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EBioMedicine. 2019 Aug;46:381-386. doi: 10.1016/j.ebiom.2019.07.062. Epub 2019 Jul 29.

Pretreatment anti-thyroid autoantibodies indicate increased risk for thyroid autoimmunity secondary to alemtuzumab: A prospective cohort study.

Author information

1
Clinic of Neurology with Institute of Translational Neurology, University of Münster, Münster, Germany. Electronic address: tobias.ruck@ukmuenster.de.
2
Clinic of Neurology with Institute of Translational Neurology, University of Münster, Münster, Germany.
3
Department of Neurology, Clinics Osnabrück, Germany.
4
Department of Neurology, University Duisburg-Essen, Essen, Germany.

Abstract

BACKGROUND:

Alemtuzumab is approved for the treatment of active relapsing-remitting multiple sclerosis (RRMS). Alemtuzumab-related secondary autoimmune disorders (sAID) are common, with thyroid sAID being the most frequent, and fundamentally affect the risk-benefit ratio. Therefore, biomarkers indicating the development of sAID are urgently needed to instruct clinical decisions.

METHODS:

We evaluated whether the anti-thyroid autoantibodies (ThyAb) anti-thyroglobulin (anti-TG) and anti-thyroid-peroxidase (anti-TPO) detected at baseline by standard testing are able to indicate increased risk for thyroid sAID following alemtuzumab treatment in a multicentre prospective cohort of 106 alemtuzumab-treated RRMS patients. We here present an interim-analysis with a median follow-up of 36 months.

FINDINGS:

Baseline characteristics demonstrated no significant differences between patients with or without thyroid sAID. 29/106 (27·4%) patients developed thyroid sAID between 5 and 51 months following alemtuzumab treatment initiation. 14/29 patients (48·3%) were positive for ThyAb at baseline and developed thyroid sAID. Hazard ratio for time to thyroid autoimmunity was 12.15 (95% CI 4.73-31.2) indicating a highly increased risk for ThyAb positive patients. Baseline ThyAb were associated with shorter time to sAID, but not with a specific disease entity of thyroid sAID. Hazard ratios for age, sex, previous treatment, disease duration, disability and smoking status demonstrated no significant association with thyroid autoimmunity.

INTERPRETATION:

Standard ThyAb-testing for anti-TPO and anti-TG antibodies at baseline was able to indicate increased risk for clinically manifest thyroid sAID and should therefore be used in clinical decisions concerning alemtuzumab treatment initiation. FUND: German Ministry of Education, Science, Research and Technology and the German Research foundation.

KEYWORDS:

Alemtuzumab; Multiple sclerosis; Risk estimation; Secondary autoimmune disorders; Thyroid autoimmunity

PMID:
31371192
DOI:
10.1016/j.ebiom.2019.07.062
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