In regard to the DAS28 extension Enzastaurin supplier phase data after 1 year of treatment, an increasing number of patients were achieving DAS28 values of not more than 3. 2 or less than 2. 6, signifying Inhibitors,Modulators,Libraries inactive RA or an increased likelihood of being in remission. Furthermore, over this time, two patients achieved up to 90% improvement. Taken together, this suggests that further therapeu tic gains could possibly be achieved given longer exposure times. Dose analysis An analysis of time to first response according to initial dosage is presented in Table 5. This analysis extends to the extension phase for a total assessment period of approximately 32 weeks. Patients randomly assigned to the 6 mg kg per day dosing group achieved a response faster than those assigned to the 3 mg kg per day, however, these differences were not statistically significant.

In cases of insufficient treatment Inhibitors,Modulators,Libraries response, dose adjustment was permitted at weeks 4 and 8, hence, the dose at time of first response was also analysed. Results reveal that approximately 65% and 73% of those patients achieving Inhibitors,Modulators,Libraries ACR20 or ACR50 scores, respectively, did so at a dosage of not more than 6 mg kg per day. Moreover, this dosage corresponded to the highest response rate for the ACR50 threshold. For those patients randomly assigned to the 3 mg kg per day dosing group, 12 22 received dose augmentation at weeks 4 or 8 due to insufficient response. Of these, 7 12 patients experienced an improved response within the initial 12 week phase whereas 5 12 patients were nonresponders, having failed to reach the ACR20 threshold.

Discussion Although the incidence of AEs was high in the study popula Inhibitors,Modulators,Libraries tion as a whole, the majority of these were mild or mod erate in severity, transitory in nature and resolved spontaneously or upon temporary treatment interruption. Moreover, because this was the first study of masitinib as treatment in a nononcologic pathology, the increased inci dence of dermatological events typically associated with this therapeutic class was understandably treated with great caution by patients and investigators alike. This may in part explain the relatively high dropout rate of patients. Of those who withdrew from the study because of AEs prior to week 12 , 9 13 patients had experienced AEs of a mild or moderate intensity, which could feasibly have been man aged without permanent interruption of treatment.

Inhibitors,Modulators,Libraries In general, AEs occurred early during the course of treatment, which is consistent with the known safety profile of TK inhibitors. This trend is clearly evident when comparing safety data from the initial and extension phases, the implication being that, although masitinib is not DOT1L completely free from side effects, the majority of these are over following 12 weeks of treatment, with good tolerance experienced thereafter during any long term treatment regimen.