Methotrexate as an oral corticosteroid-sparing agent in severe asthma: the emergence of a responder asthma endotype

Abstract

BACKGROUND Sustained use of oral corticosteroids is associated with significant side effects. It is therefore of interest to find a corticosteroid-sparing agent. In two meta-analyses, methotrexate resulted in a rather small reduction in the oral corticosteroid maintenance dose. We have used methotrexate as an oral corticosteroid-sparing agent in consecutive patients with severe bronchial asthma and find a need for a real-life observational study to evaluate the effect of methotrexate in clinical practice. METHODS We analyzed the clinical data of 13 oral corticosteroid-dependent asthma patients with a mean prednisolone dose of 15 mg/day for up to 8 years. The diagnosis of asthma based on the clinical history, positive bronchodilator reversibility test, and variable airflow obstruction was secured by bronchial biopsies in all patients. We reviewed the literature and found 12 studies evaluating methotrexate as an oral corticosteroid-sparing agent in severe asthma and calculated the mean daily reduction in mg of prednisolone. RESULTS Oral corticosteroids could be reduced in 8/13 patients, 61.5% (mean reduction 9.0 mg/day), and stopped in six of these patients. Five patients had no reduction and remained oral corticosteroid-dependent. Patients with the highest oral corticosteroid doses experienced the greatest reductions. Two patients stopped methotrexate due to side effects. FEV1 remained unaffected by methotrexate treatment and corticosteroid reduction. CONCLUSIONS Methotrexate has significant oral corticosteroid-sparing effect while maintaining an unaltered asthma control and spirometry. Methotrexate seems an effective oral corticosteroid-sparing agent in a significant proportion of patients with severe asthma. The specific asthma phenotype/endotype that responds needs further study.