A study of people at risk of RA found that taking omega-3 fatty acid supplements was linked to a lower chance of being RF positive.
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LONDON—Research continues to advance in understanding the causes, prediction and management of the stages of early arthritis before full-blown clinical disease, and an expert highlighted some of the latest of these encouraging findings at the Annual Congress of the European League Against Rheumatism (EULAR) 2016.
Many of the genetic and environmental risk factors are known, but what hasn’t been known is the stage at which they become relevant. Investigators are making progress on this question, said Karim Raza, MD, PhD, professor of clinical rheumatology at the University of Birmingham in the United Kingdom.
Predicting Progression
In one recent study, researchers found that the human leukocyte antigen (HLA) DRB1*13 alleles, known to be associated with protection from anti-citrullinated protein antibody (ACPA) positive RA, does not seem to be associated with much protection from the development of ACPA. So the relevance of this gene seems to be mostly at the level of those who are already ACPA positive, protecting against the development of RA itself.1
According to Dr. Raza, this could have a therapeutic impact. “If you can understand the mechanisms underlying this protection, then you can harness that and develop treatments for people who are ACPA positive to reduce the risk of transmission to RA,” he said.
Another study, looking at people at risk of RA, particularly first-degree relatives of those with RA, found that taking omega-3 fatty acid supplements was linked with a lower chance of being rheumatoid factor positive, among those who were positive for the shared epitope, a common RA risk factor.2
One study found that synovitis, tenosynovitis & bone marrow edema were predictive of development of clinical arthritis.
On the prediction front, researchers late last year published findings that adding ultrasound imaging variables to clinical variables helped improve the ability of a model to predict development of RA in people who are ACPA positive and have arthralgia.3 Other studies, focusing on lab values, such as adipokines, type 1 interferon and B cell signatures, and numbers of regulatory and naive T cells, all found that these factors can help with prediction as well.
“I think there’s increasing insight that by adding data from imaging and novel laboratory markers, we’ll be able to refine the accuracy of algorithms to predict RA development in individuals at risk,” Dr. Raza said.
Most people referred to a rheumatologist haven’t yet been tested for ACPA. New research offers guidance in predicting progression of those who present only with “clinically suspect arthralgia,” even when it’s not necessarily associated with ACPA positivity. One study found that synovitis, tenosynovitis and bone marrow edema were predictive of development of clinical arthritis.4
Progress in Management
Research into management is also unfolding for every stage leading up to clinical disease.
Among the symptom-free but genetically at-risk, researchers have embarked on a trial testing the effects of educating first-degree relatives of RA patients on their RA risk and on modifiable factors such as oral health, diet, weight and smoking status.5 That trial is ongoing, but is a notable one, Dr. Raza said.
“I think this conceptually is a really important development in how we think about preventing RA,” he said.
In the stage of ACPA-positive arthralgia, researchers have looked at the efficacy of giving a single, 1,000-mg infusion of rituximab. They found the treatment didn’t prevent development of arthritis, but did seem to delay it by up to 12 months.
In the stage of ACPA-positive arthralgia, researchers have looked at the efficacy of giving a single, 1,000-mg infusion of rituximab. They found the treatment didn’t prevent development of arthritis, but did seem to delay it by up to 12 months.
“Potentially that’s an important thing in people at the very early stage of a very serious disease,” Dr. Raza said.
One of the challenges in treating early symptoms is simply being able to act on them in time, but that can be hampered by difficulty in getting an appointment with a specialist. But a recent study describes the success of a “rapid access” rheumatology clinic in a low-population area in rural Austria, where blocks of appointments are set aside for brief initial assessments for people with musculoskeletal problems in whom there is an initial suspicion of RA.
Researchers found that 25 of 58 people for whom RA was suspected on the first visit were seen within three months of the first appearance of symptoms. That’s 43%, compared with just 16% seen within three months before the rapid access clinic was started.
“It shows,” Dr. Raza said, “that you can set up those kinds of clinics in a really successful and pragmatic way in a clinical environment outside the university-based teaching hospitals.”
Thomas R. Collins is a freelance medical writer based in Florida.
References
- van Heemst J, Hensvold AH, Jiang X, et al. Protective effect of HLA-DRB1*13 alleles during specific phases in the development of ACPA-positive RA. Ann Rheum Dis. 2015 Dec 29. [Epub ahead of print]
- Gan RW, Young KA, Zerbe GO, et al. Lower omega-3 fatty acids are associated with the presence of anti-cyclic citrullinated peptide autoantibodies in a population at risk for future rheumatoid arthritis: A nested case-control study. Rheumatology (Oxford). 2016 Feb;55(2):367–376.
- Rakieh C, Nam JL, Hunt L, et al. Predicting the development of clinical arthritis in anti-CCP positive individuals with non-specific musculoskeletal symptoms: A prospective observational cohort study. Ann Rheum Dis. 2015 Sep;74(9):1659–1666.
- van Steenbergen HW, van Nies JA, Huizinga TW, et al. Characterising arthralgia in the preclinical phase of rheumatoid arthritis using MRI. Ann Rheum Dis. 2015 Jun;74(6):1225–1232.
- Sparks, JA, Iversen MD, Mill Kroouze R, et al. Personalized risk estimator for rheumatoid arthritis (PRE-RA) family study: Rationale and design for a randomized controlled trial evaluating rheumatoid arthritis risk education to first-degree relatives. Contemp Clin Trials. 2014 Sep;39(1):145–157.
- Gerlag D, Safy M, Maijer K, et al. Prevention of rheumatoid arthritis by B-cell-directed therapy in the earliest phase of the disease: the PRAIRI study. Abstract OP0182. Presented June 9, 2016 at the Annual Congress of the European League Against Rheumatism. London.
- Puchner R, Janetschko R, Kaiser W, et al. Efficacy and outcome of rapid access rheumatology consultation: An office-based pilot cohort study. J Rheumatol. 2016 Jun;43(6):1130–1135.