Switching and Discontinuation Pattern of Biologic Disease-Modifying Antirheumatic Drugs and Tofacitinib for Patients With Rheumatoid Arthritis in Taiwan

Abstract

Rheumatoid arthritis (RA) is a chronic inflammatory systemic disease characterized by persistent joint synovial inflammation and swelling, leading to cartilage damage and bone erosion. This retrospective, longitudinal study is to evaluate the treatment patterns of biologic-naïve RA patients receiving index biologic disease-modifying antirheumatic drug (bDMARD) and tofacitinib by the data of Taiwan National Healthcare Insurance Claims and the Death Registry between 2012 and 2017. Drug survival and treatment patterns were determined by investigating the occurrence of switching and discontinuation from index treatment. At baseline, 70.0% of patients used tumor necrosis factor inhibitors (TNFi) bDMARD with the majority taking etanercept (27.0%) or adalimumab (26.2%). During the follow-up period, 40.0% (n = 3,464) of index users switched (n = 1,479) or discontinued (n = 1,985) the treatment with an average incidence rate of 0.18 per patient-year. Among the six index treatment groups, drug survival was the lowest for adalimumab and highest for tocilizumab. When compared with etanercept, only adalimumab had a higher cumulative probability of switching/discontinuation (adjusted HR = 1.17, 95% CI: 1.08–1.28), whereas golimumab, non-TNFi bDMARDs and tofacitinib were significantly less probable to switch or discontinue. For patients switching the index treatment, tocilizumab (31.2%) and tofacitinib (23.4%) were the main regimens being switched to. In addition, 48.2% of patients who discontinued the index treatment received further retreatment, and 63.8–77.0% of them were retreated with same agent. In conclusion, this population-based study found that TNFi were the preferred agents as the index treatments during 2012–2017. Non-TNFi and tofacitinib were more common second-line agents being switched to. Nearly half of discontinued patients received retreatment, with a majority receiving the same agent.

Real-world effectiveness of biological therapy in patients with rheumatoid arthritis: Systematic review and meta-analysis

“…Twenty-one records were eligible for inclusion in this systematic review; seven population-based cohorts ( Østergaard et al, 2007 ; Chatzidionysiou et al, 2015 ; Neovius et al, 2015 ; Acurcio et al, 2016 ; Kihara et al, 2017 ; Choi et al, 2021 ; Li et al, 2021 ), eight prospective ( Harrold et al, 2015 ; Lauper et al, 2018 ; Ebina et al, 2020a , 2020b ; Rahman et al, 2020 ; Curtis et al, 2021 ; Pappas et al, 2021a , 2021b ), and six retrospective cohort studies ( Curtis et al, 2015 ; Yun et al, 2015 ; Silvagni et al, 2018 ; Bird et al, 2020 ; Gharaibeh et al, 2020 ; Youssef et al, 2020 ), which are published from 2007 to 2021 ( Supplementary Table S2 ).…”

“…Ten studies compromised RA patients in second-line therapy ( Chatzidionysiou et al, 2015 ; Harrold et al, 2015 ; Kihara et al, 2017 ; Lauper et al, 2018 ; Ebina et al, 2020a , 2020b ; Rahman et al, 2020 ; Youssef et al, 2020 ; Choi et al, 2021 ; Curtis et al, 2021 ), nine in first-line therapy ( Østergaard et al, 2007 ; Neovius et al, 2015 ; Yun et al, 2015 ; Silvagni et al, 2018 ; Bird et al, 2020 ; Gharaibeh et al, 2020 ; Li et al, 2021 ; Pappas et al, 2021b , 2021a ), and two did not report this information ( Curtis et al, 2015 ; Acurcio et al, 2016 ) ( Table 1 ).…”

“…According to the MINORS, twenty studies were classified as high quality ( Chatzidionysiou et al, 2015 ; Curtis et al, 2015 , 2021 ; Harrold et al, 2015 ; Neovius et al, 2015 ; Yun et al, 2015 ; Acurcio et al, 2016 ; Kihara et al, 2017 ; Lauper et al, 2018 ; Silvagni et al, 2018 ; Bird et al, 2020 ; Ebina et al, 2020a , 2020b ; Gharaibeh et al, 2020 ; Rahman et al, 2020 ; Youssef et al, 2020 ; Choi et al, 2021 ; Li et al, 2021 ; Pappas et al, 2021a , 2021b ) and one as moderate quality ( Østergaard et al, 2007 ). Overall, studies scored between 14 and 24 points ( Supplementary Table S3 ).…”

“…Twelve studies assessed the effectiveness between TNFi and non-TNFi ( Curtis et al, 2015 ; Harrold et al, 2015 ; Yun et al, 2015 ; Kihara et al, 2017 ; Lauper et al, 2018 ; Ebina et al, 2020a , 2020b ; Gharaibeh et al, 2020 ; Youssef et al, 2020 ; Choi et al, 2021 ; Li et al, 2021 ; Pappas et al, 2021b ). A statistically significant lower effectiveness was observed among TNFi users than in non-TNFi users (RR: 0.88; 95% CI: 0.81–0.95; p < 0.01; I 2 = 94.0%).…”

“…Persistence in therapy is an excellent indirect and composite measure of effectiveness, safety, and tolerability, reflecting the long-term impact on the course of the disease ( Silvagni et al, 2018 ). Twelve studies evaluated the therapy persistence in this systematic review ( Curtis et al, 2015 ; Neovius et al, 2015 ; Yun et al, 2015 ; Lauper et al, 2018 ; Ebina et al, 2020a , 2020b ; Gharaibeh et al, 2020 ; Rahman et al, 2020 ; Youssef et al, 2020 ; Choi et al, 2021 ; Curtis et al, 2021 ; Li et al, 2021 ). In addition, the majority of the studies that evaluated the therapy persistence of TNFi in comparison to non-TNFi found significant differences among the therapies, favoring non-TNFi over TNFi ( Curtis et al, 2015 ; Yun et al, 2015 ; Lauper et al, 2018 ; Ebina et al, 2020a ; Youssef et al, 2020 ; Choi et al, 2021 ; Li et al, 2021 ).…”