Lihi Eder, MD, PhD, on Genetic Testing in the Diagnosis of Psoriatic Arthritis

Determining whether genetic testing can be used to predict the diagnosis of psoriatic arthritis (PsA) by a rheumatologist in a clinical setting is important, considering the reduced costs of genetic testing and the lack of reliable, objective biomarkers for PsA.

In a new study, Lihi Eder, MD, PhD, an assistant professor of medicine at the University of Toronto and a scientist at Women’s College Research Institute in Toronto, Ontario, and colleagues investigated whether a rheumatologist can use a custom multiple single-nucleotide polymorphism genetic test to predict a PsA diagnosis in patients with psoriasis with musculoskeletal symptoms.

Results showed that despite the association of several genetic markers with PsA, genetic testing had a modest effect on predicting a diagnosis of PsA in this patient population.

Rheumatology Consultant caught up with Dr Eder at the 2019 American College of Rheumatology (ACR)/Association of Rheumatology Professionals (ARP) Annual Meeting, where she presented the research.

Rheumatology Consultant: What prompted you to conduct your study?

Lihi Eder: We know that there is a strong genetic component for both PsA and psoriasis. Some studies have suggested that the familial aggregation might be stronger for PsA than in psoriasis. This triggered genetic studies within our group in Toronto, Ontario, to identify specific markers for PsA in patients with psoriasis that could potentially help with early diagnosis or identify people that are at high risk of developing PsA in the future. Previous work from our group suggested that there were a few genetic markers, particularly within the human leukocyte antigen region, that discriminate between patients with PsA and patients with psoriasis without arthritis. So, we decided to test this in a clinical setting. One of the study coinvestigators, Proton Rahman, MD, from the Memorial University of Newfoundland in St. John’s, developed a genetic panel for this study that included 42 variants in or near 20 genes based on genome-wide significance in PsA studies.

RHEUM CON: What are the key findings from the study that are important for rheumatologists to know?

LE: Every patient with psoriasis with musculoskeletal symptoms seen in the clinic at the Women’s College Hospital in Toronto, Ontario, underwent testing with our genetic panel. We hoped our genetic test would improve the early detection of PsA among patients with psoriasis. Unfortunately, it did not perform as well as we thought it would. The test’s specificity was very high, but the sensitivity was relatively low, which is not good for a screening tool. When you have a screening tool, you want it to be very sensitive. We also tried to combine the genetic test with certain clinical symptoms or blood test for Inflammatory markers to improve specificity. While it improved the specificity a little bit, it was not enough to be a good modality for screening of PsA in patients with psoriasis. This tells us that we need to find better biomarkers.

Study limitations, key takeaways >>

RHEUM CON: What was the biggest limitation of the study?

LE: The study would have been better if the sample size was larger. Also, this was a single-center study, as well as a pilot study, so you always want to try and have a multicenter study to make sure that the results apply for different populations. However, since our study showed that this genetic test has significant limitations in serving as a screening tool for PsA, we will have to consider whether we will pursue additional research using this tool.

RHEUM CON: What is the key takeaway of the study for rheumatologists?

LE: We can learn from negative study results. The key takeaway for rheumatologists is that we need to consider PsA in every patient with psoriasis with musculoskeletal symptoms. Also, genes do not change in life, they are fixed. The genes might teach us about some of the mechanisms of PsA, but they will not help us identify which patients will develop PsA or necessarily help us make clinical decisions. We need more studies looking at other objective tests or biomarkers that are more dynamic in this patient population.

Reference:

Eder L, Li Q, Jerome D, Farrer C, Rahman P, Burry TN. The performance of a multi-marker genetic test to identify patients with psoriatic arthritis among psoriasis patients [abstract 2452]. Arthritis Rheumatol. 2019;71(suppl 10). Presented at: 2019 ACR/ARP Annual Meeting; November 8-13, 2019; Atlanta, GA. https://acrabstracts.org/abstract/the-performance-of-a-multi-marker-genetic-test-to-identify-patients-with-psoriatic-arthritis-among-psoriasis-patients/. Accessed December 2, 2019.

For more on PsA, visit the Center of Excellence.