World Asthma Day was celebrated around the world on May 3rd - a day set aside to raise awareness about asthma and how those battling the condition can best equip themselves. This year, the Global Initiative for Asthma (GINA) selected “Closing Gaps in Asthma Care” as its theme, particularly in ensuring equal access to diagnosis and treatment for the disease between different socioeconomic communities and countries.
GINA estimates asthma affects 334 million people worldwide, 13 million of whom (4%) have severe, uncontrolled asthma despite attempts at treatment optimization. Even in countries with “advanced” healthcare systems, glucocorticoids are the prevalent treatment paradigm. 1 This is true despite the wide variety of side effects which has prompted considerable efforts to find pharmacological approaches to try and reduce the dose of glucocorticosteroids to minimize steroid-toxicity without compromising efficacy.2
Due to its prevalence, morbidity for glucocorticoid exposure in severe asthma is usually described at a population level. In general, glucocorticoid-related toxicity occurs in a dose-dependent manner, but this population-based finding is of little use to physicians or their severe asthma patients and has so far made it difficult to make the case for the prescription of more expensive steroid-sparing agents.
Before the creation of the Steritas GTI, the management of severe asthma lacked a validated tool that can systemically and reliably measure treatment-related adverse events.
A recent study on a cohort of severe asthma patients published in Journal of Allergy and Clinical Immunology (JACI) has shown that systematic measurement of steroid-toxicity in individual patients is important to measure patient improvement after reduction in steroid intake for patients prescribed steroid-sparing monoclonal antibodies.3
The observational study was performed by clinician investigators using the GTI for systematic assessment of glucocorticoid-associated morbidity among prednisolone-dependent patients under routine clinical care and the results show the systematic measurement of steroid-toxicity using the GTI was a far better method of determining which patients would derive the most benefit from these new therapies than simply looking at recency or dosage of glucocorticoid exposure.4
Given the purpose of new expensive biological agents is to minimize glucocorticoid use, toxicity reduction should also be a key part of the discussion around the definition of response.
A recent paper published in Seminars in Arthritis and Rheumatism5 and highlighted in this blog showed that not only did the GTI demonstrate strong associations with asthma-related quality-of-life and the St. George's Respiratory Questionnaire, but also that steroid- toxicity change did not have a significant linear correlation with oral glucocorticoid reduction.
This highlights that steroid-toxicity needs to be measured directly, using a validated instrument such as the Steritas GTI, rather than relying upon glucocorticoid reduction (either absolute or proportional) as a surrogate for steroid-toxicity.
References
1 Stephen P.Bergin MD, Craig R.Rackley MD, Managing Respiratory Failure in Obstructive Lung Disease, Clinics in Chest Medicine https://doi.org/10.1016/j.ccm.2016.07.006
2 Yanira Riffo-Vasquez, Radhakrishnan Venkatasamy, Clive P.Page, Steroid sparing effects of doxofylline, Pulmonary Pharmacology & Therapeutics, https://doi.org/10.1016/j.pupt.2017.10.008
3 P. Jane McDowell, MBBSa, et.al. Quantification of Glucocorticoid-Associated Morbidity in Severe Asthma Using the Glucocorticoid Toxicity Index JACI 10.1016/j.jaip.2020.08.032
4 Steritas asthma page: https://www.steritas.com/clinical-asthma-study
5 John H. Stone, P. Jane McDowell, David R.W. Jayne, Peter A. Merkel, Joanna Robson, Naomi J. Patel, Yuqing Zhang, Huibin Yue, Pirow Bekker, Liam G. Heaney, The glucocorticoid toxicity index: Measuring change in glucocorticoid toxicity over time, Seminars in Arthritis and Rheumatism, Volume 55, 2022, 152010, ISSN 0049-0172, https://doi.org/10.1016/j.semarthrit.2022.152010.