“…9,10 As part of the postapproval strategy, an alternate route of administration, namely, subcutaneous administration and extended interval dosing, was explored in MS subjects. Toward this commitment, 2 additional studies were conducted: (1) a pilot study evaluating the PK-PD of single and multiple (onceevery-4-week) 300-mg subcutaneous or intravenous administrations 11 and (2) a multiple-dose efficacy study testing 150 or 300 mg intravenously or subcutaneously given once every 4 or 12 weeks in MS subjects. 12 In this article, we have combined the natalizumab PK-PD data from 11 clinical studies (1 phase 1, 1 phase 2, 3 phase 3, 2 bridging bioequivalence, and 4 postmarketing clinical studies) to perform a comprehensive population PK-PD (popPK-PD) analysis that (1) characterizes natalizumab PK after intravenous and subcutaneous administration, (2) describes the natalizumab PK-PD relationship, and (3) quantifies the impact of covariates that may contribute to differences in natalizumab PK and alpha-4 integrin saturation dynamics.…”