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Review
. 2018 Nov;265(11):2494-2505.
doi: 10.1007/s00415-018-8822-y. Epub 2018 Mar 10.

Monitoring and management of autoimmunity in multiple sclerosis patients treated with alemtuzumab: practical recommendations

Virginia Devonshire  1   2 , Richard Phillips  3 , Hilary Wass  4 , Gerald Da Roza  3 , Peter Senior  5
Affiliations
Review

Monitoring and management of autoimmunity in multiple sclerosis patients treated with alemtuzumab: practical recommendations

Virginia Devonshire et al. J Neurol. 2018 Nov.

Abstract

Alemtuzumab is a humanized anti-CD52 monoclonal antibody approved in more than 65 countries for the treatment of relapsing-remitting multiple sclerosis (RRMS). Compared with subcutaneous interferon-beta-1a, alemtuzumab significantly reduced clinical disease activity and the rate of brain volume loss, and improved disability outcomes in patients with active RRMS who were either treatment naive (CARE-MS I study) or who had an inadequate response (≥ 1 relapse after ≥ 6 months of treatment) to prior therapy (CARE-MS II study). Adverse events (AEs) associated with alemtuzumab include infusion-associated reactions, infections, and autoimmunity. The most commonly reported autoimmune AEs observed with alemtuzumab involve the thyroid gland, followed by immune thrombocytopenia and nephropathies. A monitoring program was designed and implemented to facilitate the early detection of autoimmune events to ensure timely and adequate management. The aim of this article is to provide physicians (including neurologists, general practitioners, endocrinologists, hematologists, and nephrologists who may be less familiar with the symptoms and treatment of autoimmune events), with practical real-world recommendations for the monitoring and management of autoimmunity associated with alemtuzumab treatment.

Keywords: Alemtuzumab; Autoimmunity; Immune thrombocytopenia; Multiple sclerosis; Nephropathy; Thyroid disorder.

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Conflict of interest statement

Human and animal rights

All human studies reported herein were approved by the appropriate ethics committee and were performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its amendments.

Informed consent

All persons provided their informed consent prior to their inclusion in the studies.

Conflicts of interest

Virginia Devonshire has acted as a Principal Clinical Trial Investigator (Biogen, EMD Serono, MedDay, Novartis), participated in advisory boards (Biogen, EMD Serono, Novartis, Roche, Sanofi, and Teva), and received research financial support (Biogen, EMD Serono, Novartis). Gerald da Roza, Richard Phillips and Hilary Wass report no conflicts of interest. Peter Senior has received consulting and/or speaking fees and grant/research support (Sanofi).

Figures

Fig. 1
Fig. 1
Autoimmune thyroid disease. a Hyperthyroidism: Graves’ disease/thyrotoxicosis; b painless thyroiditis; and c hypothyroidism. T3 triiodothyronine, T4 thyroxine, TSH thyroid-stimulating hormone
Fig. 2
Fig. 2
Practical recommendations for the monitoring of thyroid function in patients treated with alemtuzumab. N normal, Q3 monthly every 3 months, T3 triiodothyronine, T4 thyroxine, TSH thyroid-stimulating hormone (normal: 0.4–4 mU/L), TSH-R Ab TSH-receptor antibody. Note: If patient becomes pregnant, establish a new TSH baseline and/or consider monitoring more frequently
Fig. 3
Fig. 3
Practical recommendations for the monitoring of platelet counts in patients treated with alemtuzumab. Normal platelet count = 150–400 platelets/L. CBC complete blood count. Normal reticulated platelet count percentage: 3–20% and absolute reticulated platelet count: 17 ± 6.6 (103/µL). Note: Platelet count can be highly variable
Fig. 4
Fig. 4
Practical recommendations for the monitoring of kidney function in patients treated with alemtuzumab. ACE angiotensin-converting enzyme, ACR albumin/creatinine ratio, ARB angiotensin-receptor blocker, Cr creatinine, ER emergency room, GBM glomerular basement membrane, HPF high-power field, NSAIDs nonsteroidal anti-inflammatory drugs, RBC red blood cell
See this image and copyright information in PMC

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