Mepolizumab Cuts Need for Oral Steroids in Severe Asthma

Severe asthma treatment with the interleukin-5 antagonist mepolizumab (Nucala) reduced the need to take oral corticosteroids in patients who had depended on steroids to control symptoms, according to a study presented at the annual meeting of the American Academy of Allergy, Asthma & Immunology (AAAAI).

In this exclusive MedPage Today video, study author Mark Liu, MD, of Johns Hopkins Medicine in Baltimore, takes us through his presentation from the meeting.

Following is a transcript of his remarks:

My name is Mark Liu and I am at the Johns Hopkins Asthma and Allergy Center. I am the presenting author of this study that's entitled "The clinical benefit of mepolizumab treatment is independent of maintenance oral corticosteroid use: Results from the real-world REALITI-A study." This was presented at the recent AAAAI meeting. I have some disclosures -- I've participated in clinical trials from Boehringer Ingelheim, [GlaxoSmithKline], AstraZeneca, and Gossamer Bio.

By way of background, it's well recognized that patients with severe asthma often rely on oral corticosteroids for asthma control despite the risk of complications, even at low doses. Mepolizumab is a monoclonal antibody against interleukin-5 (IL-5) that has been approved as add-on therapy for severe eosinophilic asthma. Data from randomized controlled trials and real-world studies have shown that mepolizumab significantly reduces exacerbation rate and steroid use. However, data on the impact of mepolizumab according to baseline maintenance steroid use are limited.

The objective of this interim analysis of the REALITI-A study at 1 year was determining real-world outcomes in patients receiving mepolizumab stratified by baseline steroid use and dose. The first slide shows the design of the REALITI-A study. This was a prospective, observational single-arm trial that enrolled patients from December 2016 to October 2019. Inclusion criteria included the clinical diagnosis of asthma, 18 years of age or greater, a new prescription for mepolizumab and availability of relevant medical records for the 12 months prior to enrollment. The decision to start mepolizumab was made by the patient's physician. Mepolizumab was given at the standard dose of 100 mg subcutaneously. The data set at 1 year following the start of mepolizumab included 822 patients that were also included in the study's safety analysis.

The primary endpoint for the REALITI-A study was the rate of clinically significant exacerbations, the change in maintenance steroid dose, and the rate of treatment-related adverse events. Clinically significant exacerbations were defined as exacerbations requiring an increase in steroid dosing, an emergency visit, or a hospitalization.

The data presented here is a post-hoc analysis of subgroups. First, based on whether or not patients were on maintenance steroids. And second, based on the dose of steroids divided into those patients receiving less than 10 mg of prednisone equivalent and those on 10 mg or more.

The clinical characteristics of the entire population of subgroups based on steroid use are shown in the next slide. The total study population was 822 patients, the average age was 54, and was 63% females, and asthma duration of about 20 years. 39% were on maintenance steroids at a median dose of 10 mg of prednisone per day, exacerbation rate average 4.3 in the 12 months prior to starting mepolizumab. Overall, the groups based on the use of maintenance steroids and on the dose of maintenance steroids were well matched. As we might expect, eosinophil counts were lower in patients on steroids compared to those not on steroids, and lower in patients who were on higher dose of steroids at baseline.

The next slide illustrates the effect of mepolizumab on exacerbation rate compared to pretreatment baseline for the year before. The first box plot represents the entire group followed by the four subgroups. Results show significant reductions in the entire group and in all subgroups, regardless of steroid use and dose. Exacerbation rates went from roughly 4 per year down to 1.5 per year.

The next slide shows the effect of mepolizumab on the dose of maintenance steroids in the group on maintenance steroids. Over the 1-year follow-up, average dose went from 10 mg down to 2.5 mg. This represents a 75% reduction in steroid dose. Furthermore, 43% of the patients got off steroids completely.

The next slide shows the effects of mepolizumab on the maintenance steroid groups segregated by starting dose over the 1-year follow-up. The ≥10 mg dose group went from a prednisone daily dose of 12.9 mg to 5 mg, representing a 61% reduction in steroid dose. The less than 10 mg group went from 5 mg to 0.4 mg, representing a 92% reduction -- 36% of the patients in the higher-dose group and 49% in the lower-dose group were able to discontinue steroids completely.

The next slide summarizes the rate of treatment-related adverse events. Adverse events occurred in about 10% of the overall group. Withdrawals occurred in 1%, and serious adverse events in less than 1%. These adverse events were similar among the subgroups.

In conclusion, patients receiving mepolizumab demonstrated a reduction in the risk of clinically significant exacerbations, irrespective of baseline maintenance oral steroid use or dose. All patients on maintenance use, including those in the low (<10 mg) and high (≥10 mg) daily dose, demonstrated a 61% to 92% reduction in maintenance steroid dose by the end of the follow-up period. Many patients in the low (49%) and high (36%) daily steroid use [groups] were able to stop taking their maintenance steroids by the end of the follow-up. These clinically important real-world findings indicate that patients with severe asthma treated with mepolizumab can reduce their maintenance steroid use, potentially reducing substantial risk of side effects associated with their use while improving asthma control. Thank you very much.

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