The Effect of Biological and Cytotoxic Therapy for Rheumatoid Arthritis on Human Chromosomes

Objectives: An open-label prospective, combined basic and clinical controlled study was done to investigate the effects of biological therapy using rituximab, and cytotoxic drug treatment with methotrexate on morphology and quantifitiation of chromosomes in rheumatoid arthritis patients. Methods: This study is follow-up of a prior publication, with new observations in comparison with control subjects. A total of 16 subjects were divided into two groups. Group Ⅰ comprised 8 seropositive rheumatoid arthritis patients who were analysed for the primary end point of possible cytotoxic effects of rituximab and methotrexate. Group Ⅱ included 8 healthy individuals who served as controls. Assessment was done before treatment with rituximab, and 4 weeks after initiation of therapy. Patients were randomly assigned to receive infusion of rituximab in a full dose of 2.0 g divided into two doses of 1.0 g on days 1 and 15. The lymphocytes from periphereal blood was cultured by the Moorhead method. Results: Normal male and female Karyograms were observed after full courses of therapy with rituximab. In one female patient who had been receiving longstanding cytotoxic therapy with methotrexate, 2% of chromosomal mitosis showed structural abnormalities. Following the discontinuation of methotrexate and the administration of rituximab, her karyogram became normal. Conclusion: The results from this study indicated that rituximab therapy was safe for the number and structure of human chromosomes, while methotrexate showed chromosomal aberration in one female RA patient. After discontinuation of this longstanding treatment, the karyogram of the same patient returned to normal.