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


CONCLUSIONS
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.
Karanikolas
George
G
From the 1st Propedeutic Clinic, Athens University School of Medicine, Laiko Hospital, Athens, Greece. gkaranikgr@yahoo.gr
Charalambopoulos
Dionisios
D
Andrianakos
Alexandros
A
Antoniades
Christos
C
Katsilambros
Nikolaos
N
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000368:Aged; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000503:physiopathology; D016572:Cyclosporine / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007555:Isoxazoles / Q000627:therapeutic use*; D007596:Joints / Q000187:drug effects / Q000503:physiopathology; D000077339:Leflunomide; D012720:Severity of Illness Index; D016896:Treatment Outcome
D000276:Adjuvants, Immunologic; D018501:Antirheumatic Agents; D007555:Isoxazoles; D016572:Cyclosporine; D000077339:Leflunomide