An open, randomized comparison study of cyclosporine A, cyclosporine A + methotrexate and cyclosporine A + hydroxychloroquine in the treatment of early severe rheumatoid arthritis.

PURPOSE: To determine whether a regimen of cyclosporine (CSA) and methotrexate (MTX), or CSA and hydroxychloroquine (HCQ) introduced in early rheumatoid arthritis (RA) can produce a significant improvement in clinical outcome and/or retard radiographic damage in comparison with standard monotherapy with CSA alone. METHODS: One hundred five patients with active RA of less than 36 months duration, who had never previously been treated with immunosuppressive agents, were included in a 12-month, multi-center, open, randomized trial. Patients who fulfilled the criteria for early severe RA were randomized to receive either combination therapy (CSA + MTX n = 34, CSA + HCQ n = 35) or CSA alone (n = 36). RESULTS: CSA + MTX was more effective than the other two treatment groups in controlling RA symptoms. CSA+MTX did not show a significant radiographic progression according to Larsen-Dale (0.90 +/- 3.89 compared to baseline values, P > 0.05); moreover, patients treated with CSA alone or CSA+HCQ showed a significant worsening of Larsen-Dale score (2.91 +/- 5.99 and 2.97 +/- 4.28 respectively vs baseline values, P < 0.05), although not significant when compared with the CSA + HCQ group (P = 0.56 and 0.39, respectively). CONCLUSIONS: This trial indicated that CSA+MTX was more effective than the other two treatments in improving clinical data and inhibiting radiographic progression, although the differences were not significant in this relatively small study. However, the difference was significant in favor of CSA + MTX regarding ACR 50% response.

Long-term safety and efficacy of low-dose cyclosporin A in severe psoriatic arthritis.

OBJECTIVE: The aim of this study was to evaluate the efficacy and tolerability of long-term treatment with cyclosporin A (CsA) in patients with psoriatic arthritis (PsA). METHODS: Sixty patients with PsA were enrolled in a prospective, nonrandomised study of CsA. Patients with hypertension or hypercreatinemia were excluded. Disease activity was evaluated according to clinical activity measures and the Psoriasis Area Severity Index (PASI). Assessments were made at baseline and after 3, 6, 12, 18, and 24 months. Measurements. The primary endpoints were 20% and 50% improvement in disease activity according to American College of Rheumatology (ACR) responses at 6, 12, 18, and 24 months. Other endpoints were 70% ACR responses at 6, 12, 18, and 24 months and other measures of disease activity at 3, 6, 12, 18, and 24 months. RESULTS: Forty-nine patients completed the 24-month of treatment with CsA. When all the clinical variables throughout the study were compared with baseline results, they all showed significant improvement after 6 months of treatment. Erythrocyte sedimentation rates (ESR) reached a significant improvement after 12 months of treatment (P<0.05). The PASI scores decreased from 15.1+/-4.3 to 5.2+/-2.7 after 24 months of treatment (P<0.001). Side effects included hypertrichosis (24% of patients), gum hyperplasia (12%), gastrointestinal intolerance (9%), hypertension (21%), neurological disturbance (7%), and nephrotoxicity (17%). Three patients withdrew due to treatment failure. One patient was lost to follow-up, and seven patients withdrew due to side effects. CONCLUSIONS: Cyclosporin A represents a helpful second-choice treatment for patients with active psoriatic arthritis. Administration of CsA necessitates expert and careful follow-up of patients.