Long-term efficacy, safety, and immunogenicity of the adalimumab biosimilar, PF-06410293, in patients with rheumatoid arthritis after switching from reference adalimumab (Humira®) or continuing biosimilar therapy: week 52–92 data from a randomized, double-blind, phase 3 trial

Abstract

Background/objective REFLECTIONS B538–02 is a randomized, double-blind comparative study of the adalimumab (ADL) biosimilar PF-06410293, (ADL-PF), and reference ADL sourced from the European Union (ADL-EU) in patients with active RA. Therapeutic equivalence was demonstrated based on ACR20 responses at week 12 (primary endpoint). We report long-term safety, immunogenicity, and efficacy of ADL-PF in patients who continued ADL-PF treatment throughout 78 weeks or who switched from ADL-EU to ADL-PF at week 26 or week 52. Methods Eligible patients (2010 ACR/EULAR RA diagnosis criteria for ≥ 4 months; inadequate response to MTX, ≤ 2 doses non-ADL biologic), stratified by geographic regions were initially randomized (1:1) in treatment period 1 (TP1) to ADL-PF or ADL-EU (40 mg subcutaneously, biweekly), both with MTX (10–25 mg/week). At week 26 (start of TP2), patients receiving ADL-EU were re-randomized to remain on ADL-EU or transition to ADL-PF for 26 weeks. At week 52 (start of TP3), all patients received open-label treatment with ADL-PF for 26 weeks and were followed after last treatment dose to week 92. To evaluate maintenance of response after switching or remaining on ADL-PF, ACR20, DAS28-4(CRP), and other measures of clinical response/remission were assessed through week 78 as secondary endpoints. Three groups were evaluated: biosimilar, week 26 switch, and week 52 switch. Results Overall, 507 patients participated in TP3. ACR20 response rates at week 52 were 88.4%, 88.2%, and 87.6% for the biosimilar, week 26, and week 52 switch groups, respectively. ACR20 response rates and DAS28-4(CRP) scores were sustained and comparable across groups in TP3. Incidence of treatment-emergent adverse events (AEs) during TP3 and follow-up was 42.6% (biosimilar), 37.0% (week 26 switch), and 50.8% (week 52 switch); 3 (0.6%) patients (all week 52 switch) reported treatment-related serious AEs. ADL-PF was generally well tolerated, with a comparable safety profile across groups. Overall, incidences of patients with anti-drug antibodies in TP3 and follow-up were comparable among groups (46.1%, 46.5%, and 54.2%, respectively). Conclusions There were no clinically meaningful differences in safety, immunogenicity, and efficacy for patients who were maintained on ADL-PF for 78 weeks and those who had switched from ADL-EU at week 26 or week 52. Trial registration ClinicalTrials.gov, NCT02480153. First posted on June 24, 2015; EU Clinical Trials Register; EudraCT number: 2014-000352-29. Start date, October 27, 2014

Usability Study of PF-06410293, an Adalimumab Biosimilar, by Prefilled Pen: Open-Label, Single-Arm, Sub-Study of a Phase 3 Trial in Patients with Rheumatoid Arthritis

“…1 ) to determine whether patients/caregivers could safely and effectively administer ADL-PF using a PFP device. The study design and inclusion criteria for the main study (NCT02480153) have been described in detail elsewhere [ 16 – 18 ]; features relevant to this sub-study of ADL-PF PFP are summarized below.

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“…Similarity between treatments was maintained up to week 52, regardless of whether patients switched from ADL-EU to ADL-PF at week 26 (start of TP2) [ 17 ]. Long-term efficacy and safety of ADL-PF following 78 weeks of treatment was demonstrated during TP3 and was unaffected by switching from ADL-EU to ADL-PF at week 26 or week 52 [ 18 ].…”

Use of multibiomarker disease activity scores in biosimilarity studies for the treatment of patients with rheumatoid arthritis

“…In TP2 (weeks 26–52), patients receiving ADL-EU remained blinded and were rerandomised 1:1 at week 26 either to continue receiving ADL-EU or to switch to ADL-afzb 22. Throughout TP3 (weeks 52–78), all patients received open-label treatment with ADL-afzb 23…”

“…The main studies were conducted in compliance with the provisions of the Declaration of Helsinki and the International Conference on Harmonization Good Clinical Practice Guidelines. All patients provided informed consent prior to undergoing any screening procedures 7 10 20–23…”

Systemic review of safety and efficacy of approved bio similar for management of rheumatoid arthritis

“…In Roy M Fleischmann et al 9 is a randomized, double-blind comparative study of the adalimumab (ADL) biosimilar PF-06410293, (ADL-PF), and originator ADL sourced from the European Union (ADL-EU) in patients with active RA. Therapeutic equivalence was assessed based on ACR20 responses at week 12 (primary endpoint).…”