Transition from Natalizumab to Dimethyl Fumarate in Multiple Sclerosis Patients: Clinical and MRI Outcomes

Background: Multiple Sclerosis is a complex disease for which there are now a wide variety of available treatments, some of which carry substantial risk. Guidelines to direct clinicians as to how to best transition patients from one to another immunotherapy are not yet established.  Natalizumab in particular may frequently have to be discontinued in favor of another immunotherapy.

Objectives: We assessed the outcomes of transitioning multiple sclerosis patients from natalizumab to dimethyl fumarate (DMF). Demographic data collected included age, sex, and ethnic background.  Clinical assessments included number of clinical relapses within 12 months and rate of continuation of therapy.  In addition we evaluated MRI activity within 12 months of initiation of therapy.

Methods: This retrospective cohort study utilized electronic medical records from a single center: University of Utah Health. Patient records dated from March 2012 to present. A total of 512 patients on treatment with natalizumab and/or DMF were screened.  Patients who had received at least one dose of natalizumab and who subsequently transitioned to dimethyl fumarate for at least one year were included in analysis.

Results: Twenty-eight patients met criteria (mean age 46.1 years; female: 67.8%).  Of 28 patients transitioned from natalizumab to DMF, 27 had adequate data for analysis and were compliant with DMF therapy. Only one patient had a clinical relapse.  Five patients (18.5%) demonstrated new T2 or enhancing lesions on MRI’s conducted within 1 year of initiation.   Four of five patients remained on DMF.  One patient experienced a clinical relapse within 1 year of initiating DMF (3.7%). The relapse was manifested by optic neuritis and numerous associated contrast enhancing lesions on brain MRI.

Conclusions: The transition from natalizumab to DMF was associated with a low risk of rebound and/or breakthrough clinical disease activity as indicated by relapses within 1 year of initiation.  However, our review of MRI scans indicates a modest increase in disease activity following transition suggests that careful selection and monitoring is required in patients transitioning from natalizumab to DMF.