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Journal of Neurology

, Volume 264, Issue 5, pp 891–897 | Cite as

Long-term outcomes of refractory neurosarcoidosis treated with infliximab

  • Fleur Cohen AubartEmail author
  • Diane Bouvry
  • Damien Galanaud
  • Caroline Dehais
  • Guillaume Mathey
  • Dimitri Psimaras
  • Julien Haroche
  • Corinne Pottier
  • Miguel Hie
  • Alexis Mathian
  • Hervé Devilliers
  • Hilario Nunes
  • Dominique Valeyre
  • Zahir Amoura
Original Communication

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.

Keywords

Neurosarcoidosis Infliximab Relapses Side effects 

Notes

Compliance with ethical standards

Conflicts of interest

The authors declare no conflicts of interest and no disclosures relevant to the manuscript. This work did not receive any funding.

References

  1. 1.
    Baughman RP, Drent M, Kavuru M, Judson MA, Costabel U, du Bois R, Albera C, Brutsche M, Davis G, Donohue JF, Muller-Quernheim J, Schlenker-Herceg R, Flavin S, Lo KH, Oemar B, Barnathan ES, Sarcoidosis I (2006) Infliximab therapy in patients with chronic sarcoidosis and pulmonary involvement. Am J Respir Crit Care Med 174:795–802CrossRefPubMedGoogle Scholar
  2. 2.
    Baughman RP, Winget DB, Lower EE (2000) Methotrexate is steroid sparing in acute sarcoidosis: results of a double blind, randomized trial. Sarcoidosis Vasc Diffus Lung Dis Off J Wasog/World Assoc Sarcoidosis Other Granul Disord 17:60–66Google Scholar
  3. 3.
    Carter JD, Valeriano J, Vasey FB, Bognar B (2004) Refractory neurosarcoidosis: a dramatic response to infliximab. Am J Med 117:277–279CrossRefPubMedGoogle Scholar
  4. 4.
    Chintamaneni S, Patel AM, Pegram SB, Patel H, Roppelt H (2010) Dramatic response to infliximab in refractory neurosarcoidosis. Ann Indian Acad Neurol 13:207–210CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Cinetto F, Agostini C (2016) Advances in understanding the immunopathology of sarcoidosis and implications on therapy. Expert Rev Clin Immunol 12(9):973–988Google Scholar
  6. 6.
    Delaney P (1977) Neurologic manifestations in sarcoidosis: review of the literature, with a report of 23 cases. Ann Intern Med 87:336–345CrossRefPubMedGoogle Scholar
  7. 7.
    Drent M, Cremers JP, Jansen TL, Baughman RP (2014) Practical eminence and experience-based recommendations for use of TNF-alpha inhibitors in sarcoidosis. Sarcoidosis Vasc Diffus Lung Dis Off J Wasog/World Assoc Sarcoidosis Other Granul Disord 31:91–107Google Scholar
  8. 8.
    Ferriby D, de Seze J, Stojkovic T, Hachulla E, Wallaert B, Destee A, Hatron PY, Vermersch P (2001) Long-term follow-up of neurosarcoidosis. Neurology 57:927–929CrossRefPubMedGoogle Scholar
  9. 9.
    Judson MA, Baughman RP, Costabel U, Flavin S, Lo KH, Kavuru MS, Drent M, Centocor TSI (2008) Efficacy of infliximab in extrapulmonary sarcoidosis: results from a randomised trial. Euro Respir J 31:1189–1196CrossRefGoogle Scholar
  10. 10.
    Kobylecki C, Shaunak S (2007) Refractory neurosarcoidosis responsive to infliximab. Pract Neurol 7:112–115PubMedGoogle Scholar
  11. 11.
    Lorentzen AO, Sveberg L, Midtvedt O, Kerty E, Heuser K (2014) Overnight response to infliximab in neurosarcoidosis: a case report and review of infliximab treatment practice. Clin Neuropharmacol 37:142–148CrossRefPubMedGoogle Scholar
  12. 12.
    Lower EE, Broderick JP, Brott TG, Baughman RP (1997) Diagnosis and management of neurological sarcoidosis. Arch Intern Med 157:1864–1868CrossRefPubMedGoogle Scholar
