Background/Purpose: Although treatment of rheumatoid arthritis (RA) has significantly improved during the past decades, many patients do not adequately respond or become resistant to current treatments. It is currently unknown why some patients respond well and others do not, and how the response rate could be improved. Vitamin D has strong immunomodulatory properties and it has been shown RA patients have a lower serum 25(OH)D level than healthy individuals. Moreover, vitamin D levels are correlated with disease severity. Interestingly, in vitro studies have shown that vitamin D augments the suppressive effects of etanercept in a simplified model for synovial inflammation. This suggests that vitamin D could improve the therapeutic response to etanercept in RA patients. Therefore we studied if etanercept response is related to serum vitamin D (25(OH)D) levels in RA patients.

Methods: For this study, data were used from the tREACH trial, a multicenter stratified single blinded randomized clinical trial. RA patients, according to the 2010 classification criteria, who started with etanercept within the first 12 months of the study were included in the analysis. Serum vitamin D (25(OH)D) levels were determined at the start of treatment (Tstart) and 3 months later using the LIAISON® 25 OH Vitamin D TOTAL assay . Correlation coefficients between vitamin D levels and the disease activity score (DAS) were calculated. Treatment response was determined with the EULAR response criteria, and difference in response rates was assessed using Chi-Square tests.

Results: 91 patients started etanercept in the first 12 months of the study, of which 24 did not have serum for 25(OH)D measurements at start of treatment and three months later. A total of 67 patients was included, of which 82% was female. At baseline, 45 (67%) and 48 (73%) were positive for rheumatoid factor and anti-citrullinated protein antibodies, respectively. DAS after etanercept treatment was weakly inversely correlated with serum 25(OH)D after treatment (r=-0.29, p=0.02) and the change in 25(OH)D during treatment (r=-0.25, p=0.04). After correcting for DAS and serum 25(OH)D at the start of treatment the aforementioned correlations were still found. Importantly, EULAR response rate was significantly lower in patients who were vitamin D-deficient at the start of treatment (34.6% vs 59.4%) and in patients with decreasing 25(OH)D levels during treatment (39.2% vs 57.7%).

Conclusion: RA patients with a serum 25(OH)D level below 50 nmol/L at the start of etanercept treatment or decreases during treatment have a lower EULAR response rate. Therefore, increasing serum 25(OH)D level in vitamin D deficient patients may be important to achieve optimal effects of TNFα blocking therapy.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/improved-response-to-etanercept-is-associated-with-serum-vitamin-d-levels-in-rheumatoid-arthritis/