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Alemtuzumab as rescue therapy in a cohort of 50 relapsing-remitting MS patients with breakthrough disease on fingolimod: a multi-center observational study.
J Neurol. 2018 Jul; 265(7):1521-1527.JN

Abstract

BACKGROUND

Relapsing-remitting multiple sclerosis (RRMS) requires efficient immunomodulatory treatment to reach "no evidence of disease activity" status at best. Alemtuzumab and fingolimod have proved to be efficient options in RRMS with active disease course. Yet, side effects and break-through disease may limit long-time treatment and necessitate switch of medication. Data on efficacy and safety of alemtuzumab following fingolimod treatment are limited, but useful for clinical practice.

METHODS

Clinical and MRI data of 50 RRMS patients with a history of therapy switch from fingolimod to alemtuzumab were retrospectively analyzed. Data were acquired from nine large German MS Centers from 2013 to 2016 and analyzed using descriptive statistics.

RESULTS

On average, patients with disease duration of 12.9 years and median EDSS of 3.0 at baseline switched to alemtuzumab after 68 weeks of fingolimod treatment. Thereafter, patients on alemtuzumab were followed for a mean of 64 weeks. The annualized relapse rate decreased from 2.2 in the year prior to 0.34 in the following year after switching to alemtuzumab and EDSS stabilized. In a subgroup of patients (n = 23), MRI data point to a reduction in enhancing (4.47 vs. 0.26) and new/enlarging T2 lesions (5.8 vs. 0.27) after treatment adjustment. Side effects were generally as expected from published data for alemtuzumab (autoimmunity 2/50, severe infections 1/50). One patient suffered combined lethal necrotizing leukoencephalopathy and hemolytic anemia.

DISCUSSION

Therapy switch was highly effective in reducing clinical and MRI surrogates of disease activity and was mainly well tolerated within one year of follow-up. Hence, alemtuzumab constitutes a promising therapy in RRMS with refractory disease activity despite fingolimod treatment. Further studies are warranted to confirm these beneficial findings and to reveal safety concerns in the longer-term follow-up.

Authors+Show Affiliations

Department of Neurology, University Hospital Erlangen, Friedrich-Alexander-University, Erlangen-Nürnberg, Germany. Konstantin.Huhn@uk-erlangen.de.Department of Neurology, Klinikum Augsburg, Augsburg, Germany.Department of Neurology, Julius-Maximilians-University Würzburg, Würzburg, Germany.Department of Neurology, University Hospital Essen, Essen, Germany.Department of Neurology, Klinikum Köln-Merheim, Cologne, Germany.Department of Neurology, St. Josef-Hospital/Ruhr-University Bochum, Bochum, Germany.MS Center Bamberg, Bamberg, Germany.Department of Neurology, Julius-Maximilians-University Würzburg, Würzburg, Germany. Department of Neurology, University Hospital Essen, Essen, Germany.Department of Neurology, St. Josef-Hospital/Ruhr-University Bochum, Bochum, Germany. Marianne-Strauβ-Klinik, Behandlungszentrum Kempfenhausen für Multiple Sklerose Kranke gGmbH, Milchberg 21, 82335, Berg, Germany.Department of Neurology, University Hospital Erlangen, Friedrich-Alexander-University, Erlangen-Nürnberg, Germany.Department of Neurology, Klinikum Köln-Merheim, Cologne, Germany.Department of Neurology, Caritas Krankenhaus Bad Mergentheim, Bad Mergentheim, Germany. Department of Neurology, Julius-Spital Würzburg, Würzburg, Germany.Department of Translational Neurology, University Hospital Münster, Münster, Germany.MS Center Bamberg, Bamberg, Germany. Medical Park Klinik Loipl, Bischofswiesen, Germany.Department of Translational Neurology, University Hospital Münster, Münster, Germany.Department of Neurology, St. Josef-Hospital/Ruhr-University Bochum, Bochum, Germany.Department of Neurology, University Hospital Erlangen, Friedrich-Alexander-University, Erlangen-Nürnberg, Germany.

