Methotrexate as an adjunct in the treatment of persistent mild cardiac allograft rejection

Because methotrexate arrests inflammation in autoimmune disease, we studied its efficacy in persistent low-grade cardiac allograft rejection. Seventeen patients aged 39.5 +/- 0.9 years (mean +/- SE) had persistent rejection despite previous therapy with high dose corticosteroids. Maintenance immunosuppression consisted of prednisone, azathioprine, and cyclosporine. The rejection episode treated with methotrexate occurred 180 +/- 55.4 days posttransplantation. Patients had incurred 2.7 +/- 0.3 previous episodes of rejection with the first episode occurring 30.6 +/- 6.2 days post transplant. Methotrexate was administered orally in 3 doses to an average weekly dose of 12.8 +/- 0.8 mg. The duration of methotrexate therapy was 9.0 +/- 1.1 weeks. Sixteen of the seventeen persistent rejection episodes resolved by 22.8 +/- 3.2 days of methotrexate therapy. Using methotrexate, the prednisone dose was decreased from 22.4 +/- 4.8 mg/day at initiation of methotrexate to 9.7 +/- 1.4 mg/day at the completion of methotrexate therapy (P less than 0.01). Over a 306 +/- 35-day follow-up, 9 of 17 patients (53%) have remained rejection-free. Leukopenia, necessitating reduction in azathioprine occurred in 10 patients. One patient developed herpes zoster during therapy. These data indicate that methotrexate is effective in resolving persistent cardiac allograft rejection with minimal morbidity. In addition, the use of methotrexate for treatment of rejection allows reduction in maintenance corticosteroid doses.