The efficiency and safety of tocilizumab in rheumatoid arthritis(intermediate results of a Russian multicenter study)

A search for new medicines for the treatment of rheumatoid arthritis (RA) has led to the design of the so-called genetic engineering biologicals (GEBs) whose mechanism of action lies in the depletion and impaired interaction of the cells involved in the development of i
НАУЧНО-ПРАКТИЧЕСКАЯ РЕВМАТОЛОГИЯ, 2010, № 2, 21-29
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ОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯ
nflammation or in the inhibition of proinflammatory cytokine activities. In recent years, investigators' attention has been brought to interleukin (IL) 6 (pleiotropic cytokine) that is synthesized by many cells implicated in the development of inflammation and shows a broad range of proinflammatory biological effects. Tocilizumab (TCZ) is the first and only agent that is able to suppress IL-6-dependent inflammatory reactions and that is permitted for use in RA.
The first Russian open-label, Phase IV, multicenter 24-week study of the efficacy and safety of TCZ in patients with rheumatoid arthritis (RA) is now under way. All the patients received an intravenous TCZ infusion in a dose of 8 mg/kg during continuous therapy with basic anti-inflammatory and nonsteroidal anti-inflammatory drugs (DMARDs and NSAIDs), and glucocorticoids. The patients receiving methotrexate (MT) took folic acid in a dose of at least 5 mg weekly. The study excluded patients with a history of DMARD use. To evaluate the efficiency of TCZ therapy, the authors used the EULAR criteria and analyzed individual clinical indicators of RA activity, including the intensity of pain, the duration of morning stiffness, the number of tender and swollen joints (TJC and SJC), indices of functional activity and quality of life (HAQ and EQ-5D), and laboratory parameters required to evaluate the efficiency and safety of TCZ therapy.
Clinical and laboratory studies were conducted just before and 4 weeks after the first infusion of TCZ.
Overall, the first administration of the drug caused a very rapid positive effect against all clinical indicators of disease activity (including pain magnitude, morning stiffness duration, TJC, SJC) and normalization of the indices characterizing the functional activity and quality of life of patients. The efficiency TCZ therapy was confirmed, by assessing the time course of changes in DAS 28 index values: before therapy, all the patients were observed to have a high activity of RA (DAS 28 >5,1). According to the changes in DAS 28 index values, a good/moderate effect was noted in 62% of the patients, 3 (7%) achieved remission (DAS 28 <2,6). The difference in HAQ scores was 0,5 (a reduction from 1,89 to 1,39 scores) and EQ-5D quality of life scores improved by virtually twice (from 0,28 to 0,49). There were two adverse reactions (decreased hemoglobin and respiratory infection) during the therapy. There was a moderate increase in ALT concentrations and a trend towards a decrease in the percentage of neutrophils (with their normal absolute count), which is occasionally seen during TCZ therapy.
Thus, preliminary analysis of the data of the Russian study strongly suggests that TCZ is effective in severe RA resistant to therapy with DMARDs, primarily MT. TCZ therapy makes it possible to achieve a very rapid reduction in the clinical and laboratory activity of the disease and to substantially enhance the functional activity and quality of life of patients.

tocilizumab, rheumatoid arthritis, functional activity, quality of life

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