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Clinical Effects of a Topically Applied Toll-like Receptor 9 Agonist in Active Moderate-to-Severe Ulcerative Colitis

Atreya R, Bloom S, Scaldaferri F, Gerardi V, Admyre C, Karlsson A, Knittel T, Kowalski J, Lukas M, Lofberg R, Nancey S, Petryka R, Rydzewska G, Schnabel R, Seidler U, Neurath M, Hawkey C (2016)

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Publication Type: Journal article

Publication year: 2016

Journal

Book Volume: 10

Pages Range: 1294-1302

Journal Issue: 11

DOI: 10.1093/ecco-jcc/jjw103

Abstract

Toll-like receptors [TLRs] are potential drug targets for immunomodulation. We determined the safety and efficacy of the TLR-9 agonist DNA-based immunomodulatory sequence 0150 [DIMS0150] in ulcerative colitis [UC] patients refractory to standard therapy.In this randomized, double-blind, placebo-controlled trial, 131 patients with moderate-to-severe active UC were randomized to receive two single doses of the oligonucleotide DIMS0150 [30 mg] or placebo administered topically during lower GI endoscopy at baseline and Week 4. The primary endpoint was clinical remission, defined as Clinical Activity Index [CAI] <=4, at Week 12. Secondary endpoints included mucosal healing and symptomatic remission of key patient-reported outcomes [absence of blood in stool and weekly stool frequency <35].There was no statistical significant difference between the groups in the induction of clinical remission at Week 12, with 44.4% in the DIMS0150 group vs. 46.5% in the placebo group. However, the proportion of patients who achieved symptomatic remission was 32.1% in the DIMS0150 group vs. 14.0% in the placebo group at Week 4 [p = 0.020], and 44.4% vs. 27.9% at Week 8 [p = 0.061]. More patients on DIMS0150 compared with those on placebo had mucosal healing [34.6% vs. 18.6%; p = 0.09] and histological improvement regarding the Geboes score [30.9% vs. 9.3%; p = 0.0073] at Week 4. Significantly more patients on DIMS0150 were in clinical remission with mucosal healing at Week 4: 21% vs. 4.7% in the placebo group [p = 0.02]. DIMS0150 was well tolerated, and no safety signals compared with placebo were evident.Therapy with the topically applied TLR-9 agonist DIMS0150 is a promising and well-tolerated novel therapeutic option for treatment-refractory, chronic active UC patients, warranting further clinical trials.

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How to cite

APA:

Atreya, R., Bloom, S., Scaldaferri, F., Gerardi, V., Admyre, C., Karlsson, A.,... Hawkey, C. (2016). Clinical Effects of a Topically Applied Toll-like Receptor 9 Agonist in Active Moderate-to-Severe Ulcerative Colitis. Journal of Crohns & Colitis, 10(11), 1294-1302. https://doi.org/10.1093/ecco-jcc/jjw103

MLA:

Atreya, Raja, et al. "Clinical Effects of a Topically Applied Toll-like Receptor 9 Agonist in Active Moderate-to-Severe Ulcerative Colitis." Journal of Crohns & Colitis 10.11 (2016): 1294-1302.

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