Tools May Predict Inflammatory Arthritis in At-Risk Patients

Lucy Hicks

August 02, 2023

Two scores, one simple and one comprehensive, may predict inflammatory arthritis (IA) in people who are already at elevated risk for these immune-related conditions, according to new research from England.

If validated in further studies, a new simple score using common biomarkers may help identify individuals who can be managed in primary care as well as higher-risk patients who should be referred to a rheumatologist.

The researchers designed a second comprehensive score adding genetics and ultrasound as a tool to identify patients at highest risk for IA for intervention studies and to guide clinical monitoring and care by specialists.

Dr Kevin Deane

Though there are blood markers and early symptoms in patients that may signal a higher risk for IA, "we don't know what to do with those people yet," said Kevin Deane, MD, PhD, associate professor of medicine and chair in rheumatology research at the University of Colorado Anschutz Medical Campus in Aurora.

"Understanding how to assess these people and predict who's going to go on to get full blown IA that we should actually treat is very beneficial to the field," Deane said. He was not involved with the research but had reviewed an early draft of the paper.

Study Seeks to Stratify At-Risk Population

For the study, researchers recruited 455 participants from June 2008 to November 2021, primarily through the UK Primary Care Clinical Research Network. All individuals had new musculoskeletal symptoms, a positive test for anticitrullinated protein antibodies (anti-CCP), and no clinical synovitis.

The researchers selected for anti-CCP positivity because these antibodies are associated with a more aggressive arthritis phenotype. Interventional trials have also found that these anti-CCP–positive individuals are the most responsive to disease-modifying antirheumatic therapy prior to IA development. Patients were followed for at least 48 weeks or until an IA diagnosis.

Using data from this cohort, the team ran statistical analyses guided by potential clinical impact. For the simple score, they aimed to ensure that most people who would go on to develop IA would be identified earlier in clinical practice. For the comprehensive score, they wanted to balance the potential harm of giving preventive treatment to someone who would not develop IA with failing to provide preventive treatment to someone who would develop IA, the authors write.

They developed two scores: a simple score to identify people at lower risk for IA and a comprehensive score to stratify high-risk individuals. The simple score used anti-CCP level, rheumatoid factor value, early morning stiffness, and erythrocyte sedimentation rate to calculate risk.

In addition to these factors, the comprehensive score added smoking history, ultrasound abnormalities, genetic markers for the rheumatoid arthritis shared epitope, as well as patient-reported outcomes from the Health Assessment Questionnaire and the visual analogue scale for global pain.

The study was published in the Annals of Internal Medicine on August 1, 2023.

Simple Score Rates More Than Half as Low Risk

The simple score identified 249 low-risk individuals, defined as having a less than 10% chance of developing IA within 1 year, with a 5% false-negative rate. This score can help determine which individuals do not need to be referred to a specialist even though they have some known risk factors, said Paul Emery, MD, director of the Leeds Biomedical Research Centre and clinical professor at the University of Leeds School of Medicine in England. He is a co–senior author of the research.

Dr Paul Emery

"If you had unlimited resources, you'd refer everyone. But in the real-world, we would be overloaded in secondary care, and it just wouldn't work," he said. "This is a way of making sure the right people are referred into secondary care."

The comprehensive score identified 119 high-risk individuals, defined as having a 50% chance or greater of developing IA in 5 years, with a false-positive rate of 29%. Of this high-risk group, 40% developed IA within 1 year, and 71% developed IA in 5 years.

Beyond identifying those who should be referred to specialist care, Emery noted that this score could be used in research studies to find patients for experimental clinical trials aimed at delaying or preventing the onset of IA.

Both Emery and Deane agreed that further research is needed to validate these findings in different patient populations as well as to understand how the scores could be integrated into clinical practice.

What Is the Role of Anti-CCP Tests in Primary Care?

The study also brings up additional questions about the use of anti-CCP tests in primary care, Deane said. Though previously considered a "specialty test" 10-15 years ago, "now, we really want primary care to do this test along with the rheumatoid factor test," he noted.

Because the study only included individuals with anti-CCP antibodies, it did not touch on which patients should be getting tested in the first place. Would all patients coming into primary care with joint pain benefit from these blood-marker tests, Deane asked, or would only certain patients qualify? "I think that's uncertain, and we need to learn more," he said.

An additional caveat is that the researchers used abnormal ultrasound findings as a predictor of future IA in the comprehensive model, but many clinicians already use ultrasound to identify arthritis, Deane said.

"If a rheumatologist sees power doppler signal or erosions, even if the physical examination of a joint didn't find swelling or inflammation, then they are likely to say that this person has IA now," and will start treatment, he said. "Because of that, it could be challenging to use ultrasound as a 'predictive' marker in clinical practice," he added, but additional research could help elucidate when to wait on treatment even with abnormal ultrasound findings.

This study was funded by the UK National Institute for Health and Care Research Leeds Biomedical Research Centre. Emery disclosed financial relationships with AbbVie, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Galapagos, Gilead, Novartis, and Samsung Bioepis. Deane reports receiving consulting fees from Werfen.

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