Clinical efficacy of the Toll-like receptor 9 agonist cobitolimod using patient-reported-outcomes defined clinical endpoints in patients with ulcerative colitis.

Abstract

BACKGROUND:

The Toll-like-receptor 9 (TLR-9) agonist cobitolimod (DIMS0150, Kappaproct®) is a promising therapeutic option for ulcerative colitis (UC) patients.

AIMS:

The objectives of this post-hoc analysis using the COLLECT study data was to investigate the clinical effects of cobitolimod using patient-reported-outcomes (PRO) defined endpoints.

METHODS:

Dual topical administration of cobitolimod was studied in a randomised, multicentre clinical trial named COLLECT in moderate-to-severe UC patients. Symptomatic remission (SR) was studied in 104 patients based on their e-diary records and was defined as absence of blood in stool and a mean daily stool frequency (SF) < 4.

RESULTS:

SR was achieved at week 4 in 17.1% of cobitolimod vs. 5.9% of placebo treated patients (p = 0.13), at week 8 in 35.7% vs. 17.6% (p = 0.07), and at week 12 in 38.6% vs. 17.6% (p = 0.04) of the patients, respectively. SR rates with cobitolimod and placebo in anti-TNFα experienced patients were smaller but with a broadly similar relative effect-size to anti-TNFα naïve patients. Clinical efficacy was higher in patients with moderate compared to severe disease.

CONCLUSIONS:

Application of the Toll-like-receptor 9 (TLR-9) agonist cobitolimod is able to induce remission as assessed by PRO measures in UC patients with moderate-to-severe activity as well as in anti-TNFα experienced and naïve patients supporting the overall efficacy of the substance.

• Authors: Raja Atreya, Walter Reinisch, Laurent Peyrin-Biroulet, Franco Scaldaferri, Charlotte Admyre, Thomas Knittel, Jan Kowalski, Markus Friedrich Neurath, Christopher Hawkey
• Journal: Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver (Dig Liver Dis) Vol. 50 Issue 10 Pg. 1019-1029 (10 2018) ISSN: 1878-3562 [Electronic] Netherlands
• PMID: 30120066 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial)
• Copyright: Copyright © 2018. Published by Elsevier Ltd.

Chemical References

• DIMS0150
• Toll-Like Receptor 9
• Tumor Necrosis Factor-alpha
• DNA

Topics

• Administration, Topical
• Adult
• Aged
• Colitis, Ulcerative (drug therapy)
• DNA (administration & dosage)
• Female
• Humans
• Internationality
• Logistic Models
• Male
• Middle Aged
• Multivariate Analysis
• Patient Reported Outcome Measures
• Retrospective Studies
• Severity of Illness Index
• Toll-Like Receptor 9 (agonists)
• Treatment Outcome
• Tumor Necrosis Factor-alpha (antagonists & inhibitors)
• Young Adult