RESEARCH - Sustained effect after lowering high dose Remicade in patients with RA: a prospective dose titration study

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Ann Rheum Dis. Published Online First: 31 January 2008.

doi:10.1136/ard.2007.083683

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Extended Report

Sustained effect after lowering high dose infliximab in patients with

rheumatoid arthritis: a prospective dose titration study

Bart JF Van den Bemt 1*, Alfons A den Broeder 1, Gijs F Snijders 1,

Yechiel A Hekster 2, Piet CLM van Riel 3, Bart Benraad 1, Gert-Jan

Wolbink 4 and HJ van den Hoogen 1

1 Sint Maartenskliniek, Netherlands

2 University Medical Centre Nijmegen, Netherlands

3 University Medical Center Nijmegen, Netherlands

4 Sanquin, 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.

http://ard.bmj.com/cgi/content/abstract/ard.2007.083683v1?papetoc

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