Prevention of Rheumatoid Arthritis: The Very First Steps

Abstract

Several studies have shown that appropriately treating rheumatoid arthritis (RA) during an early “window of opportunity” markedly improves patient short- and longterm outcomes1,2. Because treatment of RA is difficult, costly, and not uniformly effective, it is appealing to target susceptible individuals at some recognizable preclinical stage, where interventions could abort RA development. Strategies could then be devised and tested to alter the inappropriate ongoing pathophysiologic processes, and prevent the subsequent development of inflammation, pain, joint damage, disability, and early death. Similar to Philip K. Dick’s Minority Report, in which crimes still to be committed are visualized and their “perpetrators” arrested beforehand, will rheumatologists soon be able to see RA coming and prevent it before it becomes clinically manifest? In the current issue of The Journal 3, Smolik and colleagues studied unaffected first-degree relatives (FDR) of North American Natives (NAN) with RA from Manitoba, Canada, a group with a very high prevalence of RA. Nevertheless, because of low annual incidence (lower than 0.5%, even in this highly selected population), Smolik, et al lacked statistical power to study the definitive outcome of interest, RA development itself. Rather, they looked at plausible surrogates: the presence of rheumatoid factor (RF), second-generation anticyclic citrullinated peptide antibodies (anti-CCP2), self-reported joint symptoms, and their potential correlation. While RA-associated antibodies are well known to herald RA development4,5, this remains unproven for the presence of joint symptoms in the absence of joint inflammation. Using a screening questionnaire, the authors observed that, as a group, FDR reported more joint symptoms than NAN and non-NAN controls. This increase was significant only in the small subset of FDR that were positive for both RF and anti-CCP2. Although testing positive for both RF … Address correspondence to Dr. Boire; E-mail: Gilles.Boire{at}USherbrooke.ca