© 2016, American College of Rheumatology
Volume 68, Issue 4, pages 779–788, April 2016
Starting therapy early leads to better outcomes for rheumatoid arthritis (RA) patients. Early initiation of disease-modifying treatments is associated with less joint damage and increased chances of achieving remission. But what is early disease? Conventionally, this is taken to mean the initial phase after arthritis becomes clinically detectable. However, recent studies have challenged this presumption and have suggested that disease processes become established in the preclinical period, a phase often described as pre-RA. The corollary of this represents a paradigm shift; clinical arthritis is not the beginning of the disease but is, instead, the culmination of a whole series of well-established pathologic events.
In this review, we provide an overview of the preclinical phases of RA, with special focus on recent advances in the field. Specifically, we will review evidence suggesting that localized autoimmunity may be an important trigger in preclinical disease, an area attracting growing research interest. Newly characterized immunologic and imaging biomarkers and their significance in prospective cohorts will also be discussed. Finally, the clinical features and management of individuals at-risk of developing RA are also described.
Defining pre-RA: classification of at-risk individuals
Many important pathologic events occur before RA becomes clinically manifest. In order to standardize the terminology for the phases leading up to and including RA, the European League Against Rheumatism Standing Committee on Investigative Rheumatology devised a recommendation for nomenclature . Six phases of RA development were agreed upon (Figure 1). The categories are genetic and environmental risk factors for RA (phases A and B, respectively), systemic autoimmunity associated with RA (phase C), symptoms without clinical arthritis (phase D), and both undifferentiated arthritis and RA (phases E and F, respectively). The proposed categories are intended as a broad framework based on the current understanding of the etiology of RA. It is clear that individuals may not necessarily progress through all phases, and that individual phases are not mutually exclusive. Importantly, although individuals are at risk of RA, the terms preclinical RA and pre-RA should only be used retrospectively, as many at-risk individuals will never develop clinical arthritis or RA. This is especially true for individuals in phases A and B who are healthy individuals with risk factors that may never translate into pathologic processes.
Keep reading in the Journal. Open Access