Masitinib, a c-kit/PDGF receptor tyrosine kinase inhibitor, improves disease control in severe corticosteroid-dependent asthmatics.
BACKGROUND
Masitinib is a tyrosine kinase inhibitor targeting stem cell factor receptor (c-kit) and platelet-derived growth factor (PDGF) receptor, which are expressed on several cell types including mast cells and bronchial structural cells, respectively. We hypothesized that c-kit and PDGF receptor inhibition may decrease bronchial inflammation and interfere with airway remodeling, which are crucial features of severe asthma.


OBJECTIVE
The primary endpoint was the percent change from baseline in oral corticosteroids after 16 weeks of treatment. Change in asthma control (asthma control questionnaire), exacerbation rate, pulmonary function tests, rescue medication requirement and safety were secondary endpoints.


METHODS
A 16-week randomized, dose-ranging (3, 4.5, and 6 mg/kg/day), placebo-controlled study was undertaken in 44 patients with severe corticosteroid-dependent asthma who remained poorly controlled despite optimal asthma management.


RESULTS
At 16 weeks of treatment, a comparable reduction in oral corticosteroids was achieved with masitinib and placebo (median reduction of -78% and -57% in the masitinib and placebo arms, respectively). Despite this similar reduction, the Asthma Control Questionnaire score was significantly better in the masitinib arm as compared to placebo with a reduction by 0.99 unit at week 16 (P < 0.001) vs 0.43 unit in the placebo arm. Masitinib therapy was associated with more transient skin rash and edema.


CONCLUSIONS
Masitinib, a c-kit and PDGF-receptor tyrosine kinase inhibitor, may represent an innovative avenue of treatment in corticosteroid-dependent asthma. These preliminary results warrant further long-term clinical studies in severe asthma
Humbert
M
M
Université Paris-Sud 11, Service de Pneumologie et Réanimation Respiratoire, Hôpital Antoine-Béclère, Assistance Publique des Hôpitaux de Paris, 157 rue de la Porte de Trivaux, Clamart 92140, France.
de Blay
F
F
Garcia
G
G
Prud'homme
A
A
Leroyer
C
C
Magnan
A
A
Tunon-de-Lara
J-M
JM
Pison
C
C
Aubier
M
M
Charpin
D
D
Vachier
I
I
Purohit
A
A
Gineste
P
P
Bader
T
T
Moussy
A
A
Hermine
O
O
Chanez
P
P
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001249:Asthma / Q000188:drug therapy*; D001549:Benzamides; D004487:Edema / Q000209:etiology; D005076:Exanthema / Q000209:etiology; D005260:Female; D005602:France; D006801:Humans; D006889:Hydroxycorticosteroids / Q000008:administration & dosage; D008297:Male; D055118:Medication Adherence; D008875:Middle Aged; D010880:Piperidines; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D011725:Pyridines; D017479:Receptors, Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors*; D013844:Thiazoles / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome
D018927:Anti-Asthmatic Agents; D001549:Benzamides; D006889:Hydroxycorticosteroids; D010880:Piperidines; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D013844:Thiazoles; C099852:PDGF receptor tyrosine kinase; D019009:Proto-Oncogene Proteins c-kit; D017479:Receptors, Platelet-Derived Growth Factor; C526575:masitinib