A systemic review and meta-analysis found that natalizumab was similarly effective in both standard and extended interval dosing. However, the study also found that extended interval dosing did not improve its safety profile.
Multiple sclerosis (MS) is a chronic immune-mediated central nervous system (CNS) disease with poorly understood pathology. However, it is known that immune dysregulation in patients causes inflammatory demyelination of white and gray matter in the CNS. Natalizumab is a monoclonal antibody that reduces the entrance of lymphocytes to the CNS through the blood–brain barrier. Hence, it reduces inflammatory activity in the brain, which benefits MS patients.
Natalizumab is approved for use as a 300 mg IV infusion given every 4 weeks, the standard interval dose (SID). Although effective, it considerably increases the risk of opportunistic brain infections due to the reactivation of the John Cunningham virus [JCV], causing progressive multifocal leukoencephalopathy (PM). This risk is especially high in patients positive for JCV antibodies, and the risk increases considerably after 2 years.
Thus, many researchers have proposed increasing the interval between Natalizumab doses, especially considering that it is highly effective in preventing disease progress. A new systemic review and meta-analysis published in Acta Neurologica Belgica looked at the efficacy of extended interval dosing (EID).
The Study Suggests That Extended Dosing Is Non-Inferior, Though Not Essentially Safer
In EID, the interval between IV infusions of the drug is increased from 4 weeks to 5 to 8 weeks. Despite many reports that EID works and might have some benefits, there has been no large-scale clinical trial or systemic review to prove this. Hence, this study analyzed all the studies on the topic. After extensive review, 14 studies met the inclusion criteria. In the studies, two-thirds of patients were female, with a follow-up duration of 12–24 months.
The study found that there was an insignificant difference in clinical relapse rates in the SID and EID groups [relative risk (RR) = 0.90, (95% confidence interval (CI) 0.80, 1.02), P = 0.09]. Similarly, MRI scans could not demonstrate much difference between the groups with the risk of new or newly enlarging T2 hyperintense lesions [RR = 0.78, (95% CI 0.59, 1.04), P = 0.09]. The same was true for the comparison of the expanded disability status scale (EDSS), showing comparable outcomes [mean difference (MD) = 0.09 (95% CI −0.57, 0.76), P = 0.79]. However, there was also not much difference in the incidence of PML between the groups [RR = 1.09, (95% CI 0.24, 4.94], P = 0.91).
The Bottom Line
The study demonstrated that EID was non-inferior to SID, and both dosing regimens were similarly effective. However, the study also found that EID did not reduce PML risk, which means that EID is not essentially safer than SID. Thus, EID might be considered for specific groups of patients, especially considering that it may improve patient satisfaction levels as EID involves fewer infusions and results in lower treatment costs. The study had some limitations, like the small sample size of studies and retrospective design; therefore, further clinical studies are needed on the topic to better understand the optimal treatment regimen for natalizumab.
Source:
Rabea, E. M., Belal, M. M., Hafez, A., Elbanna, A. H., Khalifa, M. A., Nourelden, A. Z., Mahmoud, N., & Zaazouee, M. S. (2024). Safety and efficacy of extended versus standard interval dosing of natalizumab in multiple sclerosis patients: a systematic review and meta-analysis. Acta Neurologica Belgica. https://doi.org/10.1007/s13760-024-02480-6
