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Real-world efficacy and safety of advanced therapies in hospitalized patients with ulcerative colitis

  • Original Article—Alimentary Tract
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A Letter to the Editor to this article was published on 04 May 2024

Abstract

Background

This multicenter observational cohort study aimed to evaluate the utilization and short-term efficacy of advanced therapy (AT) in hospitalized patients with acute severe ulcerative colitis (ASUC).

Methods

In total, 221 patients with ASUC were enrolled between August 2020 and July 2021. The primary endpoint was clinical remission (CR, defined as a patient-reported outcome score < 2 with no blood in the stool) rate on Day 7 and 14 in hospitalized patients who received corticosteroids (CS) and AT.

Results

Among patients with ASUC, 120 and 101 patients received CS or any AT as first-line treatment, respectively. The CR rates on Day 7 and 14 were 22.5% and 35.0%, respectively, in hospitalized patients who received CS as first-line treatment. Most patients who used ATs had CS-dependent or frequent recurrences. Eight different ATs (apheresis, tacrolimus, infliximab, golimumab, tofacitinib, vedolizumab, ustekinumab, and cyclosporine) were used as first-line treatment in patients with ASUC, and the CR rates on Day 7 and 14 were 16.8% and 29.7%, respectively. Twenty-five patients received the second ATs after hospitalizations, and the CR rates on Day 7 and 14 were 0% and 12%, respectively. The CR rates on Day 14 were significantly higher in patients who changed to AT than in those whose dose of CS increased (34.0% vs 10.7%, p = 0.020) among patients who had already used CS before hospitalization.

Conclusion

Most first-use ATs were effective for patients with ASUC, while second-use ATs might have had limited benefits in inducing CR. These findings may contribute to considerations for the management of hospitalized patients.

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Abbreviations

5-ASA:

5-Aminosalicylic acid

ADA:

Adalimumab

AE:

Adverse effect

AGA:

American Gastroenterological Association

ASUC:

Acute severe ulcerative colitis

AT:

Advanced therapy

BSG:

British Society of Gastroenterology

CAP:

Apheresis

CDI:

Clostridioides difficile Infection

CI:

Confidence interval

CMV:

Cytomegalovirus

CR:

Clinical remission

CRP:

C-reactive protein

CS:

Corticosteroids

CSA:

Cyclosporine

DVT:

Deep vein thrombosis

ECCO:

European Crohn’s and Colitis Organization

ESR:

Erythrocyte sedimentation rate

GLM:

Golimumab

IFX:

Infliximab

IL:

Interleukin

JAK:

Janus kinase

MES:

Mayo endoscopic subscores

OR:

Odds ratio

PRO2:

Patient-reported outcome 2

RCT:

Randomized controlled trial

TAC:

Tacrolimus

TNF:

Tumor necrosis factor

TOFA:

Tofacitinib

TPN:

Total parenteral nutrition

UC:

Ulcerative colitis

USD:

Ustekinumab

VED:

Vedolizumab

References

  1. Naganuma M, Mizuno S, Nanki K, Sugimoto S, Kanai T. Recent trends and future directions for the medical treatment of ulcerative colitis. Clin J Gastroenterol. 2016;9:329–36.

    Article  PubMed  Google Scholar 

  2. Rutgeerts P, Sandborn WJ, Feagan BG, et al. Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2005;353:2462–76.

    Article  CAS  PubMed  Google Scholar 

  3. Sandborn WJ, van Assche G, Reinisch W, et al. Adalimumab induces and maintains clinical remission in patients with moderate-to-severe ulcerative colitis. Gastroenterology. 2012;142:257–65.

    Article  CAS  PubMed  Google Scholar 

  4. Sandborn WJ, Feagan BG, Marano C, et al. Subcutaneous golimumab induces clinical response and remission in patients with moderate-to-severe ulcerative colitis. Gastroenterology. 2014;146:85–95.

    Article  CAS  PubMed  Google Scholar 

  5. Sandborn WJ, Feagan BG, Marano C, et al. Subcutaneous golimumab maintains clinical response in patients with moderate-to-severe ulcerative colitis. Gastroenterology. 2014;146:96–109.

    Article  CAS  PubMed  Google Scholar 

  6. Ogata H, Matsui T, Nakamura M, et al. A randomised dose finding study of oral tacrolimus (FK506) therapy in refractory ulcerative colitis. Gut. 2006;55:1255–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Feagan BG, Rutgeerts P, Sands BE, et al. Vedolizumab as induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2013;369:699–710.

    Article  CAS  PubMed  Google Scholar 

  8. Sandborn WJ, Su C, Sands BE, et al. Tofacitinib as induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2017;376:1723–36.

