P4397 - Comparative Efficacy of Biologics for the Induction of Clinical Remission and Response in Biologic-Naïve Patients With Moderate-to-Severe Crohn’s Disease: Outcomes From Frequentist and Bayesian Network Meta-Analyses
Zaid Yousif, MS, PhD1, Anubhav Nangia, MSc2, Shaun Abeysinghe, 2, Jeanne Jiang, MS3, Marie Sanchirico, MD, PhD4, Tao Fan, MS, PhD3 1Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, CA; 2RTI Health Solutions, Manchester, England, United Kingdom; 3Takeda Pharmaceuticals U.S.A., Inc., Cambridge, MA; 4Takeda Pharmaceuticals, USA, Inc., Cambridge, MA
Introduction: Owing to a scarcity of head-to-head trials of biologics for Crohn’s disease (CD), network meta-analysis (NMA) has been used to assess the comparative efficacy of biologics by combining evidence from randomized controlled trials (RCTs). Broadly, there are 2 NMA modeling approaches: the frequentist, which assumes that model error follows a standard distribution and the Bayesian, which estimates the exact distribution from the available data. Here, we describe frequentist and Bayesian models used to evaluate biologics for inducing clinical remission and response in biologic-naïve patients with moderate to severe CD.
Methods: Studies included in the NMAs (12 RCTs of 9 interventions) were from a subset of studies identified by a systematic literature review. Most RCTs defined clinical remission as Crohn’s Disease Activity Index (CDAI) < 150 and response as ≥ 100-point decrease in CDAI after 4–12 weeks of treatment. In RCTs with results from multiple time points, data from the time point representative of the end of the induction period (as per the Food and Drug Administration label for the biologic) were used. For each endpoint, 4 random-effects NMAs were conducted; 3 used frequentist models and 1 used a Bayesian model (Figure 1). Treatment effects were compared using odd ratios (ORs); 95% confidence intervals (CIs) and credible intervals (CrIs) were estimated for frequentist and Bayesian NMAs, respectively. Sensitivity analyses were performed with fixed-effects models.
Results: For clinical remission and response, the CIs for ORs (biologic vs placebo) from the frequentist models differed from each other and from the CrIs generated by the Bayesian model (Figure 1). In the Bayesian NMA, pairwise comparisons favoring infliximab-based interventions over placebo for remission reached statistical significance (p< 0.05) but the ORs were characterized by the widest CrIs in the network. No other pairwise comparison reached statistical significance for either clinical remission or response (Table 1). Results from the sensitivity analyses were broadly consistent with those of the primary analyses.
Discussion: The differences in the CIs and CrIs from the frequentist models and the Bayesian model suggest that the distributional assumptions needed by the frequentist approach may be inappropriate for the network of trial evidence. The Bayesian NMA did not reveal superiority of any biologic over another for induction of clinical remission or response in biologic-naïve patients with moderate to severe CD.
Figure: Figure 1. Forest plots of odds ratios generated by random-effects frequentist and Bayesian network meta-analyses for induction of clinical remission and response for biologics versus placebo in biologic-naïve patients with CD.
CD, Crohn’s disease; FDA, Food and Drug Administration; IV, intravenous; NCT, National Clinical Trial number; NMA, network meta-analysis; OR, odds ratio; PO, per os; RCT, randomized controlled trial; SC, subcutaneous; W0, 1 dose at week 0; 0/2, 2 doses at weeks 0 and 2; W0/2/6, 3 doses at week 0, 2, and 6; QD, every day; Q4W, every 4 weeks. ORs are reported with 95% confidence intervals for the frequentist NMAs, and 95% credible intervals for the Bayesian NMA.
a Data for clinical remission were from 12 RCTs: ADVANCE (NCT03105128), C87085 (NCT00552058), CLASSIC 1 (NCT00055523), ENACT 1 (NCT00032799), GALAXI 1 (NCT03466411), GEMINI 3 (NCT01224171), M14-233 (NCT02499783), PRECISE 1 (NCT00152490), SEAVUE (NCT03464136), SONIC (NCT00094458), Targan 1997 (NCT00269854), and UNITI 2 (NCT01369342). b Data for clinical response were from 7 RCTs: ADVANCE, C87085, CLASSIC 1, GALAXI 1, GEMINI 3, PRECISE 1, and SEAVUE. c As of June 2023, guselkumab is not FDA-approved for treating CD. d As of June 2023, the infliximab and azathioprine combination is not FDA-approved for treating CD.
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Note: The table for this abstract can be viewed in the ePoster Gallery section of the ACG 2024 ePoster Site or in The American Journal of Gastroenterology's abstract supplement issue, both of which will be available starting October 27, 2024.
Disclosures:
Zaid Yousif: Takeda Pharmaceuticals U.S.A., Inc. – Consultant.
Anubhav Nangia: RTI Health Solutions – Employee. Takeda Pharmaceuticals U.S.A., Inc. – RTI Health Solutions was contracted by Takeda Pharmaceuticals U.S.A., Inc. to conduct the study.
Shaun Abeysinghe: RTI Health Solutions – Employee. Takeda Pharmaceuticals U.S.A., Inc. – RTI Health Solutions was contracted by Takeda Pharmaceuticals U.S.A., Inc. to conduct the study.
Jeanne Jiang: Takeda Pharmaceuticals U.S.A., Inc. – Employee, Stock Options.
Marie Sanchirico: Takeda Pharmaceuticals U.S.A., Inc. – Employee, Stock Options.
Tao Fan: Takeda Pharmaceuticals U.S.A., Inc. – Employee, Stock Options.
Zaid Yousif, MS, PhD1, Anubhav Nangia, MSc2, Shaun Abeysinghe, 2, Jeanne Jiang, MS3, Marie Sanchirico, MD, PhD4, Tao Fan, MS, PhD3. P4397 - Comparative Efficacy of Biologics for the Induction of Clinical Remission and Response in Biologic-Naïve Patients With Moderate-to-Severe Crohn’s Disease: Outcomes From Frequentist and Bayesian Network Meta-Analyses, ACG 2024 Annual Scientific Meeting Abstracts. Philadelphia, PA: American College of Gastroenterology.
