Pixantrone: a B-cell-depleting immunosuppressant for multiple sclerosis patients with active disease.
Mitoxantrone has been approved for patients with worsening relapsing-remitting (RR) or secondary progressive multiple sclerosis (SPMS), but its long-term use is limited by its cardiotoxicity. Pixantrone (PIX) is an analog of mitoxantrone.



The aim of this open-label, multicenter, noncomparative Phase I/II trial was to explore the immunosuppressive effect of PIX, its impact on clinical disease activity and cerebral gadolinium-enhanced (Gd(+)) lesions, and its safety.



Eighteen patients with active RRMS and SPMS (⩾ 1 cerebral Gd(+) lesion) despite approved immunomodulatory therapy received four intravenous PIX injections every 21 days. A neurological examination, hematology, lymphocyte subsets, and biochemistry were performed at Day 1, Weeks 3, 6 and 9, and Months 3, 6, 9 and 12. Echocardiography was performed before each infusion, at Months 3, 6 and 12. Cerebral MRI was performed at baseline, and at Months 6 and 12.



CD19+ cells were reduced by 95% at Month 3 and by 47% at Month 12. Gd+ lesions were reduced by 86% at Month 12 (p = 0.01). The annual relapse rate was reduced by 87% (p < 10(-4)). Two patients experienced a transient reduction in left ventricular fraction.



These preliminary data indicate the efficacy of PIX in active RRMS and SPMS.
Department of Clinical Research, National Center for Multiple Sclerosis, Belgium.
Richard
R
Gonsette
Department of Neurology, Hôpital Central, CHU Nancy, France.
Marc
M
Debouverie
Department of Neurology, Cliniques universitaires Saint-Luc, Belgium.
Christian
C
Sindic
Department of Radiology, CHRU de Rennes, France.
Jean-Christophe
JC
Ferré
Department of Neurology, CHU Rennes, France gilles.edan@chu-rennes.fr.
Gilles
G
Edan
D000328:Adult; D001402:B-Lymphocytes / Q000187:drug effects*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D007546:Isoquinolines / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D020528:Multiple Sclerosis, Chronic Progressive / Q000188:drug therapy*; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy*; D017063:Outcome Assessment, Health Care; D059005:Topoisomerase II Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*
D007166:Immunosuppressive Agents; D007546:Isoquinolines; D059005:Topoisomerase II Inhibitors; C086548:pixantrone
B-cell depletion; Multiple sclerosis; active disease; disease-modifying therapies; immunosuppression; pixantrone