Vitamin B-6 Status Correlates with Disease Activity in Rheumatoid Arthritis Patients During Treatment with TNFα Inhibitors

Background: A frequent observation in inflammatory conditions, including rheumatoid arthritis (RA), is low circulating amounts of pyridoxal 5'-phosphate (PLP), the metabolically active form of vitamin B-6. Recently, a functional marker of vitamin B-6 status, the ratio of 3-hydroxykynurenine (HK): xanthurenic acid (XA) in plasma (HK: XA), was proposed. Objective: We investigated vitamin B-6 status in patients with RA before and after established treatment with TNF alpha inhibitors. Methods: We performed a longitudinal study of RA patients (n = 106, 36% men, median age 54 y) starting first treatment with a TNF alpha inhibitor (infliximab, etanercept, adalimumab, golimumab, or certolizumab). Clinical assessment (Disease Activity Score for 28 standard joints, DAS28), joint ultrasonography, and blood draw were performed at baseline and after 3 mo treatment. Plasma concentrations of PLP, HK, and XA were measured by liquid chromatography-tandem mass spectrometry. Associations of changes in vitamin B-6 markerswith change in DAS28 were assessed by generalized additive models regression and with European League Against Rheumatism (EULAR) response categories by linear regression. Results: At baseline PLP was inversely correlated with CRP (rho = -0.27, P = 0.007), whereas HK: XA correlated with DAS28 (rho = 0.46, P < 0.001), CRP (rho = 0.36, P < 0.001), and ultrasonography scores (rho = 0.29-0.35, P = 0.003). After 3mo treatment, the change (a 33% overall reduction) in DAS28 was related to changes in both PLP (beta=-0.28, P = 0.01) and HK: XA (beta = 0.33, P < 0.001). Good responders (45%) according to EULAR criteria experienced a 31% increase in PLP (P = 0.003) and an 11% decrease in HK: XA (P = 0.1), whereas nonresponders (24%) experienced a 25% increase in HK: XA (P = 0.02). Conclusion: Two independent measures of vitamin B-6 status confirm an association with disease activity in RA patients. The association of HK: XA with disease activity may also imply perturbations in kynurenine metabolism in RA.