SLE research is progressing at a rapid rate, with recent discoveries about diagnostic and prognostic tools holding the potential to revolutionize lupus management. During the Tuesday session Emerging Biomarkers: Precision Medicine in Lupus, Jill Buyon, MD, reviewed these advances and their potential clinical applications.
“We’re at a very timely and exciting place in rheumatology right now as we learn more and more about new and emerging biomarkers and the potential for delivering precision medicine in lupus,” said Dr. Buyon, Professor of Medicine and Director of the Lupus Center at New York University School of Medicine/New York University Langone Health.
“The major obstacles we face in biomarker discovery, validation, and precision in lupus, however, are inherent in the disease itself, with population and phenotypic heterogeneity.”
Further complicating the challenge, she said, is the addition of a third major set of classification criteria — the ACR/EULAR criteria.
“The nature of lupus would suggest, because clinical expression is diverse and severity is variable, that there might be 333 patients that are actually different phenotypic subsets,” Dr. Buyon said. “And these criteria involve the skin, the serosa, arthritis, nephritis, cytopenias; therefore, we would predict that there are multiple components of the innate and acquired immune system that are likely to be candidate biomarkers, from the cells to the cytokines to the autoantibodies.”
The “holy grail” in the quest to identify and validate new biomarkers, she said, is the hope that biomarkers will fulfill certain promises — that they will aid the clinician in managing the patient, help to sort out phenotypic heterogeneity, inform about pathogenesis, and provide targets for therapy to achieve “biomarker coverage.”
“Biomarkers should be considered in the context of what they are being used for, i.e. diagnostic, prognostic, or predictive categories,” Dr. Buyon said. “Practical application of biomarkers to patient care and decision making will likely require a panel of tests that can be compiled into an ‘index’ that provides a level of certainty — possible, probable, or definite — in an individual patient with regard to diagnosis, prediction of flare, choice of therapy and response, and/or overall prognosis.”
Other categories of biomarkers, she said, include pharmacodynamic biomarkers — which are highly relevant to clinical trials, as they can identify at-risk populations, inform biologic effects of a drug and confirm target has been hit, and carry the expectation that if target is treated it will associate with clinical benefit — and menopausal biomarkers, which she said do not represent a target but rather an ineffective feedback loop initiated in a futile response to an injured tissue.
“All in all, technology is moving faster than we can recruit patients for evaluation,” Dr. Buyon said. “Transcriptome analysis of whole blood or targeted immune cells and the diseased organs themselves deliver the promise of precision medicine.”