Predictors of response to TNF inhibitors in rheumatoid arthritis: an individual patient data pooled analysis of randomised controlled trials.

ABSTRACT

OBJECTIVE: To identify patient characteristics associated with responsiveness to tumour necrosis factor inhibitors (TNFi) in rheumatoid arthritis (RA). MATERIALS AND METHODS: Individual patient data from 29 randomised controlled trials (RCTs) evaluating the efficacy of a TNFi versus placebo or conventional therapy were obtained. Response to treatment was assessed in subgroups according to the following baseline characteristics smoking status, physical activity, sex, age, body mass index, autoantibody profile, disease duration, high initial disease activity defined by Disease Activity Score on 28 joints (DAS28)(C reactive protein (CRP)) >5.1. The primary outcome was the between-treatment group difference in DAS28(CRP) change from baseline to 6 months. The secondary endpoints were the between-treatment group difference in final DAS28(CRP) measured until 6 months and EULAR response criteria until 6 months. Data from each RCT were then pooled by the Mantel-Haenszel method using a random effects model. A linear metaregression was also carried out on two data-sharing platforms separately to support the results. RESULTS: Individual data of 11 617 patients from 29 RCTs were analysed. Until 6 months, a significantly higher EULAR non-response rate was observed in obese patients (OR 0.52 vs 0.36 for non-obese, p=0.01). A multivariable regression model performed on 7457 patients indicated that patients treated by TNFi had a final DAS28(CRP) decreased by 0.02 for each year of disease duration (p<0.001), and a 0.21 decreased for patients with a baseline DAS28(CRP) >5.1 (p<0.001). CONCLUSIONS: In RA, patients who are more responsive to TNFi are those who are non-obese, have a long disease duration and have a high initial disease activity.