Steroids must be tapered early to avoid long-term steroid-toxicities, according to a landmark 3-year observational study of severe asthma patients. The latest data, published in the Journal of Allergy and Clinical Immunology, shows patients can develop long-term steroid-toxicities that do not improve even with a reduction in steroids.^[1] The publication continues the work highlighted in a previous publication, extending the observational window from 1 year to 3 years.^[2]

The longitudinal study compared OCS-related toxicity levels in 101 patients with severe asthma at the start of biologic treatment to levels after 1 and 3 years (n=89), respectively. Steroid-toxicity was measured using the Steritas Glucocorticoid Toxicity Index (GTI), a weighted validated clinical outcome assessment that quantifies steroid-related toxicity in individual patients. 

All patients met the UK’s National Institute for Health and Care Excellence (NICE) criteria for receiving biologics.^[1] Maintenance oral corticosteroids (mOCS) were tapered after 3 months of biologic treatment using the clinic’s tapering protocol. Primary and secondary care records were used to verify patient-reported exacerbations and acute care attendance. Patients had a clinical review at each assessment, and patient-reported outcome measures (PROS) were collected using asthma-specific and quality-of-life measures.

While biologics improve outcomes for most patients, early monitoring of OCS-related toxicity is critical

The benefit of biological therapies was demonstrated in this study by improved lung function, an overall reduction in airway inflammation and reduced steroid exposure over the 3 years of biologic treatment. Less than half the patients experienced asthma exacerbations in the third year, with fewer patients receiving maintenance OCS or developing further steroid-toxicity as captured by lower GTI scores. Reduction in acute care attendance and improvements in patient-reported outcomes seen at 1 year were sustained across the 3 years of biologic therapy.

• Continued presentation of new toxicities despite a substantial reduction in OCS exposure
• There was no difference in baseline characteristics (including age) that predicted which patients did or didn’t show reduction in steroid-toxicities
• There were also no differences in OCS from baseline across the 3 years of biologic treatment that could account for the difference; both groups had a similar total (mg) and percentage reduction in mean daily OCS

Accumulation of new toxicities in this group was higher between years 1-3 than in year 1, and was not directly associated with ongoing OCS treatment, as demonstrated by the lack of difference in the accumulated toxicities between patients with or without ongoing steroid treatment.

Critically, changes in GTI-scored toxicity at year 1 were predictive of changes at year 3, demonstrating that changes in GTI scores could be used early on in biologic treatment to identify patients unlikely to achieve toxicity reduction with reduced OCS exposure. This is important because it presents an opportunity to prevent longer-term morbidity by discontinuing steroid treatment.

Patient-reported outcome measures showed substantial improvement at year 1, which was sustained across the 3 years. The only patient-related outcome measure that showed continued improvement across the entire cohort between years 1 and 3 was the EuroQol Utility index, which reflects improved health-associated quality of life. There was a median improvement of 0.9 points for this instrument, which would account for a gain of one quality-adjusted life year (QALY) and an economic value of ~£20-30,000 per patient if sustained for 11 years. The study also demonstrated a close correlation between steroid-toxicity reduction and improved quality of life (EuroQol utility score 0.81 (0.65,0.95) versus 0.69 (0.51,0.81), p=0.01).

Earlier use of biologics and monitoring of steroid-toxicity could improve outcomes

This study demonstrates that most severe asthma patients treated with biologics have a substantial reduction in total steroid-toxicity and lower accumulation of new toxicity, resulting in improved quality of life. There is, however, a subset of patients who continue to accumulate OCS-related toxicities, even when OCS treatment has been removed or substantially reduced.  

Commenting on these findings in a recent interview, Dr Jane McDowell, MBBS BSc PhD said, “It is disheartening to report that a considerable number of patients do not have much toxicity improvement even when steroid exposure is negligible.”

For these patients, OCS-related toxicities are irreversible, suggesting that earlier use of biologics for all patients is likely to result in improved outcomes. The study also demonstrates that this subset of patient can be identified early in their biologic treatment through monitoring changes in toxicity with the GTI. This would identify patients early who are not showing an improvement in toxicity, offering the opportunity to intervene with strategies to reduce OCS-related morbidities. Together, these two strategies could improve patient outcomes and quality of life for most patients with severe asthma.

References

1. McDowell PJ, Busby J, Stone JH, Butler CA, Heaney LG. Longitudinal assessment of glucocorticoid toxicity reduction in patients with severe asthma treated with biologic therapies. Journal of Allergy and Clinical Immunology: In Practice. In Press, 2024 https://doi.org/10.1016/j.jaip.2024.10.024  
2. McDowell PJ, Stone JH, Zhang Y, Honeyford K, Dunn L, Logan J et al. Quantification of glucocorticoid-associated morbidity in severe asthma using the Glucocorticoid Toxicity Index. The Journal of Allergy and Clinical Immunology: In practice. 9: 365–372. 2021  https://doi.org/10.1016/j.jaip.2020.08.032
   
   

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