placebo group (P< 0.001 for both comparisons with placebo). In the OCTAVE Induction 1 and 2 trials, the rates of overall infection and serious infection were higher with tofacitinib than with placebo. In the OCTAVE Sustain trial, the rate of serious infection was similar across the three treatment groups, and the rates of overall infection and herpes zoster infection were higher with tofacitinib than with placebo. Across all three trials, adjudicated nonmelanoma skin cancer occurred in five patients who received tofacitinib and in one who received placebo, and adjudicated cardiovascular events occurred in five who received tofacitinib and in none who received placebo; as compared with placebo, tofacitinib was associated with increased lipid levels.CONCLUSIONS: In patients with moderately to severely active ulcerative colitis, tofacitinib was more effective as induction and maintenance therapy than placebo. (Funded by Pfizer; OCTAVE Induction 1, OCTAVE Induction 2, and OCTAVE Sustain ClinicalTrials.gov numbers, NCT01465763 , NCT01458951 , and NCT01458574 , respectively.). PMID: 28467869
Faculty Opinions recommendation of Effects of concomitant immunomodulators on the pharmacokinetics, efficacy and safety of adalimumab in patients with Crohn's disease or ulcerative colitis who had failed conventional therapy.
2018-08-02

Read the full review for this Faculty Opinions recommended article: Effects of concomitant immunomodulators on the pharmacokinetics, efficacy and safety of adalimumab in patients with Crohn's disease or ulcerative colitis who had failed conventional therapy.
Faculty Opinions recommendation of Discrepancies between patient-reported outcomes, and endoscopic and histological appearance in UC.
2018-08-02

OBJECTIVE: Both endoscopy and histology may be included in the definition of mucosal healing in UC. This study aimed to establish the association between patient-reported outcomes, specifically symptom measures, and the presence of inflammation as measured by endoscopy and histology in UC.DESIGN: Using patient data from an observational multicentre study of UC (n=103), rectal bleeding (RB) and stool frequency (SF) symptom subscores of the Mayo Clinic Score (MCS) were compared with the endoscopic subscore (MCSe) and histology. Faecal calprotectin and biopsy cytokine expression were also evaluated.RESULTS: When identifying UC patients with inactive disease, RB scores were superior to SF scores and the combination (sensitivity/specificity: MCSe=0/1, RB 77%/81%, SF 62%/95%, RB+SF 54%/95%; MCSe=0, RB 87%/66%, SF 76%/83%, RB+SF 68%/86%). Across different definitions of mucosal healing (MCSe≤1; 0; or 0 plus inactive histology), a larger subset of patients reported increased SF (39%, 25% and 27%, respectively) compared with RB (24%, 13% and 10%). Faecal calprotectin and inflammatory cytokine expression were higher in patients with active disease compared with patients with mucosal healing, but there were no differences between patients using increasingly stringent definitions of mucosal healing.CONCLUSIONS: Endoscopically inactive disease is associated with absence of RB but not with complete normalisation of SF. Achieving histological remission did not improve symptomatic relief. In addition, in these patients, higher inflammatory biomarker levels were not observed. These data suggest that non-inflammatory changes, such as bowel damage, may contribute to SF in UC.Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/. PMID: 27590995
Faculty Opinions recommendation of Impact of Histological and Endoscopic Remissions on Clinical Recurrence and Recurrence-free Time in Ulcerative Colitis.
2018-08-02

