Er-Hsiang Yang; Nai-Yu Chen; Ching-Lan Cheng; Yu-Ching Chang; Po-Chuan Chen; Lu-Hsuan Wu; Jui-Wen Kang; Hsueh-Chien Chiang; Po-Jun Chen; Bo-Wen Lin; Hsin-Yu Kuo; Chiao-Hsiung Chuang

doi:10.5217/ir.2025.00003

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Original Article Evolution of surgical trends in Crohn’s disease during the biologic era: population-based cohort insights from Taiwan, a low-endemicity region: Er-Hsiang Yang^1,*, Nai-Yu Chen^2,3,*, Ching-Lan Cheng^2,4,5, Yu-Ching Chang⁵, Po-Chuan Chen⁶, Lu-Hsuan Wu^2,4, Jui-Wen Kang¹, Hsueh-Chien Chiang¹, Po-Jun Chen¹, Bo-Wen Lin⁶, Hsin-Yu Kuo¹, Chiao-Hsiung Chuang¹; DOI: https://doi.org/10.5217/ir.2025.00003
Published online: November 25, 2025

¹Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan

²School of Pharmacy, Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan

³Department of Pharmacy, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan

⁴Department of Pharmacy, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan

⁵Health Outcome Research Center, National Cheng Kung University, Tainan, Taiwan

⁶Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan

Correspondence to Chiao-Hsiung Chuang, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, 1 University Road, Tainan 70101, Taiwan. E-mail: chuang.chiaohsiung@gmail.com

*These authors contributed equally to this study as first authors.

• Received: January 10, 2025 • Revised: August 6, 2025 • Accepted: August 21, 2025

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.

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Abstract
INTRODUCTION
METHODS
RESULTS
DISCUSSION
NOTES
Supplementary Material
REFERENCES

Abstract

Background/Aims
Surgery remains a crucial treatment option for Crohn’s disease (CD), even with the introduction of biological agents. This nationwide cohort study in Taiwan investigates surgery trends and the impacts of biologics in a region with a low prevalence of CD.
Methods
This retrospective population-based cohort study used Taiwan’s National Health Insurance Database from 2003 to 2018. The cohort included 725 CD patients. Patient characteristics, surgery outcomes, and impact of the biologic era on surgical risk were analyzed.
Results
During the study period, 292 CD patients (40.3%) underwent surgery, with 125 in the pre-biologic era and 167 in the post-biologic era. The incidences of intestinal surgery (IS) and perianal surgery (PS) have significantly decreased. The cumulative probabilities of IS were 20%, 35%, and 44% after 1, 5, and 10 years, respectively; the PS incidences were 3%, 5%, and 7%, respectively. The cumulative incidence of IS was significantly lower in the post-biologic era compared to the pre-biologic era (P=0.049). CD patients had high second IS incidences of 31% at 5 years after the first IS.
Conclusions
Our study demonstrates the surgical incidences have decreased in the biologic era but remained relatively high in a region with low disease prevalence. This suggests the need for further improvements in CD management.
Keywords: Crohn disease; Surgery; Biological therapy

INTRODUCTION

Crohn’s disease (CD) poses multifaceted challenges due to persistent intestinal inflammation, giving rise to complications such as intestinal obstruction, abscess, fistula, and fulminant colitis. Consequently, surgical intervention is common, with approximately 70%−80% of patients with CD undergoing surgery at some point in their lives [1,2]. Notably, up to 70% of postoperative CD patients require additional surgical intervention, indicating the relapsing nature of the disease process [3].

Biologic treatments targeting tumor necrosis factor have demonstrated efficacy in reducing the risk of surgery in CD patients, as evidenced by randomized controlled studies [4]. However, real-world studies present inconsistent findings regarding the effectiveness of biologics in reducing surgery rates. Some population-based studies indicate a declining trend in surgery rates during the biologic era [5], whereas others report no significant differences [6-8]. This variability may result from factors beyond biologic treatment, such as early and accurate diagnosis or multidisciplinary management, potentially influencing prognosis. Furthermore, perianal involvement poses a significant risk for CD-related surgeries [9,10]. However, the current status and trends of perianal surgeries are inadequately represented in real-world data.

Most existing studies on the impact of biologics on surgery rates predominantly focus on regions with high endemicity, such as Europe and North America. Although a study from Korea demonstrated a decline in surgical rates among CD patients in the post-biologic era [11], studies on CD surgical rates remain scarce in regions with a low prevalence of CD. Notably, the incidence of CD has increased in newly urbanized countries over the past decades, including Taiwan [12,13]. Hence, exploring the conditions in these regions is crucial. Therefore, this study analyzes the trends and impact of the biologic era on intestinal surgery (IS) and perianal surgery (PS) in a nationwide register-based cohort of CD patients in Taiwan.

METHODS

1. Ethical Approval

Approval for the study protocol was obtained from the National Cheng Kung University Hospital Institutional Review Board (approval number: A-EX-108-049). The informed consent was waived.

