Single, high-dose intramuscular triamcinolone acetonide versus weekly oral methotrexate in life-threatening asthma: A double-blind study

Effective and less toxic treatments are needed for patients with severe, steroid-dependent asthma. Both low-dose oral methotrexate and high-dose intramuscular triamcinolone have been recommended for these patients. We compared the effects of these two medications on pulmonary function, peak flow rates, airway reactivity, oral steroid use, emergency room (ER) visits, and hospitalizations in patients with steroid-dependent, life-threatening asthma. In a randomized, placebo-controlled, double-blind study, we investigated 19 such patients. Six of the patients (Group I) received a single dose of 360 mg triamcinolone intramuscularly with placebo methotrexate; seven patients (Group II) received placebo triamcinolone followed by low-dose oral methotrexate (a first dose of 7.5 mg followed by 15 mg weekly); and six patients (Group III) received placebo triamcinolone with placebo methotrexate. All patients used the same high-dose inhaled steroids. The patients took tapering courses of oral steroids when needed, but attempted to reduce their oral steroid use whenever possible. Methacholine challenge testing was performed every 6 wk, pulmonary function tests every 4 wk, and home peak-flow measurements twice daily. Oral steroid use, ER visits, and hospitalizations were also monitored. The patients in the triamcinolone treatment group showed a significant and sustained increase in home peak- flow rates, and their FEV₁ persistently improved by a mean of 40% (p < 0.05), whereas the FEV₁ of the patients in the methotrexate treatment and placebo groups remained near baseline. The PC₂₀ in the triamcinolone group increased progressively (p > 0.05), and the improvements in total mean reactivity were greater in this group than in either of the other two groups (p < 0.05). The triamcinolone-treated patients had a total of one ER visit and one hospitalization, the placebo patients nine ER visits and three hospitalizations with one intubation, and the methotrexate-treated patients 12 ER visits and five hospitalizations. Triamcinolone produced more steroid side effects than did placebo, but these resolved over a period of 2 to 3 mo while the clinical improvement continued. There were transient elevations in serum transaminases in the methotrexate-treated patients. We conclude that in patients with severe asthma, single injections of high-dose triamcinolone significantly improve FEV₁, peak-flow rates, and airway hyperresponsiveness in a sustained pattern over a period of 6 mo, and reduce ER visits and hospitalizations when compared with the effects of low-dose methotrexate.