    Article  CAS  PubMed  Google Scholar 

  9. Sands BE, Sandborn WJ, Panaccione R, et al. Ustekinumab as induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2019;381:1201–14.

    Article  CAS  PubMed  Google Scholar 

  10. Feagan BG, Danese S, Loftus EV Jr, et al. Filgotinib as induction and maintenance therapy for ulcerative colitis (SELECTION): a phase 2b/3 double-blind, randomised, placebo-controlled trial. Lancet. 2021;397:2372–84.

    Article  CAS  PubMed  Google Scholar 

  11. Danese S, Vermeire S, Zhou W, et al. Upadacitinib as induction and maintenance therapy for moderately to severely active ulcerative colitis: results from three phase 3, multicenter, double-blind, randomised trials. Lancet. 2022;399:2113–28.

    Article  CAS  PubMed  Google Scholar 

  12. Singh S, Allegretti JR, Siddique SM, et al. AGA Clinical practice guidelines on the management of moderate to severe ulcerative colitis. Gastroenterology. 2020;158:1465–96.

    Article  CAS  PubMed  Google Scholar 

  13. Lamb CA, Kennedy NA, Raine T, et al. British Society of Gastroenterology consensus guidelines on the management of inflammatory bowel disease in adults. Gut. 2019;68:s1–106.

    Article  PubMed  Google Scholar 

  14. Chaparro M, Czuber-Dochan W, Eder P, et al. ECCO Guidelines on therapeutics in ulcerative colitis: surgical treatment. J Crohns Colitis. 2022;16:179–89.

    Article  PubMed  Google Scholar 

  15. Dinesen LC, Walsh AJ, Protic MN, et al. The pattern and outcome of acute severe colitis. J Crohns Colitis. 2010;4:431–7.

    Article  PubMed  Google Scholar 

  16. Kennedy NA, Jones GR, Lamb CA, et al. British Society of Gastroenterology guidance for management of inflammatory bowel disease during the COVID-19 pandemic. Gut. 2020;69:984–90.

    Article  CAS  PubMed  Google Scholar 

  17. Nakase H, Matsumoto T, Matsuura M, et al. Expert Opinions on the Current therapeutic management of inflammatory bowel disease during the COVID-19 pandemic: Japan IBD COVID-19 Taskforce, Intractable Diseases, the Health and Labor Sciences Research. Digestion. 2021;102:814–22.

    Article  CAS  PubMed  Google Scholar 

  18. Brenner EJ, Ungaro RC, Gearry RB, et al. Corticosteroids, but not TNF antagonists, are associated with adverse COVID-19 outcomes in patients with inflammatory bowel diseases: results from an international registry. Gastroenterology. 2020;159:481–91.

    Article  CAS  PubMed  Google Scholar 

  19. Ungaro RC, Brenner EJ, Gearry RB, et al. Effect of IBD medications on COVID-19 outcomes: results from an international registry. Gut. 2021;70:725–32.

    Article  CAS  PubMed  Google Scholar 

  20. Choshen S, Finnamore H, Auth MK, et al. Corticosteroid dosing in pediatric acute severe ulcerative colitis: a propensity score analysis. J Pediatr Gastroenterol Nutr. 2016;63:58–64.

    Article  CAS  PubMed  Google Scholar 

  21. Turner D, Walsh CM, Steinhart AH, et al. Response to corticosteroids in severe ulcerative colitis: a systematic review of the literature and a meta-regression. Clin Gastroenterol Hepatol. 2007;5:103–10.

    Article  CAS  PubMed  Google Scholar 

  22. Hindryckx P, Jairath V, D’Haens G. Acute severe ulcerative colitis: from pathophysiology to clinical management. Nat Rev Gastro Hepatol. 2016;13:654–64.

    Article  CAS  Google Scholar 

  23. Laharie D, Bourreille A, Branche J, et al. Ciclosporin versus infliximab in patients with severe ulcerative colitis refractory to intravenous steroids: a parallel, open- label randomised controlled trial. Lancet. 2012;380:1909–15.

    Article  CAS  PubMed  Google Scholar 

  24. Williams JG, Alam MF, Alrubaiy L, et al. Infliximab versus ciclosporin for steroid- resistant acute severe ulcerative colitis (CONSTRUCT): a mixed methods, open- label, pragmatic randomised trial. Lancet Gastroenterol Hepatol. 2016;1:15–24.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Narula N, Marshall JK, Colombel JF, et al. Systematic review and meta-analysis: infliximab or cyclosporine as rescue therapy in patients with severe ulcerative colitis refractory to steroids. Am J Gastroenterol. 2016;111:477–91.