2. Data Source

This study utilized data from the National Health Insurance (NHI) Database of Taiwan, spanning from January 1, 2003, to December 30, 2018. As a comprehensive data repository, the NHI database encompasses health information for over 99.9% of Taiwan’s population [14], facilitated by the single-payer NHI program initiated on March 1, 1995. Extracted from the claims data of NHI beneficiaries, the database comprises, ambulatory care claims, inpatient claims, prescriptions, medical facilities, and board-certified specialists. To ease the financial burden on families dealing with major illnesses, the NHI recognizes 31 categories of catastrophic illness, including CD. Patients with CD can apply for a Catastrophic Illness Certificate (CIC), exempting them from copayments.

3. Study Population

This study included patients with a CIC for CD (ICD-9-CM: 555 or ICD-10-CM: K50) from 2004 to 2017 (Supplementary Table 1). The CIC application process involves a detailed review of clinical, radiologic, endoscopic, and histologic findings by experienced gastroenterologists, ensuring a high level of diagnostic accuracy. Included patients were required to have a follow-up period of at least 1 year both before and after their initial CD diagnosis. To minimize diagnostic overlap with infectious colitis in the early stages of disease, we further refined our study population by considering their medical records within the 3 years following their initial diagnosis. Specifically, we included patients who had at least 1 hospitalization or 4 outpatient visits related to CD or those who had at least 4 prescriptions for CD-related medications in any given year within this 3-year period.

To identify new incidence cases, this study excluded patients who had any CD-related medical records in the year prior to their initial CD diagnosis. To verify the diagnosis of CD, patients who only received corticosteroid treatment in the first year following their initial diagnosis were also excluded. Moreover, patients under the age of 18 or those without registered age or sex information were also excluded.

In this study, the start date for follow-up was defined as the date of the first prescription for CD-related medication, which is also defined as the diagnosis date of CD. This study followed patients from the diagnosis date and censored them until the occurrence of surgery, death, or the end of the study period in the database (i.e., December 31, 2018), whichever came first. Additionally, the biologic era was defined as starting from July 01, 2011, coinciding with the availability of the first biologic (adalimumab) in Taiwan. The Anatomical Therapeutic Chemical codes for biologics are provided in Supplementary Table 2.

The NHI program reimburses biologics for CD patients with CIC who meet 1of the following criteria: (1) uncontrolled disease (Crohn’s Disease Activity Index ≥ 300) or severe drug-related side effects after more than 6 months of conventional treatment (5-aminosalicylic acid, steroids, and immunosuppressants); (2) unhealed perianal or abdominal wall fistulas (Crohn’s Disease Activity Index ≥ 100) despite over 6 months of conventional treatment or surgery; or (3) undergone 2 or more surgeries within a year due to CD complications despite adequate conventional treatment. The reimbursement period for biologics treatment is limited to 12 months.

4. Study Outcomes

This study focused on 2 primary outcomes concerning surgical interventions in CD patients, namely IS and PS. IS was further categorized into small bowel surgery and ileocolonic surgery. Small bowel surgery included procedures involving the small bowel and ileocolonic surgery included operations on the ileocolon, colon, or both the colon and small bowel. Restorative surgery, such as colostomy reversal, was excluded from the count of surgeries in this study. PS included surgery for anal fistula or abscess. Detailed procedure codes for these surgeries can be found in the supporting information (Supplementary Tables 3 and 4). This study assessed the annual IS and PS rates from 2007 to 2018 in CD patients and obtained the cumulative probabilities of the first and second surgeries using Kaplan-Meier curves.

5. Statistical Analysis

The statistical results are presented as counts (percentages), means (standard deviations), or medians (interquartile ranges). The surgery rate was calculated as the number of surgeries in a given year divided by the total number of CD patients in that year. To assess the trend in surgery rates over time, we conducted a linear regression analysis, treating the year as a continuous independent variable and the surgery rate as the dependent variable. The cumulative probability of surgery was evaluated using the Kaplan-Meier method, and the curves for patients in the pre- and post-biologic eras were compared using the log-rank test. The Cox proportional hazards model was used to estimate hazard ratios and 95% confidence intervals for comparing the cumulative probability of first IS and PS between the pre- and post-biologic eras. All statistical computations in this study were performed using SAS software, version 9.4 (SAS Institute Inc., Cary, NC, USA).

RESULTS

1. Baseline Clinical and Demographic Features at CD Diagnosis

A total of 725 eligible CD patients were included. The screening process of the study is shown in the Supplementary Fig. 1. The basic characteristics of the included patients are given in Table 1, and the diagnostic codes used to define baseline characteristics are provided in Supplementary Tables 5 and 6. Among CD patients, males were slightly more prevalent, and the mean age at diagnosis was 38.7 ±15.4 years. The occurrence of anemia was 24.7% in CD patients. The proportion of patients with concurrent immunosuppressive diseases, extraintestinal manifestations, or cancer was less than 10% for CD patients. During the observation period, the proportion of surgeries was 35.9% for IS and 8.7% for PS among CD patients.

In Taiwan, adalimumab was the first biologic agent available for CD patients and became accessible in 2011. Vedolizumab and infliximab were introduced in late 2017, followed by golimumab in 2018. Consequently, the majority of patients in our study who received biologic therapy were treated with adalimumab (92.2%), while 6% received vedolizumab, and 1.8% were treated with either golimumab or infliximab. The mean duration from CD diagnosis to initiation of biologic therapy was 4.46 ± 3.52 years.

