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Original Article
IBD Histologic healing and clinical outcomes in ulcerative colitis -
Raymond Fueng-Hin Liang1
, Huiyu Lin1, Cora Yuk-Ping Chau2, Wee Chian Lim1 -
Intestinal Research 2025;23(2):182-192.
DOI: https://doi.org/10.5217/ir.2024.00058
Published online: September 19, 2024
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Correspondence to Raymond Fueng-Hin Liang, Department of Gastroenterology and Hepatology, Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng, Singapore 308433. E-mail: raymond_fh_liang@ttsh.com.sg
• Received: April 21, 2024 • Revised: June 30, 2024 • Accepted: July 22, 2024
© 2025 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.
Abstract
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Background/Aims
- Growing evidence suggests histologic healing (HH) improves clinical outcomes in ulcerative colitis (UC) patients beyond endoscopic healing (EH). We hypothesize that HH is associated with better clinical outcomes in Asian UC patients, for whom data is lacking.
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Methods
- We performed a retrospective study of UC patients in clinical remission (CR) with a follow-up colonoscopy and minimum 1-year follow-up post-colonoscopy. Primary outcome was clinical relapse (CRL), defined as either a Simple Clinical Colitis Activity Index score of > 2, medication escalation, hospitalization or colectomy. Predictors of CRL and HH were assessed.
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Results
- One hundred patients were included with a median follow-up of 22 months. At index colonoscopy, 80 patients were in EH. On follow-up, 41 patients experienced CRL. Of 80 patients in EH, 34 (42.5%) had persistent histologic activity (Nancy Index ≥ 2) and 29 (36.3%) relapsed during the follow-up period. Amongst patients in CR and EH, those with HH had lower CRL rate (26.1% vs. 50.0%, P=0.028) and longer CRL-free survival (mean 46.1 months vs. 31.5 months, P=0.015) than those with persistent histologic activity. On bivariable analysis of 100 patients in CR, HH, and Mayo endoscopic score (MES) of 0 were significantly associated with lower risk of CRL. On multivariable analysis, only MES 0 remained predictive of lower CRL risk.
-
Conclusions
- Above and beyond CR and EH, achieving HH improves clinical outcomes in Asian UC patients. However, HH may not confer incremental benefit if MES 0 has been achieved. Further prospective studies evaluating the benefit of histologically guided therapeutic decisions are needed.
INTRODUCTION
METHODS
RESULTS
DISCUSSION
-
Funding Source
This work was supported by Ferring Pharmaceuticals.
-
Conflict of Interest
This work was supported by Ferring Pharmaceuticals. Except for that, no potential conflict of interest relevant to this article was reported.
-
Data Availability Statement
All study-related data is included in the publication or provided as supplementary information.
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Author Contributions
Conceptualization: Liang RFH, Lim WC. Data curation: Liang RFH, Lin H. Formal analysis: Liang RFH. Investigation: Liang RFH, Lin H, Chau CYP, Lim WC. Methodology: Liang RFH, Lim WC. Project administration: Liang RFH, Lin H, Lim WC. Supervision: Lim WC. Writing - original draft: Liang RFH, Lin H. Writing - review & editing: Liang RFH, Lin H, Chau CYP, Lim WC. Approval of final manuscript: all authors.
NOTES
Fig. 1.Kaplan-Meier analysis of the effect of endoscopic healing on clinical relapse-free survival in patients with clinical remission.
Fig. 2.Kaplan-Meier analysis of the effect of histologic healing on clinical relapse-free survival in patients with clinical and endoscopic healing.
Fig. 3.Kaplan-Meier analysis of the effect of Mayo endoscopic score (MES) 0 versus MES 1 on clinical relapse-free survival in patients with clinical remission and endoscopic healing.
Fig. 4.Kaplan-Meier analysis of the effect of histologic healing on clinical relapse-free survival in patients with clinical remission and Mayo endoscopic score 0.
