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International Ophthalmology

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01-10-2017 | Case Report

Alemtuzumab-induced remission of multiple sclerosis-associated uveitis

Authors: Mark D. Willis, Trevor P. Pickersgill, Neil P. Robertson, Richard W. J. Lee, Andrew D. Dick, Ester Carreño

Published in: International Ophthalmology | Issue 5/2017

Abstract

Purpose

The purpose of the study was to report a case of multiple sclerosis (MS)-associated uveitis refractory to conventional immunosuppressants, with subsequent remission following treatment with alemtuzumab.

Methods

Case report Patient was treated with intravenous alemtuzumab, a lymphocyte depleting anti-CD52 monoclonal antibody that has recently been approved for use in relapsing MS.

Results

A 17-year-old female presented with bilateral optic neuritis and subsequently bilateral intermediate uveitis and secondary macular oedema. She was diagnosed with active relapsing MS for which she received treatment with alemtuzumab. The intraocular inflammation previously refractory to conventional immunosuppressants responded to alemtuzumab, inducing remission.

Conclusions

To our knowledge, this is the first such report of alemtuzumab treatment in MS-associated ocular inflammatory disease and may demonstrate a potential utility for this drug in related conditions.

Cohen JA, Coles AJ, Arnold DL, Confavreux C, Fox EJ, Hartung H-P, Havrdova E, Selmaj KW, Weiner HL, Fisher E, Brinar VV, Giovannoni G, Stojanovic M, Ertik BI, Lake SL, Margolin DH, Panzara MA, Compston DAS (2012) Alemtuzumab versus interferon beta 1a as first-line treatment for patients with relapsing-remitting multiple sclerosis: a randomised controlled phase 3 trial. Lancet 380(9856):1819–1828. doi:10.1016/s0140-6736(12)61769-3 CrossRefPubMed

Coles AJ, Fox E, Vladic A, Gazda SK, Brinar V, Selmaj KW, Bass AD-D, Wynn DR, Margolin DH, Lake SL, Moran S, Palmer J, Smith MS, Compston DAS (2011) Alemtuzumab versus interferon beta-1a in early relapsing-remitting multiple sclerosis: post hoc and subset analyses of clinical efficacy outcomes. Lancet Neurol 10(4):338–348. doi:10.1016/s1474-4422(11)70020-5 CrossRefPubMed

Coles AJC, Compston DA, Selmaj KW et al (2008) Alemtuzumab vs. interferon beta-1a in early multiple sclerosis. N Engl J Med 359(17):1786–1801CrossRefPubMed

Hale G (2001) The CD52 antigen and development of the CAMPATH antibodies. Cytotherapy 3(3):137–143. doi:10.1080/146532401753174098 CrossRefPubMed

Rao SP, Sancho J, Campos-Rivera J, Boutin PM, Severy PB, Weeden T, Shankara S, Roberts BL, Kaplan JM (2012) Human peripheral blood mononuclear cells exhibit heterogeneous CD52 expression levels and show differential sensitivity to alemtuzumab mediated cytolysis. PLoS One 7(6):e39416. doi:10.1371/journal.pone.0039416 CrossRefPubMedPubMedCentral

Klotz L, Meuth SG, Wiendl H (2012) Immune mechanisms of new therapeutic strategies in multiple sclerosis-A focus on alemtuzumab. Clin Immunol 142(1):25–30. doi:10.1016/j.clim.2011.04.006 CrossRefPubMed

Becker MD, Heiligenhaus A, Hudde T, Storch-Hagenlocher B, Wildemann B, Barisani-Asenbauer T, Thimm C, Stubiger N, Trieschmann M, Fiehn C (2005) Interferon as a treatment for uveitis associated with multiple sclerosis. Br J Ophthalmol 89(10):1254–1257. doi:10.1136/bjo.2004.061119 CrossRefPubMedPubMedCentral

Messenger W, Hildebrandt L, Mackensen F, Suhler E, Becker M, Rosenbaum JT (2015) Characterisation of uveitis in association with multiple sclerosis. Br J Ophthalmol 99(2):205–209. doi:10.1136/bjophthalmol-2014-305518 CrossRefPubMed

Dick AD, Meyer P, James T, Forrester JV, Hale G, Waldmann H, Isaacs JD (2000) Campath-1H therapy in refractory ocular inflammatory disease. Br J Ophthalmol 84:107–109CrossRefPubMedPubMedCentral

10.

