Does ketotifen have a steroid-sparing effect in childhood asthma?

Abstract

In view of the possible systemic side-effects of inhaled corticosteroids (ICS), a study was performed to determine whether ketotifen (versus placebo) can replace or allow a reduction in the dose of ICS required for the maintenance treatment of childhood asthma.Sixty six children (aged 6-13 yrs) with asthma (confirmed by methacholine challenge), who were maintained on ICS, at a dose of ≤1 mg·day -1 , were selected, and 52 subjects completed the trial. Children on long-term oral steroids or cromoglycate were excluded. After a 4 week baseline period, the children were randomized to receive ketotifen, 2 mg·day -1 , or placebo for 32 Weeks. Between weeks 13-20 of the study, the daily dose of steroid was tapered by 25% every second week to the minimum dose tolerated by the patients. For the remainder of the study (Weeks 21-32) the patients continued on this dose (if tolerated). Beta 2 -agonists were allowed, as necessary, for symptom relief During the baseline period, the mean daily ICS dosage was 432 µg in the ketotifen group versus 408 µg in the placebo group (NS). Among the patients who completed the study, the average ICS dosage during the final phase of the study (Weeks 21-32) was only 18% of baseline in the ketotifen group versus 35% in the placebo group (NS). Lung function, diurnal variability in peak flow rates and methacholine sensitivity (provocative concentration producing a 20% fall in forced expiratory volume in one second (PC20)) remained unchanged in both groups throughout the study. During the last 12 weeks of the study, the ketotifen-treated patients were symptomatically better controlled.In the present study, ketotifen did not have a greater steroid-sparing effect than placebo.

Third International Pediatric Consensus statement on the management of childhood asthma

“…However, its clinical effect is small in established asthma, and ketotifen has no greater steroid-sparing effect than placebo. 107 Cetirizine has properties that may make it particularly useful in infancy. 108 Nedocromil sodium has been recommended for mild to moderate asthma in adults.…”

Ketotifen and Cardiovascular Risk in Patients with Type 2 Diabetes Mellitus

“…While compared to the other groups there was no significant difference. Former preclinical studies supporte the ability of ketotifen to decrease weight [14][15][16], while other studies on human showed that ketotifen induce weight gain [17][18][19]. So, the effect of ketotifen on weight is controversial and this may be due to different mechanisms at different doses [20] or difference in metabolic pathway between animal and human [15].…”

Alternative strategies in the treatment of bronchial asthma

“…Effects of ketotifen, a first generation H 1 ‐specific receptor antagonist, seemed to be promising because of possible intrinsic anti‐inflammatory properties resulting in reduction of eosinophilic activation and migration, and normalization of β‐receptor expression thus preventing tachyphylaxis [ 130, 131]. Since then, many double‐blind, placebo‐controlled studies estimating clinical efficacy of ketotifen in asthma have been performed [ 131–151]. Overall, ketotifen (1 mg bid) seems to ameliorate asthma severity slightly (especially in children), with improvement of symptoms, rescue medication use and number of exacerbations.…”