Table 1.Patient Characteristics at Index Colonoscopy
| Variable | All patients (n = 100) | HH (n = 46) | No HH (n = 54) | P-value |
|---|---|---|---|---|
| Age (yr) | 56 (44–64) | 53.9 ± 13.3 | 54.0 ± 13.8 | 0.957 |
| Disease duration (mo) | 107.0 (50.0–176.0) | 101.7 (55.7–210.3) | 111.7 (46.5–163.4) | 0.527 |
| BMI (kg/m2) | 24.2 (22.0–26.7) | 24.9 (22.3–27.2) | 23.9 (21.9–25.6) | 0.181 |
| CRP (mg/L) | 1.1 (0.6–3.0) | 0.9 (0.6–2.5) | 1.5 (0.6–4.0) | 0.352 |
| Stool calprotectin (µg/g) | 104 (40–256) | 44 (30–104) | 183 (101–388) | < 0.001a |
| Sex | 0.150 | |||
| Female | 38 (38) | 14 (30.4) | 24 (44.4) | |
| Male | 62 (62) | 32 (69.6) | 30 (55.6) | |
| Ethnicity | 0.529 | |||
| Chinese | 71 (71) | 34 (73.9) | 37 (68.5) | |
| Malay | 10 (10) | 3 (6.5) | 7 (13.0) | |
| Indian | 15 (15) | 8 (17.4) | 7 (13.0) | |
| Others | 4 (4) | 1 (2.2) | 3 (5.6) | |
| Smoking status | 0.828 | |||
| Never | 70 (70) | 35 (76.1) | 35 (64.8) | |
| Smoker | 4 (4) | 2 (4.3) | 2 (3.7) | |
| Ex-smoker | 19 (19) | 8 (17.4) | 11 (20.4) | |
| Endoscopic extent | < 0.001a | |||
| Normal | 25 (25) | 18 (39.1) | 7 (13.0) | |
| Proctitis | 37 (37) | 20 (43.5) | 17 (31.5) | |
| Left-sided | 16 (16) | 3 (6.5) | 13 (24.1) | |
| Extensive | 22 (22) | 5 (10.9) | 17 (31.5) | |
| Histologic extent | ||||
| Normal | 19 (19) | 19 (41.3) | - | |
| Proctitis | 31 (31) | 17 (37.0) | 14 (25.9) | |
| Left-sided | 17 (17) | 4 (8.7) | 13 (24.1) | |
| Extensive | 33 (33) | 6 (13.0) | 27 (50.0) | |
| Mayo endoscopic score | < 0.001a | |||
| 0 | 43 (43) | 33 (71.7) | 10 (18.5) | |
| 1 | 37 (37) | 13 (28.3) | 24 (44.4) | |
| 2 | 14 (14) | 0 | 14 (25.9) | |
| 3 | 6 (6) | 0 | 6 (11.1) | |
| Nancy Index | ||||
| 0 | 30 (30) | 30 (65.2) | - | |
| 1 | 16 (16) | 16 (34.8) | - | |
| 2 | 30 (30) | - | 30 (55.6) | |
| 3 | 12 (12) | - | 12 (22.2) | |
| 4 | 12 (12) | - | 12 (22.2) | |
| Medications | ||||
| Steroids | 37 (37) | 17 (37.0) | 20 (37.0) | 0.993 |
| 5-ASA | 98 (98) | 45 (97.8) | 53 (98.1) | 0.909 |
| Immunomodulators | 31 (31) | 12 (26.1) | 19 (35.2) | 0.327 |
| Biologics | 3 (3) | 1 (2.2) | 2 (3.7) | 1.000b |
Table 2.CRL Rates at 2-Year Follow-up for Patients with Endoscopic Healing at Index Colonoscopy
| CRL | No CRL | P-value | |
|---|---|---|---|
| MES 0 (n = 43) | 9 (20.9) | 34 (79.1) | 0.002a |
| HH (n = 10) | 1 (10.0) | 9 (90.0) | 0.330 |
| No HH (n = 33) | 8 (24.2) | 25 (75.8) | |
| MES 1 (n = 37) | 20 (54.1) | 17 (45.9) |
Table 3.Cox Regression Analysis of Clinical Variables Associated with Time to Clinical Relapse
| Variable |
Bivariable regression |
Multivariable regression |
||
|---|---|---|---|---|
| HR (95% CI) | P-value | HR (95% CI) | P-value | |
