Expert cautions: 'No set of criteria can replace clinical judgment'
DESTIN, Fla. — In a session here, Ronald F. van Vollenhoven, MD, PhD, of the Amsterdam University Medical Center, discussed the clinical utility of biomarkers to diagnose, predict disease activity and guide treatment decisions in rheumatoid arthritis and systemic lupus erythematosus.
“RA is everywhere you look,” he said. “It’s a common disease and it’s a good thing we’ve already made so much progress improving people afflicted by this disease, especially over the last 20 to 30 years; lots of things have happened.”
According to van Vollenhoven, biomarkers currently available for the diagnosis of RA and those used to assess inflammatory activity — such as CRP or ESR — are effective. However, additional biomarkers are needed to assess the risk for progressive disease and to help clinicians choose therapies, especially as more treatments become available, he said.
Vectra DA (Crescendo Bioscience), a multi-biomarker disease activity (MBDA) panel marketed in the U.S., has been shown in clinical trials to be a marker of disease activity and radiologic progression in early-stage RA. Specifically, patients with low MBDA levels at baseline are less likely to experience radiologic progression with irreversible changes within 2 years of diagnosis. Conversely, patients with high MBDA at baseline are at 20% to 30% higher risk for significant radiographic progression.
According to van Vollenhoven, knowing whether a patient has lower or higher levels can help guide treatment decisions in terms of initiating conservative or aggressive therapy.
SLE is a disease characterized by serum abnormalities; therefore, biomarkers are commonly used and there are a host of options. The test holding the most interest is the anti-dsDNA, according to van Vollenhoven. It is a good indicator of disease activity and nephritis risk, and higher titers have been shown to predict flare, he said.
Additional biomarkers include anti-C1q antibodies, BLyS, C3, C4, CH50 and EC4D, among others.
Lastly, van Vollenhoven discussed the surge in development of criteria for all kinds of diseases, frequently under the auspices of American College of Rheumatology and/or EULAR. While in the past, criteria were sometimes labeled “diagnostic,” more recently they are labeled “classification” to emphasize that they should not be used to make a diagnosis.
“My personal opinion is that won’t work,” he said. “If you publish criteria, you can call it what you want, but people will look at them to make a diagnosis. It’s inevitable, and I don’t think it’s necessarily to have the criteria be part of diagnostic process, but you can’t blindly apply them. ... I don’t think it helps to quibble about whether it’s classification or diagnostic; to me, it seems more a question of how you approach the use of criteria.”
In 2012, van Vollenhoven and colleagues developed the SLICC criteria for SLE, which includes a list of both clinical and immunological criteria. Like ACR, patients must have at least four features of disease, including one clinical and one immunological. Though the sensitivity of SLICC is marginally better than the ACR criteria, it still isn’t enough to make a diagnosis with confidence, he said.
New, unpublished criteria for SLE supported by both ACR and EULAR were recently presented. These state that a patient can be classified as having lupus if (s)he has positive ANA and at least 10 points from a list of other clinical criteria. Though they performed a bit better than the ACR and SLICC criteria, van Vollenhoven cautioned that “no set of criteria can ever replace the clinical judgment by an experienced clinician.”
A similar sentiment applies to treatment recommendations, or guidelines.
“We need to use our clinical judgment, insights and wisdom and art of practicing medicine and rheumatology. Practice medicine as though it’s ... an art, but also remember the science.” – by Stacey L. Adams
van Vollenhoven R. Biomarkers in systemic lupus & rheumatoid arthritis. Presented at: Congress of Clinical Rheumatology; May 2-5, 2018; Destin, Florida.
Disclosure s : van Vollenhoven reports research grants from AbbVie, BMS, GlaxoSmithKline, Pfizer and UCB; consulting fees from AbbVie, AstraZeneca, Biogen, Biotest, Bristol-Myers Squibb, Celgene, Gilead, GlaxoSmithKline, Janssen, Eli Lilly, Novartis, Pfizer, Servier and UCB; and speaking fees from AbbVie, Eli Lilly, Pfizer and UCB.