Effects of interleukin 1 receptor antagonist alone and in combination withmethotrexate in adjuvant arthritic rats

Objective. To determine the benefit of combination treatment with the inter leukin 1 receptor antagonist (IL-1ra) and methotrexate (MTX) in adjuvant ar thritic rats. Methods. Rats with adjuvant arthritis were treated by continuous sc infusio n with IL-1ra (5 mg/kg/h), Effects of IL-1ra treatment alone were compared to treatment with daily oral MTX (0.048, 0.06, or 0.075 mg/kg) or MTX in co mbination with IL-1ra. Efficacy was monitored by sequential caliper measure ment of ankle joints, final paw weights, and histologic evaluation with par ticular emphasis on bone lesions, Results, Treatment with IL-1ra alone resulted in 6% inhibition of paw swell ing assessed by final paw weight. Treatment with MTX (0.075 mg/kg PO) gave 47% inhibition and the combination resulted in an 84% decrease in swelling. Histologic evaluation of ankle joints revealed 53% inhibition of bone reso rption with IL-1ra alone, 58% inhibition with MTX alone, and 97% inhibition in combination treated rats. Lower doses of MTX in combination with IL-1ra also provided additive benefit on arthritis variables. Conclusion. Combination therapy with IL-1ra and MTX results in additive or synergistic benefit, with excellent inhibition of all arthritis variables. These data support clinical investigation of the use of combination therapy of IL-1ra and MTX in patients with rheumatoid arthritis.