| Agea | 0.99 (0.97–1.01) | 0.436 | ||
| Disease duration | 1.00 (0.96–1.00) | 0.310 | ||
| Duration of clinical remission | 1.04 (1.00–1.09) | 0.034e | 1.05 (0.95–1.16) | 0.336 |
| BMI | 0.95 (0.88–1.02) | 0.168 | ||
| CRP | 1.05 (1.01–1.10) | 0.030e | 1.04 (0.99–1.09) | 0.108 |
| Stool calprotectin | 1.00 (1.00–1.00) | 0.049e | ||
| Sexb | 0.93 (0.49–1.77) | 0.834 | ||
| Current smokerc | 0.55 (0.08–4.03) | 0.557 | ||
| Endoscopic extentd | 1.53 (0.82–2.87) | 0.186 | ||
| EH | 0.28 (0.14–0.56) | < 0.001e | ||
| MES 0 | 0.25 (0.12–0.52) | < 0.001e | 0.37 (0.15–0.94) | 0.037e |
| HH | 0.34 (0.17–0.67) | 0.002e | 0.59 (0.26–1.35) | 0.209 |
| Baseline medications | ||||
| Steroids | 0.71 (0.36–1.39) | 0.313 | ||
| 5-ASA | 0.90 (0.12–6.60) | 0.920 | ||
| Immunomodulators | 0.65 (0.31–1.36) | 0.247 | ||
| Biologics | 2.50 (0.60–10.42) | 0.210 | ||
a HR given per each year increase in age.
b HR for male sex, with female sex as comparator.
c HR for current smoking, with ex-smoking or non-smoking status as comparator.
d HR for left-sided or extensive disease, with proctitis or normal colon as comparator.
e Statistically significant.
HR, hazard ratio; CI, confidence interval; BMI, body mass index; CRP, C-reactive protein; EH, endoscopic healing; MES, Mayo endoscopic score; HH, histologic healing; 5-ASA, 5-aminosalicylic acid.
Table 4.Logistic Regression Analysis of Clinical Variables Associated with Histologic Healing
| Variable |
Bivariable regression |
Multivariable regression |
||
|---|---|---|---|---|
| HR (95% CI) | P-value | HR (95% CI) | P-value | |
| Agea | 1.00 (0.97–1.03) | 0.956 | ||
| Disease duration | 1.00 (1.00–1.01) | 0.373 | ||
| Duration of clinical remission | 1.01 (0.95–1.09) | 0.701 | ||
| BMI | 1.05 (0.95–1.15) | 0.355 | ||
| CRP | 0.94 (0.84–1.06) | 0.294 | ||
| Stool calprotectin | 0.99 (0.99–1.00) | 0.004e | 0.99 (0.99–1.00) | 0.014e |
| Sexb | 0.55 (0.24–1.25) | 0.152 | ||
| Current smokerc | 1.07 (0.14–7.93) | 0.947 | ||
| Endoscopic extentd | 0.17 (0.07–0.43) | < 0.001e | 0.40 (0.10–1.53) | 0.180 |
| MES 0 | 11.17 (4.36–28.59) | < 0.001e | 19.12 (4.08–89.68) | < 0.001e |
| Medications | ||||
| Steroids | 1.00 (0.44–2.25) | 0.993 | ||
| 5-ASA | 0.85 (0.05–13.96) | 0.909 | ||
| Immunomodulators | 0.65 (0.27–1.54) | 0.328 | ||
| Biologics | 0.58 (0.05–6.59) | 0.659 | ||
a OR given per each year increase in age.
b OR for male sex, with female sex as comparator.
c OR for current smoking, with ex-smoking or non-smoking status as comparator.
d OR for left-sided or extensive disease, with proctitis or normal colon as comparator.
e Statistically significant.
