Objectives To describe disease course of patients without rheumatoid factor (RF) and anti-citrullinated protein auto-antibodies (ACPA) in an inception cohort of early arthritis patients. To determine baseline predictors of fulfilling 2010 ACR/EULAR criteria for rheumatoid arthritis (RA) at 3 years in these patients
Methods Patients presenting with synovitis of at least 2 joints for 6 weeks to 6 months were included in the multicenter French ESPOIR cohort. Following data were collected at baseline for those who were negative for IgM RF and ACPA (anti-CCP2): clinical and biological features of arthritis, HLA-DRB1* typing, socio economic factors, comorbidities, radiographs of hands, wrists, and feet (modified Sharp score). RA was defined according to the 2010 ACR/EULAR classification criteria (1) at any visit during the first 3 years of follow-up or by typical RA erosion (2). Alternative diagnoses were reported among patients who did not fulfill ACR/EULAR criteria. Logistic regression was performed to evaluate the association between RA diagnosis at 3 years and baseline variables.
Results Of the 813 recruited patients, 406 (49.9%) were negative for both RF and anti-CCP2. They had the following features: age 49±13 years, females 77%, mean disease duration: 102±50 days, DAS28 4.95±1.3, HAQ score 0.93±0.68, CRP 18.6±34.2 mg/l; 57 (14.1%) had antinuclear antibodies (ANA) and 39 (9.6%) were RF-IgA positive. 246/387 patients (63.6%) fulfilled ACR/EULAR 2010 criteria for RA at baseline (56.3% had a score ≥6 and 19.8% had typical RA erosion) and 269/374 (71.9%) at 3 years.
In this seronegative cohort, diagnosis of RA at 3 years was associated with the following initial factors: symmetric involvement (OR=3 [1.41; 6.39], p=0.004), morning stiffness (>median: 45 min) (OR=2.48 [1.34; 4.57], p=0.004), pain at rest on a VAS (>median: 34/100) (OR=2.14 [1.14; 4.01], p=0.017), number of tender joints (>median: 6) (OR=3.51 [1.78; 6.92], p<0.001) and presence of feet erosions (OR=2.96 [1.19; 7.40], p=0.020). Presence of ANA (OR=0.38 [0.17; 0.87], p=0.021), transaminases elevation (OR=0.52 [0.28; 0.94], p=0.032) and living in the south of France (OR=0.45 [0.22; 0.90], p=0.024) may contribue in protecting the patient from developping RA. No association between extra-articular manifestations, HLA-DR3 and “seronegative RA” was observed. Among the 105 patients who did not fulfill ACR/EULAR 2010 criteria for RA at 3 years, 44 had another definite diagnosis: psoriatic arthritis (n=10), spondyloarthritis (n=7), erosive hand osteoarthritis (n=5), connective tissue disease and vasculitis (n=8), polymyalgia rheumatica or RS3PE syndrome (n=3).
Conclusions Patients with early arthritis and without RF and ACPA are more liable to have RA at 3 years if they have typical inflammatory characteristic of pain, symmetric involvement of numerous joints and feet erosions. Detection of ANA and transaminases elevation should suggest non RA diagnosis.
Aletaha D, Neogi T, Silman AJ, et al. Ann Rheum Dis. 2010;69(9):1580-8.
van der Heijde D, van der Helm-van Mil AH, Aletaha D, et al. Ann Rheum Dis. 2013 Apr;72(4):479-81.
Disclosure of Interest : None declared
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