Background/Purpose: Identifying individuals at risk for rheumatoid arthritis (RA) development is a prerequisite to understand preclinical events and to develop prevention. Based on a systematic review of the literature, our goals were to determine the risk of RA in first degree relatives (FDR) of RA patients (Q1), to study the serological status of FDR (Q2), to determine risk of developing RA among asymptomatic subjects seropositive either for RF or anti-CCP (Q3) and to determine whether being seropositive for RF or anti-CCP increases RA risk among subjects complaining of arthralgia (Q4).

Methods: 3185 articles were screened using various databases until june 2016 and data was extracted independently by two authors. Meta-analysis were performed to assess odds-ratios (OR) for each studied group using the inverse variance approach to estimate pooled OR with their 95% confidence interval. Heterogeneity was assessed according to Cochran Q-test and I² values. Calculations were made with the Cochrane RevMan 5.3 software. P-values less than 0,05 were considered as significant.

Results: For Q1 : FDR of RA patients have a two to fourfold risk of RA, compared to controls. For Q2 : IgM-RF were positive among 14,4% of FDR and 5,7% of unrelated controls, resulting in an OR 3,19 (1,27-8,01 ; I²=66%). Anti-CCP were found among 4,4% of FDR and 2,1% of unrelated controls, resulting in an OR 2,42 (IC95% 1,22-4,79 ; I²=0%)  (figure 1). For Q3 : the risk of developing RA among asymptomatic seropositive subjects was OR 7,89 (IC95% 4,54-13,72; I²=54%) when positive for IgM-RF, and OR 21,60 (IC95% 5,8-80,37 ; I²=92%) when positive for anti-CCP, compared to seronegative subjects (figure 2). For Q4 : arthralgia subjects showed an increased risk for arthritis with an OR 3,53 (IC95% 1,49-8,39; I²=88%) if these subjects were positive for IgM-RF and OR 12,67 (IC95% 5,37-29,90; I²=61%) when positive for anti-CCP, compared to seronegative arthralgia subjects (figure 3).  

Conclusion: Our study allows to quantify the increased risk conferred by a family history of RA, and a seropositivity for IgM-RF or anti-CCP among asymptomatic and arthralgia subjects. These results should help the physician to answer questions often asked by RA patients, and should help him to better define and to monitor closely at risk subjects with the aim of early screening and earlier treatment