THU0193 Body Weight and Sex Influence the Pharmacokinetics of Adalimumab in Rheumatoid Arthritis

Abstract

Background Adalimumab, an anti-TNF-α monoclonal antibody, is effective in active rheumatoid arthritis (RA). Subcutaneous injections of adalimumab lead to highly variable trough concentrations between patients [1] that may partly explain the variability of response. To date, adalimumab pharmacokinetics (PK) after subcutaneous route has never been described. Objectives The goal of this study is to analyse the quantitative influence of individual factors on adalimumab PK in RA patients. Methods One hundred and twenty seven samples from 30 RA patients were used to measure adalimumab concentration [in a post-hoc analysis]. All patients received adalimumab 40 mg subcutaneously every other week. CRP levels and RA disease activity score (DAS28) were available at baseline, weeks 6, 12, 24 and 52. Adalimumab PK was described using a single compartment model with first-order absorption and elimination rates. A population approach was used. Sex, age, body weight, corticosteroid use and CRP levels were tested as covariates on each pharmacokinetic parameter. Results The following pharmacokinetic parameters were estimated (interidividual coefficient of variation): apparent volume of distribution (Vd/F) = 12.4 L (75%), apparent clearance (CL/F) = 0.31 L/day (17%) and first-order absorption constant (ka) = 0.41 day-1. Apparent clearance increased with body weight and was higher in men. Age, CRP levels, and concomitant treatment with corticosteroid had no effect on pharmacokinetic parameters. Adalimumab concentrations reached steady state after 20 weeks in men and 28 weeks in women. Conclusions Men eliminate adalimumab faster than women and the rate of elimination increases with weight in RA. Monitoring of serum adalimumab concentrations may be useful to avoid underexposure and treatment failure. Time to steady state was long and raises the question of a loading dose of adalimumab at initiation. References Bartelds GM et al. Clinical response to adalimumab: relationship to anti-adalimumab antibodies and serum adalimumab concentrations in rheumatoid arthritis. Ann Rheum Dis. 2007; 66(7):921-926. Acknowledgements Pr Christian Marcelli, CHU Caen. Pr René-Marc Flipo, CHU Lille. Pr Patrice Fardellone, CHU d’Amiens Disclosure of Interest None Declared