An open study of Auranofin in the treatment of steroid-dependent asthma

Abstract

To determine the efficacy of oral gold in asthma, 20 patients with steroid-dependent asthma received auranofin at a dose of 3 mg by mouth, twice daily, in a 24-week open clinical trial. Prospective evaluation of bronchial responsiveness to methacholine was determined before and 8 and 16 weeks after initiation of auranofin therapy. Serial spirometry (FEV 1 and FVC), lung volumes, and diffusing capacities (single breath carbon monoxide diffusing capacity of the lungs) were measured before and at 10 and 20 weeks after treatment. All subjects were required to record concomitant medications, symptom scores, and morning and evening peak expiratory flow rates. In vitro immunologic studies performed before and after 8 and 20 weeks of auranofin therapy included leukocyte histamine release in response to antihuman IgE, lymphocyte blast transformation in response to concanavalin A and phytohemagglutinin, and leukocyte inhibitory factor activity in response to Candida albicans and tetanus toxoid antigens. In 18 patients evaluated, there were no significant differences between baseline and posttreatment spirometry, single breath carbon monoxide diffusing capacity of the lungs, and lung volumes. At week 16 of treatment, the steroid cumulative dose or the total prednisone dose administered from 7 days before through 10 days after each methacholine test day decreased from a mean of 293 ± 125 mg at baseline to 192 ± 115 mg. At week 16, nine of 18 patients (50%) exhibited decreased methacholine responsiveness as defined by a more than one-half log 10 increase in the concentration of methacholine causing a 20% decrease in FEV 1. A significant correlation (r = 0.60) was observed between the increase in the concentration of methacholine causing a 20% decrease in FEV 1 and the decrease in steroid cumulative dose after 16 weeks of treatment. Leukocyte histamine release to anti-IgE exhibited significant reductions from baseline at week 20 to 10 −2 ( p < 0.002) and at 10 −3 ( p < 0.005) dilutions. At week 20, leukocyte inhibitory factor activity in response to Candida increased from baseline at the 0.1 mg per well ( p = 0.025) and 1 mg per well ( p = 0.05) concentrations; similarly, the responses to tetanus toxoid increased at the 1 mg per well ( p < 0.05) and 0.1 mg per well ( p < 0.01) concentrations. This study suggests that auranofin treatment may have potential benefit in the treatment of steroid-dependent asthma by decreasing airway hyperresponsiveness and daily steroid requirements. It exerts immunomodulatory activity on an IgE-dependent system without compromising the competence of cell-mediated immunity. Based on suggestive clinical findings, an acceptable risk: benefit ratio, and the unique laboratory effects noted in this preliminary study, controlled clinical trials of auranofin in steroid-dependent patients with asthma are warranted.