The efficacy and safety of salmeterol compared to theophylline: meta-analysis of nine controlled studies

Abstract

The aim of this study was to compare the efficacy and safety of salmeterol vs theophylline in asthma management using meta-analysis of clinical trials. Nine clinical studies, containing a total of 1330 patients, met meta-analysis inclusion criteria: randomized, controlled study, minimum 2-week treatment duration with either salmeterol or theophylline. The main outcome measurements were morning and evening peak expiratory flow rate (PEFR), morning and evening symptom scores, use of salbutamol as rescue medication, and withdrawal from treatment for any cause. During the second week of treatment, salmeterol patients had a 10 l min-1 greater increase in mean morning PEFR from baseline than theophylline patients (P < 0.001). Similarly, in the second week, the increase in mean evening PEFR from baseline observed with salmeterol was significantly greater (P < 0.01) than that observed with theophylline. Salmeterol also produced a significantly greater increase in mean morning and evening PEFR than theophylline at weeks 3 and 4. Patients receiving salmeterol were free from daytime symptoms for a mean of 51% of days in the second week compared to 39% for theophylline patients (P < 0.001). Salmeterol patients experienced a mean of 63% symptom-free nights compared to 52% for theophylline patients (P < 0.001). Rescue medication with salbutamol was not required on 49% of days for salmeterol patients and 34% of days for theophylline patients. All results were maintained in the third and fourth weeks of treatment. Withdrawal and incidence of adverse events leading to withdrawal were significantly less frequent in patients receiving salmeterol (P < 0.001). Thus, this meta-analysis suggests that salmeterol has a superior safety and efficacy profile to theophylline in the management of symptoms of chronic asthma.

Global strategy for asthma management and prevention: GINA executive summary

“…Sustained-release theophylline has little effect as a first-line controller [112] but may provide benefit, although less than that provided by long-acting inhaled b 2 -agonists [113,114], as addon therapy in patients who do not achieve control on inhaled glucocorticosteroids alone [115][116][117]. Side-effects of theophylline, particularly at higher doses (o10 mg?kg -1 body weight per day), are significant and detract from their usefulness but can be reduced by careful dose selection and monitoring, and generally decrease or disappear with continued use.…”

Long-Acting Beta-Agonists in Adult Asthma: Evidence that these Drugs are Safe

“…Meta-analyses have confirmed that adding a LABA to a dose of ICS which is failing to control asthma adequately produces a superior reduction of symptoms and use of rescue medication, and superior improvement in pulmonary function, when compared with doubling (or more than doubling) the dose of ICS [14]. A meta-analysis of nine randomized, controlled studies of salmeterol vs. theophylline, in which the majority were using inhaled corticosteroids, similarly showed salmeterol to be superior in terms C o p y r ig h t G e n e r a l P r a c t ic e A ir w a y s G r o u p R e p r o d u c t io n p r o h ib it e d of both symptoms and pulmonary function [15]. At least three studies have compared, in patients whose asthma was not adequately controlled by low dose inhaled corticosteroids, the addition of salmeterol or a leukotriene receptor antagonist [16][17][18].…”

The corticosteroid dose-response curve in asthma and how to identify patients for adjunctive and alternate therapies

“…LABA are also superior to theophylline as add-on agents. 24 The other alternative is a leukotriene antagonist. These agents are particularly useful in children, and in those who have difficulty with coordination, who prefer a tablet and who are prone to non-compliance with inhalers.…”