RESEARCH - Sustained effect after lowering high-dose Remicade in patients with RA

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Published Online First: 31 January 2008. doi:10.1136/ard.2007.083683

ls of the Rheumatic Diseases 2008;67:1697-1701

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CLINICAL AND EPIDEMIOLOGICAL RESEARCH

Sustained effect after lowering high-dose infliximab in patients with

rheumatoid arthritis: a prospective dose titration study

B J F van den Bemt 1, A A den Broeder 2, G F Snijders 2, Y A Hekster

3, P L C M van Riel 4, B Benraad 1, G J Wolbink 5, F H J van den

Hoogen 1,2

1 Department of Pharmacy, Sint Maartenskliniek, Nijmegen, The Netherlands

2 Department of Rheumatology, Sint Maartenskliniek, Nijmegen, The Netherlands

3 Department of Clinical Pharmacy, University Medical Centre Nijmegen,

Nijmegen, The Netherlands

4 Department of Rheumatology, University Medical Centre Nijmegen,

Nijmegen, The Netherlands

5 Department of Immunopathology, Sanquin, Amsterdam, The Netherlands

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 weeks). 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 patients with RA 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 three

infusions. At every visit, 28-joint Disease Activity Score (DAS28),

infliximab serum trough levels and anti-infliximab antibody levels

were assessed. Inversed European League Against Rheumatism (EULAR)

criteria (flare criteria) were used as the endpoint.

Results: A total of 18 patients were included in the study. Mean (SD)

DAS28 scores before dose reduction and after first and second low dose

were 3.2 (1.2), 3.2 (1.8) and 3.3 (1.2), respectively (values not

significant). One patient (6%, 95% CI 0% to 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/litre) or high (>5 mg/litre) serum trough levels.

Anti-infliximab antibodies were detected in four patients.

Conclusion: Infliximab dosages of 5 mg/kg can be lowered in the

majority of patients with RA 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/67/12/1697?etoc

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