331 Case Studies

The 331 patients included in this study were recruited from the outpatient Rheumatology clinic without any selection except fulfilling the ACR classification criteria. They showed characteristics of established RA as shown in Table 1, with an excess of women, advanced age and long time since the start of the first disease symptoms (Data in S1 Table). They were also typical in the fraction showing RA-specific autoantibodies: RF = 60.1 %, anti-CCP = 64.7 % and anti-CarP = 32.9 %, and in the overlap between them (Fig. 1), corresponding with concordances of γ = 0.82 between anti-CCP and RF, 0.66 between anti-CCP and anti-CarP, and 0.64 between RF and anti-CarP (p for all of them < 2.0 x 10-16). The frequency of ever smokers was low (Table 1), but

This variable showed a significant association with mortality (HR = 1.25, 95% CI 1.06 to 1.48, p = 0.008), but it was dependent on the presence of the anti-CarP antibodies, not on the contribution of the other two autoantibodies. These results were obtained by conditional analysis: the number of autoantibodies did not remain associated in analysis conditional on anti-CarP status (HR = 1.08, 95% CI 0.84 to 1.39, p = 0.6), whereas it remained significantly associated, and was nominally more marked, conditional on RF, or on anti-CCP status (Fig. 5). Finally, we addressed the autoantibody titers, which were only available for the anti-CCP and anti-CarP antibodies. None of them was associated with a higher HR of death (not shown).
When the specific causes of death were considered, only the deaths attributed to diseases of the respiratory system were associated with the anti-CarP antibodies. The HR was considerably larger than the observed in the all-cause of mortality analysis reported above (HR = 3.19, 95 % CI 1.52 to 6.69, p = 0.002). The deaths attributed to neoplasms showed also a trend to increased HR in patients with anti-CarP antibodies (HR = 2.45, 95 % CI 0.93 to 6.43, p = 0.07). The other two RA autoantibodies did not show association with any of the analyzed causes of