Background: To evaluate the efficacy of methotrexate in patients with systemic lupus erythematosus (SLE) without major organ involvement resistant to medium-high doses of prednisone.
Methods: Crossover, open clinical trial with two treatment periods, the first of 3 months and the second of 6 months, an intermediate control period of 3 months and another at the end of 6 months. A sample of 15 consecutive patients with SLE who, with no major organ damage, had active disease in spite of receiving more than 10 mg/day of prednisone or who relapsed on reduction of this doses during a period of at least 3 months. 7.5 mg/week of methotrexate were administered orally, divided into three doses of 2.5 mg/12 hours. Statistical significance was evaluated by Student's paired t test and chi 2; the strength of association by the Mantel-Haenzel odds ratio (OR) method and the precision, by Miettinen's confidence interval (CI). A p value of less than 0.05 was considered significant.
Results: Two patients failed to finish the study; one for worsening of cutaneous lesions of necrotizing vasculitis which she already had previously, and the other for an increase in her transaminase levels. In the remaining 13 there were 10 flares of disease activity during the control phases, 2 severe, versus 2 flares during the periods of methotrexate use (OR 7.69 (95% confidence interval, 1.67 to 33.33; p = 0.021). There were no significant changes in analytical results or prednisone requirements. During treatment six patients had oral aphthae and five had dyspepsia; three had an increase in transaminase levels, which in one caused the treatment to be stopped. There were two urinary infections, one community acquired pneumonia and one upper airway symptoms requiring antibiotic treatment; one female patient had acute cholecystitis with cholelithiasis necessitating surgical intervention.
Conclusions: Weekly low doses of methotrexate may prevent flares of activity of SLE in this type of patients, but it does not reduce the requirements of prednisone, nor modify analytical data. Toxic effects are rare and reversible upon interrupting medication.