BACKGROUND: Clinical and endoscopic remissions constitute the therapeutic goals in ulcerative colitis (UC). Histological healing is currently not a target in UC. This study aims to determine the impact of the definition of endoscopic remission (Mayo endoscopic subscore [MSe] 0-1) and histological activity in the recurrence of UC and recurrence-free survival time.METHODS: Patients with UC in clinical remission (partial Mayo score ≤ 1) and endoscopic remission (MSe ≤ 1) who underwent colonoscopy with biopsies between March 2010 and December 2013 were included. The validated Nancy score was used to evaluate histological activity, which considers inactivity if 0 to 1 and activity if 2 to 4. The recurrence-free time was evaluated and recurrence was defined as partial Mayo score ≥ 2, therapy to induce remission, hospitalization, or colectomy. Predictive factors associated with recurrence and time to recurrence were determined.RESULTS: Sixty patients were included; 58.3% (n = 35) were women, with a mean age of 52.7 years. MSe = 1 was observed in 46.7% (n = 28) and histological activity in 38.3% (n = 23). Clinical recurrence occurred in 31.7% (n = 19) of patients, with a cumulative risk of 17.1%/24.5%/26.7%/40.1% at 12/24/36/48 months, respectively. MSe = 1 (P = 0.02) and histological activity (P = 0.007) were significantly associated with recurrence. Of these, only histological activity (P = 0.03) was an independent predictive factor of recurrence. Patients with MSe = 1 (P = 0.02) and with histological activity (P = 0.01) had a significantly shorter recurrence-free time in univariate analysis. In multivariate analysis, only histological activity (P = 0.02) was an independent predictive factor of lower recurrence-free time.CONCLUSION: The presence of histological activity represents an independent predictive factor of recurrence and time to recurrence, which was not verified with MSe 0 to 1. PMID: 28991857
Faculty Opinions recommendation of Postoperative Outcomes in Vedolizumab-Treated Patients Undergoing Major Abdominal Operations for Inflammatory Bowel Disease: Retrospective Multicenter Cohort Study.
2018-08-02

Read the full review for this Faculty Opinions recommended article: Postoperative Outcomes in Vedolizumab-Treated Patients Undergoing Major Abdominal Operations for Inflammatory Bowel Disease: Retrospective Multicenter Cohort Study.
Faculty Opinions recommendation of Systematic review: the safety of vedolizumab for the treatment of inflammatory bowel disease.
2018-08-02

BACKGROUND: Vedolizumab specifically recognises the α4β7 integrin and selectively blocks gut lymphocyte trafficking: potentially, it offers gut-specific immunosuppression.AIM: To review the safety of vedolizumab and summarise post-marketing data to assess if any safety concerns that differ from registration trials have emerged.METHOD: A systematic bibliographic search identified six registration trials and nine cohort studies.RESULTS: Integrated data from registration trials included 2830 vedolizumab-exposed patients (4811 person-years exposure [PYs]) and 513 placebo patients. This reported lower exposure-adjusted incidence rates of infection (63.5/100 PYs; 95% CI: 59.6-67.3) and serious adverse events (20.0/100 PYs; 95% CI: 18.5-21.5) compared to placebo (82.9/100 PYs; 95% CI: 68.3-97.5) and (28.3/100 PYs 95% CI: 20.6-35.9) respectively. Higher, but statistically insignificant rates of enteric infections occurred in vedolizumab-exposed patients (7.4/100 PYs; 95% CI: 6.6-8.3) compared to placebo (6.7 PYs; 95% CI: 3.2-10.1). Six post-marketing cohort studies (1049 patients, 403 PYs) demonstrated rates of infection of 8% (82/1049); enteric infection of 2% (21/1049) and adverse events of 16% (166/1049). Multivariate analysis in one cohort study suggested increased risk of surgical site infection with perioperative VDZ. Human experience in pregnancy is limited.CONCLUSIONS: Post-marketing data confirm the excellent safety of vedolizumab observed in registration trials. The signal of post-operative complications should be interpreted with caution, but warrants further study. Although comparative studies are needed, Vedolizumab may be a safe alternative in patients who best avoid systematic immunosuppression, including those pre-disposed to infection, malignancy or the elderly.© 2017 John Wiley & Sons Ltd. PMID: 28449273
Faculty Opinions recommendation of Faecal Microbiota Transplantation for Inflammatory Bowel Disease: A Systematic Review and Meta-analysis.
2018-08-02

