Reducing return of disease activity in patients with relapsing multiple sclerosis transitioned from natalizumab to teriflunomide: 12-month interim results of teriflunomide therapy

Stanley L Cohan, Keith Edwards, Lindsay Lucas, Tiffany Gervasi-Follmar, Judy O'Connor, Jessica Siuta, Vineetha Kamath, Lore Garten, Chiayi Chen, James Thomas, Kyle Smoot, Kiren Kresa-Reahl, Kateri J Spinelli, Stanley L Cohan, Keith Edwards, Lindsay Lucas, Tiffany Gervasi-Follmar, Judy O'Connor, Jessica Siuta, Vineetha Kamath, Lore Garten, Chiayi Chen, James Thomas, Kyle Smoot, Kiren Kresa-Reahl, Kateri J Spinelli

Abstract

Background: Natalizumab is an effective treatment for relapsing multiple sclerosis. Return of disease activity upon natalizumab discontinuance creates the need for follow-up therapeutic strategies.

Objective: To assess the efficacy of teriflunomide following natalizumab discontinuance in relapsing multiple sclerosis patients.

Methods: Clinically stable relapsing multiple sclerosis patients completing 12 or more consecutive months of natalizumab, testing positive for anti-John Cunningham virus antibody, started teriflunomide 14 mg/day, 28 ± 7 days after their final natalizumab infusion. Physical examination, Expanded Disability Status Scale, laboratory assessments, and brain magnetic resonance imaging were performed at screening and multiple follow-up visits.

Results: Fifty-five patients were enrolled in the study. The proportion of patients relapse-free was 0.94, restricted mean time to first gadolinium-enhancing lesion was 10.9 months and time to 3-month sustained disability worsening was 11.8 months. The mean number of new or enlarging T2 lesions per patient at 12 months was 0.42. Exploratory analyses revealed an annualized relapse rate of 0.08, and a proportion of patients with no evidence of disease activity of 0.68. Forty-seven patients (85.5%) reported adverse events, 95% of which were mild to moderate.

Conclusions: Teriflunomide therapy initiated without natalizumab washout resulted in a low rate of return of disease activity. Clinicians may consider this a worthwhile strategy when transitioning clinically stable patients off natalizumab to another therapy.ClinicalTrials.gov Identifier: NCT01970410.

Keywords: Relapsing multiple sclerosis; anti-JC virus antibodies; disease recurrence; natalizumab; switch strategy; teriflunomide.

Figures

Figure 1.
Figure 1.
Patient attrition diagram. TFM: teriflunomide.
Figure 2.
Figure 2.
Survival analysis. Results indicate a high proportion of patients free from (a) relapse, (b) sustained disability worsening, (c) new or enlarging T2 lesions, (d) new gadolinium-enhancing lesions, and (e) evidence of disease activity. (f) Subgroup analyses indicate that patients with disease duration of less than 15 years are more likely to have new gadolinium-enhancing (GAD+) lesions. For panels (a) to (e), solid lines denote Kaplan–Meier estimate and shaded areas denote 95% confidence intervals.

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