Inter-regional pharmacokinetics and exposure-response analyses of belimumab in patients with system lupus erythematosus.

AIMS

The pharmacokinetics (PK) of belimumab, a human immunoglobulin G1λ (IgG1λ) monoclonal antibody treatment for systemic lupus erythematosus (SLE), have been well reported. Clinical PK data in healthy participants and patients with SLE from Mainland China suggest lower-than-expected belimumab exposure. This study assessed inter-regional differences in belimumab exposure and efficacy via the exposure-response relationship to inform any dose-adjustment requirements.

METHODS

Data from nine interventional belimumab studies in healthy participants and patients with SLE were used to update two-compartment PK models with first-order subcutaneous (SC) absorption, and a logistic regression model characterizing the 52-week SLE Responder Index (SRI) response in adult and paediatric patients with SLE. Covariates of belimumab PK and efficacy were identified using forward selection (P > .05) and backward elimination (P < .01). The models were evaluated using statistical tests and visual predictive checks.

RESULTS

Baseline fat-free mass was the most significant covariate affecting belimumab PK; baseline albumin and IgG concentrations were also PK covariates. After adjusting for covariates, Mainland Chinese patients had significantly higher observed belimumab clearance (28%) and central volume of distribution (20%) than other populations, leading to lower-than-expected exposures. Despite this, following the same dose, they were expected to have almost identical SRI response rates vs. other populations from the exposure-response analysis.

CONCLUSIONS

Belimumab 10 mg kg intravenously every 4 weeks, or 200 mg SC every week, would achieve the maximum treatment effect for North East Asian patients with SLE (including Mainland Chinese) and similar responses to patients from other regions, despite lower reported exposures in Chinese patients.