Platelet-activating factor (PAF) may be a major mediator of
asthma and
bronchial hyperreactivity through its many proinflammatory actions. Specific antagonism of PAF might offer an alternative anti-inflammatory treatment to inhaled
corticosteroids. To test this, we have studied the effect of an orally active PAF antagonist,
WEB 2086, on the inhaled
steroid requirements of symptomatic atopic asthmatics in a double-blind randomized placebo-controlled parallel group study. The inhaled
corticosteroid dose required for symptomatic control of
asthma was established and further
steroid reduction was attempted
after treatment with
WEB 2086 40 mg three times daily for 12 wk. Of 106 patients recruited, 68 entered the treatment phase and 65 completed 6 wk of treatment. The mean daily
corticosteroid dose (SE) at study entry was 1,257 (75) micrograms which was reduced by 323 (66) micrograms during the run-in period without loss of symptomatic control. A further 416 (57) micrograms reduction in inhaled
corticosteroid dosage was possible during the treatment phase but this was almost identical in the
WEB 2086 and placebo-treated groups, amounting to 353 (92) and 481 (65) micrograms/day respectively (not significant [NS]). Rate of relapse following
corticosteroid reduction was a continuous variable and relapse occurred at different times depending on the variable used to define it. Time to relapse measured by an increase in symptoms correlated with disease duration (r = 0.41, p < 0.01) and with the dose of inhaled
corticosteroid at study entry (r = 0.36, p < 0.01) but no other measured variable predicted the time to relapse.(ABSTRACT TRUNCATED AT 250 WORDS)