    Article  CAS  PubMed  Google Scholar 

  26. Filippi J, Altwegg R, Brixi H, et al. Efficacy and safety of induction therapy with calcineurin inhibitors in combination with vedolizumab in patients with refractory ulcerative colitis. Clin Gastroenterol Hepatol. 2019;17:494–501.

    Article  PubMed  Google Scholar 

  27. Tarabar D, El Jurdi K, Traboulsi C, et al. A prospective trial with long term follow-up of patients with severe, steroid-resistant ulcerative colitis who received induction therapy with cyclosporine and were maintained with vedolizumab. Inflamm Bowel Dis. 2022;28:1549–54.

    Article  PubMed  Google Scholar 

  28. Christensen B, Gibson PR, Micic D, et al. Safety and efficacy of combination treatment with calcineurin inhibitors and vedolizumab in patients with refractory inflammatory bowel disease. Clin Gastroenterol Hepatol. 2019;17:486–93.

    Article  CAS  PubMed  Google Scholar 

  29. Berinstein JA, Steiner CA, Regal RE, et al. Efficacy of induction therapy with high-intensity tofacitinib in 4 patients with acute severe ulcerative colitis. Clin Gastroenterol Hepatol. 2019;17:988–90.

    Article  PubMed  Google Scholar 

  30. Santos S, Gamelas V, Saraiva R, et al. Tofacitinib: an option for acute severe ulcerative colitis? GE Port J Gastroenterol. 2021;29:132–4.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Xiao Y, Benoit N, Sedano R, et al. Effectiveness of tofacitinib for hospitalized patients with acute severe ulcerative colitis: Case series. Dig Dis Sci. 2022;67:5213–9.

    Article  CAS  PubMed  Google Scholar 

  32. Gilmore R, Hilley P, Srinivasan A, et al. Sequential use of high-dose tofacitinib after infliximab salvage therapy in acute severe ulcerative colitis. J Crohns Colitis. 2022;16:166–8.

    Article  PubMed  Google Scholar 

  33. Berinstein JA, Sheehan JL, Dias M, et al. Tofacitinib for biologic-experienced hospitalized patients with acute severe ulcerative colitis: a retrospective case-control study. Clin Gastroenterol Hepatol. 2021;19:2112–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Shaffer SR, Traboulsi C, Krugliak Cleveland N, et al. Combining cyclosporine with ustekinumab in acute severe ulcerative colitis. ACG Case Rep J. 2021;8: e00604.

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

Collaborators of the study: Reiko Kunisaki (Yokohama City University Medical Center), Shojiro Yamamoto, Souichiro Ogawa, Hotaka Tamura, Keisuke Uchida (Miyazaki University), Toshiro Fukui, Norimasa Fukata (Kansai Medical University), Katsuyoshi Matsuoka (Toho University Sakura Medical Center), Ami Kawamoto, Masakazu Nagahori, Ryuichi Okamoto (Tokyo Medical and Dental University), Daisuke Saito, Miki Miura, Tadakazu Hisamatsu (Kyorin University), Kosaku Nanki, Yusuke Yoshimatsu (Keio University), Kazuyuki Narimatsu, Ryota Hokari (National Defense University), Hisashi Shiga, Yoichi Kakuta (Tohoku University), Tomohiro Fukuda, Aya Hojyo, Shintaro Sagami, Taku Kobayashi, Toshufumi Hibi (Kitasato University, Kitasato Institute Hospital), Yasuhisa Sakata, Motohiro Esaki (Saga University), Shinichiro Yoshioka, Kozo Tsuruta, Masaru Morita, Keiichi Mitsuyama (Kurume University), Shingo Kato (Saitama Medical Center, Saitama Medical University), Naoki Shibuya, Ryosuke Miyazaki, Masayuki Saruta (Tokyo Jikei Medical University), Ryohei Hayashi, Shinji Tanaka (Hiroshima University Hospital), Eriko Yasutomi, Sakiko Hiraoka (Okayama University), Kaoru Yokoyama, Kiyonori Kobayashi (Kitasato University), Mariko Kajiwara, Tomohisa Takagi (Kyoto Manufactural University), Kei Moriya (Nara Medical University), Yoshikazu Tsuzuki, Hiroyuki Imaeda (Saitama Medical University), Eri Tokunaga, Mitsuru Ooi (Kobe University), Nobuhiro Ueno, Mikihiro Fujiya (Asahikawa Medical University), Toshiyuki Tahara (Saiseikai Utsunomiya Hospital), Ayumu Yokoyama, Atsushi Nakazawa (Saiseikai General Hospital), Shun Mirasugi, Tomoko Kuriyama, Teppei Ohmori (Tokyo Women’s Medical University), Ken Takeuchi (Tsujinala Hospital Kashiwanoha), Shinichi Hashimoto (Yamaguchi University), Daisuke Hirayama, Tomoe Kazama, Hiroshi Nakase (Sapporo Medical University), Takako Miyazaki, Shiro Nakamura (Osaka Medical University), Akihiko Oka, Kohsaku Kawashima, Shunji Ishihara (Shimane University). Shunichi Yanai, Takayuki Matsumoto (Iwate Medical University), Toshiyuki Sato, Yoko Yokoyama, Kenji Watanabe (Hyogo Medical University), Yasunori Yamamoto, Yoichi Hiasa (Ehime University), Hideki Bamba, Akira Ando (Shiga University), Yuki Ohta, Kengo Kanayama, Jun Kato (Chiba University), Naoki Ohmiya (Fujita Medical University), and Sohachi Nanjyo (Toyama University).

