Randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of etanercept in patients with moderately active rheumatoid arthritis despite DMARD therapy.

Kathryn Hobbs,James Chung,Bojena Bitman,Brian Wang,Atul Deodhar,Joyce Nussbaum,David H Collier

doi:10.1186/s40064-015-0895-9

Abstract

This study evaluated the efficacy and safety of adding etanercept to disease-modifying antirheumatic drugs (DMARDs) in patients with moderately active rheumatoid arthritis (RA). This randomized, double-blind, placebo-controlled study (ClinicalTrials.gov #NCT01313208) enrolled RA patients with Disease Activity Score using 28 joints with C-reactive protein (DAS28-CRP) >3.2 and ≤5.1 (moderate disease) despite stable DMARD therapy. Patients were randomized to etanercept 50 mg or placebo weekly for 12 weeks; all patients then received etanercept 50 mg weekly through week 24. Primary endpoint was low disease activity (LDA) at week 12; secondary endpoints included DAS28-CRP remission at week 12; Clinical Disease Activity Index (CDAI) and Simplified Disease Activity Index (SDAI) LDA; American College of Rheumatology (ACR) responses; change in Health Assessment Questionnaire Disability Index (HAQ-DI), and safety. For 210 patients with moderate disease at screening, (104 placebo; 106 etanercept), only 58% still had moderate disease at baseline. At week 12, 33% on etanercept and 21% on placebo achieved LDA (P = 0.055); remission was achieved in 19% and 12%, respectively (P = 0.14). At week 12, ACR20, ACR50, and ACR70 responses were observed in 29%, 13%, and 1% respectively, in patients on placebo, and 41%, 21%, and 6% of patients on etanercept. Mean (SD) change from baseline in HAQ-DI score was −0.20 (0.43) for placebo patients and −0.39 (0.54) for etanercept patients at week 12. No new safety signals were observed. LDA was achieved by more patients on etanercept than placebo in patients with moderate disease at screening, but the difference was not statistically significant at week 12.

Highlights

The American College of Rheumatology (ACR) recommends a treatment goal of either low disease activity (LDA) or remission in all patients with early rheumatoid arthritis (RA) and established RA by using diseasemodifying antirheumatic drugs (DMARDs) or biologic agents (Singh et al 2012)
Patients A total of 210 patients were enrolled in the study from 38 centers in the US and Canada; 104 patients were randomized to the placebo-etanercept group and 106 were randomized to the etanercept-etanercept group
The primary endpoint of the study was not reached for the entire study population, a post hoc analysis of the subset of patients who fulfilled the entry criterion of moderate disease activity at baseline showed that the addition of etanercept to methotrexate resulted in a greater proportion of patients achieving DAS28CRP LDA at week 12

Summary

Introduction

The American College of Rheumatology (ACR) recommends a treatment goal of either low disease activity (LDA) or remission in all patients with early rheumatoid arthritis (RA) and established RA by using diseasemodifying antirheumatic drugs (DMARDs) or biologic agents (Singh et al 2012). Etanercept, a modified p75 receptor of tumor necrosis factor (TNF) that inhibits the action of TNF, has been shown to be efficacious for the treatment of moderate to severe RA in patients with early (Bathon et al 2000) and established (Moreland et al 2006) disease. The objective of this study was to evaluate whether adding etanercept 50 mg per week to standard-of-care DMARD therapy in patients with moderately active RA is superior in inducing very good control of disease compared with continued DMARD therapy.

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Conclusion