Ileocolic resection versus medical therapy for Crohn’s disease in the post-biologic era: a systematic review

Introduction

Crohn’s disease (CD) is a chronic, idiopathic inflammatory condition with a rising incidence worldwide. Globally, the prevalence of inflammatory bowel disease (IBD) increased from 3.7 million in 1990 to 6.8 million in 2017 (1), with the most pronounced rise observed in regions undergoing rapid industrialization, such as Asia, Latin America, and the Middle East, as well as among pediatric populations.

CD can affect any segment of the gastrointestinal (GI) tract and is often discontinuous, with transmural inflammation that may extend to adjacent structures. The terminal ileum or ileocolonic disease is the most common site of involvement, being involved in isolation in approximately one-third of cases (2). Clinically, CD follows a relapsing-remitting course, with symptoms varying according to the severity and anatomical distribution of inflammation. Moreover, the disease exhibits heterogeneous phenotypes, including inflammatory, stricturing, or fistulizing forms, and can present with extraintestinal manifestations (3).

The therapeutic landscape of CD was profoundly changed with the introduction of biologic agents in the 1990s. Traditionally, surgery has been regarded as a measure of last resort, reserved for complications refractory to medical management, a perception that remains prevalent among patients and healthcare professionals. More recent studies estimate that the risk of surgery in patients with CD within 10 years decreased from 46.6% (in population meta-analysis studies before 2000) to approximately 26.2% (in a cohort studied from 2000 to 2017), as previously therapeutic options were limited to corticosteroid therapy and salicylates (4).

Ileocecal CD patients who do not respond adequately to conventional therapies are usually escalated to biologics. However, surgical resection may provide equally favorable outcomes in both the short and long term. Evidence from the multicenter randomized controlled LIR!C trial, conducted in the Netherlands and the United Kingdom, showed that laparoscopic ileocecal resection and infliximab (IFX) achieved comparable improvements in health-related quality of life (5).

Despite such evidence, surgery is still underutilized and often viewed exclusively as a salvage strategy rather than as a proactive therapeutic option. This perception contributes to delays in surgical referral and may limit patient access to potentially effective treatment alternatives. There remains a need to clarify the role of surgery in the current treatment paradigm for ileocecal CD.

Therefore, this systematic review (SR) aimed to evaluate and compare the outcomes of surgical and medical management in patients with ileocecal CD. The analysis focused on the rates of clinical and endoscopic remission, disease recurrence, re-hospitalization, and the occurrence of treatment-related complications. We present this article in accordance with the PRISMA reporting checklist (6) (available at https://tgh.amegroups.com/article/view/10.21037/tgh-25-131/rc).

Methods

The SR was registered on the PROSPERO platform under the identification number CRD42024582836. A comprehensive search was conducted across multiple databases, including PubMed, PubMed PMC, BVS/BIREME, CINAHL, Web of Science, Embase, Cochrane Library, and ProQuest, using a combination of controlled descriptors (MeSH terms) and free-text keywords. The timeframe of the retrieved studies was up to July 2025. Search terms included “CD”, “ileocecal resection”, “surgery”, “medical therapy”, “biologics”, “immunosuppressive”, “hemicolectomy”, “ileocolectomy”, “monoclonal antibody”, “laparoscopic ileocecal resection”, “ileocolitis”, “ileum resection”, and “small intestine resection”. The search strategy was designed to identify studies evaluating the outcomes of surgical and/or medical management for ileocecal CD.

Studies were included if they involved patients with CD, either compared outcomes between surgical and biologic therapy or reported results for a single treatment arm. Only studies focusing on ileocecal resection, or ileotyphlectomy for localized ileocecal disease, were considered, while studies comparing different biologics were excluded. Studies were also excluded if they addressed other IBD, such as ulcerative colitis, if patients had received biologics before surgery, or if non-biologic medications, including corticosteroids or mesalazine, were the primary intervention. The variables assessed in the studies are summarized in Figure 1.

Figure 1 Variables assessed in the SR, stratified according to treatment categories. Created in BioRender. Genaro LM [2026]. SR, systematic review.

All retrieved records were exported to Rayyan (7). Initially, 1,056 records were screened based on titles and abstracts by two independent reviewers; any discrepancies were resolved by a third reviewer. After screening and removal of duplicates, 96 studies were assessed in full text, resulting in eight studies that met all inclusion criteria and were incorporated into the final analysis. A PRISMA flow diagram was applied to document the selection process, ensuring transparency and reproducibility (Figure 2).

Figure 2 PRISMA flow diagram illustrating the process of identification, screening, eligibility assessment, and inclusion of studies in the SR. SR, systematic review.

Results

General characteristics of the studies

Eight original studies were included in this SR (Table 1), comprising six retrospective cohorts and two randomized controlled trials (5,8-14). Two of the eight studies presented both arms and directly compared surgical and clinical management. The total study population included 942 patients with ileocecal CD. Seven studies were conducted in Europe (the Netherlands, Sweden, Austria, France, Germany, and Switzerland), and one in Canada.

Mean ages ranged from 15.2 to 33.4 years across the cohorts, with only one study focusing on a pediatric population, which reported a higher risk of early recurrence. These age distributions highlight the prevalence of CD in younger productive individuals. Regarding sex distribution, three studies reported a male predominance ranging from 35% to 62.1%, while female representation ranged from 37.9% to 65%.

