Sustained effect after lowering high-dose infliximab in patients with rheumatoid arthritis: a prospective dose titration study
- B J F van den Bemt1,
- A A den Broeder2,
- G F Snijders2,
- Y A Hekster3,
- P L C M van Riel4,
- B Benraad1,
- G J Wolbink5,
- F H J van den Hoogen1,2
- 1Department of Pharmacy, Sint Maartenskliniek, Nijmegen, The Netherlands
- 2Department of Rheumatology, Sint Maartenskliniek, Nijmegen, The Netherlands
- 3Department of Clinical Pharmacy, University Medical Centre Nijmegen, Nijmegen, The Netherlands
- 4Department of Rheumatology, University Medical Centre Nijmegen, Nijmegen, The Netherlands
- 5Department of Immunopathology, Sanquin, Amsterdam, The Netherlands
- B J F van den Bemt, Department of Pharmacy, Sint Maartenskliniek, PO Box 9011, 6500 GM, Nijmegen, The Netherlands;
- Accepted 20 January 2008
- Published Online First 31 January 2008
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.
Competing interests: None.
Ethics approval: Approval from the Research Ethics Committee (MREC) was not necessary after consultation because dose adaptation was performed as part of usual care.