title: Pattern of demyelination occurring during anti-TNF-α therapy: a French national survey.
abstract: OBJECTIVE
  To determine the pattern of demyelinating disorders (DDs) occurring during anti-TNF-α therapy.
  
  
  METHODS
  Between June 2005 and April 2008, 1800 French rheumatologists and internists were contacted to report cases of DDs occurring in patients treated with anti-TNF-α.
  
  
  RESULTS
  After a median of 10.2 (1.5-39.9) months of treatment, 33 patients developed DDs: 22 had CNS and 11 peripheral nervous system (PNS) involvement. Underlying diseases were RA (n = 16), AS (n = 11), PsA (n = 4), JIA (n = 1) and PM (n = 1). Anti-TNF-α was infliximab (n = 15), etanercept (n = 12) or adalimumab (n = 6). CNS involvement was encephalic lesions (n = 16), transverse myelitis (n = 8) or retrobulbar optic neuritis (n = 5). Cerebrospinal fluid (CSF) analysis in 16 patients and MRI in 20 patients were abnormal. All patients discontinued anti-TNF-α. Fifteen patients required steroids. Twenty patients initially improved. Five patients developed multiple sclerosis. PNS involvement was chronic (n = 9) or acute inflammatory demyelinating polyneuropathy (n = 2). CSF analysis revealed an increased protein level in nine patients. Nerve conduction studies confirmed DD in all these patients. Anti-TNF-α was discontinued in 10 patients and 8 received i.v. immunoglobulins. Two patients relapsed after introduction of another anti-TNF-α. Overall, a causal relationship between anti-TNF-α and DD was considered as probable in 31 patients and definite in 2 who had positive rechallenge.
  
  
  CONCLUSIONS
  Causal relationship between anti-TNF-α and induction of DD remains unclear, but in some cases the chronology of clinical events is suggestive. Nevertheless, DD might persist despite treatment discontinuation, suggesting that anti-TNF-α could trigger the demyelinating process, which further evolves independently.
authors.affiliation: Assistance Publique Hopitaux de Paris, Biceêtre University Hospital, Department of Rheumatology, INSERM U802, France. raphaele.se@gmail.com
authors.forename: Raphaèle
authors.initials: R
authors.lastname: Seror
authors.forename: Christophe
authors.initials: C
authors.lastname: Richez
authors.forename: Christelle
authors.initials: C
authors.lastname: Sordet
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Rist
authors.forename: Laure
authors.initials: L
authors.lastname: Gossec
authors.forename: Guillaume
authors.initials: G
authors.lastname: Direz
authors.forename: Eric
authors.initials: E
authors.lastname: Houvenagel
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Berthelot
authors.forename: Christian
authors.initials: C
authors.lastname: Pagnoux
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Dernis
authors.forename: Sylvie
authors.initials: S
authors.lastname: Melac-Ducamp
authors.forename: Beatrice
authors.initials: B
authors.lastname: Bouvard
authors.forename: Caroline
authors.initials: C
authors.lastname: Asquier
authors.forename: Antoine
authors.initials: A
authors.lastname: Martin
authors.forename: Xavier
authors.initials: X
authors.lastname: Puechal
authors.forename: Xavier
authors.initials: X
authors.lastname: Mariette
mesh_terms: D000068879:Adalimumab; D000293:Adolescent; D000328:Adult; D017677:Age Distribution; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects; D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000188:drug therapy; D003430:Cross-Sectional Studies; D003711:Demyelinating Diseases / Q000139:chemically induced* / Q000453:epidemiology* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D000068800:Etanercept; D005260:Female; D005500:Follow-Up Studies; D005602:France / Q000453:epidemiology; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000009:adverse effects; D015994:Incidence; D000069285:Infliximab; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000175:diagnosis / Q000188:drug therapy; D018124:Receptors, Tumor Necrosis Factor / Q000008:administration & dosage; D012219:Rheumatology / Q000379:methods; D018570:Risk Assessment; D017678:Sex Distribution; D018709:Statistics, Nonparametric; D011795:Surveys and Questionnaires; D015996:Survival Rate; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000009:adverse effects* / Q000037:antagonists & inhibitors*; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068879:Adalimumab; D000068800:Etanercept