Population pharmacokinetics of ustekinumab in patients with active psoriatic arthritis.

PURPOSE

To characterize the population pharmacokinetics of subcutaneous ustekinumab, a human IgG1Kappa; monoclonal antibody against interleukin-12/23p40, using data from a randomized, double-blind, placebo-controlled Phase II study in patients with active psoriatic arthritis (PsA).

METHODS

A total of 786 quantifiable serum ustekinumab concentrations from 130 patients were analyzed using a nonlinear mixed-effects modeling approach. A 1-compartment model with first-order absorption and elimination was selected as the structural model.

RESULTS

The population typical mean (percent relative standard error (%RSE)) values for apparent clearance (CL/F), apparent volume of distribution (V/F), and absorption rate constant (ka) obtained from the final covariate model were 0.465 l × day-1 (5.1%), 14.3 l (4.4%), and 0.427 day-1 (3.9%), respectively. The between-subject variability in CL/F, V/F, and ka were 53.9%, 42.3%, and 82.4%, respectively. Patient body weight and antibody-to-ustekinumab status were significant covariates affecting the CL/F and/or V/F of ustekinumab. None of the other factors evaluated, such as age, sex, race, baseline disease characteristics, concomitant methotrexate or nonsteroidal anti-inflammatory drugs, and past use of immunosuppressives, biologics, systemic corticosteroids, or disease-modifying antirheumatic drugs, were found to have significant effects on the pharmacokinetics of ustekinumab.

CONCLUSION

The pharmacokinetics of ustekinumab in patients with PsA are comparable to those in patients with moderate-to-severe plaque psoriasis which was previously investigated.