S currently being developed for the treatment of gastrointestinal stromal and other tumours, but the trial presented here is the first report on the use of masitinib in non-oncological pathology. The lead compound of such tyrosine kinase inhibitors is imatinib mesylate (Gleevec; Novartis Pharmaceuticals Corp, Basel, Switzerland). Imatinib is approved for the treatment of chronic myeloid leukaemia, in which it inhibits a tyrosine kinase produced by the bcr-abl fusion gene. In addition to the tyrosin kinase produced by bcr-abl, imatinib inhibits the tyrosine kinase signalling of other proteins, such as the receptors of platelet-derived growth factor (PDGF), stem cell factor and macrophage colony-stimulating factor, all of which have been implicated in the pathogenesis of RA [3,4]. In synovial fluid mononuclear cells derived from RA patients, imatinib was found to attenuate tumour necrosis factor (TNF) production [5]. Imatinib was also shown to induce mast cellMasitinib in rheumatoid arthritisTebib and coworkers [1] present the first study of masitinib in non-oncological pathology. Masitinib was given twice daily, either at an initial dose of 3 mg/kg per day or 6 mg/kg per day. Dose escalations were allowed during the 12-week study period. Half of the RA patients included had previously failed a TNF- inhibitor. American College of Rheumatology (ACR)20, ACR50 and ACR70 responses were achieved in 54 , 26 and 8 of the RA patients, respectively. With the higher initial masitinib dose, the median time to achieve PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/29072704 an ACR20 response was 29 days and to achieve an ACR 50 response was 73 days. It should be noted, however, that the efficacy analysis of this phase II study is hampered by the lack of a placebo group. Thus, a significant proportion of the study population could have improved by regression to the mean and other effects. With regard to safety, 37 of the patients included in the masitinib study withdrew before they reached the 12-week end-point, primarily because of adverse events. The overall incidence of adverse events was 91 and included rash (30 ), oedema (mainly of the face; 26 ), nausea (23 ) and diarrhoea (18.6 ). In 21 of individuals the adverse eventsACR = American College of Rheumatology; PDGF = platelet-derived growth factor; RA = rheumatoid arthritis; TNF = tumour necrosis factor.Page 1 of(page number not for citation purposes)Arthritis Research TherapyVol 11 NoWalkerwere severe. In some RA patients who were followed beyond week 12, however, no instances of rash, nausea, vomiting or diarrhoea were reported, although oedema persisted in a sizeable proportion.Safety profile of tyrosine kinase Vercirnon web inhibitorsThe side-effect profile of masitinib appears to be similar to that observed in preclinical models and those of other tyrosine kinase inhibitors. The occurrence of diarrhoea with this drug class can be explained by the pharmacological activity on the stem cell factor receptor on Cajal cells in the intestine [10], whereas oedema is linked to PDGF receptor blockade in the periorbital region. The side effects were similar in the canine masitinib study [2] and commonly involved the gastrointestinal tract. Several data suggest that tyrosine kinase inhibitors may have adverse effects that were not addressed in the human masitinib study. The canine study, for example, found hair loss to be among the most common side effects of masitinib. Stem cell factor and PDGF signalling pathways also appear to regulate the postnatal formation of.