Pixantrone: a B-cell-depleting immunosuppressant for multiple sclerosis patients with active disease.
BACKGROUND
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.


OBJECTIVES
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.


METHODS
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.


RESULTS
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.


CONCLUSION
These preliminary data indicate the efficacy of PIX in active RRMS and SPMS.
['Gonsette|Richard|R|', 'Debouverie|Marc|M|', 'Sindic|Christian|C|', 'Ferré|Jean-Christophe|JC|', 'Edan|Gilles|G|']
D000328:Adult D001402:B-Lymphocytes D005260:Female D006801:Humans D007166:Immunosuppressive Agents D007546:Isoquinolines D008297:Male D008875:Middle Aged D020528:Multiple Sclerosis, Chronic Progressive D020529:Multiple Sclerosis, Relapsing-Remitting D017063:Outcome Assessment, Health Care D059005:Topoisomerase II Inhibitors
pixantrone immunosuppression Multiple sclerosis active disease B-cell depletion disease-modifying therapies