2. Characteristics of Enrolled CD Patients Who Underwent Surgery

Among the cohort, 292 CD patients underwent CD-related operations. Their characteristics are shown in Table 2. The patients were predominantly male, with a mean age of 40.4 years at the time of surgery. Prior to diagnosis, 65 of these patients (22.3%) had undergone IS and 26 (8.9%) had undergone PS. The medication profiles preceding the first operation are also shown in Table 2. The “Operation before diagnosis” variable in Table 2 refers to surgeries performed before the confirmatory CD diagnosis (22.3% in IS, 8.9% in PS).

3. Time Trends in Surgery Rates

The time trend in surgery rates for CD patients is shown in Fig. 1. A statistically significant reduction in the rate of IS was observed in CD patients (P=0.001), from 25.3% in 2007 to 4.5% in 2018. The rate of PS also significantly decreased in CD patients (P=0.028) during the study period, dropping from 5.1% in 2007 to 1.6% in 2018.

4. Cumulative Risks of First Surgery

The initial surgery risks were analyzed. The results are shown in Fig. 2. In individuals with CD, the cumulative probabilities of IS were 20%, 35%, and 44% after 1, 5, and 10 years, respectively. The cumulative probabilities of PS in CD patients were 3%, 5%, and 7% after 1, 5, and 10 years, respectively. Remarkably, 8.9% of CD patients had already undergone IS before the official disease diagnosis.

5. Impact of the Biologic Era on Surgical Risk in CD

The cumulative incidence of first IS at 1, 5, and 10 years after diagnosis was 18.4%, 29.0%, and 63.6%, respectively, in the pre-biologic era. In the post-biologic era, the cumulative incidence of first IS was 12.1% at 1 year and 21.6% at 5 years after diagnosis. The cumulative incidence of first IS was significantly lower in the post-biologic era compared to the pre-biologic era (P=0.049, log-rank test) (Fig. 3). The hazard ratio for IS in the post-biologic era compared with the pre-biologic era was 0.73 (95% confidence interval, 0.53–0.99). There was no significant difference in the cumulative incidence of PS between the pre-biologic and post-biologic eras (P=0.739, log-rank test). The hazard ratio for PS in the post-biologic era compared with the pre-biologic era was 1.18 (95% confidence interval, 0.45–3.08).

6. Cumulative Risks for Second Surgery

In individuals diagnosed with CD, the cumulative probabilities of having a second IS were 16%, 26%, and 31% at 1, 3, and 5 years after the first surgery, respectively. Similarly, the cumulative probabilities of second PS for CD patients were 17%, 29%, and 32% (Fig. 4).

DISCUSSION

This national population-based study revealed significant reductions in operation rates for CD patients in Taiwan from 2007 to 2018, consistent with previous Western or Asian findings [5,11]. While various factors may have contributed, advancements in biologic therapies likely played an important role in reducing surgery rates among inflammatory bowel disease patients [15,16]. Biologic therapy has been reported with a 26% reduction in the risk of surgery for CD patients compared to that of patients without such treatment [16]. Our data further show that, according to national data, the incidence of IS in this low-endemic area had decreased significantly in patients diagnosed in the post-biologic era (Fig. 3).

Beyond the use of biologics, several other factors can be associated with the surgical rate, such as penetrating behavior, ileal involvement, disease severity, and duration [17]. Additional unmeasured confounders, including physician experience, diagnostic awareness, the use of monitoring tools, and treatment escalation strategies, could also have impacts. Due to limitations of the NHI database, key clinical variables such as disease behavior, location, and severity were not available. Given these constraints, assessing only on database available parameters might lead to an incomplete understanding of their individual effects. Therefore, our study focused on evaluating the overall influence of the biologic era at a population level, rather than evaluating specific predictors.

Despite these limitations, we sought to address concerns regarding potential confounding factors. A prospectively registered study from Taiwan showed similar rates of penetrating disease (18% in 2006–2015 vs. 16.67% in 2016–2023) and ileal involvement (33.33% in 2006–2015 vs. 30.77% in 2016–2023) [18]. Therefore, we speculated that the phenotypic distribution of CD was likely stable during the period of our study. Although azathioprine may represent a potential confounder, previous meta-analyses and 1 clinical study have not demonstrated a significant association between its use and a reduced risk of surgery [19,20]. Moreover, our recently published study also based on NHI database but in different definition showed the most characteristics of patients diagnosed in pre- and post-biological era were similar [21]. Therefore, based on current literature, surgery-related confounders appear to have a limited impact on our study conclusions, although the possibility of residual confounding cannot be entirely excluded.

