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November 14, 2017; 89 (20) Article

Infliximab for the treatment of CNS sarcoidosis

A multi-institutional series

Jeffrey M. Gelfand, Michael J. Bradshaw, Barney J. Stern, David B. Clifford, Yunxia Wang, Tracey A. Cho, Laura L. Koth, Stephen L. Hauser, Jason Dierkhising, NgocHanh Vu, Subramaniam Sriram, Harold Moses, Francesca Bagnato, Jeffrey A. Kaufmann, Deidre J. Ammah, Tsion H. Yohannes, Mark J. Hamblin, Nagagopal Venna, Ari J. Green, Siddharama Pawate
First published October 13, 2017, DOI: https://doi.org/10.1212/WNL.0000000000004644
Jeffrey M. Gelfand
From the Department of Neurology (J.M.G., S.L.H., J.D., A.J.G.), Division of Pulmonary and Critical Care, Department of Medicine (L.L.K.), and Department of Ophthalmology (A.J.G.), University of California San Francisco; Department of Neurology (M.J.B., N.V., S.S., H.M., F.B., S.P.), Vanderbilt University Medical Center, Nashville, TN; Department of Neurology (B.J.S., J.A.K., D.J.A.), University of Maryland Medical Center, Baltimore; Departments of Neurology and Medicine (D.B.C., T.H.Y.), Washington University in St. Louis, MO; Department of Neurology (Y.W., M.J.H.), University of Kansas Medical Center, Kansas City; and Department of Neurology (T.A.C., N.V.), Massachusetts General Hospital, Boston.
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Michael J. Bradshaw
From the Department of Neurology (J.M.G., S.L.H., J.D., A.J.G.), Division of Pulmonary and Critical Care, Department of Medicine (L.L.K.), and Department of Ophthalmology (A.J.G.), University of California San Francisco; Department of Neurology (M.J.B., N.V., S.S., H.M., F.B., S.P.), Vanderbilt University Medical Center, Nashville, TN; Department of Neurology (B.J.S., J.A.K., D.J.A.), University of Maryland Medical Center, Baltimore; Departments of Neurology and Medicine (D.B.C., T.H.Y.), Washington University in St. Louis, MO; Department of Neurology (Y.W., M.J.H.), University of Kansas Medical Center, Kansas City; and Department of Neurology (T.A.C., N.V.), Massachusetts General Hospital, Boston.
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Barney J. Stern
From the Department of Neurology (J.M.G., S.L.H., J.D., A.J.G.), Division of Pulmonary and Critical Care, Department of Medicine (L.L.K.), and Department of Ophthalmology (A.J.G.), University of California San Francisco; Department of Neurology (M.J.B., N.V., S.S., H.M., F.B., S.P.), Vanderbilt University Medical Center, Nashville, TN; Department of Neurology (B.J.S., J.A.K., D.J.A.), University of Maryland Medical Center, Baltimore; Departments of Neurology and Medicine (D.B.C., T.H.Y.), Washington University in St. Louis, MO; Department of Neurology (Y.W., M.J.H.), University of Kansas Medical Center, Kansas City; and Department of Neurology (T.A.C., N.V.), Massachusetts General Hospital, Boston.
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David B. Clifford
From the Department of Neurology (J.M.G., S.L.H., J.D., A.J.G.), Division of Pulmonary and Critical Care, Department of Medicine (L.L.K.), and Department of Ophthalmology (A.J.G.), University of California San Francisco; Department of Neurology (M.J.B., N.V., S.S., H.M., F.B., S.P.), Vanderbilt University Medical Center, Nashville, TN; Department of Neurology (B.J.S., J.A.K., D.J.A.), University of Maryland Medical Center, Baltimore; Departments of Neurology and Medicine (D.B.C., T.H.Y.), Washington University in St. Louis, MO; Department of Neurology (Y.W., M.J.H.), University of Kansas Medical Center, Kansas City; and Department of Neurology (T.A.C., N.V.), Massachusetts General Hospital, Boston.
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Yunxia Wang
From the Department of Neurology (J.M.G., S.L.H., J.D., A.J.G.), Division of Pulmonary and Critical Care, Department of Medicine (L.L.K.), and Department of Ophthalmology (A.J.G.), University of California San Francisco; Department of Neurology (M.J.B., N.V., S.S., H.M., F.B., S.P.), Vanderbilt University Medical Center, Nashville, TN; Department of Neurology (B.J.S., J.A.K., D.J.A.), University of Maryland Medical Center, Baltimore; Departments of Neurology and Medicine (D.B.C., T.H.Y.), Washington University in St. Louis, MO; Department of Neurology (Y.W., M.J.H.), University of Kansas Medical Center, Kansas City; and Department of Neurology (T.A.C., N.V.), Massachusetts General Hospital, Boston.
