Sodium cromoglicate: an ineffective drug or meta‐analysis misused?

Abstract

Sodium cromoglicate (SCG) has been available since around 1970 for the treatment of asthma and other allergic disorders in both adults and children. It has been approved for use around the world. Over the period of its development, a number of different formulations were introduced. In 1999, a systematic review of SCG use in childhood asthma was carried out and reported initially as a poster. Further systematic reviews and papers followed from the same authors and finally a Cochrane Collaboration review was published in 2003. All concluded that SCG was ineffective in paediatric asthma. Both the British Thoracic Society Guidelines for the treatment of paediatric asthma and the Model List of Essential Drugs of the WHO now reflect these conclusions. This paper looks carefully at the conclusions of these systematic reviews and raises concerns about the interpretation of the results. These failed to take adequate account of the changes with time in both the formulations used and the age groups examined, and also failed to take adequate note of the totality of information available over all end-points. One primary end-point was based on only four out of the 24 studies included in the review. Rather than having no effect, it is demonstrated that a considerable body of evidence favours SCG compared to placebo and, far from being ineffective, the drug appears to be effective particularly in older children. This article replaces a previously published version. DOI: 10.1002/pst.258.

Rethinking the Pathogenesis of Asthma

“…While these drugs were used for many years in asthma prophylaxis, especially in children, they eventually fell out of favor on account of their limited efficacy across the asthma spectrum (van der Wouden et al, 2008). However, its efficacy and safety in a subset of allergic and exercise-induced asthma is unquestionable; the problem was how to identify those that best respond-another example of stratified medicine (Stevens et al, 2007).…”

The mast cell and allergic diseases: role in pathogenesis and implications for therapy

“…It is unsubstantiated and unsupported statements made in reviews of this kind that can influence clinical usage and deny safe and effective treatments to patients. My colleagues and I and others criticized reviews of inhaled SCG in childhood asthma that concluded that SCG was no better than placebo [16]. These reviews led to the drug being removed as recommended treatment for childhood asthma in national guidelines and to its removal from the WHO essential drug list.…”

Trials and tribulations in identifying new biologic treatments for asthma

“…Although it has been shown to be an effective antiasthmatic drug, especially in children [8], subsequent meta-analysis and Cochrane Review of SCG trials have concluded that, across a wide age range of young people, 'there was insufficient evidence to be sure about the efficacy of SCG over placebo' [11]. SCG has subsequently been withdrawn from the WHO List of Drugs, despite evidence that the conclusions drawn from the Cochrane Review may be challenged [12]. One problem with this class of drugs is that no mechanism has been found to explain inhibition of mast cell activation, apart from inhibiting chloride flux [13].…”