Efficacy and Safety of Alemtuzumab over 6 Years: Final Results of the 4-year CARE-MS Extension Trial

Overview

Journal Ther Adv Neurol Disord

Specialty Neurology

Date 2021 May 26

PMID 34035833

Citations 27

Authors

Alasdair J Coles

Douglas L Arnold

Ann D Bass

Aaron L Boster

D Alastair S Compston

Oscar Fernandez

Eva Kubala Havrdova

Kunio Nakamura

Anthony Traboulsee

Tjalf Ziemssen

Alan Jacobs

David H Margolin

Xiaobi Huang

Nadia Daizadeh

Madalina C Chirieac

Krzysztof W Selmaj

Affiliations

Soon will be listed here.

Abstract

Background: In the 2-year CARE-MS I and II trials, alemtuzumab 12 mg administered on 5 consecutive days at core study baseline and on 3 consecutive days 12 months later significantly improved outcomes subcutaneous interferon beta-1a (SC IFNB-1a) in relapsing-remitting multiple sclerosis patients. Here, we present the final 6-year CARE-MS extension trial results (CAMMS03409), and compare outcomes over 6 years in patients randomized to both treatment groups at core study baseline.

Methods: Over a 4-year extension, alemtuzumab patients (alemtuzumab-only) received as-needed additional alemtuzumab (⩾12 months apart) for disease activity after course 2. SC IFNB-1a patients who entered the extension discontinued SC IFNB-1a and received 2 alemtuzumab 12 mg courses (IFN-alemtuzumab), followed by additional, as-needed, alemtuzumab.

Results: Through year 6, 63% of CARE-MS I and 50% of CARE-MS II alemtuzumab-only patients received neither additional alemtuzumab nor other disease-modifying therapy, with lasting suppression of disease activity, improved disability, and slowing of brain volume loss (BVL). In CARE-MS I patients (treatment-naive; less disability; shorter disease duration), disease activity and BVL were significantly reduced in IFN-alemtuzumab patients, similar to alemtuzumab-only patients at year 6. Among CARE-MS II patients (inadequate response to prior treatment; more disability; longer disease duration), alemtuzumab significantly improved clinical and magnetic resonance imaging outcomes, including BVL, in IFN-alemtuzumab patients; however, disability outcomes were less favorable alemtuzumab-only patients. Safety profiles, including infections and autoimmunities, following alemtuzumab were similar between treatment groups.

Conclusion: This study demonstrates the high efficacy of alemtuzumab over 6 years, with a similar safety profile between treatment groups.

Clinicaltrialsgov Identifiers: NCT00530348; NCT00548405; NCT00930553.

Citing Articles

Long-term efficacy and safety of alemtuzumab in participants with highly active MS: TOPAZ clinical trial and interim analysis of TREAT-MS real-world study.

Ziemssen T, Bass A, Van Wijmeersch B, Eichau S, Richter S, Hoffmann F Ther Adv Neurol Disord. 2025; 18:17562864241306575.

PMID: 39935588 PMC: 11811979. DOI: 10.1177/17562864241306575.

Multiple sclerosis in Colombia: A review of the literature.

Miranda-Acuna J, Casallas-Vanegas A, McCauley J, Castro-Castro P, Amezcua L Mult Scler J Exp Transl Clin. 2024; 10(4):20552173241293921.

PMID: 39600996 PMC: 11590136. DOI: 10.1177/20552173241293921.

SCALA: a randomized phase I trial comparing subcutaneous and intravenous alemtuzumab in patients with progressive multiple sclerosis.

Montalban X, Rodriguez-Acevedo B, Nos C, Resina M, Forner M, Wu Y Ther Adv Neurol Disord. 2024; 17:17562864241291655.

PMID: 39513023 PMC: 11542112. DOI: 10.1177/17562864241291655.

Dermatological Neoplastic Diseases Complicating Treatment with Monoclonal Antibodies for Multiple Sclerosis.

Bile F, Sparaco M, Ruocco E, Miele G, Maida E, Vele R J Clin Med. 2024; 13(17).

PMID: 39274345 PMC: 11396336. DOI: 10.3390/jcm13175133.

Phase 1 Trials of Gatralimab, a Next-Generation Humanized Anti-CD52 Monoclonal Antibody, in Participants with Progressive Multiple Sclerosis.

Albach F, Geier C, Keicher C, Posch M, Schreiber S, Grutz G Neurol Ther. 2024; 13(6):1607-1625.

PMID: 39251561 PMC: 11541066. DOI: 10.1007/s40120-024-00659-w.

