Six-month asthma control score on mepolizumab predicts remission in eosinophilic asthma
Key takeaways:
- Area under the curve (AUC) below 0.7 signaled no accuracy in “identifying asthma remission at 12 months.”
- At 6 months, researchers found an AUC above 0.7 when using Asthma Control Questionnaire scores.
Of four treatment response measures recorded at 6 months of mepolizumab treatment, an Asthma Control Questionnaire score was deemed “best predictor” of 12-month remission in patients with severe eosinophilic asthma, according to study data.
“The [5-item Asthma Control Questionnaire (ACQ-5)] score at 6 months in mepolizumab-treated patients was the best predictor of achieving clinical remission or clinical remission plus optimization/stabilization of lung function at 12 months,” Yuto Hamada, MD, PhD, visiting academic at the University of Newcastle in Australia, and colleagues wrote.
In this study published in The Journal of Allergy and Clinical Immunology: In Practice, Hamada and colleagues evaluated 255 patients (median age, 59.3 years; 58.8% female) with severe eosinophilic asthma from the Australian Mepolizumab Registry receiving 100 mg mepolizumab to uncover if future asthma remission could be predicted by early response (3 or 6 months) to mepolizumab (Nucala, GSK).
Researchers also sought to determine which treatment response measure — ACQ-5, oral corticosteroid dose, exacerbation frequency and postbronchodilator FEV1 — is the best predictor of reaching clinical remission at 12 months.
Notably, three factors had to be met to classify a patient as achieving clinical remission, according to the study: ACQ-5 score of 1 or lower at 12 months, zero exacerbations in past 6 months and no receipt of oral corticosteroids in past 6 months.
Based on the above definition, researchers reported attainment of clinical remission in 78 patients (30.6%).
Comparing models made up of either all four treatment response measures at 3 months or all four measures at 6 months, the study noted that the better predictor of remission achievement was the 6-month model, as demonstrated by a higher area under the curve (P = .029).
“Our results suggest that assessing asthma symptoms at 6 months rather than at 3 months is better for predicting who will go on to achieve clinical remission at 12 months,” Hamada and colleagues wrote.
Researchers observed significantly decreased odds for clinical remission achievement at the 12-month mark as the ACQ-5 score at 3 months went up by 1 unit (adjusted OR = 0.55; 95% CI, 0.4-0.74). This was also the case for the ACQ-5 score at 6 months (aOR = 0.31; 95% CI, 0.2-0.46).
Similar to the above finding, the odds for clinical remission achievement at 12 months significantly dropped with maintenance oral corticosteroid dose rises of 1 mg per day when collected at 3 months (aOR = 0.84; 95% CI, 0.76-0.92), as well as at 6 months (aOR = 0.8; 95% CI, 0.68-0.9).
Further, researchers found significantly lower odds for clinical remission achievement at the 12-month mark as exacerbation frequency at 3 months went up by 1 unit (aOR = 0.3; 95% CI, 0.13-0.6). This was also the case for rises in exacerbation frequency at 6 months (aOR = 0.54; 95% CI, 0.35-0.78).
According to the study, an area under the curve (AUC) below 0.7 signaled no accuracy in terms of “identifying asthma remission at 12 months.” Each of the four treatment response measures recorded at 3 months had an apparent AUC and an optimism-corrected AUC below 0.7.
At 6 months, researchers found the highest optimism-corrected AUC when using ACQ-5 score with a cutoff of 1.5 (0.778) vs. oral corticosteroid dose (0.638), exacerbation frequency (0.631) and postbronchodilator FEV1 (0.522). The predictive abilities of different ACQ-5 score cutoffs at 6 months were assessed following this observation.
The study highlighted that the sensitivity was high with both an ACQ-5 cutoff of 1.5 (85.9%) and an ACQ-5 less than 1.5 (85.9%). Switching to an ACQ-5 less than 0.75, researchers found that this cutoff had a better specificity than a cutoff of 1.5 (84.7% vs. 58.2%).
Notably, the findings above for clinical remission achievement were comparable to the findings when researchers considered clinical remission plus optimization/stabilization of lung function achievement.
“Further studies are needed to investigate predictive factors of treatment response to different biologics for achieving asthma remission,” Hamada and colleagues wrote.
Perspective
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While it is known that mepolizumab can induce remission on therapy in a subgroup of asthmatics and there are data indicating which asthmatics are likely to respond, this study adds to our ability to optimize care, demonstrating that ACQ-5 score at 6 months was the best predictor of achieving remission at 1 year. The authors suggest that these findings can be used to enhance the treat to target paradigm for asthma and this in turn can translate to improve the cost effectiveness of this therapy.
Perspective
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Asthma remission is an important concept that has gained popularity in recent years with the rise of targeted biologic therapies and the successful focus on achieving remission in numerous other diseases, such as inflammatory bowel disease. Despite this, however, remission in asthma remains a lofty goal for many, with the majority of data suggesting that only 20% to 30% of individuals on biologic therapy for asthma will achieve this state. Thus, it is crucial to understand who is able to achieve remission and maximize benefit from targeted therapies.
This paper by Hamada and colleagues contributes to our understanding of who exactly is most likely to achieve asthma remission, in this case with the anti-IL-5 medication mepolizumab. In this study, the authors identified ACQ-5 scores at 6 months on mepolizumab treatment as the most accurate predictor of subsequent remission at 12 months. In addition, oral corticosteroid dose and exacerbation frequency were predictors of remission, consistent with known findings.
The results of this study may help clinicians to determine that a patient is unlikely to achieve remission or significant disease control after 6 months of mepolizumab, and perhaps consider transitioning to a different therapy earlier, rather than waiting a full year to reassess. While earlier data had demonstrated that 3 months may be sufficient to identify the likelihood of remission in early responders, this study supports the continued reassessment of those who may not fit into the early responder category.
Future studies which include functional and biomarker assessments will add to the work done by Hamada and colleagues, and allow better characterization of these patients with severe eosinophilic asthma, in order to best target therapies and increase the likelihood of achieving remission for these individuals.
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