On September 4, 1948, the first dose of a glucocorticoid was administered to a bed-ridden 24-year-old woman with rheumatoid arthritis. The treatment of rheumatoid arthritis with cortisone resulted in a dramatic improvement in the levels of inflammation, function and sense of well-being. That patient’s ability to rise from bed and walk the following day astonished her physicians and ultimately marked a new era in the lives of millions of patients around the world.
Just 23 days after the first dose of steroid, the first toxicities of this new therapeutic approach were reported. The next day, the first steroid taper began.
By 1960, the full range of 80+ steroid-toxicities had been described. Although debates raged about the proper use of steroids, by then the drugs had become entrenched as “necessary evils” in the struggle to manage inflammatory disease. The challenges of measuring and monitoring such a wide range of toxicities were not even approached until 2016 when a group of subspecialty experts from around the world convened to develop the Glucocorticoid Toxicity Index (GTI) - a validated clinical outcome assessment that captures and quantifies the nuances of change in steroid-toxicity.
The development of the GTI led to the founding of Steritas and the creation of an eCOA suite (electronic clinical outcome assessments). The collection includes the GTI, the pGTI (pediatric), and the GTI-MD (a point-of-care instrument).
“The GTI was first used by Chemocentryx in the ADVOCATE trial, a study of avacopan in ANCA-associated vasculitis, which reported results in 2021. That trial demonstrated the superiority of avacopan to a prednisone-based standard of care with respect to sustained remission. In addition, use of the GTI as the most important secondary endpoint for efficacy confirmed the superiority of avacopan over standard of care for glucocorticoid toxicity reduction at both 13 and 26 weeks,” said Martha N. Stone, CEO of Steritas.
Avacopan was approved as an adjunct to the standard approach for remission induction that same year.
“Since the ADVOCATE trial, Steritas has licensed the GTI in more than 20 diseases across 80 countries for use in industry and academic research. Several industry trials using the GTI are reporting soon,” Ms Stone adds.
Because steroids are so effective at reducing inflammation quickly - albeit at significant cost of patient suffering and healthcare expense - proving superiority, or at least non-inferiority, of newer, more targeted therapeutics, has been a key challenge for pharmaceutical companies. The Steritas eCOA suite enables researchers to demonstrate that more targeted approaches are as effective and have improved safety profiles compared to glucocorticoids.
The pGTI provides a systematic approach to assessing steroid-toxicity in children between the ages of 2 and 18 years and does so with special attention paid to growth impairment.
The addition of the GTI-MD enables clinicians to monitor steroid-toxicity at point-of-care through seamless integration into existing clinical workflows. The GTI-MD also has a role to play in interrogating health insurance claims and EHR datasets to understand the implications of steroid-toxicity across populations.
“I believe the very commitment to measuring steroid-toxicity in the clinic will begin to alter prescribing patterns. It's vital to see how patients are doing over time and adjust steroid dosage before it causes lasting harm,” comments Ms Stone.
She continues to explain how she hopes that by measuring steroid-toxicity at point of care, clinicians will be better positioned to adopt best practices.
“In a clinical trial protocol involving a new therapy, a steroid taper may be from 60 mg/day to zero in just 12 weeks. Clinical experts submit that in practice we taper patients much more slowly - perhaps 60 mg/day to a maintenance dose of 5 mg/day over the course of a year. This can be due to fears of disease flares, or lack of a method to measure steroid-induced harm.”
An opportunity for implementation is to avoid additional burden to the clinician that is already overstretched while making sure the deleterious effects of the treatments are recognized and monitored closely. There will need to be a system-wide change so that everyone treated at a certain dose of glucocorticoid is automatically measured and monitored in the background and clinicians can alter their prescribing behavior when they are alerted to worsening toxicity from steroid exposure.
This will provide an educational opportunity, which Steritas is currently working on with a range of partners, as there is currently no unifying source of information about steroid-toxicity available in a patient-friendly format.
“Since its founding, Steritas has been leading conversations about steroid-toxicity and, as the 75th anniversary of the first steroid dose approaches, is aiming to play its part in shifting prescriber behavior.
We like to think that our work in this area is somehow a new phenomenon. But the effort to lower steroid exposure really started in 1948 with the report of the first toxic side-effect.
Every doctor, patient, medical director, and academic researcher since then has been playing a role in lowering steroids to the minimum therapeutically effective dose to reduce harm to the patient. Steritas’ role is to bring attention to steroid-toxicity, to measure it, and monitor it, not just in the research, but in the clinic, and then to engage many of the 50 million adults on chronic glucocorticoid treatment. These are just some of ways we can begin to hold steroids accountable.”
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