Efficacy of Combination Therapy with rhTNFR:Fc and Methotrexate in the Patients with Disease-modifying Antirheumatic Drug -resistant Rheumatoid Arthritis

Abstract

Rheumatoid arthritis (rheumatoid arthritis, RA) is a chronic progressive systemic inflammatory disease, prevalence rate of Chinese is 0.32 percent to 0.36 percent, to 1% of the Western countries [1]. Tumor necrosis factor-α (TNF-α) is an important physiological inflammatory mediators in the host-mediated inflammatory response, resulting in tissue damage plays an important role. RA patients with synovial immunohistochemistry analysis showed the existence of TNF-α in synovial lining cells, especially at the junction of cartilage and pannus [2]. RA patients after treatment, serum levels of TNF-α significantly decreased according to the same period improved arthritis index.Recombinant human tumor necrosis factor-α receptor II IgG FC fusion protein(rhTNFR: Fc) is a fusion protein producd using recombinant DNA technology,which can specific block the interactions between TNF-α and its receptor on the cell surface. Many clinical trials of rhT-NFR: Fc abroad have confirmed the clinical efficacy in early RA, active RA patients and in patients with disease-modifying antirheumatic drug (DMARD)-resistant rheumatoid arthritis [3-6].This study is to observe the efficacy of combining rhTNFR:Fc and MTX in patients with DMARD-resistant rheumatoid arthritis. Information and Methods Select case 64 cases of patients were inpatients or outpatients selected from the department of rheumatology, Shengjing Hospital, China Medical University. Selection criteria: (1)in line with the American Institute of Rheumatology in 1987 RA classification criteria; (2)the disease is active before medication (the judging index for activity is: a. joint swelling number≥ 6; b.number of joint tenderness ≥ 6; c. The duration of morning stiffness ≥ 45min; d. erythrocyte sedimentation rate (ESR) ≥ 28mm/lh and / or C-reactive protein (CRP) ≥ 20μg/ml); (3) have undergone, including methotrexate (MTX), at least two anti-rheumatic drug (DMARD) treatment ,but the effect was not obvious. Elimination criteria: (1) with severe heart, liver, kidney and blood, and other important organs disease, endocrine system disease and the history of those diseases; (2) pregnant women, breast-feeding women; (3) previously received biological agents (infliximab, etanercept, adalimumab) treatment; (4)being infected and / or with the high opportunity to be infected; (5) cancer patients or in the family of the susceptible population to tumor; (6)have undergone glucocorticoid in the last month. Of the 64 patients, 56 cases are female, 8 cases are men; age 32 to 73 years old, the average age is 54.2 years old; course :24 to 96 months, average course:57.5 months. According to the patients gender, age, duration and extent of disease activity, were randomly divided into two groups comparable. Before test, patients were accounted for with common adverse drug reactions and possible adverse events, and obtained written informed consent, then identified as subjects.