Background: Faecal microbiota transplantation [FMT] has been investigated as a potential treatment for inflammatory bowel disease [IBD]. We thus performed a systematic review and meta-analysis assessing the effectiveness and safety of FMT in IBD.Methods: A systematic review was conducted until January 2017. Studies were excluded if patients had co-infection or data were pooled across disease subtypes (ulcerative colitis [UC], Crohn's disease [CD], pouchitis). Clinical remission was established as the primary outcome. Pooled effect sizes and 95% confidence intervals were obtained using the random effects model.Results: In all, 53 studies were included [41 in UC, 11 in CD, 4 in pouchitis]. Overall, 36% [201/555] of UC, 50.5% [42/83] of CD, and 21.5% [5/23] of pouchitis patients achieved clinical remission. Among cohort studies, the pooled proportion achieving clinical remission was 33% (95% confidence interval [CI] = 23%-43%] for UC and 52% [95% CI = 31%-72%] for CD, both with moderate risk of heterogeneity. For four RCTs in UC, significant benefit in clinical remission (pooled odds ratios [[P-OR] = 2.89, 95% CI = 1.36-6.13, p = 0.006) with moderate heterogeneity [Cochran's Q, p = 0.188; I2 = 37%] was noted. Sub-analyses suggest remission in UC improved with increased number of FMT infusions and lower gastrointestinal tract administration. Most adverse events were transient gastrointestinal complaints. Microbiota analysis was performed in 24 studies, with many identifying increased diversity and a shift in recipient microbiota profile towards the donor post-FMT.Conclusions: FMT appears effective in UC remission induction, but long-term durability and safety remain unclear. Additional well-designed controlled studies of FMT in IBD are needed, especially in CD and pouchitis.Copyright © 2017 European Crohn's and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com PMID: 28486648
Faculty Opinions recommendation of The effects of aminosalicylates or thiopurines on the risk of colorectal cancer in inflammatory bowel disease.
2018-08-02

BACKGROUND: Whether aminosalicylates or thiopurines reduce the risk of colorectal cancer (CRC) in inflammatory bowel (IBD) disease is controversial.AIM: To assess simultaneously the chemopreventive effect of aminosalicylates or thiopurines in a case-control study nested in the CESAME observational cohort that enrolled consecutive patients with IBD between May 2004 and June 2005. Patients were followed up to December 2007.METHODS: Study population comprised 144 case patients who developed CRC from the diagnosis of IBD (65 and 79 cases diagnosed, respectively, before and from 2004, starting year of the prospective observational period of CESAME) and 286 controls matched for gender, age, IBD subtype and year of diagnosis, and cumulative extent of colitis. Exposure to aminosalicylates or thiopurines was defined by an exposure to the treatment during the year of the diagnosis of cancer. The propensity of receiving 5-ASA and thiopurines was quantified by a composite score taking into account patient and IBD characteristics. The role of aminosalicylates or thiopurines was assessed by multivariate analysis. Propensity scores and the history of primary sclerosing cholangitis were entered into the multivariate model for adjustment.RESULTS: By multivariate analysis adjusted for propensity, a significant protective effect of exposure to drugs during the year of cancer was found for aminosalicylates (OR = 0.587, 95% CI: 0.367-0.937, P = 0.0257), but not for thiopurines (OR = 0.762, 95% CI: 0.432-1.343, P = 0.3468).CONCLUSION: In a case-control study nested in the CESAME cohort, a significant decrease in the risk of colorectal cancer in IBD was associated with exposure to aminosalicylates, not to thiopurines.© 2016 John Wiley & Sons Ltd. PMID: 27995656 Funding information This work was supported by: Department of Health, United Kingdom Grant ID: RC-PG-0407-10054 Versus Arthritis, United Kingdom Grant ID: 20639 Versus Arthritis, United Kingdom Grant ID: 18475 Arthritis Research UK, United Kingdom Grant ID: 18475
Faculty Opinions recommendation of Endoscopic score vs. fecal biomarkers for predicting relapse in patients with ulcerative colitis after clinical remission and mucosal healing.
2018-08-02

Read the full review for this Faculty Opinions recommended article: Endoscopic score vs. fecal biomarkers for predicting relapse in patients with ulcerative colitis after clinical remission and mucosal healing.