Effectiveness of Inhaled Reliever Therapies in Patients With Asthma

For asthma – should we use SABA, ICS–SABA, or ICS–LABA?

I still remember using aminophylline at the hospital to treat patients with asthma. When salbutamol, a short-acting beta agonist (SABA), came along, it was like a miracle. Patients treated themselves anywhere. They were no longer tied to the hospital. Unfortunately, SABAs were not treating the airway inflammation, which was the cause of the constriction. The effects of the SABA only lasted for a few hours, and, then, the airways would constrict again. Patients needed to use SABAs frequently. In fact, the bronchial muscles were getting a workout. They relax for 4 hours, then they contract, then they relax again, and then contract. It’s like doing bicep curls. The bronchial muscles got stronger, and so the attacks became worse, which led to even further SABA usage.

The solution was simple. Use inhaled corticosteroids (ICS) to put out the inflammation. However, ICS do not start acting within a few minutes; hence, patients felt that the SABA worked but ICS did not. Hence, patients continued to only use SABA and ignored ICS. The key was to combine the two medications such that when patients use the SABA, then they also get the ICS.

Recently the FDA approved an ICS–SABA combination. We already have several ICS–LABA (long-acting beta agonists) combinations, and the GINA guidelines have already stated that a fast-acting LABA is preferred for asthma. The guidelines state that ICS–formoterol, is preferred over using SABA as a reliever therapy for asthma. But, now the question is would this ICS–SABA be useful and where should it fit in the guideline recommendations?

This paper conducted a network meta-analysis with 27 clinical trials involving over 50,000 patients. The placebos of all the trials were tied together to create a common placebo group, and the authors compared the different treatment arms with each other through the common placebo.

Compared with SABA alone, ICS–SABA was associated with 16% fewer severe exacerbations (RR, 0.84; 95% CI, 0.73–0.95). Compared with SABA alone, ICS–formoterol was associated with 35% fewer severe exacerbations (RR, 0.65; 95% CI, 0.60–0.72).

When the authors compared ICS–SABA with ICS–formoterol, there were 12% fewer severe exacerbations with the ICS–formoterol (RR, 0.78; 95% CI, 0.66–0.92). This might be because using LABA means there is no bronchial muscle training. The LABA keeps the muscles relaxed for the full duration, and they do not contract every 4 hours. Perhaps this means the muscles are calmer and may not be as strong.

Whatever the mechanism, this analysis means that the GINA guideline recommendation of ICS–formoterol as the preferred agent still stands even with this new option of ICS–SABA being available.

When the authors looked at side effects, there were no increases in the frequency of side effects in any of the groups.

So, it is clear that ICS–formoterol is the preferred option. Now, if there are cost, access, or supply issues and ICS–formoterol is not available, then ICS–SABA is another alternative. SABA alone should not be used unless there are no other combination options available.

We should help move our patients switch from SABA alone to the ICS–formoterol option. I tell my patients "you don’t have to give up the SABA but every time you reach for the SABA, just reach for this new combination therapy." It will open your lungs up like the SABA and also put out the fire that is causing the spasm. I also tell them — "you can use the SABA in addition, but you will find that you don’t need to if you use this new combination therapy." Furthermore, I tell them that using the combination therapy is like getting a new upgrade on their smartphones. Now, the combination therapy can do more for you.