OR, odds ratio; CI, confidence interval; BMI, body mass index; CRP, C-reactive protein; MES, Mayo endoscopic score; 5-ASA, 5-aminosalicylic acid.
- 1. Rubin DT, Ananthakrishnan AN, Siegel CA, Sauer BG, Long MD. ACG clinical guideline: ulcerative colitis in adults. Am J Gastroenterol 2019;114:384–413.ArticlePubMed
- 2. 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–s106.ArticlePubMedPMC
- 3. Bessissow T, Lemmens B, Ferrante M, et al. Prognostic value of serologic and histologic markers on clinical relapse in ulcerative colitis patients with mucosal healing. Am J Gastroenterol 2012;107:1684–1692.ArticlePubMedPDF
- 4. Flores BM, O’Connor A, Moss AC. Impact of mucosal inflammation on risk of colorectal neoplasia in patients with ulcerative colitis: a systematic review and meta-analysis. Gastrointest Endosc 2017;86:1006–1011.ArticlePubMed
- 5. Kirchgesner J, Svrcek M, Le Gall G, et al. Nancy Index scores of chronic inflammatory bowel disease activity associate with development of colorectal neoplasia. Clin Gastroenterol Hepatol 2020;18:150–157.ArticlePubMed
- 6. Bryant RV, Burger DC, Delo J, et al. Beyond endoscopic mucosal healing in UC: histological remission better predicts corticosteroid use and hospitalisation over 6 years of follow-up. Gut 2016;65:408–414.ArticlePubMed
- 7. Shehab M, Al Akram S, Hassan A, Alrashed F, Jairath V, Bessissow T. Histological disease activity as predictor of clinical relapse, hospitalization, and surgery in inflammatory bowel disease: systematic review and meta-analysis. Inflamm Bowel Dis 2024;30:563–572.ArticlePubMedPDF
- 8. Mosli MH, Parker CE, Nelson SA, et al. Histologic scoring indices for evaluation of disease activity in ulcerative colitis. Cochrane Database Syst Rev 2017;5–CD011256.Article
- 9. Schroeder KW, Tremaine WJ, Ilstrup DM. Coated oral 5-aminosalicylic acid therapy for mildly to moderately active ulcerative colitis: a randomized study. N Engl J Med 1987;317:1625–1629.ArticlePubMed
- 10. Marchal-Bressenot A, Salleron J, Boulagnon-Rombi C, et al. Development and validation of the Nancy histological index for UC. Gut 2017;66:43–49.ArticlePubMed
- 11. Silverberg MS, Satsangi J, Ahmad T, et al. Toward an integrated clinical, molecular and serological classification of inflammatory bowel disease: report of a Working Party of the 2005 Montreal World Congress of Gastroenterology. Can J Gastroenterol 2005;19 Suppl A:5A–36A.ArticlePubMedPDF
- 12. Narula N, Alshahrani AA, Yuan Y, Reinisch W, Colombel JF. Patient-reported outcomes and endoscopic appearance of ulcerative colitis: a systematic review and meta-analysis. Clin Gastroenterol Hepatol 2019;17:411–418.ArticlePubMed
- 13. Restellini S, Chao CY, Martel M, et al. Clinical parameters correlate with endoscopic activity of ulcerative colitis: a systematic review. Clin Gastroenterol Hepatol 2019;17:1265–1275.ArticlePubMed
- 14. Baars JE, Nuij VJ, Oldenburg B, Kuipers EJ, van der Woude CJ. Majority of patients with inflammatory bowel disease in clinical remission have mucosal inflammation. Inflamm Bowel Dis 2012;18:1634–1640.ArticlePubMed
- 15. Rosenberg L, Nanda KS, Zenlea T, et al. Histologic markers of inflammation in patients with ulcerative colitis in clinical remission. Clin Gastroenterol Hepatol 2013;11:991–996.ArticlePubMedPMC
- 16. Shah SC, Colombel JF, Sands BE, Narula N. Mucosal healing is associated with improved long-term outcomes of patients with ulcerative colitis: a systematic review and meta-analysis. Clin Gastroenterol Hepatol 2016;14:1245–1255.ArticlePubMed
- 17. Park S, Abdi T, Gentry M, Laine L. Histological disease activity as a predictor of clinical relapse among patients with ulcerative colitis: systematic review and meta-analysis. Am J Gastroenterol 2016;111:1692–1701.ArticlePubMedPDF
- 18. Yoon H, Jangi S, Dulai PS, et al. Incremental benefit of achieving endoscopic and histologic remission in patients with ulcerative colitis: a systematic review and meta-analysis. Gastroenterology 2020;159:1262–1275.ArticlePubMedPMC
- 19. Gupta A, Yu A, Peyrin-Biroulet L, Ananthakrishnan AN. Treat to target: the role of histologic healing in inflammatory bowel diseases: a systematic review and meta-analysis. Clin Gastroenterol Hepatol 2021;19:1800–1813.ArticlePubMed
- 20. Battat R, Duijvestein M, Guizzetti L, et al. Histologic healing rates of medical therapies for ulcerative colitis: a systematic review and meta-analysis of randomized controlled trials. Am J Gastroenterol 2019;114:733–745.ArticlePubMed
- 21. Sands BE, Sandborn WJ, Panaccione R, et al. Ustekinumab as induction and maintenance therapy for ulcerative colitis. N Engl J Med 2019;381:1201–1214.ArticlePubMed
- 22. Feagan BG, Danese S, Loftus EV, et al. Filgotinib as induction and maintenance therapy for ulcerative colitis (SELECTION): a phase 2b/3 double-blind, randomised, placebo-controlled trial. Lancet 2021;397:2372–2384.ArticlePubMed
- 23. Sandborn WJ, Feagan BG, D’Haens G, et al. Ozanimod as induction and maintenance therapy for ulcerative colitis. N Engl J Med 2021;385:1280–1291.ArticlePubMed
- 24. 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, multicentre, double-blind, randomised trials. Lancet 2022;399:2113–2128.ArticlePubMed
- 25. Sandborn WJ, Vermeire S, Peyrin-Biroulet L, et al. Etrasimod as induction and maintenance therapy for ulcerative colitis (ELEVATE): two randomised, double-blind, placebo-controlled, phase 3 studies. Lancet 2023;401:1159–1171.ArticlePubMed
- 26. D’Haens G, Dubinsky M, Kobayashi T, et al. Mirikizumab as induction and maintenance therapy for ulcerative colitis. N Engl J Med 2023;388:2444–2455.ArticlePubMed
- 27. Feagan BG, Sands BE, Sandborn WJ, et al. Guselkumab plus golimumab combination therapy versus guselkumab or golimumab monotherapy in patients with ulcerative colitis (VEGA): a randomised, double-blind, controlled, phase 2, proof-of-concept trial. Lancet Gastroenterol Hepatol 2023;8:307–320.ArticlePubMed
- 28. Li K, Marano C, Zhang H, et al. Relationship between combined histologic and endoscopic endpoints and efficacy of ustekinumab treatment in patients with ulcerative colitis. Gastroenterology 2020;159:2052–2064.ArticlePubMed
- 29. Viscido A, Valvano M, Stefanelli G, et al. Systematic review and meta-analysis: the advantage of endoscopic Mayo score 0 over 1 in patients with ulcerative colitis. BMC Gastroenterol 2022;22:92.ArticlePubMedPMCPDF
- 30. Turner D, Ricciuto A, Lewis A, et al. STRIDE-II: an update on the selecting therapeutic targets in inflammatory bowel disease (STRIDE) initiative of the international organization for the study of IBD (IOIBD). Determining therapeutic goals for treat-to-target strategies in IBD. Gastroenterology 2021;160:1570–1583.ArticlePubMed
- 31. Jauregui-Amezaga A, López-Cerón M, Aceituno M, et al. Accuracy of advanced endoscopy and fecal calprotectin for prediction of relapse in ulcerative colitis: a prospective study. Inflamm Bowel Dis 2014;20:1187–1193.PubMed
- 32. Jangi S, Yoon H, Dulai PS, et al. Predictors and outcomes of histological remission in ulcerative colitis treated to endoscopic healing. Aliment Pharmacol Ther 2020;52:1008–1016.ArticlePubMedPMCPDF
- 33. Osada T, Ohkusa T, Yokoyama T, et al. Comparison of several activity indices for the evaluation of endoscopic activity in UC: inter- and intraobserver consistency. Inflamm Bowel Dis 2010;16:192–197.ArticlePubMed
- 34. Leung CM, Tang W, Kyaw M, et al. Endoscopic and histological mucosal healing in ulcerative colitis in the first year of diagnosis: results from a population-based inception cohort from six countries in Asia. J Crohns Colitis 2017;11:1440–1448.ArticlePubMed
- 35. Narang V, Kaur R, Garg B, et al. Association of endoscopic and histological remission with clinical course in patients of ulcerative colitis. Intest Res 2018;16:55–61.ArticlePubMedPMCPDF
- 36. Kanazawa M, Takahashi F, Tominaga K, et al. Relationship between endoscopic mucosal healing and histologic inflammation during remission maintenance phase in ulcerative colitis: a retrospective study. Endosc Int Open 2019;7:E568–E575.ArticlePubMedPMC
- 37. Park J, Kang SJ, Yoon H, et al. Histologic evaluation using the robarts histopathology index in patients with ulcerative colitis in deep remission and the association of histologic remission with risk of relapse. Inflamm Bowel Dis 2022;28:1709–1716.ArticlePubMedPDF
- 38. Seong G, Song JH, Kim JE, et al. Histologic activity and steroid use history are risk factors of clinical relapse in ulcerative colitis with mayo endoscopic subscore of 0 or 1. Inflamm Bowel Dis 2023;29:238–244.ArticlePubMedPDF
- 39. Theede K, Holck S, Ibsen P, Ladelund S, Nordgaard-Lassen I, Nielsen AM. Level of fecal calprotectin correlates with endoscopic and histologic inflammation and identifies patients with mucosal healing in ulcerative colitis. Clin Gastroenterol Hepatol 2015;13:1929–1936.ArticlePubMed
- 40. Magro F, Lopes SI, Lopes J, et al. Histological outcomes and predictive value of faecal markers in moderately to severely active ulcerative colitis patients receiving infliximab. J Crohns Colitis 2016;10:1407–1416.ArticlePubMed
- 41. Jairath V, Zou G, Wang Z, et al. P588 Interim results from the randomised VERDICT trial to determine the optimal treatment target in patients with ulcerative colitis. J Crohns Colitis 2023;17(Suppl 1): i716–i717.ArticlePDF
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Histologic healing and clinical outcomes in ulcerative colitis
Fig. 1. Kaplan-Meier analysis of the effect of endoscopic healing on clinical relapse-free survival in patients with clinical remission.
Fig. 2. Kaplan-Meier analysis of the effect of histologic healing on clinical relapse-free survival in patients with clinical and endoscopic healing.
Fig. 3. Kaplan-Meier analysis of the effect of Mayo endoscopic score (MES) 0 versus MES 1 on clinical relapse-free survival in patients with clinical remission and endoscopic healing.
Fig. 4. Kaplan-Meier analysis of the effect of histologic healing on clinical relapse-free survival in patients with clinical remission and Mayo endoscopic score 0.
Fig. 1.
Fig. 2.
Fig. 3.
Fig. 4.
Histologic healing and clinical outcomes in ulcerative colitis
| Variable | All patients (n = 100) | HH (n = 46) | No HH (n = 54) | P-value |
|---|---|---|---|---|
| Age (yr) | 56 (44–64) | 53.9 ± 13.3 | 54.0 ± 13.8 | 0.957 |
| Disease duration (mo) | 107.0 (50.0–176.0) | 101.7 (55.7–210.3) | 111.7 (46.5–163.4) | 0.527 |
| BMI (kg/m2) | 24.2 (22.0–26.7) | 24.9 (22.3–27.2) | 23.9 (21.9–25.6) | 0.181 |
| CRP (mg/L) | 1.1 (0.6–3.0) | 0.9 (0.6–2.5) | 1.5 (0.6–4.0) | 0.352 |
| Stool calprotectin (µg/g) | 104 (40–256) | 44 (30–104) | 183 (101–388) | < 0.001 |
| Sex | 0.150 | |||
| Female | 38 (38) | 14 (30.4) | 24 (44.4) | |
| Male | 62 (62) | 32 (69.6) | 30 (55.6) | |
| Ethnicity | 0.529 | |||
| Chinese | 71 (71) | 34 (73.9) | 37 (68.5) | |
| Malay | 10 (10) | 3 (6.5) | 7 (13.0) | |
| Indian | 15 (15) | 8 (17.4) | 7 (13.0) | |
| Others | 4 (4) | 1 (2.2) | 3 (5.6) | |
| Smoking status | 0.828 | |||
| Never | 70 (70) | 35 (76.1) | 35 (64.8) | |
| Smoker | 4 (4) | 2 (4.3) | 2 (3.7) | |
| Ex-smoker | 19 (19) | 8 (17.4) | 11 (20.4) | |
| Endoscopic extent | < 0.001 |
|||
| Normal | 25 (25) | 18 (39.1) | 7 (13.0) | |
| Proctitis | 37 (37) | 20 (43.5) | 17 (31.5) | |
| Left-sided | 16 (16) | 3 (6.5) | 13 (24.1) | |
| Extensive | 22 (22) | 5 (10.9) | 17 (31.5) | |
| Histologic extent | ||||
| Normal | 19 (19) | 19 (41.3) | - | |
| Proctitis | 31 (31) | 17 (37.0) | 14 (25.9) | |
| Left-sided | 17 (17) | 4 (8.7) | 13 (24.1) | |
| Extensive | 33 (33) | 6 (13.0) | 27 (50.0) | |
| Mayo endoscopic score | < 0.001 |
|||
| 0 | 43 (43) | 33 (71.7) | 10 (18.5) | |
| 1 | 37 (37) | 13 (28.3) | 24 (44.4) | |
| 2 | 14 (14) | 0 | 14 (25.9) | |
| 3 | 6 (6) | 0 | 6 (11.1) | |
| Nancy Index | ||||
| 0 | 30 (30) | 30 (65.2) | - | |
| 1 | 16 (16) | 16 (34.8) | - | |
| 2 | 30 (30) | - | 30 (55.6) | |
| 3 | 12 (12) | - | 12 (22.2) | |
| 4 | 12 (12) | - | 12 (22.2) | |
| Medications | ||||
| Steroids | 37 (37) | 17 (37.0) | 20 (37.0) | 0.993 |
| 5-ASA | 98 (98) | 45 (97.8) | 53 (98.1) | 0.909 |
| Immunomodulators | 31 (31) | 12 (26.1) | 19 (35.2) | 0.327 |
| Biologics | 3 (3) | 1 (2.2) | 2 (3.7) | 1.000 |
| CRL | No CRL | P-value | |
|---|---|---|---|
| MES 0 (n = 43) | 9 (20.9) | 34 (79.1) | 0.002 |
| HH (n = 10) | 1 (10.0) | 9 (90.0) | 0.330 |
| No HH (n = 33) | 8 (24.2) | 25 (75.8) | |
| MES 1 (n = 37) | 20 (54.1) | 17 (45.9) |
| Variable | Bivariable regression |
Multivariable regression |
||
|---|---|---|---|---|
| HR (95% CI) | P-value | HR (95% CI) | P-value | |
| Age |
0.99 (0.97–1.01) | 0.436 | ||
| Disease duration | 1.00 (0.96–1.00) | 0.310 | ||
| Duration of clinical remission | 1.04 (1.00–1.09) | 0.034 |
1.05 (0.95–1.16) | 0.336 |
| BMI | 0.95 (0.88–1.02) | 0.168 | ||
| CRP | 1.05 (1.01–1.10) | 0.030 |
1.04 (0.99–1.09) | 0.108 |
| Stool calprotectin | 1.00 (1.00–1.00) | 0.049 |
||
| Sex |
0.93 (0.49–1.77) | 0.834 | ||
| Current smoker |
0.55 (0.08–4.03) | 0.557 | ||
