MILAN — Benralizumab (Fasenra) allowed patients with severe eosinophilic asthma to reduce inhaled corticosteroid (ISC) use without compromising control, the SHAMAL phase IV randomized trial found.

After 32 weeks, 92% of patients on the monoclonal antibody with planned tapering from high-dose ICS plus formoterol were able to reduce their use, reported David J. Jackson, MD, of King’s College London, who presented the findings at the annual European Respiratory Society congress.

That benefit persisted to week 48 during the maintenance period of the study, with another 1.7% having decreased ICS/formoterol use and only 2.5% having to increase it.

Exacerbations were uncommon, occurring in 8.0% of tapering intervention patients compared with 2.3% of the control group without planned tapering. Asthma symptom control, as measured by the five-item Asthma Control Questionnaire, did not differ significantly between the two groups.

“I think what the SHAMAL fundamentally demonstrates is that you can safely reduce from high-dose down to low-dose without lung function decline, which is a massive win for patients because all the side effects are really at the high-dose,” Jackson said at the session.

Because high-dose ICSs have been associated with adverse effects, including glaucoma, cataracts, and more, the Global Initiative for Asthma (GINA) updated guidelines say “that patients should be reduced from a high-dose, if possible, on biologics,” Jackson noted. “But, unusually for GINA, this recommendation was not based on any evidence whatsoever, because SHAMAL is the first study that’s actually been done prospectively to assess whether this is safe and possible.”

A total of 168 patients were included in the study (53% female, 75% white, average age 57.7 years) who had already taken at least three consecutive doses of benralizumab for severe eosinophilic asthma prior to entry and were on a high-dose ICS and long-acting beta agonist.

All received benralizumab 30 mg subcutaneously every 8 weeks, 43 patients were randomized to stay on 400 mg ICS/12 µg formoterol twice daily with a short-acting beta agonist reliever as needed, while 168 were randomized to a dose reduction strategy. That group lowered their use of ICS/formoterol to 200 mg ICS/6 µg formoterol twice daily, then once daily, and then to reliever use as needed only over the course of 32 weeks. After that, they were set to maintain their new usage level for 16 weeks.

Of the patients who were able to reduce use, 61% moved to using an inhaler as needed, 17% switched to a low-dose medication, and 15% to a medium-dose medication. Only 4% increased their dosage during the study’s maintenance phase.

However, among those in the reduction group, there was a reduction of forced expiratory volume in the first second (FEV₁), potentially indicating a decline in lung function. Jackson pointed out that with further analysis, overall lung function decline was only seen among those in the reduction group who had fully reduced their medication usage to only an anti-inflammatory reliever.

On the other hand, patients in the medication reduction group did see an increase in the fractional exhaled nitric oxide (FeNO) at both 32 and 48 weeks. Jackson encouraged further research on this matter.

When asked in a Q&A session about a study referencing nitric oxide as a predictor of quicker decline in lung function in some patients with asthma and about what he does for his own patients, Jackson stood by the results of the SHAMAL trial.

For “those patients that come off completely, there is this rise in FeNO, and it’s that that is associated with a loss of lung function. So, what would I do in clinic? What do I do in clinic is I use FeNO routinely to make sure we are not putting our patients at greater risk of airway remodeling, lung function decline, through IL-13 mechanisms that FeNO fundamentally relates to,” he said. “And you monitor lung function. The key thing is getting the high-dose down to a safer lower dose, which now has been shown to be safe with benralizumab.”

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