Polymorphisms in genes controlling inflammation and tissue repair in rheumatoid arthritis: a case control study.

BACKGROUND: Various cytokines and inflammatory mediators are known to be involved in the pathogenesis of rheumatoid arthritis (RA). We hypothesized that polymorphisms in selected inflammatory response and tissue repair genes contribute to the susceptibility to and severity of RA. METHODS: Polymorphisms in TNFA, IL1B, IL4, IL6, IL8, IL10, PAI1, NOS2a, C1INH, PARP, TLR2 and TLR4 were genotyped in 376 Caucasian RA patients and 463 healthy Caucasian controls using single base extension. Genotype distributions in patients were compared with those in controls. In addition, the association of polymorphisms with the need for anti-TNF-α treatment as a marker of RA severity was assessed. RESULTS: The IL8 781 CC genotype was associated with early onset of disease. The TNFA -238 G/A polymorphism was differentially distributed between RA patients and controls, but only when not corrected for age and gender. None of the polymorphisms was associated with disease severity. CONCLUSIONS: We here report an association between IL8 781 C/T polymorphism and age of onset of RA. Our findings indicate that there might be a role for variations in genes involved in the immune response and in tissue repair in RA pathogenesis. Nevertheless, additional larger genomic and functional studies are required to further define their role in RA.

Survival, comorbidities and joint damage 11 years after the COBRA combination therapy trial in early rheumatoid arthritis.

BACKGROUND: COBRA (for 'COmbinatie therapie Bij Rheumatoide Artritis') combination therapy is effective for the treatment of rheumatoid arthritis (RA), but long-term safety is unknown. This study evaluates survival, comorbidities and joint damage in the original COBRA trial cohort. METHODS: In the COBRA trial, 155 patients with early RA were treated with sulfasalazine (SSZ) monotherapy (SSZ group) or a combination of step-down prednisolone, methotrexate (MTX) and SSZ (COBRA group). The current 11-year follow-up study of the COBRA trial invited all original patients and performed protocollised scrutiny of clinical records, questionnaires, physical examination, laboratory and imaging tests. RESULTS: In all, 152 out of 155 patients yielded at least partial data. After a mean of 11 years follow-up, 18 (12%) patients had died, 6 COBRA patients and 12 SSZ patients, HR 0.57 (95% CI 0.21 to 1.52). Treatment for hypertension was significantly more prevalent in the COBRA group (p=0.02) with similar trends for diabetes and cataract. Conversely, hypercholesterolaemia, cancer and infection showed a trend in favour of COBRA. Other comorbidities such as cardiovascular disease and fractures appeared in similar frequency. Radiographic findings suggest as a minimum sustained benefit for COBRA therapy, that is, difference in joint damage but similar subsequent progression rates after 5 years. Imputation to compensate for selective dropout suggests increasing benefit for COBRA, that is, difference in yearly progression rates similar to that seen in the first 5 years of follow-up. CONCLUSIONS: After 11 years, initial COBRA combination therapy resulted in numerically lower mortality and similar prevalence of comorbidity compared with initial SSZ monotherapy. In addition, lower progression of joint damage suggests long-term disease modification.

Identifying axial spondyloarthritis in Dutch primary care patients, ages 20-45 years, with chronic low back pain.

OBJECTIVE: To identify axial spondyloarthritis (SpA) in Dutch primary care patients with chronic low back pain (CLBP), and to design a simple referral model for general practitioners (GPs) that would identify patients at risk for axial SpA. METHODS: Patients (ages 20-45 years) with CLBP were identified from GP records. Assessments included inflammatory back pain questionnaires, medical interviews, physical examinations, HLA-B27, C-reactive protein level, conventional radiography, and magnetic resonance imaging. The outcome measure was axial SpA defined by the Assessment of SpondyloArthritis international Society (ASAS) criteria. Multivariable regression analysis with bootstrapping was used to develop the referral model. RESULTS: A total of 364 patients (mean ± SD age 36.3 ± 6.8 years) was recruited with a median symptom duration of 9.0 years. Eighty-six patients (24%) fulfilled the ASAS criteria for axial SpA. Of all potential determinants, the ASAS inflammatory back pain questionnaire, good response to nonsteroidal antiinflammatory drugs, family history of SpA, and symptom duration were identified as most relevant for diagnosing axial SpA by multivariable regression analysis related to axial SpA. The shrunken regression coefficients were, respectively, 1.04, 0.83, 0.73, and 0.23. The combination of these 4 items proved a useful area under the receiver operating characteristic curve of 0.75 (SE 0.03). In a simplified score model, at the suggested cutoff value of 1.5, the sensitivity was 83% and specificity was 59%. CONCLUSION: This study shows that 1 of 4 primary care patients with CLBP was classified as having axial SpA. A preselection in primary care based on a combination of clinical items may be useful to facilitate the identification of patients at risk of axial SpA.