AMISELIMOD SAFETY PROFILE FOR CROHN'S DISEASE, STRATIFIED BY PREVIOUS TREATMENT WITH ANTI-TNF AGENTS

Abstract Background Anti-TNF agents are an established treatment modality for ulcerative colitis (UC); however, as many as 30% of patients do not respond to anti-TNF agents, and almost 50% of responders lose clinical benefits after a year of treatment. Furthermore, numerous safety concerns are associated with long-term use of anti-TNF agents. An alternative treatment in development for autoimmune-mediated diseases, including Crohn’s disease (CD) and UC, are sphingosine 1-phosphate receptor modulators such as amiselimod (AMS). Methods The safety and efficacy of oral AMS 0.4 mg/d in adults with moderate to severe active CD over 14 wks were evaluated in a multicenter, randomized, double-blind, parallel-group, placebo (PBO)-controlled (DBPC), phase 2a clinical trial, followed by an open-label extension (OLE) study with AMS for up to 36 wks. Patients had previously used anti-TNF-α agents, immunosuppressants, or corticosteroids. Safety data (adverse events [AEs]) were stratified by patients with and without prior anti-TNF treatment. Results Of the 78 patients randomized 1:1 to receive AMS (n=40) or PBO (n=38), 78% (n=61) completed the DBPC treatment phase. Of those patients continuing into the OLE, 26 patients (AMS/AMS [n=14]; PBO/AMS [n=12]) completed it. Oral AMS 0.4 mg for 12 wks did not have a significant effect on clinical disease activity in CD. Patients previously treated with anti-TNF agents had more serious AEs (SAEs) (27% AMS [n=22]; 4% PBO [n=25]) than did patients without prior anti-TNF treatment (0 AMS and 0 PBO patients). Relative numbers of treatment-emergent AEs (TEAEs) were similar between groups receiving prior anti-TNF agents (68% AMS [n=22]; 68% PBO [n=25]) and no prior treatment (65% AMS [n=17]; 31% PBO [n=13]). There was a trend toward more mild TEAEs and less severe AEs in patients not previously treated with anti-TNF agents compared to those previously treated. Conversely, in the OLE, patients not previously treated with anti-TNF agents had more AEs (100% AMS/AMS [n=11]; 67% PBO/AMS [n=9]) than those with prior treatment (60% AMS/AMS [n=10]; 87% PBO/AMS [n=16]). All of these TEAEs were mild or moderate. In the OLE, only 1 patient receiving AMS/AMS with no prior anti-TNF treatment had an SAE versus no patients with prior treatment. Conclusions Previous treatment with anti-TNF agents did not significantly affect the TEAEs associated with AMS. While SAEs appeared to be more common in previously treated patients in the DBPC, patients had fewer AEs during the OLE. This analysis suggests that previous treatment with anti-TNF agents should be considered when assessing the AE profile of AMS in future trials.