Vitamin B-6 Status Correlates with Disease Activity in Rheumatoid Arthritis Patients During Treatment with TNFα Inhibitors
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 ac...
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| Veröffentlicht in: | The Journal of nutrition 2019-05, Vol.149 (5), p.770-775 |
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| creator | Sande, Jon Sigurd Ulvik, Arve Midttun, Øivind Ueland, Per M Hammer, Hilde B Valen, Merete Apalset, Ellen M Gjesdal, Clara G |
| description | 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 |
| doi_str_mv | 10.1093/jn/nxz001 |
| format | Article |
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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 3 mo 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.</description><identifier>ISSN: 0022-3166</identifier><identifier>EISSN: 1541-6100</identifier><identifier>DOI: 10.1093/jn/nxz001</identifier><identifier>PMID: 31050750</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>3-hydroxykynurenine: xanthurenic acid ratio ; Adult ; Arthritis ; Arthritis, Rheumatoid - blood ; Arthritis, Rheumatoid - drug therapy ; Biomarkers - blood ; C-Reactive Protein - metabolism ; Correlation ; Correlation analysis ; Etanercept ; Female ; functional vitamin B-6 status ; Humans ; Inflammation ; Infliximab ; Inhibitors ; Joint diseases ; Kynurenine - analogs & derivatives ; Kynurenine - blood ; Liquid chromatography ; Longitudinal Studies ; Male ; Mass spectrometry ; Mass spectroscopy ; Medical treatment ; Metabolism ; Middle Aged ; Monoclonal antibodies ; Nutritional Status ; Patients ; pyridoxal 5′-phosphate ; Pyridoxal Phosphate - blood ; Regression analysis ; Rheumatoid arthritis ; TNF inhibitors ; TNFα inhibitors ; Treatment Outcome ; Tumor Necrosis Factor Inhibitors - therapeutic use ; Tumor Necrosis Factor-alpha - antagonists & inhibitors ; Tumor Necrosis Factor-alpha - blood ; Tumor necrosis factor-α ; Ultrasound ; Vitamin B ; Vitamin B 6 - blood ; Vitamin B 6 Deficiency - blood ; Vitamin B 6 Deficiency - complications ; Xanthurenates - blood ; Xanthurenic acid</subject><ispartof>The Journal of nutrition, 2019-05, Vol.149 (5), p.770-775</ispartof><rights>2019 American Society for Nutrition.</rights><rights>Copyright © American Society for Nutrition 2019.</rights><rights>Copyright American Institute of Nutrition May 2019</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c392t-c311f58580ddc6678066a1422f2d41e6d39d558c187eaa86fbecf7ec0883264a3</citedby><cites>FETCH-LOGICAL-c392t-c311f58580ddc6678066a1422f2d41e6d39d558c187eaa86fbecf7ec0883264a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,781,785,27929,27930</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31050750$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sande, Jon Sigurd</creatorcontrib><creatorcontrib>Ulvik, Arve</creatorcontrib><creatorcontrib>Midttun, Øivind</creatorcontrib><creatorcontrib>Ueland, Per M</creatorcontrib><creatorcontrib>Hammer, Hilde B</creatorcontrib><creatorcontrib>Valen, Merete</creatorcontrib><creatorcontrib>Apalset, Ellen M</creatorcontrib><creatorcontrib>Gjesdal, Clara G</creatorcontrib><title>Vitamin B-6 Status Correlates with Disease Activity in Rheumatoid Arthritis Patients During Treatment with TNFα Inhibitors</title><title>The Journal of nutrition</title><addtitle>J Nutr</addtitle><description>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 3 mo 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.