Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2020 Jan;26(1):48-56.
doi: 10.1177/1352458518816612. Epub 2019 Feb 20.

Immune thrombocytopenia in alemtuzumab-treated MS patients: Incidence, detection, and management

Adam Cuker  1 , Ann D Bass  2 , Congor Nadj  3 , Mark A Agius  4 , Brian Steingo  5 , Krzysztof W Selmaj  6 , Timothy Thoits  7 , Alexandre Guerreiro  8 , Bart Van Wijmeersch  9 , Tjalf Ziemssen  10 , Sven G Meuth  11 , Christopher C LaGanke  12 , Karthinathan Thangavelu  13 , Claudio E Rodriguez  13   14 , Darren P Baker  13 , David H Margolin  13   15 , Ann Jannsens  16
Affiliations
Randomized Controlled Trial

Immune thrombocytopenia in alemtuzumab-treated MS patients: Incidence, detection, and management

Adam Cuker et al. Mult Scler. 2020 Jan.

Abstract

Background: Alemtuzumab is a highly effective therapy for relapsing-remitting multiple sclerosis (RRMS), and immune thrombocytopenia (ITP) has been identified as a risk.

Objective: To examine ITP incidence, treatment, and outcomes during the clinical development of alemtuzumab for RRMS and discuss postmarketing experience outside clinical trials.

Methods: CAMMS223 and Comparison of Alemtuzumab and Rebif® Efficacy in Multiple Sclerosis (CARE-MS) I and II investigated two annual courses of alemtuzumab 12 mg (or 24 mg in CAMMS223/CARE-MS II) versus subcutaneous interferon beta-1a three times per week. Patients completing core studies could enroll in an extension. Monthly monitoring for ITP continued until 48 months after the last alemtuzumab infusion.

Results: Of 1485 alemtuzumab-treated MS patients in the clinical development program, 33 (2.2%) developed ITP (alemtuzumab 12 mg, 24 [2.0%]; alemtuzumab 24 mg, 9 [3.3%]) over median 6.1 years of follow-up after the first infusion; most had a sustained response to first-line ITP therapy with corticosteroids, platelets, and/or intravenous immunoglobulin. All cases occurred within 48 months of the last alemtuzumab infusion. Postmarketing surveillance data suggest that the ITP incidence is not higher in clinical practice than in clinical trials.

Conclusion: Alemtuzumab-associated ITP occurs in approximately 2% of patients and is responsive to therapy. Careful monitoring is key for detection and favorable outcomes.

Keywords: Alemtuzumab; disease-modifying therapy; immune thrombocytopenia; relapsing-remitting multiple sclerosis; safety.

PubMed Disclaimer

Conflict of interest statement

Declaration of Conflicting Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: A.C. has received consulting fees from Kedrion, Sanofi, and Synergy and institutional grant support from Alexion, Bayer, Bioverativ, Novo Nordisk, Pfizer, Shire, Spark Therapeutics, and Syntimmune. A.D.B. has received consulting fees, fees for non-CME services, and research support from Biogen, Mallinckrodt, Novartis, Roche-Genentech, Sanofi, and Teva Neuroscience. C.N. has received consulting fees and speaking fees from Bayer, Bayhill, Biogen, Merck, Novartis, Roche, Sanofi, and Teva. M.A.A. has received consulting and lecture fees and institutional grant support from Biogen, Celgene, MedImmune, Novartis, Roche/Genentech, Sanofi, and Serono. B.S. has received consulting, speaking fees, and/or grant/research support from Acorda, Biogen, EMD Serono, Mallinckrodt, Novartis, Sanofi, and Teva. K.W.S. has received fees for consulting and/or speaking from Biogen, Merck, Novartis, Roche, Sanofi, and Synthon. T.T. has nothing to disclose. A.G. has nothing to disclose. B.V.W. has received research and travel grants, honoraria for MS expert advice, and speaking fees from Bayer-Schering, Biogen, Merck Serono, Novartis, Roche, Sanofi, and Teva. T.Z. has received consulting or speaking fees from Almirall, Bayer, Biogen, Merck, Novartis, Roche, Sanofi, and Teva and grant/research support from Biogen, Novartis, Sanofi, and Teva. S.G.M. has received honoraria for lecturing, travel expenses for attending meetings, and financial research support from Almirall, Bayer HealthCare, Biogen, Diamed, Merck Serono, Novartis, Novo Nordisk, ONO Pharma, Roche, Sanofi, and Teva. C.C.L. has received compensation for consulting from Acorda Therapeutics, Bayer, Biogen, Cephalon, EMD Serono, Novartis, Pfizer, Questcor, Sanofi, Strativa, Teva, and UCB. K.T. and D.P.B. are employees of Sanofi. C.E.R. was an employee of Sanofi at the time of the analysis and is currently employed by Sunovion Pharmaceuticals. D.H.M. was an employee of Sanofi at the time of the analysis and is currently employed by Cerevance, Inc. A.J. has received educational grant support from Janssen and consultancy fees from Abbvie, Janssen, Roche, and Sanofi.

Figures

Figure 1.
Figure 1.
Platelet count monitoring to facilitate detection of ITP. *Weekly CBC protocol: weekly platelet counts for ⩾8 weeks. Monthly monitoring could be resumed when platelet counts were either within the normal range for eight readings, or were stabilized (i.e. eight consecutive readings ⩾ 100 × 109/L and average of last four counts ⩾ average of four prior counts). CBC: complete blood count; ITP: immune thrombocytopenia; LLN: lower limit of normal.
Figure 2.
Figure 2.
Timing of ITP onset relative to alemtuzumab administration: (a) time from the most recent course to ITP onset and (b) time from the first course to ITP onset.
See this image and copyright information in PMC

References

    1. Brinar V, Giovannoni G, Havrdova E, et al. A phase 3b/4 long-term study of alemtuzumab in patients with relapsing-remitting multiple sclerosis: TOPAZ study design. Neurology 2015; 84: P7.219.
    1. Cohen JA, Coles AJ, Arnold DL, et al. Alemtuzumab versus interferon beta 1a as first-line treatment for patients with relapsing-remitting multiple sclerosis: A randomised controlled phase 3 trial. Lancet 2012; 380: 1819–1828. - PubMed
    1. Coles AJ, Cohen JA, Fox EJ, et al. Alemtuzumab CARE-MS II 5-year follow-up: Efficacy and safety findings. Neurology 2017; 89: 1117–1126. - PMC - PubMed
    1. Coles AJ, Compston DA, Selmaj KW, et al. Alemtuzumab vs. interferon beta-1a in early multiple sclerosis. N Engl J Med 2008; 359: 1786–1801. - PubMed
    1. Coles AJ, Twyman CL, Arnold DL, et al. Alemtuzumab for patients with relapsing multiple sclerosis after disease-modifying therapy: A randomised controlled phase 3 trial. Lancet 2012; 380: 1829–1839. - PubMed

Publication types

MeSH terms

LinkOut - more resources