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Differing contribution of methotrexate polyglutamates to adalimumab blood levels as compared with etanercept

Published on Mar 18, 2019in Annals of the Rheumatic Diseases14.30
· DOI :10.1136/annrheumdis-2018-214860
Thierry Dervieux13
Estimated H-index: 13
,
Joel M. Kremer69
Estimated H-index: 69
,
Michael E. Weinblatt77
Estimated H-index: 77
(Brigham and Women's Hospital)
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Abstract
Methotrexate (MTX) is known to improve blood levels and clinical outcome to anti-tumour necrosis factor (anti-TNF) therapy by reducing the formation of antidrug antibodies.1 Recent findings indicate that MTX prevents immunisation against TNF inhibitors through de novo purine biosynthesis inhibition and generation of immunosuppressive adenosine.2 This effect is mediated by activation of MTX prodrug to MTX polyglutamates (MTXPG), and we previously reported that MTXPG levels were associated with improved steady state levels of infliximab.3 In this study, we extended these observations and evaluated the impact of MTXPG on adalimumab and etanercept levels. The study was cross-sectional by design, multicentred (three sites) and enrolled 169 consecutive consented adult rheumatoid arthritis subjects under MTX in combination with adalimumab (83 subjects) or etanercept (86 subjects). All patients enrolled were inadequate responders to MTX prior to starting anti-TNF therapy and had received MTX with anti-TNF therapy for least 3 months. …
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References6
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Published on Jun 23, 2018in Annals of the Rheumatic Diseases14.30
Samuel Bitoun1
Estimated H-index: 1
,
Gaetane Nocturne15
Estimated H-index: 15
+ 15 AuthorsKimberly Florence1
Estimated H-index: 1
(GSK: GlaxoSmithKline)
Objectives TNF inhibitors (TNFi) can induce anti-drug antibodies (ADA) in patients with autoimmune diseases (AID) leading to clinical resistance. We explored a new way of using methotrexate (MTX) to decrease this risk of immunisation. Methods We treated BAFF transgenic (BAFFtg) mice, a model of AID in which immunisation against biologic drugs is high, with different TNFi. We investigated the effect of a single course of MTX during the first exposure to TNFi. Wild-type (WT) and BAFFtg mice were c...
Published on Apr 1, 2018in Annals of the Rheumatic Diseases14.30
Denis Mulleman24
Estimated H-index: 24
(François Rabelais University),
Alejandro Balsa40
Estimated H-index: 40
(Hospital Universitario La Paz)
Drug monitoring consists of observing, recording or detecting the effects of a substance administered to an individual. Therapeutic drug monitoring (TDM) aims at improving patient care based on drug concentration measurement in order to adjust the dose or time interval individually.1 TDM is based on the assumption of a definable relation between dose and plasma/blood drug concentration and between concentration and therapeutic effects. In ARD , l’Ami et al conducted an open-label randomised tria...
Published on Apr 1, 2018in Annals of the Rheumatic Diseases14.30
M.J. l’Ami2
Estimated H-index: 2
,
C. Krieckaert7
Estimated H-index: 7
+ 4 AuthorsGerrit Jan Wolbink30
Estimated H-index: 30
Objective High adalimumab serum concentrations do not result in better response in patients with rheumatoid arthritis (RA), suggesting overexposure. We investigated whether patients with adalimumab concentrations >8 µg/mL can prolong their dosing interval by 50% without a clinically relevant change in disease activity. Methods Consecutive patients with RA, treated with adalimumab 40 mg every other week for at least 28 weeks, were approached for this randomised, open-label, non-inferiority trial....
Published on Dec 1, 2013in Annals of the Rheumatic Diseases14.30
S. Garcês5
Estimated H-index: 5
(IGC: Instituto Gulbenkian de Ciência),
Jocelyne Demengeot27
Estimated H-index: 27
(IGC: Instituto Gulbenkian de Ciência),
Elizabeth Benito-Garcia3
Estimated H-index: 3
Background Immunogenicity of aTNFs is one of the mechanisms behind treatment failure. Objective To assess the effect of anti-drug antibodies (ADA) on drug response to infliximab, adalimumab and etanercept, and the effect of immunosuppression on ADA detection, in patients with Rheumatoid Arthritis, Spondyloarthritis, Psoriasis and Inflammatory Bowel Diseases. Data sources PubMed, EMBASE, Cochrane databases, article reference lists (through August 19 2012). Study selection Out of 2082 studies, 17 ...
Published on Jun 1, 2013in Annals of the Rheumatic Diseases14.30
Thierry Dervieux13
Estimated H-index: 13
(AmeriCorps VISTA),
Michael E. Weinblatt77
Estimated H-index: 77
(Brigham and Women's Hospital)
+ 1 AuthorsJoel M. Kremer69
Estimated H-index: 69
Objective The combination of methotrexate (MTX) with infliximab can modify infliximab pharmacokinetics and lower the incidence of antibodies against infliximab (ATIs). We hypothesised that the pharmacokinetic interaction between MTX and infliximab is related to activation of MTX to immunosuppressive MTX polyglutamates (MTXPGs). Methods Adult patients with rheumatoid arthritis receiving weekly MTX with infliximab for more than 3 months were enrolled in a cross-sectional study. Blood was collected...
Published on Nov 1, 2012in Annals of the Rheumatic Diseases14.30
Charlotte L. M. Krieckaert12
Estimated H-index: 12
,
Michael T. Nurmohamed16
Estimated H-index: 16
(VUmc: VU University Medical Center),
Gerrit Jan Wolbink30
Estimated H-index: 30
Immunogenicity of adalimumab could impair important treatment outcome parameters in patients with rheumatoid arthritis (RA). Patients who developed antiadalimumab antibodies (AAA) during a 3 year time period achieved less often minimal disease activity or remission and treatment failure occurred more often compared with patients without AAA.1 There were remarkable baseline differences: patients developing AAA had more long-standing, severe disease and less often used concomitant medication inclu...
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