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

Abstract : 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 \textless 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
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Submitted on : Wednesday, June 1, 2016 - 1:23:41 PM
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Richard Gonsette, Marc Debouverie, Christian Sindic, Jean-Christophe Ferré, Gilles Edan. Pixantrone: a B-cell-depleting immunosuppressant for multiple sclerosis patients with active disease. MULTIPLE SCLEROSIS JOURNAL, 2016, 22 (6), pp.817-821. ⟨10.1177/1352458515601902⟩. ⟨hal-01324700⟩

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