Funding

This study was partly funded by a grant from the Japan Agency for Medical Research and Development (20314259).

Author information

Authors and Affiliations

Authors

Consortia

Contributions

MN conceived the study. MN and TK designed the main concept of this study. MN, TK, KM, SY, and TH drafted the main protocol. MN and TA participated in the statistical analysis. All authors participated in patient enrollment and clinical data acquisition. MN drafted and wrote the manuscript. All authors contributed to critical review and approved the final draft.

Corresponding author

Correspondence to Makoto Naganuma.

Ethics declarations

Conflict of interest

Makoto Naganuma received grants from Mitsubishi Tanabe Pharma Corporation, AbbVie GK, Kyorin Pharmaceutical Co., Ltd., and lecture fees from Tanabe Pharma Corporation, AbbVie GK, Kyorin Pharmaceutical Co., Ltd. Kissei Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., JIMRO Co., Ltd., Janssen Pharmaceutical K.K., Pfizer Japan Inc., EA Pharma Co., Ltd., Miyarisan Pharmaceutical Co., Ltd., and Mochida Pharmaceutical Co., Ltd., Corporation, AbbVie GK outside the submitted work. Taku Kobayashi received lecture fees from Takeda Pharmaceutical Co. Ltd. Activaid, Alfresa Pharma Corporation, Zeria Pharmaceutical Co., Ltd., Kyorin Pharmaceutical Co., Ltd., Nippon Kayaku Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Abbie GK, Pfizer Japan Inc., Janssen Pharmaceutical K.K., Thermo Fisher Diagnostics K.K., and JIMRO Co., Ltd., and received research grants from Abbvie GK, Activaid, Alfresa Pharma Corporation, JMDC Inc., Gilead Sciences, Inc., Nippon Kayaku Co., Ltd., Eli Lilly Japan K.K., Mochida Pharmaceutical Co., Ltd., Janssen Pharmaceutical K.K., Pfizer Japan Inc., Takeda Pharmaceutical Co., Ltd., Ferring Pharmaceuticals, and Bristol-Myers Squibb, and received scholarship contributions from Mitsubishi Tanabe Pharma Corporation, Zeria Pharmaceutical Co., Ltd., Nippon Kayaku Co., Ltd., and belonged to the study group sponsorship by Otsuka Holdings, Abbvie GK, EA Pharma Co., Ltd., Zeria Pharmaceutical Co., Ltd., JIMRO Co., Ltd., Kyorin Pharmaceutical Co., Ltd., and Mochida Pharmaceutical Co., Ltd. Advisory/consultancy fees were obtained from Janssen Pharmaceutical K.K., EA Pharma Co., Ltd., KISSEI Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Activaid, Pfizer Japan Inc., Nippon Kayaku Co., Ltd., Alfresa Pharma Corporation, Kyorin Pharmaceutical Co., Ltd., Abbie GK, Mochida Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Celltrion, Gilead Sciences, Inc., Ferring Pharmaceuticals, Eli Lilly Japan K.K., and Daiichi Sankyo Company outside the submitted work. Reiko Kunisaki received research grant and lecture fees from AbbVie, Astellas, EA Pharma, Janssen Pharmaceutical, Kyorin, Nippon Kayaku, Mitsubishi Tanabe, Takeda, Zeria, Janssen, Eli Lilly, and Pfizer outside the submitted work. Hisashi Shiga received lecture fees from Mitsubishi Tanabe Pharma Corp., AbbVie Inc., EA Pharma Co. Ltd., Janssen Pharmaceutical K.K., Takeda Pharmaceutical Co. Ltd., and Pfizer Inc outside the submitted work. Shingo Kato received lecture fees from Mitsubishi Tanabe Pharma Corporation, AbbVie GK, Takeda Pharmaceutical Co., Ltd., Janssen Pharmaceutical K.K outside the submitted work. Motohiro Esaki received research grants from Mitsubishi Tanabe Pharma Corporation, EA Pharma Co., Ltd., AbbVie GK, Kyorin Pharmaceutical Co., Ltd., and Alfresa Pharma Corporation, and lecture fee from Mitsubishi Tanabe Pharma Corporation, Janssen Pharmaceutical K.K., Takeda Pharmaceutical Co., Ltd., AbbVie