comparison of complarate® (tocilizumab biosimilar) and actemra® in patients with rheumatoid arthritis

Conditions: Rheumatoid Arthritis

Summary: this is a randomized double-blind comparative parallel group study of the efficacy and safety of tocilizumab biosimilar complarate® and actemra® in the treatment of patients with rheumatoid arthritis with moderate to high disease activity. participants received an intravenous dose of tocilizumab 8 mg/kg once 4 weeks. the time on study treatment was 24 weeks.

complarate® (inn: tocilizumab) is being developed as a biosimilar to the drug actemra®, a concentrate for the preparation of a solution for infusion. tocilizumab is a recombinant humanized monoclonal antibody to the human interleukin-6 (il-6) receptor from the immunoglobulin g1 (igg1) subclass of immunoglobulins. tocilizumab binds to and inhibits both soluble and membrane il-6 receptors. this iii phase study is aimed to compare the effectiveness, safety and immunogenicity of complarate® and actemra®. the study included patients aged 18-75 years at the time of signing the informed consent form with a documented diagnosis of rheumatoid artritis, established according to the 2010 acr/eular classification criteria, at least 6 months before screening, with moderate or high degree of disease activity and insufficient response to methotrexate monotherapy (preservation of moderate/high disease activity for at least 3 months) and/or poor tolerability of methotrexate (including the subcutaneous form of the drug) and/or insufficient response to or intolerance to other synthetic disease-modifying anti-inflammatory drugs (sdmards) with or without methotrexate inclusive, who meet all criteria for participation in the study. the study included a screening period and a treatment period. allocation of patients to treatment groups was carried out by randomization in a ratio of 2:1 to the study drug (complarate®) and comparator drug (actemra®). 465 patients (310 to the study drug group and 155 to the comparator drug group) were randomized.

Eligibility criteria:
inclusion criteria: * availability of written informed consent obtained from the patient before the start of any procedures related to the study. * men and women 18-75 years of age, inclusive, at the time of signing the informed consent form. * patients with a documented diagnosis of rheumatoid artritis (ra), established according to the 2010 acr/eular classification criteria at least 6 months before screening, with moderate to high disease activity and an insufficient response to methotrexate monotherapy (maintaining moderate/high disease activity for at least 3 months) and/or poor tolerability of methotrexate (including the subcutaneous form of the drug) and/or insufficient response to or intolerance to other synthetic disease-modifying anti-inflammatory drugs (sdmards) in combination with methotrexate or without methotrexate. * the number of swollen and/or painful joints is 6 or more. * no changes in the dosage regimen of standard ra therapy with oral glucocorticosteroids and nsaids for ≥ 4 weeks before screening. * no changes in the dosing regimen of standard ra sdmard therapy for ≥ 4 weeks before screening. * agreement to adhere to adequate methods of contraception throughout the study and for 3 months after the end of tocilizumab therapy. exclusion criteria: * a history of rheumatic autoimmune disease other than rheumatoid arthritis. * functional class iv according to the acr functional status classification or wheelchair/bedridden. * development of pronounced extra-articular (systemic) manifestations of the disease and complications (rheumatoid vasculitis, amyloidosis, felty's syndrome, neuropathy, damage to the organ of vision). * use of oral corticosteroids in doses greater than \>10 mg daily prednisolone equivalent, or change in oral corticosteroid dose within 4 weeks before or during screening. * use of injectable corticosteroids (including intra-articular corticosteroids) or intra-articular hyaluronic acid injections within 4 weeks before or during screening. * therapy with tumor necrosis factor-alfa (tnf-alpha) inhibitors or any other genetically engineered biological drugs within 1 month before screening. * history of tocilizumab therapy. * major surgery (including joint surgery) within 8 weeks before the start of the study or elective surgery within 6 months after the start of the study. * a history of an adverse drug reaction to any of the components of the study drug or a reference drug. * immunization with any live or live attenuated vaccine within 1 month before the first dose of the study or comparator drug. * a history of a disease associated with the accumulation of immune complexes (including serum sickness). * concomitant diseases and conditions that, in the opinion of the investigator and/or sponsor, jeopardize the safety of the patient during participation in the study, or which will influence the analysis of safety data. * active systemic infection (bacterial, viral or fungal) within 14 days before signing the informed consent form or at the time of screening. * blood donation or blood loss (450 ml of blood or more) less than 2 months before the start of the study. * pregnancy or breastfeeding. * history of demyelinating disease of the central nervous system. * history of diverticulosis/intestinal diverticulitis or chronic ulcerative diseases of the lower gastrointestinal tract, such as crohn's disease, ulcerative colitis. * history of tuberculosis. * positive/doubtful test with tuberculosis allergen. * participation in clinical trials of drugs less than 3 months before signing the informed consent form. * positive tests for hepatitis b or c, hiv or syphilis. * unwillingness or inability to comply with the recommendations prescribed by this protocol. * identification during screening of other diseases/conditions not listed above that, in the opinion of the physician-researcher, prevent the inclusion of the patient in the study.

Keywords: tocilizumab humanized monoclonal antibodies safety rheumatoid arthritis equivalence biosimilar american college of rheumatology (acr) das28 disease-modifying anti-rheumatic drugs (dmards) rheumatic autoimmune disease european league against rheumatism (eular) immunogenicity clinical disease activity index (cdai) simplified disease activity index (sdai)