Real world treatment patterns and temporal variations among rheumatoid arthritis patients in China: Insights from a Chinese national registry of rheumatoid arthritis

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To the Editor: Despite the increasing implementation of treatment guidelines for rheumatoid arthritis (RA), the burden on disability among patients with RA in China remains high. An observational study at 40 teaching hospitals across China in 2018 revealed a remission rate of only 10.9%.[1] In a recent large real-world study in China, only 1/5 of newly diagnosed RA patients received conventional synthetic disease modifying antirheumatic drug (csDMARD) monotherapy.[2] Given the availability of new DMARDs over the past decades, we conducted a real-world study based on the Chinese Rheumatism Data Center (CRDC) registry to determine the prevalence and temporal changes of medication use among Chinese RA patients from January 2014 to December 2023. This study protocol was approved by the Ethics Committee of Peking Union Medical College Hospital (PUMCH), Beijing, China (No. S-478) and each participating center. Patient consent was waived given that the data extraction process automatically identified and selected the necessary fields and the specific drugs of interest. Besides, de-identified data were utilized. We collected patient-level data from the CRDC registry. For inclusion in the analysis, patients must be aged 18 years or older and the diagnosis of RA must be established according to either the American Rheumatism Association (ARA) 1987 revised criteria or the American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) 2010 criteria. Disease activity was categorized based on DAS28-hsCRP.[3] Detailed information on the analyses of temporal trends and temporal variations in therapeutic regimens and statistical analysis is presented in Supplementary Materials, https://links.lww.com/CM9/C534. The study included 235,856 visits for the analysis of temporal trends in the use of RA medications. Throughout the period, csDMARDs were the most frequently prescribed drugs, followed by glucocorticoids [Figure 1A]. The proportion of treatment with glucocorticoids was largely stable between 35.7% and 42.5% from 2014 to 2020, followed by a gradual dip to 26.1% in 2023. The proportion of treatment with biological DMARDs (bDMARDs) increased from 4.2% in 2015 to 27.9% in 2020 but declined thereafter. The use of targeted synthetic DMARDs (tsDMARDs) increased steadily since entering the market in 2017, reaching 18.2% in 2023.Figure 1: The crude proportions of the documented treatments from 2014 to 2023 by drug classes (A), individual csDMARDs (B), b/tsDMARDs (C), and individual tsDMARDs (Janus kinase inhibitors) (D). Glucocorticoids include prednisone, prednisolone, and methylprednisolone; csDMARDs include methotrexate, leflunomide, sulfasalazine, hydroxychloroquine, and iguratimod; bDMARDs include tumor necrosis factor inhibitors (etanercept, infliximab, adalimumab, and others), interleukin 6 inhibitor tocilizumab, anti-CD20 monoclonal antibody rituximab, and CTLA-4 fusion protein/T-cell activation inhibitor abatacept; tsDMARDs (Janus kinase inhibitors) include tofacitinib, baricitinib, and upadacitinib. b/tsDMARDs: Biologic/targeted synthetic disease-modifying antirheumatic drugs; CD20: Cluster of differentiation 20; csDMARDs: Conventional synthetic disease-modifying antirheumatic drugs; CTLA-4: Cytotoxic T lymphocyte antigen-4; TNF: Tumor necrosis factor; tsDMARDs: Target synthetic disease-modifying antirheumatic drugs.In 2014, the most commonly prescribed csDMARD was leflunomide (32.0%), followed by methotrexate (30.4%) [Figure 1B]. Since 2017, there was a decrease in the prescription proportion of leflunomide (26.1% in 2023) and an increase in methotrexate (55.6% in 2023). TNF antagonists were almost the exclusive b/tsDMARDs prescribed prior to 2018. The proportion of treatment with a TNF antagonist was 16.5% in 2014. However, the use of TNF antagonists decreased with the availability of other bDMARDs and tsDMARDs. TNF antagonists remained the second