학술논문
A comparative clinical study of PF-06410293, a candidate adalimumab biosimilar, and adalimumab reference product (Humira[R]) in the treatment of active rheumatoid arthritis
Document Type
Report
Author
Source
Arthritis Research & Therapy. August 15, 2018, Vol. 20 Issue 1
Subject
Language
English
ISSN
1478-6354
Abstract
Author(s): Roy M. Fleischmann[sup.1] , Rieke Alten[sup.2] , Margarita Pileckyte[sup.3] , Kasia Lobello[sup.4] , Steven Y. Hua[sup.5] , Carol Cronenberger[sup.4] , Daniel Alvarez[sup.4] , Amy E. Bock[sup.6] and K. Lea [...]
Background This double-blind, randomized, 78-week study evaluated the efficacy, safety, immunogenicity, pharmacokinetics, and pharmacodynamics of PF-06410293, a candidate adalimumab biosimilar, versus adalimumab reference product (Humira.sup.[R]) sourced from the EU (adalimumab-EU) in biologic-naïve patients with active rheumatoid arthritis (RA) despite methotrexate (MTX) (10-25 mg/week). We report results for the first 26 weeks of treatment. Methods Patients with active RA (N = 597) were randomly assigned (1:1) to PF-06410293 or adalimumab-EU, while continuing with MTX treatment. The primary endpoint was American College of Rheumatology 20% improvement (ACR20) at week 12. Therapeutic equivalence was concluded if the two-sided 95% confidence interval (CI) for the ACR20 difference between the two arms was entirely contained within the symmetric equivalence margin ([+ or -]14%). Additionally, a two-sided 90% CI was calculated by using an asymmetric equivalence margin (-12%, 15%). Secondary efficacy endpoints to week 26 included ACR20/50/70, change from baseline Disease Activity Score based on high-sensitivity C-reactive protein [DAS28-4(CRP)], European League Against Rheumatism (EULAR) response, DAS28-4(CRP) of less than 2.6, and ACR/EULAR remission. QuantiFERON-TB testing was performed at screening and week 26. Results Patients (78.7% of whom were female and whose mean age was 52.5 years) had a mean baseline RA duration of 6.8 years. The mean baseline DAS28-4(CRP) values were 5.9 (PF-06410293) and 6.1 (adalimumab-EU). The observed week-12 ACR20 values were 68.7% (PF-06410293) and 72.7% (adalimumab-EU) in the intention-to-treat population. With non-responder imputation, the treatment difference in week-12 ACR20 was -2.98% and corresponding CIs--95% CI (-10.38%, 4.44%) and 90% CI (-9.25%, 3.28%)--were entirely contained within the equivalence margins (symmetric and asymmetric, respectively). The secondary efficacy endpoints were similar between arms. Over 26 weeks, injection-site reactions occurred in 1.7% versus 2.0%, hypersensitivity events in 4.4% versus 8.4%, pneumonia in 0.7% versus 2.0%, and opportunistic infections in 2.4% versus 1.7% in the PF-06410293 and adalimumab-EU arms, respectively. One death due to myocardial infarction occurred (adalimumab-EU arm). Rates of anti-drug antibody incidence were 44.4% (PF-06410293) and 50.5% (adalimumab-EU). Conclusions The study results demonstrate that efficacy, safety, and immunogenicity of PF-06410293 and adalimumab-EU were similar during the first 26 weeks of treatment in patients with active RA on background MTX. Trial registration ClinicalTrials.gov Identifier: NCT02480153. First posted on June 24, 2015; EU Clinical Trials Register EudraCT number: 2014-000352-29. Start date: October 27, 2014. Keywords: Rheumatoid arthritis, Adalimumab, Biosimilar, Comparative clinical study
Background This double-blind, randomized, 78-week study evaluated the efficacy, safety, immunogenicity, pharmacokinetics, and pharmacodynamics of PF-06410293, a candidate adalimumab biosimilar, versus adalimumab reference product (Humira.sup.[R]) sourced from the EU (adalimumab-EU) in biologic-naïve patients with active rheumatoid arthritis (RA) despite methotrexate (MTX) (10-25 mg/week). We report results for the first 26 weeks of treatment. Methods Patients with active RA (N = 597) were randomly assigned (1:1) to PF-06410293 or adalimumab-EU, while continuing with MTX treatment. The primary endpoint was American College of Rheumatology 20% improvement (ACR20) at week 12. Therapeutic equivalence was concluded if the two-sided 95% confidence interval (CI) for the ACR20 difference between the two arms was entirely contained within the symmetric equivalence margin ([+ or -]14%). Additionally, a two-sided 90% CI was calculated by using an asymmetric equivalence margin (-12%, 15%). Secondary efficacy endpoints to week 26 included ACR20/50/70, change from baseline Disease Activity Score based on high-sensitivity C-reactive protein [DAS28-4(CRP)], European League Against Rheumatism (EULAR) response, DAS28-4(CRP) of less than 2.6, and ACR/EULAR remission. QuantiFERON-TB testing was performed at screening and week 26. Results Patients (78.7% of whom were female and whose mean age was 52.5 years) had a mean baseline RA duration of 6.8 years. The mean baseline DAS28-4(CRP) values were 5.9 (PF-06410293) and 6.1 (adalimumab-EU). The observed week-12 ACR20 values were 68.7% (PF-06410293) and 72.7% (adalimumab-EU) in the intention-to-treat population. With non-responder imputation, the treatment difference in week-12 ACR20 was -2.98% and corresponding CIs--95% CI (-10.38%, 4.44%) and 90% CI (-9.25%, 3.28%)--were entirely contained within the equivalence margins (symmetric and asymmetric, respectively). The secondary efficacy endpoints were similar between arms. Over 26 weeks, injection-site reactions occurred in 1.7% versus 2.0%, hypersensitivity events in 4.4% versus 8.4%, pneumonia in 0.7% versus 2.0%, and opportunistic infections in 2.4% versus 1.7% in the PF-06410293 and adalimumab-EU arms, respectively. One death due to myocardial infarction occurred (adalimumab-EU arm). Rates of anti-drug antibody incidence were 44.4% (PF-06410293) and 50.5% (adalimumab-EU). Conclusions The study results demonstrate that efficacy, safety, and immunogenicity of PF-06410293 and adalimumab-EU were similar during the first 26 weeks of treatment in patients with active RA on background MTX. Trial registration ClinicalTrials.gov Identifier: NCT02480153. First posted on June 24, 2015; EU Clinical Trials Register EudraCT number: 2014-000352-29. Start date: October 27, 2014. Keywords: Rheumatoid arthritis, Adalimumab, Biosimilar, Comparative clinical study