Oral corticosteroids (OCS) are widely used and effective in treating chronic inflammatory conditions such as arthritis, asthma, and autoimmune diseases. They work by reducing inflammation, relieving pain, and calming the immune system. However, more than 1 in 10 patients develop side effects, especially when steroids are used for a long period of time. Until now, it has been difficult to identify people who would react in this way, but research to be presented today (Sunday) at the annual meeting of the European Society of Human Genetics shows that incorporating genetic data into steroid prescriptions could improve risk prediction and allow doctors to prescribe better.
Dr. Deniz Turkmen, a postdoctoral researcher at the AGE Group at the University of Exeter in Exeter, UK, and his colleagues studied data from around 38,000 UK Biobank participants who had been prescribed steroids. They calculated how much steroid each took over time. Whether higher doses are associated with more side effects. We investigated whether genetic differences could help explain who is at risk. And finally, we tested whether adding genetic information would improve risk assessment. They found that certain genetic mutations increase the risk of side effects in patients treated with steroids. CYP3A4 osteoporosis and CTLA4 Especially for strokes and cataracts.
We were also able to show a clear relationship between steroid dosage and side effects. This precise analysis shows the increased risks associated with long-term treatment. ”
Dr Deniz Turkmen, Postdoctoral Researcher, University of Exeter AGE Group, Exeter, UK
By incorporating a polygenic risk score (PRS) for osteoporosis, researchers were able to further improve steroid risk assessment. This improvement exceeded routinely available factors such as age and gender, and was particularly pronounced in younger people at the time of first prescription. “Currently, in the absence of efficient predictive methods, clinicians seek to reduce risk by using only short-term steroids, prescribing the lowest possible doses, or switching to steroid-sparing alternative treatments such as biologics. However, biologic treatments are often more expensive and not readily available to all patients. These strategies may also be inadequate for individuals with chronic conditions that require repeated or long-term steroid treatment. Routine use of genetic information could in the future mean that high-risk patients can be identified and administered earlier, either by choosing steroid-sparing treatments or closely monitoring side effects, she says.
Given the widespread use of steroids, large-scale implementation of PRS in their formulation will be a major challenge. The most practical use is likely to be in high-risk populations, particularly those whose steroid use may be long-term. The findings need to be studied in other cohorts to ensure they have broader applicability, the researchers said. Larger and more ethnically diverse populations may also enhance predictive performance, as the pharmacogenetic effects observed in this study are consistent with other biological mechanisms influencing steroid metabolism and immune responses.
“We expected to find a clear relationship between dose and adverse outcomes. Although we were reassured that the genetic findings for CKD were consistent with their role in steroid metabolism and immune regulation, the improvement in osteoporosis prediction when incorporating polygenic risk score data was particularly pronounced in younger patients. Although the impact has been relatively limited, we hope that traits such as bone density will improve risk prediction and, over time, increase the availability of genetic data at a population level, allowing us to integrate genomics into everyday medical care, which will be a major step toward providing personalized medicine for everyone.”
Professor Alexandre Raymond, chair of the conference, who was not involved in the study, said: “We are now seeing more and more examples of estimates that combine the predicted risk for rare, high-impact variants with the risk for common, low-impact variants.”
sauce:
European Society of Human Genetics
