Combination of cyclosporine and leflunomide versus single therapy in severe rheumatoid arthritis

• Published in: Journal of rheumatology 2006-03, Vol.33 (3), p.486-489
• Main Authors: KARANIKOLAS, George, CHARALAMBOPOULOS, Dionisios, ANDRIANAKOS, Alexandros, ANTONIADES, Christos, KATSILAMBROS, Nikolaos
• Format: Article
• Language: English
• Subjects: Adjuvants, Immunologic - therapeutic use; Aged; Antirheumatic Agents - therapeutic use; Arthritis, Rheumatoid - drug therapy; Arthritis, Rheumatoid - physiopathology; Biological and medical sciences; Bones, joints and connective tissue. Antiinflammatory agents; Cyclosporine - therapeutic use; Diseases of the osteoarticular system; Drug Therapy, Combination; Female; Humans; Inflammatory joint diseases; Isoxazoles - therapeutic use; Joints - drug effects; Joints - physiopathology; Medical sciences; Pharmacology. Drug treatments; Severity of Illness Index; Treatment Outcome
• ISSN: 0315-162X; 1499-2752

OBJECTIVE: This study assessed the efficacy and safety of combination (COMB) of cyclosporine (CSA) and leflunomide (LEF) versus each drug alone, in the treatment of severe rheumatoid arthritis (RA). METHODS: One hundred six patients with active RA refractory to at least one disease modifying antirheumatic drug (methotrexate obligatorily) were entered into a 12-month open, prospective trial and were randomly allocated to receive either CSA 2.5 to 5 mg/kg/day, or LEF 20 mg/day, or the combination of both at the same initiating dose. RESULTS: The American College of Rheumatology 50% (ACR50) response rates for the 3 groups were COMB 80%, CSA 40%, and LEF 42% (p = 0.001). Combination therapy was also significantly better than CSA and LEF at the more stringent 70% response rate (69% vs 34% vs 30%, respectively; p = 0.001). Comparable Disease Activity Score 28 reduction rates were noted at trial termination for all 3 treatment arms: COMB -2.74 vs CSA -2.53 vs LEF -2.28 (p nonsignificant). Discontinuation rates were more common in LEF vs CSA arm (p = 0.046). No unexpected or serious adverse drug effects were identified in the combination group during the 12-month period. CONCLUSION: The combination of CSA and LEF in patients with refractory RA provided statistically significant benefit in ACR50 and ACR70. Adverse events were not substantially increased.