Deaths and disability from natalizumab are no longer tolerable: Yes.

MULTIPLE SCLEROSIS MSJ JOURNAL Multiple sclerosis (MS) has an unpredictable course; while its course varies greatly from one individual to another, the overall life expectancy is 95% of normal. In the Vancouver cohort, secondary progression is attained 19 years after onset 1 and the median time to Expanded Disability Status Scale (EDSS) 6.0 is 28 years. 2 There is some evidence that the course of MS is not as aggressive as before. Interferons (IFNs) and glatiramer acetate (GA) have been available for almost 20 years, with moderate efficacy, but low toxicity. A few cases of fulminant hepatic necrosis, necessitating a liver graft, have been reported in patients on IFNs; about 10% of patients on IFNs experience low and reversible increases of liver enzymes, or thyroid dysfunc-tion. It has been reported that IFNs reduces mortality. No serious adverse effects and no mortality have been associated with GA. Natalizumab (NTZ) is the first humanized monoclonal antibody used in MS. In 2011 a systematic review of trials evaluating NTZ for relapsing forms of MS 3 showed that NTZ significantly reduced the risk of having a relapse (relative risk [RR] 0.57) and the risk of experiencing progression (RR 0.74). In these trials, 60% of NTZ-treated patients had no new MRI lesions. In addition, 64% of patients were 'disease free', but in other trials this percentage decreased to 37.8%. It is unknown if this level of efficacy will be retained over the long term. NTZ was pulled from the market in 2005 after three cases of progressive multifocal leukoencephalitis (PML) had been reported. It was reintroduced in 2006, under a strict surveillance program. The manufacturer, Biogen-Idec, has been diligent in reporting new cases of PML. In the last (available at time of writing) report (February 2012): 95,300 MS patients had been exposed to NTZ, resulting in 207 PML cases and 44 (21%) deaths, with at least as many severely disabled. When 1,000,000 patients will have been exposed, we will number 2172 PML cases, 461 deaths and 461 severely disabled. These extremely serious adverse events are incurred for a disabling but not fatal disease, whose prognosis is obscure. Is this accepta-ble? Can we justify exposing patients to that degree of risk? Three factors increasing the risk for PML have been identified: prior use of immunosuppression (IS), having received ≥24 infusions and a positive test for antibodies against the JC virus (JC Abs). A recent paper has …