FRI0087\u2005EFFICACY, SAFETY, AND IMMUNOGENICITY RESULTS OF THE SWITCH FROM REFERENCE ADALIMUMAB (REFADL) TO SANDOZ BIOSIMILAR ADALIMUMAB (GP2017, SDZ-ADL) FROM ADMYRA PHASE 3 STUDY IN PATIENTS WITH MODERATE-TO-SEVERE RHEUMATOID ARTHRITIS (RA)

Abstract

Background SDZ-ADL is approved by EMA in all indications of refADL based on preclinical and clinical study results. EMA submission data included results of a Phase 3 study in patients with plaque psoriasis. ADMYRA was a Phase 3 study comparing efficacy and safety of SDZ-ADL and refADL in patients with moderate-to-severe RA with inadequate response to disease modifying anti-rheumatic drugs, including methotrexate (NCT02744755). Objectives The ADMYRA study was designed to compare the efficacy of SDZ-ADL and refADL over 24 weeks of treatment, and to evaluate long-term efficacy, safety, and immunogenicity of SDZ-ADL up to Week (Wk) 48. The study also investigated the effect of the switch from refADL to SDZ-ADL at Wk 24 on efficacy, safety, and immunogenicity up to Wk 48. This abstract focuses on the data after switch from refADL to SDZ-ADL. Methods Eligible patients were randomized 1:1 to receive 40 mg subcutaneous SDZ-ADL or refADL every other week from Wk 0–22. At Wk 24, patients in the refADL arm were switched to receive SDZ-ADL; treatment continued until Wk 46. The primary endpoint was change in Disease Activity Score-28 including high-sensitivity C-reactive protein (DAS28-CRP) from baseline at Wk 12. Secondary endpoints included mean changes in DAS28-CRP scores, the proportion of patients fulfilling EULAR responses, EULAR and Boolean remission criteria, safety, and immunogenicity. EULAR remission was defined as DAS28-CRP <2.6. Boolean remission was defined as tender joint count 28 ≤1, swollen joint count 28 ≤1, CRP ≤1 mg/dL, and patient global assessment ≤10 on a 100 mm scale. Results As reported previously, mean change in DAS28-CRP from baseline at Wk 12 was -2.16 for SDZ-ADL (N=140) and -2.18 for refADL (N=144).1 Efficacy in both treatment arms was maintained throughout the study, also after the switch from refADL to SDZ-ADL at Wk 24. Mean change in DAS28-CRP from baseline at Wk 48 was -2.90 and -2.92 for refADL/switched and SDZ-ADL groups, respectively. At Wk 48, the proportion of patients with moderate/good EULAR response was 29.6/68.0% in refADL/switched group and 29.0/69.2% in SDZ-ADL group. At Wk 48, the proportion of patients in EULAR remission was 54.4 and 51.4% and in Boolean remission was 21.6 and 16.8% for refADL/switched and SDZ-ADL groups, respectively. As previously reported, safety and immunogenicity were similar in both arms before switch.1 No new safety concerns were identified after switch. After switch, 32.5% of patients in the refADL/switched group and 36.5% of patients in the SDZ-ADL group experienced adverse events (AEs); serious AEs were reported by 3.6 and 2.5%, respectively. The proportion of patients reporting injection site reactions after switch was 1.2% in the refADL/switched group and 0.6% in the SDZ-ADL group, respectively. After switch, 26.3 and 24.0% of patients were positive for antidrug antibodies (ADAs) in refADL/switched and SDZ-ADL groups, respectively. Of these, 81.0 vs 72.2% were neutralizing. ADA positivity had no clinically meaningful impact on safety. Conclusion After the switch from reference to biosimilar, the rates of EULAR remission/response and Boolean remission were high and maintained until Week 48. Treatment switch from refADL to SDZ-ADL at Wk 24 did not impact efficacy, safety, or immunogenicity. Reference [1] Wiland P, et al. Arthritis Rheumatol 2018;70(suppl 10). Disclosure of Interests Piotr Wiland Speakers bureau: Novartis, Pfizer, Abbvie, Gedeon-Richter, Lilly, Roche and Sandoz, Sławomir Jeka: None declared, Eva Dokoupilova: None declared, Juan Manuel Miranda Limon: None declared, Julia Jauch-Lembach Employee of: Hexal AG, Anjali Thakur Employee of: Hexal AG, Halimuniyazi Haliduola Employee of: Hexal AG, Norman Gaylis Grant/research support from: Multiple clinical research trials, BMS, AbbVie, GSK, Janssen, Amgen, Pfizer, Regeneron, UCB, Sanofi, SetPoint, ImmunPharma, Astra Zeneca, Sandoz, Novartis, Gilead, Consultant for: electroCore