Industry Insight
Opportunities to reduce steroid toxicity and embrace new treatment options for autoimmune patients
John Stone at Steritas analyses the benefits that a quantifiable index system can have for researchers looking into steroid toxicity, and how this can allow them to work with larger sets of patient data
Steroids, the common term for glucocorticoids or corticosteroids, play a critical role in the treatment of a range of autoimmune diseases. Through the suppression of physiological pathways associated with inflammatory and immune responses, steroids provide a fast-acting treatment for conditions ranging from asthma and arthritis to Crohn’s disease and rare diseases including vasculitis and myasthenia gravis. However, shortly after their first clinical application in 1948, the first toxicities were reported. The spectre of these adverse effects and the challenges of using steroids safely have cast a long shadow on the treatment of inflammatory diseases that continues to the present day.
Impacts of long-term steroid use
Although the short-term benefits are clear, steroids are not a cure and the side effects of their chronic use can dramatically decrease patients’ quality of life. These side effects range from anxiety and depression to osteoporosis, muscle weakening, hypertension, atrial fibrillation, infection and diabetes. Unfortunately, novel treatments demonstrating the same therapeutic effects are not always accessible and steroids remain the standard of care for many autoimmune diseases.
A seemingly inexpensive steroid treatment must consider the costs of steroid toxicity along with those of the underlying disease. The suffering of patients and the chronic burden on healthcare systems are recognised but rarely appreciated. A recent study highlights this, showing that asthma patients using oral corticosteroids cost healthcare systems significantly more than those who either do not use or only periodically use steroids. In spite of this, 85% of asthma patients were prescribed at least one dose of steroids over a 12-month period, with more than half unaware that alternative therapies are available.1
Quantifying steroid toxicity
A tool capable of quantifying and monitoring steroid toxicity will enhance treatment practices by proactively assessing steroid-treated patients, enabling the early detection of toxicity before it becomes irreversible. The Glucocorticoid Toxicity Index (GTI), developed in 2017 by an international group of 17 physician investigators, provides a standardised measure of glucocorticoid toxicity.2 These experts from multiple subspecialties developed inclusion criteria, selected dynamic side-effects that might be expected to change with adjustments in treatment, assigned weights to each domain, and validated their use in both paper cases and a large, randomised, placebo-controlled trial in vasculitis.3 Health domains included metabolic measures – such as blood pressure, skin toxicity and glucose metabolism – and clinical domains including muscle strength, neuropsychiatric toxicity and infections.
The GTI has also been used in clinical practice in multiple diseases, including asthma and inflammatory arthritis, and has been deployed in more than 30 disease indications overall.4,5,6,7 This tool simplifies the scoring of steroid toxicities and provides a new approach to assessing the effectiveness of novel steroid-sparing therapeutics and steroid tapering protocols.
The future of steroid treatment
The introduction of the GTI as a tool for monitoring steroid toxicity is facilitating advancements in the development of alternative treatments for autoimmune diseases. Novel biologics are facilitating a reduction in steroid dependence. For example, benralizumab, a monoclonal antibody therapeutic used to treat severe asthma, has allowed 80% of trial patients to halve their steroid dosage and 62.9% to eliminate glucocorticoid use entirely, demonstrating the future of autoimmune treatment.5 Other clinical trials of novel steroid-sparing therapies are using the GTI to quantify not simply a reduction in steroid dose but a reduction in toxicity, supporting the early tapering of steroid treatments.7
The GTI has also been applied to neurological diseases using large data sets. Myasthenia gravis, a debilitating autoimmune condition where neuromuscular junctions are affected, is often treated with steroids. A recent study used an abridged version of the GTI that includes the standard four metabolic domains and unmasked data that showed myasthenia gravis patients who received steroids to have significantly greater steroid toxicity scores, which increased further with higher steroid doses.8 Steroid toxicity monitoring can, therefore, inform and direct the course of treatment in individuals suffering from rare diseases as well as common ones. Myasthenia gravis affects fewer than 200 people per million population.9
Empowering patients through shared decision-making
Looking at the growing evidence base, the introduction of steroid toxicity monitoring tools, alongside novel biologic therapies, will improve clinical practices, reducing over-reliance on steroids and relieving the costly impact of steroid toxicities on healthcare systems. In addition to new discoveries in clinical science, patient-facing platforms can educate and equip steroid-treated patients to take ownership of their own health.10 A combined approach of quantitating steroid toxicity in research and supporting shared decision-making between patients and clinicians will facilitate a global shift in steroid-prescribing patterns, improving patient quality of life and minimising healthcare burden.
Author's Opinion:
Despite recent advancements in steroid-sparing therapeutics, too many patients with autoimmune diseases are given steroids and too many are left on them for too long. This heavy--handed treatment leads to dozens of steroid toxicities. Although several successful trials have demonstrated the steroid-sparing effects of alternative medications, routine clinical practice is still over-reliant on steroids, which frequently offer short-term relief but only at the cost of both near-term consequences and long-term suffering.
It is very clear that the ability to measure and monitor steroid toxicity is essential to changing steroid prescribing patterns. Recognising this decades-old challenge, a panel of experts in the field developed the Glucocorticoid Toxicity Index (GTI) as the basis of a set of tools that enable the assessment of steroid toxicity both in clinical trials and clinical practice. The GTI reduces the complexity of steroid toxicity to a score. Thus, it is now possible for researchers to interrogate large sets of patient data to compare the impact of steroids to alternative therapies, providing an evidence-based approach to tackling the steroid toxicity epidemic.
References
- Visit: aafa.org/asthma/asthmatreatment/asthma-treatment-oralcorticosteroids-prednisone/
- Visit: pubmed.ncbi.nlm.nih. gov/35486995/
- Jayne DRW et al (2021), 'Avacopan for the Treatment of ANCA-Associated Vasculitis', The New England journal of medicine, 384(7), 599–609.
- Visit: academic.oup.com/rheumatology/advance-article
- Menzies-Gow A (2022), 'Oral corticosteroid elimination via a personalised reduction algorithm in adults with severe, eosinophilic asthma treated with benralizumab (PONENTE): a multicentre, open-label, singlearm study', The Lancet. Respiratory medicine, 10(1), 47-58
- Menzies-Gow A et al (2019), 'Corticosteroid tapering with benralizumab treatment for eosinophilic asthma: PONENTE Trial' ERJ open research, 5(3)
- McDowell P (2024), 'Longitudinal Assessment of Glucocorticoid Toxicity Reduction in Patients With Severe Asthma Treated With Biologic Therapies', The journal of allergy and clinical immunology: in practice, pS2213-2198(24)
- Phillips G (2024), 'Adaptation of the Glucocorticoid Toxicity Index-Metabolic Domains to Electronic Health Records to Evaluate Steroid Toxicity in Adults with Myasthenia Gravis in the United States', Value in Health, S399(27)
- Visit: pmc.ncbi.nlm.nih.gov/articles/PMC8196750/
- Visit: acrabstracts.org/abstract/apatient-focused-program-for-usingsteroids-wisely/
John H Stone MD MPH graduated from Harvard Medical School and completed his internal medicine training at Johns Hopkins Hospital, both US. He trained in rheumatology at the University of California-San Francisco, US. Dr Stone is currently a Rheumatologist and Professor of Medicine at Harvard Medical School, and the Edward A. Fox chair in Medicine at Massachusetts General Hospital. Dr Stone is chair of the Scientific Advisory Board at Steritas.
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