A Risk-Benefit Assessment of Methotrexate in Corticosteroid-Dependent Asthma

Abstract

Methotrexate is a folic acid antagonist with proven anti-inflammatory properties. This originally led to its use in the therapy of some rheumatic and dermatological inflammatory disorders and, since the early 1980s, as a corticosteroid-sparing agent in the therapy of bronchial asthma. Although the exact anti-inflammatory mechanism is not known, it appears that in some patients with severe corticosteroid-dependent bronchial asthma, a reduction of at least 50% in the maintenance corticosteroid dosage can be achieved. Controversies regarding methotrexate efficacy may be a result of the small size and heterogeneity of the patient populations studied and the variable definition of corticosteroid "dependence'. Although the potential for serious short and long term adverse effects resulting from methotrexate therapy cannot be ignored, overall, methotrexate appears to be well tolerated at low dosages. Hepatic and pulmonary toxicity are the main adverse effects of concern. The "lesser evil' approach is logical, but it is imperative to administer the drug for at least 3 months to adequately assess its efficacy in a specific patient.

Asthma that is unresponsive to usual care

“…Methotrexate, gold and cyclosporin A have corticosteroid-sparing effects clinically that must be weighed against a serious adverse effect profile. [46][47][48][49][50][51][52][53][54] For example, low-dose oral methotrexate therapy, widely used in the treatment of rheumatologic diseases, has been reported to reduce the need for systemic corticosteroids in severe asthma, but study results have been inconsistent. 46−50 A few patients have been reported to benefit from oral gold therapy, 53,54 and intravenous immunoglobulin has been reported to be of benefit, but only in uncontrolled studies.…”

Alternativen zur Standardtherapie des Asthma bronchiale

“…Jg., Nr. 51/52 auch erst nach einer dreimonatigen Behandlungszeit evident wird, ein Übermaß an Nebenwirkungen gegenüber(33).Die in den publizierten Studien verabreichten wöchentlichen Dosen reichen von 5-25 mg bzw. 30-50 mg, gegeben jeweils als Einzeldosis über einen mittleren Zeitraum von 14 Monaten (33).…”