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Alemtuzumab as rescue therapy in a cohort of 16 aggressive multiple sclerosis patients previously treated by Mitoxantrone: an observational study

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Abstract

Our study aimed to describe safety and neurological impact of alemtuzumab as last-line rescue therapy in aggressive multiple sclerosis (MS) patients, previously treated by Mitoxantrone (MITOX). Between June 2004 and October 2013, 13 patients received alemtuzumab at 20 mg/day and 3 at 12 mg/day for 5 days. EDSS, relapses, secondary progression were prospectively assessed 12 and 6 months before treatment, at baseline and every 3 months. Mean follow-up was 6.2 years [1–10]. Mean age at alemtuzumab start was 40 years [26–49] for 8 Secondary Progressive (SP) and 30 years [26–35] for 8 Relapsing-Remitting (RR) patients. MS duration was 13.7 (±3) and 8.3 (±4) years, respectively. During the 12 months before alemtuzumab, annual relapse rate was 0.75 and 3.14, respectively and the 16 patients accumulated 2–30 new gadolinium enhancing lesions. 4 patients (suboptimal responders) received alemtuzumab during MITOX and 12 patients 1–7.8 years after MITOX. Out of 8 SPMS, 2 were disease free up to last visit (4.7 and 8 years), 5 improved or stabilized but only transiently and 1 worsened. Out of 8 RRMS, 1 remained stable up to last visit (8.7 years) despite 1 relapse and active MRI at 18 months and 7 improved (1–4 point EDSS): 4 remained disease free up to last visit (12, 24, 38 months and 7 years), 2 were successfully retreated at 25 and 33 months and 1 worsened progressively 24 months after alemtuzumab. 2 patients developed Grave’s disease and 1 hypothyroidism. Alemtuzumab controls aggressive RRMS despite previous use of MITOX.

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Conflicts of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

Ethical standard

Alemtuzumab was approved by the US Food and Drug administration (FDA: as CAMPATH) and the European Medicine Evaluation Agency (EMEA: as MABCAMPATH) in hematologic malignancies in May and July 2001, respectively. The present study was approved by the local committee COMEDIMS (Comité du Médicament et Dispositifs Médicaux-Sanitaires) in the University Hospital Pontchaillou, Rennes, France, promoting this study. The EDMUS database received approval from the French “Comission Nationale Informatique et Liberté”.

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Authors and Affiliations

  1. Departement of Neurosciences, University Hospital Pontchaillou, 2 Rue Henri Guilloux, 35000, Rennes Cedex, France

    Emmanuelle Le Page, Véronique Deburghgraeve & Gilles Edan

  2. Departement of Pharmacology, University Hospital Pontchaillou, 2 Rue Henri Guilloux, 35000, Rennes Cedex, France

    Marie-Antoinette Lester & Isabelle Cardiet

  3. Biostatistics Department, EHESP, Avenue du Professeur Léon-Bernard, 35043, Rennes, France

    Emmanuelle Leray

Authors
  1. Emmanuelle Le Page
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  2. Véronique Deburghgraeve
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  3. Marie-Antoinette Lester
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  4. Isabelle Cardiet
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  5. Emmanuelle Leray
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  6. Gilles Edan
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Correspondence to Emmanuelle Le Page.

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Le Page, E., Deburghgraeve, V., Lester, MA. et al. Alemtuzumab as rescue therapy in a cohort of 16 aggressive multiple sclerosis patients previously treated by Mitoxantrone: an observational study. J Neurol 262, 1024–1034 (2015). https://doi.org/10.1007/s00415-015-7653-3

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  • DOI: https://doi.org/10.1007/s00415-015-7653-3

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