A single-arm, open-label study to assess the immunogenicity, safety, and efficacy of etanercept manufactured using the serum-free, high-capacity manufacturing process administered to patients with rheumatoid arthritis

Abstract

Objective: To evaluate the immunogenicity, safety, and efficacy of etanercept (ETN) manufactured using the serum-free, high-capacity manufacturing (SFHCM) process in patients with rheumatoid arthritis (RA).

Methods: In this global, multicenter, open-label, single-arm study (NCT02378506), 187 adult patients with moderate to severe RA received ETN 50 mg once weekly for 24 weeks manufactured using the SFHCM process. Immunogenicity (presence of antidrug antibodies (ADAs) and neutralizing antibodies (NAbs)) was assessed at 12 and 24 weeks. Safety and efficacy were evaluated at 4, 12, and 24 weeks.

Results: Eight (4.5%) patients tested positive for ADA, and there were no NAbs detected at any time throughout the study. Ninety (48.1%) patients reported treatment-emergent adverse events (AEs), of which 27 (14.4%) reported injection-site reactions, and 43 (23.0%) reported infections. The majority of AEs were mild or moderate in severity, and the drug was well tolerated. Throughout the duration of the study (week 4 to week 24), there was a progressive increase in the American College of Rheumatology (ACR)-defined responses (ACR20: 55.9%-82.0%, ACR50: 16.1%-57.8%, and ACR70: 3.2%-26.7%) from baseline and the proportion of patients achieving low disease activity and remission, with a corresponding decrease in measures of disease activity.

Conclusion: The immunogenicity, safety, and efficacy of ETN manufactured using the SFHCM process were similar to the current approved ETN formulation. ClinicalTrials.gov registration: NCT02378506.

Conflict of interest statement

Conflict of Interest: P. Polák is the primary external reviewer and a consultant for Pfizer on this study and principal investigator. P. Peric is a principal investigator and a consultant for Pfizer on this study. I.L. is an advisor in rheumatology for Bristol-Myers Squibb, Novartis, Pfizer, and Roche, and a principal investigator on clinical studies sponsored by Amgen, AstraZeneca, Baxalta, Bristol-Myers Squibb, Celgene, Coherus, Eli Lilly, Janssen, and Pfizer. J.C.B. is an employee of Becker Clinical Research Consulting LLC, who was a paid consultant to Pfizer in connection with the development of this manuscript and owns stock in Pfizer. S.M.G., T.W., R.P., J.K.B., B.V. are employees of Pfizer and own stock in Pfizer.

Figures

Figure 1

Patient disposition ADA: antidrug antibody

Figure 2. a–c

Clinical responses Proportions of patients achieving ACR20, ACR50, and ACR70 (b); DAS28-ESR and DAS28-CRP scores (b); proportions of patients achieving LDA and remission according to the DAS28-ESR and DAS28-CRP criteria at 24 weeks (c). For composite measures, missing component values were imputed using the last observation carried forward ACR20; ACR50; ACR70: American College of Rheumatology criteria for RA, CRP: C-reactive protein, DAS28: disease activity score based on 28 joint count, ESR: erythrocyte sedimentation rate, LDA: low disease activity, SD: standard deviation

Figure 3. a–c

Clinical responses by the ADA status Proportions of ADA+ and ADA− patients achieving ACR20, ACR50, and ACR70 (a); DAS28-ESR and DAS28-CRP scores in ADA+ and ADA− patients (b); proportions of ADA+ and ADA− patients achieving LDA and remission according to the DAS28-ESR and DAS28-CRP criteria at 24 weeks (c). For composite measures, missing component values were imputed using the last observation carried forward ACR20; ACR50; ACR70: American College of Rheumatology criteria for RA, ADA: antidrug antibody, CRP: C-reactive protein, DAS28: disease activity score based on 28 joint count, ESR: erythrocyte sedimentation rate, LDA: low disease activity, SD: standard deviation

Figure 4

Summary of efficacy assessments at 24 weeks HAQ-DI: Health Assessment Questionnaire-Disability Index, PGA: Physician Global Assessment, PtGA: Patient Global Assessment, SD: standard deviation, SJC: swollen joint count, TJC: tender joint count, VAS: Visual Analog Scale