Potential risk of progressive multifocal leukoencephalopathy with natalizumab therapy: possible interventions.
Natalizumab (Tysabri) is an effective therapy for multiple sclerosis. Recently, 3 patients who were treated with natalizumab developed progressive multifocal leukoencephalopathy (PML), an opportunistic infection of the brain with the polyomavirus JC. The pathogenesis of natalizumab-associated PML may be different from that of PML not associated with the drug. We reviewed biologically feasible interventions for patients diagnosed as having PML or other infections while receiving natalizumab therapy. Existing interventions include antiviral treatment, immunomodulatory therapies, hematopoietic growth factors, plasma exchange, intravenous immunoglobulins, and leukapheresis and autotransfusion of leukocytes. In addition, we examined the feasibility of experimental therapies, including small interfering RNA, the in vivo use of antiserum, and recombinant natalizumab-blocking molecules. There is only circumstantial evidence that any of the proposed treatments will benefit patients with multiple sclerosis treated with natalizumab who may develop PML. In addition, the expected incidence of PML in this patient population will likely be too low to test any of the proposed interventions in a controlled manner. Because it is currently impossible to identify patients at risk, and thus to prevent PML as a consequence of natalizumab therapy, it is important that neurologists be aware of possible therapeutic interventions.
Stüve
Olaf
O
Neurology Section, Medical Service, Veterans Affairs North Texas Health Care System, Dallas, TX, USA. olaf.stuve@utsouthwestern.edu
Marra
Christina M
CM
Cravens
Petra D
PD
Singh
Mahendra P
MP
Hu
Wei
W
Lovett-Racke
Amy
A
Monson
Nancy L
NL
Phillips
J Theodore
JT
Tervaert
Jan W Cohen
JW
Nash
Richard A
RA
Hartung
Hans-Peter
HP
Kieseier
Bernd C
BC
Racke
Michael M
MM
Frohman
Elliot M
EM
Hemmer
Bernhard
B
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D006801:Humans; D007275:Injections, Intravenous / Q000379:methods; D016023:Integrins / Q000276:immunology*; D007968:Leukoencephalopathy, Progressive Multifocal / Q000188:drug therapy*; D000069442:Natalizumab; D034741:RNA, Small Interfering / Q000627:therapeutic use
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D016023:Integrins; D000069442:Natalizumab; D034741:RNA, Small Interfering