Switching from Natalizumab to Teriflunomide in Multiple Sclerosis Patients Who Have Received Natalizumab for More Than 12 Months

Background: Teriflunomide is an oral immunomodulator approved for use in MS patients with relapsing forms of MS. In order to reduce the risk of progressive multifocal leukoencephalopathy (PML), a need exists for the safe transition to another disease modifying therapy for certain patients who have received natalizumab (NAT) for more than 12 months. Many MS patients have significant exacerbations after stopping NAT.

Objectives: To review the efficacy and safety in 30 consecutive patients who have been switched from NAT to teriflunomide and have received teriflunomide for at least 6 months.

Methods: This study is a retrospective data review of 30 MS patients who had received at least 12 NAT treatments and all were clinically stable while on NAT.  The patients usually were able to begin teriflunomide within 4 weeks of their last NAT treatment.  Clinical examination and cranial MRI were obtained at time of last NAT treatment and at 3 and 6 months after last NAT treatment for evaluation of possible PML and for any new MS activity.   ALT values were measured monthly for 6 months after starting teriflunomide.  Side effects were recorded.

Results: Of the 30 patients regarding their risk for PML, 11 were triple positive (for receiving more than 24 NAT treatments, having prior immunosuppression and being positive for anti-JCV-antibody), 13 were positive for anti-JCV- antibody and 6 tested negative for anti-JCV-antibody.   The mean number of NAT treatments was 39 (range 14-81), mean age of patients was 52 (range 28 to 70).  Seventy-six percent were female.  Mean duration of teriflunomide treatment after NAT discontinuation was 9 months (range 6-13).

Of the 30 patients evaluated, 25 are still on teriflunomide. No patients developed PML. One patient discontinued teriflunomide due to a significant exacerbation and 3 others had minor exacerbations responding to IVMP and continued teriflunomide. Two other patients discontinued due to persistent diarrhea and abdominal cramps and 1 discontinued because of hair thinning.  Minor diarrhea and transient hair thinning occurred in 7 and 5 patients respectively.  There were no LFTs abnormalities.  

Conclusions: Teriflunomide may be an effective and safe alternative for patients switching from NAT.   A reduced “washout” period after NAT may be important to lessen breakthrough disease.