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dc.contributor.authorRoos, Jonathan CP
dc.contributor.authorMoran, Carla
dc.contributor.authorChatterjee, Krishna
dc.contributor.authorJones, Joanna
dc.contributor.authorColes, Alasdair
dc.contributor.authorMurthy, Rachna
dc.date.accessioned2018-12-21T00:30:17Z
dc.date.available2018-12-21T00:30:17Z
dc.date.issued2019-02
dc.identifier.issn0950-222X
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/287288
dc.description.abstractAlemtuzumab-a monoclonal antibody targeting the CD52 glycoprotein expressed by most mature leucocytes-effectively decreases relapse rate and disability progression in early, relapsing-remitting multiple sclerosis (MS). However, secondary autoimmune disorders complicate therapy in nearly 50% of treated patients, with Graves' disease being the most common. Rarely, thyroid eye disease (TED) ensues; only seven such cases have been reported. Our aim was to analyse the largest series of MS patients developing thyroid eye disease after alemtuzumab treatment. We performed a retrospective chart review of MS patients treated with alemtuzumab (1995-2018) and subsequently identified by their treating physicians as having developed TED and referred to our ophthalmology service. As an original trial centre for alemtuzumab, our hospital has treated approximately 162 MS patients with this novel therapy. In total, 71 (44%) developed thyroid dysfunction, most of whom (87%) developed Graves' disease, with ten (16%) referred for ophthalmological evaluation. Two developed active orbitopathy following radioiodine treatment; one occurred after cessation of anti-thyroid drug treatment. Three developed sight-threatening disease requiring systemic immunosuppression, with one refractory to multiple immunosuppressants. The remaining patients were treated conservatively. TSH-receptor antibody (TRAb) levels were significantly raised in all cases, when ascertained. We report sight-threatening as well as mild TED in MS patients after treatment with alemtuzumab. Endocrine instability, radioiodine treatment and positive TRAb are all likely risk factors. The data support at least 6-monthly biochemical and clinical assessment with a low threshold for referral to an ophthalmologist, particularly for those with higher TRAb levels who may be at greater risk of orbitopathy.
dc.format.mediumPrint-Electronic
dc.languageeng
dc.publisherSpringer Science and Business Media LLC
dc.subjectHumans
dc.subjectMultiple Sclerosis
dc.subjectDisease Progression
dc.subjectRecurrence
dc.subjectReceptors, Thyrotropin
dc.subjectAutoantibodies
dc.subjectMagnetic Resonance Imaging
dc.subjectEnzyme-Linked Immunosorbent Assay
dc.subjectRisk Factors
dc.subjectRetrospective Studies
dc.subjectAdolescent
dc.subjectAdult
dc.subjectMiddle Aged
dc.subjectFemale
dc.subjectMale
dc.subjectGraves Ophthalmopathy
dc.subjectImmune Reconstitution
dc.subjectAntineoplastic Agents, Immunological
dc.subjectAlemtuzumab
dc.titleImmune reconstitution after alemtuzumab therapy for multiple sclerosis triggering Graves' orbitopathy: a case series.
dc.typeArticle
prism.endingPage229
prism.issueIdentifier2
prism.publicationDate2019
prism.publicationNameEye (Lond)
prism.startingPage223
prism.volume33
dc.identifier.doi10.17863/CAM.34592
dcterms.dateAccepted2018-11-06
rioxxterms.versionofrecord10.1038/s41433-018-0282-1
rioxxterms.versionAM
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2019-02
dc.contributor.orcidChatterjee, Krishna [0000-0002-2654-8854]
dc.contributor.orcidJones, Joanna [0000-0003-4974-1371]
dc.contributor.orcidColes, Alasdair [0000-0003-4738-0760]
dc.identifier.eissn1476-5454
rioxxterms.typeJournal Article/Review
pubs.funder-project-idWellcome Trust (105924/Z/14/Z)
pubs.funder-project-idWellcome Trust (105924/Z/14/A)
pubs.funder-project-idWellcome Trust (105924/Z/14/Z)
pubs.funder-project-idWellcome Trust (105924/Z/14/A)
pubs.funder-project-idMedical Research Council (G1100114)
cam.issuedOnline2018-11-29
rioxxterms.freetoread.startdate2019-11-29


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