Persistent Clinical Response of Infliximab Therapy in Patients with Refractory Rheumatoid Arthritis, over a 3-Year Period

Paraskevi   V.   Voulgari; Yannis      Alamanos; Alexandros   A.   Drosos

doi:10.2174/157488406775268264

Abstract

Infliximab, a chimeric monoclonal anti-tumor necrosis factor alpha antibody is approved for the treatment of patients with rheumatoid arthritis (RA) who had an inadequate response to methotrexate (MTX) therapy. This report provides analyses by using infliximab in combination with various disease modifying anti-rheumatic drugs, infliximab "survival" over a period of three years, and its effectiveness on synovial tissue damage using magnetic resonance (MR) imaging. The study was started in 1999 as an open label study using infliximab in combination with cyclosporin A (CsA) in refractory RA patients who were unable to tolerate MTX. A total of 18 RA patients were investigated. After a year of treatment, 80% of patients achieved the 20% American College of Rheumatology Response criteria. Two patients dropped out; one because of an immediate hypersensitivity reaction and the other because of the development of pulmonary tuberculosis. In a subsequent study we investigated infliximab "survival" over a period of 3 years. A total of 84 RA patients were included in the study. After 3 years of therapy, 59% of patients still continued receiving infliximab. The factor that was associated with infliximab "survival" was the concomitant use of MTX. A total of 28 (33%) patients discontinued this study. More specifically, 16 (19%) presented adverse drug reactions, 9 (11%) had drug failure, and 3 (3%) were lost from follow-up. Finally, to evaluate by MR imaging the inflammatory tissue changes in refractory RA patients treated with infliximab, 16 patients were examined with MR imaging of the dominant affected wrist and hand before and one year after therapy. The volume of the enhancing inflammatory tissue (VEIT) was evaluated. A significant decrease of VEIT was observed in 88% of patients after therapy. We conclude that in refractory RA patients infliximab was proved to be efficacious and well tolerated in combination with CsA. The clinical response of infliximab was persistent over a 3-year period and was associated with the concomitant use of MTX. This clinical improvement was also associated with the reduction of inflammatory disease tissue damage.

Keywords: Rheumatoid arthritis, Infliximab, Long-term, Methotrexate, Cyclosporine A, Magnetic resonance imaging

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