Background/Purpose: Treatment with biologicals is based on the principle of ‘one size fits all’ without taking differences into account for dosing schemes, patients’ characteristics and pharmacokinetics. The aim of this study is to compare disease activity after 26 weeks between adalimumab dose interval prolongation and continuation of the regular dose in rheumatoid arthritis (RA) patients with high adalimumab serum concentration¹ .

Methods:  In this open randomized controlled trial, patients with an adalimumab concentration >8 mL/L were randomly (1:1) assigned to continuation of 40 mg adalimumab every other week (continuation group) or prolongation of the dosage interval to once every 3 weeks (tapering group). This was independently of disease activity score in 28 joints (DAS28). Before the study, patients were treated with adalimumab 40 mg subcutaneous every other week for at least 28 weeks. Visits were scheduled at baseline, 13 and 26 weeks thereafter. The change in DAS28 (deltaDAS28) after 26 weeks compared to baseline was taken as outcome measurement. A clinical relevant difference was defined as a deltaDAS28 >0.6. Based on an intention to treat analysis, an independent t-test was used to compare mean deltaDAS28 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 assigned to continuation group and 27 to tapering group. Baseline characteristics did not differ significantly between the two groups. After 26 weeks, mean deltaDAS28 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) (see figure). The groups were not significant different (p=0.06). 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.

Conclusion:  This study 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.

Reference: Pouw MF, Krieckaert CL, Nurmohamed, MT, van der Kleij D, Aarden L, Rispens T, Wolbink G. Key findings towards optimising adalimumab treatment: the concentration-effect curve. Ann Rheum Dis, 2015;74;513-8