most frequently prescribed b/tsDMARDs (12.2%), after JAK inhibitors (18.2%), in 2023 [Figure 1C]. IL-6 inhibitor tocilizumab was prescribed in <5% of patient visits prior to 2020 and between 8.2% and 16.8% from 2020 to 2023. The proportion of patient visits with treatment with rituximab and abatacept was negligible (<0.05%) throughout the study period. The use of JAK inhibitors increased from 0.5% in 2017 to 18.2% in 2023 [Figure 1D]. Tofacitinib was the most frequently prescribed JAK inhibitor (14.4%) in 2023 compared to 3.5% for baricitinib and 0.3% for upadacitinib. We further characterized medication patterns of RA patients from a time perspective. Of 95,590 eligible patients in the registry, 37,613 were included from 2014–2018 and 57,977 from 2019–2023 [Supplementary Figure 1, https://links.lww.com/CM9/C534]. In comparison to the 2014–2018 period, patients during the 2019–2023 period had shorter disease duration (3.0 years vs. 4.0 years) and lower DAS28-hsCRP (4.3 ± 1.6 vs. 4.5 ± 1.7), SDAI, and CDAI scores. In both the 2014–2018 and 2019–2023 periods, glucocorticoids-free csDMARD combination therapy was the most frequently prescribed regimen (37.8% [14,224/37,613] and 31.3% [18,160/57,977, respectively), followed by csDMARDs plus glucocorticoids (34.9% [13,138/37,613 and 23.7% [13,712/57,977], respectively) and about one in five patients received glucocorticoids-free csDMARD monotherapy (18.1% [6793/37,613] and 21.2% [12,306/57,977], respectively). Besides, tsDMARDs was the least frequently prescribed regimen in both period (0.6% [227/37,613] in 2014–2018 and 10.3% [5950/57,977] in 2019–2023) [Supplementary Figure 2A, https://links.lww.com/CM9/C534]. While compared to the 2014–2018 period, patients receiving either bDMARDs or tsDMARDs during the 2019–2023 period were older and had lower DAS28-ESR, DAS28-hsCRP, and CDAI scores. In comparison to the 2014–2018 period, patients receiving either bDMARDs or tsDMARDs during the 2019–2023 period had shorter disease duration and lower disease activity. In both the 2014–2018 and 2019–2023 periods, the most frequently prescribed regimen in patients with moderate-to-high disease activity was glucocorticoids-free csDMARD combination therapy, followed by csDMARDs plus glucocorticoids, glucocorticoids-free csDMARD monotherapy, and bDMARDs. However, compared to the 2014–2018 period, the use of glucocorticoids-free csDMARD combination therapy in patients with moderate-to-high disease activity decreased during 2019–2023 period (38.0% vs. 30.3%) [Supplementary Figure 2B, https://links.lww.com/CM9/C534]. The real-world treatment practices of rheumatoid arthritis may vary considerably for a diversity of reasons. Here we provide insights into the characteristics and treatment patterns among patients with rheumatoid arthritis in China. Consistent with guideline recommendation of csDMARDs as first line therapy for RA,[4] csDMARDs was the most frequently prescribed drug throughout the study period. The percentage of visits with recorded treatment with csDMARDs increased from 71.0% in 2014 to 92.5% in 2023. Among the csDMARDs, methotrexate monotherapy is preferred by the guideline and leflunomide or sulfasalazine monotherapy in patients who are contraindicated to methotrexate. Consistent with that reported in the same period (2018-2019) in a national registry of RA (NARRA),[5] methotrexate was the most frequently prescribed csDMARD in this study. The use of methotrexate, however, was lower than that reported by a survey of RA patients in 15 countries (83%).[6] Similar proportions of patients received leflunomide and iguratimod in recent years. Iguratimod is approved and mainly prescribed in China and Japan. Its effectiveness has been demonstrated in real-world clinical practice. Sulfasalazine was prescribed in few patients (<6%), which was lower than reported in other countries.[6] The 2016 and 2019 EULAR updates recommend the use of glucocorticoids for patients with moderate-to-high disease activity or those who fail to respond to csDMARDs while the 2016 EULAR upda

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