Australian registry data shows mepolizumab reduces toxic oral corticosteroid exposure while halving symptoms of depression and anxiety in severe eosinophilic asthma.
Biologic therapy with mepolizumab not only reduces oral corticosteroid exposure in severe eosinophilic asthma but also provides substantial improvements in patient mental health, including reductions in symptoms of depression and anxiety, Australian researchers have found.
They say the results reinforce the importance of OCS stewardship in clinical practice and highlight the broader benefits of targeted biologic treatment in severe asthma management.
The observational Australian Mepolizumab Registry (AMR) study followed 412 patients across 21 specialist clinics who commenced mepolizumab therapy between 2017 and 2024. Results have been published in Respiratory Medicine.
“Our real-world study confirms and extends the evidence regarding mepolizumab as an OCS-minimising treatment in SEA, further highlighting the importance of OCS stewardship initiatives in clinical practice,” the authors wrote.
“Moreover, we demonstrate the associated improvement in OCS-related complications, including depression and anxiety, which are of particular clinical importance in the management of type-2 severe asthma. This further highlights the role of biologics in oral steroid stewardship initiatives.”
Participants had a median age of 59 years, and nearly 60% were female. All patients had uncontrolled severe eosinophilic asthma despite maximal inhaled therapy, with many already experiencing high levels of OCS use.
Data were collected prospectively at regular intervals over a two-year period, with assessments of OCS exposure, exacerbations, asthma control, quality of life and symptoms of depression and anxiety using validated questionnaires.
Prior to mepolizumab treatment, OCS exposure was extensive, with 95% of patients having required at least one OCS burst in the preceding year.
Almost two-thirds (64%) had received a toxic cumulative dose equivalent to 1000mg or more of prednisolone, a level known to significantly increase the risk of adverse outcomes. Maintenance OCS use was common, reported in 42% of patients at baseline.
Toxic-level OCS exposure was strongly associated with increased disease burden and higher rates of doctor-diagnosed depression, reported in 27% of patients compared with 15% in those with lower exposure.
Hospital Anxiety and Depression Scale (HADS) scores at baseline also revealed a high prevalence of clinically relevant symptoms, with 37% meeting criteria for depression and 44% for anxiety.
Treatment with mepolizumab resulted in significant and sustained reductions in OCS exposure over the 24-month observation period.
The proportion of patients requiring maintenance OCS dropped from 42% at baseline to 18% at two years, with the median daily dose halving over the same period. Similarly, the need for OCS bursts fell sharply, with 44% requiring a course for exacerbations by year two, compared with 95% in the year prior to commencing therapy.
Cumulative exposure was also markedly reduced, with only one-quarter of patients experiencing toxic OCS levels in the second year of treatment, compared with nearly two-thirds prior to initiation.
Alongside reductions in OCS burden, patients experienced improvements in asthma symptom control and quality of life. Mean Asthma Control Questionnaire (ACQ-5) scores fell significantly, and quality of life gains were sustained across the two years.
Notably, improvements extended to mental health outcomes. Symptoms of depression and anxiety were both approximately halved, with the proportion of patients scoring above the clinical threshold for depression reduced from 37% at baseline to 15% at two years; while anxiety dropped from 44% to 25%.
Reductions in HADS scores were consistent across patient groups, regardless of baseline OCS use, although higher steroid doses during treatment remained correlated with worse mental health outcomes. Improvements in psychological measures were also closely linked with improvements in asthma-related quality of life, suggesting a synergistic effect of reduced disease burden and reduced steroid exposure.
Patients also reported a reduction in the intensity of common OCS-related adverse effects. Those who had been on maintenance OCS at baseline described improvements in sleep, appetite and weight changes, mood disturbances and physical side effects such as bruising and swelling.
Female patients reported experiencing some of these side effects more intensely, particularly memory difficulties, weight gain and facial swelling (commonly known as “moon face”, but these too improved during mepolizumab treatment.
“Interestingly, a qualitative study in severe asthma has reported that female participants, particularly, expressed embarrassment or unhappiness about the effects of OCS on their physical appearance,” the authors noted.
“These findings may be due to physiological differences between the sexes and/or differences in perception or reporting of these effects.”
Their findings echo previous qualitative research highlighting the heavy physical and psychological toll of long-term OCS use and underscore the importance of minimising steroid exposure whenever possible.
These registry data confirm the essential role of biologic therapy within an OCS stewardship framework, which aims to reduce both acute and cumulative steroid burden and prevent associated complications.
The researchers said the strengths of their study lay in the national recruitment approach and sample size, however there were some limitations.
“Patients have been carefully evaluated with regular follow-up over a two-year period. Whilst free from the limitations of randomised controlled trials including strict inclusion criteria, the observational design has inherent limitations,” they wrote.
“Patients were not a randomised population and the study was not controlled or blinded; it is therefore subject to bias and confounding factors. OCS exposure data were self-reported, resulting in potential for recall bias, however the recall period between assessments was limited to six months, which would minimise this effect.
“Our assessment of cumulative OCS exposure level prior to mepolizumab commencement was limited to a single year. As such, categorisation of patients by recent toxic level exposure (≥1000 mg prednisolone equivalent in a year) did not take into account an individual’s previous, or lifetime, cumulative exposure. It is possible that patients categorised as having recent toxic level exposure (≥1000 mg in a year) had far exceeded the lifetime toxic threshold.
“It is also possible that patients categorised as having <1000 mg exposure in the single year had experienced lifetime toxic exposure. This may be a confounding factor when assessing OCS associated complications. Nevertheless, the 1000 mg threshold is informative, as this level is known to definitively increase the risk of harm in isolation, with an additive risk observed for each subsequent year with 1000 mg exposure.”
