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  • Title: Pharmacokinetics and pharmacodynamics of natalizumab in pediatric patients with RRMS.
    Author: Ghezzi A, Comi G, Grimaldi LM, Moiola L, Pozzilli C, Fantaccini S, Gallo P.
    Journal: Neurol Neuroimmunol Neuroinflamm; 2019 Sep; 6(5):e591. PubMed ID: 31355324.
    Abstract:
    OBJECTIVE: This phase I study investigated pharmacokinetic (PK) and pharmacodynamic (PD) profiles of natalizumab in pediatric patients with relapsing-remitting MS (RRMS). METHODS: Pediatric patients with RRMS who were prescribed natalizumab 300 mg IV every 4 weeks were enrolled. Blood samples were collected on days 1, 2, 8, 15, and 22 and at weeks 4, 8, 12, and 16 to estimate PK parameters; PD properties were evaluated by measuring α4-integrin saturation and lymphocyte counts over time. Natalizumab's safety profile was also evaluated. RESULTS: PK parameters were similar to those reported in adult patients; natalizumab concentrations peaked approximately 1 day after infusion in most of the participants (Cmax 142.9 μg/mL, AUClast 47389.4 hr*μg/mL), followed by a biphasic decline with a rapid distribution phase and a slow elimination phase, with a terminal half-life of 215.1 hours. In terms of PD, both time course and magnitude of α4-integrin saturation and increase in lymphocyte counts were similar to those observed in adults. During the 16-week study follow-up, 3 adverse events attributed to natalizumab were observed; no unexpected safety events occurred. CONCLUSIONS: PK profile, α4-integrin saturation, lymphocyte counts, and safety observed in these pediatric patients are comparable to those reported in adults. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that natalizumab PK/PD parameters and safety profile are similar in adults and pediatric patients in the short term. Longer studies, also including a larger number of younger subjects (aged 10-12 years), are required to further inform about long-term PK and PD parameters in pediatric patients with MS.
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