Background Limited data are available on biological therapy de-escalation after prior escalation in inflammatory bowel disease (IBD) patients. This study aimed to assess the frequency and success rate of de-escalation of biological therapy in IBD patients after prior dose escalation and to evaluate which measures are used to guide de-escalation. Methods This multicentre retrospective cohort study enrolled IBD patients treated with infliximab (IFX), adalimumab (ADA) or vedolizumab (VEDO) in whom therapy was de-escalated after prior biological escalation. De-escalations were considered pharmacokinetic-driven if based on clinical symptoms combined with therapeutic or supratherapeutic trough levels, and disease activity-driven if based on faecal calprotectin less than or equal to 200 µg/g or resolution of perianal fistula drainage or closure or endoscopic remission. Successful de-escalation was defined as remaining on the same or lower biological dose for greater than or equal to 6 months after de-escalation without the need for corticosteroids. Results In total, 206 IFX users, 85 ADA users and 55 VEDO users underwent therapy escalation. Of these patients, 34 (17%) on IFX, 18 (21%) on ADA and 8 (15%) on VEDO underwent therapy de-escalation. De-escalation was successful in 88% of IFX patients, 89% of ADA and 100% of VEDO. The probability of remaining on the de-escalated regimen or further de-escalation after 1 year was 85% for IFX, 62% for ADA and 100% for VEDO. Disease activity-driven de-escalations were more often successful (97%) than pharmacokinetic- and no marker-driven de-escalations (76%); P = 0.017. Conclusion De-escalation after biological dose escalation was successful in the majority of carefully selected IBD patients. Objective assessment of remission increased the likelihood of successful de-escalation.
Objective: Smoking has been reported as influencing disease activity in inflammatory bowel disease. The aim of our study was to elucidate the relationship between smoking and aspects of disease-specific quality of life in inflammatory bowel disease. Design: Cross-sectional study. Methods: In 1105 prevalent patients with inflammatory bowel disease, diagnosed according to the criteria of Lennard-Jones and Truelove and Witts, disease-specific quality of life was investigated using the Inflammatory Bowel Disease Questionnaire (IBDQ). Results: In Crohn's disease, smoking females reported a lower quality of life than non-smoking females (all four dimensions of the IBDQ). Using an explanatory model of relationships between the four dimensions for the analysis, it became evident that smoking is associated with more bowel symptoms in young Crohn's disease females, with more emotional dysfunction in all Crohn's disease females, and with more systemic symptoms in all three diagnostic groups with marked bowel symptoms. Moderately smoking male ulcerative colitis patients reported fewer bowel complaints compared with non-smoking male ulcerative colitis patients. Conclusion: There is a relationship between smoking and disease-specific quality of life in both ulcerative colitis and Crohn's disease. The hypothesis is presented that a part of the observed differences in the studied quality of life dimensions with respect to age, sex and disease group are related to concomitant oral contraceptive use. European Journal of Gastroenterology & Hepatology 1996, 8:1075–1081
Abstract Objectives Fatigue is a prevalent and burdensome problem in patients with inflammatory bowel disease (IBD), even when the disease is in remission. Evidence-based psychological interventions for managing IBD-related fatigue are still lacking. This study aimed to examine the efficacy of Mindfulness-Based Cognitive Therapy (MBCT) for reducing fatigue in patients with IBD in remission. Method A two-arm multicenter randomized controlled trial was conducted in 113 IBD outpatients in remission with elevated levels of fatigue (i.e., Checklist Individual Strength — subjective fatigue ≥ 27). Patients were randomly assigned to an 8-week MBCT program ( n = 56) or a waiting-list condition ( n = 57). All participants completed questionnaires at baseline and directly post-intervention. The primary outcome was fatigue, assessed with the Checklist Individual Strength-20. Secondary outcomes included fatigue interference in daily life, depression, anxiety, and IBD-specific quality of life. Analysis of covariance (ANCOVA) was performed to examine treatment outcomes. Results Intention-to-treat analyses showed significant reductions in the subjective experience of fatigue in patients receiving MBCT, compared to the waiting-list control condition ( p = 0.03; Cohen’s d = 0.46; clinically relevant improvement in 36% vs. 10%). No significant effects were found on other fatigue aspects or secondary outcomes. Conclusions An 8-week MBCT group program effectively reduced the subjective experience of fatigue in patients with IBD in remission. Results do not support effects for other aspects of fatigue or secondary outcomes. Preregistration ClinicalTrials.gov Identifier: NCT03162575.
