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. 2024 Sep 19:11:1458998.
doi: 10.3389/fmed.2024.1458998. eCollection 2024.

Comparison of ustekinumab, infliximab and combination therapy in moderately to severely active ulcerative colitis - a study protocol of a randomized, multicenter, head-to-head COMBO-UC trial

Renata Talar-Wojnarowska  1 , Adam Fabisiak  1 , Hubert Zatorski  1 , Katarzyna Płoszka  2 , Katarzyna Błaziak  2 , Wojciech Fendler  2 , Grażyna Rydzewska  3 , Ewa Małecka-Wojciesko  1 , Piotr Eder  4
Affiliations

Comparison of ustekinumab, infliximab and combination therapy in moderately to severely active ulcerative colitis - a study protocol of a randomized, multicenter, head-to-head COMBO-UC trial

Renata Talar-Wojnarowska et al. Front Med (Lausanne). .

Abstract

Background: Ulcerative colitis (UC) is a chronic inflammatory bowel disease with a complex etiology that affects the large intestine. Characterized by chronic, bloody diarrhea, UC can lead to severe complications, including an increased risk of colorectal cancer. Despite advancements in conservative treatment, including biologics like anti-TNF agents and ustekinumab (UST), many patients do not achieve full remission. Dual targeted therapy (DTT) combining infliximab (IFX) and UST is a promising approach to improve treatment outcomes.

Methods: This prospective, randomized, multicenter, head-to-head controlled trial will evaluate the efficacy and safety of UST, IFX, and combination therapy (UST + IFX) in 172 patients with moderate to severe active UC across eight gastroenterology centers in Poland. The study includes a 14-16 week remission induction period followed by a 52-week maintenance phase. Patients will be randomly assigned to one of three treatment arms: IFX monotherapy, UST monotherapy, or IFX + UST combination therapy. Primary endpoint is clinical and endoscopic remission post-induction. Secondary endpoints include clinical response, biochemical remission, histological remission, and quality of life assessments using the Inflammatory Bowel Diseases Questionnaire and 36-Item Short Form Survey. Safety will be monitored through adverse event and serious adverse event reporting.

Discussion: This trial aims to determine whether combining IFX and UST can achieve higher remission rates and better long-term outcomes compared to monotherapy. The results could provide crucial insights into the optimal use of biologic agents in UC treatment, potentially establishing DTT as a standard therapy. The study's design, including extensive follow-up and robust endpoint measures, will contribute to understanding the therapeutic potential and safety profile of this combination therapy.

Keywords: dual biological therapy; inflammatory bowel diseases; infliximab; ulcerative colitis; ustekinumab.

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Conflict of interest statement

RT-W received lecture fees and/or travel grants from Abbvie, Astellas, Bristol-Myers-Squibb, Celtrion, Ferring, Janssen, Pfizer, Recordati, Sandoz, Takeda. AF received lecture fees and/or travel grants from Pro. Med.CS, Pfizer, Polpharma. HZ received lecture fees and/or travel grants from Nutricia, Fresenius Kabi, Ferring, Zentiva, Pro.Med.CS. EM-W received financial from Polpharma, Pfizer, Abbott, Mylan, Janssen, Celltrion, Varimed, Polpharma, Pro.Med.CS, Abbott, Mylan, Varimed, Takeda, Eli Lilly. PE received lecture fees and/or travel grants from Abbvie, Bristol-Myers-Squibb, Ferring, Janssen, Pfizer, Eli Lilly, Takeda, Sandoz, Pro.Med.CS, Sanofi. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

Figures

Figure 1
Figure 1
Allocation of patients to treatment arms and map of centers recruited for the study (A). Basic scheme of treatment arms (B).
Figure 2
Figure 2
Scheme of medical procedures during screening, in the remission induction phase and maintenance phase in arm A.
Figure 3
Figure 3
Scheme of medical procedures during screening, in the remission induction phase and maintenance phase in arm B.
Figure 4
Figure 4
Scheme of medical procedures during screening, in the remission induction phase and maintenance phase in arm C.
Figure 5
Figure 5
Total Mayo score with its subtypes: modified Mayo score and PRO-2.
See this image and copyright information in PMC

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References

    1. Eder P, Łodyga M, Gawron-Kiszka M, Dobrowolska A, Gonciarz M, Hartleb M, et al. . Guidelines for the management of ulcerative colitis. Recommendations of the polish Society of Gastroenterology and the polish National Consultant in gastroenterology. Gastroenterol Rev. (2023) 18:1–42. doi: 10.5114/pg.2023.125882 - DOI - PMC - PubMed
    1. Raine T, Bonovas S, Burisch J, Kucharzik T, Adamina M, Annese V, et al. . ECCO guidelines on therapeutics in ulcerative colitis: medical treatment. J Crohns Colitis. (2022) 16:2–17. doi: 10.1093/ecco-jcc/jjab178, PMID: - DOI - PubMed
    1. Spinelli A, Bonovas S, Burisch J, Kucharzik T, Adamina M, Annese V, et al. . ECCO guidelines on therapeutics in ulcerative colitis: surgical treatment. J Crohns Colitis. (2022) 16:179–89. doi: 10.1093/ecco-jcc/jjab177, PMID: - DOI - PubMed
    1. De Lange KM, Moutsianas L, Lee JC, Lamb CA, Luo Y, Kennedy NA, et al. . Genome-wide association study implicates immune activation of multiple integrin genes in inflammatory bowel disease. Nature Genet. (2017) 49:256–61. doi: 10.1038/ng.3760, PMID: - DOI - PMC - PubMed
    1. De Souza HSP, Fiocchi C. Immunopathogenesis of IBD: current state of the art. Nat Rev Gastroenterol Hepatol. (2015) 13:13–27. doi: 10.1038/nrgastro.2015.186 - DOI - PubMed

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