Effect of suplatast tosilate, a Th2 cytokine inhibitor, on steroid-dependent asthma: a double-blind randomised study. Tokyo Joshi-Idai Asthma Research Group

Lancet. 2000 Jul 22;356(9226):273-8. doi: 10.1016/s0140-6736(00)02501-0.

Abstract

Background: Th2 cytokines play an important part in the pathogenesis of asthma. Our aim was to study the effect of suplatast tosilate, a selective Th2 cytokine inhibitor, on asthma control and asthma exacerbations during reduction of inhaled corticosteroid dose in patients with steroid-dependent asthma.

Methods: 85 patients with moderate to severe asthma taking high doses (> or = 1500 microg per day) of inhaled beclometasone dipropionate, were assigned suplatast tosilate (100 mg three times daily) or placebo for 8 weeks in a double-blind, randomised, parallel-group, multicentre trial. During the first 4 weeks, other medications remained unchanged (add-on phase); during the next 4 weeks, the doses of beclometasone were halved (steroid-reduction phase). Main outcome measures were pulmonary function, asthma symptoms, and use of beta2-agonists.

Findings: Data were available from 77 patients. During the add-on phase, suplatast tosilate treatment, compared with placebo, was associated with higher forced expiratory volume in 1 s (mean difference between groups for changes from baseline at week 4, 0.20 L [95% CI 0.16-0.24], p=0.043), morning peak expiratory flow (18.6 L/min [14.1-23.1], p=0.037), and less diurnal variation in peak expiratory flow rate, asthma symptom scores (7.1 [6.6-7.6], p=0.029), and serum concentrations of eosinophil cationic protein and IgE. In the steroid-reduction phase, pulmonary function, asthma symptoms, and use of beta2-agonist deteriorated significantly more in the placebo group than in the suplatast group.

Interpretation: Treatment with a Th2 cytokine inhibitor in steroid-dependent asthma improves pulmonary function and symptom control, and allows a decrease in dose of inhaled corticosteroid without significant side-effects. Some improvements in pharmacokinetics are, however, needed.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Administration, Oral
  • Anti-Allergic Agents / administration & dosage
  • Anti-Allergic Agents / therapeutic use*
  • Anti-Asthmatic Agents / administration & dosage
  • Anti-Asthmatic Agents / therapeutic use
  • Arylsulfonates / administration & dosage
  • Arylsulfonates / therapeutic use*
  • Asthma / drug therapy*
  • Beclomethasone / administration & dosage
  • Beclomethasone / therapeutic use
  • Circadian Rhythm
  • Cytokines / antagonists & inhibitors*
  • Double-Blind Method
  • Female
  • Forced Expiratory Volume
  • Humans
  • Male
  • Middle Aged
  • Peak Expiratory Flow Rate
  • Sulfonium Compounds / administration & dosage
  • Sulfonium Compounds / therapeutic use*
  • Th2 Cells

Substances

  • Anti-Allergic Agents
  • Anti-Asthmatic Agents
  • Arylsulfonates
  • Cytokines
  • Sulfonium Compounds
  • suplatast tosilate
  • Beclomethasone