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Introduction <p>This study was conducted to fulfill the FDA requirement for the designation of adalimumab-fkjp, an FDA-approved biosimilar, as an ‘interchangeable’ biosimilar to the reference adalimumab. The primary objective was to evaluate the interchangeability of adalimumab-fkjp (low concentration, 40&#xa0;mg/0.8&#xa0;mL) with reference adalimumab (high concentration, 40&#xa0;mg/0.4&#xa0;mL) by comparing adalimumab steady-state pharmacokinetics (PK) between switching and non-switching arms. The efficacy, safety, and immunogenicity were also evaluated.</p> Methods <p>In this randomized, double-blind, parallel-group study in patients with moderate-to-severe chronic plaque psoriasis (PPs) a total of 386 patients (134 F/252&#xa0;M) with PPs for&#xa0;≥&#xa0;6&#xa0;months involving body surface area&#xa0;≥&#xa0;10% and having a Psoriasis Area and Severity Index (PASI)&#xa0;≥&#xa0;12 and static Physicians Global Assessment (sPGA)&#xa0;≥&#xa0;3 (moderate) were enrolled into the run-in period to receive reference adalimumab (80&#xa0;mg, Week 1; 40&#xa0;mg biweekly, Weeks 2–10). At Week 12, patients with PASI&#xa0;≥&#xa0;50 (<i>n</i>&#xa0;=&#xa0;374) were randomized 1:1 to continue receiving reference adalimumab (<i>n</i>&#xa0;=&#xa0;193; 40&#xa0;mg/0.4&#xa0;mL biweekly, Weeks 12–26) or undergo repeated switches between 40&#xa0;mg/0.8&#xa0;mL adalimumab-fkjp and 40&#xa0;mg/0.4&#xa0;mL reference adalimumab (<i>n</i>&#xa0;=&#xa0;181; reference adalimumab-fkjp, Weeks 12 and 14; adalimumab, Weeks 16 and 18; and adalimumab-fkjp, Weeks 20, 22, 24, and 26). The assessments included PK (primary endpoints: AUC<sub>τ,26–28</sub> and C<sub>max,26–28</sub>; secondary endpoints: T<sub>max,26–28</sub>, C<sub>min,26–28</sub>, and C<sub>trough</sub>), efficacy (proportion of PASI-50, PASI-75, PASI-90, and PASI-100 responders and sPGA success of clear or almost clear at Week 28), safety, and immunogenicity.</p> Results <p>The mean steady-state serum PK profiles were similar in both switching and non-switching arms. The 90% confidence intervals of LS mean ratios for AUC<sub>τ,26–28</sub> [104.76 (98.23–111.74%)], C<sub>max,26–28</sub> [104.23 (95.85–113.36%)], and C<sub>min,26–28</sub> [107.85 (99.99–116.37%)] were within the bioequivalent range of 80.00–125.00%. The overall number and proportion of patients with PASI responses and sPGA success were highly similar between the two arms at Week 28. Safety and immunogenicity profiles were comparable between treatment arms.</p> Conclusion <p>Patients receiving adalimumab-fkjp (low concentration) and reference adalimumab (high concentration) in alternate fashion had similar PK, efficacy, safety, and immunogenicity profile. Interchangeability status has been granted to adalimumab-fkjp.</p> Trial Registration <p>Clinicaltrial.gov identifier: NCT05637515, EudraCT No:2021-006015-29.</p>

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Multiple Switches Between Adalimumab-fkjp and Reference Adalimumab in Moderate-to-Severe Chronic Plaque Psoriasis: A Multicenter, Double-Blind, Parallel Group, Randomized Clinical Trial for Interchangeability

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  • 发表日期：

    2025年6月10日

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  • Sarika Deodhar,
  • Subramanian Loganathan,
  • Ramesh Kadadanamari Subbarama Reddy,
  • Gopinath M. Ranganna,
  • Shiyao Liu,
  • Matthew A. Hummel,
  • Stefan Daniluk,
  • Anna Hanczewska,
  • Kamelia Vekovska,
  • Maria Zegadlo-Mylik,
  • Grazyna Pulka,
  • Elena Wolff -Holz

摘要

Introduction

This study was conducted to fulfill the FDA requirement for the designation of adalimumab-fkjp, an FDA-approved biosimilar, as an ‘interchangeable’ biosimilar to the reference adalimumab. The primary objective was to evaluate the interchangeability of adalimumab-fkjp (low concentration, 40 mg/0.8 mL) with reference adalimumab (high concentration, 40 mg/0.4 mL) by comparing adalimumab steady-state pharmacokinetics (PK) between switching and non-switching arms. The efficacy, safety, and immunogenicity were also evaluated.

Methods

In this randomized, double-blind, parallel-group study in patients with moderate-to-severe chronic plaque psoriasis (PPs) a total of 386 patients (134 F/252 M) with PPs for ≥ 6 months involving body surface area ≥ 10% and having a Psoriasis Area and Severity Index (PASI) ≥ 12 and static Physicians Global Assessment (sPGA) ≥ 3 (moderate) were enrolled into the run-in period to receive reference adalimumab (80 mg, Week 1; 40 mg biweekly, Weeks 2–10). At Week 12, patients with PASI ≥ 50 (n = 374) were randomized 1:1 to continue receiving reference adalimumab (n = 193; 40 mg/0.4 mL biweekly, Weeks 12–26) or undergo repeated switches between 40 mg/0.8 mL adalimumab-fkjp and 40 mg/0.4 mL reference adalimumab (n = 181; reference adalimumab-fkjp, Weeks 12 and 14; adalimumab, Weeks 16 and 18; and adalimumab-fkjp, Weeks 20, 22, 24, and 26). The assessments included PK (primary endpoints: AUCτ,26–28 and Cmax,26–28; secondary endpoints: Tmax,26–28, Cmin,26–28, and Ctrough), efficacy (proportion of PASI-50, PASI-75, PASI-90, and PASI-100 responders and sPGA success of clear or almost clear at Week 28), safety, and immunogenicity.

Results

The mean steady-state serum PK profiles were similar in both switching and non-switching arms. The 90% confidence intervals of LS mean ratios for AUCτ,26–28 [104.76 (98.23–111.74%)], Cmax,26–28 [104.23 (95.85–113.36%)], and Cmin,26–28 [107.85 (99.99–116.37%)] were within the bioequivalent range of 80.00–125.00%. The overall number and proportion of patients with PASI responses and sPGA success were highly similar between the two arms at Week 28. Safety and immunogenicity profiles were comparable between treatment arms.

Conclusion

Patients receiving adalimumab-fkjp (low concentration) and reference adalimumab (high concentration) in alternate fashion had similar PK, efficacy, safety, and immunogenicity profile. Interchangeability status has been granted to adalimumab-fkjp.

Trial Registration

Clinicaltrial.gov identifier: NCT05637515, EudraCT No:2021-006015-29.