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

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. At the time of a single visit, anticoagulated blood was collected randomly …