Background Vedolizumab is a humanised monoclonal antibody against α4β7-integrin capable of blocking the migration of several immune cells across endothelium expressing MAdCAM-1. This new class of biological drugs has shown efficacy in treating inflammatory bowel disease (IBD) in randomised clinical trials. Vedolizumab is registered since October 2014 in the Netherlands. Here, we describe the clinical experience in 3 centres using vedolizumab for ulcerative colitis (UC) and Crohn’s disease (CD). Methods We retrospectively analysed clinical activity and clinical response determined by a composite score based on a VAS scale for pain and fatigue, number of liquid stools, choice of treatment, patient’s ability to work or study, and the conclusion of the attending physician. Further laboratory parameters and the use of vedolizumab was studied. Results From October 2014 until November 2015, 48 patients with moderate/severe IBD (mean age 43, 39.6% male, 27; CD and 21 UC patients) were included; 90% had failed at least 1 tumour necrosis factor (TNF) antagonist before treatment. The average duration of disease before treatment with vedolizumab was 9.4 years (range 1–38 years). The average duration of vedolizumab treatment was 25.7 weeks (average 5.6 infusions administered). Concomitant medication included mesalazine (20%), MTX or Thiopurines (20%), Steroids (33%), and 27% was treated with vedolizumab as monotherapy. Further, 27 patients, 56 % (17 CD patients and 10 UC patients) responded to vedolizumab (average 6.8 doses; follow-up 32 weeks) 44% of these responders (7 CD patients and 5 UC patients) reached remission after average 7.2 infusions (41 weeks follow-up). In addition, 15 patients, 31% (7 CD patients, 8 UC patients) were primary non-responders. Moreover, 5 patients, 10% (2 CD patients, 3 UC patients) showed loss of response; 1 of them underwent surgery. In 1 CD patient (2%), vedolizumab was stopped after 1 infusion because of side effects (nasopharyngitis). Conclusion In this Dutch real-life IBD cohort with 90% prior anti-TNF failure, vedolizumab showed a 56% response and 25% remission rate without showing major adverse events.
IntroductionInflammatory bowel diseases are chronic conditions that might cause a severe impact on social life. The aim of the study was to assess employment, chronic work disability, and sick leave in patients with inflammatory bowel disease.
Biological sex affects numerous aspects of biology, yet how sex influences different biological processes has not been extensively studied at the molecular level. Caenorhabditis elegans, with both hermaphrodites (functionally females as adults) and males, is an excellent system to uncover how sex influences physiology. Here, we describe a method to isolate large quantities of C. elegans males by conditionally degrading DPY-27, a component of the dosage compensation complex essential for hermaphrodite, but not male, development. We show that germ cells from males isolated following DPY-27 degradation undergo meiosis and spermiogenesis like wild type and are competent to mate and produce viable offspring. We demonstrate the efficacy of this system by analyzing gene expression and performing affinity pull-downs from male worm extracts.
This study was designed to assess the healing rate of complex perianal fistulas in Crohn's disease after a multistep strategy, including induction treatment with Infliximab in case of active proctitis, followed by definitive surgery.From 2000 to 2003, all consecutive patients with complex fistulas and Crohn's disease underwent pretreatment with noncutting setons and, in case of severe recurrent fistulas or abscesses, a diverting stoma. Infliximab was added in cases of active proctitis. After definitive surgical treatment, patients were examined.Seventeen patients were included (median age, 34 (range, 22-58) years). Seven patients were treated by surgery only, and in ten patients Infliximab was added. After a median follow-up of 19 (range, 8-40) months, fistula healing was observed in 17 patients (100 percent). One patient of the Infliximab group developed a recurrent fistula (10 percent) after 24 months, and in one patient (10 percent) soiling occurred. Two patients of the surgical group developed a recurrent fistula (29 percent) and soiling occurred in two patients (29 percent).A multistep strategy followed by definitive surgery for the treatment of complex perianal fistulas in patients with Crohn's disease is a promising treatment modality. The preliminary results of this study suggest that Infliximab treatment has a beneficial additive effect in the multistep treatment followed by definitive surgery of complex anal fistulas and active proctitis in Crohn's disease.
BackgroundNOD2/CARD15, the first identified susceptibility gene in Crohn's disease (CD), is associated with ileal stenosis and increased frequency of surgery. Anti-Saccharomyces cerevisiae antibody (ASCA), a serological marker for CD, is associated with ileal location and a high likelihood for surgery. We hypothesized that the presence of ASCA and NOD2/CARD15 mutations could predict increased health care cost in CD.
