Pearls of Wisdom: In Persistent Asthma, ICS Is Better Than LKTR, Right?

Jenny is a 12-year-old girl with asthma who has recently started using daily inhaled corticosteroids (ICSs) with little effect. Her mother asks whether any alternative treatments might offer better control of Jenny's asthma.

Are ICSs always the best initial treatment option for persistent asthma?

A. Yes, because ICSs always provide better first-second forced expiratory volume (FEV₁) improvement than leukotriene receptor (LKTR) antagonists.
B. Yes, because ICSs are safer than LKTR antagonists.
C. Yes, because ICSs are equally as effective as LKTR antagonists but are less expensive.
D. No, sometimes LKTR antagonists perform as well as ICSs or even outperform them for bronchodilation.

What is the correct answer?

Louis Kuritzky, MD, has been involved in medical education since the 1970s. Drawing upon years of clinical experience, he has crafted each year for almost 3 decades a collection of items that are often underappreciated by clinicians, yet important for patients. These “Pearls of Wisdom” often highlight studies that may not have gotten traction within the clinical community and/or may have been overlooked since their time of publishing, but warrant a second look.


Answer: Sometimes LKTR antagonists perform as well as ICSs or even outperform them for bronchodilation.

The consensus among asthma guidelines is that ICSs are "stronger" in their control of FEV₁ than are LKTR antagonists (eg, montelukast), but what does stronger really mean?

Generally, this means that ICSs produce a stronger effect on average FEV₁ increase than LKTR antagonists do. The catch is that within this average, there is a range of responses. For example, one patient may have a moderate response to ICSs but a stronger response to LKTR antagonists, while the next patient has a much stronger response to ICSs than to LKTR antagonists.

ICSs vs LKTR Antagonists: What Does "Stronger" Mean?

This means that while one option is generally stronger than the other, occasionally the "weaker" medicine is actually the better option.

So, why should we bother asking if ICSs are actually stronger than LKTR antagonists rather than simply opting for what is generally the more effective option?

The Research

A recent study examined whether LKTR antagonists should be considered as first-line controllers or as add-on controller therapy for asthma. The research included data from 2 non-industry–sponsored, parallel, randomized, multicenter trials including a total of 658 asthma patients.

Participants were assigned 1 of 2 LKTR antagonists (montelukast or zafirlukast), an ICS, or an ICS supplemented with a long-acting β-agonist (LABA). The main outcomes were quality of life and exacerbations of asthma.

ICSs vs LKTR Antagonists

The Results

After 2 months, the researchers measured the effects of the different treatment options and found that treatment with an LKTR antagonist was just as effective as treatment with an ICS and treatment with an ICS plus a LABA. They also found little difference between the effectiveness of supplementing an ICS with a LABA vs with a LKTR antagonist.

What’s the "Take-Home"?

Even though most guidelines recommend an ICS as first-line treatment, an LKTR antagonist appears to be just as effective in alleviating asthma exacerbations in real-world effectiveness. While utilization of ICSs is still appropriate as a first-line choice, LKTR antagonists start to look quite attractive for patients who do not tolerate corticosteroids well, for parents who are concerned about the growth impact of ICSs, or for patients who experience adverse effects (eg, thrush pharyngitis) from ICSs.

When it comes to picking the "first-line" treatment, one limiting factor is that only ICSs have been shown to prevent the airway remodeling that (uncommonly) can cause long-term structural changes in asthmatic lungs. The researchers in this study cautioned that little data exist detailing the effects of long-term use of LKTR antagonists and their effects on airway remodeling.

Price D, Musgrave SD, Shepstone L, et al. Leukotriene antagonists as first-line or add-on asthma-controller therapy. N Engl J Med. 2011;364(18)1695-1707.