Patients are unaffected by the switch from ADL-EU to ADL-PF.
Roy Fleischmann, MD
New study findings suggest comparable efficacy, safety, and immunogenicity between PF-06410293 (ADL-PF) and reference adalimumab sourced from the European Union (ADL-EU) was maintained up to week 56 for patients with rheumatoid arthritis.
The findings, presented online as part of the European E-Congress of Rheumatology 2020 (EULAR 2020), were unaffected by a blind switch from ADL-EU to ADL-PF at week 26.
Roy Fleischmann, MD, from the University of Texas, and colleagues from Pfizer and Schlosspark Klinik evaluated the efficacy, safety, and immunogenicity of ADL-PF (an adalimumab biosimilar approved for the treatment of several inflammatory and autoimmune indications) and ADL-EU in patients with moderate to severe rheumatoid arthritis on longer-term treatment. The team also evaluated a treatment switch from ADL-EU to ADL-PF in a subset of patients.
In the multinational, randomized, double-blind, parallel-group study, Fleischmann and the investigators compared ADL-PF and ADL-EU in essentially biologic-naïve patients with rheumatoid arthritis despite methotrexate. During the initial treatment period, patients were randomized to 40 mg subcutaneous injection of ADL-PF or ADL-EU every 2 weeks for 26 weeks while continuing 10-25 mg per week of methotrexate. The primary endpoint of the first treatment period was to achieve an American College of Rheumatology response (ACR20) at week 12.
At the start of the second treatment period at week 26, patients who received ADL-EU were blindly rerandomized to either remain on the treatment or switch to ADL-PF for 26 weeks. The other patients continued receiving ADL-EU in a blinded manner. Secondary endpoints were assessed at weeks 26, 30, 36, 44, and 52 and included ACR20/50/70, European Language Against Rheumatism response, Disease Activity Score <2.6, and ACR/EULAR defined remission. Endpoints also included safety events and the percentage of patients with anti-drug antibodies.
During the first treatment period, 597 patients were randomized to ADL-PF (n=297) or ADL-EU (n=300). At week 26, 552 patients were then rerandomized for the second treatment period (continued ADL-PF, n=283; continued ADL-EU, n=135; switched from ADL-EU to ADL-PF, n=134). Patients moved onto the second treatment period if they demonstrated at least minimal efficacy.
ACR20 rates were comparable between both treatment groups during all visits in the second study period. Deep response measures such as ACR70 and EULAR good response showed maintained efficacy during the second study period in both groups.
The total number of incidences of anti-drug antibodies through week 52 were comparable between treatment groups (47.3%, 54.1%, and 45.9% for patients who continued ADL-PF, continued ADL-EU, or switched from ADL-EU to ADL-PF). Among those who switched from ADL-EU to ADL-PF compared to those who continued ADL-EU, the increase in anti-drug antibodies incidence over the second treatment was .8% (45.1% to 45.9%) versus 6.7% (47.4% to 54.1%).
Overall, the second treatment period results showed comparable and maintained efficacy, safety, and immunogenicity between ADL-PF and ADL-EU. Patients were unaffected by the switch from ADL-EU to ADL-PF.
The study abstract, “Efficacy, Safety and Immunogenicity In Patients With Rheumatoid Arthritis Comparing PF-06410293 (ADL-PF), An Adalimumab (ADL) Biosimilar, And Reference ADL: Results From Week 26-52 Of A Double-Blind, Randomized Phase 3 Study Including Patients Who Switched From ADL-PF To Reference ADL At Week,” was published online on the EULAR 2020 website.