Safety and Efficacy of Extended Dose Natalizumab in Multiple Sclerosis: An Ongoing Multicenter Study. (P3.267)

Objective: Investigate safety and efficacy of extended dose (ED) Natalizumab (NTZ) schedules. Background: NTZ is highly effective treatment for management of RRMS. However, its use is limited by susceptibility to PML in patients with prior immunosuppressive treatment or JC virus exposure. To mitigate risk, we are exploring the effect of ED schedule for NTZ. We hypothesize that less frequent dosing may result in sub-maximal α4β1-integrin receptor saturation, adequate to exclude auto-reactive T cells from entry into CNS (‘MS-protective’), but sufficiently permissive to enable CNS lymphocyte scavenging of JC virus to occur (‘PML-protective’). Method: Recurrent planned retrospective chart review of NTZ-treated patients from 6 MS centers every six months is ongoing. Patients are stratified into 4 groups: (1) standard dosing (SD)(n=674): q4wks; (2) early extended dosing (EED) (n= 231): q4w3d-6w6d; (3) late extended dosing (LED) (n=245): q7 - 8.5wks; (4) variable extended dosing (VED) (n=208): patients alternating between EED and LED. Adjusted annualized relapse rate (ARR), frequency of steroid usage, new T2 lesions, T1 enhancing lesions, and disease free rate (No Evidence of Disease Activity- NEDA) is calculated. Results: ED groups show comparable efficacy across both clinical and radiological measures compared to SD group. ED ARR has remained low at 0.12 compared to SD of 0.14 with 83[percnt] of ED patients having no evidence of radiological activity, compared to 82[percnt] in SD cohort. No cases of PML have yet been seen in the ED group, compared to 2 captured in SD. Although the trend is favorable with 861 JCV - antibody positive person years collected thus far, we will need 1248 patient years to reach statistical significance. Conclusion: ED of NTZ up to q8.5wks maintains the excellent efficacy profile of drug, with promising risk reduction of PML. Further efficacy and safety monitoring in this cohort is ongoing.