  13. 13.
    Luke RA, Stern BJ, Krumholz A, Johns CJ (1987) Neurosarcoidosis: the long-term clinical course. Neurology 37:461–463CrossRefPubMedGoogle Scholar
  14. 14.
    Moravan M, Segal BM (2009) Treatment of CNS sarcoidosis with infliximab and mycophenolate mofetil. Neurology 72:337–340CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Morcos Z (2003) Refractory neurosarcoidosis responding to infliximab. Neurology 60:1220–1221CrossRefPubMedGoogle Scholar
  16. 16.
    O’Reilly MW, Sexton DJ, Dennedy MC, Counihan TJ, Finucane FM, O’Brien T, O’Regan AW (2015) Radiological remission and recovery of thirst appreciation after infliximab therapy in adipsic diabetes insipidus secondary to neurosarcoidosis. QJM Mon J Assoc Phys 108:657–659Google Scholar
  17. 17.
    Pereira J, Anderson NE, McAuley D, Bergin P, Kilfoyle D, Fink J (2011) Medically refractory neurosarcoidosis treated with infliximab. Intern Med J 41:354–357CrossRefPubMedGoogle Scholar
  18. 18.
    Pettersen JA, Zochodne DW, Bell RB, Martin L, Hill MD (2002) Refractory neurosarcoidosis responding to infliximab. Neurology 59:1660–1661CrossRefPubMedGoogle Scholar
  19. 19.
    Santos E, Shaunak S, Renowden S, Scolding NJ (2010) Treatment of refractory neurosarcoidosis with Infliximab. J Neurol Neurosurg Psychiatry 81:241–246CrossRefPubMedGoogle Scholar
  20. 20.
    Sollberger M, Fluri F, Baumann T, Sonnet S, Tamm M, Steck AJ, Brutsche M (2004) Successful treatment of steroid-refractory neurosarcoidosis with infliximab. J Neurol 251:760–761CrossRefPubMedGoogle Scholar
  21. 21.
    Valeyre D, Prasse A, Nunes H, Uzunhan Y, Brillet PY, Muller-Quernheim J (2014) Sarcoidosis. Lancet 383:1155–1167CrossRefPubMedGoogle Scholar
  22. 22.
    Vorselaars AD, Verwoerd A, van Moorsel CH, Keijsers RG, Rijkers GT, Grutters JC (2014) Prediction of relapse after discontinuation of infliximab therapy in severe sarcoidosis. Euro Respir J 43:602–609CrossRefGoogle Scholar
  23. 23.
    Zajicek JP, Scolding NJ, Foster O, Rovaris M, Evanson J, Moseley IF, Scadding JW, Thompson EJ, Chamoun V, Miller DH, McDonald WI, Mitchell D (1999) Central nervous system sarcoidosis–diagnosis and management. QJM Month J Assoc Phys 92:103–117Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • Fleur Cohen Aubart
    • 1
    • 2
    Email author
  • Diane Bouvry
    • 3
  • Damien Galanaud
    • 2
    • 4
  • Caroline Dehais
    • 5
  • Guillaume Mathey
    • 6
  • Dimitri Psimaras
    • 5
  • Julien Haroche
    • 1
    • 2
  • Corinne Pottier
    • 7
  • Miguel Hie
    • 1
  • Alexis Mathian
    • 1
  • Hervé Devilliers
    • 8
  • Hilario Nunes
    • 3
  • Dominique Valeyre
    • 3
  • Zahir Amoura
    • 1
    • 2
  1. 1.AP-HP, Service de Médecine Interne 2, Institut e3m, Centre National de Référence Maladies Auto-immunes Systémiques RaresGroupe Hospitalier Pitié-SalpétrièreParis Cedex 13France
  2. 2.Université Paris VI Pierre et Marie Curie, Sorbonnes UniversitésParisFrance
  3. 3.AP-HP, Service de PneumologieHôpital AvicenneBobignyFrance
  4. 4.AP-HP, Service de Neuroradiologie Diagnostique et FonctionnelleGroupe Hospitalier Pitié-SalpêtrièreParisFrance
  5. 5.AP-HP, Service de NeurologieGroupe Hospitalier Pitié-SalpêtrièreParisFrance
  6. 6.Service de NeurologieCentre hospitalier Régional de Metz-ThionvilleArs-LaquenexyFrance
  7. 7.Service de NeurologieCentre Hospitalier René DubosPontoiseFrance
  8. 8.Service de Médecine InterneUniversity HospitalDijonFrance

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