Dataset Information

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

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).

SUBMITTER: Pelle J

PROVIDER: S-EPMC10043118 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature

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Publications

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

Pelle Juliette J Briant Anais R AR Branger Pierre P Derache Nathalie N Arnaud Charlotte C Lebrun-Frenay Christine C Cohen Mikael M Mondot Lydiane L De Seze Jerome J Bigaut Kevin K Collongues Nicolas N Kremer Laurent L Ricard Damien D Bompaire Flavie F Ohlmann Charlotte C Sallansonnet-Froment Magali M Ciron Jonathan J Biotti Damien D Pignolet Beatrice B Parienti Jean-Jacques JJ Defer Gilles G

Neurology and therapy 20230210 2

<h4>Introduction</h4>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.<h4>Methods</h4>We conducted a retrospective, multicenter cohort study among adults with RRMS receiving stable standard interval dosing (SID ...[more]

PMID: 36763307

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Project description:BackgroundExtended interval dosing (ED) for inhibitors of programmed cell death protein 1 (anti-PD-1) (nivolumab, pembrolizumab) or its ligand (anti-PD-L1) (durvalumab) were recently approved based on pharmacokinetic model results that predicted a benefit-risk profile comparable with the standard dosing (SD) regimen. However, safety data in real-world condition of use are lacking. The objective was to compare the incidence and the risk factors of serious immune-related adverse events (irAEs) and any-grade irAEs between the SD and ED regimens in patients treated with anti-PD-1 or anti-PD-L1.Materials and methodsIrAEs were assessed from medical records in all new users of nivolumab, pembrolizumab, or durvalumab between 1 January 2019 and 31 December 2020 across two oncology centers in France. The incidence of irAEs was compared between both dosing regimens using Cox proportional hazards models adjusting for the main available confounders.ResultsAmong 686 patients included, 63% were new users of an SD regimen, 14% of ED regimen, and 23% started with SD and switched to ED regimen during follow-up. Overall, 34.6% of patients experienced at least one irAE of any grade and 11.4% presented at least one serious grade ≥3 irAE. No statistical difference was found between the SD and ED regimen on the risk of grade ≥3 irAEs [adjusted hazard ratio (HR) 1.40, 95% confidence interval (CI) 0.71-2.76] but our results suggest an increased risk of any-grade irAEs with the ED regimen (adjusted HR 1.46, 95% CI 1.00-2.12, P = 0.048). IrAEs resolved without sequelae in 46.4% of cases, and they were fatal for three patients (0.4%). Autoimmune pre-existing condition was confirmed as a risk factor for grade ≥3 irAEs (HR 2.56, 95% CI 1.53-4.27) and for all-grade irAEs (HR 1.60, 95% CI 1.17-2.20).ConclusionsIn a real-world setting, according to the regimen chosen by the oncologist based on clinical characteristics, we did not observe an increase in grade ≥3 irAE incidence between the SD and ED regimens.

Dataset Information

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

Introduction

Methods

Results

Conclusion

Clinical trials

Publications

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

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