GK, Pfizer Japan Inc. and EA Pharma Co., Ltd. outside the submitted work. Masayuki Saruta received grants from EPS Corporation and scholarship grants form Mochida Pharmaceutical Co., Ltd., and EA Pharma Co., Ltd. and lecture fees from Abbvie GK, EA Pharma Co., Ltd., Janssen Pharmaceutical, GK, Mochida Pharmaceutical Co., Ltd, Takeda Pharmaceutical Co., EA Pharma Co., Ltd outside the submitted work. Kaoru Yokoyama received lecture fees from Takeda Pharmaceutical Co., Ltd. and Mochida Pharmaceutical Co., Ltd outside the submitted work. Yoshikazu Tsuzuki received grants from AbbVie GK and Mitsubishi Tanabe Pharma Corporation, and lecture fee from AbbVie GK, EA Pharma Co., Ltd., Kyorin Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Janssen Pharmaceutical K.K., Mochida Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., and Pfizer Japan Inc. outside the submitted work. Mikihiro Fujiya reports grants, personal fees from EA Pharma Co., Ltd., grants, personal fees from Ayumi Pharmaceutical Corporation, grants, personal fees from AbbVie Inc, grants, personal fees from Otsuka Pharmaceutical Co., Ltd., grants, personal fees from Zeria Pharmaceutical Co., Ltd., grants, personal fees from Nippon Kayaku Co., Ltd., grants, personal fees from Nobelpharma Co., Ltd., grants, personal fees from Pfizer Inc, grants, personal fees from Janssen Pharmaceutical K.K., grants, personal fees from Kyorin Pharmaceutical Co., Ltd., grants, personal fees from Mochida Pharmaceutical Co., Ltd, grants, personal fees from Daiichi Sankyo Company, Limited, grants, personal fees from Mitsubishi Tanabe Pharma Corporation, grants, personal fees from Takeda Pharmaceutical Company Limited, grants, personal fees from Yakult Honsha Co., Ltd., personal fees from OLYNPUS Co., Ltd., personal fees from celltrionhealthcare.jp, personal fees from Alfresa Pharma Corporation, personal fees from Mylan Inc., personal fees from Boston Scientific Corporation, personal fees from Covidien Japan, Inc., personal fees and non-financial support from FUJIFILM Corporation, grants from Fuji Chemical Industries Co., Ltd., grants from JIMRO Co., Ltd., and grants from Kamui Pharma. Inc. Tadakazu Hisamatsu has performed joint research with Alfresa Pharma Co., Ltd. and EA Pharma Co., Ltd.; received grant support from Mitsubishi Tanabe Pharma Corporation, EA Pharma Co., Ltd., AbbVie GK, JIMRO Co., Ltd., Zeria Pharmaceutical Co., Ltd., Daiichi-Sankyo, Kyorin Pharmaceutical Co., Ltd., Nippon Kayaku Co., Ltd., Takeda Pharmaceutical Co., Ltd., Pfizer Inc., and Mochida Pharmaceutical Co., Ltd.; and received consulting and lecture fees from Mitsubishi Tanabe Pharma Corporation, AbbVie GK, Celgene K.K., EA Pharma Co., Ltd., Kyorin Pharmaceutical Co. Ltd., JIMRO Co., Janssen Pharmaceutical K.K., Mochida Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., KISSEI pharmaceutical Co., LTD., Ltd., Eli Lilly & Co., Gilead Sciences, Inc., and Pfizer Inc outside the submitted work.

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We would also like to thank Editage (www.editage.jp) for English language editing.

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The members of the Japanese UC Study Group are mentioned in the Acknowledgements section.

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Naganuma, M., Kobayashi, T., Kunisaki, R. et al. Real-world efficacy and safety of advanced therapies in hospitalized patients with ulcerative colitis. J Gastroenterol 58, 1198–1210 (2023). https://doi.org/10.1007/s00535-023-02048-w

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