The effect of the orally active platelet-activating factor antagonist WEB 2086 in the treatment of asthma.
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)
Spence
D P
DP
Fazakerley Hospital, Liverpool, United Kingdom.
Johnston
S L
SL
Calverley
P M
PM
Dhillon
P
P
Higgins
C
C
Ramhamadany
E
E
Turner
S
S
Winning
A
A
Winter
J
J
Holgate
S T
ST
D000280:Administration, Inhalation; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D000420:Albuterol / Q000008:administration & dosage; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D001381:Azepines / Q000008:administration & dosage*; D001507:Beclomethasone / Q000008:administration & dosage; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010366:Peak Expiratory Flow Rate / Q000187:drug effects; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D014230:Triazoles / Q000008:administration & dosage*
D001381:Azepines; D010972:Platelet Activating Factor; D014230:Triazoles; C052518:WEB 2086; D001507:Beclomethasone; D000420:Albuterol