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Tracey A. Cho
From the Department of Neurology (J.M.G., S.L.H., J.D., A.J.G.), Division of Pulmonary and Critical Care, Department of Medicine (L.L.K.), and Department of Ophthalmology (A.J.G.), University of California San Francisco; Department of Neurology (M.J.B., N.V., S.S., H.M., F.B., S.P.), Vanderbilt University Medical Center, Nashville, TN; Department of Neurology (B.J.S., J.A.K., D.J.A.), University of Maryland Medical Center, Baltimore; Departments of Neurology and Medicine (D.B.C., T.H.Y.), Washington University in St. Louis, MO; Department of Neurology (Y.W., M.J.H.), University of Kansas Medical Center, Kansas City; and Department of Neurology (T.A.C., N.V.), Massachusetts General Hospital, Boston.
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Laura L. Koth
From the Department of Neurology (J.M.G., S.L.H., J.D., A.J.G.), Division of Pulmonary and Critical Care, Department of Medicine (L.L.K.), and Department of Ophthalmology (A.J.G.), University of California San Francisco; Department of Neurology (M.J.B., N.V., S.S., H.M., F.B., S.P.), Vanderbilt University Medical Center, Nashville, TN; Department of Neurology (B.J.S., J.A.K., D.J.A.), University of Maryland Medical Center, Baltimore; Departments of Neurology and Medicine (D.B.C., T.H.Y.), Washington University in St. Louis, MO; Department of Neurology (Y.W., M.J.H.), University of Kansas Medical Center, Kansas City; and Department of Neurology (T.A.C., N.V.), Massachusetts General Hospital, Boston.
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Stephen L. Hauser
From the Department of Neurology (J.M.G., S.L.H., J.D., A.J.G.), Division of Pulmonary and Critical Care, Department of Medicine (L.L.K.), and Department of Ophthalmology (A.J.G.), University of California San Francisco; Department of Neurology (M.J.B., N.V., S.S., H.M., F.B., S.P.), Vanderbilt University Medical Center, Nashville, TN; Department of Neurology (B.J.S., J.A.K., D.J.A.), University of Maryland Medical Center, Baltimore; Departments of Neurology and Medicine (D.B.C., T.H.Y.), Washington University in St. Louis, MO; Department of Neurology (Y.W., M.J.H.), University of Kansas Medical Center, Kansas City; and Department of Neurology (T.A.C., N.V.), Massachusetts General Hospital, Boston.
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Jason Dierkhising
From the Department of Neurology (J.M.G., S.L.H., J.D., A.J.G.), Division of Pulmonary and Critical Care, Department of Medicine (L.L.K.), and Department of Ophthalmology (A.J.G.), University of California San Francisco; Department of Neurology (M.J.B., N.V., S.S., H.M., F.B., S.P.), Vanderbilt University Medical Center, Nashville, TN; Department of Neurology (B.J.S., J.A.K., D.J.A.), University of Maryland Medical Center, Baltimore; Departments of Neurology and Medicine (D.B.C., T.H.Y.), Washington University in St. Louis, MO; Department of Neurology (Y.W., M.J.H.), University of Kansas Medical Center, Kansas City; and Department of Neurology (T.A.C., N.V.), Massachusetts General Hospital, Boston.
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NgocHanh Vu
From the Department of Neurology (J.M.G., S.L.H., J.D., A.J.G.), Division of Pulmonary and Critical Care, Department of Medicine (L.L.K.), and Department of Ophthalmology (A.J.G.), University of California San Francisco; Department of Neurology (M.J.B., N.V., S.S., H.M., F.B., S.P.), Vanderbilt University Medical Center, Nashville, TN; Department of Neurology (B.J.S., J.A.K., D.J.A.), University of Maryland Medical Center, Baltimore; Departments of Neurology and Medicine (D.B.C., T.H.Y.), Washington University in St. Louis, MO; Department of Neurology (Y.W., M.J.H.), University of Kansas Medical Center, Kansas City; and Department of Neurology (T.A.C., N.V.), Massachusetts General Hospital, Boston.
