Background Combination therapy with cyclosporin-A (CsA) and methotrexate (MTX) has shown to be advantageous in early RA. A major concern is still the possibility of synergistically increased toxicity.

Objectives To assess whether long-term combination therapy wit CsA and MTX results in more renal and hepatic toxicity than CsA alone.

Design A randomised double blind placebo controlled trial of 48 weeks duration.

Methods 120 patients with active RA: mean age 52 yrs, mean disease duration 3 months. Patients received CsA and MTX or CsA and placebo. MTX was started at 7.5 mg/week, and was increased to 15 mg/wk after 16 weeks. CsA was started at 2.5 mg/kg/day, and was increased to a maximum of 5 mg/kg/day. Additionally, all patients used folic acid 1 mg/d. Patients who did not have an ACR 20 response at week 24 were withdrawn.

Results The mean CsA dosage at 48 weeks was 2.8 mg/kg/day in the CsA and placebo group and 3.0 mg/kg/day in the CsA and MTX group. After 48 weeks of treatment mean creatinine rose significantly 19μmol/L (+25%) in the CsA and placebo group, and 21μmol/L (+28%) in the CsA and MTX group (p = 0.28 between groups). Changes in blood pressure and liver enzymes were not significant and clinically different between the two groups.

Table 1: premature discontinuations due to:

Conclusion Therapy with CsA and MTX in early RA does on average not result in more clinically relevant renal or hepatic toxicity than CsA alone, but a trend towards more discontinuations due to renal toxicity and hypertension was observed