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

Abstract

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. We investigated vitamin B-6 status in patients with RA before and after established treatment with TNFα inhibitors. We performed a longitudinal study of RA patients (n=106, 36% men, median age 54 y) starting first treatment with a TNFα 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 markers with change in DAS28 were assessed by generalized additive models regression and with European League Against Rheumatism (EULAR) response categories by linear regression. At baseline PLP was inversely correlated with CRP (ρ=-0.27, P=0.007), whereas HK: XA correlated with DAS28 (ρ=0.46, P<0.001), CRP (ρ=0.36, P<0.001), and ultrasonography scores (ρ=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 (ß=-0.28, P=0.01) and HK: XA (ß=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). 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. This trial was registered at helseforskning.etikkom.no as 2011/490.