Authors’ Response to Letter to the Editor Regarding Comparative Efficacy of JAK Inhibitors for Moderate-to-Severe Rheumatoid Arthritis: A Network Meta-Analysis

Abstract

We thank Dr. Fakhouri et al. for their comments on our study. The comments note possible heterogeneity resulting from differences in study designs and patient characteristics among the trials included in our network meta-analysis (NMA), which are limitations common to all meta-analyses. In particular, Dr. Fakhouri raised concerns relating to cross-trial differences in prior exposure to biologic disease-modifying antirheumatic drugs (bDMARDs), number of prior conventional synthetic disease-modifying antirheumatic drug (csDMARD) failures, background dose of methotrexate (MTX), and placebo arm response rates among all the trials included in the network. In this response letter, we will discuss the approaches taken to mitigate and estimate the heterogeneity of trials included in the NMA and introduce supportive evidence to address the concerns raised by Dr. Fakhouri. To minimize confounding differences between the trial populations in our NMA, the studies included in the NMA were required to meet the pre-defined selection criteria to be eligible for inclusion in the analysis. Specifically, the studies were required to be phase III randomized controlled trials evaluating Janus kinase (JAK) inhibitors among patients who had an inadequate response or were intolerant to at least one csDMARD (csDMARD-IR). In addition, patients were eligible for inclusion if the patient population was naı̈ve to bDMARDs or if no more than 20% of patients in the trial had prior exposure to bDMARDs. These inclusion criteria were selected on the basis of prior publications, health technology assessment reports, and clinical input to reduce the heterogeneity between trials [1–3]. Additionally, a random-effects model was implemented to account for the potential between-trial heterogeneity in treatment contrasts and ensure proper statistical inference under such heterogeneity. The tau heterogeneity parameter, which is the precision parameter of the distribution of the underlying true effects across studies and quantifies the between-trial J. Pope (&) University of Western Ontario, London, ON, Canada e-mail: [email protected]