A pioneering study titled ESCORT-NGSK, recently published in Drug Discoveries & Therapeutics, provides critical insights into the real-world efficacy of switching from the etanercept reference product (RP) to its biosimilar in patients with rheumatoid arthritis (RA). The study, which incorporated both clinical indices and musculoskeletal ultrasound (MSUS) assessments, demonstrated that patients who transitioned to the biosimilar maintained disease stability, suggesting that switching does not compromise therapeutic benefits.
The ESCORT-NGSK study was an interventional, multicenter, open-label, single-arm clinical trial designed to evaluate the efficacy of switching from etanercept-RP to its biosimilar. A total of 20 patients were enrolled, all of whom had been on etanercept-RP for at least 24 weeks and had achieved low disease activity (LDA) or remission. These patients were then switched to the biosimilar, with some having their dosage reduced from 50 mg/week to 25 mg/week at the 24-week mark. The patients were followed for either 24 weeks or 52 weeks, allowing for an extended assessment of disease stability post-switch.
At the 24-week mark, around 94% (16 out of 17) of the patients who switched to the biosimilar maintained LDA or remission, as assessed by the Disease Activity Score 28 using the ESR (DAS28-ESR). This result, with a 95% confidence interval (CI) of 71.3–99.9, indicates that the majority of patients experienced no loss of efficacy after the transition. Moreover, in a subgroup of 11 patients whose dosage was halved from 50 mg/week to 25 mg/week, 81.8% (9 out of 11) maintained LDA or remission at the 52-week follow-up (95% CI: 48.2–97.7). No significant worsening in disease activity was observed across various disease activity scores, including DAS28-CRP, SDAI, and CDAI. The MSUS assessments confirmed these findings, with the median total power Doppler (PD) score remaining at 0, indicating no active inflammation.
Further extending the evidence, a long-term open-label extension study by Park et al. evaluated the efficacy, safety, and immunogenicity of LBEC0101, an etanercept biosimilar, in patients who either continued on the biosimilar or switched from the etanercept reference product. After completing a prior 52-week phase III trial, a total of 148 patients were enrolled, with 70 continuing LBEC0101 and 78 switching from etanercept-RP. Over a 48-week treatment period, patients received weekly subcutaneous injections of LBEC0101 (50 mg) alongside methotrexate.
The results showed that disease activity remained stable in both groups, with consistent DAS28-ESR scores and comparable ACR20, ACR50, and ACR70 response rates. Moreover, the incidence of adverse events and the development of antidrug antibodies were similar across both groups, suggesting that switching to the biosimilar did not introduce new safety concerns. These findings underscore that LBEC0101 maintains long-term efficacy, a favorable safety profile, and low immunogenicity, supporting its use as a continuous treatment or as an alternative to etanercept-RP.
The ESCORT-NGSK study, along with the long-term extension study, highlights the potential of biosimilars as viable, cost-effective alternatives to reference biologic therapies, especially in rheumatoid arthritis. Organizations like the European League Against Rheumatism (EULAR), American College of Rheumatology (ACR), and Japan College of Rheumatology all recognize the role of biosimilars in RA management, with some guidelines even recommending their use for patients with stable disease. Furthermore, the Japanese government has been actively promoting the use of biosimilars due to their potential to reduce the economic burden on healthcare systems. The ESCORT-NGSK study, in particular, reinforces the feasibility of switching from etanercept-RP to its biosimilar without sacrificing disease control, thus supporting the broader adoption of biosimilars in routine rheumatology practice.
The ESCORT-NGSK study and accompanying long-term studies provide robust evidence that switching from the etanercept reference product to its biosimilar can be done safely and effectively, even with subsequent dose reduction. By combining clinical data with musculoskeletal ultrasound findings, the study offers strong evidence that patients with well-controlled RA can maintain disease stability while transitioning to a biosimilar. These results pave the way for biosimilars to become integral to RA treatment, offering cost-effective solutions without compromising therapeutic benefits.
References
- Sumiyoshi R, Kawashiri SY, Shimizu T, et al. Efficacy of etanercept biosimilar switching from etanercept reference product, using ultrasound and clinical data in outcomes of real world therapy (ESCORT-NGSK Study). Drug Discov Ther. 2025 Mar 6;19(1):29-37.
- Park MC, Matsuno H, Kim J, et al. Long-term efficacy, safety and immunogenicity in patients with rheumatoid arthritis continuing on an etanercept biosimilar (LBEC0101) or switching from reference etanercept to LBEC0101: an open-label extension of a phase III multicentre, randomised, double-blind, parallel-group study. Arthritis Res Ther. 2019 May 21;21(1):122.