However, our study revealed a reduction only in IS rates, not PS rates, among CD patients in the post-biologic era. This result aligns with a recent study showing that the probability of the first PS for CD has remained stable across different eras [22]. This stability may be attributed to the refractory nature of perianal CD and its predisposition to relapse. Additionally, biological therapy has not demonstrated a dramatic effect on treating perianal CD. Two studies found that the incidence and recurrence rates of perianal CD remain unchanged in the biologic era [10,22]. One study reported that only 24% and 32% of CD patients with perianal fistulas achieved radiological healing after 1 and 3 years of combination therapy with thiopurines and anti-tumor necrosis factor, respectively [23]. The study found that 57% of CD patients who achieved healing experienced recurrent fistula after discontinuing biologics [23]. Therefore, many patients with perianal CD still require surgical intervention despite biologic therapy [9]. Another possible explanation is the restrictions imposed by Taiwan’s NHI on biologic reimbursement policy due to budgetary considerations. According to the policy, CD patients must exhibit an inadequate response to conventional therapy for over 6 months before biologics are initiated, with treatment discontinuation mandated after 52 weeks [24]. This limitation may impede the efficacy of biologics in preventing surgery, especially for perianal disease, a common complication requiring early and long-term continuous biologic therapy [25,26].

The cumulative risk of IS for CD patients in our study is consistent with a prior meta-analysis reported in 2013 [27]. However, a more recent meta-analysis reported that contemporary risks in the 21st century for IS rate in CD patients were 12.3%, 18.0%, and 26.2% at 1, 5, and 10 years post-diagnosis, which are lower than those found in our study [28]. The higher surgery rate observed in our CD patient cohort may be attributed to several factors. First, low awareness of IBD due to the low CD prevalence led to delayed diagnosis and treatment, resulting in higher complications and operation rates [29-31]. Second, endemic gastrointestinal infections in Taiwan pose diagnostic and therapeutic challenges due to conflicting therapies for infection and CD, particularly tuberculosis [32]. Finally, the first biologic was not available until 2011, and several restrictions on the application of biologics in Taiwan’s NHI program, as mentioned earlier, could have contributed to the relatively inadequate treatment compared to that in other countries.

In contrast, cumulative risk of first PS in our study is substantially lower than in previous studies [33]. This finding may be attributed to the low prevalence of perianal CD in Taiwan, which was reported to be 14.8% in a recent study [34]. Consequently, the proportion of perianal CD-related surgeries among all patients is relatively low. Moreover, perianal CD in East Asia may present with less severe disease and a better prognosis compared to Western countries [35]. The low surgical rate may also be associated with multidisciplinary management and medical and radiologic treatment advancements [36]. However, the cumulative risk of second PS was high, which could be attributed to relapsing and refractory characteristics of perianal CD, as mentioned previously [10,22,37].

Our study identified a higher incidence of second IS than those in recent studies, which reported second IS rates of 11%−14% at 5 years and 16% at 10 years after diagnosis in the 21st century [38-40]. This disparity may be attributed to factors similar to those contributing to the higher first IS rate observed in our study, especially the policy of forced discontinuation of biologics after 52 weeks. In Taiwan, after the forced discontinuation of biologics, 3-quarters of CD patients experienced disease relapse [41], and more than half of CD patients encountered suboptimal outcomes within 1-2 years [24]. It is reasonable that the high cumulative probability of a second IS for CD under this policy results from the short duration of the biologic treatment (52 weeks), which may not achieve endoscopic remission in most patients [42]. Given the chronic and relapsing nature of CD, consistent and uninterrupted disease control in the therapeutic window following the first operation is crucial to preventing a second IS.

Similar to the case of Taiwan’s NHI program, limitations on biologic treatment coverage in public insurance have been reported in Canada and Mexico, leading to increased hospitalizations and emergency room visits [43,44]. Belgium and U.S. studies also showed that adherence to biologic treatment has been associated with reduced healthcare costs [45], decreased hospitalization expenses [46], and improved overall survival and quality of life for patients with inflammatory bowel disease [47]. Moreover, reimbursing biologics was cost-effective and led to a decrease in the lifelong surgery rate for Chinese CD patients [47]. This evidence highlights the need to reevaluate biologic insurance reimbursement policies in Taiwan and other countries with similar budget constraints, advocating for more flexible approaches to enhance care for CD patients.

The strengths of our study include the utilization of the NHI database, which covers over 99.9% of Taiwan’s population, and the inclusion of CD patients with catastrophic illness registration, ensuring comprehensive and accurate data. Moreover, focusing on current practice patterns and outcomes in Taiwan, a low-endemicity region, provides valuable insights. Nevertheless, our study has several limitations. As an observational study, establishing direct causality for the observed reduction in surgery rates is challenging. The absence of detailed clinical data, including disease characteristics, severity, and specific surgery types, limits a comprehensive understanding [5,48]. Second, the majority of patients receiving biologic therapy in our study were treated with adalimumab (92%). The long-term impact of newer advanced therapy on surgical trends needs further investigation. Third, some CD patients may not have been included due to the absence of CIC registration. However, because CIC registration is required for accessing biologic therapy, the most clinically relevant cases were likely captured. Although the lack of non-CIC patients may affect estimates of first-surgery rates, the impact on second-surgery rates and comparisons between the pre- and post-biologic eras is expected to be minimal. Fourth, the limited sample size in our study precluded a meaningful analysis of the impact of the biologic era on the risk of a second surgery.

