Effectiveness of Etanercept Biosimilar Initiating for Etanercept-Naive Patients, Using Ultrasound, Clinical, and Biomarker Assessments in Outcomes of Real-World Therapy (ENPORT-NGSK Study): An Interventional, Multicenter, Open-Label, Single-Arm Clinical Trial

Abstract

Background/Objectives: This study aimed to investigate the effectiveness of etanercept biosimilar 1 under real-world clinical conditions in patients with rheumatoid arthritis (RA), using not only clinical evaluation but also musculoskeletal ultrasound (MSUS). Methods: This multicenter, interventional, open-label, single-arm clinical trial conducted a 24-week follow-up. Patients with RA with moderate to high disease activity received weekly subcutaneous injections of etanercept biosimilar 1 at 50 mg/dose for 24 weeks. The effectiveness was evaluated with clinical indices and MSUS. Results: Twenty-three patients were evaluated during the study period. The primary endpoint involves a change in the Global OMERACT-EULAR Synovitis Score by MSUS in bilateral second-fifth metacarpophalangeal joints from baseline, demonstrating median (IQR) values of 0 (-4, 1), including 4 (1, 9.8) and 2 (0, 5) at baseline and 24 weeks, respectively. The clinical endpoints exhibited a good treatment response, with 15 (68%) and 18 (86%) patients achieving low disease activity or remission at 12 weeks and 24 weeks, respectively. Additionally, MSUS scores improved at both 12 and 24 weeks compared to baseline. The patients who achieved power doppler remission (total power doppler score = 0) at 24 weeks demonstrated a shorter disease duration and no previous use of biological disease-modifying antirheumatic drugs compared to those with no power doppler remission. Conclusions: Etanercept biosimilar 1 exhibited significant improvements not only in clinical indices but also in MSUS assessment, indicating its effectiveness at the structural level.

Keywords: biomarkers; biosimilar; etanercept; musculoskeletal ultrasound (MSUS); rheumatoid arthritis (RA).

Figure 1

Assessment of effectiveness. (a) Assessment of effectiveness in clinical measures. The p-values and 95% CI for baseline to 12 weeks, baseline to 24 weeks, and 12–24 weeks were as follows. DAS28-CRP: p < 0.0001 [−2.13, −1.35], p < 0.0001 [−2.40, −1.53], and p < 0.01 [−0.50, −0.02]. DAS28-ESR: p < 0.0001 [−2.51, −1.62], p < 0.0001 [−2.82, −1.76], and p = 0.03 [−0.52, 0.04]. SDAI: p < 0.0001 [−17.4, −10.8], p < 0.0001 [−18.4, −11.7], and p = 0.02 [−2.88, −0.03]. CDAI: p < 0.0001 [−16.4, −9.84], p < 0.0001 [−17.6, −11.1], and p = 0.02 [−3.02, −0.16]. HAQ-DI: p < 0.001 [−0.48, −0.13], p < 0.001 [−0.45, −0.12], and p = 0.93 [−0.11, 0.15]. (b) Assessment of effectiveness in MSUS. The p-values and 95% CI for baseline to 12 weeks, baseline to 24 weeks, and 12–24 weeks were as follows. Total GS score: p < 0.01 [−5.60, −1.13], p < 0.01 [−7.58, −1.85], and p = 0.03 [−3.34, −0.09]. Total PD Score: p < 0.0001 [−6.18, −2.36], p < 0.0001 [−7.17, −2.83], and p < 0.01 [−1.51, −0.30]. GLOESS: p < 0.01 [−5.77, −1.22], p < 0.001 [−7.76, −1.96], and p = 0.03 [−3.34, −0.09]. GLOESS of bilateral second–fifth MCP joints: p = 0.11 [−2.37, 0.10], p = 0.13 [−3.38, −0.05], and p = 0.20 [−1.76, 0.34]. CDAI, clinical disease activity index; CRP, C-reactive protein; DAS28, Disease Activity Score—28; ESR, erythrocyte sedimentation rate; GLOESS, Global OMERAC EULAR Synovitis Score; GS, gray scale; HAQ-DI, Health Assessment Questionnaire–Disability Index; MCP, metacarpophalangeal; ns, not significant; PD, power Doppler; SDAI, simplified disease activity index.