P441. Low colectomy rate in treatment refractory ulcerative colitis patients following treatment with the Toll-like receptor 9 agonist DIMS0150
E. Musch1, T. Lutfi1, P. von Stein2, A. Zargari2, M. Malek1, T. Knittel2, R. Löfberg3, O. von Stein2, 1Marienhospital, Clinic of Colo-Proctology, Bottrop, Germany, 2InDex Pharmaceuticals, Stockholm, Sweden, 3IBD unit Sophiahemmet and the Dept of Medicine, Karolinska Institutet, Stockholm, Sweden
Background
Patients with treatment refractory ulcerative colitis represent an area of high unmet medical need as the only remaining option is normally colectomy. DIMS0150 is a DNA based immunomodulatory oligonucleotide that targets the Toll-like receptor 9 (TLR9) present in immune cells. The aim of the study was to determine whether DIMS1050 treatment could serve as a rescue therapy in treatment refractory ulcerative colitis patients scheduled for colectomy.
Methods
We treated a total of 14 ulcerative colitis patients classed as treatment failures who were elected for colectomy with the immunomodulatory agent DIMS0150 as add on to their current therapies. Eleven patients received a single topical dose of 30 mg/50 mL via endoscopy to or proximal to the inflamed area. Three patients received three doses with four weeks between dosing within the initial 12 week period. Some patients received additional doses beyond the 12 week period. Efficacy evaluations were determined in terms of colitis activity index, endoscopic improvement and histologic disease activity assessed primarily at week 12 with a follow-up period monitory colectomy rates of over two years.
Results
All patients demonstrated a pronounced reduction in their colitis activity index within 1 week following a single intracolonic dose of DIMS0150. Further improvements were evident at week 4 resulting in a clinical response and remission rate for the single dose treatment of 71% (8/11) and 27% (3/11) respectively. By week 12, the clinical response and remission rates had reached 91% (10/11) and 73% (8/11) respectively. Endoscopic remission rates in the single dose group were 27% (3/11) at week 4 and 45% (5/11) at week 12. Marked histological improvement was observed in 64% (7/11) of the single dose treated patients at week 12. Those patients who received three doses of DIMS0150 demonstrated an improved response to the measured parameters when compared to those patients who received a single dose of DIMS0150.
A follow-up period of over 3 years post treatment indicated that 85% (12/14) of the treated patients had avoided the need for colectomy giving a colectomy rate of <10% per year with the longest patient being in symptom free remission for over 40 months.
Conclusion
DIMS0150 has the potential to be an effective agent for treatment refractory chronic active ulcerative colitis patients with the prospect to avoid colectomy on a long term basis and is currently the subject of a clinical phase III study (EudraCT number: 2011–003130–14).