Despite their seemingly miraculous efficacy, the long-term adverse effects of glucocorticoids pose significant challenges. This reality led Ali A. Habib, MD and Pushpa Narayanaswami, MD to author an editorial in the journal Muscle and Nerve, asking, “Would glucocorticoids be approved if discovered today?”[1]
First discovered in the late 1940s, steroids revolutionized medicine by providing rapid and effective relief for a wide range of autoimmune and inflammatory diseases. Drs Philip S. Hench, Edward C. Kendall, and Tadeus Reichstein, who identified these hormones, were awarded the 1950 Nobel Prize in Medicine.
Since their discovery, steroids have become a keystone treatment for autoimmune and inflammatory diseases, as their ability to swiftly and effectively bring symptoms under control often makes them indispensable. However, the persistence of these conditions frequently necessitates long-term use, increasing the risk of steroid-toxicities.
Tracking the Toxicities
The first side effects of steroids were recognized shortly after their clinical introduction. Patients treated with glucocorticoids in the 1950s exhibited significant adverse events, including cushingoid appearance and psychosis. Over time, other serious steroid-toxicities have been well documented, including osteoporosis, cardiovascular complications and infection risks. Despite these risks, formal guidelines to manage these effects only emerged decades later, reflecting a historical underestimation of their severity.
The authors cite a recent study[2] that surveyed Canadian neuromuscular neurologists to assess their practices in managing chronic glucocorticoid therapy. Findings revealed substantial variability in screening, monitoring and prophylaxis against steroid-toxicity. While most clinicians discussed risks like osteoporosis and hyperglycemia with their patients, there was inconsistency in vaccination recommendations and other preventive measures.
Improving the Management of Glucocorticoids
Addressing the adverse events of glucocorticoids requires coordinated efforts across specialties. Clear delineation of responsibilities among prescribing clinicians, primary care providers and specialists is crucial. Utilizing electronic health records with automatic reminders and clinical decision-support tools can enhance the monitoring and management of steroid-toxicities. The authors also suggest adopting validated tools like the Steritas Glucocorticoid Toxicity Index (GTI) to track and mitigate effects in the clinic.
Would Glucocorticoids Pass Modern Regulatory Scrutiny?
According to the authors, the extensive adverse events caused by glucocorticoids make it debatable whether they would pass modern regulatory scrutiny. Current clinical trials would bring into question whether the risk-benefit ratio of these powerful drugs would make their development viable. If a more recent medication were to cause such significant adverse events, would it be withdrawn from the market?
While glucocorticoids remain a cornerstone in treating autoimmune and inflammatory diseases, their use today necessitates a careful, informed approach. Incorporating guidelines from related specialties, employing advanced monitoring tools, and fostering interdisciplinary collaboration are essential steps in optimizing glucocorticoid therapy.
The authors stress that, given the hazards associated with glucocorticoids, their use should be approached with caution. Thorough patient education and rigorous monitoring should be ensured to balance their benefits against the harms.
References
- Habib AA, Narayanaswami P. Would glucocorticoids be approved for clinical use if discovered today? Muscle Nerve. 2024 Jul;70(1):9-11. https://doi.org/10.1002/mus.28111 Epub 2024 May 8. PMID: 38720486.
- Stepanian L, Laughlin R, Bacher C, et al. Chronic glucocorticoid management in neuromuscular disease: a survey of neuromuscular neurologists. Muscle Nerve. 2024;70(1):52-59. https://doi.org/10.1002/mus.28069
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