Effectiveness of Mindfulness-Based Cognitive Therapy in reducing psychological distress and improving sleep in patients with Inflammatory Bowel Disease: study protocol for a multicentre randomised controlled trial (MindIBD).

BACKGROUND: Many patients with Inflammatory Bowel Diseases (IBD) suffer from psychological distress, fatigue and sleep disturbances, which are associated with reduced quality of life (QoL) and increased societal costs. Only limited psychosocial treatment options are available. As Mindfulness-Based Cognitive Therapy (MBCT) has demonstrated to improve psychological distress, QoL and sleep in other populations, MBCT might also be effective in patients with IBD. METHODS: The MindIBD study is a prospective, multicentre, randomised controlled trial comparing MBCT plus Treatment As Usual (TAU) versus TAU alone in a targeted number of 136 IBD patients in remission, aged 16 years and older with at least mild psychological distress (Hospital Anxiety and Depression Scale (HADS) total score ≥ 11). Primary outcome is reduction of psychological distress post-intervention, measured by the HADS. In addition, the effect of MBCT on sleep quality (including actigraphy and electroencephalography recordings), fatigue, disease activity, perceived disease control, QoL and positive mental health will be examined. Assessments will be conducted at baseline and at 3, 6, 9 and 12 months follow-up. Cost-effectiveness will be determined and a process evaluation will be conducted. DISCUSSION: This study will provide valuable insight into the clinical effect of MBCT on psychological distress, sleep quality, fatigue and QoL in IBD patients and into the cost-effectiveness. If effective, MBCT can be a valuable addition to the available psychosocial interventions for patients with IBD. Moreover, findings from this study may also be applicable in patients with other chronic conditions. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04646785, registered on 30/11/2020.

Impact of Biological Therapies and Tofacitinib on Real-world Work Impairment in Inflammatory Bowel Disease Patients: A Prospective Study.

BACKGROUND: There are limited real-world data on the change in total work impairment (TWI) in biological-treated patients with inflammatory bowel disease (IBD). This study aimed to evaluate the real-world effects of initiating biological therapy or tofacitinib on change in TWI in IBD patients. METHODS: This multicenter prospective cohort study enrolled IBD patients who started treatment with biological therapy or tofacitinib. Subjects completed the work productivity and activity impairment (WPAI) questionnaire and short inflammatory bowel disease questionnaire at therapy initiation and at week 26. Total work impairment comprises working hours missed due to sick leave and impact of disease during working hours (range 0%-100%). Clinical disease activity was assessed using the Harvey-Bradshaw Index and Simple Clinical Colitis Activity Index (SCCAI). RESULTS: We included 137 IBD patients for analyses (median age 38 years, 58% Crohn's disease [CD]). The median baseline TWI was 50% and decreased by a median of 10%-points of points after 26 weeks. Patients with continued biological therapy or tofacitinib use, clinical disease activity at baseline, and clinical response or remission at week 26 showed a greater median TWI reduction (22%-points) than the remaining study patients (7%-points; P = .014). Ulcerative colitis (UC) and IBD-unclassified (IBD-U) patients showed a greater median TWI reduction (26%-points) than CD patients (6%-points); P = .041. Correlations were observed between decrease in TWI and decrease in SCCAI, decrease in fatigue and increase in quality of life. CONCLUSIONS: Work impairment in IBD patients decreased following biological therapy or tofacitinib initiation. Patients achieving clinical remission or response showed the greatest improvement, especially UC and IBD-U patients.

De-escalation of biological therapy in inflammatory bowel disease patients following prior dose escalation.

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.

Discrepancy between patient- and healthcare provider-reported adverse drug reactions in inflammatory bowel disease patients on biological therapy.

BACKGROUND: Only limited data is available on the extent and burden of adverse drug reactions (ADRs) to biological therapy in inflammatory bowel disease (IBD) patients in daily practice, especially from a patient's perspective. OBJECTIVE: The aim of this study was to systematically assess patient-reported ADRs during biological therapy in IBD patients and compare these with healthcare provider (HCP)-reported ADRs. METHODS: This multicentre, prospective, event monitoring study enrolled IBD patients on biological therapy. Patients completed bimonthly comprehensive web-based questionnaires regarding description of biological induced ADRs, follow-up of previous ADRs and experienced burden of the ADR using a five-point Likert scale. The relationship between patient-reported ADRs and biological therapy was assessed. HCP-reported ADRs were extracted from the electronic healthcare records. RESULTS: In total, 182 patients (female 51%, mean age 42.2 [standard deviation 14.2] years, Crohn's disease 77%) were included and completed 728 questionnaires. At baseline, 60% of patients used infliximab, 30% adalimumab, 9% vedolizumab and 1% ustekinumab. Fifty percent of participants reported at least one ADR with a total of 239 unique ADRs. Fatigue (n = 26) and headache (n = 20) resulted in the highest burden and a correlation in time with the administration of the biological was described in 56% and 85% respectively. Out of 239 ADRs, 115 were considered biological-related. HCPs reported 119 ADRs. Agreement between patient-reported ADRs and HCP-reported ADRs was only 13%. CONCLUSION: IBD patients often report ADRs during biological therapy. We observed an important significant difference between the type and frequency of patient-reported ADRs versus HCP-reported ADRs, leading to an underestimation of more subjective ADRs and patients' ADR-related burden.

High mucosal healing rates in 5-ASA-treated ulcerative colitis patients: results of a meta-analysis of clinical trials.

BACKGROUND: Recently, mucosal healing (MH) is regarded as an important treatment goal in ulcerative colitis (UC). 5-Aminosalicylates (5-ASA) are the standard treatment in mild-to-moderate UC, but the effect on MH is less known. The aim of this study was to systematically review the medical literature in order to compare different preparations of 5-ASA for the effect on MH. METHODS: We conducted a structured search of PubMed and the Cochrane Central Register of Controlled Trials to identify randomized controlled clinical trials with 5-ASA in UC providing data about MH. We calculated the sample size-weighted pooled proportion of patients with MH, and performed meta-analysis of head-to-head comparisons. RESULTS: Out of 645 hits, we included 90 treatment arms, involving 3977 patients using oral 5-ASA (granulate and tablets) and 2513 patients using rectal 5-ASA (suppositories, enema, and foam). Overall, 43,7% of 5-ASA treated patients achieved MH (oral 36,9%; rectal 50,3%). In oral studies, 49% of patients using granulate (7 treatment-arms) achieved MH compared to 34,9% using tablets (43 treatment-arms). In rectal studies the proportion of MH was 62% for suppositories (eight treatment arms), 51% for foam (nine treatment arms), and 46% for enema (23 treatment arms), respectively. CONCLUSIONS: 5-ASA preparations achieved MH in nearly 50% of UC patients. There were no significant differences in MH between the various 5-ASA agents, either in the oral or the rectal treatment groups.