Add-on multiple submucosal injections of the RNA oligonucleotide GUT-1 to anti-TNF antibody treatment in patients with moderate-to-severe ulcerative colitis: an open-label, proof-of concept study

Suzuki K, Sameshima Y, Yokoyama J, Terai S, Yoneyama H, Atreya R, Neurath M, Hibi T, Asakura H (2024)

Publication Type: Journal article

Publication year: 2024

Journal

Inflammation and Regeneration Japanese Society of Inflammation and Regeneration

Book Volume: 44

Article Number: 22

Journal Issue: 1

DOI: 10.1186/s41232-024-00332-7

Abstract

Background: Carbohydrate sulfotransferase 15 (CHST15) is an enzyme biosynthesizing matrix glycosaminoglycan that modulates tissue remodeling. We evaluated the efficacy of add-on submucosal injections of GUT-1, the RNA oligonucleotide inhibitor of CHST15, to ongoing anti-tumor necrosis factor (TNF) antibody treatment in patients with moderate-to-severe ulcerative colitis (UC). Methods: This was an open-label study of 250 nM of GUT-1 by endoscopic submucosal injections at weeks 0, 2, 4 in five UC patients who lost response during maintenance treatment to anti-TNF antibodies. The primary endpoint was the rate of endoscopic improvement at week 6 and secondary endpoints included the rates of clinical remission by modified Mayo Score (mMS). Patients received follow-up observation with continuous maintenance treatment by the same anti-TNF antibody till the time of clinical recurrence or for overall 52 weeks. Results: At week 6, rates of endoscopic improvement and clinical remission were 80% (n = 4/5) and 60% (n = 3/5), respectively. The mean Endoscopy Subscore was reduced from 2.4 (95%CI: 1.7 to 3.1) at baseline, to 1.0 (95%CI: 0.1 to 1.9) at week 6. The mean mMS was reduced from 7.8 (95%CI: 6.2 to 9.4) to 1.3 (95%CI: 2.9 to 4.3). GUT-1 was well tolerated. Three patients did not show clinical recurrence for 52 weeks. All three corticosteroid-dependent patients showed no corticosteroid exposure for at least 24 weeks after achieving clinical remission. Multiple dosing was also well tolerated. Conclusions: Add-on multiple injections of GUT-1 to ongoing anti-TNF antibody was able to induce rapid and durable clinical responses in UC patients who lost response to anti-TNF therapy. Trial registration: Clinical trial Registration Number (Japan): UMIN000020900.

Authors with CRIS profile

Raja Atreya Professur für Translationale Immunforschung bei chronisch entzündlichen Darmerkrankungen (Heisenberg-Professur) Markus Neurath Lehrstuhl für Innere Medizin I (Medizin 1)

Involved external institutions

Niigata University Medical & Dental Hospital JP Japan (JP) Sameshima Hospital JP Japan (JP) Gut Inc. JP Japan (JP) Kitasato University / 北里大学 (Kitasato Daigaku) JP Japan (JP)

How to cite

APA:

Suzuki, K., Sameshima, Y., Yokoyama, J., Terai, S., Yoneyama, H., Atreya, R.,... Asakura, H. (2024). Add-on multiple submucosal injections of the RNA oligonucleotide GUT-1 to anti-TNF antibody treatment in patients with moderate-to-severe ulcerative colitis: an open-label, proof-of concept study. Inflammation and Regeneration, 44(1). https://doi.org/10.1186/s41232-024-00332-7

MLA:

Suzuki, Kenji, et al. "Add-on multiple submucosal injections of the RNA oligonucleotide GUT-1 to anti-TNF antibody treatment in patients with moderate-to-severe ulcerative colitis: an open-label, proof-of concept study." Inflammation and Regeneration 44.1 (2024).

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