Effects of adalimumab treatment on endothelial cell activation markers in the skeletal muscle of patients with rheumatoid arthritis.

OBJECTIVES: Patients with rheumatoid arthritis (RA), particularly those with severe disease, have increased risk of cardiovascular disease (CVD). Previous studies suggest that endothelial cell activation may contribute to this co-morbidity, and that treatment with tumour necrosis factor (TNF) inhibitors could reduce the risk of CVD in these patients. The aim of this study was to investigate endothelial cell activation markers in muscle tissue of patients after adalimumab treatment. METHODS: Patients with active RA who started treatment with adalimumab 40 mg every two weeks were included. Muscle biopsies taken before and 3 months after start of treatment were available from 11 patients (9 females, mean age 54.2 years, median disease duration 6.5 years, 91% anti-CCP positive, 7 on methotrexate [median dose 20 mg/week]). None of the patients had clinical signs of myopathy. IL-1α and HLA-DQ were investigated by immunohistochemistry. Quantification was performed by computer assisted image analysis. RESULTS: Disease activity, measured by DAS28 decreased (mean 5.5 vs. 4.1; p=0018). A good or moderate EULAR response was seen in 6/11 patients. HLA-DQ was mainly expressed in endothelial cells in capillaries, whereas IL-1α was mainly seen in larger vessels. HLA-DQ expression decreased significantly after treatment (p=0.041). There was a similar trend for IL-1α, in particlar in EULAR good/moderate responders. CONCLUSIONS: Adalimumab treatment was associated with decreased expression of endothelial markers previously associated with severe systemic inflammation in RA. Our findings indicate a reduced endothelial activation in patients treated with anti-TNF drugs, which might contribute to a lower risk of cardiovascular co-morbidity.

Reliability, validity and responsiveness of a new leisure index: the Patient-Specific Leisure Scale (PSLS).

OBJECTIVES: To investigate the reliability, validity and responsiveness of a new Patient-Specific Leisure Scale (PSLS), constructed to identify goals and outcomes for individual patients with rheumatoid arthritis (RA). METHODS: Forty-nine patients with RA were used to evaluate test-retest reliability, and 100 consecutive RA patients were used for construct validity. Twenty-five RA patients, commencing with treatment on tumour necrosis factor (TNF) inhibitors, were evaluated before the start and after three months of therapy, to test responsiveness. The most important leisure activity (as judged by the patients) was used when evaluating reliability and validity. The perceived difficulty with each activity was scored from 0 to 10 (0 = able to perform activity without difficulty, 10 = unable to perform activity). RESULTS: Test-retest reliability indicated a good agreement (0.62-0.87) using weighted kappa. Construct validity was demonstrated by modest positive correlation between leisure activity and Health Assessment Questionnaire (HAQ) (r(s) = 0.27, p = 0.005) visual analogue scale (VAS) pain (r(s) = 0.28, p = 0.004) VAS global (r(s) = 0.22, p = 0.027), VAS fatigue (r(s) = 0.24, p = 0.013), joint index of 28 swollen joints (r(s) = 0.22, p = 0.027) and negative correlations with short-form-36 (SF-36) physical functioning (r(s) = -0.18, p = 0.008), bodily pain (r(s) = -0.31, p < 0.001), general health (r(s) = -0.23, p = 0.019), vitality (r(s) = -0.31, p < 0.001), social function (r(s) = -0.24, p = 0.016) and role-emotional (r(s) = -0.28, p = 0.005). Mean improvement for the most important leisure activity was 1.36, (p = 0.036, 95% confidence interval 0.10-2.62). Standardized response mean and effect size for the most important activity in PSLS was 1.05 and 0.72, respectively, and for HAQ 0.34 and 0.28, respectively. CONCLUSIONS: PSLS appears to be feasible, reliable, valid and responsive for measuring leisure activities in RA. It provides both an individual result which is useful in clinical work, and results at a group level.