Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Apr;12(2):529-542.
doi: 10.1007/s40120-023-00440-5. Epub 2023 Feb 10.

Real-World Effectiveness of Natalizumab Extended Interval Dosing in a French Cohort

Juliette Pelle  1 , Anais R Briant  2 , Pierre Branger  1 , Nathalie Derache  1 , Charlotte Arnaud  1 , Christine Lebrun-Frenay  3 , Mikael Cohen  3 , Lydiane Mondot  3 , Jerome De Seze  4 , Kevin Bigaut  4 , Nicolas Collongues  4 , Laurent Kremer  4 , Damien Ricard  5 , Flavie Bompaire  5 , Charlotte Ohlmann  6 , Magali Sallansonnet-Froment  5 , Jonathan Ciron  7 , Damien Biotti  7 , Beatrice Pignolet  7 , Jean-Jacques Parienti  2 , Gilles Defer  8
Affiliations

Real-World Effectiveness of Natalizumab Extended Interval Dosing in a French Cohort

Juliette Pelle et al. Neurol Ther. 2023 Apr.

Abstract

Introduction: Natalizumab, a therapy for relapsing-remitting multiple sclerosis (RRMS), is associated with a risk of progressive multifocal leukoencephalopathy (PML). Over the last several years, practitioners have used off-label extended interval dosing (EID) of natalizumab to reduce PML risk, despite the absence of a large-scale efficacy evaluation.

Methods: We conducted a retrospective, multicenter cohort study among adults with RRMS receiving stable standard interval dosing (SID), defined as a ≥ 12-month consecutive period of ≥ 11 natalizumab infusions/year in France. We compared the 12-month risk difference of remaining relapse-free (primary endpoint) between patients who switched to EID (≤ 9 natalizumab infusions) and those who remained on SID, with a noninferiority margin of - 11%. We used propensity score methods such as inverse probability treatment weighting (IPTW) and 1:1 propensity score matching (PSM). Secondary endpoints were annualized relapse rate, disease progression, and safety.

Results: Baseline characteristics were similar between patients receiving EID (n = 147) and SID (n = 156). The proportion of relapse-free patients 12 months postbaseline was 142/147 in the EID (96.6%) and 144/156 in the SID group (92.3%); risk difference (95% CI) 4.3% (- 1.3 to 9.8%); p < 0.001 for non-inferiority. There were no significant differences between relapse rates (0.043 vs. 0.083 per year, respectively; p = 0.14) or Expanded Disability Status Scale mean scores (2.43 vs. 2.72, respectively; p = 0.18); anti-JC virus index values were similar (p = 0.23); and no instances of PML were reported. The comparisons using IPTW (n = 306) and PSM (n = 204) were consistent.

Conclusion: These results support the pertinence of using an EID strategy for RRMS patients treated with natalizumab.

Clinical trials: gov identifier (NCT04580381).

Keywords: Extended interval dosing; Multiple sclerosis; Natalizumab; Real-world evidence.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
Study design
Fig. 2
Fig. 2
a Percentage of patients with at least one relapse during the follow-up according to therapy group and b risk differences between therapy groups
See this image and copyright information in PMC

References

    1. Havrdova E, Galetta S, Hutchinson M, et al. Effect of natalizumab on clinical and radiological disease activity in multiple sclerosis: a retrospective analysis of the Natalizumab Safety and Efficacy in Relapsing–Remitting Multiple Sclerosis (AFFIRM) study. Lancet Neurol. 2009;8:254–260. doi: 10.1016/S1474-4422(09)70021-3. - DOI - PubMed
    1. Miller DH, Khan OA, Sheremata WA, et al. A controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med. 2003;348:15–23. doi: 10.1056/NEJMoa020696. - DOI - PubMed
    1. Polman CH, O'Connor PW, Havrdova E, et al. A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med. 2006;354:899–910. doi: 10.1056/NEJMoa044397. - DOI - PubMed
    1. Butzkueven H, Kappos L, Wiendl H, et al. Long-term safety and effectiveness of natalizumab treatment in clinical practice: 10 years of real-world data from the Tysabri Observational Program (TOP). J Neurol Neurosurg Psychiatry. 2020;91:660–8. - PMC - PubMed
    1. Horakova D, Uher T, Krasensky J, et al. Long-term effectiveness of natalizumab on MRI outcomes and no evidence of disease activity in relapsing-remitting multiple sclerosis patients treated in a Czech Republic real-world setting: a longitudinal, retrospective study. Mult Scler Relat Disord. 2020;46:102543. - PubMed

Associated data