Clinical and radiologic analysis of on-demand use of etanercept for disease flares in patients with rheumatoid arthritis for 2 years: The RESUME study: A case-control study

Abstract

To reduce costs of biological disease-modifying antirheumatic drugs (bDMARDs), we evaluated the efficacy of repeated etanercept (ETN) discontinuation and restarting in rheumatoid arthritis (RA) patients in a case-control study.Thirty-one bDMARD-naive RA patients with moderate to high disease activity received ETN until low disease activity (LDA) was achieved, after which ETN was discontinued. Upon flaring, ETN was readministered with observation every 2 months for 2 years, and radiographically evaluated in comparison with a historical control group treated continuously with ETN. Statistical methods including Fisher exact test, analysis of variance (ANOVA), Kruskal-Wallis test, multiple regression analysis, and Student t test were conducted as appropriate.Thirteen patients with inadequate response to ETN were withdrawn from the study, and 5 had no flare-up after ETN discontinuation. In the remaining 13 patients, ETN was used on-demand to maintain LDA. Multivariate analysis revealed that MTX was significantly correlated with ETN. All 13 patients achieved LDA at final follow-up. Although joint damage progressed in patients using ETN on-demand, structural damage progression in the on-demand group was not significantly different from that in controls.On-demand use of ETN for flaring reduced disease activity but not structural damage in 50% of patients (though not significantly). However, inhibition of joint damage was achieved in 50% of patients after 2 years, supporting on-demand use of ETN as a treatment option for patients with RA who cannot afford bDMARD or targeted synthetic DMARD therapy.

Figure 1

Study protocol. When disease activity score reached low disease activity or remission evaluated by disease activity score-28–erythrocyte sedimentation rate (DAS28-ESR), administration of etanercept (ETN) was discontinued (ETN-Off). If DAS28-ESR became moderate or higher in these patients, ETN was readministered with observation every 2 months (ETN-On). Patients who could not achieve low disease activity within 6 months were considered to be discontinued from the study.

Figure 2

(A) Courses of all individual cases of disease activity score-28–erythrocyte sedimentation rate (DAS28-ESR) in the on-demand group. Thick dotted line indicates the mean DAS28-ESR score. Thin dotted straight transverse line indicates DAS28-ESR = 3.2. (B) Disease activity score-28–erythrocyte sedimentation rate (DAS28-ESR) course for 21 sets in 13 patients in the on-demand group of “start-stop-start-stop,” “ON” indicates the time when etanercept was administered, and “OFF” indicates the time when etanercept was discontinued. All 21 sets achieved low disease activity. During the observation period, 1 set of peak and trough levels was observed in 7 patients, 2 sets in 4 patients, and 3 sets in 2 patients.