Efficacy, safety and tolerability of vidofludimus in patients with inflammatory bowel disease: the ENTRANCE study.

BACKGROUND: Vidofludimus (SC12267) is a novel oral immunomodulator inhibiting dihydroorotate dehydrogenase (DHODH) and the expression of proinflammatory cytokines including interleukin-17 (IL17A and IL17F) and interferon-gamma. The objective of the study was to explore the efficacy, safety and tolerability of vidofludimus in steroid-dependent inflammatory bowel disease (IBD). METHODS: The open label uncontrolled ENTRANCE study (ClinicalTrials.gov NCT00820365) has been conducted at 13 study centers in Germany, Bulgaria and Romania. Thirty-four steroid-dependent patients with a confirmed diagnosis of Crohn's disease (CD) or ulcerative colitis (UC) were treated with a once daily 35mg oral dose of vidofludimus over 12weeks. Steroids were tapered during the first 8weeks followed by a steroid-free treatment period of 4weeks. Complete response was defined as steroid-free clinical remission at week 12; partial response was defined as being in remission at steroid dose equal or lower than the individual patient's threshold dose for relapse. RESULTS: Of the thirty-four patients enrolled in this trial 26 were evaluable for primary efficacy assessment. After completion of the 12weeks treatment phase 8 out of 14 (57.1%) patients with CD and 6 out of 12 (50.0%) patients with UC were in steroid-free remission (complete responders). Another 4 (28.6%) patients in CD and 5 (41.7%) patients in UC were partial responders. Vidofludimus was well tolerated, no drug-related serious adverse events were observed. CONCLUSIONS: This trial provides first evidence of clinical efficacy of vidofludimus in IBD. Although the safety and tolerability profile seems favorable, long-term controlled studies are needed to further investigate its potential as novel IBD therapy.