Glucocorticoids have saved countless lives since being discovered 75 years ago. Yet, long-term exposure is associated with a range of toxicities including an increased risk of devastating adverse events such as fractures, infections, gastrointestinal bleeding,^[1] and even death.^[2] Despite this, steroid-toxicities are inconsistently monitored in clinical practice.

This bleak picture could be about to change thanks to an international team of researchers led by John H. Stone, MD MPH, Professor of Medicine at Harvard Medical School, and the Edward A. Fox Chair in Medicine at the Massachusetts General Hospital. Dr Stone’s team has developed an abridged version of the Steritas Glucocorticoid Toxicity Index (GTI) that is easy to integrate into existing clinical workflows. The new instrument is called the GTI-MD (Metabolic Domains) and is described in detail in a new study published in Lancet Rheumatology.^[3]

“The GTI-MD utilizes data points that are routinely measured in clinical practice and can be seamlessly integrated into clinic workflows, potentially working without a clinician even knowing it is present until it is needed. The GTI-MD has the potential to optimize the treatment of inflammatory diseases, and improve the quality of patient care in routine clinical settings,” stated Dr Stone.

The parent GTI is a clinical outcome assessment that measures the change in steroid-toxicity over time. It is used in clinical trials to demonstrate when investigational therapies reduce steroid-toxicity when compared to standard of care in inflammatory diseases.^[4] 

In clinical practice, inducing and maintaining remission of inflammatory diseases often requires long-term steroid treatments that increase the risks of steroid-toxicity related adverse events.^[5,6] While efforts are made to minimize the impact of steroid-toxicity, clinicians are faced with the unenviable task of balancing disease remission against long-term toxicities. 

To complicate matters further, clinicians grapple with high patient volume, limited insurance coverage, the need to manage patients with complex diseases and multiple comorbidities that limit time for additional evaluations.^[3]

Dr Stone and colleagues recognized the need to facilitate monitoring steroid-toxicity in clinical practice settings and hypothesized that an abridged, streamlined version of the GTI could be the solution. 

In a post-hoc analysis of data collected during the ADVOCATE trial, the researchers found that four metabolic GTI domains; body mass index, glucose tolerance, blood pressure, and lipid metabolism, differentiated the two arms of the trial. These four quantitative health domains comprise the GTI-MD and are routinely and easily captured during a typical clinic visit.

The ability of the GTI-MD to reliably identify clinically relevant steroid-toxicity was then tested and validated using two different disease cohorts comprised of asthma patients and autoimmune blistering disease patients. The analyses confirmed the GTI-MD correlates well with the parent GTI.

Steritas is making the GTI-MD available via its FDA 21 CFR Part 11-enabled, HIPAA-compliant platform that can be integrated into electronic health records, enabling automated monitoring of steroid-toxicity without input from physicians. 

The physician is alerted only when the algorithm flags a toxicity warning, minimizing the burden on already stretched clinical practice while preventing treatment-related morbidity, and reducing long-term costs to health systems. 

Using the GTI-MD in digital health applications could also allow patients to track their own GTI-MD scores, motivating them to actively participate in their treatment by advocating for the lowest therapeutically effective dose of steroids.^[3]

References

1. Rice JB, White AG, Scarpati LM, Wan G, Nelson WW. Long-term Systemic Corticosteroid Exposure: A Systematic Literature Review. Clin Ther. 2017 Nov;39(11):2216-2229. doi: 10.1016/j.clinthera.2017.09.011. Epub 2017 Oct 19. PMID: 29055500.
2. Einarsdottir MJ, Ekman P, Molin M, Trimpou P, Olsson DS, Johannsson G, Ragnarsson O. High Mortality Rate in Oral Glucocorticoid Users: A Population-Based Matched Cohort Study. Front Endocrinol (Lausanne). 2022 Jul 8;13:918356. doi: 10.3389/fendo.2022.918356. PMID: 35872995; PMCID: PMC9304700.
3. Patel NJ, Jayne, DRW,  Merkel PA, Bekker P, Zhang Y, McDowel PJl, Johal J, Heaney LG, Murrel D, Stone MN, Yue H, Stone JH, The Glucocorticoid Toxicity Index-Metabolic Domains, an abridged version of the Glucocorticoid Toxicity Index: post-hoc analysis of data from the ADVOCATE trial, The Lancet Rheumatology, Volume 5, Issue 7, 2023, e413-e421, https://doi.org/10.1016/S2665-9913(23)00131-5.
4. Stone JH et al. The glucocorticoid toxicity index: Measuring change in glucocorticoid toxicity over time. Semin Arthritis Rheum. 2022;55:152010.
5. Gale S et al. Risk Associated with Cumulative Oral Glucocorticoid Use in Patients with Giant Cell Arteritis in Real-World Databases from the USA and UK. Rheumatol Ther. 2018;5(2):327-340.
6. Ponticelli C and Locatelli F. Glucocorticoids in the Treatment of Glomerular Diseases: Pitfalls and Pearls. Clin J Am Soc Nephrol. 2018;7;13(5):815-822