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Subramaniam Sriram
From the Department of Neurology (J.M.G., S.L.H., J.D., A.J.G.), Division of Pulmonary and Critical Care, Department of Medicine (L.L.K.), and Department of Ophthalmology (A.J.G.), University of California San Francisco; Department of Neurology (M.J.B., N.V., S.S., H.M., F.B., S.P.), Vanderbilt University Medical Center, Nashville, TN; Department of Neurology (B.J.S., J.A.K., D.J.A.), University of Maryland Medical Center, Baltimore; Departments of Neurology and Medicine (D.B.C., T.H.Y.), Washington University in St. Louis, MO; Department of Neurology (Y.W., M.J.H.), University of Kansas Medical Center, Kansas City; and Department of Neurology (T.A.C., N.V.), Massachusetts General Hospital, Boston.
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Harold Moses
From the Department of Neurology (J.M.G., S.L.H., J.D., A.J.G.), Division of Pulmonary and Critical Care, Department of Medicine (L.L.K.), and Department of Ophthalmology (A.J.G.), University of California San Francisco; Department of Neurology (M.J.B., N.V., S.S., H.M., F.B., S.P.), Vanderbilt University Medical Center, Nashville, TN; Department of Neurology (B.J.S., J.A.K., D.J.A.), University of Maryland Medical Center, Baltimore; Departments of Neurology and Medicine (D.B.C., T.H.Y.), Washington University in St. Louis, MO; Department of Neurology (Y.W., M.J.H.), University of Kansas Medical Center, Kansas City; and Department of Neurology (T.A.C., N.V.), Massachusetts General Hospital, Boston.
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Francesca Bagnato
From the Department of Neurology (J.M.G., S.L.H., J.D., A.J.G.), Division of Pulmonary and Critical Care, Department of Medicine (L.L.K.), and Department of Ophthalmology (A.J.G.), University of California San Francisco; Department of Neurology (M.J.B., N.V., S.S., H.M., F.B., S.P.), Vanderbilt University Medical Center, Nashville, TN; Department of Neurology (B.J.S., J.A.K., D.J.A.), University of Maryland Medical Center, Baltimore; Departments of Neurology and Medicine (D.B.C., T.H.Y.), Washington University in St. Louis, MO; Department of Neurology (Y.W., M.J.H.), University of Kansas Medical Center, Kansas City; and Department of Neurology (T.A.C., N.V.), Massachusetts General Hospital, Boston.
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Jeffrey A. Kaufmann
From the Department of Neurology (J.M.G., S.L.H., J.D., A.J.G.), Division of Pulmonary and Critical Care, Department of Medicine (L.L.K.), and Department of Ophthalmology (A.J.G.), University of California San Francisco; Department of Neurology (M.J.B., N.V., S.S., H.M., F.B., S.P.), Vanderbilt University Medical Center, Nashville, TN; Department of Neurology (B.J.S., J.A.K., D.J.A.), University of Maryland Medical Center, Baltimore; Departments of Neurology and Medicine (D.B.C., T.H.Y.), Washington University in St. Louis, MO; Department of Neurology (Y.W., M.J.H.), University of Kansas Medical Center, Kansas City; and Department of Neurology (T.A.C., N.V.), Massachusetts General Hospital, Boston.
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Deidre J. Ammah
From the Department of Neurology (J.M.G., S.L.H., J.D., A.J.G.), Division of Pulmonary and Critical Care, Department of Medicine (L.L.K.), and Department of Ophthalmology (A.J.G.), University of California San Francisco; Department of Neurology (M.J.B., N.V., S.S., H.M., F.B., S.P.), Vanderbilt University Medical Center, Nashville, TN; Department of Neurology (B.J.S., J.A.K., D.J.A.), University of Maryland Medical Center, Baltimore; Departments of Neurology and Medicine (D.B.C., T.H.Y.), Washington University in St. Louis, MO; Department of Neurology (Y.W., M.J.H.), University of Kansas Medical Center, Kansas City; and Department of Neurology (T.A.C., N.V.), Massachusetts General Hospital, Boston.
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Tsion H. Yohannes
