Progressive multifocal leukoencephalopathy and rheumatoid arthritis treatments.
Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system due to reactivation of the JC virus (JCV). PML is extremely uncommon despite the high prevalence of the virus in the general population. No specific treatment is available, and the prognosis is bleak. The diagnosis is based on brain imaging findings, detection of the JCV genome in cerebrospinal fluid samples and, in some cases, histological studies of the brain lesions. The pathophysiological mechanisms that drive the development of PML are incompletely understood. However, a consistent feature is the presence of a predisposing factor, most notably immunosuppression. The risk of developing PML varies with the underlying disease (e.g., HIV infection or autoimmune disease) and with the drugs used to treat them. Biologics have been ranked according to the risk of PML during their use. Natalizumab, a monoclonal antibody given to treat multiple sclerosis, is among the drugs associated with a high risk of PML. Patients given natalizumab are now closely monitored based on anti-JCV antibody titers and index values. In rheumatology, the expanding use of biologics has led to an increase in cases of PML, with rituximab being associated with the highest risk. Given the absence of specific recommendations, exhaustive registries and postmarketing observational studies are urgently needed to gauge the risk of PML according to the underlying disease and drug treatments, with the goal of defining optimal monitoring protocols.
Service de médecine interne, Fondation A. de Rothschild, 25-29, rue Manin, 75019 Paris, France; Inserm UMR 1125, 74, rue Marcel-Cachin, 93017 Bobigny, France; Sorbonne Paris Cité, université Paris 13, 74, rue Marcel-Cachin, 93017 Bobigny, France. Electronic address: gclavel@for.paris.
Gaëlle
G
Clavel
Service de neurologie, Fondation A. de Rothschild, 75019 Paris, France.
Antoine
A
Moulignier
Inserm UMR 1125, 74, rue Marcel-Cachin, 93017 Bobigny, France; Sorbonne Paris Cité, université Paris 13, 74, rue Marcel-Cachin, 93017 Bobigny, France; Service de rhumatologie, groupe hospitalier Avicenne Jean-Verdier-René-Muret, Assistance publique-Hopitaux de Paris (AP-HP), 93017 Bobigny, France.
Luca
L
Semerano
D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects*; D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000188:drug therapy*; D001688:Biological Products / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D015658:HIV Infections / Q000175:diagnosis / Q000188:drug therapy; D006801:Humans; D015994:Incidence; D007968:Leukoencephalopathy, Progressive Multifocal / Q000453:epidemiology / Q000209:etiology* / Q000503:physiopathology; D008297:Male; D000069442:Natalizumab / Q000009:adverse effects* / Q000627:therapeutic use; D011379:Prognosis; D035583:Rare Diseases; D018570:Risk Assessment; D000069283:Rituximab / Q000009:adverse effects* / Q000627:therapeutic use; D012720:Severity of Illness Index
D000911:Antibodies, Monoclonal; D001688:Biological Products; D000069442:Natalizumab; D000069283:Rituximab
Biotherapies; Progressive multifocal leukoencephalopathy; Rheumatoid arthritis; Rituximab; TNFα antagonists