Baseline serum levels of cross-linked carboxy-terminal telopeptide of type I collagen predict abatacept treatment response in methotrexate-naive, anticitrullinated protein antibody-positive patients with early rheumatoid arthritis
Objective To investigate correlations between biomarkers of bone remodelling and extracellular matrix turnover with baseline disease activity and treatment response in patients with early rheumatoid arthritis (RA).Methods Assessing Very Early Rheumatoid arthritis Treatment-2 (AVERT-2; NCT02504268) i...
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| Format: | Article |
| Language: | English |
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BMJ Publishing Group
2022-11-01
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| Series: | RMD Open |
| Online Access: | https://rmdopen.bmj.com/content/8/2/e002683.full |
| _version_ | 1797783990404382720 |
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| author | Roy Fleischmann Yoshiya Tanaka Paul Emery Vivian P Bykerk Sean E Connolly Chun Wu Robert Wong Jinqi Liu Peter Schafer Yanhua Hu Anne-Christine Bay-Jensen Signe Holm Nielsen Thomas WJ Huizinga |
| author_facet | Roy Fleischmann Yoshiya Tanaka Paul Emery Vivian P Bykerk Sean E Connolly Chun Wu Robert Wong Jinqi Liu Peter Schafer Yanhua Hu Anne-Christine Bay-Jensen Signe Holm Nielsen Thomas WJ Huizinga |
| author_sort | Roy Fleischmann |
| collection | DOAJ |
| description | Objective To investigate correlations between biomarkers of bone remodelling and extracellular matrix turnover with baseline disease activity and treatment response in patients with early rheumatoid arthritis (RA).Methods Assessing Very Early Rheumatoid arthritis Treatment-2 (AVERT-2; NCT02504268) included disease-modifying antirheumatic drug-naive, anti-citrullinated protein antibody (ACPA)-positive patients randomised to weekly subcutaneous abatacept+methotrexate (MTX) or abatacept placebo+MTX for 56 weeks. This post hoc exploratory subanalysis assessed the association between baseline disease activity and eight biomarkers (Spearman’s correlation coefficient), and whether baseline biomarkers (continuous or categorical variables) could predict treatment response at weeks 24 and 52 (logistic regression).Results Patient characteristics were similar between overall (n=752) and biomarker subgroup (n=535) populations and across treatments. At baseline, neoepitopes of matrix metalloproteinase-mediated degradation products of types III and IV collagen and of C reactive protein (CRP) showed the greatest correlations with disease activity; cross-linked carboxy-terminal telopeptide of type I collagen (CTX-I) showed weak correlation. Only CTX-I predicted treatment response; baseline CTX-I levels were significantly associated with achieving Simplified Disease Activity Index remission and Disease Activity Score in 28 joints (DAS28 (CRP)) <2.6 (weeks 24 and 52), and American College of Rheumatology 70 response (week 52), in patients treated with abatacept+MTX but not abatacept placebo+MTX. CTX-I predicted significant differential response between arms for DAS28 (CRP) <2.6 (week 24). Treatment differences were greater for abatacept+MTX in patients with medium/high versus low baseline CTX-I.Conclusion In MTX-naive, ACPA-positive patients with early RA, baseline CTX-I predicted treatment response to abatacept+MTX but not abatacept placebo+MTX. |
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| id | doaj.art-2a9e02db78e349b3ae668131a832d057 |
| institution | Directory Open Access Journal |
| issn | 2056-5933 |
| language | English |
| last_indexed | 2024-03-13T00:33:37Z |
| publishDate | 2022-11-01 |
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| series | RMD Open |
| spelling | doaj.art-2a9e02db78e349b3ae668131a832d0572023-07-10T07:00:06ZengBMJ Publishing GroupRMD Open2056-59332022-11-018210.1136/rmdopen-2022-002683Baseline serum levels of cross-linked carboxy-terminal telopeptide of type I collagen predict abatacept treatment response in methotrexate-naive, anticitrullinated protein antibody-positive patients with early rheumatoid arthritisRoy Fleischmann0Yoshiya Tanaka1Paul Emery2Vivian P Bykerk3Sean E Connolly4Chun Wu5Robert Wong6Jinqi Liu7Peter Schafer8Yanhua Hu9Anne-Christine Bay-Jensen10Signe Holm Nielsen11Thomas WJ Huizinga12Metroplex Clinical Research Center, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, USAThe First Department of Internal Medicine, University of Occupational and Environmental Health Japan, Kitakyushu, JapanUniversity of Leeds and Leeds NIHR Biomedical Research Centre, Leeds, UKRheumatology, Hospital for