Open Access Highly Accessed Research article

Masitinib treatment in patients with progressive multiple sclerosis: a randomized pilot study

Patrick Vermersch1*, Rabah Benrabah2, Nicolas Schmidt3, Hélène Zéphir1, Pierre Clavelou4, Cyrille Vongsouthi5, Patrice Dubreuil67, Alain Moussy6 and Olivier Hermine68*

Author Affiliations

1 Department of Neurology, University of Lille Nord de France (EA2686), Hôpital Roger Salengro, CHU de Lille, Lille cedex, 59037, France

2 Private Practice, Paris, France

3 Private Practice, Rueil-Malmaison, France

4 Hôpital Gabriel Montpied, Clermont-Ferrand, France

5 Private Practice, Montpellier, France

6 AB Science, SA, Paris, France

7 Inserm U891, Centre de Recherche en Cancérologie de Marseille, Signalisation, Hematopoiesis and Mechanisms of Oncogenesis, Centre de référence des mastocytoses, Marseille, France; Institut PaoliCalmettes, Marseille, France, Université Méditerranée, Marseille, France

8 Service d’hématologie adulte, Centre de référence des mastocytoses, CNRS UMR 8147, Hôpital Necker, Université Paris Descartes, 149 - 161 rue de Sèvres, Paris, 75743, France

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BMC Neurology 2012, 12:36  doi:10.1186/1471-2377-12-36

Published: 12 June 2012



Treatment options for patients suffering from progressive forms of multiple sclerosis (MS) remain inadequate. Mast cells actively participate in the pathogenesis of MS, in part because they release large amounts of various mediators that sustain the inflammatory network. Masitinib, a selective oral tyrosine kinase inhibitor, effectively inhibits the survival, migration and activity of mast cells. This exploratory study assessed the safety and clinical benefit of masitinib in the treatment of primary progressive MS (PPMS) or relapse-free secondary progressive MS (rfSPMS).


Multicenter, randomized, placebo-controlled, proof-of-concept trial. Masitinib was administered orally at 3 to 6 mg/kg/day for at least 12 months, with dose adjustment permitted in event of insufficient response with no toxicity. The primary response endpoint was the change relative to baseline in the multiple sclerosis functional composite score (MSFC). Clinical response was defined as an increase in MSFC score relative to baseline of > 100%.


Thirty-five patients were randomized to receive masitinib (N = 27) or placebo (N = 8). Masitinib was relatively well tolerated with the most common adverse events being asthenia, rash, nausea, edema, and diarrhea. The overall frequency of adverse events was similar to the placebo group, however, a higher incidence of severe and serious events was associated with masitinib treatment. Masitinib appeared to have a positive effect on MS-related impairment for PPMS and rfSPMS patients, as evidenced by an improvement in MSFC scores relative to baseline, compared with a worsening MSFC score in patients receiving placebo; +103% ± 189 versus -60% ± 190 at month-12, respectively. This positive, albeit non-statistically significant response was observed as early as month-3 and sustained through to month-18, with similar trends seen in the PPMS and rfSPMS subpopulations. A total of 7/22 (32%) assessable masitinib patients reported clinical response following 12 months of treatment (according to the modified intent-to-treat population, observed cases) compared with none in the placebo group. The Expanded Disability Status Scale remained stable for both treatment groups.


These data suggest that masitinib is of therapeutic benefit to PPMS and rfSPMS patients and could therefore represent an innovative avenue of treatment for this disease. This exploratory trial provides evidence that may support a larger placebo-controlled investigation.

Multiple sclerosis; Primary progressive multiple sclerosis; Secondary progressive multiple sclerosis; Tyrosine kinase inhibitor; Masitinib; Mast cells