From the Department of Neurology (J.M.G., S.L.H., J.D., A.J.G.), Division of Pulmonary and Critical Care, Department of Medicine (L.L.K.), and Department of Ophthalmology (A.J.G.), University of California San Francisco; Department of Neurology (M.J.B., N.V., S.S., H.M., F.B., S.P.), Vanderbilt University Medical Center, Nashville, TN; Department of Neurology (B.J.S., J.A.K., D.J.A.), University of Maryland Medical Center, Baltimore; Departments of Neurology and Medicine (D.B.C., T.H.Y.), Washington University in St. Louis, MO; Department of Neurology (Y.W., M.J.H.), University of Kansas Medical Center, Kansas City; and Department of Neurology (T.A.C., N.V.), Massachusetts General Hospital, Boston.
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Mark J. Hamblin
From the Department of Neurology (J.M.G., S.L.H., J.D., A.J.G.), Division of Pulmonary and Critical Care, Department of Medicine (L.L.K.), and Department of Ophthalmology (A.J.G.), University of California San Francisco; Department of Neurology (M.J.B., N.V., S.S., H.M., F.B., S.P.), Vanderbilt University Medical Center, Nashville, TN; Department of Neurology (B.J.S., J.A.K., D.J.A.), University of Maryland Medical Center, Baltimore; Departments of Neurology and Medicine (D.B.C., T.H.Y.), Washington University in St. Louis, MO; Department of Neurology (Y.W., M.J.H.), University of Kansas Medical Center, Kansas City; and Department of Neurology (T.A.C., N.V.), Massachusetts General Hospital, Boston.
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Nagagopal Venna
From the Department of Neurology (J.M.G., S.L.H., J.D., A.J.G.), Division of Pulmonary and Critical Care, Department of Medicine (L.L.K.), and Department of Ophthalmology (A.J.G.), University of California San Francisco; Department of Neurology (M.J.B., N.V., S.S., H.M., F.B., S.P.), Vanderbilt University Medical Center, Nashville, TN; Department of Neurology (B.J.S., J.A.K., D.J.A.), University of Maryland Medical Center, Baltimore; Departments of Neurology and Medicine (D.B.C., T.H.Y.), Washington University in St. Louis, MO; Department of Neurology (Y.W., M.J.H.), University of Kansas Medical Center, Kansas City; and Department of Neurology (T.A.C., N.V.), Massachusetts General Hospital, Boston.
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Ari J. Green
From the Department of Neurology (J.M.G., S.L.H., J.D., A.J.G.), Division of Pulmonary and Critical Care, Department of Medicine (L.L.K.), and Department of Ophthalmology (A.J.G.), University of California San Francisco; Department of Neurology (M.J.B., N.V., S.S., H.M., F.B., S.P.), Vanderbilt University Medical Center, Nashville, TN; Department of Neurology (B.J.S., J.A.K., D.J.A.), University of Maryland Medical Center, Baltimore; Departments of Neurology and Medicine (D.B.C., T.H.Y.), Washington University in St. Louis, MO; Department of Neurology (Y.W., M.J.H.), University of Kansas Medical Center, Kansas City; and Department of Neurology (T.A.C., N.V.), Massachusetts General Hospital, Boston.
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Siddharama Pawate
From the Department of Neurology (J.M.G., S.L.H., J.D., A.J.G.), Division of Pulmonary and Critical Care, Department of Medicine (L.L.K.), and Department of Ophthalmology (A.J.G.), University of California San Francisco; Department of Neurology (M.J.B., N.V., S.S., H.M., F.B., S.P.), Vanderbilt University Medical Center, Nashville, TN; Department of Neurology (B.J.S., J.A.K., D.J.A.), University of Maryland Medical Center, Baltimore; Departments of Neurology and Medicine (D.B.C., T.H.Y.), Washington University in St. Louis, MO; Department of Neurology (Y.W., M.J.H.), University of Kansas Medical Center, Kansas City; and Department of Neurology (T.A.C., N.V.), Massachusetts General Hospital, Boston.
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Full PDF
Citation
Infliximab for the treatment of CNS sarcoidosis
A multi-institutional series
Jeffrey M. Gelfand, Michael J. Bradshaw, Barney J. Stern, David B. Clifford, Yunxia Wang, Tracey A. Cho, Laura L. Koth, Stephen L. Hauser, Jason Dierkhising, NgocHanh Vu, Subramaniam Sriram, Harold Moses, Francesca Bagnato, Jeffrey A. Kaufmann, Deidre J. Ammah, Tsion H. Yohannes, Mark J. Hamblin, Nagagopal Venna, Ari J. Green, Siddharama Pawate
Neurology Nov 2017, 89 (20) 2092-2100; DOI: 10.1212/WNL.0000000000004644

