Sustained effect after lowering high-dose infliximab in patients with rheumatoid arthritis: A prospective dose titration study

Department of Pharmacy, Sint Maartenskliniek, PO Box 9011, 6500 GM, Nijmegen, The Netherlands.
Annals of the rheumatic diseases (Impact Factor: 10.38). 12/2008; 67(12):1697-701. DOI: 10.1136/ard.2007.083683
Source: PubMed


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.
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.
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.
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.

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Available from: Gijs F Snijders, Jul 02, 2014
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    • "This criterion has been validated recently, and has been shown to have the optimal tradeoff between sensitivity and specificity, and the best construct and criterion validity [40]. As it has been shown that flares are frequently temporary and occur and disappear without regimen change, a flare is only considered a flare if it is confirmed after at least 4 weeks [11]. Patients are however not left untreated, and when a flare in disease activity occurs, all bridging therapy including i.a. or im steroids or NSAID can be given and are allowed. "
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    • "Increasing the dose or reducing the intervals of administration may have additional benefit. When achieving remission or dealing with a low disease activity, an ongoing therapeutic effect may be sustained successfully despite a lowering of the dose [13]. In contrast, when failing to evoke any response, continued administration of a TNF inhibitor should be appraised critically. "
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