Discontinuation of Natalizumab Therapy at the UT Southwestern MS Center (P01.157)

OBJECTIVE: Ascertain the reasons for discontinuation of natalizumab therapy at our institution. BACKGROUND: Natalizumab is the currently most effective immunomodulating therapy for MS. Despite clear indications to start therapy, there are no clear guidelines to manage patients following discontinuation. Since treatment interruption may lead to resurgent disease activity, understanding the reasons and rationale that culminate in therapy discontinuation is an important part of managing MS patients. DESIGN/METHODS: We analyzed data from MS patients followed at our institution who were treated with natalizumab between July 2006 to October 2012. RESULTS: From a total of 469 patients who received natalizumab, 136 who discontinued therapy qualified for this study. The majority (32.4%) were concerned about the risk for progressive multifocal leukencephalopathy (PML); most were either JC virus IgG seropositive or had received more than 24 consecutive infusions. The second most common reason (18.4%) was intolerable side effects (infusion-related or increased infections). 9.6% cited a lack of perceived benefit. 11.8% had either worsening deficits or transitioned to secondary progression. Twelve (8.8%) patients developed natalizumab neutralizing-antibodies; while almost all developed neutralizing-antibodies within the first year of starting therapy, one patient seroconverted after 41 infusions (with an associated relapse). Six patients experienced a relapse while on therapy (one patient only had a single infusion); these patients had no neutralizing-antibodies. Only one patient developed PML throughout this period. CONCLUSIONS: Even though PML is a rare entity, a perceived unfavorable risk-benefit ratio is the main cause of natalizumab treatment discontinuation at our center. A surprisingly large number of patients reported intolerable side effects. The incidence of neutralizing-antibodies was slightly higher than the AFFIRM and SENTINEL trials; several patients seroconverted after the first 6 months of therapy (where transient seropositivity may be observed). By understanding the rationale of therapy discontinuation, neurologists may help patients come to better informed decisions about stopping natalizumab treatment. Disclosure: Dr. Beh has received research support from Biogen Idec. Dr. Bates has received personal compensation for activities with Teva Neuroscience and Biogen Idec. Dr. Greenberg has received personal compensation for activities with Elan, Sanofi-Aventis, Diogenix, Biogen Idec, Accorda and MedicalLogix for consulting and from MSAA for honoraria. Dr. Greenberg hold stock and/or stock options in DioGenix, Inc., which sponsored research in which Dr. Greenberg was an investigator. Dr. Greenberg has received research support from Amplimmune, Guthy-Jackson Charitable Foundation, Accelerated Cure Project.