Dataset Information

Impact of Obesity on Short- and Intermediate-Term Outcomes in Inflammatory Bowel Diseases: Pooled Analysis of Placebo Arms of Infliximab Clinical Trials.

ABSTRACT: Background and aims:To assess whether obesity may affect natural history of inflammatory bowel diseases (IBD), we conducted an individual participant data (IPD) pooled analysis of placebo arms, using data from clinical trials of infliximab in IBD and using the Yale Open Data Access (YODA) Project. Methods:We obtained IPD from 4 placebo-controlled trials of infliximab in adults with IBD (ACCENT-I and ACCENT-II; ACT-1 and ACT-2). Patients were categorized into quartiles based on body mass index (BMI) or weight at time of trial entry. Primary outcome was clinical remission (Crohn's disease activity index [CDAI]<150, Mayo Clinic Score <3); secondary outcomes were clinical response and mucosal healing. Using multivariable logistic regression analysis, we compared association between quartiles of BMI (or weight) and achieving remission, after adjusting for sex, smoking, disease activity, and concomitant prednisone or immunomodulators. Results:We included 575 placebo-treated patients (mean age 38 years, 51.6% males, 16% obese). Obesity was not associated with odds of achieving clinical remission (Q4 vs Q1: adjusted OR, 1.36; 95% CI, 0.65-2.89; P-value for trend = 0.57), clinical response (Q4 vs Q1: adjusted OR, 1.31; 95% CI, 0.61-2.81; P = 0.45), or mucosal healing remission (Q4 vs Q1: adjusted OR, 0.55; 95% CI, 0.12-2.34; P = 0.31). These results were consistent across strata based on disease type (CD and ulcerative colitis) and trial design (induction and maintenance therapy). Conclusions:Based on IPD pooled analysis of placebo arms, obesity does not significantly impact short- and intermediate-term clinical outcomes in patients with IBD. The impact of obesity on long-term patient-important outcomes like surgery and hospitalization merits evaluation.

SUBMITTER: Singh S

PROVIDER: S-EPMC6140448 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Impact of Obesity on Short- and Intermediate-Term Outcomes in Inflammatory Bowel Diseases: Pooled Analysis of Placebo Arms of Infliximab Clinical Trials.

Singh Siddharth S Proudfoot James J Xu Ronghui R Sandborn William J WJ

Inflammatory bowel diseases 20180901 10

<h4>Background and aims</h4>To assess whether obesity may affect natural history of inflammatory bowel diseases (IBD), we conducted an individual participant data (IPD) pooled analysis of placebo arms, using data from clinical trials of infliximab in IBD and using the Yale Open Data Access (YODA) Project.<h4>Methods</h4>We obtained IPD from 4 placebo-controlled trials of infliximab in adults with IBD (ACCENT-I and ACCENT-II; ACT-1 and ACT-2). Patients were categorized into quartiles based on bod ...[more]

PMID: 29788260

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Project description:Background:There is debate in the literature as to whether inclusion of a placebo arm may alter characteristics of antidepressant trials. However, previous research has focused on response rates of various antidepressants on average only, ignoring potential differences among drugs or other aspects of trial findings. Little is known about the impact of a placebo arm on all-cause dropout and dropout due to adverse events. Methods:We carried out a systematic review of published and unpublished double-blind randomized controlled trials (RCTs) for the acute treatment of unipolar major depression (update: January 2016). The probability of being allocated to placebo (?) was the exposure of interest, and we examined its influence on responders (efficacy), all-cause dropouts (acceptability) and dropouts due to adverse events (tolerability), while accounting for differences in drugs, trials and patient characteristics in multivariate random effects meta-regression. Results:We included 421 studies (68 305 participants) comparing 16 antidepressants or placebo; ? ranged from 20% to 50%. Response rate was lower [risk ratio (RR) 0.87; 95% confidence interval (CI) 0.83, 0.92] and all-cause dropout rate higher (RR 1.19; 95% CI 1.08, 1.31) for the same antidepressants in placebo-controlled trials compared with head-to-head trials. The probability of responding decreased by 3% (95% CI 2-5%) for every 10% increase in ?, whereas the risk of all-cause dropout increased by 4% (95% CI 1-7%). Tolerability was unaffected by ?. Response rate was inversely correlated with dropouts due to any cause (correlation coefficient -0.48; 95% CI -0.58, -0.36) and due to adverse events (-0.34; 95% CI -0.44, -0.23). Conclusions:For the same antidepressant, response rate was on average smaller and dropouts higher when placebo was included; however, no association was found with dropouts due to adverse events. Decreased patient expectations, larger dropout rates and use of inappropriate statistical methods to impute missing data may explain this phenomenon. The findings call for caution in the integration of randomized evidence involving placebo arms.

Project description:Background:In multiple clinical studies, teduglutide reduced parenteral support (PS) with a consistent safety profile in adults with short bowel syndrome-associated intestinal failure (SBS-IF). The objective of this study was to assess adverse events (AEs) from a pooled data set. Methods:Safety data from four prospective clinical trials of teduglutide in patients with SBS-IF were assimilated. AEs were evaluated in patient groups based on treatment received in each study and in populations stratified to create distinct subgroups based on aetiology, bowel anatomy and baseline PS volume requirements. Results:Safety data are reported for up to 2.5?years, totalling 222?person-years exposure to teduglutide. In most patients, AEs were reported as mild or moderate in severity in all patient groups and occurred at comparable rates between patients who received teduglutide or placebo. Several common gastrointestinal AEs, including abdominal pain, nausea and abdominal distension, were reported more frequently earlier in the course of treatment, with their frequency declining over time. Fewer gastrointestinal AEs were reported in patients with vascular causes of SBS-IF and patients with most of their colon-in-continuity than in other patient subgroups. Across the patient stratification subgroups, the predominant treatment-emergent AEs for which patients receiving teduglutide had a significantly increased relative risk were abdominal distension and gastrointestinal stoma complication compared with patients receiving placebo. Conclusions:Teduglutide had a safety profile consistent with prior adult data and no new safety concerns were identified. The most frequently reported AEs were gastrointestinal in origin, consistent with the underlying disease condition and intestinotrophic actions of teduglutide. Clinical Trial Registry information:NCT00081458/EudraCT, 2004-000438-35; NCT00798967/EudraCT, 2008-006193-15; NCT00172185/EudraCT, 2004-000439-27; NCT00930644/EudraCT, 2009-011679-65.

Dataset Information

Impact of Obesity on Short- and Intermediate-Term Outcomes in Inflammatory Bowel Diseases: Pooled Analysis of Placebo Arms of Infliximab Clinical Trials.

Publications

Impact of Obesity on Short- and Intermediate-Term Outcomes in Inflammatory Bowel Diseases: Pooled Analysis of Placebo Arms of Infliximab Clinical Trials.

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