In conclusion, our study reveals a significant reduction in operation rates for CD patients in Taiwan, a region with a low disease incidence. The impact on reducing surgical incidence in biologic era is demonstrated, particularly for IS. Although establishing a direct cause-and-effect relationship remains challenging, the observed trends suggest the importance of continuous application of biologic therapy. Our findings also suggest that the cumulative risks of first and second surgeries are higher compared to those reported in contemporary studies, indicating the need for ongoing improvement in CD management.

NOTES

Funding Source

This research was supported by research grants from the Ministry of Health and Welfare (MOHW113-TDU-B-211-114008), National Cheng Kung University Hospital (NCKUH-11302055), and National Science and Technology Council (NSTC 113-2314-B-006-057-MY3).

Conflict of Interest

No potential conflict of interest relevant to this article was reported.

Data Availability Statement

The data used for this research were obtained from the National Health Insurance (NHI) Database of Taiwan. Data will be made available on request.

Author Contributions

Conceptualization: Yang EH, Chen NY, Cheng CL, Chuang CH. Data curation: Yang EH, Chen NY, Chang YC. Formal analysis: Yang EH, Chen NY, Cheng CL, Chang YC, Chuang CH. Funding acquisition: Chuang CH. Investigation: Chen NY, Cheng CL, Chen PC, Wu LH, Kang JW, Chiang HC, Chen PJ, Lin BW, Kuo HY, Chuang CH. Methodology: Yang EH, Chen NY, Cheng CL, Chuang CH. Project administration: Chuang CH. Resources: Cheng CL, Chuang CH. Software: Chen NY, Chang YC. Supervision: Cheng CL, Chuang CH. Validation: Cheng CL, Chen PC, Wu LH, Chuang CH. Visualization: Yang EH, Chen NY, Chang YC. Writing - original draft: Yang EH. Writing - review & editing: all authors. Approval of final manuscript: all authors.

Supplementary Material

Supplementary materials are available at the Intestinal Research website (https://www.irjournal.org).

Supplementary Table 1.

Operational Definitions for Inflammatory Bowel Disease Diagnosis

ir-2025-00003-Supplementary-Table-1.pdf

Supplementary Table 2.

Operational Definitions for Biologics

ir-2025-00003-Supplementary-Table-2.pdf

Supplementary Table 3.

Intestinal Surgery Procedure Code and Definition

ir-2025-00003-Supplementary-Table-3.pdf

Supplementary Table 4.

Perianal Surgery Procedure Code and Definition

ir-2025-00003-Supplementary-Table-4.pdf

Supplementary Table 5.

Operational Definitions for Inflammatory Bowel Disease-Related Surgery

ir-2025-00003-Supplementary-Table-5.pdf

Supplementary Table 6.

Operational Definitions for Baseline Disease

ir-2025-00003-Supplementary-Table-6.pdf

Supplementary Fig. 1.

Flow diagram of study population selection. IBD, inflammatory bowel disease; CIC, Catastrophic Illness Certificate; NHI, National Health Insurance; CD, Crohn's disease.

ir-2025-00003-Supplementary-Fig-1.pdf

Fig. 1.

Annual intestinal and perianal surgery rates from 2007 to 2018 among Crohn’s disease patients.

Fig. 2.

Cumulative probability of first intestinal surgery (IS) and perianal surgery (PS) in patients with Crohn’s disease (CD).

Fig. 3.

Cumulative probability of first intestinal surgery in patients with Crohn’s disease (CD) in the pre-biologic era and the post-biologic era.

Fig. 4.

Cumulative probability of second intestinal surgery (IS) and perianal surgery (PS) in patients with Crohn’s disease (CD).

Table 1.

Baseline Characteristics at Diagnosis of 725 Crohn’s Disease Patients

Baseline characteristics at diagnosis	Value (n = 725)
Male sex	492 (67.9)
Age at diagnosis (yr), mean ± SD	38.7 ± 15.4
Charlson-Deyo Comorbidity Index, Median (IQR)	1 (0–2)
Anemia	179 (24.7)
Extraintestinal manifestations
Joint	34 (5.8)
Skin	31 (4.7)
Eye	9 (4.3)
Cancer
Colorectal cancer	33 (4.6)
Non-Hodgkin’s lymphoma	12 (1.7)
Other cancer	4 (0.6)
Operation before diagnosis
Intestinal surgery	65 (8.9)
Perianal surgery	26 (3.6)

Values are presented as number (%) unless otherwise indicated.

SD, standard deviation; IQR, interquartile range.

Table 2.

Baseline Characteristics at Diagnosis for 292 Crohn's Disease Patients with Operation

Baseline characteristics at diagnosis	Value (n = 292)
Male sex	209 (71.6)
Age at diagnosis (yr), mean ± SD	39.5 ± 15.9
Age at operation (yr), mean ± SD	40.4 ± 16.1
Follow-up period (yr), median (IQR)	6.5 (3.7–10.1)
Era at diagnosis
Pre-biologic (before 2011/7/1)	125 (42.8)
Post-biologic (after 2011/7/1)	167 (57.2)
Operation before diagnosis
Intestinal surgery	65 (22.3)
Small bowel	37 (12.7)
Ileocolonic	32 (11.0)
Perianal surgery	26 (8.9)
Medication (1 yr before first operation)
Oral steroid	105 (36.0)
Intravenous steroid	107 (36.6)
5-Aminosalicylic acid	155 (53.1)
Immune modulating medications	56 (19.2)
Biologics	30 (10.3)

Values are presented as number (%) unless otherwise indicated.

