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Background & Aims: Understanding placebo rates is critical for efficient clinical trial design. We assessed placebo rates and associated factors using individual patient data from Crohn's disease trials., Methods: We conducted a meta-analysis of phase 2/3 placebo-controlled trials evaluating advanced therapies in moderate to severe Crohn's disease (2010-2021). Deidentified individual patient data were obtained through Vivli Inc and the Yale University Open Data Access Project. Primary outcomes were clinical response and remission. Pooled placebo rates and 95% confidence intervals (CIs) were estimated using 1- and 2-stage meta-analytic approaches. Regression analyses identified patient-level factors associated with placebo rates., Results: Analysis of individual patient data from 8 induction (n = 1147) and 4 maintenance (n = 524) trials showed overall placebo clinical response and remission rates for induction were 27% (95% CI, 23%-32%) and 10% (95% CI, 8%-14%), respectively, and 32% (95% CI, 23%-42%) and 22% (95% CI, 14%-33%) for maintenance, respectively. Among biologic (bio)-naïve patients, placebo response and remission rates during induction were 29% (95% CI, 24%-35%) and 11% (95% CI, 8%-15%) respectively, and 26% (95% CI, 20%-33%) and 10% (95% CI, 8%-14%) for biologic (bio)-exposed patients, respectively. During maintenance, biologic-naïve response and remission rates were 41% (95% CI, 34%-48%) and 32% (95% CI, 24%-40%), respectively, and 29% (95% CI, 24%-34%) and 16% (95% CI, 13%-21%) for bio-exposed, respectively. Higher baseline C-reactive protein concentration predicted lower placebo rates, whereas higher baseline albumin levels and body mass index increased the odds of placebo outcomes. Increased baseline Crohn's Disease Activity Index and 2-item patient-reported outcome scores predicted higher response rates in induction, lower response rates in maintenance, and lower remission rates in induction and maintenance., Conclusions: Patient- and trial-level characteristics influence placebo rates in Crohn's disease trials. Careful implementation of eligibility criteria, outcome definitions, and patient stratification may reduce placebo rates., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Proactive therapeutic drug monitoring (TDM) has been proposed to improve outcomes in patients with inflammatory bowel disease (IBD) treated with tumor necrosis factor (TNF)α antagonists. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing proactive TDM with conventional management in patients with IBD., Methods: We identified RCTs in patients with IBD treated with TNFα antagonists comparing proactive TDM (routine assessments of trough concentration with dose adjustments to maintain predetermined trough concentration, regardless of disease activity) with conventional management (clinically driven dose adjustments). The primary outcome was failure to maintain clinical remission. Certainty of evidence was appraised using Grading of Recommendations, Assessment, Development and Evaluations., Results: On meta-analysis of 9 RCTs (8 RCTs in adults, and focusing on maintenance phase), there was no significant difference in the risk of failing to maintain clinical remission in patients who underwent proactive TDM (267/709; 38%) vs conventional management (292/696; 42%) (relative risk [RR], 0.96; 95% confidence interval [CI], 0.81-1.13) with moderate heterogeneity (inconsistency index = 36%) (Grading of Recommendations, Assessment, Development and Evaluations; low certainty evidence), with no differences in patients with Crohn's disease (RR, 0.87 ; 95% CI, 0.66-1.15) and ulcerative colitis (RR, 0.88; 95% CI, 0.72-1.07). Disease duration, concomitant immunomodulators, disease activity at baseline, and optimization of therapy before randomization did not modify this association. No differences were observed in risk of developing antidrug antibodies or serious adverse events. Patients in the proactive TDM arm were more likely to undergo dose escalation (RR, 1.56; 95% CI, 1.25-1.94)., Conclusions: Routine proactive TDM to target biologic concentration to specific thresholds, regardless of disease activity, did not offer clinical benefit in patients with IBD treated with TNFα antagonists in RCTs conducted to date. We cannot exclude the possibility of benefit in disease subtypes and phases of therapy (induction) not represented in these RCT populations., (Copyright © 2022 AGA Institute. Published by Elsevier Inc. All rights reserved.)