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.
Robert-Bosch-Hospital Stuttgart, Gastroenterology & Endocrinology, Stuttgart, Germany. k.herrlinger@asklepios.com
K R
KR
Herrlinger
M
M
Diculescu
K
K
Fellermann
H
H
Hartmann
S
S
Howaldt
R
R
Nikolov
A
A
Petrov
W
W
Reindl
J M
JM
Otte
S
S
Stoynov
U
U
Strauch
A
A
Sturm
R
R
Voiosu
A
A
Ammendola
B
B
Dietrich
B
B
Hentsch
E F
EF
Stange
D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D001379:Azathioprine / Q000627:therapeutic use; D001713:Biphenyl Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D001799:Blood Sedimentation; D002097:C-Reactive Protein / Q000378:metabolism; D003093:Colitis, Ulcerative / Q000097:blood / Q000188:drug therapy*; D003424:Crohn Disease / Q000097:blood / Q000188:drug therapy*; D003998:Dicarboxylic Acids / Q000009:adverse effects / Q000627:therapeutic use*; D000090722:Dihydroorotate Dehydrogenase; D004791:Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D005243:Feces / Q000737:chemistry; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000009:adverse effects / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D057194:Intention to Treat Analysis; D039841:Leukocyte L1 Antigen Complex / Q000032:analysis; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000037:antagonists & inhibitors; D011239:Prednisolone / Q000627:therapeutic use; D012074:Remission Induction; D012720:Severity of Illness Index; D055815:Young Adult
D000893:Anti-Inflammatory Agents; D001713:Biphenyl Compounds; D003998:Dicarboxylic Acids; D000090722:Dihydroorotate Dehydrogenase; D004791:Enzyme Inhibitors; D007155:Immunologic Factors; D007166:Immunosuppressive Agents; D039841:Leukocyte L1 Antigen Complex; C553728:vidofludimus; D002097:C-Reactive Protein; D011239:Prednisolone; D044925:Oxidoreductases Acting on CH-CH Group Donors; D001379:Azathioprine; D008727:Methotrexate