Longer-term follow-up supports earlier evidence that treatment switch from adalimumab-EU to PF-06410293 does not impact treatment safety, immunogenicity, and efficacy in patients with moderate-to-severe, active rheumatoid arthritis.
A randomized, double-blind, comparative clinical trial (NCT02480153) evaluated the long-term safety, immunogenicity, and efficacy of the adalimumab biosimilar, PF-06410293 (ADL-PF), in patients with moderate-to-severe, active rheumatoid arthritis (RA) who continued ADL-PF treatment throughout 78 weeks or who switched from reference adalimumab sourced from the European Union (adalimumab-EU) to ADL-PF at week 26 or week 52. The results from Treatment Period 3 (TP3; weeks 52-92) were presented at the American College of Rheumatology (ACR) Convergence 2020 meeting.
Included in the study were patients who met 2010 ACR/European League Against Rheumatism RA diagnosis criteria for ≥4 months, had an inadequate response to methotrexate, and had received ≤2 doses of 1 lymphocyte-depleting or non-adalimumab biologic. The treatment sequence was in 3 stages. In Treatment Period 1 (TP1), eligible patients were randomized to receive ADL-PF or adalimumab-EU (40 mg subcutaneously every other week) with methotrexate; stratification was by geographic regions. At the start of Treatment Period 2 (TP2; week 26), patients who received adalimumab-EU were re-randomized to either continue adalimumab-EU or switch to ADL-PF for an additional 26 weeks. At the start of TP3 (week 52), all patients received open-label ADL-PF for an additional 26 weeks. The primary end point was ≥20% clinical improvement of ACR criteria (ACR20, a composite measure defined as both improvement of 20% in the number of tender and swollen joints, and a 20% improvement in 3 of the following 5 criteria: patient global assessment, physician global assessment, functional ability measure [most often Health Assessment Questionnaire], visual analog pain scale, and erythrocyte sedimentation rate or C-reactive protein [CRP]) at week 12; secondary efficacy end points included ACR20 at other time points and Disease Activity Score in 28 joints comprising 4 variables based on high-sensitivity CRP (DAS28-4 CRP). Response assessment was done in 3 groups corresponding to the treatment sequence (ie, biosimilar randomization, week 26 switch, and week 52 switch).
A total of 597 patients were randomized in TP1; of these, 552 continued to TP2 at week 26, and 507 received open-label ADL-PF in TP3. In the TP3 study population, the majority of patients were female (78.1%) and white (86.6%). Overall, ACR20 response rates and DAS28-4 CRP scores were comparable across groups and were maintained from previous treatment periods.
The safety profiles were comparable across groups. During TP3 and the 16-week follow-up period, the incidence of treatment-emergent adverse events (AEs) was 42.6% in the biosimilar cohort, 37.0% in the week 26 switch cohort, and 50.8% in the week 52 switch cohort. Overall, 3 treatment-related serious AEs were reported, all in the week 52 switch group; 1 death occurred in the week 52 switch group.
Also during TP3 or the follow-up period, among patients who tested negative for antidrug antibodies (ADAs) on entry to TP3, incidence rates of ADAs were 8.9%, 6.3%, and 8.3% for the biosimilar, week 26 switch, and week 52 switch groups, respectively; overall, incidences of patients with ADAs in TP3 and the follow-up period were comparable among groups (46.1%, 46.5%, and 54.2%, respectively).
These results from TP3 and the follow-up period demonstrated no clinically meaningful differences in safety, immunogenicity, and efficacy among treatment groups, which was consistent with earlier findings from this study, indicating that treatment switch from adalimumab-EU to ADL-PF did not impact treatment outcomes.
Reference
Fleischmann R, et al. Arthritis Rheumatol. 2020;72(suppl 10):Abstract 798.