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Abstract

Objective: To describe clinical and imaging responses in neurosarcoidosis to infliximab, a monoclonal antibody against tumor necrosis factor–α.

Methods: Investigators at 6 US centers retrospectively identified patients with CNS sarcoidosis treated with infliximab, including only patients with definite or probable neurosarcoidosis following rigorous exclusion of other causes.

Results: Of 66 patients with CNS sarcoidosis (27 definite, 39 probable) treated with infliximab for a median of 1.5 years, the mean age was 47.5 years at infliximab initiation (SD 11.7, range 24–71 years); 56.1% were female; 62.1% were white, 37.0% African American, and 3% Hispanic. Sarcoidosis was isolated to the CNS in 19.7%. Using infliximab doses ranging from 3 to 7 mg/kg every 4–8 weeks, MRI evidence of a favorable treatment response was observed in 82.1% of patients with imaging follow-up (n = 56), with complete remission of active disease in 51.8% and partial MRI improvement in 30.1%; MRI worsened in 1 patient (1.8%). There was clinical improvement in 77.3% of patients, with complete neurologic recovery in 28.8%, partial improvement in 48.5%, clinical stability in 18.2%, worsening in 3%, and 1 lost to follow-up. In 16 patients in remission when infliximab was discontinued, the disease recurred in 9 (56%), typically in the same neuroanatomic location.

Conclusions: Most patients with CNS sarcoidosis treated with infliximab exhibit favorable imaging and clinical treatment responses, including some previously refractory to other immunosuppressive treatments.

Classification of evidence: This study provides Class IV evidence that for patients with CNS sarcoidosis infliximab is associated with favorable imaging and clinical responses.

GLOSSARY

CI=
confidence interval;
CVID=
combined variable immunodeficiency;
OR=
odds ratio;
TNF-α=
tumor necrosis factor–α

Footnotes

  • ↵* These authors contributed equally to this work and should be considered co–first authors.

  • Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Supplemental data at Neurology.org

  • Received April 14, 2017.
  • Accepted in final form August 30, 2017.
  • © 2017 American Academy of Neurology
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Letters: Rapid online correspondence

  • Author response: Infliximab for the treatment of CNS sarcoidosis: A multi-institutional series
    • Michael J Bradshaw, Neuroimmunology/Autoimmune Neurology Fellow, Brigham and Women's Hospital; Massachusetts General Hospital; Harvard Medical School
    • Jeffrey M Gelfand, Assistant Professor of Neurology, University of California, San Francisco
    • Siddharama Pawate, Assistant Professor of Neurology, Vanderbilt University Medical Center
    Submitted March 09, 2018
  • Infliximab in neurosarcoidosis
    • Jagannadha Avasarala, Associate Professor of Neurology, USC School of Medicine (Greenville, SC)javasarala@ghs.org
    Submitted December 04, 2017
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Neurology: 100 (21)

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