Isaacs JD, Hale G, Waldmann H, Dick AD, Haynes R, Forrester JV, Watson P, Meyer PA (1995) Monoclonal antibody therapy of chronic intraocular inflammation using Campath-1H. Br J Ophthalmol 79(11):1054–1055CrossRefPubMedPubMedCentral

11.

Lockwood CM, Hale G, Waldman H, Jayne DR (2003) Remission induction in Behcet’s disease following lymphocyte depletion by the anti-CD52 antibody CAMPATH 1-H. Rheumatology 42(12):1539–1544. doi:10.1093/rheumatology/keg424 CrossRefPubMed

12.

Caspi RR (2011) Understanding autoimmune uveitis through animal models. The Friedenwald Lecture. Invest Ophthalmol Vis Sci 52(3):1872–1879. doi:10.1167/iovs.10-6909 CrossRefPubMed

13.

Hill-Cawthorne GA, Button T, Tuohy O, Jones JL, May K, Somerfield J, Green A, Giovannoni G, Compston DA, Fahey MT, Coles AJ (2012) Long term lymphocyte reconstitution after alemtuzumab treatment of multiple sclerosis. J Neurol Neurosurg Psychiatry 83(3):298–304. doi:10.1136/jnnp-2011-300826 CrossRefPubMed

14.

Kousin-Ezewu OAL, Parker RA et al (2014) Accelerated lymphocyte recovery after alemtuzumab does not predict multiple sclerosis activity. Neurology 82(24):2158–2164CrossRefPubMedPubMedCentral

15.

Thompson SA, Jones JL, Cox AL, Compston DA, Coles AJ (2010) B-cell reconstitution and BAFF after alemtuzumab (Campath-1H) treatment of multiple sclerosis. J Clin Immunol 30(1):99–105. doi:10.1007/s10875-009-9327-3 CrossRefPubMed

16.

Ej F (2010) Alemtuzumab in the treatment of relapsing-remitting multiple sclerosis. Expert Rev Neurother 10(12):1789–1797CrossRef

17.

Hu Y, Turner MJ, Shields J, Gale MS, Hutto E, Roberts BL, Siders WM, Kaplan JM (2009) Investigation of the mechanism of action of alemtuzumab in a human CD52 transgenic mouse model. Immunology 128(2):260–270. doi:10.1111/j.1365-2567.2009.03115.x CrossRefPubMedPubMedCentral

18.

Stanglmaier M, Reis S, Hallek M (2004) Rituximab and alemtuzumab induce a nonclassic, caspase-independent apoptotic pathway in B-lymphoid cell lines and in chronic lymphocytic leukemia cells. Ann Hematol 83(10):634–645. doi:10.1007/s00277-004-0917-0 CrossRefPubMed

19.

Willis MD, Harding KE, Pickersgil T et al (2015) Alemtuzumab for multiple sclerosis: Long term follow-up in a multi-centre cohort. Mult Sclerosis 22(9):1215–1223CrossRef

Title: Alemtuzumab-induced remission of multiple sclerosis-associated uveitis
Authors: Mark D. Willis
Trevor P. Pickersgill
Neil P. Robertson
Richard W. J. Lee
Andrew D. Dick
Ester Carreño
Publication date: 01-10-2017
Publisher: Springer Netherlands
Published in: International Ophthalmology / Issue 5/2017
Print ISSN: 0165-5701
Electronic ISSN: 1573-2630
DOI: https://doi.org/10.1007/s10792-016-0370-9

At a glance: The STEP trials

Springer Medicine

Alemtuzumab-induced remission of multiple sclerosis-associated uveitis

Abstract

Purpose

Methods

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

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