The effective threshold dose of etanercept biosimilars in patients with methotrexate- resistant rheumatoid arthritis

Abstract

Abstract Background: The therapy of rheumatoid arthritis (RA) was advanced by biological agents, yet costly. This study aims to identify the effective threshold dose of etanercept (ENT) biosimilars and evaluate the efficacy, safety and cost-effectiveness in methotrexate (MTX)-resistant RA in real world.Methods: Eligible patients had an inadequate response (DAS28-ESR＞3.2) to initial MTX monotherapy, and subsequently received biosimilar of etanercept. The effective cutoff value of cumulative dose was identified to maintain remission response (DAS28-ESR＜2.6) at month 24 by using restricted cubic splines. Remission rate, LDA rate, glucocorticoid exposure, safety, and cost-effectiveness were compared between the saturated and non-saturated dose groups divided by cutoff dose. Results:78 (14.2%) of 549 enrolled patients were eligible, and 72 patients completed follow-up. The 2-year cumulative cutoff dose that maintained remission response at 24 months was 1975 mg. And the recommended threshold dosing strategy of etanercept biosimilars was twice weekly (BIW) for the first 6 months, every week (QW) for the next six months, and every 2 weeks (Q2W) and every month (QM) for the second year. Greater net changes in DAS28-ESR score were observed in the ENT saturated dose group than in non-saturated dose group (average change 0.569, 95%CI 0.236-0.901, p=0.001). The proportion of patients achieving remission (27.8% vs 72.2%, p<0.001) and LDA (58.3% vs 83.3%, p=0.020) in non-saturated group were both significantly lower than in saturated group at 24 months. The ICER of the saturated group referred to the non-saturated group was 5791.2 $/QALY.Conclusions: In refractory RA patients, the effective cumulative cutoff dose of etanercept biosimilars for sustained remission at 24 months was calculated as 1975 mg, and receiving saturated dose was more effective and cost-effective than with non-saturated dose.