</description><subject>3-hydroxykynurenine: xanthurenic acid ratio</subject><subject>Adult</subject><subject>Arthritis</subject><subject>Arthritis, Rheumatoid - blood</subject><subject>Arthritis, Rheumatoid - drug therapy</subject><subject>Biomarkers - blood</subject><subject>C-Reactive Protein - metabolism</subject><subject>Correlation</subject><subject>Correlation analysis</subject><subject>Etanercept</subject><subject>Female</subject><subject>functional vitamin B-6 status</subject><subject>Humans</subject><subject>Inflammation</subject><subject>Infliximab</subject><subject>Inhibitors</subject><subject>Joint diseases</subject><subject>Kynurenine - analogs & derivatives</subject><subject>Kynurenine - blood</subject><subject>Liquid chromatography</subject><subject>Longitudinal Studies</subject><subject>Male</subject><subject>Mass spectrometry</subject><subject>Mass spectroscopy</subject><subject>Medical treatment</subject><subject>Metabolism</subject><subject>Middle Aged</subject><subject>Monoclonal antibodies</subject><subject>Nutritional Status</subject><subject>Patients</subject><subject>pyridoxal 5′-phosphate</subject><subject>Pyridoxal Phosphate - blood</subject><subject>Regression analysis</subject><subject>Rheumatoid arthritis</subject><subject>TNF inhibitors</subject><subject>TNFα inhibitors</subject><subject>Treatment Outcome</subject><subject>Tumor Necrosis Factor Inhibitors - therapeutic use</subject><subject>Tumor Necrosis Factor-alpha - antagonists & inhibitors</subject><subject>Tumor Necrosis Factor-alpha - blood</subject><subject>Tumor necrosis factor-α</subject><subject>Ultrasound</subject><subject>Vitamin B</subject><subject>Vitamin B 6 - blood</subject><subject>Vitamin B 6 Deficiency - blood</subject><subject>Vitamin B 6 Deficiency - complications</subject><subject>Xanthurenates - blood</subject><subject>Xanthurenic acid</subject><issn>0022-3166</issn><issn>1541-6100</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpt0c9u1DAQBnALUdGlcOAFkCUucAj1n8RxjsuWQqUKECxcLa89YWe1cYrtFApP1RfhmXCVlgPiMpZGP32y5iPkCWcvOevk8S4chx8_GeP3yII3Na8UZ-w-WTAmRCW5UofkYUo7VkTd6QfkUHLWsLZhC_LrC2Y7YKCvKkU_ZZunRFdjjLC3GRL9jnlLTzCBTUCXLuMl5ita-MctTIPNI3q6jHkbMWOiH2xGCDnRkyli-ErXEWweymbOWb87_X1Nz8IWN5jHmB6Rg97uEzy-fY_I59PX69Xb6vz9m7PV8rxyshO5TM77Rjeaee-UajVTyvJaiF74moPysvNNox3XLVirVb8B17fgmNZSqNrKI_J8zr2I47cJUjYDJgf7vQ0wTskIITohZdu2hT77h-7GKYbyu6Ik04J3vCnqxaxcHFOK0JuLiIONV4Yzc9OI2QUzN1Ls09vEaTOA_yvvKihAzgDKCS4RokmuXNGBxwguGz_if2L_ADUSmkA</recordid><startdate>201905</startdate><enddate>201905</enddate><creator>Sande, Jon Sigurd</creator><creator>Ulvik, Arve</creator><creator>Midttun, Øivind</creator><creator>Ueland, Per M</creator><creator>Hammer, Hilde B</creator><creator>Valen, Merete</creator><creator>Apalset, Ellen M</creator><creator>Gjesdal, Clara G</creator><general>Elsevier Inc</general><general>American Institute of Nutrition</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope></search><sort><creationdate>201905</creationdate><title>Vitamin B-6 Status Correlates with Disease Activity in Rheumatoid Arthritis Patients During Treatment with TNFα Inhibitors</title><author>Sande, Jon Sigurd ; Ulvik, Arve ; Midttun, Øivind ; Ueland, Per M ; Hammer, Hilde B ; Valen, Merete ; Apalset, Ellen M ; Gjesdal, Clara G</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c392t-c311f58580ddc6678066a1422f2d41e6d39d558c187eaa86fbecf7ec0883264a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>3-hydroxykynurenine: xanthurenic acid ratio</topic><topic>Adult</topic><topic>Arthritis</topic><topic>Arthritis, Rheumatoid - blood</topic><topic>Arthritis, Rheumatoid - drug therapy</topic><topic>Biomarkers - blood</topic><topic>C-Reactive Protein - metabolism</topic><topic>Correlation</topic><topic>Correlation analysis</topic><topic>Etanercept</topic><topic>Female</topic><topic>functional vitamin B-6 status</topic><topic>Humans</topic><topic>Inflammation</topic><topic>Infliximab</topic><topic>Inhibitors</topic><topic>Joint diseases</topic><topic>Kynurenine - analogs & derivatives</topic><topic>Kynurenine - blood</topic><topic>Liquid chromatography</topic><topic>Longitudinal Studies</topic><topic>Male</topic><topic>Mass spectrometry</topic><topic>Mass spectroscopy</topic><topic>Medical treatment</topic><topic>Metabolism</topic><topic>Middle Aged</topic><topic>Monoclonal antibodies</topic><topic>Nutritional Status</topic><topic>Patients</topic><topic>pyridoxal 5′-phosphate</topic><topic>Pyridoxal Phosphate - blood</topic><topic>Regression analysis</topic><topic>Rheumatoid arthritis</topic><topic>TNF inhibitors</topic><topic>TNFα inhibitors</topic><topic>Treatment Outcome</topic><topic>Tumor Necrosis Factor Inhibitors - therapeutic use</topic><topic>Tumor Necrosis Factor-alpha - antagonists & inhibitors</topic><topic>Tumor Necrosis Factor-alpha - blood</topic><topic>Tumor necrosis factor-α</topic><topic>Ultrasound</topic><topic>Vitamin B</topic><topic>Vitamin B 6 - blood</topic><topic>Vitamin B 6 Deficiency - blood</topic><topic>Vitamin B 6 Deficiency - complications</topic><topic>Xanthurenates - blood</topic><topic>Xanthurenic acid</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sande, Jon Sigurd</creatorcontrib><creatorcontrib>Ulvik, Arve</creatorcontrib><creatorcontrib>Midttun, Øivind</creatorcontrib><creatorcontrib>Ueland, Per M</creatorcontrib><creatorcontrib>Hammer, Hilde B</creatorcontrib><creatorcontrib>Valen, Merete</creatorcontrib><creatorcontrib>Apalset, Ellen M</creatorcontrib><creatorcontrib>Gjesdal, Clara G</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><jtitle>The Journal of nutrition</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sande, Jon Sigurd</au><au>Ulvik, Arve</au><au>Midttun, Øivind</au><au>Ueland, Per M</au><au>Hammer, Hilde B</au><au>Valen, Merete</au><au>Apalset, Ellen M</au><au>Gjesdal, Clara G</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Vitamin B-6 Status Correlates with Disease Activity in Rheumatoid Arthritis Patients During Treatment with TNFα Inhibitors</atitle><jtitle>The Journal of nutrition</jtitle><addtitle>J Nutr</addtitle><date>2019-05</date><risdate>2019</risdate><volume>149</volume><issue>5</issue><spage>770</spage><epage>775</epage><pages>770-775</pages><issn>0022-3166</issn><eissn>1541-6100</eissn><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 3 mo 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.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>31050750</pmid><doi>10.1093/jn/nxz001</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | The Journal of nutrition, 2019-05, Vol.149 (5), p.770-775 |
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| subjects | 3-hydroxykynurenine: xanthurenic acid ratio Adult Arthritis Arthritis, Rheumatoid - blood Arthritis, Rheumatoid - drug therapy Biomarkers - blood C-Reactive Protein - metabolism Correlation Correlation analysis Etanercept Female functional vitamin B-6 status Humans Inflammation Infliximab Inhibitors Joint diseases Kynurenine - analogs & derivatives Kynurenine - blood Liquid chromatography Longitudinal Studies Male Mass spectrometry Mass spectroscopy Medical treatment Metabolism Middle Aged Monoclonal antibodies Nutritional Status Patients pyridoxal 5′-phosphate Pyridoxal Phosphate - blood Regression analysis Rheumatoid arthritis TNF inhibitors TNFα inhibitors Treatment Outcome Tumor Necrosis Factor Inhibitors - therapeutic use Tumor Necrosis Factor-alpha - antagonists & inhibitors Tumor Necrosis Factor-alpha - blood Tumor necrosis factor-α Ultrasound Vitamin B Vitamin B 6 - blood Vitamin B 6 Deficiency - blood Vitamin B 6 Deficiency - complications Xanthurenates - blood Xanthurenic acid |
| title | Vitamin B-6 Status Correlates with Disease Activity in Rheumatoid Arthritis Patients During Treatment with TNFα Inhibitors |
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