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Alemtuzumab-induced thyroid events in multiple sclerosis: a systematic review and meta-analysis

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Abstract

Purpose

Autoimmune thyroid events (ATEs) are common side effects after alemtuzumab (ALZ) therapy in patients with multiple sclerosis (MS). Our purpose was to reach more robust evidence on prevalence and outcome of the spectrum of alemtuzumab-induced autoimmune thyroid events in patients with multiple sclerosis.

Methods

PubMed and Scopus were systematically searched through July 2019. Studies dealing with patients without personal history of thyroid dysfunctions and affected by MS treated with ALZ and reporting ATEs were selected. Data on prevalence and outcome of ATEs were extracted. A proportion of meta-analysis with random-effects model was performed.

Results

Considering the overall pooled number of 1362 MS patients treated with ALZ (seven included studies), a 33% prevalence of newly diagnosed ATEs was recorded. Among all ATEs, Graves’ disease (GD) was the most represented [63% of cases, 95% confidence interval (CI) 52–74%], followed by Hashimoto thyroiditis (15%, 95% CI 10–22%). Interestingly, GD showed a fluctuating course in 15% of cases (95% CI 8–25%). Of all GD, 12% (95% CI 2–42%) likely had spontaneous remission, 56% (95% CI 34–76%) required only antithyroid drugs, 22% (95% CI 13–32%) needed additional RAI, and 11% (95% CI 0.9–29%) underwent definitive surgery.

Conclusion

Among different categories of ATEs, Graves’ hyperthyroidism was the most common thyroid dysfunction, occurring in more than half of cases. Antithyroid drugs should represent the first-line treatment for ALZ-induced GD patients. However, alemtuzumab-induced GD could not be considered as having a more favourable outcome than conventional GD, given the substantial chance to encounter a fluctuating and unpredictable course.

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Abbreviations

ALZ:

Alemtuzumab

AAEs:

Adverse autoimmune events

MS:

Multiple sclerosis

ATE(s):

Autoimmune thyroid event(s)

GD:

Graves’ disease

GREAT:

Graves’ recurrent events after therapy

CSS:

Clinical severity score

CLL:

Chronic lymphocytic leukemia

RCTs:

Randomized controlled trials

TPOAb:

Thyroid peroxidase antibody

TRAb:

Thyrotropin receptor antibodies

HT:

Hashimoto thyroiditis

ST:

Silent thyroiditis

GO:

Graves’ orbitopathy

ATD:

Antithyroid drugs

RAI:

Radioiodine

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Acknowledgements

L.S. would like to thank the University of Federico II (Naples, Italy) for the internal grant (in “STAR program”) which allow him to work as research fellow in Department of Nuclear Medicine and Thyroid Centre, Ente Ospedaliero Cantonale (Lugano and Bellinzona, Switzerland).

Funding

No financial support to declare.

Author information

Authors and Affiliations

  1. Unit of Endocrinology and Metabolic Diseases, University of Campania “L.Vanvitelli”, 80138, Naples, Italy

    L. Scappaticcio & G. Bellastella

  2. Department of Nuclear Medicine and Thyroid Centre, Ente Ospedaliero Cantonale, Bellinzona, Switzerland

    L. Giovanella & P. Trimboli

  3. Section of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, University of Bari Aldo Moro, Bari, Italy

    M. Castellana

  4. Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy

    C. Virili & M. Centanni

  5. Department of Human Pathology of Adulthood and Childhood “G. Barresi”, University of Messina, Messina, Italy

    S. Cannavò

  6. Unit of Endocrinology, “G. Martino” University Hospital, University of Messina, Messina, Italy

    S. Cannavò & R. M. Ruggeri

  7. Department of Biomedical and Dental Sciences and Morpho-Functional Imaging, Nuclear Medicine Unit, University of Messina, Messina, Italy

    A. Campennì

  8. Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy

    R. M. Ruggeri

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  1. L. Scappaticcio
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Contributions

LS and PT designed and conceptualized the study, analyzed the data, and drafted the manuscript for intellectual content; all the co-authors interpreted the data and revised the manuscript for intellectual content.

Corresponding author

Correspondence to L. Scappaticcio.

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Below is the link to the electronic supplementary material. Supplemental Fig. 1. Risk of bias summary: review authors’ judgements about each risk of bias item for included non-RCTs. Supplemental Fig. 2. Risk of bias summary: review authors’ judgements about each risk of bias item for included RCTs. Supplemental Table 1. Overall studies characteristics.

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Scappaticcio, L., Castellana, M., Virili, C. et al. Alemtuzumab-induced thyroid events in multiple sclerosis: a systematic review and meta-analysis. J Endocrinol Invest 43, 219–229 (2020). https://doi.org/10.1007/s40618-019-01105-7

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  • DOI: https://doi.org/10.1007/s40618-019-01105-7

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