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


CONCLUSIONS
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.
van den Bemt
B J F
BJ
Department of Pharmacy, Sint Maartenskliniek, PO Box 9011, 6500 GM, Nijmegen, The Netherlands. b.vandenbemt@maartenskliniek.nl
den Broeder
A A
AA
Snijders
G F
GF
Hekster
Y A
YA
van Riel
P L C M
PL
Benraad
B
B
Wolbink
G J
GJ
van den Hoogen
F H J
FH
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000097:blood / Q000276:immunology / Q000627:therapeutic use; D000917:Antibody Formation; D018501:Antirheumatic Agents / Q000008:administration & dosage* / Q000097:blood / Q000276:immunology / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004812:Epidemiologic Methods; D005260:Female; D006801:Humans; D000069285:Infliximab; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab