1Department of Internal Medicine, Incheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Incheon, Korea
2Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea
3Department of Internal Medicine, Ewha Womans University School of Medicine, Seoul, Korea
4Department of Internal Medicine, Dankook University College of Medicine, Cheonan, Korea
5Department of Gastroenterology and Inflammatory Bowel Disease Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
6Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Korea
7Department of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
8Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
9Department of Gastroenterology, College of Medicine, Kyung Hee University, Seoul, Korea
10Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
11Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
12Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
13National Evidence-based Healthcare Collaborating Agency, Seoul, Korea
© Copyright 2023. Korean Association for the Study of Intestinal Diseases.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Funding Source
The authors received no financial support for the research, authorship, and/or publication of this article.
Conflict of Interest
Keum B is an editorial board member of the journal but was not involved in the peer reviewer selection, evaluation, or decision process of this article. No other potential conflicts of interest relevant to this article were reported.
Data Availability Statement
Not applicable.
Author Contribution
Conceptualization: Na SY, Choi CH, Kim JS. Data curation: Na SY, Choi CH, Song EM, Bang KB, Park SH, Kim ES, Park JJ, Keum B, Lee CK, Lee BI, Ryoo SB. Formal analysis: Choi M. Investigation: Choi CH. Methodology: Choi M. Project administration: Na SY, Choi CH, Kim JS. Supervision: Choi CH, Kim JS. Validation: Choi CH, Bang KB, Park SH, Kim ES, Park JJ, Keum B, Lee CK, Lee BI, Ryoo SB. Writing - original draft: Na SY, Song EM, Bang KB, Park SH, Kim ES, Park JJ, Keum B, Lee CK, Lee BI, Ryoo SB, Koh SJ, Choi M. Writing - review & editing: all authors. Approval of final manuscript: all authors.
Non-Author Contribution
The draft was reviewed and approved by the external advisory committee: Kang-Moon Lee (St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea), Won Moon (Kosin University College of Medicine), Geom Seog Seo (Wonkwang University School of Medicine), Jong Pil Im (Seoul National University College of Medicine), Sang-Bum Kang (Daejeon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea).
No. | Committee | Year | Title | Country | Publication |
---|---|---|---|---|---|
1 | American Gastroenterological Association [19] | 2020 | AGA clinical practice guidelines on the management of moderate to severe ulcerative colitis | USA | Gastroenterology |
2 | American College of Gastroenterology [20] | 2019 | ACG clinical guideline: ulcerative colitis in adults | USA | American Journal of Gastroenterology |
3 | British Society of Gastroenterology [21] | 2019 | British Society of Gastroenterology consensus guidelines on the management of inflammatory bowel disease in adults | UK | Gut |
4 | National Institute for Health and Care Excellence [22] | 2019 | Ulcerative colitis: management | UK | www.nice.org.uk/guidance |
5 | European Crohn’s and Colitis Organisation [23] | 20217 | Third European evidence-based consensus on diagnosis and management of ulcerative colitis. Part 2: current management | EU | Journal of Crohn’s and Colitis |
6 | Korean Association for the Study of Intestinal Diseases [16] | 2017 | Second Korean guidelines for the management of ulcerative colitis | Korea | Intestinal Research |
7 | Asia-Pacific Working Group on Inflammatory Bowel Disease [24] | 2019 | Best practices on immunomodulators and biologic agents for ulcerative colitis and Crohn's disease in Asia | Asia | Journal of Gastroenterology and Hepatology |
No. | Question | Population | Intervention | Comparator | Outcome |
---|---|---|---|---|---|
1 | In moderate-to-severe UC patients, what is the efficacy of infliximab, adalimumab, golimumab, vedolizumab, ustekinumab, and tofacitinib for induction of remission? | Moderate-to-severe UC patients | Biologics or small molecules | Placebo | Induction of remission |
2 | In moderate-to-severe UC patients who are in remission after induction with infliximab, adalimumab, golimumab, vedolizumab, ustekinumab, and tofacitinib, what is the efficacy of the same agent for maintenance of remission? | Moderate-to-severe UC patients | Biologics or small molecules | Placebo | Maintenance of remission |
3 | In moderate-to-severe UC patients treated with anti-TNF agents, what is the efficacy of drug monitoring to determine the therapeutic effect of anti-TNF agents for induction and maintenance of remission? | Moderate-to-severe UC patients | Drug monitoring | No drug monitoring | Induction and maintenance of remission |
4 | In moderate-to-severe UC patients who have lost their response to 1 anti-TNF agent, what is the efficacy of dose escalation? | Patients who have lost their response to 1 anti-TNF agent | Dose escalation | Standard dose | Maintenance of remission |
5 | In moderate-to-severe UC patients who have an inadequate response to 1 anti-TNF agent, what is the efficacy of switching to an alternative anti-TNF agent? | Patients who have an inadequate response to 1 anti-TNF agent | Switch to an alternative anti-TNF agent | No change | Induction of remission |
6 | In moderate-to-severe UC patients, is combination therapy with an anti-TNF agent and an immunomodulator superior to anti-TNF monotherapy? | Moderate-to-severe UC patients | Anti-TNF combination therapy | Anti-TNF monotherapy | Induction and maintenance of remission |
7 | In moderate-to-severe UC patients who have an inadequate response to anti-TNF agents, what is the efficacy of changing to vedolizumab for induction of remission? | Patients who have an inadequate response to anti-TNF agents | Vedolizumab | Placebo | Induction of remission |
8 | In moderate-to-severe UC patients, is combination therapy with vedolizumab and an immunomodulator superior to vedolizumab monotherapy? | Moderate-to-severe UC patients | Vedolizumab combination therapy | Vedolizumab monotherapy | Induction and maintenance of remission |
9 | In moderate-to-severe UC patients who have lost their response to vedolizumab, what is the efficacy of dose escalation? | Patients who have lost their response to vedolizumab | Dose escalation | Standard dose | Maintenance of remission |
10 | In moderate-to-severe UC patents who have an inadequate response to vedolizumab, what is the efficacy of changing to anti-TNF agents, ustekinumab, or tofacitinib? | Patients who have an inadequate response to vedolizumab | Change to a different class of therapy | No change | Induction of remission |
11 | In moderate-to-severe UC patients who have an inadequate response to anti-TNF agents, what is the efficacy of changing to ustekinumab for induction of remission? | Patients who have an inadequate response to anti-TNF agents | Ustekinumab | Placebo | Induction of remission |
12 | In moderate-to-severe UC patients, is combination therapy with ustekinumab and an immunomodulator superior to ustekinumab monotherapy? | Moderate-to-severe UC patients | Ustekinumab combination therapy | Ustekinumab monotherapy | Induction and maintenance of remission |
13 | In moderate-to-severe UC patients who have lost their response to ustekinumab, what is the efficacy of dose escalation? | Patients who have lost their response to ustekinumab | Dose escalation | Standard dose | Maintenance of remission |
14 | In moderate-to-severe UC patients who have an inadequate response to anti-TNF agents, what is the efficacy of changing to tofacitinib for induction of remission? | Patients who have an inadequate response to anti-TNF agents | Tofacitinib | Placebo | Induction of remission |
15 | In moderate-to-severe UC patients who have lost their response to tofacitinib, what is the efficacy of dose escalation? | Patients who have their lost response to tofacitinib | Dose escalation | Standard dose | Maintenance of remission |
16 | In moderate-to-severe UC patients, is the biosimilar equivalent to the originator in terms of efficacy and safety for induction and maintenance of remission? | Moderate-to-severe UC patients | Biosimilar | Originator | Induction and maintenance of remission |
17 | In moderate-to-severe UC patients, what is the efficacy of switching from the originator to the biosimilar after induction of remission? | Moderate-to-severe UC patients | Biosimilar | Originator | Maintenance of remission |
18 | In hospitalized patients with acute severe UC who are refractory to intravenous corticosteroids, what is the appropriate rescue therapy? | ASUC patients who are refractory to intravenous corticosteroids | Infliximab or ciclosporin | Placebo | Induction of remission |
19 | In moderate-to-severe UC patients, does preoperative use of anti-TNF agents increase postoperative complications? | Moderate-to-severe UC patients | Anti-TNF agents | No use of anti-TNF agents | Postoperative complications |
No. | Committee | Year | Title | Country | Publication |
---|---|---|---|---|---|
1 | American Gastroenterological Association [19] | 2020 | AGA clinical practice guidelines on the management of moderate to severe ulcerative colitis | USA | Gastroenterology |
2 | American College of Gastroenterology [20] | 2019 | ACG clinical guideline: ulcerative colitis in adults | USA | American Journal of Gastroenterology |
3 | British Society of Gastroenterology [21] | 2019 | British Society of Gastroenterology consensus guidelines on the management of inflammatory bowel disease in adults | UK | Gut |
4 | National Institute for Health and Care Excellence [22] | 2019 | Ulcerative colitis: management | UK | |
5 | European Crohn’s and Colitis Organisation [23] | 20217 | Third European evidence-based consensus on diagnosis and management of ulcerative colitis. Part 2: current management | EU | Journal of Crohn’s and Colitis |
6 | Korean Association for the Study of Intestinal Diseases [16] | 2017 | Second Korean guidelines for the management of ulcerative colitis | Korea | Intestinal Research |
7 | Asia-Pacific Working Group on Inflammatory Bowel Disease [24] | 2019 | Best practices on immunomodulators and biologic agents for ulcerative colitis and Crohn's disease in Asia | Asia | Journal of Gastroenterology and Hepatology |
Quality grade | Definition |
---|---|
High | We are very confident that the true effect is similar to the estimate of the effect. |
Moderate | We are moderately confident in the effect estimate. The true effect is likely to be similar to the estimate of the effect, but there is a possibility that it is substantially different. |
Low | Our confidence in the effect estimate is limited. The true effect may be substantially different from the estimate of the effect. |
Very low | We have very little confidence in the effect estimate. The true effect is likely to be substantially different from the estimate of the effect. |
Strength of recommendation | Wording in the statement | For clinicians |
---|---|---|
Strong | Recommend | Most patients should receive the recommended course of action |
Conditional | Suggest | Different choices are appropriate for different patients |
Mild | Moderate (between mild and severe) | Severe | |
---|---|---|---|
(1) Bloody stools per day | <4 | 4 or more if | ≥ 6 and |
(2) Pulse | < 90/min | ≤ 90/min | > 90/min or |
(3) Temperature | < 37.5°C | ≤ 37.8°C | > 37.8°C or |
(4) Hemoglobin level | > 11.5 g/dL | ≥ 10.5 g/dL | < 10.5 g/dL or |
(5) ESR | < 20 mm/hr | ≤ 30 mm/hr | > 30 mm/hr or |
(6) CRP level | Normal | ≤ 30 mg/L | > 30 mg/L |
Variable | Definition | Score |
---|---|---|
Stool frequency | Normal number of stools for the patient | 0 |
1–2 stools more than normal | 1 | |
3–4 stools more than normal | 2 | |
5 or more stools more than normal | 3 | |
Rectal bleeding | No blood seen | 0 |
Streaks of blood with stools less than half the time | 1 | |
Obvious blood with stools most of the time | 2 | |
Blood alone passes | 3 | |
Findings on endoscopy | Normal or inactive disease | 0 |
Mild disease (erythema, decreased vascular pattern, mild friability) | 1 | |
Moderate disease (marked erythema, lack of vascular pattern, friability, erosions) | 2 | |
Severe disease (spontaneous bleeding, ulceration) | 3 | |
Physician’s global assessment | Normal | 0 |
Mild disease | 1 | |
Moderate disease | 2 | |
Severe disease | 3 |
No. | Statement | Quality of evidence | Recommendation |
---|---|---|---|
1 | We recommend infliximab, adalimumab, golimumab, vedolizumab, ustekinumab, or tofacitinib for induction of remission in patients with moderate-to-severe UC who are refractory to or intolerant of conventional treatments. | High | Strong for |
2 | In patients with moderate-to-severe UC who achieve a clinical response or remission with infliximab, adalimumab, golimumab, vedolizumab, ustekinumab, or tofacitinib, we recommend continuing the same agent to maintain the response or remission. | High | Strong for |
3 | We suggest therapeutic drug monitoring to optimize treatment in patients with moderate-to-severe UC who have lost their response to anti-TNF agents. | Very low | Conditional for |
4 | We recommend infliximab in combination with thiopurines for induction of remission in patients with moderate-to-severe UC over infliximab monotherapy. | Moderate | Strong for |
5 | We recommend vedolizumab for induction of remission in patients with moderate-to-severe UC who have an inadequate response to anti-TNF agents. | Moderate | Strong for |
6 | We recommend ustekinumab for induction of remission in patients with moderate-to-severe UC who have an inadequate response to anti-TNF agents. | Moderate | Strong for |
7 | We recommend tofacitinib for induction of remission in patients with moderate-to-severe UC who have an inadequate response to anti-TNF agents. | Moderate | Strong for |
8 | We recommend that currently approved anti-TNF biosimilars can be used for induction and maintenance of remission in patients with moderate-to-severe UC. | Low | Strong for |
9 | We recommend that patients with UC receiving originator anti-TNF agents can be switched to currently approved anti-TNF biosimilars if they are stable. | Moderate | Strong for |
10 | We recommend infliximab or cyclosporine as a rescue therapy in patients with acute severe UC who are refractory to intravenous corticosteroids. | Moderate | Strong for |
11 | We suggest that discontinuation of anti-TNF agents is not mandatory prior to surgery in patients with moderate-to-severe UC. | Low | Conditional against |
PICO, population, intervention, comparator, patient-important outcomes; UC, ulcerative colitis; TNF, tumor necrosis factor; ASUC, acute severe UC.
K-AGREE II, Korean Appraisal of Guidelines for Research and Evaluation II.
ESR, erythrocyte sedimentation rate; CRP, C-reactive protein.
Score: 3-5, mild disease activity; 6-10, moderate disease activity; 11-12, severe disease activity.
UC, ulcerative colitis; TNF, tumor necrosis factor.