Methotrexate (MTX) Plus Hydroxychloroquine versus MTX Plus Leflunomide in Patients with MTX-Resistant Active Rheumatoid Arthritis: A 2-Year Cohort Study in Real World

Le Zhang; Fangfang Chen; Shikai Geng; Xiaodong Wang; Liyang Gu; Yitian Lang; Ting Li; Shuang Ye

doi:10.2147/JIR.S282249

Methotrexate (MTX) Plus Hydroxychloroquine versus MTX Plus Leflunomide in Patients with MTX-Resistant Active Rheumatoid Arthritis: A 2-Year Cohort Study in Real World

J Inflamm Res. 2020 Dec 18:13:1141-1150. doi: 10.2147/JIR.S282249. eCollection 2020.

Authors

Le Zhang^#^{1

2}, Fangfang Chen^#², Shikai Geng^#², Xiaodong Wang², Liyang Gu², Yitian Lang¹, Ting Li², Shuang Ye²

Affiliations

¹ Department of Pharmacy, Ren Ji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China.
² Department of Rheumatology, Ren Ji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China.

^# Contributed equally.

Abstract

Purpose: To compare the efficacy, safety, and cost-effectiveness of methotrexate (MTX) plus hydroxychloroquine (HCQ) vs MTX plus leflunomide (LEF) in established rheumatoid arthritis (RA) with inadequate response to MTX monotherapy in a real-world Chinese cohort.

Patients and methods: A prospective RA cohort (n=549) was screened with eligible patients who had inadequate response (disease activity score in 28 joints using erythrocyte sedimentation rate, DAS28-ESR>3.2) to initial MTX monotherapy and subsequently received either MTX+HCQ or MTX+LEF. Propensity score matching (PSM) was applied to adjust the possible baseline confounders between two groups. The primary outcome was the proportion of patients achieving first remission (DAS28-ESR<2.6) during follow-up by log rank test. Secondary outcomes were changes of DAS28, glucocorticoids (GCs) exposure, safety, cost-effectiveness, sustained remission, and low disease activity (LDA) rate after 24-month follow-up.

Results: Overall, 222 eligible patients were subjected to the aforementioned two treatment protocols (MTX+HCQ, n=102; MTX+LEF, n=120). After PSM adjustment, 97 patients in each group were analyzed. A higher remission rate was observed in the MTX+HCQ group than in the MTX+LEF group (70.1% vs 56.7%, P=0.048). The median time to remission was 11 and 16 months in the two groups, respectively. At the endpoint, more patients achieved remission (46.8% vs 32.5%, P=0.063) and maintained sustained LDA in the HCQ group (53.2% vs 38.6%, P=0.062) and also more patients withdrew GCs in this group (32% vs 16.7%, P=0.053) than those in the LEF group. Safety profiles were non-alarming, with no significant difference between the two groups. The incremental cost-effectiveness ratio yielded by MTX+HCQ over MTX+LEF was $1,111.8 per quality-adjusted life-year (QALY), within the cost-effective threshold set as the per capita gross domestic product (GDP) of China.

Conclusion: The MTX+HCQ combination was seemingly superior to MTX+LEF in a real-world cohort of Chinese RA patients with inadequate response to methotrexate monotherapy in respect of the efficacy and cost-effectiveness.

Keywords: cost-effectiveness; efficacy; hydroxychloroquine; leflunomide; methotrexate-resistant; rheumatoid arthritis.

Grants and funding

This study was funded by National Natural Science Foundation Youth Project (71804109), Cooperative Research Project of Innovation of Translational Medicine from Shanghai Jiaotong University (TM201807), 2018 Pujiang Outstanding Youth Project of Renji Hospital South Campus (RJPJYQ2018), and Minhang District Municipal Commission of Health scientific research project (2019MW33). Le Zhang, Fangfang Chen, and Shikai Geng are co-first authors for this study.