SD, standard deviation; IQR, interquartile range.

REFERENCES

1. Mowat C, Cole A, Windsor A, et al. Guidelines for the management of inflammatory bowel disease in adults. Gut 2011;60:571–607.Article PubMed
2. Bouguen G, Peyrin-Biroulet L. Surgery for adult Crohn’s disease: what is the actual risk? Gut 2011;60:1178–1181.Article PubMed
3. De Cruz P, Kamm MA, Prideaux L, Allen PB, Desmond PV. Postoperative recurrent luminal Crohn’s disease: a systematic review. Inflamm Bowel Dis 2012;18:758–777.Article PubMed
4. Vermeire S, van Assche G, Rutgeerts P. Review article: altering the natural history of Crohn’s disease: evidence for and against current therapies. Aliment Pharmacol Ther 2007;25:3–12.Article
5. Peyrin-Biroulet L, Oussalah A, Williet N, Pillot C, Bresler L, Bigard MA. Impact of azathioprine and tumour necrosis factor antagonists on the need for surgery in newly diagnosed Crohn’s disease. Gut 2011;60:930–936.Article PubMed
6. Jones DW, Finlayson SR. Trends in surgery for Crohn’s disease in the era of infliximab. Ann Surg 2010;252:307–312.Article PubMed
7. Slattery E, Keegan D, Hyland J, O’donoghue D, Mulcahy HE. Surgery, Crohn’s disease, and the biological era: has there been an impact? J Clin Gastroenterol 2011;45:691–693.PubMed
8. Burke JP, Velupillai Y, O’Connell PR, Coffey JC. National trends in intestinal resection for Crohn’s disease in the post-biologic era. Int J Colorectal Dis 2013;28:1401–1406.Article PubMed PDF
9. Atia O, Asayag N, Focht G, et al. Perianal Crohn’s disease is associated with poor disease outcome: a nationwide study from the epiIIRN cohort. Clin Gastroenterol Hepatol 2022;20:e484–e495.Article PubMed
10. Wewer MD, Zhao M, Nordholm-Carstensen A, Weimers P, Seidelin JB, Burisch J. The incidence and disease course of perianal Crohn’s disease: a Danish nationwide cohort study, 1997-2015. J Crohns Colitis 2021;15:5–13.Article PubMed PDF
11. Ye BD, Hong SN, Seo SI, et al. Changes in the long-term prognosis of Crohn’s disease between 1986 and 2015: the population-based Songpa-Kangdong inflammatory bowel disease cohort study. Gut Liver 2022;16:216–227.Article PubMed PMC
12. Ng SC, Shi HY, Hamidi N, et al. Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: a systematic review of population-based studies. Lancet 2017;390:2769–2778.Article PubMed
13. Yen HH, Weng MT, Tung CC, et al. Epidemiological trend in inflammatory bowel disease in Taiwan from 2001 to 2015: a nationwide population based study. Intest Res 2019;17:54–62.Article PubMed PMC PDF
14. Executive Yuan. National Health Insurance coverage statistics [Internet]. c2014;[cited 2025 Mar 26]. https://www.ey.gov.tw/state/A01F61B9E9A9758D/fa06e0d2-413f-401e-b694-20c2db86f404.
15. Zhulina Y, Udumyan R, Tysk C, Montgomery S, Halfvarson J. The changing face of Crohn’s disease: a population-based study of the natural history of Crohn’s disease in Örebro, Sweden 1963-2005. Scand J Gastroenterol 2016;51:304–313.Article PubMed
16. Khoudari G, Mansoor E, Click B, et al. Rates of intestinal resection and colectomy in inflammatory bowel disease patients after initiation of biologics: a cohort study. Clin Gastroenterol Hepatol 2022;20:e974–e983.Article PubMed
17. Ng SC, Zeng Z, Niewiadomski O, et al. Early course of inflammatory bowel disease in a population-based inception cohort study from 8 countries in Asia and Australia. Gastroenterology 2016;150:86–e14.Article PubMed
18. Huang CW, Wei SC, Shieh MJ, et al. Epidemiology and temporal trends of adult inflammatory bowel disease in Taiwan: multicenter study from the TSIBD registration. J Formos Med Assoc 2025;Jan 31 [Epub]. https://doi.org/10.1016/j.jfma.2025.01.018.Article PMC
19. Mao EJ, Hazlewood GS, Kaplan GG, Peyrin-Biroulet L, Ananthakrishnan AN. Systematic review with meta-analysis: comparative efficacy of immunosuppressants and biologics for reducing hospitalisation and surgery in Crohn’s disease and ulcerative colitis. Aliment Pharmacol Ther 2017;45:3–13.Article PubMed PDF
20. Rungoe C, Langholz E, Andersson M, et al. Changes in medical treatment and surgery rates in inflammatory bowel disease: a nationwide cohort study 1979-2011. Gut 2014;63:1607–1616.Article PubMed
21. Chen NY, Chuang CH, Chang YC, et al. Epidemiology and steroid dependency reduction in Crohn’s disease during the biologics era: a nationwide population-based study. Adv Ther 2025;42:4318–4334.Article PubMed PMC PDF
22. Göttgens KW, Jeuring SF, Sturkenboom R, et al. Time trends in the epidemiology and outcome of perianal fistulizing Crohn’s disease in a population-based cohort. Eur J Gastroenterol Hepatol 2017;29:595–601.Article PubMed
23. Tozer P, Ng SC, Siddiqui MR, et al. Long-term MRI-guided combined anti-TNF-α and thiopurine therapy for Crohn’s perianal fistulas. Inflamm Bowel Dis 2012;18:1825–1834.Article PubMed
24. Chen NY, Chuang CH, Chang YC, Kao Yang YH, Chen PH, Cheng CL. Suboptimal outcomes and retreatment rate of patients with Crohn’s disease after forced discontinuation of biologics: a nationwide population-based study. Clin Pharmacol Ther 2023;114:914–921.PubMed
