Plain language summary
Regular treatment with formoterol and inhaled steroids for chronic asthma: serious adverse events
Asthma is a disease of the lungs. Symptoms include wheezing, breathlessness and chest tightness. Two main features of asthma have been identified: underlying inflammation, which can be treated with daily steroids, and bronchoconstriction (tightening of the muscles around small tubes in the lungs), which can be treated with a beta2-agonist to relax the muscles.
When asthma is not controlled by daily low-dose inhaled steroids, many asthma guidelines recommend additional daily long-acting beta2-agonists (such as formoterol). Although we know that long-acting beta2-agonists are beneficial for lung function, symptoms, quality of life, and exacerbations, long-standing controversy surrounds the safety of regular use of beta2-agonists in people with asthma. This is the topic we sought to explore in this review.
We assessed the risk of death and of non-fatal serious adverse events in clinical trials comparing regular formoterol and inhaled steroids with the same dose of inhaled steroids in adults and children with asthma.
We analysed data from 20 studies in adults and 7 in children; these studies included participants with a range of asthma severity, and most participants had been previously treated with regular inhaled steroids (over a wide range of doses). The number of children studied was insufficient to allow a solid conclusion. However, a large trial in children is now in progress.
Seven deaths were reported among 13,366 participants. Six of these deaths, including one related to asthma, were reported in adults taking formoterol and inhaled steroids, and one death occurred in a participant who was taking inhaled steroids alone. Because few deaths were reported in these trials, we cannot conclusively state whether taking formoterol and inhaled steroids reduces or increases the risk of death compared with taking inhaled steroids alone.
The number of people experiencing serious adverse events of any cause was very similar in adults with and without formoterol. A significant reduction in serious adverse events was noted in adult participants with asthma who were taking regular formoterol in combination with inhaled corticosteroids.
Quality of the evidence
The quality of the data was moderate for adults but low in children because data in children were insufficient. All trials were sponsored by drug manufacturers. We were therefore concerned that bias might have been introduced in the attribution of asthma as the cause of serious events, as this was not independently assessed. The trials were double-blind; however, formoterol can have a big impact on asthma symptoms, and those who decided on the cause of the events may have guessed which treatment was being given.
We are not able to confidently state that adding formoterol to inhaled steroids carries no risk of increasing the number of deaths in comparison with inhaled steroids alone. On the other hand, we found no conclusive evidence of serious harm, and only one asthma-related death was reported over 4200 patient-years of observation of those treated with formoterol. With the addition of new studies in 2012, we have found a lower risk of non-fatal serious adverse events attributed to asthma when formoterol is combined with inhaled steroids.
Glossary: serious adverse events: events that are life threatening, require inpatient hospitalisation or prolongation of existing hospitalisation, or result in persistent or significant disability/incapacity or a birth defect.
This Cochrane plain language summary is current as of August 2012.
Événements indésirables graves sous formotérol et corticoïdes inhalés en traitement de fond
Certaines inquiétudes ont été soulevées sur la possibilité d'une augmentation des événements indésirables suivant l'administration de formotérol, un bêta-agoniste à longue durée d'action chez les asthmatiques. Nous avons analysé les données de 14 études chez l'adulte et sept chez l'enfant. Trop peu de décès sont survenus dans les essais pour pouvoir conclure de façon rassurante que le formotérol en traitement de fond avec des corticoïdes inhalés réduit le risque de mortalité ou ne l'augmente pas (les quatre décès survenus, dont celui lié à de l'asthme, étaient parmi 6 594 patients sous formotérol avec corticoïdes inhalés.) Des événements indésirables graves étaient très similaires chez les adultes avec ou sans formotérol. Bien qu'il se soit produit plus d'événements sous formotérol chez les enfants, la différence n'était pas assez importante pour écarter l'idée d'une coïncidence. De même, la diminution du risque d'événements indésirables graves liés à l'asthme chez les adultes et le risque accru parmi les enfants sous formotérol pourrait aussi être une coïncidence.
Notes de traduction
Traduit par: French Cochrane Centre 1st October, 2012
Traduction financée par: Ministère du Travail, de l'Emploi et de la Santé Français