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Safety and Tolerability of Subcutaneous Cladribine Therapy in Progressive Multiple Sclerosis

Published online by Cambridge University Press:  18 September 2015

R. Selby ,
J. Brandwein  and
P. O'Connor
R. Selby
Affiliation:
Division of Hematology, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada.
J. Brandwein
Affiliation:
Division of Hematology, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada.
P. O'Connor*
Affiliation:
The Toronto Hospital and Division of Neurology, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada.
*
Division of Neurology, St. Michael's Hospital, 30 Bond Street, Suite 3133-D, Toronto, Ontario, Canada M5B 1W8
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Abstract:

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Objective:

To evaluate the safety and tolerability of subcutaneous (s.c.) cladribine therapy in patients with chronic progressive multiple sclerosis (CPMS), and to evaluate the effects on lymphocyte subsets.

Background:

Cladribine, a synthetic antineoplastic agent with immunosuppressive effects, may favourably affect the course of CPMS. However results of a previous reported clinical trial showed significant myelosuppression in some patients.

Design/Methods:

19 patients with severe (mean extended disability status score [EDSS] = 6.7) CPMS were treated on a compassionate basis with cladribine 0.07 mg/kg/ day s.c. for 5 days per cycle, repeated every 4 weeks for a total of 6 cycles. Patients underwent clinical evaluation, EDSS, and hematologic analysis before, during, and following therapy.

Results:

The treatment was very well tolerated with no clinically significant side effects observed. Between baseline and the end of cycle 6, mean decreases were noted in absolute lymphocyte count from 1697 to 463 (p = 0.000012), CD4 count from 865 to 187 (p = 0.0000008), CD8 from 418 to 165 (p = 0.005) and CD19 from 197 to 26 (p = 0.000002). Platelet, granulocyte and RBC counts were unaffected. Approximately one year after completion of therapy, some recovery of CD4 and CD8 counts had occurred although both counts remained suppressed compared to baseline (302 and 227 respectively); the CD19 count had recovered essentially to normal by one year. EDSS scores post-therapy revealed some deterioration in 8 patients and stable scores in the remaining 11. Global patient evaluations of the treatment were mixed.

Conclusions:

Cladribine therapy, at lower doses than previously reported, was remarkably well tolerated in CPMS, with no significant myelosuppression. Profound effects occurred in total lymphocyte count and CD4, CD8 and CD19 subsets.

Résumé:

RÉSUMÉ: But:

D'évaluer la sécurité et la tolérabilité de la cladribine sous-cutanée (s.c.) chez les patients atteints de sclérose en plaques progressive chronique (SEPPC) et d'évaluer ses effets sur différentes populations lymphocy-taires.

Introduction:

La cladribine, un agent antinéoplasique synthétique qui a des propriétés immunosuppressives peut influencer favorablement l'évolution de la SEPPC. Cependant, les résultats des essais thérapeutiques rapportés à date ont montré une myélosuppression significative chez certains patients.

Méthodes:

19 patients atteints de SEPPC sévère (score moyen à l'échelle d'invalidité EDSS = 6.7) ont été traités sur une base humanitaire avec la cladribine à la dose de 0.07 mg/kg/jour par voie s.c. pendant 5 jours par cycle, à toutes les 4 semaines, pour un total de 6 cycles. Les patients ont subi une évaluation clinique, EDSS, et des analyses hématologiques avant, pendant et après le traitement.

Résultats:

Le traitement a été très bien toléré, sans effet secondaire cliniquement significatif. Entre la phase pré-traitement et la fin du sixième cycle, des diminutions moyennes du décompte absolu des lymphocytes de 1697 à 463 (p = 0.000012), du décompte CD4 de 865 à 187 (p = 0.0000008), du décompte CD8 de 418 à 165 (p = 0.005) et CD19 de 197 à 26 (p = 0.000002) ont été observées. Le décompte des plaquettes, des granulocytes et des globules rouges n'était pas atteint. Environ un an après la fin du traitement, une récupération du décompte CD4 et CD8 était évidente, bien que ces deux décomptes demeuraient supprimés en comparaison avec ceux de la phase pré-traitement (302 et 227 respectivement); le décompte CD19 était revenu à la normale à un an. Les scores EDSS post-traitement ont montré une détérioration chez 8 patients et des scores stables chez les 11 autres. L'évaluation globale du traitement par les patients était mixte.

Conclusions:

La cladribine s.c, à dose plus faible que dans les études rapportées antérieurement, a été remarquablement bien tolérée chez les patients atteints de SEPPC, sans myélosuppression significative. Des effets marqués ont été notés sur le décompte lymphocytaire total et sur les sous-populations CD4, CD8 et CD19.

Type
Original Articles
Information
Canadian Journal of Neurological Sciences , Volume 25 , Issue 4 , November 1998 , pp. 295 - 299
Copyright
Copyright © Canadian Neurological Sciences Federation 1998

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