Masitinib for the treatment of canine atopic dermatitis: a pilot study

Abstract

There is an on-going need to identify medications suitable for the long-term treatment of canine atopic dermatitis (CAD). Masitinib mesilate is a potent and selective tyrosine kinase inhibitor of the c-KIT receptor. A strong relationship exists between the SCF/c-KIT pathway and pathogenesis of CAD, suggesting that masitinib may potentially fulfil the above role. This study reports on an uncontrolled pilot study of masitinib in CAD. Masitinib was administered orally to 11 dogs at a mean dose of 11.0 +/- 1.83 mg/kg/day (free base) for 28 days. Treatment response was assessed by evolution of clinical appearance according to a modified version of the Canine Atopic Dermatitis Extent and Severity Index (mCADESI), pruritus scale and surface area of lesions. Masitinib improved CAD with a mean reduction in mCADESI of 50.7 +/- 29.8% (95% C.I. = 29.4-72.0; p = 0.0004) at day 28 relative to baseline, with 8/10, 8/10 and 4/10 dogs showing improvement of >or=33%, >or=40% and >or=50%, respectively. Improvement was further evidenced by a decrease in pruritus score and the surface area of lesions. No serious or severe adverse events occurred during this trial, although 6/11 dogs presented with mild to moderate treatment related adverse events. There is sufficient compelling evidence to warrant further investigation.

Environmental and phenotype-related risk factors for owner-reported allergic/atopic skin symptoms and for canine atopic dermatitis verified by veterinarian in a Finnish dog population

“…Recently, an association between c- KIT , a gene that partakes in mast cell development, and white spots on German shepherd dogs was found [58]. Strong connections between c-KIT and CAD in dogs [59, 60], as well as psoriasis [61] and asthma in humans [62] has also been reported. White Akita-inu dogs [63] and yellow Labrador and golden retrievers [64, 65] have been reported to be homozygous for the R306ter mutation of MC1R , a gene found in melanocytes.…”

Masitinib as an adjunct therapy for mild-to-moderate Alzheimer's disease: a randomised, placebo-controlled phase 2 trial

“…On this latter point, it is a common misnomer to describe masitinib, and similar tyrosine kinase inhibitors, as a chemotherapeutic agent because - unlike cytotoxic chemotherapies that kill all dividing cells, including healthy cells - masitinib is a targeted therapy. Moreover, depending on which kinases are targeted, tyrosine kinase inhibitors are equally well suited for the treatment of nononcology diseases, as has been previously demonstrated for masitinib in inflammatory and autoimmune diseases with mast cell involvement, such as rheumatoid arthritis [16], asthma [17], mastocytosis [30], and atopic dermatitis [31], as well as experimental allergic encephalomyelitis, an animal model of brain inflammation.…”

Masitinib decreases signs of canine atopic dermatitis: a multicentre, randomized, double‐blind, placebo‐controlled phase 3 trial

“…Composition and dispensing of the test drug and control treatment were identical except for omission of the active ingredient from the control. The initial masitinib dose of 12.5 mg/kg/day was selected based upon results from a pilot study, 9 as well as toxicity and bioavailability studies in dogs and rats (Patrice Dubreuil, 2010; personal communication). Treatment interruption or changes to dose were permitted for dogs experiencing mild to moderate toxicity following predefined criteria: treatment could be temporarily interrupted and resumed at the same dose upon resolution; if toxicity was recurrent, dosage could be decreased by 2.5 mg/kg/day; and in the case of persistent toxicity following dose reduction, treatment was discontinued.…”

“…There is a growing body of evidence implicating the involvement of mast cells in the pathogenesis of CAD 8–10 . These cells release large amounts of various mediators that sustain the inflammatory network, which in turn is responsible for many of the clinical manifestations of the disease.…”

“…There is a growing body of evidence implicating the involvement of mast cells in the pathogenesis of CAD. [8][9][10] These cells release large amounts of various mediators that sustain the inflammatory network, which in turn is responsible for many of the clinical manifestations of the disease. Molecules that are able to inhibit the survival and ⁄ or activation of mast cells may therefore be valuable tools for the treatment of CAD.…”