Population Pharmacokinetics and Immunogenicity of Adalimumab in Adult Patients with Moderate-to-Severe Hidradenitis Suppurativa.

INTRODUCTION: Hidradenitis suppurativa (HS) is a serious, debilitating, chronic inflammatory skin disease. Adalimumab is a fully human, immunoglobulin G1 monoclonal antibody specific for tumor necrosis factor-alpha recently approved for use in patients with HS. The aim of this study is to describe the population pharmacokinetics and immunogenicity of adalimumab in adult patients with HS.
METHODS: Data from one phase II and two phase III studies were included in the analysis. Serial serum adalimumab concentrations and anti-adalimumab antibody (AAA) development status were used to develop the population pharmacokinetic model. The population pharmacokinetic analysis involved evaluating the effects of potential covariates on adalimumab pharmacokinetics.
RESULTS: Mean serum adalimumab concentrations after 40-mg weekly dosing reached steady state (10-12 µg/mL in the phase II study and 7 µg/mL in the phase III studies) by week 2 and were maintained through week 12. The percentage of patients testing positive for AAA was low (10% in the phase II study and 7% in the phase III studies). Adalimumab pharmacokinetics was described by a one-compartment model with first-order absorption. Significant covariates for clearance included the presence of AAA, baseline C-reactive protein, and baseline body weight.
CONCLUSIONS: Adalimumab pharmacokinetics in HS patients was described using a one-compartment model with weight, baseline C-reactive protein, and AAA affecting adalimumab exposure. AAA development results in decreased adalimumab concentrations with a potential decrease in efficacy. Serum adalimumab concentrations in HS patients receiving 40-mg weekly dosing were similar to those observed in other indications under approved dosing regimens.

RCT Entities:   Population Interventions Outcomes