| Endoscopic extent |
1.53 (0.82–2.87) | 0.186 | ||
| EH | 0.28 (0.14–0.56) | < 0.001 |
||
| MES 0 | 0.25 (0.12–0.52) | < 0.001 |
0.37 (0.15–0.94) | 0.037 |
| HH | 0.34 (0.17–0.67) | 0.002 |
0.59 (0.26–1.35) | 0.209 |
| Baseline medications | ||||
| Steroids | 0.71 (0.36–1.39) | 0.313 | ||
| 5-ASA | 0.90 (0.12–6.60) | 0.920 | ||
| Immunomodulators | 0.65 (0.31–1.36) | 0.247 | ||
| Biologics | 2.50 (0.60–10.42) | 0.210 | ||
| Variable | Bivariable regression |
Multivariable regression |
||
|---|---|---|---|---|
| HR (95% CI) | P-value | HR (95% CI) | P-value | |
| Age |
1.00 (0.97–1.03) | 0.956 | ||
| Disease duration | 1.00 (1.00–1.01) | 0.373 | ||
| Duration of clinical remission | 1.01 (0.95–1.09) | 0.701 | ||
| BMI | 1.05 (0.95–1.15) | 0.355 | ||
| CRP | 0.94 (0.84–1.06) | 0.294 | ||
| Stool calprotectin | 0.99 (0.99–1.00) | 0.004 |
0.99 (0.99–1.00) | 0.014 |
| Sex |
0.55 (0.24–1.25) | 0.152 | ||
| Current smoker |
1.07 (0.14–7.93) | 0.947 | ||
| Endoscopic extent |
0.17 (0.07–0.43) | < 0.001 |
0.40 (0.10–1.53) | 0.180 |
| MES 0 | 11.17 (4.36–28.59) | < 0.001 |
19.12 (4.08–89.68) | < 0.001 |
| Medications | ||||
| Steroids | 1.00 (0.44–2.25) | 0.993 | ||
| 5-ASA | 0.85 (0.05–13.96) | 0.909 | ||
| Immunomodulators | 0.65 (0.27–1.54) | 0.328 | ||
| Biologics | 0.58 (0.05–6.59) | 0.659 | ||
Table 1. Patient Characteristics at Index Colonoscopy
Values are presented as median (interquartile range), mean±standard deviation, or number (%). Statistically significant. Fisher exact test. HH, histologic healing; BMI, body mass index; CRP, C-reactive protein; 5-ASA, 5-aminosalicylic acid.
Table 2. CRL Rates at 2-Year Follow-up for Patients with Endoscopic Healing at Index Colonoscopy
Statistically significant. CRL, clinical relapse; MES, Mayo endoscopic score; HH, histologic healing.
Table 3. Cox Regression Analysis of Clinical Variables Associated with Time to Clinical Relapse
HR given per each year increase in age. HR for male sex, with female sex as comparator. HR for current smoking, with ex-smoking or non-smoking status as comparator. HR for left-sided or extensive disease, with proctitis or normal colon as comparator. Statistically significant. HR, hazard ratio; CI, confidence interval; BMI, body mass index; CRP, C-reactive protein; EH, endoscopic healing; MES, Mayo endoscopic score; HH, histologic healing; 5-ASA, 5-aminosalicylic acid.
Table 4. Logistic Regression Analysis of Clinical Variables Associated with Histologic Healing
OR given per each year increase in age. OR for male sex, with female sex as comparator. OR for current smoking, with ex-smoking or non-smoking status as comparator. OR for left-sided or extensive disease, with proctitis or normal colon as comparator. Statistically significant. OR, odds ratio; CI, confidence interval; BMI, body mass index; CRP, C-reactive protein; MES, Mayo endoscopic score; 5-ASA, 5-aminosalicylic acid.
