A new study published in ACR Open Rheumatology¹ by clinical researchers from Massachusetts General Hospital in Boston has found it is possible to evaluate the risk of a patient encountering future glucocorticoid toxicity; paving the way for the development of risk prediction models for steroid-related adverse effects.

This is the first time an approach for determining the overall potential for glucocorticoid toxicity has been established for patients and is an exciting development for patients with autoimmune inflammatory diseases. The researchers believe baseline steroid-toxicity assessment could help guide clinical decision-making about starting steroid-sparing immunosuppressive therapies that improve patient outcomes.

The team, led by John Stone MD. MPH, Edward Fox Chair of Medicine and Professor of Medicine at Harvard Medical School and principal developer of the Steritas Glucocorticoid Toxicity Index (GTI), retrospectively analyzed baseline glucocorticoid-related toxicity scores of giant cell arteritis patients enrolled in the GiACTA trial (Tocilizumab in Giant Cell Arteritis) and compared differences between those with newly-diagnosed disease versus those with relapsing disease.

"Many patients are already veterans of steroids by the time they are started on a steroid-sparing agent. Most, in fact, may have been treated for months or even years with just steroids alone for whatever their problem is. As a result, patients starting new therapies ALREADY have toxicity from their previous treatment,” says Dr Stone.

Data collected from 250 giant cell arteritis patients in the GiACTA trial were analyzed with baseline steroid-toxicity scores calculated for twelve domains derived from the Steritas GTI. Scores were calculated using data from patients’ medical history, vital signs, baseline medications, and laboratory values. 

The twelve domains examined were body mass index, glucose tolerance, blood pressure, lipid metabolism, bone/tendon, glucocorticoid myopathy, skin toxicity, neuropsychiatric effects, infection, ocular toxicity, gastrointestinal injury, and adrenal function. The Boston team found the domains that contributed most to overall scores were blood pressure, glucose tolerance, and neuropsychiatric effects. 

The scores for newly diagnosed (and therefore somewhat steroid naive), and relapsing disease, were compared. Baseline glucocorticoid toxicity scores were found to be higher in patients with relapsing disease compared to those with newly-diagnosed disease, enabling the two groups to be distinguished from one another. The body mass index and neuropsychiatric domain scores were significantly higher in patients with relapsing disease.

The data showed that body mass index for patients with relapsing disease was higher than that of the general population at the time of enrollment. The investigators hypothesize this is primarily due to prior exposure to glucocorticoids, although there may also be a bidirectional relationship in which body mass index may impact the risk of relapse of giant cell arteritis.

Dr Stone postulates “the Baseline Glucocorticoid Toxicity Score (BGCTS) may be a useful predictor of patients at risk for further steroid-toxicity if these agents are not used carefully. I can envision the day, in fact, that a high BGCTS is used as an appropriate justification for using less prednisone at the start of treatment or strong rationale for beginning a steroid-sparing agent early, with the goal of discontinuing prednisone altogether at the soonest possible time."

Read the full article: ACR Open Rheumatology

References

1. Patel, N.J., Fu, X., Zhang, Y. and Stone, J.H. (2023), Baseline Glucocorticoid-Related Toxicity Scores in Giant Cell Arteritis: A Post Hoc Analysis of the GiACTA Trial. ACR Open Rheumatology. https://doi.org/10.1002/acr2.11520