Background Treatment with biologicals is based on the principle of “one size fits all” without taking differences in dosing schemes, patients characteristics and pharmacokinetics into account.
Objectives To compare disease activity 26 weeks after dose interval prolongation versus continuation of the regular dose in rheumatoid arthritis (RA) patients with high serum adalimumab concentration1.
Methods In the interim analysis of this open randomised controlled trial, patients with an adalimumab concentration >8 mL/L were randomly (1:1) assigned to continuation of adalimumab every other week (continuation group) or prolongation of the dosage interval to once every 3 weeks (tapering group), independently of disease activity score in 28 joints (DAS28). Patients were treated with adalimumab 40 mg subcutaneous every other week for at least 28 weeks before start of the study. Visits were scheduled at baseline, 13 and 26 weeks thereafter. The change in DAS28 (ΔDAS28) after 26 weeks compared to baseline was taken as outcome measurement and a clinical relevant difference was defined as a ΔDAS28 >0.6. Based on an intention to treat analysis, an independent t-test was used to compare mean ΔDAS28 between the two groups. A total of 102 patients was calculated as a priori sample size.
Results Fifty-three patients out of 142 screened patients (37%) had adalimumab concentrations >8 mL/L and were included in the study. All patients completed follow up. Twenty-six patients were randomly assigned to continuation group and 27 patients were assigned to tapering group. Patients characteristics at baseline did not differ significantly between the two groups. After 26 weeks, mean ΔDAS28 did not meet the criteria for a clinically relevant difference in both continuation group (0.29± 0.58 standard deviation (SD)) and tapering group (-0.06±0.58 SD) and did not significantly differ (p=0.06) between groups (see figure). Six patients in the continuation group developed active inflammation (defined as an increase of ≥1 swollen joint compared to baseline) during follow-up. In the tapering group, two patients developed active inflammation of whom one returned to standard dose of adalimumab. Despite the absence of inflammatory signs, eight other patients in the tapering group returned to standard dose on request of patient or treating rheumatologist.
Conclusions This interim analysis shows that disease activity remains stable in RA patients with adalimumab concentrations >8 mL/L who prolonged their dose interval to once in the three weeks compared to patients who continued adalimumab every other week.
Pouw MF, Krieckaert CL, Nurmohamed MT, van der Kleij D, Aarden L, Rispens T, Wolbink GJ. Key findings towards optimising adalimumab treatment: the concentration-effect curve. Ann Rheum Dis, 2015;74(3);513–8
Disclosure of Interest M. l'Ami: None declared, A. Marsman Speakers bureau: Pfizer, C. Krieckaert Speakers bureau: Pfizer, J. Ruwaard: None declared, E. Kneepkens Speakers bureau: Pfizer, M. Nurmohamed Grant/research support from: AbbVie, BMS, Pfizer, UCB, Roche, Consultant for: Abbott, BMS, Pfizer, Roche, Speakers bureau: AbbVie, Pfizer, Roche, G. Wolbink Grant/research support from: Pfizer, Consultant for: Pfizer, AbbVie, UCB, Munidfarma, BMS, Speakers bureau: Pfizer, UCB
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