Immunological effects of adalimumab in rheumatoid arthritis: Results of a Russian national study

Abstract

A reduction in immunological parameters during therapy for rheumatoid arthritis (RA) can yield new data on the mechanisms of anti-inflammatory action and be of great practical importance since this allows judgment of the depth of impact on the immunological process and therefore may be regarded as one of the components of improvement and remission. Objective: to study the effect of the tumor necrosis factor-a (TNF-а) inhibitor adalimumab (ADA) on a number of key immunological parameters in RA. Subjects and methods. The study included 100 patients (11 men and 89 women) diagnosed with RA from 5 research centers. The patients were observed to have high RA activity: at baseline, DAS28 6.22+0.84 scores; C-reactive protein (CRP) 37.1+34.7 mg/l. The mean number of disease-modifying antirheumatic drugs (DMARDs) used by a patient in the history was 2.1. During 24-week treatment, the patients took ADA in a subcutaneous dose of 40 mg every 2 weeks both alone and in combination with DMARDs. The time course of changes in the serum levels of CRP, IGM rheumatoid factor (RF) and in the concentration of anti-cyclic citrullinated peptide 2 (anti-CCP2) antibodies was determined by enzyme immunoassay (EIA) using the Axis-Shield Diagnostics commercial kits (United Kingdom). The levels of TNF-a, interleukin (IL) 6, 12, matrix metalloproteinase 3 (MMP3) were measured in pg/ml by EIA using the Bender MedSystems commercial kits (USA) according to the manufacturer's directions. Results. During ADA therapy, there was a rapid reduction in the level of CRP from 34.3 to 11.317.2 mg/l following 2 weeks (p<0.001), which thereafter remained low (11.9 mg/l), with some fluctuations, until week 24 of the study. There was a significant reduction in blood RF levels from 169.24 to 111.97 at 24 weeks (p<0.001). After 12 weeks of ADA treatment, there was virtually a two-fold decrease in IL-6 content from 8.87 to 4.87 pg/ml and later on to 4.03 pg/ml at week 24 (p>0,05). The mean levels of anti-CCP2 antibodies, IL-12, VEGF, and MMP3 remained unchanged. Conclusion. The time course of changes in immunological parameters during ADA treatment demonstrates the rapid and deep effect of TNF-a inhibitors on the different components of the pathogenesis of RA.

Keywords

• rheumatoid arthritis
• immunological parameters
• adalimumab
• russian national study