Pub Type(s)

Journal Article
Multicenter Study
Observational Study

Language

eng

PubMed ID

29696498

Citation

Huhn, Konstantin, et al. "Alemtuzumab as Rescue Therapy in a Cohort of 50 Relapsing-remitting MS Patients With Breakthrough Disease On Fingolimod: a Multi-center Observational Study." Journal of Neurology, vol. 265, no. 7, 2018, pp. 1521-1527.
Huhn K, Bayas A, Doerck S, et al. Alemtuzumab as rescue therapy in a cohort of 50 relapsing-remitting MS patients with breakthrough disease on fingolimod: a multi-center observational study. J Neurol. 2018;265(7):1521-1527.
Huhn, K., Bayas, A., Doerck, S., Frank, B., Gerbershagen, K., Hellwig, K., Kallmann, B., Kleinschnitz, C., Kleiter, I., Lee, D. H., Limmroth, V., Mäurer, M., Meuth, S., Rieckmann, P., Ruck, T., Gold, R., & Linker, R. A. (2018). Alemtuzumab as rescue therapy in a cohort of 50 relapsing-remitting MS patients with breakthrough disease on fingolimod: a multi-center observational study. Journal of Neurology, 265(7), 1521-1527. https://doi.org/10.1007/s00415-018-8871-2
Huhn K, et al. Alemtuzumab as Rescue Therapy in a Cohort of 50 Relapsing-remitting MS Patients With Breakthrough Disease On Fingolimod: a Multi-center Observational Study. J Neurol. 2018;265(7):1521-1527. PubMed PMID: 29696498.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Alemtuzumab as rescue therapy in a cohort of 50 relapsing-remitting MS patients with breakthrough disease on fingolimod: a multi-center observational study. AU - Huhn,Konstantin, AU - Bayas,Antonios, AU - Doerck,Sebastian, AU - Frank,Benedikt, AU - Gerbershagen,Kathrin, AU - Hellwig,Kerstin, AU - Kallmann,Boris, AU - Kleinschnitz,Christoph, AU - Kleiter,Ingo, AU - Lee,De-Hyung, AU - Limmroth,Volker, AU - Mäurer,Mathias, AU - Meuth,Sven, AU - Rieckmann,Peter, AU - Ruck,Tobias, AU - Gold,Ralf, AU - Linker,Ralf A, Y1 - 2018/04/25/ PY - 2018/02/10/received PY - 2018/04/12/accepted PY - 2018/04/06/revised PY - 2018/4/27/pubmed PY - 2018/10/5/medline PY - 2018/4/27/entrez KW - Alemtuzumab KW - Disease-modifying treatment KW - Fingolimod KW - Multiple sclerosis SP - 1521 EP - 1527 JF - Journal of neurology JO - J. Neurol. VL - 265 IS - 7 N2 - BACKGROUND: Relapsing-remitting multiple sclerosis (RRMS) requires efficient immunomodulatory treatment to reach "no evidence of disease activity" status at best. Alemtuzumab and fingolimod have proved to be efficient options in RRMS with active disease course. Yet, side effects and break-through disease may limit long-time treatment and necessitate switch of medication. Data on efficacy and safety of alemtuzumab following fingolimod treatment are limited, but useful for clinical practice. METHODS: Clinical and MRI data of 50 RRMS patients with a history of therapy switch from fingolimod to alemtuzumab were retrospectively analyzed. Data were acquired from nine large German MS Centers from 2013 to 2016 and analyzed using descriptive statistics. RESULTS: On average, patients with disease duration of 12.9 years and median EDSS of 3.0 at baseline switched to alemtuzumab after 68 weeks of fingolimod treatment. Thereafter, patients on alemtuzumab were followed for a mean of 64 weeks. The annualized relapse rate decreased from 2.2 in the year prior to 0.34 in the following year after switching to alemtuzumab and EDSS stabilized. In a subgroup of patients (n = 23), MRI data point to a reduction in enhancing (4.47 vs. 0.26) and new/enlarging T2 lesions (5.8 vs. 0.27) after treatment adjustment. Side effects were generally as expected from published data for alemtuzumab (autoimmunity 2/50, severe infections 1/50). One patient suffered combined lethal necrotizing leukoencephalopathy and hemolytic anemia. DISCUSSION: Therapy switch was highly effective in reducing clinical and MRI surrogates of disease activity and was mainly well tolerated within one year of follow-up. Hence, alemtuzumab constitutes a promising therapy in RRMS with refractory disease activity despite fingolimod treatment. Further studies are warranted to confirm these beneficial findings and to reveal safety concerns in the longer-term follow-up. SN - 1432-1459 UR - https://www.unboundmedicine.com/medline/citation/29696498/Alemtuzumab_as_rescue_therapy_in_a_cohort_of_50_relapsing_remitting_MS_patients_with_breakthrough_disease_on_fingolimod:_a_multi_center_observational_study_ L2 - https://dx.doi.org/10.1007/s00415-018-8871-2 DB - PRIME DP - Unbound Medicine ER -