Special Surgery, New York City, New York, USABristol Myers Squibb, Princeton, New Jersey, USA1 Department of Cardiothoracic Surgery, Chongqing Medical University Affiliated Children`s Hospital, Chongqing, China4 Gastroenterology and Hepatology, Alameda Health System, Oakland, California, USABristol Myers Squibb, Princeton, New Jersey, USATranslational Medicine Department, Bristol-Myers Squibb Co, Princeton, New Jersey, USAKing’s College LondonNordic Bioscience, Herlev, DenmarkNordic Bioscience, Herlev, DenmarkLeiden University Medical Center, Leiden, NetherlandsObjective To investigate correlations between biomarkers of bone remodelling and extracellular matrix turnover with baseline disease activity and treatment response in patients with early rheumatoid arthritis (RA).Methods Assessing Very Early Rheumatoid arthritis Treatment-2 (AVERT-2; NCT02504268) included disease-modifying antirheumatic drug-naive, anti-citrullinated protein antibody (ACPA)-positive patients randomised to weekly subcutaneous abatacept+methotrexate (MTX) or abatacept placebo+MTX for 56 weeks. This post hoc exploratory subanalysis assessed the association between baseline disease activity and eight biomarkers (Spearman’s correlation coefficient), and whether baseline biomarkers (continuous or categorical variables) could predict treatment response at weeks 24 and 52 (logistic regression).Results Patient characteristics were similar between overall (n=752) and biomarker subgroup (n=535) populations and across treatments. At baseline, neoepitopes of matrix metalloproteinase-mediated degradation products of types III and IV collagen and of C reactive protein (CRP) showed the greatest correlations with disease activity; cross-linked carboxy-terminal telopeptide of type I collagen (CTX-I) showed weak correlation. Only CTX-I predicted treatment response; baseline CTX-I levels were significantly associated with achieving Simplified Disease Activity Index remission and Disease Activity Score in 28 joints (DAS28 (CRP)) <2.6 (weeks 24 and 52), and American College of Rheumatology 70 response (week 52), in patients treated with abatacept+MTX but not abatacept placebo+MTX. CTX-I predicted significant differential response between arms for DAS28 (CRP) <2.6 (week 24). Treatment differences were greater for abatacept+MTX in patients with medium/high versus low baseline CTX-I.Conclusion In MTX-naive, ACPA-positive patients with early RA, baseline CTX-I predicted treatment response to abatacept+MTX but not abatacept placebo+MTX.https://rmdopen.bmj.com/content/8/2/e002683.full |
| spellingShingle | Roy Fleischmann Yoshiya Tanaka Paul Emery Vivian P Bykerk Sean E Connolly Chun Wu Robert Wong Jinqi Liu Peter Schafer Yanhua Hu Anne-Christine Bay-Jensen Signe Holm Nielsen Thomas WJ Huizinga Baseline serum levels of cross-linked carboxy-terminal telopeptide of type I collagen predict abatacept treatment response in methotrexate-naive, anticitrullinated protein antibody-positive patients with early rheumatoid arthritis RMD Open |
| title | Baseline serum levels of cross-linked carboxy-terminal telopeptide of type I collagen predict abatacept treatment response in methotrexate-naive, anticitrullinated protein antibody-positive patients with early rheumatoid arthritis |
| title_full | Baseline serum levels of cross-linked carboxy-terminal telopeptide of type I collagen predict abatacept treatment response in methotrexate-naive, anticitrullinated protein antibody-positive patients with early rheumatoid arthritis |
| title_fullStr | Baseline serum levels of cross-linked carboxy-terminal telopeptide of type I collagen predict abatacept treatment response in methotrexate-naive, anticitrullinated protein antibody-positive patients with early rheumatoid arthritis |
| title_full_unstemmed | Baseline serum levels of cross-linked carboxy-terminal telopeptide of type I collagen predict abatacept treatment response in methotrexate-naive, anticitrullinated protein antibody-positive patients with early rheumatoid arthritis |
| title_short | Baseline serum levels of cross-linked carboxy-terminal telopeptide of type I collagen predict abatacept treatment response in methotrexate-naive, anticitrullinated protein antibody-positive patients with early rheumatoid arthritis |
| title_sort | baseline serum levels of cross linked carboxy terminal telopeptide of type i collagen predict abatacept treatment response in methotrexate naive anticitrullinated protein antibody positive patients with early rheumatoid arthritis |
| url | https://rmdopen.bmj.com/content/8/2/e002683.full |
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