Natalizumab progressive multifocal

Adelman B, Sandrock A, Panzara MA (2005) Natalizumab and progressive multifocal leukoen-cephalopathy. N Engl J Med 353 432-433... 

Natalizumab was approved by the U.S. FDA for the treatment of MS in November 2004, and is being evaluated in Phase 3 clinical trials for IBD and CD.105 Based on Phase 3 clinical trials in MS patients, natalizumab appeared to be safe, since an increased rate of infection was not observed after 1 year of treatment.106 The safety of combined treatment with immunosuppressants, other than short courses of corticosteroids, was not evaluated and was not recommended because of the potential for an increased risk of infections. Flowever, barely three months after its approval, natalizumab was voluntarily withdrawn from the MS market by its manufacturer and all ongoing clinical trials were suspended due to the occurrence of a rare neurological disease, progressive multifocal leukoencephalopathy (PML), in 3 out of approximately 3,000 patients enrolled in clinical trials (2 in MS and 1 in CD).107 108 109... 

Van Assche, G. et al., Progressive multifocal leukoencephalopathy after natalizumab therapy for Crohn s disease, N. Engl. J. Med., 353, 2005. 

Natalizumab has shown significant efficacy for a subset of patients with moderate to severe Crohn s disease. Unfortunately, in initial clinical trials of patients with Crohn s disease and multiple sclerosis, 3 of 3100 patients treated with natalizumab developed progressive multifocal leukoencephalopathy due to reactivation of a human... 

Langer-Gould, A., S.W. Atlas, A.J. Green, A.W. Bollen, and D. Pelletier. 2005. Progressive multifocal leukoencephalopathy in a patient treated with natalizumab. 

Natalizumab (Tysabri), an anti-a4 integrin monoclonal antibody approved for the treatment of multiple sclerosis, was recently withdrawn from the market temporarily due to cases of progressive multifocal leukoencephalopathy, a demyelinating disease of the central nervous system associated with immunosuppression [32], These cases highlight our incomplete understanding of the immune system and the translation of preclinical results to humans. 

MYCOPHENOLATE NATALIZUMAB T risk of infections including progressive multifocal leuko-encephalopathy, a potentially fatal virus infection of the brain Due to additive immunosuppressant effects. Natalizumab inhibits migration of leukocytes into the CNS Avoid co-administration... 

While inflammation is associated negatively with vasculitis and autoimmune disease, it is also necessary to protect normal cells from viral and bacterial infection. Many of the therapies that act positively as immunosuppressants have an initial inflammatory response. While lENp is an effective therapy in the inflammatory phases of MS, the initial response to each injection is an increase in inflammatory cytokines, IL-2 and lENy (Elliott et al., 2001). Conversely, natalizumab a therapy that show ed great potential in phase EE trials for aggressive MS by blocking activated lymphocyte trafficking into the CNS was withdrawn because of deaths due to progressive multifocal leukoencephalopathy. 

YousryTA,Major EO,Ryschkewitsch C,Eahle G, Eischer S,Hou J, Curfman B, Miszkiel K, MueUer-Lenke N, Sanchez E, Barkhof E, Radue EW, lager HR, Clifford DB. Evaluation of patients treated with natalizumab for progressive multifocal leuko-encephalopathy. N Engl J Med 2006 354(9) 924-933. 

Natalizumab 4 inlegrin Recombinant endogenous proteins Multiple sclerosis Hypersenisitivy, progressive multifocal leukoencephalopathy (PML)... 

Bartt RE. Multiple sclerosis, natalizumab therapy, and progressive multifocal leukoencephalopathy. Current Opinion in Neurology. 2006 19(4) 341-9. 

Nervous system Progressive multifocal leukoencephalopathy, due to reactivation of JC virus, occurs in some patients with multiple sclerosis who receive natalizumab, and many so affected die as a result. No new cases occurred during the first 2 years of natalizumab marketing, but by the end of November 2009, there were 28 confirmed cases, of which 8 were fatal. The median... 

Carson KR, Focosi D, Major EO, Petrini M, Richey EA, West DP, Bennett CL. Monoclonal antibody-associated progressive multifocal leucoen-cephalopathy in patients treated with rituximab, natalizumab, and efalizumab a Review from the Research on Adverse Drug Events and Reports (RADAR) Project. Lancet Oncol 2009 10(8) 816-24. 

Nervous system Subclinical reactivation of JC virus is common in patients with multiple sclerosis who are treated with natalizumab [249 ] and there is an increased risk of JC virus-associated progressive multifocal leukoencephalopathy, which can be fatal or result in severe disability. The risk appears to increase with treatment duration, especially beyond 2 years. There is limited experience in patients who have received natalizumab for more than 3 years and the risk in these patients cannot therefore currently be estimated. 

Wenning W, Haghikia A, Laubenberger J, Clifford DB, Behrens PF, Chan A, Gold R. Treatment of progressive multifocal leukoencephalopathy associated with natalizumab. N Engl J Med 2009 361(11) 1075-80. 

LindS H, von Heijne A, Major EO, Ryschkewitsch C, Berg J, Olsson T, Martin C. Progressive multifocal leukoencephalopathy after natalizumab monotherapy. N Engl J Med 2009 361(11) 1081-7. 

Nervous system Progressive multifocal leucoencephalopathy (PML) with immune reconstitution inflammatory syndrome (IRIS) may be a severe complication of natalizumab. Although natalizumab is often an effective treatment for patients with multiple sclerosis (MS), the mAb carries an associated risk of PML. A retrospective review of the first 40 natali-zumab-treated patients with MS revealed that 10 were also diagnosed with IRIS [174 ]. 

Yousry TA, Pelletier D, Cadavid D, Gass A, Richert ND, Radue EW, et al. Magnetic resonance imaging pattern in natalizumab-associated progressive multifocal leukoencephalopathy. Ann Neurol 2012 72(5) 779-87. 

Metz 1, Radue E-W, Oterino A, Kumpfel T, Wiendl H, Schlppling S, et al. Pathology of immune reconstitution inflammatory syndrome in multiple sclerosis with natalizumab-associated progressive multifocal leukoencephalopathy. Acta Neuropathol 2012 123(2) 235-45. 

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