PMID- 33119861 OWN - NLM STAT- MEDLINE DCOM- 20210412 LR - 20210412 IS - 1179-190X (Electronic) IS - 1173-8804 (Print) IS - 1173-8804 (Linking) VI - 34 IP - 6 DP - 2020 Dec TI - Switching to Biosimilar SDZ-ADL in Patients with Moderate-to-Severe Active Rheumatoid Arthritis: 48-Week Efficacy, Safety and Immunogenicity Results From the Phase III, Randomized, Double-Blind ADMYRA Study. PG - 809-823 LID - 10.1007/s40259-020-00447-6 [doi] AB - BACKGROUND: Sandoz adalimumab SDZ-ADL (GP-2017) is an approved adalimumab biosimilar with similar efficacy and comparable safety and immunogenicity to reference adalimumab (ref-ADL) as confirmed by analytical, pharmacokinetic and confirmatory studies. ADMYRA, a phase III double-blind study, was conducted with an aim to generate efficacy, safety and immunogenicity comparability data in patients with moderate-to-severe rheumatoid arthritis (RA) having inadequate response to disease-modifying anti-rheumatic drugs (DMARDs) including methotrexate (MTX). The study also evaluated an aspect of 'switching' reference product to the biosimilar in terms of efficacy, safety and immunogenicity up to Week 48. METHODS: Eligible patients (N = 353) were randomized 1:1 to receive subcutaneous (sc) SDZ-ADL 40 mg (n = 177) or ref-ADL (n = 176) every other week from Week 0 to Week 24. At Week 24, all patients with at least a moderate response by Disease Activity Score-28 including high-sensitivity C-reactive protein (DAS28-CRP) in the SDZ-ADL group continued SDZ-ADL (n = 159), and in the ref-ADL group were switched to SDZ-ADL (n = 166), treated for up to 46 weeks. The primary endpoint was change in DAS28-CRP from baseline at Week 12. Other efficacy endpoints included proportion of patients with European League Against Rheumatism (EULAR) response, EULAR remission, Boolean remission, safety and immunogenicity. RESULTS: The DAS28-CRP score changes from baseline at Week 12 were similar between SDZ-ADL (- 2.16) and ref-ADL (- 2.18) with a mean difference (95% CI) of 0.02 (- 0.24 to 0.27), which was within the pre-specified equivalence margin of +/- 0.6. After switching treatment from ref-ADL to SDZ-ADL, the mean DAS28-CRP change was similar between the SDZ-ADL and 'ref-ADL/switched SDZ-ADL' group (- 3.09 vs - 3.05). The proportion of patients with good/moderate EULAR response was 69.2%/29.0% in the SDZ-ADL group and 68.0%/29.6% in the 'ref-ADL/switched SDZ-ADL' group. The proportion of patients in EULAR remission was 51.4% and 54.4% and in Boolean remission was 16.8% and 21.6% for SDZ-ADL and 'ref-ADL/switched SDZ-ADL' groups, respectively. The secondary endpoints were similar across the treatment groups. The incidence of adverse events (AEs) and injection-site reactions were low and similar between SDZ-ADL and 'ref-ADL/switched SDZ-ADL' groups (AEs 70.6% vs 68.8%, injection-site reactions 4.0% vs 6.3%), and most of these patients experienced AEs of mild or moderate severity. Antidrug antibodies were detected in 24.2% and 25.6% of patients treated with SDZ-ADL and 'ref-ADL/switched SDZ-ADL', respectively, from baseline to Week 48, of which 72.5% in SDZ-ADL and 79.1% in 'ref-ADL/switched SDZ-ADL' groups were neutralizing. CONCLUSIONS: In patients with moderate-to-severe RA who had an inadequate response to DMARDs, SDZ-ADL demonstrated a similar efficacy