Background/Purpose: Sleep problems affect over 60% of rheumatoid arthritis (RA) patients. However, little is known about the association between sleep problems and inflammatory pathways in RA. In the general population, studies have shown that sleep problems are associated with elevations in inflammatory biomarkers, notably CRP and the inflammatory cytokines, TNF-a and IL-6.  The goal of this study was to examine the cross-sectional association between biomarkers associated with RA disease activity and sleep quantity and quality in patients with RA.

Methods: 208 patients in a RA registry were enrolled in a substudy on sleep and psychosocial distress. All subjects completed the Medical Outcomes Study (MOS) Sleep Scale. Of these 208 patients, 189 also had 12 biomarkers of disease activity (EGF, VEGF-A, leptin, IL-6, SAA, CRP, VCAM-1, MMP-1, MMP-3, TNFRI, YKL-40 and resistin) measured using a quantitative multiplex immunoassay. Biomarkers with non-normal distributions were transformed. The primary independent variables were the individual biomarkers and a composite disease activity score, calculated according to a validated algorithm. The primary dependent variables were sleep quantity (in hours) and sleep quality, measured by the MOS Sleep Problems Index II (0-100 scale with 100 indicating greater sleep problems). Linear regression models were used to examine the association between biomarkers and sleep quantity and quality, adjusted for age, sex, RA disease duration and RF or anti-CCP seropositivity. To elucidate the impact of TNF inhibitors on this association, secondary analyses were performed including an indicator variable for TNF inhibitor use. Using the Bonferroni correction for multiple comparisons, the threshold for significance was set at p < 0.002.

Results: The study population (N = 189) included 85.2% women. The average age was 58.2 ± 11.2 years. The average DAS28-CRP was 2.95 ± 1.29. 17.5% were taking corticosteroids. 59.8% were taking non-biologic disease-modifying anti rheumatic drugs, and 54.0% were taking TNF inhibitors. 61.9% were either RF or anti-CCP positive. After adjustment for multiple comparisons, neither the composite disease activity score nor the individual biomarkers of disease activity were significantly associated with sleep quantity or the MOS Sleep Problems Index II (Table). Similarly, neither the composite disease activity score nor the individual biomarkers were significantly associated with sleep quantity or the MOS Sleep Problems Index II in secondary analyses including TNF inhibitor use as an indicator variable.

Conclusion: Contrary to previous studies in the general population, no associations were observed between inflammatory biomarkers and measures of sleep quantity and quality in this cross-sectional study of established RA patients. These findings suggest that RA disease activity may not be the primary driver of sleep problems in RA.