The results of a 24-month controlled, prospective study of relapsing multiple sclerosis patients at risk for progressive multifocal encephalopathy, who switched from prolonged use of natalizumab to teriflunomide

Stanley Cohan, Tiffany Gervasi-Follmar, Aneesh Kamath, Vineetha Kamath, Chiayi Chen, Kyle Smoot, Elizabeth Baraban, Keith Edwards, Stanley Cohan, Tiffany Gervasi-Follmar, Aneesh Kamath, Vineetha Kamath, Chiayi Chen, Kyle Smoot, Elizabeth Baraban, Keith Edwards

Abstract

Background: Natalizumab (NTZ) is a highly effective disease modifying treatment for relapsing multiple sclerosis (RMS), but it increases risk of progressive multifocal leukoencephalopathy (PML) in patients with serum anti- John Cunningham virus (JCV) antibodies.

Objective: To assess the safety and efficacy of rapid transition, from NTZ to teriflunomide (TFM) in RMS patients.

Methods: Clinically stable NTZ-treated, anti-JCV antibody positive RMS patients were switched to TFM 28 ± 7 days after their last dose of NTZ. The primary endpoint was proportion of relapse free patients at 24 months.

Results: Median [IQR] age of the 55 enrolled patients was 47 [40.7, 56.3] years, 76% were female. The median [IQR] number of prior NTZ treatments was 34 [18, 64]. annualized relapse rate (ARR) was 0.07 and 77% of the patients were relapse free at 24 months. Mean time to first GAD + lesion was 19.6 months, and to new/enlarging T2 lesion was 19.2 months. Mean time to 3 month sustained disability worsening (SDW) was 22 months and proportion free of 3-month SDW was 0.87. There were no cases of PML.

Conclusions: The washout-free transition of NTZ to TFM was an efficacious and safe strategy for patients at risk of developing PML.ClinicalTrials.gov Identifier: NCT01970410.

Keywords: John Cunningham virus; natalizumab; progressive multifocal leukoencephalopathy; relapsing multiple sclerosis; teriflunomide.

Conflict of interest statement

Declaration of conflicting interests: SC has served on advisory boards or steering committees for Biogen, Novartis, Sanofi Genzyme, AbbVie, and EMD Serono and received research support from Biogen, Novartis, Sanofi Genzyme, MedDay, and Roche Genentech, and speaker honoraria from Biogen, Novartis, Sanofi Genzyme, Bristol Myers Squibb, and Roche Genentech. KS has received research support from AbbVie, Biogen, Roche Genentech, and EMD Serono and consulting fees from Bristol Myers Squibb, Janssen, Acorda, Biogen, EMD Serono, Sanofi Genzyme, Roche Genentech, Novartis, and Teva. KE has received honoraria for speaking and consulting from Biogen and EMD Serono and research/grant support from Biogen, Sanofi Genzyme, F. Hoffmann-La Roche and Genentech, EMD Serono, and Novartis. AK, TGF, VK, EB, and CC have no disclosures.

© The Author(s), 2021.

Figures

Figure 1.
Figure 1.
Survival analysis. Results indicate the proportion of patients free of relapse. Solid lines denote Kaplan-Meier estimates and shaded areas denote the 95% confidence intervals.
Figure 2.
Figure 2.
a & b. Survival analysis. Results indicate the proportion of patients free from new gadolinium-enhancing lesions and new or enlarging T2 lesions. Solid lines denote Kaplan-Meier estimates and shaded areas denote the 95% confidence intervals.

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