Rheumatology
Rheumatoid Arthritis
Moving From Treatment to Prevention of Rheumatoid Arthritis
Overview
Clinical Study Title: Towards Prevention of Autoantibody-Positive Rheumatoid Arthritis: From Lifestyle Modification to Preventive Treatment
Clinical Study Abstract: Recent advances in research into the earliest phases of RA have provided additional insights into the processes leading from the healthy to the diseased state. These insights have opened the way for the development of preventive strategies for RA, which represents a significant paradigm shift from treatment to prevention and will have major implications for patients as well as society. It would be a huge step forward if clinical signs and symptoms, disability, impaired quality of life and the need for chronic immunosuppressive treatment could be prevented. RA can be seen as a prototypic autoimmune disease, and discoveries about the preclinical diseased state for RA could potentially facilitate research into prevention of other immune-mediated inflammatory diseases such as type 1 diabetes, SLE and multiple sclerosis. This review focuses on the current knowledge of factors contributing to the development of RA and discusses the opportunities for intervention.
Reference: Gerlag DM, Norris JM, Tak PP. Towards prevention of autoantibody-positive rheumatoid arthritis: from lifestyle modification to preventive treatment. Rheumatology (Oxford). 2016;55(4):607-614.
Expert Commentary
Jonathan Kay, MD
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“Although we have evolved from treating established RA to treating early inflammatory arthritis, thereby preventing progression to established disease, we do not have a method by which to identify patients who are at risk for developing RA and to initiate treatment with a medication that addresses the underlying pathophysiology that precedes clinically evident disease.”
Currently, we lack an effective way to intervene before rheumatoid arthritis (RA) becomes clinically apparent to prevent the disease from manifesting. Although we have evolved from treating established RA to treating early inflammatory arthritis, thereby preventing progression to established disease, we do not have a method by which to identify patients who are at risk for developing RA and to initiate treatment with a medication that addresses the underlying pathophysiology that precedes clinically evident disease. Thus, a major focus of research is to develop strategies to prevent RA. The review by Gerlag and colleagues conveys the importance of RA prevention and identifies several potential approaches to intervene during the preclinical phase of the disease.
An interesting development regarding early recognition of RA is the increasing use of anti-citrullinated peptide antibody (ACPA) testing by primary care providers. Thus, a patient with joint discomfort, but no overt evidence of joint swelling, and ACPA of >250 U/mL might be referred to see a rheumatologist for consideration of an intervention to prevent the onset of clinically evident inflammatory arthritis. We know that circulating autoantibodies and elevation of acute-phase reactants, cytokines, and chemokines can precede the clinical onset of RA by many years. Although we do not yet have reliable biomarkers to detect the earliest pathophysiologic events, this is the stage at which there may be the greatest opportunity to disrupt the natural history of the disease.
Some of the most interesting ongoing clinical trials are investigating the possibility of preventing RA development in high-risk patients. Gerlag and colleagues are treating patients at risk for RA development with a single dose of rituximab; the results of this study are pending. Another ongoing trial in the United States, the Strategy to Prevent the Onset of Clinically-Apparent Rheumatoid Arthritis (StopRA) study, is evaluating the use of hydroxychloroquine to prevent the onset of clinically evident RA in individuals with elevated ACPA levels.
These studies that are evaluating strategies to prevent the expression of RA in at-risk individuals are of great interest. Although studies of specific strategies may yield negative results, the approach of targeting this preclinical phase to prevent RA in the population at risk is exciting.
References
Gerlag DM, Norris JM, Tak PP. Towards prevention of autoantibody-positive rheumatoid arthritis: from lifestyle modification to preventive treatment. Rheumatology (Oxford). 2016;55(4):607-614.
Hähnlein JS, Nadafi R, de Jong T, et al. Impaired lymph node stromal cell function during the earliest phases of rheumatoid arthritis. Arthritis Res Ther. 2018;20(1):35.
Hilliquin S, Hugues B, Mitrovic S, Gossec L, Fautrel B. Ability of disease-modifying antirheumatic drugs to prevent or delay rheumatoid arthritis onset: a systematic literature review and meta-analysis. Ann Rheum Dis. 2018 Jun 8. pii: annrheumdis-2017-212612. doi: 10.1136/annrheumdis-2017-212612. [Epub ahead of print]
Ioan-Facsinay A, el-Bannoudi H, Scherer HU, et al. Anti-cyclic citrullinated peptide antibodies are a collection of anti-citrullinated protein antibodies and contain overlapping and non-overlapping reactivities. Ann Rheum Dis. 2011;70(1):188-193.
Strategy to Prevent the Onset of Clinically-Apparent Rheumatoid Arthritis (StopRA). ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT02603146. Accessed May 9, 2018.
van Zanten A, Arends S, Roozendaal C, et al. Presence of anticitrullinated protein antibodies in a large population-based cohort from the Netherlands. Ann Rheum Dis. 2017;76(7):1184-1190.
