THE COMPARISON OF EFFECTIVENESS IN SECOND-LINE BIOLOGIC THERAPY FOR PATIENTS WITH RHEUMATOID ARTHRITIS WHO FAILED ONE TNF INHIBITOR: RESULTS FROM THE NATIONAL KOREAN REGISTRY

Abstract

Background RA treatment has improved significantly with the introduction of TNF inhibitor, but it has little or no effect in about 30% of treated patients. According to EULAR recommendation, patients who failed to TNF inhibitor should switch to a different TNF inhibitor or other biologics including abatacept (ABT), rituximab, or tocilizuamb. However, no consensus has been reached on the strategy of switching.

Objectives To compare the effectiveness of second-line biologic therapy in RA patients who failed to their fist TNF inhibitor.

Methods We recruited 161 patients who switched biologics after failure of one TNF inhibitor from BIOlogics Pharmacoepidemiologic StudY (BIOPSY), a prospective, national biologics registry in Korea. They were divided into two groups according to the first TNF inhibitor: 101 patients with anti-TNF monoclonal antibodies (MABs: infliximab, adalimumab, golimumab) and 60 patients with etanercept (ETN). The patients who failed with the previous MABs were categorized by MABs→MABs (n=21), MABs→ETN (n=41) and MABs→ABT (n=39). The patients who failed with ETN were divided by two groups of ETN→MABs (n=32) and ETN→ABT (n=28). Drug retention rates were compared across the three or two groups according to the first TNF inhibitor using Kaplan-Meier analysis and log-rank test. The Cox regression model was used to compare risk of drug for discontinuation between groups.

Results Among three groups from patients treated with MABs, the demographic and clinical characteristics were comparable with age (p=0.99), gender (p=0.35), their disease duration (p=0.24). Concomitant medication with corticosteroid (p=0.86) and methotrexate (p=0.79) were not different, but duration of previous MABs treatment showed statistical significance (10.2±8.3 in MABs→MABs vs. 6.0±6.9 in MABs→ETN vs. 11.4±12.0 in MABs→ABT, months, p=0.03). At starting time of second biologics, disease activity (DAS28ESR 6.4±1.4 vs. 6.0±1.1 vs. 6.4±1.0, p=0.19) and functional disability (HAQ-DI 1.3±0.7 vs. 1.4±0.7 vs. 1.5±0.7, p=0.51) had no statistical significance between three groups. The drug retention rates during 20 months were comparable (53.2% in MABs→MABs vs. 55.9% in MABs→ETN, 66.0% in MABs→ABT, p=0.39). After adjusting confounding factors, the groups of MABs→ABT (HR 0.32, 95% CI 0.11-0.92) and MABs→ETN (HR 0.34, 95% CI 0.12-0.96) showed lower rate of discontinuation of second biologics compared to MABs→MABs as reference.

For patients who failed to ENT, demographic and clinical characteristics were comparable between two groups. At starting time of second biologics, disease activity was higher in ETN→ABT than that of ENT→MABs (6.2±1.2 vs. 5.5±1.2, p=0.02), but the drug retention rates during 20months were not statistical different between two groups (29.8% in ENT→MABs vs. 45.7% in ENT→ABT, p=0.14).

Conclusions In the clinical practice, switching to ETN or ABT in patients who failed to MABs showed more favorable drug continuation. For patients with previous ETN, both MABs and ABT had similar drug continuation rate.