Abstract
Use more budesonide/formoterol when you need it, and less when you don't http://bit.ly/2PKsCOH
To the Editor:
We appreciated reading the eloquent editorial from Beasley et al. [1], who make a cogent evidence-based case for using budesonide/formoterol (BUD/FM) on demand (p.r.n.) as the preferred asthma reliever, in keeping with the latest GINA guidelines. They proffer what appears at first sight to be a pragmatic stepwise treatment algorithm and associated action plan for using BUD/FM p.r.n. as anti-inflammatory reliever (AIR)±maintenance therapy across Global Initiative for Asthma steps 1 to 3.
It is worth noting that a large proportion of the evidence base was using BUD/FM as maintenance and reliever therapy. Despite the overwhelming evidence in favour of AIR described by Beasley et al. [1], the only study comparing BUD/FM AIR versus BUD/FM maintenance showed a 10.3% difference in treatment failure in favour of the latter [2].
However, we believe their proposal over complicates what should be an intuitive patient-centred regimen that always ensures perfect concordance between inhaled corticosteroid (ICS) and reliever therapy. In particular, we feel their suggested asthma action plan might be difficult to penetrate and be confusing for patients taking AIR in terms of artificially distinguishing between maintenance and reliever therapy, especially when referring to various treatment steps. Surely the whole point of using AIR is to make things simpler for the patient. In this respect, our proposed mantra for using AIR would be to simply advise patients to “use more puffs of BUD/FM when they need it and less when they don't” [3] (figure 1). This way the patient will effectively self-titrate their ICS dose requirement according to prevailing type 2 inflammation, so that there is a seamless process of escalation and de-escalation, rather than considering distinct treatment steps per se. The current licensed indication states that a total daily dose of up to 12 puffs per day may be used for a limited period with the usual regimen being up to 8 puffs per day. This is presumably based on the adverse effects of the FM moiety, such as tremor, tachycardia and hypokalaemia. Nonetheless, it has been shown that with regular exposure to FM in conjunction with ICS there is blunting of systemic responses due to beta-2 receptor downregulation and uncoupling [4]. It is also worth noting that an application has been submitted for BUD/FM metered dose inhaler to mirror the same indications as BUD/FM dry powder inhaler, including AIR. There are no data to support the AIR indication in children.
The flexible dosing regimen with BUD/FM p.r.n. empowers the patient to be in control of their own asthma and avoids patients being continually exposed to unnecessarily higher fixed doses of ICS. Indeed, this reflects the nature of the disease in that asthma severity can vary over time depending on prevailing trigger factors. The challenge for prescribers will be to persuade patients that they no longer need a separate short-acting β-agonist reliever inhaler, especially for those who have become over dependent on salbutamol. Thus, we would also advocate checking the glycine-16-arginine β2 receptor genotype for those patients who end up requiring persistently higher doses of BUD/FM [5]. Furthermore, using fractional exhaled nitric oxide at routine follow up will allow the clinician to assess whether AIR is adequately suppressing underlying type 2 inflammation [6].
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Footnotes
Conflict of interest: B. Lipworth reports non-financial support (equipment) from GSK, grants, personal fees for advisory board work, consultancy and lectures, and non-financial support for meeting attendance from AstraZeneca and Teva, personal fees for consultancy from Lupin, Glenmark, Vectura, Dr Reddy and Sandoz, during the conduct of the study; grants, personal fees for consultancy and lectures, and non-financial support for meeting attendance from Boehringer Ingelheim, grants and personal fees for advisory board work, consultancy and lectures from Mylan, grants and personal fees for advisory board work and consultancy from Sanofi Regeneron, outside the submitted work; and has a family member who is an employee of AstraZeneca.
Conflict of interest: C.R. Kuo reports personal fees for meeting attendance from AstraZeneca, personal fees for meeting attendance and lectures from Chiesi, personal fees for advisory board work from Circassia, outside the submitted work.
Conflict of interest: R. Chan has nothing to disclose.
- Received February 7, 2020.
- Accepted February 15, 2020.
- Copyright ©ERS 2020