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Alemtuzumab-related thyroid disease in people with multiple sclerosis is associated with age and brainstem phenotype at disease onset.
Mult Scler J Exp Transl Clin. 2020 Apr-Jun; 6(2):2055217320933928.MS

Abstract

Background

Autoimmune thyroid disease (AITD) occurs in 40%-50% of alemtuzumab-treated persons with multiple sclerosis (pwMS), most of whom will develop Graves' Disease (GD).

Objective

To explore contributory factors for alemtuzumab-related AITD in pwMS.

Methods

A retrospective patient chart review was performed.

Results

Sixteen out of 52 (30.8%) pwMS developed AITD. GD occurred in 56.3% (n = 9), the majority (n = 7, 77.8%) symptomatic. All but one (85.7%) pwMS with symptomatic GD developed atypical, large and rapid fluctuations in thyroid hormone levels unexplained by effect of anti-thyroid medication alone. All symptomatic GD cases were age ≤32 years when starting alemtuzumab (ɸ = 0.60, p = 0.03). PwMS who started alemtuzumab at a younger age developed thyroid disease earlier (r = 0.51, p = 0.04). PwMS with clinical and radiological evidence of brainstem involvement at onset of multiple sclerosis were 11 times more likely to develop symptomatic GD compared with those with other phenotypes (p < 0.01).

Conclusion

Alemtuzumab-induced reconstitution GD may result from early and increased cross-reactivity between antigens common to the brainstem and thyroid, or presence of shared Human Leukocyte Antigen (HLA) alleles that determine brainstem and thyroid involvement. We suggest cautious use of alemtuzumab in younger (≤32 years) pwMS with early brainstem involvement, especially those actively planning pregnancy, where alternative therapies are readily available.

Authors+Show Affiliations

Department of Neurology, St. Vincent's University Hospital, Dublin, Ireland.Department of Neurology, St. Vincent's University Hospital, Dublin, Ireland.Department of Endocrinology, St. Vincent's University Hospital, Dublin, Ireland; School of Medicine, University College Dublin, Dublin, Ireland.Department of Neurology, St. Vincent's University Hospital, Dublin, Ireland.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32612846

Citation

Yap, Siew Mei, et al. "Alemtuzumab-related Thyroid Disease in People With Multiple Sclerosis Is Associated With Age and Brainstem Phenotype at Disease Onset." Multiple Sclerosis Journal - Experimental, Translational and Clinical, vol. 6, no. 2, 2020, p. 2055217320933928.
Yap SM, Dillon M, Crowley RK, et al. Alemtuzumab-related thyroid disease in people with multiple sclerosis is associated with age and brainstem phenotype at disease onset. Mult Scler J Exp Transl Clin. 2020;6(2):2055217320933928.
Yap, S. M., Dillon, M., Crowley, R. K., & McGuigan, C. (2020). Alemtuzumab-related thyroid disease in people with multiple sclerosis is associated with age and brainstem phenotype at disease onset. Multiple Sclerosis Journal - Experimental, Translational and Clinical, 6(2), 2055217320933928. https://doi.org/10.1177/2055217320933928
Yap SM, et al. Alemtuzumab-related Thyroid Disease in People With Multiple Sclerosis Is Associated With Age and Brainstem Phenotype at Disease Onset. Mult Scler J Exp Transl Clin. 2020 Apr-Jun;6(2):2055217320933928. PubMed PMID: 32612846.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Alemtuzumab-related thyroid disease in people with multiple sclerosis is associated with age and brainstem phenotype at disease onset. AU - Yap,Siew Mei, AU - Dillon,Mary, AU - Crowley,Rachel K, AU - McGuigan,Christopher, Y1 - 2020/06/18/ PY - 2020/04/09/received PY - 2020/05/22/accepted PY - 2020/7/3/entrez PY - 2020/7/3/pubmed PY - 2020/7/3/medline KW - Alemtuzumab KW - brainstem KW - multiple sclerosis KW - pregnancy KW - thyroid SP - 2055217320933928 EP - 2055217320933928 JF - Multiple sclerosis journal - experimental, translational and clinical JO - Mult Scler J Exp Transl Clin VL - 6 IS - 2 N2 - Background: Autoimmune thyroid disease (AITD) occurs in 40%-50% of alemtuzumab-treated persons with multiple sclerosis (pwMS), most of whom will develop Graves' Disease (GD). Objective: To explore contributory factors for alemtuzumab-related AITD in pwMS. Methods: A retrospective patient chart review was performed. Results: Sixteen out of 52 (30.8%) pwMS developed AITD. GD occurred in 56.3% (n = 9), the majority (n = 7, 77.8%) symptomatic. All but one (85.7%) pwMS with symptomatic GD developed atypical, large and rapid fluctuations in thyroid hormone levels unexplained by effect of anti-thyroid medication alone. All symptomatic GD cases were age ≤32 years when starting alemtuzumab (ɸ = 0.60, p = 0.03). PwMS who started alemtuzumab at a younger age developed thyroid disease earlier (r = 0.51, p = 0.04). PwMS with clinical and radiological evidence of brainstem involvement at onset of multiple sclerosis were 11 times more likely to develop symptomatic GD compared with those with other phenotypes (p < 0.01). Conclusion: Alemtuzumab-induced reconstitution GD may result from early and increased cross-reactivity between antigens common to the brainstem and thyroid, or presence of shared Human Leukocyte Antigen (HLA) alleles that determine brainstem and thyroid involvement. We suggest cautious use of alemtuzumab in younger (≤32 years) pwMS with early brainstem involvement, especially those actively planning pregnancy, where alternative therapies are readily available. SN - 2055-2173 UR - https://www.unboundmedicine.com/medline/citation/32612846/Alemtuzumab-related_thyroid_disease_in_people_with_multiple_sclerosis_is_associated_with_age_and_brainstem_phenotype_at_disease_onset L2 - http://journals.sagepub.com/doi/full/10.1177/2055217320933928?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -
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