Vermersch et al said that the treatment for progressive multiple sclerosis remained “inadequate” and the study sought to prove the safety and clinical benefit of masitinib treatment for primary progressive multiple sclerosis (PPMS) and relapse-free progressive phase multiple sclerosis (rfSPMS). Vermersch et al aimed to investigate the hypothesis that masitinib targets inhibitory action on mast cells which would therefore reduce symptoms and progression in multiple sclerosis.
In the study, 35 patients aged 18–60 suffering from PPMS or rfSPMS? as diagnosed by the McDonald criteria?and having an Expanded Disability Status Scale (EDSSS) score between 2 and 6.5 with a progression >1 within two years prior to were randomised with 27 in the masitinib group and eight in the placebo group. From the 27 masitinib patients, 12 were started on 3 mg/kg/day and (after a median of two months) were switched to 6 mg/kg/day for 12 months and followed up every three months. The authors compared efficacy and safety parameters against the patient’s baseline, measured prior to treatment.
The authors observed that there were similar safety profiles between the masitinib group and the placebo group and efficacy was not significantly different. However, Vermersch et al said: “It does suggest a positive effect of masitinib on multiple sclerosis-related impairment and potential retardation of disease progression.” Adverse effects included rash, nausea, edema and diarrhoea with rash being the most recurrent cause for discontinuation of treatment.
In the study it was postulated that the favourable outcomes of masitinib on progressive multiple sclerosis was because replase remitting multiple sclerosis (RRMS) and secondary progressive multiple sclerosis (SPMS) are different stages of the same disease whereas PPMS and rfSPMS “may imply a different process.” The authors expanded on this saying: “The distinction in multiple sclerosis types appears to be reflected by the unsuccessful treatment of PPMS with powerful disease modifying-drugs.”
The authors suggested that mast cell activation could influence the mechanism of chronic neuodegenerative diseases of the nervous system and lead to neurodamage by inducing astroglia to produce neurotoxic quantities of nitric oxide (NO) which is implicated in the pathogenesis of multiple sclerosis (especially PPMS) and that, according to Vermersch et al: “Masitinib inhibitory action also effects the activiation of dendritic cells.” The study, according to the authors: “Provides evidence that supports a larger placebo-controlled investigation” as there are “practically no currently available” treatments for PPMS.
Amy Bowen, director of service development at the MS Trust, spoke to NeuroNews on the masitinib study, she said: “The number of drugs being trialled for people with primary or secondary progressive multiple sclerosis is few and far between. The findings in this small phase II study are encouraging and will hopefully lead to further, larger studies. A safe and effective treatment option for progressive multiple sclerosis remains on the horizon and hopefully this study helps bring the possibility closer to becoming a reality.”