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Formation of antibodies against infliximab and adalimumab strongly correlates with functional drug levels and clinical responses in rheumatoid arthritis.
  1. Timothy RDJ Radstake (t.radstake{at}reuma.umcn.nl)
  1. University Medical Center Nijmegen, Netherlands
    1. Morten Svenson
    1. Institute for Inflammation Research (IIR), Rigshospitalet National University Hospital Copenhagen, Denmark
      1. Agnes M Eijsbouts
      1. Sint Maartenskliniek, Netherlands
        1. Frank HJ van den Hoogen (f.vandenhoogen{at}maartenskliniek.nl)
        1. Sint Maartenskliniek, Netherlands
          1. Christian Enevold
          1. Institute for Inflammation Research (IIR), Rigshospitalet National University Hospital Copenhagen, Denmark
            1. Piet LCM van Riel (p.vanriel{at}reuma.umcn.nl)
            1. University Medical Center Nijmegen, Netherlands
              1. Klaus Bendtzen
              1. Institute for Inflammation Research (IIR), Rigshospitalet National University Hospital Copenhagen, Denmark

                Abstract

                Introduction: TNF-alpha neutralizing antibody constructs are increasingly being used to treat rheumatoid arthritis (RA). The current study focused on potential differences in clinical responses, soluble drug levels and antibody formation between RA patients receiving infliximab and adalimumab.

                Methods: RA patients, 69, fulfilling the 1987 ACR criteria and about to start treatment with infliximab or adalimumab, were enrolled consecutively. All patients had active disease DAS28 > 3.2. Infliximab was given intravenously at 3 mg/kg at baseline and after 2, 6 and 14 weeks. Adalimumab was administered as 40 mg biweekly s.c. Concomitant medication was monitored and continued at constant dosage during the study. All sera were tested for infliximab/adalimumab levels and anti-infliximab/anti-adalimumab antibodies.

                Results: Infliximab was administered to 35 patients, 34 received adalimumab. At six months, 15 (43%), 6 (17%) and 14 (40%) of the infliximab-treated patients fulfilled the EULAR criteria for good, moderate and non-responders, respectively, whereas the corresponding figures for adalimumab treated patients were 16 (47%), 8 (24%) and 10 (29%). Clinical responses correlated with the levels of S-infliximab/adalimumab and the formation of anti-infliximab/anti-adalimumab antibodies.

                Discussion: We demonstrate that the clinical response to two anti-TNF-alpha biologicals closely follows the trough drug levels and the presence of antibodies directed against the drugs. Further studies that focus on the underlying pathways leading to antibody formation are warranted to predict immunogenicity of these expensive biologicals and treatment outcomes.

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