title: Long-term outcomes of refractory neurosarcoidosis treated with infliximab.
abstract: Central nervous system localizations of sarcoidosis may be refractory to conventional treatment such as steroids and immunosuppressive drugs. Infliximab, a TNF-α antagonist chimeric antibody, has been shown to be effective for treatment of these localizations. The aim of this study was to evaluate the efficacy and safety, in particular the long-term outcomes, of the use of infliximab for the treatment of neurosarcoidosis. We retrospectively reviewed medical records of patients with neurosarcoidosis who had been treated with infliximab between 2009 and 2015. All patients had histologically proven non-caseating granulomas. Eighteen patients with histologically proven sarcoidosis were included in this study. All had neurological involvement consisting of meningeal (n = 16), cerebral (n = 10), spinal cord (n = 6), and/or optic nerve (n = 5) involvement. Sixteen patients had previously received at least one immunosuppressive drug in addition to corticosteroids, including cyclophosphamide in 11 patients. All patients received treatment with infliximab (3-7.5 mg/kg) associated with corticosteroids (n = 18), low-dose methotrexate (n = 15), azathioprine (n = 2), or mycophenolate (n = 1). Sixteen out of 18 patients improved clinically (initial median modified Rankin scale score of 3, final median score of 1; p < 0.0001). At 6 months after initiation of infliximab, six patients obtained complete remission (33%), ten attained partial remission (56%), and two had stable disease (11%). The median follow-up time was 20 months (range 6-93). Nine patients relapsed during follow-up (50%). Eight patients developed toxic side effects and seven of these side effects were infectious events. Infliximab is an efficacious treatment of refractory neurosarcoidosis. However, relapses frequently occurred during follow-up.
authors.affiliation: AP-HP, Service de Médecine Interne 2, Institut e3m, Centre National de Référence Maladies Auto-immunes Systémiques Rares, Groupe Hospitalier Pitié-Salpétrière, 47-83 Boulevard de l'hôpital, 75013, Paris Cedex 13, France. fleur.cohen@aphp.fr.|Université Paris VI Pierre et Marie Curie, Sorbonnes Universités, 75013, Paris, France. fleur.cohen@aphp.fr.
authors.forename: Fleur
authors.initials: F
authors.lastname: Cohen Aubart
authors.affiliation: AP-HP, Service de Pneumologie, Hôpital Avicenne, 93000, Bobigny, France.
authors.forename: Diane
authors.initials: D
authors.lastname: Bouvry
authors.affiliation: Université Paris VI Pierre et Marie Curie, Sorbonnes Universités, 75013, Paris, France.|AP-HP, Service de Neuroradiologie Diagnostique et Fonctionnelle, Groupe Hospitalier Pitié-Salpêtrière, 75013, Paris, France.
authors.forename: Damien
authors.initials: D
authors.lastname: Galanaud
authors.affiliation: AP-HP, Service de Neurologie, Groupe Hospitalier Pitié-Salpêtrière, 75013, Paris, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Dehais
authors.affiliation: Service de Neurologie, Centre hospitalier Régional de Metz-Thionville, 57530, Ars-Laquenexy, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Mathey
authors.affiliation: AP-HP, Service de Neurologie, Groupe Hospitalier Pitié-Salpêtrière, 75013, Paris, France.
authors.forename: Dimitri
authors.initials: D
authors.lastname: Psimaras
authors.affiliation: AP-HP, Service de Médecine Interne 2, Institut e3m, Centre National de Référence Maladies Auto-immunes Systémiques Rares, Groupe Hospitalier Pitié-Salpétrière, 47-83 Boulevard de l'hôpital, 75013, Paris Cedex 13, France.|Université Paris VI Pierre et Marie Curie, Sorbonnes Universités, 75013, Paris, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Haroche
authors.affiliation: Service de Neurologie, Centre Hospitalier René Dubos, 95300, Pontoise, France.
authors.forename: Corinne
authors.initials: C
authors.lastname: Pottier
authors.affiliation: AP-HP, Service de Médecine Interne 2, Institut e3m, Centre National de Référence Maladies Auto-immunes Systémiques Rares, Groupe Hospitalier Pitié-Salpétrière, 47-83 Boulevard de l'hôpital, 75013, Paris Cedex 13, France.
authors.forename: Miguel
authors.initials: M
authors.lastname: Hie
authors.affiliation: AP-HP, Service de Médecine Interne 2, Institut e3m, Centre National de Référence Maladies Auto-immunes Systémiques Rares, Groupe Hospitalier Pitié-Salpétrière, 47-83 Boulevard de l'hôpital, 75013, Paris Cedex 13, France.
authors.forename: Alexis
authors.initials: A
authors.lastname: Mathian
authors.affiliation: Service de Médecine Interne, University Hospital, 21000, Dijon, France.
authors.forename: Hervé
authors.initials: H
authors.lastname: Devilliers
authors.affiliation: AP-HP, Service de Pneumologie, Hôpital Avicenne, 93000, Bobigny, France.
authors.forename: Hilario
authors.initials: H
authors.lastname: Nunes
authors.affiliation: AP-HP, Service de Pneumologie, Hôpital Avicenne, 93000, Bobigny, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Valeyre
authors.affiliation: AP-HP, Service de Médecine Interne 2, Institut e3m, Centre National de Référence Maladies Auto-immunes Systémiques Rares, Groupe Hospitalier Pitié-Salpétrière, 47-83 Boulevard de l'hôpital, 75013, Paris Cedex 13, France.|Université Paris VI Pierre et Marie Curie, Sorbonnes Universités, 75013, Paris, France.
authors.forename: Zahir
authors.initials: Z
authors.lastname: Amoura
mesh_terms: D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D002493:Central Nervous System Diseases / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D000069285:Infliximab / Q000627:therapeutic use*; D008137:Longitudinal Studies; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D012189:Retrospective Studies; D012507:Sarcoidosis / Q000188:drug therapy*; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D007166:Immunosuppressive Agents; D000069285:Infliximab; D008727:Methotrexate
keywords: Infliximab; Neurosarcoidosis; Relapses; Side effects