Study | Population studied | Cohort size | Risk factor | Frequency assessed | Main outcome |
Asymptomatic | |||||
del Puente et al9 | Healthy NAN | 2712 | RF | Multiple: bi-annually | RA development Incidence of RA (cases per 1000 person-years) increased according to RF titre (p<0.001): cases per 1000 person-years=2.4 (RF titre <1:2); 6.7 (titre 1:2–1:16); 11.0 (titre 1:32–1:256); 48.3 (titre >1:256) |
Ramos-Remus et al6 | FDRs and relatives of RA probands | 819 relatives of 252 RA probands | Relatives of RA probands | Once (BL) | Development of RA All relatives Anti-CCP2+/RF+ versus seronegative: HR 52.5 (95% CI 19.1 to 144.1), p<0.01 Offspring versus other relatives HR 3.1 (95% CI 1.2 to 8.1) |
Gan et al52 | Anti-CCP3-positive individuals screened from the general population | 35 | Anti-CCP3 | Once (BL) | Development of IA Anti-CCP3: 14/35 (40%) of anti-CCP3+ individuals developed IA at 2.56 years follow-up |
Verheul et al60 | Pre-RA individuals, FDRs | 379 (pre-RA) 246 (FDR) | Anti-CCP RF Anti-CarP | Meta-analysis | Development of RA Number of different autoantibodies present: one antibody: OR 12 (95% CI 6 to 21) two antibodies: OR 30 (95% CI 11 to 83) three antibodies: OR 112 (95% CI 6 to 2122) |
Tanner et al7 | Unaffected relatives of NAN RA-probands in Canada and Alaska | 374 | ACPA RF | Multiple: BL and annually | Development of IA Cases of IA per 1000 person-years: ACPA+/RF+ 97.1 ACPA−/RF+ 7.2 ACPA+/RF− 36.4 |
Hafkenscheid et al8 | ACPA-positive FDRs of patients with RA, in NANs | 126 | IgG ACPA V‐domain glycosylation | Development of RA IgG ACPA variable‐domain glycosylation: HR=6.07 (95% CI 1.46 to 25.2, p=0.013) | |
MSK symptoms without arthritis | |||||
Bos et al11 | Seropositive arthralgia (ACPA and/or RF) | 147 (50 ACPA+, 52 RF+, 45 ACPA+/RF+) | Anti-CCP2 IgM RF | Once (BL) | Development of IA Compared with RF: anti-CCP: HR 6.0 (95% CI 1.8 to 19.8); p=0.004 In anti-CCP+ only: anti-CCP+/IgM RF+: HR 3.0 (95% CI 1.4 to 6.9), p=0.01. High anti-CCP level: HR 1.7; (95% CI 1.1 to 2.5), p=0.008 |
van de Stadt et al12 | Seropositive arthralgia (ACPA and/or RF) | 244 | Reactivity to five citrullinated peptides: cFib1 cFib2 cFib3 enolase vimentin | Once (BL) | Development of IA Recognition of 2–5 additional citrullinated peptides: HR 1.7 (95% CI 0.93 to 3.16), p=0.08 |
Shi et al16 | Seropositive arthralgia (anti-CCP2 and/or RF) | 340 | Anti-CarP Ab | Once (BL) | Development of IA Anti-CarP antibodies: HR=1.56 (95% CI 1.06 to 2.29), p=0.003. In anti-CCP+ subgroup only: anti-CarP antibodies: HR=2.23 (95% CI 1.31 to 3.79), p=0.003 |
Ten Brinck et al13 | CSA | 241 | ACPA, RF and anti-CarP Ab | Once (BL) | Development of IA Anti-CCP2: HR=5.1 (95% CI 2.0 to 13.2) RF: 2.0 (95% CI 0.81 to 4.9) Anti-CarP: 1.04 (95% CI 0.46 to 2.4) |
Early clinical arthritis | |||||
Kudo-Tanaka et al17 | Recent-onset (<2 years) UA (arthritis in ≥2 joints not meeting RA or other classification criteria) | 146 | Anti-CCP IgM RF MMP3 CARF | Once (BL) | RA development (PPV, NPV and diagnostic accuracy) anti-CCP2: 65.2%, 97.2%, 91.7%, respectively; IgM RF: 34.1%, 95.6%, 76.3%, respectively; CARF: 30.2%, 97.5%, 70.5%, respectively; MMP3: 25.0%, 91.5%, 69.0%, respectively |
van der Linden et al19 | Early (<2 years) UA | 625 | Anti-CCP2 Anti-CCP3 Anti-MCV | Once (BL) | RA development (PPV) Anti-CCP2: 67.1% Anti-CCP3: 64% Anti-MCV: 56.3% |
Mjaavatten et al18 | UA (≥1 clinically swollen joint of ≤16 weeks duration) | 376 | Anti-CCP2 IgM RF Anti-CCP2+/IgM RF+ | Once (BL) | Development of persistent IA Anti-CCP: OR 3.567 (95% CI 1.572 to 8.094) IgM RF: OR 2.716 (95% CI 1.189 to 6.202) Anti-CCP+/RF+: OR 7.948 (95% CI 2.659 to 23.752) |
HR/OR and 95% CIs have been reported where available.
+, positive; Ab, antibodies; ACPA, anticyclic citrullinated peptide antibodies; BL, baseline; CARF, anti-agalactosyl IgG antibodies; CarP, carbamilated protein; CCP, cyclic citrullinated peptide; CCP2, second-generation anti-CCP Ab; CCP3, third-generation anti-CCP Ab; CSA, clinically suspect arthralgia; FDRs, first-degree relatives; IA, inflammatory arthritis; MCV, mutated citrullinated vimentin; MMP-3, matrix metalloproteinase 3; NAN, native American nations; NPV, negative predictive value; PPV, positive predictive value; RA, rheumatoid arthritis; RF, rheumatoid factor; UA, undifferentiated arthritis.