OP002 Histopathological response and remission after dual topical application of the Toll-like receptor 9 agonist DIMS0150 in patients with moderate-to-severe ulcerative colitis
R. Atreya*1, A. Öst2, C. Admyre3, A. Karlsson3, T. Knittel3, J. Kowalski3, F. Scaldaferi4, M. Neurath1, C. Hawkey5
1University of Erlangen-Nuernberg, Department of Medicine 1, Erlangen, Germany, 2Aleris Medilab, Department of Pathology and Cytology, Täby, Sweden, 3Index Pharmaceuticals, Stockholm, Sweden, 4Catholic University of Rome, Internal Medicine Department / Gastroenterology Division, Rome, Italy, 5Nottingham University Hospitals, Department of Gastroenterology, Nottingham, United Kingdom
Background
The Toll-like receptor (TLR) 9 agonist DIMS0150 might offer a new treatment option for patients with active ulcerative colitis. DIMS0150 was evaluated in treatment refractory active ulcerative colitis patients for its efficacy to induce histopathological responses besides remission defined by patient-reported outcomes or mucosal appearance.
Methods
The oligonucleotide DIMS0150 was studied in a randomised, double-blind, placebo-controlled, multicentre, pan-European phase III trial (COLLECT) in 131 patients with moderate-to-severe, chronic active ulcerative colitis and endoscopic Mayo score index of at least 2. Patients were randomly allocated to receive 2 single doses of DIMS0150 (30 mg) or placebo in a 2:1 ratio, administered topically to the inflamed mucosa via endoscopy at baseline and after 4 weeks. Endoscopy was performed at week 0, 4, and 12, and biopsies were obtained from the most affected area of the colon or rectum for histological evaluation according to the method described by Geboes (score 0 [normal mucosa] to score 5 [erosions/ulcerations]).
Results
At baseline 38.9% of patients had a histopathological score of 5; 8.4% a score of 4; 32.1% a score 3; 10.7% a score of 2; 6.9% a score of 1; and 0% a score of 0, whereas mucosal appearance was graded as Mayo score 3 in 57.3% of patients and as score 2 in 42.7% of patients. Mucosal healing (MH) defined as endoscopic Mayo score of 0 or 1 was achieved in 34.6% of the DIMS0150 vs 18.6% of the placebo-treated patients (p = 0.09) at week 4. At week 4, a clear improvement in the histological score was also observed. A Geboes score of 0–2 was evident in 30.9% of the DIMS0150 vs 9.3% of the placebo-treated patients (p = 0.0073), and a score of 0–1 indicating absence of acute inflammation was evident in 13.6% of the DIMS0150 vs 2.3% of the placebo-treated patients (p = 0.056). At week 12 and thereby 8 weeks after the second DIMS0150 application, there was no striking difference in the rate of mucosal healing or the histopathological scoring between the 2 groups.
Conclusion
The results of the COLLECT study provide evidence that topical administration of the TLR 9 agonist DIMS0150 can induce mucosal healing and histopathological response in patients with chronic active, moderate-to-severe ulcerative colitis.