Clinical Outcomes in Discontinuation and Restart of Natalizumab

Background: Disease modifying therapies in multiple sclerosis (MS) are discontinued for a variety of reasons. Most commonly, therapies are stopped due to lack of efficacy or intolerable side effects. Natalizumab (Tysabri®) remains one of the most effective therapies in multiple sclerosis. We have treated over 1000 patients with natalizumab at the Multiple Sclerosis Center of Atlanta (MSCA). Natalizumab carries a life threatening risk of an infection from the JC Virus, PML (progressive multifocal leukencephalopathy). As with all therapies, clinicians must weigh the risk and benefit of natalizumab use. The Research Department at the MSCA hopes to obtain patient data and characteristics that will guide patients and clinicians in navigating the risk/benefit ratio. 

Objectives: To examine the patient population that stopped and then restarted treatment with natalizumab.  To examine the clinical course and treatments before natalizumab initiation, reasons for stopping, and restarting. To examine the prescribed interim treatments and response to these treatments prior to a natalizumab restart.  

Methods: A chart review was performed on all patients that stopped and then restarted natalizumab therapy at our center.  

Results: A total of 33 patients met all criteria.  22 patients were JC Virus antibody (JCV Ab) positive, 11 were negative.  79% initially started natalizumab due to active disease, 21% due to side effects of prior therapy. Natalizumab was discontinued in 45% of patients due to JCV Ab status, 24% due to financial reasons, 24% due to convenience, 12% due to breakthrough disease, and 6% due to side effects. Natalizumab was restarted in 67% of patients due to disease progression while only 15% was due to side effects of alternative medications.  The average initial natalizumab therapy was 56 months, while the average time off therapy before restarting was 13 months. Results between the JCV Ab positive and negative groups, response to alternative therapies used, and clinical and MRI activity 1 year after restarting natalizumab will be presented.  

Conclusions: Natalizumab is an effective therapy for the treatment of MS.  Despite risks, there is a subset of patients who preferentially respond to natalizumab. Within an average of 13 months off natalizumab, it becomes clear that alternative therapies are not going to be as effective in a subset of patients.  We will continue to evaluate our entire natalizumab cohort to guide clinicians in the risk/benefit analysis of natalizumab use.