25. Gonczi L, Lakatos L, Golovics PA, et al. Burden of perianal disease in Crohn’s disease: accelerating medical therapy and high rates of perianal surgery over the last four decades: results from a population-based study over four decades. Aliment Pharmacol Ther 2024;59:656–665.Article PubMed
26. Tarrant KM, Barclay ML, Frampton CM, Gearry RB. Perianal disease predicts changes in Crohn’s disease phenotype-results of a population-based study of inflammatory bowel disease phenotype. Am J Gastroenterol 2008;103:3082–3093.Article PubMed
27. Frolkis AD, Dykeman J, Negrón ME, et al. Risk of surgery for inflammatory bowel diseases has decreased over time: a systematic review and meta-analysis of population-based studies. Gastroenterology 2013;145:996–1006.Article PubMed
28. Tsai L, Ma C, Dulai PS, et al. Contemporary risk of surgery in patients with ulcerative colitis and Crohn’s disease: a meta-analysis of population-based cohorts. Clin Gastroenterol Hepatol 2021;19:2031–2045.Article PubMed PMC
29. Chuang CH, Lin SH, Chen CY, Sheu BS, Kao AW, Wang JD. Increasing incidence and lifetime risk of inflammatory bowel disease in Taiwan: a nationwide study in a low-endemic area 1998-2010. Inflamm Bowel Dis 2013;19:2815–2819.PubMed
30. Banerjee R, Pal P, Mak JW, Ng SC. Challenges in the diagnosis and management of inflammatory bowel disease in resource-limited settings in Asia. Lancet Gastroenterol Hepatol 2020;5:1076–1088.Article PubMed
31. Li Y, Ren J, Wang G, et al. Diagnostic delay in Crohn’s disease is associated with increased rate of abdominal surgery: a retrospective study in Chinese patients. Dig Liver Dis 2015;47:544–548.Article PubMed
32. Weng MT, Wei SC, Lin CC, et al. Seminar report from the 2014 Taiwan Society of Inflammatory Bowel Disease (TSIBD) Spring Forum (May 24th, 2014): Crohn’s disease versus intestinal tuberculosis infection. Intest Res 2015;13:6–10.Article PubMed PMC
33. Tsai L, McCurdy JD, Ma C, Jairath V, Singh S. Epidemiology and natural history of perianal Crohn’s disease: a systematic review and meta-analysis of population-based cohorts. Inflamm Bowel Dis 2022;28:1477–1484.Article PubMed PMC PDF
34. Weng MT, Lin KL, Huang YL, et al. Epidemiology, disease course, and clinical outcomes of perianal fistulas and fissures Crohn’s disease: a nationwide population-based study in Taiwan. Crohns Colitis 360 2023;5:otad035.Article PubMed PMC PDF
35. Song EM, Lee HS, Kim YJ, et al. Incidence and outcomes of perianal disease in an Asian population with Crohn’s disease: a nationwide population-based study. Dig Dis Sci 2020;65:1189–1196.Article PubMed PDF
36. Parian AM, Obi M, Fleshner P, Schwartz DA. Management of perianal Crohn’s disease. Am J Gastroenterol 2023;118:1323–1331.Article PubMed
37. McCurdy JD, Reid J, Yanofsky R, et al. Fecal diversion for perianal Crohn disease in the era of biologic therapies: a multicenter study. Inflamm Bowel Dis 2022;28:226–233.Article PubMed PDF
38. Frolkis AD, Lipton DS, Fiest KM, et al. Cumulative incidence of second intestinal resection in Crohn’s disease: a systematic review and meta-analysis of population-based studies. Am J Gastroenterol 2014;109:1739–1748.Article PubMed PDF
39. Domènech E, Garcia V, Iborra M, et al. Incidence and management of recurrence in patients with Crohn’s disease who have undergone intestinal resection: the Practicrohn study. Inflamm Bowel Dis 2017;23:1840–1846.PubMed
40. Burr NE, Lord R, Hull MA, Subramanian V. Decreasing risk of first and subsequent surgeries in patients with Crohn’s disease in England from 1994 through 2013. Clin Gastroenterol Hepatol 2019;17:2042–2049.Article PubMed
41. Lin WC, Chou JW, Yen HH, et al. Outcomes of limited period of adalimumab treatment in moderate to severe Crohn’s disease patients: Taiwan Society of Inflammatory Bowel Disease Study. Intest Res 2017;15:487–494.Article PubMed PMC PDF
42. Rutgeerts P, Van Assche G, Sandborn WJ, et al. Adalimumab induces and maintains mucosal healing in patients with Crohn’s disease: data from the EXTEND trial. Gastroenterology 2012;142:1102–1111.Article PubMed
43. Rumman A, Candia R, Sam JJ, et al. Public versus private drug insurance and outcomes of patients requiring biologic therapies for inflammatory bowel disease. Can J Gastroenterol Hepatol 2017;2017:7365937.Article PubMed PMC PDF
44. Yamamoto-Furusho JK, Parra-Holguín NN. Diagnostic delay of inflammatory bowel disease is significantly higher in public versus private health care system in Mexican Patients. Inflamm Intest Dis 2022;7:72–80.Article PubMed PMC PDF
45. Wan GJ, Kozma CM, Slaton TL, Olson WH, Feagan BG. Inflammatory bowel disease: healthcare costs for patients who are adherent or non-adherent with infliximab therapy. J Med Econ 2014;17:384–393.Article PubMed
46. Carter CT, Waters HC, Smith DB. Effect of a continuous measure of adherence with infliximab maintenance treatment on inpatient outcomes in Crohn’s disease. Patient Prefer Adherence 2012;6:417–426.Article PubMed PMC
47. Chen H, Shi J, Pan Y, et al. Cost-effectiveness of reimbursing infliximab for moderate to severe Crohn’s disease in China. Adv Ther 2020;37:431–449.Article PubMed PDF
48. Bernell O, Lapidus A, Hellers G. Risk factors for surgery and postoperative recurrence in Crohn’s disease. Ann Surg 2000;231:38–45.Article PubMed PMC

