The role of ACT score in mepolizumab discontinuation

Abstract

Background: Mepolizumab is a therapy for severe asthma. We have little knowledge of the characteristics of people in the US that discontinue mepolizumab in clinical care.

Objective: To investigate the real-world efficacy and time to clinical discontinuation of mepolizumab, we evaluated individuals with asthma started on mepolizumab at the Cleveland Clinic. We hypothesized that individuals that discontinue mepolizumab have more severe and uncontrolled asthma at baseline.

Methods: Between 2016 and 2022, patients who started on mepolizumab consented to be assessed over 18 months. At baseline, a questionnaire including demographic and medical history was collected. Laboratory findings such as ACT score, F_ENO (Fractional Excretion of Nitric Oxide), and spirometry were recorded. At the conclusion of the observation period, the participants were divided into two categories: Group A and Group B.

Results: Group B [N = 28] discontinued mepolizumab (p < 0.05) at an average of 5.8 months (SD 4.2 months). Group A [N = 129] stayed on the therapy for at least 1 year. A participant with an ACT score less than 13 has an odds ratio of 6.64 (95% CI, 2.1 - 26.0) of discontinuing mepolizumab therapy. For a male, the odds of discontinuing mepolizumab therapy is 3.39 (95% CI, 1.1-11.2).

Conclusion: In this real-world study, we find that high eosinophil count may not be adequate in screening which individuals will benefit from mepolizumab. Up to 17% of patients fail therapy within 6 months, with male sex and low ACT score increasing risk of mepolizumab discontinuation at Cleveland Clinic.

Keywords: Asthma; asthma control; mepolizumab.

Figure 1.

Flowchart for Mepolizumab. This flowchart delineates information collected at visits at baseline, 3 months, 6 months, 12 months, and 18 months. Questionnaires were collected at every visit. ACT, medication use, and spirometry results were also recorded at every visit. Definitions: F_ENO = fractional exhaled nitric oxide; CBC = Complete Blood Count; ACT = Asthma Control Test

Figure 2

A. Mepolizumab Registry. The registry has 199 people initiated on mepolizumab between the years of 2016 and 2022. 27 people were removed for having only one visit recorded within the database. 15 people were removed for stopping mepolizumab for reasons other than clinical failure. Of the remaining 157 participants, 129 people are clinically considered mepolizumab responders as defined by an asthma specialist. Figure 2B is a pie chart demonstrating the reasons people were removed from this study. Most people that were removed had only a single visit recorded or were lost to follow up.

Figure 3.

Attrition in Study. The number of participants per visit is shown in this bar graph which shows attrition over subsequent visits.

Figure 4.

Mepolizumab Outcomes. Panel A demonstrates median ACT scores. Each visit has an increase in ACT scores. Panel B demonstrates the greatest increase in median FEV₁% occurs between visit 1 and visit 3. Panel C shows the decrease in prednisone use for participants while on mepolizumab. The asterisk (*) is for P < 0.05.

Figure 5.

Time to Discontinuation. Time to discontinuation of mepolizumab or censorship between the two cohorts is different with P < 0.05. The Kaplan – Meier curve demonstrates the average time someone from Group B is on mepolizumab and the average time to censorship for Group A. Group B stay on mepolizumab for a mean of 5.8 months (standard deviation [SD] 4.2 months). Group A are on mepolizumab for a mean of 12.3 months (SD 4.6 months) to the time of censorship. The tick marks for group A represent when our database stops recording the participant’s information though they may still be on mepolizumab.

Figure 6

A. Mean ACT score in Group A and B over 12 months. This graph depicts the mean ACT score with standard deviation of Group A, which is the group of people that remained on mepolizumab. Through subsequent visits, the mean ACT score of the group significantly improves from the baseline ACT score. Graph 6B demonstrates the mean ACT score for Group B does not significantly change between the baseline visit and 12 months.

Figure 7.

Baseline Median ACT scores in Group A and Group B. Group B present with a remarkably lower baseline ACT score prior to starting mepolizumab therapy compared to those who stay on mepolizumab for longer than 6 months (ACT: Median [IQR], Group B, 9 [ 4]; Group A, 13 [IQR9]). Definitions: ACT = Asthma Control Test

Figure 8.

Receiver Operative Curve in Asthma. Receiver operating curve (ROC) for ACT score in all participants started on mepolizumab showed an ACT cutoff score of 13. Definitions: ROC = Receiver Operating Curve; AUC = Area Under the Curve

Figure 9.

Characteristics Impacting Mepolizumab Discontinuation. For a participant who has an ACT score of 13, the odds ratio of discontinuing mepolizumab therapy is 6.64 (95% CI, 2.1 – 26.0). For a male, the odds ratio of discontinuing mepolizumab therapy is 3.39 (95% CI, 1.1 – 11.2). Definitions: ACT = Asthma Control Test; BMI = Body Mass Index; F_ENO = fractional exhaled nitric oxide