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OP0226 Randomized, Double-Blind Study Comparing Chs-0214 with Etanercept in Patients with Active Rheumatoid Arthritis (RA) despite Methotrexate (MTX) Therapy
  1. J. O'Dell1,
  2. T. Takeuchi2,
  3. Y. Tanaka3,
  4. I. Louw4,
  5. T. Tiabut5,
  6. M. Kai6,
  7. M. Oribe7,
  8. S. Nakashima8,
  9. B. Finck9,
  10. on behalf of RApsody Study Group
  1. 1University of Nebraska Medical Center, Omaha, United States
  2. 2Division of Rheumatology, Dept of Internal Medicine, Keio University School of Medicine, Tokyo
  3. 3First Dept of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan
  4. 4Panorama Medical Center, Cape Town, South Africa
  5. 5City Clinical Hospital No. 1 of Minsk, Minsk, Belarus
  6. 6Kai Clinic Rheumatology and Orthopedics, Miyazaki
  7. 7Oribe Clinic of Rheumatism and Medicine, Oita
  8. 8Daiichi Sankyo Co., Ltd., Tokyo, Japan
  9. 9Clinical Science, Coherus Biosciences, Redwood City, United States

Abstract

Background CHS-0214 is a proposed biosimilar of etanercept, a fusion protein inhibiting tumor necrosis factor that is approved for several inflammatory autoimmune diseases.

Objectives This Phase III multi-center study compared the efficacy, safety, and immunogenicity of CHS-0214 with etanercept for 24 weeks (Part 1) in patients with moderate/severe RA who had an inadequate response to MTX; then all patients received open-label CHS-0214 for 24 weeks with a final evaluation at Week 52 (Part 2).

Methods Patients were randomized to 50 mg of CHS-0214 or etanercept subcutaneously QWx24 weeks (Part 1). The primary endpoint was the ACR20 response rate at Week 24. To establish the equivalence of CHS-0214 to etanercept, the 95% confidence interval (CI) of the treatment difference between groups had to be within [–15%, 15%]. Secondary efficacy endpoints (ACR50, ACR 70, and change in DAS28-CRP), safety, and immunogenicity were also evaluated.

Results In 13 countries, 644 patients on MTX were randomized and received treatment. Baseline characteristics were comparable between treatment groups. Part 1 results are reported here. At 24 weeks, 512 patients were evaluable for efficacy. The ACR20 response rate was 91.0% (233/256) in the CHS-0214 group and 90.6% (232/256) in the etanercept group. The 95% CI of the treatment difference was [- 4.55, 5.37], which was within the pre-defined equivalence range. The response rates at 24 weeks were 67.6% vs. 63.7% for ACR50 and 38.3% vs. 37.9% for ACR70 in the CHS-0214 and etanercept groups, respectively. Mean (±SD) DAS28-CRP scores were 5.45 (± 1.00) and 5.42 (±1.00) at baseline and decreased to 2.67 (± 1.18) and 2.73 (±1.14) at 24 weeks in the CHS-0214 and etanercept groups, respectively (See Figure).

Among the 644 patients, adverse events (AEs) occurred in 60.8% and 65.0% of patients in the CHS-0214 and etanercept groups, respectively, including all infections combined in 34.3% and 32.2%, respectively. Investigator-designated treatment-related AEs occurred in 16.4% and 21.9% of patients, respectively, and most commonly included: injection site reactions (2.2% and 13.4%) and all infections combined (7.7% and 5.3%). Treatment-related serious AEs occurred in 3 (0.9%) patients treated with CHS-0214 (cholecystitis, increased blood creatinine phosphokinase, and bronchospasm) and 1 (0.3%) patient treated with etanercept (sepsis). Binding anti-drug antibodies occurred in 1.3% and 4.7% of patients in the CHS-0214 and etanercept groups.

Conclusions These results demonstrated equivalence of CHS-0214 to etanercept with respect to efficacy as measured by the primary endpoint (ACR20 at Week 24) and other measures (ACR50, ACR70, and DAS28-CRP). CHS-0214 was well tolerated with no clinically meaningful differences to etanercept with regard to safety and immunogenicity.

Disclosure of Interest J. O'Dell: None declared, T. Takeuchi: None declared, Y. Tanaka: None declared, I. Louw: None declared, T. Tiabut: None declared, M. Kai: None declared, M. Oribe: None declared, S. Nakashima Employee of: Daiichi Sankyo Co., Ltd., B. Finck Shareholder of: Coherus Biosciences, Employee of: Coherus Biosciences

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