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Evolution of surgical trends in Crohn’s disease during the biologic era: population-based cohort insights from Taiwan, a low-endemicity region

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Evolution of surgical trends in Crohn’s disease during the biologic era: population-based cohort insights from Taiwan, a low-endemicity region

Fig. 1. Annual intestinal and perianal surgery rates from 2007 to 2018 among Crohn’s disease patients.

Fig. 2. Cumulative probability of first intestinal surgery (IS) and perianal surgery (PS) in patients with Crohn’s disease (CD).

Fig. 3. Cumulative probability of first intestinal surgery in patients with Crohn’s disease (CD) in the pre-biologic era and the post-biologic era.

Fig. 4. Cumulative probability of second intestinal surgery (IS) and perianal surgery (PS) in patients with Crohn’s disease (CD).

Fig. 1.

Fig. 2.

Fig. 3.

Fig. 4.

Evolution of surgical trends in Crohn’s disease during the biologic era: population-based cohort insights from Taiwan, a low-endemicity region

Baseline characteristics at diagnosis	Value (n = 725)
Male sex	492 (67.9)
Age at diagnosis (yr), mean ± SD	38.7 ± 15.4
Charlson-Deyo Comorbidity Index, Median (IQR)	1 (0–2)
Anemia	179 (24.7)
Extraintestinal manifestations
Joint	34 (5.8)
Skin	31 (4.7)
Eye	9 (4.3)
Cancer
Colorectal cancer	33 (4.6)
Non-Hodgkin’s lymphoma	12 (1.7)
Other cancer	4 (0.6)
Operation before diagnosis
Intestinal surgery	65 (8.9)
Perianal surgery	26 (3.6)

Baseline characteristics at diagnosis	Value (n = 292)
Male sex	209 (71.6)
Age at diagnosis (yr), mean ± SD	39.5 ± 15.9
Age at operation (yr), mean ± SD	40.4 ± 16.1
Follow-up period (yr), median (IQR)	6.5 (3.7–10.1)
Era at diagnosis
Pre-biologic (before 2011/7/1)	125 (42.8)
Post-biologic (after 2011/7/1)	167 (57.2)
Operation before diagnosis
Intestinal surgery	65 (22.3)
Small bowel	37 (12.7)
Ileocolonic	32 (11.0)
Perianal surgery	26 (8.9)
Medication (1 yr before first operation)
Oral steroid	105 (36.0)
Intravenous steroid	107 (36.6)
5-Aminosalicylic acid	155 (53.1)
Immune modulating medications	56 (19.2)
Biologics	30 (10.3)

Table 1. Baseline Characteristics at Diagnosis of 725 Crohn’s Disease Patients

Values are presented as number (%) unless otherwise indicated.

SD, standard deviation; IQR, interquartile range.

Table 2. Baseline Characteristics at Diagnosis for 292 Crohn's Disease Patients with Operation

Values are presented as number (%) unless otherwise indicated.

SD, standard deviation; IQR, interquartile range.