To evaluate the long-term tolerance of methotrexate (MTX) administered in a cohort of steroid-dependent asthmatic patients.
Type of study: prospective, observational. Population: patients treated from 1992 to 2004 in our asthma clinic for steroid-dependent asthma (requirement of at least 7.5 mg per day of prednisolone for ≥ than one year). Treatment: 10 mg per week of oral MTX + one weekly dose of folic acid the day after MTX intake. Instrumentation: blood analysis were performed at every three months including leukocyte differential count, CD4 and CD8 level, renal and hepatic function, immunoglobulin level (including IgG subclasses); sputum culture when infection and at the end of the follow-up; hepatic ultrasonography when an accumulated dose of 1,500 mg was reached or whenever hepatic function was altered.
45 patients have been followed for a mean period of 91.3±39.5 months (range 12-144). The mean accumulated dose of MTX was: 3,499±2,207 mg (range: 470- 7,125). Hematology at entry: Leukocyte: 9,046±2,470/mm3; CD4: 49.3±7.1%; CD8: 25.0±8%; Hct: 40.6±5.2%; Platelet count: 258,543±73,761/mm3; Mean Corpuscular Volume: 89.1±3.9fL; GOT: 19±7 U/L; IgA: 214±113; IgM: 128±90; IgE: 156±331; IgG: 882±344; IgG1: 554±274; IgG2: 279±133; IgG3: 69±58; IgG4: 24±26 (mg/dL). No statistically significant changes were found during the follow-up. Side-effects: 4 patients showed mild elevation of hepatic enzymes that normalized after drug suppression (MTX could be reintroduced and ultrasonography was normal), one alopecia and one asthma. None sputum culture evidenced infection of Aspergillus, Nocardia or Pneumocystis.
1) The concomitant administration of folic acid avoids macrocytic anemia. 2) Liver function should be monitored although seems to be infrequently affected. 3) After liver function recoveries, MTX can be reintroduced safely. 4) Immunity is not affected.
1) Long-term administration of a low-weekly dose of MTX is safe. 2) The accumulated dose of 1,500 mg is not a therapeutic limitation.
Christian Domingo, None.