Liam O'Neil, MD, on Rheumatoid Arthritis Among First-Degree Relatives of First Nations RA Patients

Dr O'Neil discusses his research into assessing risk of developing rheumatoid arthritis (RA) among first-degree relatives of First Nations patients who have RA.

Liam O'Neil, MD, is an assistant professor of medicine and researcher at the University of Manitoba in Winipeg, Manitoba, Canada.

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TRANSCRIPT:

Liam O'Neil:  My name is Liam O'Neil. I am a rheumatologist and a clinician scientist, an assistant professor of Medicine and Immunology at the University of Manitoba. Today, I'm going to discuss a recent publication in The Journal of Rheumatology called Functional Disability to Evaluate the Risk of Arthritis in First-degree Relatives of Patients with Rheumatoid Arthritis.

First, I wanted to describe why we study First Nations as it pertains to rheumatoid arthritis risk. There's a strong genetic predisposition to develop future rheumatoid arthritis in First Nations. There's an increased prevalence of the disease, potentially due to known environmental risk factors such as smoking cigarettes and periodontitis.

First Nations develop a unique disease phenotype. Their age of onset is earlier than other populations. They typically develop treatment-resistant disease and substantially more large joint involvement which leads to functional problems.

A cohort was established by Dr. Hani El-Gabalawy, who's my mentor, was funded by the Canadian Institutes of Health Research more than a decade ago of first-degree relatives, which is what this publication is based on.

These are first-degree relatives that are identified through our study and enrolled into a longitudinal study. Individuals with rheumatoid arthritis are asked to recruit their first-degree relatives to partake and better understand rheumatoid arthritis risk.

We know that most individuals who develop anticitrullinated protein antibodies, or ACPA, are at high risk to develop disease. These are the antibodies that are found in individuals with established rheumatoid arthritis. It's well-known now that they actually begin to develop well before the disease onset.

This is what we consider to be a good biomarker to predict or identify individuals who are at particularly high risk. Individuals who have these antibodies may exhibit symptoms that are typical of rheumatoid arthritis, such as joint pain or stiffness. It's not well-understood the importance of the symptoms and how they relate to arthritis risk.

The major findings from our publication are the following. We identified that self-reported joint symptoms and functional disability is more prevalent in first-degree relatives of patients with rheumatoid arthritis compared to non-first-degree relatives.

We use a modified HAQ questionnaire, which is short for the health assessment questionnaire, which asks day-to-day functioning questions such as getting in and out of the car or bending over. A standard HAQ score is basically a summary score of the level of disability across these functional domains.

The finding that first-degree relatives of RA patients actually have higher joint symptoms and functional disability was never been shown before. We're interested to understand this a little bit more.

It may have something to do with the perception of first-degree relatives knowing somebody who has rheumatoid arthritis, someone typically that's close to them, understanding the symptoms of arthritis and understanding their own risks.

The next important thing that we found was that ACPA-positive, or anti-citrullinated-protein antibody positive. We were interested in finding that first-degree relatives of RA patients had more joint symptoms and worse functional disability compared to non-first-degree relatives. We think this may be because first-degree relatives have a better understanding of what rheumatoid is, and are more self-reflective of their personal risks.

The next major finding was that autoantibody-positive first-degree relatives reported increased functional disability compared to those without antibodies. There was no difference in their joint symptoms, things like hand pain and hand stiffness, symptoms that are typically associated with individuals who have established rheumatoid arthritis.

We observed higher HAQ scores, on average, in individuals with antibodies, those who are at the highest risk to develop future disease. This is the first time this has been shown in the literature. The strongest signal was difficulty with walking. There's increasing evidence on the basis of joint imaging by MRI and ultrasound at the very earliest areas of inflammation in preclinical RA begin in the feet.

We extracted joint examination and found a positive relationship between joint pain on exam and difficulty walking, suggesting that some of the functional disability may be explained by joint pain that is representative of early stages of arthritis.

In summary, we better defined functional disability and symptoms of arthritis in individuals who are at high risk to develop future disease on the basis of being a first-degree relative.

We hope that other preclinical rheumatoid arthritis cohorts are able to replicate our findings and attempt to show similar association between functional disability and autoantibody status, those who are at the highest risk to develop future disease.

We think this will help rheumatologists and impact their practice, as referrals for individuals with autoantibodies who do not have rheumatoid arthritis are likely representative of those who are at imminent risk to develop RA.

We hope that clinicians are able to use these functional questions to better understand the increased risk of developing future arthritis and the relationship with autoantibodies. This may help individuals understand their symptoms better as it pertains to future arthritis risk.

We're hoping that one day we'll be able to prevent arthritis onset and really reverse these functional changes that we observe in individuals who have the highest risk to develop future disease.