Abstract
In this study we aimed to identify the predictors of drug survival for biologic and targeted synthetic DMARDs (bDMARDs and tsDMARDs) among patients with rheumatoid arthritis (RA) in a real-world setting. Data from RA patients receiving bDMARDs and tsDMARDs between 2007 and 2019 were extracted from the Taiwan Rheumatology Association Clinical Electronic Registry (TRACER). Patients were categorized into tumor necrosis factor-alpha (TNF-α) inhibitors, non-TNF-α inhibitors, and tofacitinib groups. The primary outcome was 3-year drug retention and the causes of bDMARDs and tsDMARDs discontinuation were recorded. Baseline demographic data before the initiation of bDMARDs and tsDMARDs treatment were analyzed to identify the predictors of 3-year drug survival. A total of 1,270 RA patients were recruited (TNF-α inhibitors: 584; non-TNF-α inhibitors: 535; tofacitinib: 151). The independent protective factors for 3-year drug survival were positive rheumatoid factor (RF) (HR: 0.48, 95% CI: 0.27-0.85, p = 0.013) and biologics-naïve RA (HR: 0.61, 95% CI: 0.39-0.94, p = 0.024). In contrast, positive anti-citrullinated protein antibody (ACPA) (HR: 2.24, 95% CI: 1.32-3.79, p = 0.003) and pre-existing latent tuberculosis (HR: 2.90, 95% CI: 2.06-4.09, p<0.001) were associated with drug discontinuation. RA patients treated with TNF-α inhibitors exhibited better drug retention, especially in the biologics-naïve subgroup (p = 0.037). TNF-α inhibitors were associated with lower cumulative incidence of discontinuation due to inefficacy and adverse events (both p<0.001). Baseline RF and ACPA positivity in abatacept-treated patients were associated with a better 3-year drug survival. However, negative ACPA levels predicted superior drug survival of TNF-α inhibitors and tofacitinib. In conclusion, bio-naïve status predicted better drug survival in TNF-α inhibitors-treated RA patients. RF and ACPA positivity predicted better abatacept drug survival. In contrast, ACPA negativity was associated with superior TNF-α inhibitors and tofacitinib survival.
Highlights
Rheumatoid arthritis (RA) is a chronic and debilitating form of arthritis, and is one of the most prevalent autoimmune inflammatory rheumatic diseases [1]
anti-citrullinated protein antibody (ACPA) negativity was associated with superior TNF-α inhibitors and tofacitinib survival
We found that rheumatoid factor (RF) positivity and biologic-naïve status (HR: 0.61, 95% CI: 0.39–0.94, p = 0.024) were protective factors for drug retention
Summary
Rheumatoid arthritis (RA) is a chronic and debilitating form of arthritis, and is one of the most prevalent autoimmune inflammatory rheumatic diseases [1]. According to the American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) recommendations for management of RA, the aim of treatment should be to reach a target of sustained remission or low disease activity in every patient with either biologic disease-modifying anti-rheumatic drugs (bDMARDs) or targeted synthetic DMARDs (tsDMARDs) [2, 3]. In Taiwan, the first bDMARD, etanercept, was made available to patients via Taiwan’s National Health Insurance (NHI) program in 2002. This marked the first time in Taiwan that a tumor necrosis factor-alpha (TNF-α) inhibitor had been used to treat active RA patients with inadequate response to methotrexate (MTX)-based conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs).
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