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Anti-infliximab and anti-adalimumab antibodies in relation to response to adalimumab in infliximab switchers and anti-TNF naive patients: a cohort study.
  1. Geertje M Bartelds (m.bartelds{at}
  1. Jan van Breemen Institute, Netherlands
    1. Carla A Wijbrandts (c.a.wijbrandts{at}
    1. AMC/University Medical Center, Netherlands
      1. Michael T Nurmohamed (m.nurmohamed{at}
      1. VU University medical center, Netherlands
        1. Steven O Stapel (s.stapel{at}
        1. Sanquin, Netherlands
          1. Willem F Lems (wf.lems{at}
          1. VU University Medical Center, Netherlands
            1. Lucien Aarden (l.aarden{at}
            1. Sanquin, Netherlands
              1. Ben A C Dijkmans (bac.dijkmans{at}
              1. VU University Medical Center, Netherlands
                1. Paul Peter Tak (p.p.tak{at}
                1. AMC Amsterdam, Netherlands
                  1. Gerrit Jan Wolbink (g.wolbink{at}
                  1. Jan van Breemen Institute, Netherlands


                    Objective To investigate how antibodies against anti-TNF agents influence response after switching from infliximab to adalimumab in rheumatoid arthritis (RA).

                    Methods: This cohort study consisted of 235 RA patients, all treated with adalimumab. At baseline fifty-two patients (22%) were previously treated with infliximab ("switchers"), and 183(78%) were anti-TNF naive. Disease activity (using the DAS28score) and presence of antibodies against infliximab and adalimumab was assessed. Clinical response to adalimumab was compared between switchers and anti-TNF naive patients and their anti-infliximab and anti-adalimumab antibody status.

                    Results After 28 weeks of adalimumab therapy the decrease in DAS28 (ΔDAS28) for the 235 patients was 1.6±1.5 (mean±SD). Anti-adalimumab antibodies were detected in 46 patients (20%). ΔDAS28 was 1.8±1.4 in patients without anti-adalimumab and 0.6±1.3 in patients with anti-adalimumab (P<0.0001). Thirty-three out of the 52 switchers (63%) had anti-infliximab antibodies. Patients with anti-infliximab more often developed anti-adalimumab than anti-TNF naive patients, (14(27%) versus 32(18%);(P=0.039)). ΔDAS28 was greater for anti-TNF naive patients (1.7±1.5) compared to switchers without anti-infliximab antibodies (ΔDAS28=0.9±1.4) (P=0.009). ΔDAS28 for switchers with anti-infliximab was 1.2±1.3 and did not differ significantly from anti-TNF naive patients (P=0.262).

                    Conclusion Switchers with anti-infliximab antibodies more often develop antibodies against adalimumab than anti-TNF naive patients. Response to adalimumab was limited in switchers without anti-infliximab antibodies, which raises the question whether a second anti-TNF therapy should be offered to RA-patients who fail on initial treatment with anti-TNF, in the absence of anti-biological antibodies.

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