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Monday, December 3, 2012

Revisiting LABAs with the help of Macbeth

Szefler and Busse provide an entertaining and thoughtful editorial this month on the predicament of LABA step-down by invoking Macbeth’s notorious witches’ ominous chant (J Allergy Clin Immunol 2012;130:1256-1259). Likening the clinician’s dilemma at the FDA recommendation to withdraw LABAs for safety reasons from treatment of well-controlled asthma to the troubling brew of the witches, the authors review the history of long-acting beta 2 agonists’ use and the evidence that supports the safety concerns that prompted the FDA’s action. Szefler and Busse note that a recent evidence review does not concur that LABAs are unsafe when used in combination with ICS and, in fact, concludes that withdrawal of LABAs in that treatment context results in asthma worsening.

At the heart of the controversy are several “Catch-22s”: how and when to step down and, critically, with what to replace LABAs if control is lost. Clinicians and researchers are concerned that the delay in safety reporting will also delay the development of new asthma drugs in the LABA category. Further, the FDA safety trial does not address how to step-down LABAs in the event of a poor safety profile. This would require yet another set of trials, which implies further delays.

Results from the current FDA-mandated safety study are expected to be reported in 2016. Until then, the authors provide approaches for possible step-down in patients on ICS and LABA combination products. Among these, they suggest that clinicians consider the asthma natural history, especially over the previous year, the possibility of adjusting either the ICS or the LABA, and alternative supportive treatments, such as omalizumab or tiotropium, if they decide to step-down the LABA. Szefler and Busse emphasize that there is no current evidence that supports changing the current EPR-3 guidelines, which already advise against LABA monotherapy.

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