A pioneering analysis of electronic health record (EHR) data from the Optum® EHR database has shown that it is finally possible to quantify the risk-to-benefit ratio of prescribing glucocorticoids, achieving a result that has, until now, eluded health economics outcome researchers (HEOR).
Using the Steritas GTI-MD, a team comprised of researchers from Harvard Medical School, Argenx, ZS Associates, and Steritas showed that steroid-toxicity is significantly higher in myasthenia gravis (MG) patients with higher strength and repeated steroid usage.[1]
The ability to accurately measure the impact of steroids not only enhances patient outcomes but also paves the way for the development and approval of new, more effective medications. This breakthrough is expected to drive innovation and investment in pharmaceuticals, offering substantial economic benefits to the healthcare industry.
Myasthenia gravis is an autoimmune disease in which the immune system attacks neuromuscular junctions, causing muscle weakness. The disease was first described as long ago as the 1670s, but the term myasthenia gravis – meaning grave muscle weakness – wasn’t used until the 1880s. Myasthenia gravis is an uncommon disease with a prevalence of about 14 cases per 100,000 in the US, meaning there are fewer than 100,000 patients in the US.[2]
Glucocorticoids are the front-line therapy for patients with myasthenia gravis, due to their fast-acting immunosuppressive and anti-inflammatory effects. The benefits of glucocorticoid use in this disease are, however, tempered by the side effects associated with both short- and long-term use, including osteoporosis, hyperglycemia, and adrenal suppression.
The ability to quantify steroid-toxicity is therefore critical in informing drug development investment decisions and supporting the economic rationale behind new therapeutic launches.
The GTI-MD measures steroid-toxicity changes over time with two scores: the cumulative worsening score (CWS) and aggregate improvement scores (AIS).
This retrospective, real-world study was conducted via the US-based Optum® EHR database (with all lab values required by the GTI-MD algorithm), using data collected between January 2013 to December 2022. The key inclusion criteria were:
- ≥18 years of age with at least 2 MG terms used in the medical record diagnosis codes (≥30–≤730 days apart)
- Prescription of glucocorticoids for treatment of MG
- Follow-up 1-year post 90-day steroid exposure
The study compared the CWS and AIS over time in two age/gender-matched groups of patients:
- Steroid initiators (n=377; intervention)
- Steroid naïve (n=305; control)
In addition, the study evaluated differences in glucocorticoid toxicity among patients in the steroid initiators group who received multiple courses of glucocorticoids during the period of interest as opposed to only one course, and in the group of patients whose daily prednisone dose began at > 20 mg/day as opposed to < 20 mg/day.
The GTI-MD effectively quantifies steroid-toxicity from EHRs
GTI-MD scores were higher in the steroid-initiated group, with a CWS of 22.6 compared to a CWS of 18.7 (p < 0.05) in the steroid-naive group, indicating worse steroid-toxicity in the group that initiated glucocorticoids. The steroid-initiated cohort exhibited a significant difference in worsening for the BMI domain and a greater proportion of patients exceeding the minimal clinically important difference (MCID) compared to the steroid-naïve cohort.
Even more telling were subgroup analyses among the steroid-initiating group. Among the steroid-treated patients who received multiple prescription refills during the period of interest as opposed to only one refill, both the CWS and AIS scores were higher in the multiple dose group, again indicating higher steroid-toxicity in that group. The CWS values between the two groups were 25.7 (multiple-course group) versus 19.2 (single-course) (P < 0.05), and the AIS values were 9.6 and -0.3 (P < 0.5) for the multiple-course and single-course patients, respectively. Similar findings were observed among patients whose prednisone started at doses > 20 mg/day as opposed to < 20 mg/day. In addition, higher percentages of patients in the multiple-course group exceeded the MCID difference for steroid-toxicity for both the CWS and AIS values.
These results demonstrate the ability of the GTI-MD to quantify steroid-toxicity from an EHR. The study further demonstrates that the GTI-MD is a practical tool for monitoring glucocorticoid-related adverse events in patients with myasthenia gravis and facilitating informed treatment decisions.
The ability to calculate steroid-toxicity from electronic records also makes the GTI-MD ideal for health economic and outcomes research studies utilizing large data sets to help drug developers and healthcare decision-makers get a better picture of how glucocorticoid toxicities influence the value, cost and cost-effectiveness of available treatments.
The authors believe that further research should be carried out to explore the ability of the GTI-MD to predict steroid-toxicity and reduce the long-term burden of steroids in other therapeutic areas. As outlined by Dr Gelinas, the GTI is an important tool in the development of new steroid-sparing therapies and for guiding the steroid-taper process to benefit patients.
References
- Phillips G, Stone JH, Qi CZ, Stone M, Gelinas D, Chamberas A, Amirthaganesan D, Kulkarni R and Whangbo A. 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, Volume 27, Issue 6, S1 (June 2024)
- Myasthenia Gravis – Muscular Dystrophy Association (USA). https://www.mda.org/disease/myasthenia-gravis accessed May 2024
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