References

Gajofatto A, Benedetti M . Treatment strategies for multiple sclerosis: When to start, when to change, when to stop?. World J Clin Cases. 2015; 3(7):545-55. PMC: 4517331. DOI: 10.12998/wjcc.v3.i7.545. View

Vavasour I, Tam R, Li D, Laule C, Taylor C, Kolind S . A 24-month advanced magnetic resonance imaging study of multiple sclerosis patients treated with alemtuzumab. Mult Scler. 2018; 25(6):811-818. DOI: 10.1177/1352458518770085. View

Brown J, Carrasco F, Eshaghi A, Sudre C, Button T, Pardini M . Periventricular magnetisation transfer ratio abnormalities in multiple sclerosis improve after alemtuzumab. Mult Scler. 2019; 26(9):1093-1101. DOI: 10.1177/1352458519852093. View

Clerico M, De Mercanti S, Artusi C, Durelli L, Naismith R . Active CMV infection in two patients with multiple sclerosis treated with alemtuzumab. Mult Scler. 2017; 23(6):874-876. DOI: 10.1177/1352458516688350. View

Canham L, Manara A, Fawcett J, Rolinski M, Mortimer A, Inglis K . Mortality from Listeria monocytogenes meningoencephalitis following escalation to alemtuzumab therapy for relapsing-remitting Multiple Sclerosis. Mult Scler Relat Disord. 2018; 24:38-41. DOI: 10.1016/j.msard.2018.05.014. View

Saarela M, Senthil K, Jones J, Tienari P, Soilu-Hanninen M, Airas L . Hemophagocytic lymphohistiocytosis in 2 patients with multiple sclerosis treated with alemtuzumab. Neurology. 2018; 90(18):849-851. DOI: 10.1212/WNL.0000000000005420. View

Brown J, Coles A, Horakova D, Havrdova E, Izquierdo G, Prat A . Association of Initial Disease-Modifying Therapy With Later Conversion to Secondary Progressive Multiple Sclerosis. JAMA. 2019; 321(2):175-187. PMC: 6439772. DOI: 10.1001/jama.2018.20588. View

Ferraro D, Camera V, Vitetta F, Zennaro M, Ciolli L, Nichelli P . Acute coronary syndrome associated with alemtuzumab infusion in multiple sclerosis. Neurology. 2018; 90(18):852-854. DOI: 10.1212/WNL.0000000000005417. View

Phelps R, Winston J, Wynn D, Habek M, Hartung H, Kubala Havrdova E . Incidence, management, and outcomes of autoimmune nephropathies following alemtuzumab treatment in patients with multiple sclerosis. Mult Scler. 2019; 25(9):1273-1288. PMC: 6681440. DOI: 10.1177/1352458519841829. View

10.

Coles A, Cohen J, Fox E, Giovannoni G, Hartung H, Havrdova E . Alemtuzumab CARE-MS II 5-year follow-up: Efficacy and safety findings. Neurology. 2017; 89(11):1117-1126. PMC: 5595276. DOI: 10.1212/WNL.0000000000004354. View

11.

Jones J, Thompson S, Loh P, Davies J, Tuohy O, Curry A . Human autoimmunity after lymphocyte depletion is caused by homeostatic T-cell proliferation. Proc Natl Acad Sci U S A. 2013; 110(50):20200-5. PMC: 3864306. DOI: 10.1073/pnas.1313654110. View

12.

Gross C, Ahmetspahic D, Ruck T, Schulte-Mecklenbeck A, Schwarte K, Jorgens S . Alemtuzumab treatment alters circulating innate immune cells in multiple sclerosis. Neurol Neuroimmunol Neuroinflamm. 2016; 3(6):e289. PMC: 5063395. DOI: 10.1212/NXI.0000000000000289. View

13.

Havrdova E, Arnold D, Cohen J, Hartung H, Fox E, Giovannoni G . Alemtuzumab CARE-MS I 5-year follow-up: Durable efficacy in the absence of continuous MS therapy. Neurology. 2017; 89(11):1107-1116. PMC: 5595278. DOI: 10.1212/WNL.0000000000004313. View

14.

Liu G, Wang J, Liu K, Snavely D . Confidence intervals for an exposure adjusted incidence rate difference with applications to clinical trials. Stat Med. 2005; 25(8):1275-86. DOI: 10.1002/sim.2335. View

15.

Turner M, LaMorte M, Chretien N, Havari E, Roberts B, Kaplan J . Immune status following alemtuzumab treatment in human CD52 transgenic mice. J Neuroimmunol. 2013; 261(1-2):29-36. DOI: 10.1016/j.jneuroim.2013.04.018. View

16.

Rudick R, Fisher E, Lee J, Simon J, Jacobs L . Use of the brain parenchymal fraction to measure whole brain atrophy in relapsing-remitting MS. Multiple Sclerosis Collaborative Research Group. Neurology. 1999; 53(8):1698-704. DOI: 10.1212/wnl.53.8.1698. View

17.

Kim Y, Kim G, Shin H, Hyun J, Kim S, Lee E . Restoration of regulatory B cell deficiency following alemtuzumab therapy in patients with relapsing multiple sclerosis. J Neuroinflammation. 2018; 15(1):300. PMC: 6206644. DOI: 10.1186/s12974-018-1334-y. View

18.

Cohen J, Coles A, Arnold D, Confavreux C, Fox E, Hartung H . 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(9856):1819-28. DOI: 10.1016/S0140-6736(12)61769-3. View

19.

Cox A, Thompson S, Jones J, Robertson V, Hale G, Waldmann H . Lymphocyte homeostasis following therapeutic lymphocyte depletion in multiple sclerosis. Eur J Immunol. 2005; 35(11):3332-42. DOI: 10.1002/eji.200535075. View

20.

Holmoy T, Fevang B, Olsen D, Spigset O, Bo L . Adverse events with fatal outcome associated with alemtuzumab treatment in multiple sclerosis. BMC Res Notes. 2019; 12(1):497. PMC: 6689881. DOI: 10.1186/s13104-019-4507-6. View