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Sustained effect after lowering high dose infliximab in patients with rheumatoid arthritis: a prospective dose titration study
  1. Bart JF Van den Bemt (b.vandenbemt{at}maartenskliniek.nl)
  1. Sint Maartenskliniek, Netherlands
    1. Alfons A den Broeder (a.denbroeder{at}maartenskliniek.nl)
    1. Sint Maartenskliniek, Netherlands
      1. Gijs F Snijders (g.snijders{at}maartenskliniek.nl)
      1. Sint Maartenskliniek, Netherlands
        1. Yechiel A Hekster (y.hekster{at}akf.umcn.nl)
        1. University Medical Centre Nijmegen, Netherlands
          1. Piet CLM van Riel (p.vanriel{at}reuma.umcn.nl)
          1. University Medical Center Nijmegen, Netherlands
            1. Bart Benraad (b.benraad{at}maartenskliniek.nl)
            1. Sint Maartenskliniek, Netherlands
              1. Gert-Jan Wolbink (g.wolbink{at}janvanbreemen.nl)
              1. Sanquin, Netherlands
                1. Frank HJ van den Hoogen (f.vandenhoogen{at}maartenskliniek.nl)
                1. Sint Maartenskliniek, Netherlands

                  Abstract

                  Objectives: In clinical trials only a small subset of patients with Rheumatoid Arthritis (RA) benefits from higher than standard dose of infliximab (> 3 mg/kg/8 wks). However, dose escalation of infliximab is frequently applied in clinical practice. Individual adjustment of infliximab treatment based on actual disease activity, instead of subjective clinical judgement, could prevent possible unwarranted dose escalation.

                  Methods: The infliximab dose of all RA patients treated at our centre was decreased from 5 mg/kg to 3 mg/kg, leaving dosing intervals unaltered. Subsequently patients were followed for at least 3 infusions. At every visit DAS28, infliximab serum trough levels and anti-infliximab-antibody levels were assessed. Inversed EULAR criteria (flare criteria) were used as endpoint.

                  Results: 18 patients were included. Mean (± SD) DAS28-scores before dose reduction and after first and second low dose was 3.2 (± 1.2), 3.2 (± 1.8) and 3.3 (± 1.2) respectively (NS). One patient (6%, CI 0-17%) developed a persistent flare that subsided after increasing infliximab doses and one patient stopped infliximab because of a lupus like reaction. In all other patients (n=16) lowering infliximab resulted in unaltered disease activity. Infliximab levels showed that most patients had either low- (< 1 mg/l) or high (> 5 mg/l) serum trough levels. Anti-infliximab antibodies were detected in 4 patients.

                  Conclusion: Infliximab dosages of 5 mg/kg can be lowered in the majority of RA patients using DAS28 guided dose titration without increase of disease activity. Lowering the dose of infliximab should be considered in every patient receiving higher doses infliximab.

                  • RA
                  • antiTNF-alpha
                  • dose titration
                  • infliximab
                  • treatment outcome

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