and a comparable safety and immunogenicity profile to ref-ADL. Efficacy was sustained after switching from ref-ADL to SDZ-ADL with no impact on safety (NCT02744755). FAU - Wiland, Piotr AU - Wiland P AD - Department of Rheumatology and Internal Medicine, Medical University, Wroclaw, Poland. pwiland1@gmail.com. FAU - Jeka, Slawomir AU - Jeka S AD - Department of Rheumatology and Connective Tissue Diseases, University Hospital No. 2, Collegium Medicum UMK, Bydgoszcz, Poland. FAU - Dokoupilova, Eva AU - Dokoupilova E AD - MEDICAL PLUS s.r.o., University of Veterinary and Pharmaceutical sciences, Faculty of Pharmacy, Uherske Hradiste, Czech Republic. FAU - Brandt-Jurgens, Jan AU - Brandt-Jurgens J AD - Rheumatology Private Practice, Berlin, Germany. FAU - Miranda Limon, Juan Manuel AU - Miranda Limon JM AD - RM Pharma Specialists, Mexico City, Mexico. FAU - Cantalejo Moreira, Miguel AU - Cantalejo Moreira M AD - Unidad de Reumatologia, Hospital Universitario de Fuenlabrada, Fuenlabrada, Madrid, Spain. FAU - Cabello, Raul Veiga AU - Cabello RV AD - Hospital Central de la Defensa, Glorieta Ejercito, 1, 28047, Madrid, Spain. FAU - Jauch-Lembach, Julia AU - Jauch-Lembach J AD - Global Clinical Development, Biopharmaceuticals, Hexal AG (A Sandoz Company), Holzkirchen, Germany. FAU - Thakur, Anjali AU - Thakur A AD - Global Clinical Development, Biopharmaceuticals, Hexal AG (A Sandoz Company), Holzkirchen, Germany. FAU - Haliduola, Halimuniyazi AU - Haliduola H AD - Global Clinical Development, Biopharmaceuticals, Hexal AG (A Sandoz Company), Holzkirchen, Germany. FAU - Brueckmann, Ines AU - Brueckmann I AD - Global Medical Affairs, Biopharmaceutical, Hexal AG (A Sandoz Company), Holzkirchen, Germany. FAU - Gaylis, Norman B AU - Gaylis NB AD - Arthritis and Rheumatic Disease Specialties, Aventura, FL, USA. LA - eng SI - ClinicalTrials.gov/NCT02744755 PT - Clinical Trial, Phase III PT - Journal Article PT - Randomized Controlled Trial PL - New Zealand TA - BioDrugs JT - BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy JID - 9705305 RN - 0 (Antirheumatic Agents) RN - 0 (Biosimilar Pharmaceuticals) SB - IM MH - Activities of Daily Living MH - *Antirheumatic Agents/adverse effects MH - *Arthritis, Rheumatoid/drug therapy MH - *Biosimilar Pharmaceuticals/adverse effects MH - Double-Blind Method MH - Female MH - Humans MH - Treatment Outcome PMC - PMC7669771 COIS- Piotr Wiland: None declared. Slawomir Jeka: None declared. Eva Dokoupilova: Research grants from AbbVie, Eli Lilly, GSK, Novartis, Pfizer, UCB, Sanofi-Aventis and Hexal AG. Jan Brandt-Jurgens: None declared. Juan Manuel Miranda Limon: None declared. Miguel Cantalejo Moreira: None declared. Raul Veiga Cabello: None declared. Julia Jauch-Lembach: Employee of Sandoz. Anjali Thakur: Employee of Sandoz. Halimuniyazi Haliduola: Employee of Sandoz. Ines Brueckmann: Employee of Sandoz. Norman B. Gaylis: None declared. EDAT- 2020/10/30 06:00 MHDA- 2021/04/13 06:00 PMCR- 2020/10/29 CRDT- 2020/10/29 17:15 PHST- 2020/10/30 06:00 [pubmed] PHST- 2021/04/13 06:00 [medline] PHST- 2020/10/29 17:15 [entrez] PHST- 2020/10/29 00:00 [pmc-release] AID - 10.1007/s40259-020-00447-6 [pii] AID - 447 [pii] AID - 10.1007/s40259-020-00447-6 [doi] PST - ppublish SO - BioDrugs. 2020 Dec;34(6):809-823. doi: 10.1007/s40259-020-00447-6.