Background: Natalizumab (NTZ) is sometimes discontinued in patients with multiple sclerosis, mainly due to concerns about the risk of progressive multifocal leukoencephalopathy. However, NTZ interruption may result in recrudescence of disease activity. Objective: The objective of this study was to summarize the available evidence about NTZ discontinuation and to identify which patients will experience post-NTZ disease reactivation through meta-analysis of existing literature data. Methods: PubMed was searched for articles reporting the effects of NTZ withdrawal in adult patients (⩾18 years) with relapsing–remitting multiple sclerosis (RRMS). Definition of disease activity following NTZ discontinuation, proportion of patients who experienced post-NTZ disease reactivation, and timing to NTZ discontinuation to disease reactivation were systematically reviewed. A generic inverse variance with random effect was used to calculate the weighted effect of patients’ clinical characteristics on the risk of post-NTZ disease reactivation, defined as the occurrence of at least one relapse. Results: The original search identified 205 publications. Thirty-five articles were included in the systematic review. We found a high level of heterogeneity across studies in terms of sample size (10 to 1866 patients), baseline patient characteristics, follow up (1–24 months), outcome measures (clinical and/or radiological), and definition of post-NTZ disease reactivation or rebound. Clinical relapses were observed in 9–80% of patients and peaked at 4–7 months, whereas radiological disease activity was observed in 7–87% of patients starting at 6 weeks following NTZ discontinuation. The meta-analysis of six articles, yielding a total of 1183 patients, revealed that younger age, higher number of relapses and gadolinium-enhanced lesions before treatment start, and fewer NTZ infusions were associated with increased risk for post-NTZ disease reactivation ( p ⩽ 0.05). Conclusions: Results from the present review and meta-analysis can help to profile patients who are at greater risk of post-NTZ disease reactivation. However, potential reporting bias and variability in selected studies should be taken into account when interpreting our data.
ObjectiveThis phase I study investigated pharmacokinetic (PK) and pharmacodynamic (PD) profiles of natalizumab in pediatric patients with relapsing-remitting MS (RRMS).MethodsPediatric 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.ResultsPK 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.ConclusionsPK profile, α4-integrin saturation, lymphocyte counts, and safety observed in these pediatric patients are comparable to those reported in adults.Classification of evidenceThis 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.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.