Vol.21 No.6

Original Article

Primary lack of efficacy of infliximab therapy for rheumatoid arthritis: pharmacokinetic characterization and assessment of switching to tocilizumab

Authors

Shunsuke Mori1 , Yukitaka Ueki2

  • Department of Rheumatology, Clinical Research Center for Rheumatic Disease, NHO Kumamoto Saishunsou National Hospital, 2659 Suya, Kohshi, Kumamoto, 861-1196, Japan
  • Rheumatic and Collagen Disease Center, Sasebo Chuo Hospital, Nagasaki, Japan
Received:

18 January 2011

Accepted:

13 April 2011

Published online:

1 May 2011

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Abstract

To characterize primary failure to infliximab
and determine the efficacy of switching to tocilizumab in
patients with rheumatoid arthritis (RA), we examined 24 RA
patients who had started on infliximab therapy (3 mg/kg) as
their first biological agent. Nine of the 24 patients were
found to be primary nonresponders, defined as patients who
had never achieved a 20% clinical improvement according
to the American College of Rheumatology criteria
(ACR20) during induction therapy. The remaining 15
patients had achieved an ACR20 response to infliximab,
without any relapses, for at least the first 14 weeks. A
higher baseline health assessment questionnaire score was
markedly associated with primary unresponsiveness to
infliximab (p = 0.0005). Six of the 9 primary nonresponders
showed rapid clearance of infliximab: their trough
concentrations of infliximab were under 1 lg/ml. The other
3 were classified as exhibiting the residual type of unresponsiveness, which was defined as unresponsiveness in
patients who maintained serum infliximab levels above
1 lg/ml. Human antichimeric antibody was not detected
in the rapid-clearance nonresponders. Dose escalation
(5 mg/kg) was insufficiently effective. Primary nonresponders
to infliximab were started on tocilizumab therapy
(8 mg/kg, every 4 weeks), and their responses were
assessed after 24 weeks of this second attempt at therapy.
All the nonresponders, except for a single rapid-clearance
patient, had achieved an ACR20 clinical improvement at the
time of assessment. In conclusion, primary nonresponders to
infliximab can be classified into rapid-clearance and residual types, based on their trough concentrations of infliximab, but both types of nonresponders seem to benefit from an early decision to discontinue infliximab therapy and switch to tocilizumab.

Key words

Infliximab - Pharmacokinetics - Rheumatoid arthritis - Switching - Tocilizumab