POS0209 ASSOCIATION OF FIRST, SECOND, AND THIRD-LINE BDMARDS AND TSDMARD WITH DRUG SURVIVAL AMONG RHEUMATOID ARTHRITIS PATIENTS: A COHORT STUDY
Authors: B. Ghang, S. Choi, E. Y. Lee
Journal: Annals of the Rheumatic Diseases (2021)

Background: Since tofacitnib is a tsDMARD with a different mechanism of action compared to bDMARDs, along with the fact that recent releases of bDMARDs or tsDMARDs have led to numerous possible switching patterns, there is a need for comparative studies of bDMARDs and tofacitinib with subsequent drug survival among RA patients. Objectives: To determine the association of first, second, and third-line biologic disease- modifying antirheumatic drugs (bDMARDs) and tofacitinib with drug survival among rheumatoid arthritis (RA) patients. Methods: The study population was composed of 8,018 seropositive RA patients who were prescribed bDMARDs or tofacitinib between January 2014 and January 2019 from the Korean Health Insurance Review and Assessment Service database. First, second, and third-line choice of tumor necrosis factor inhibitors (TNFi) including etanercept, infliximab, adalimumab, and golimumab, as well as non-TNFi including tocilizumab, rituximab, tofacitinib, and abatacept were assessed. Multivariate Cox proportional hazards regression was used to determine the adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for drug failure according to bDMARD or tofacitinib choice starting from the initial prescription date. Results: Compared to first etanercept users, patients with first tocilizumab (aHR 0.56, 95% CI 0.46-0.68), tofacitinib (aHR 0.27, 95% CI 0.18-0.42), or abatacept (aHR 0.83, 95% CI 0.69- 0.99) had lower risk of drug failure. Second choice of tocilizumab (aHR 0.38, 95% CI 0.25- 0.55), tofacitinib (aHR 0.23, 95% CI 0.15-0.37), or abatacept (aHR 0.54, 95% CI 0.35-0.84) was associated with lower drug failure risk compared to second etanercept users. Finally, third choice of tocilizumab (aHR 0.32, 95% CI 0.16-0.62) or tofacitinib (aHR 0.35, 95% CI 0.19- 0.63) was associated with lower drug failure risk compared to third TNFi users. Conclusion: First and second-line tocilizumab, tofacitinib, or abatacept may lead to improved drug survival. Third choices of tocilizumab or tofacitinib may be beneficiary in reducing drug failure risk among RA patients. References: [1].Neovius M, Arkema EV, Olsson H, et al. Drug survival on TNF inhibitors in patients with rheumatoid arthritis comparison of adalimumab, etanercept and infliximab. Ann Rheum Dis 2015;74(2):354-60. Table 1. Risk of drug failure on rheumatoid arthritis patients according to first, second, and third choice of bDMARD or tofacitinib. Events Person-years Incidence aHR 95% CI First-line choice (n=8,018) Etanercept 290 2,396 121 1.00 reference Infliximab 236 1,417 167 1.36 1.14-1.62 Adalimumab 449 2,718 165 1.28 1.10-1.48 Golimumab 258 1,955 132 1.06 0.90-1.26 Tocilizumab 171 2,623 65 0.56 0.46-0.68 Rituximab 1 29 34 0.29 0.04-2.08 Tofacatinib 24 502 48 0.27 0.18-0.42 Abatacept 216 2,207 98 0.83 0.69-0.99 Second-line choice (n=1,645) Etanercept 41 151 272 1.00 reference Infliximab 16 51 314 1.04 0.58-1.88 Adalimumab 85 275 309 1.07 0.72-1.60 Golimumab 41 204 201 0.79 0.51-1.23 Tocilizumab 85 918 93 0.38 0.25-0.55 Rituximab 4 31 129 0.52 0.18-1.46 Tofacatinib 35 484 72 0.23 0.15-0.37 Abatacept 46 299 154 0.54 0.35-0.84 Third-line choice (n=353) Etanercept 3 19 158 1.00 reference Infliximab 5 10 500 1.27 0.27-5.91 Adalimumab 5 17 294 0.99 0.22-4.38 Golimumab 13 22 591 2.23 0.60-8.25 Tocilizumab 17 127 134 0.47 0.13-1.68 Rituximab 3 22 136 0.60 0.12-3.09 Tofacatinib 23 162 142 0.50 0.14-1.77 Abatacept 17 59 288 1.11 0.31-3.96 Adjusted hazard ratios calculated by multivariate Cox proportional hazards regression after adjustments for age, sex, hospital type, number of csDMARDs, first bDMARDs or tofacitinib for second and third-line choice analysis, Charlson comorbidity index, and enrollment year. Incidence calculated as the number of events per 1,000 person-years. Acronyms: aHR, adjusted hazard ratio; CI, confidence interval. Disclosure of Interests: Byeongzu Ghang: None declared, Seulggie Choi: None declared, Eun Young Lee Grant/research support from: This work was supported by grants from the Korea Health Technology R&amp;D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health and Welfare, Republic of Korea [HI14C1277] and Britol-Myers Squibb [IM101-735].