Surgical interventions were predominantly ileocolic resections, performed either laparoscopically or via open surgery. In comparative studies, control groups received biologic therapy, mainly IFX.

Treatment modalities investigated

Among the eight studies, two directly compared ileocolic resection with biologic therapy (IFX), while the remaining studies evaluated surgical intervention exclusively. In addition to IFX, some studies reported the use of adalimumab and ustekinumab.

Clinical and endoscopic remission rates

Clinical remission rates in the surgical groups were consistently high in the short term. Riss et al. [2014] reported remission rates of 96.5% at 5 years and 88% at 10 years of follow-up (8). In the pediatric cohort, Glenisson et al. [2024] reported an 83.7% remission rate at 1 year, which decreased to 65% over 2–3 years (14). Endoscopic remission rate was assessed in five studies (29%, 53% and 79% in the surgical group and 48% and 84% in the biological group), with follow-up intervals ranging from 6 months to 5 years. In the LIR!C trial, Ponsioen et al. reported comparable rates between surgery (79%) and IFX (84%) at 7–18 months (5). Not all patients underwent follow-up endoscopy, so these findings reflect only the subgroups assessed.

Complications and readmissions

Postoperative complications among patients who underwent bowel resection were reported in five studies, with an incidence ranging from 9.5% to 38%. Early complications included anastomotic fistula (up to 12%), intra-abdominal abscess (up to 10%, with two cases requiring percutaneous drainage), paralytic ileus, and bowel obstruction. Hemorrhage and hematomas were less frequent but clinically significant, occasionally necessitating transfusion.

Late complications (beyond 30 days) included incisional hernia (up to 6%) and anastomotic stenosis (up to 9%), sometimes requiring reoperation or endoscopic dilation. Severe complications (Clavien-Dindo ≥ IIIa) were reported in 11% of patients in one study, primarily early reoperations and abscess drainages. In the medically treated group, complications were less frequent; the LIR!C trial reported 3% (hospital-acquired pneumonia and perianal abscess) compared to 11% in the surgical group (5). Readmission rates were similar between groups, as seen in the LIR!C trial: in the IFX cohort, 15 of 70 patients required hospital readmission (mean stay: 7 days), whereas 13 of 73 surgical patients were readmitted (mean stay: 5 days), including two admissions to intensive care units (mean stay: 17 days).

Mortality

No deaths were reported in any of the included studies as a direct consequence of either surgical or biologic interventions, supporting the short-term safety of both approaches.

Predictors of clinical failure

Factors associated with failure of medical therapy included stricturing disease, fistulizing behavior, extensive ileocolic involvement, early age at diagnosis, and delayed initiation of treatment. In these contexts, early surgical intervention appeared more favorable, with improved control of inflammation and lower recurrence rates.

Disease recurrence

Postoperative recurrence in the surgery group was assessed in six studies, with rates ranging from 21% at 7–18 months to 35% at 2 years and 27% at 5 years. Long-term follow-up at 10 years indicated that 58% of patients required additional therapy. Early endoscopic recurrence was also substantial; Hammoudi et al. [2020] reported 32% of recurrence in the neoterminal ileum at 6 months post-surgery (12). In other studies, disease recurrence rates were 21–29% within 1 year, 51% within 2 years, and 77% within 5 years after surgery. In the medically treated group, two studies evaluated recurrence: in one, 16% experienced clinical relapse within 18 months, while in the other, 62% required therapy escalation over 10 years, and 48% ultimately underwent intestinal surgery, with a median time to intervention of 17 months.

Follow-up

The follow-up duration ranged from 2 to 10 years, allowing for the assessment of both short-term outcomes (complications and hospitalization length) and long-term outcomes (clinical and endoscopic recurrence, as well as the need for reoperation). However, the wide range of follow-up periods limited direct comparability across studies. In studies directly comparing surgery and biological therapy, only one study reported the need for subsequent biologic treatment during follow-up, finding similar proportions in both groups.

Evaluation of risk of bias for the included studies

A comprehensive risk-of-bias evaluation was conducted for all studies included in this review. Observational studies were examined using ROBINS-I (15), while randomized controlled trials were assessed with RoB2 (16). As detailed in Table S1, most observational studies were classified as having a moderate risk of bias. This judgment largely reflected limitations inherent to non-randomized designs, including residual confounding despite statistical adjustment, non-random participant selection, and, in some cases, partial reliance on retrospectively collected outcome data.

The assessment of the randomized controlled trial, summarized in Table S2, revealed a wider range of methodological quality. The trial conducted by Ponsioen et al. was judged to have a high overall risk of bias. This conclusion was driven mainly by the open-label design and the considerable crossover between treatment groups, both of which increased the likelihood of deviations from intended interventions and may have affected the measurement of patient-reported outcomes such as quality of life.

Although data completeness was satisfactory and selective reporting was not evident, the absence of blinding in evaluating subjective outcomes remained a notable concern. Taken together, these assessments indicate that the methodological robustness of the available evidence varies considerably. While the observational studies consistently demonstrated moderate limitations, the randomized trials ranged from moderately reliable to at higher risk of bias. These factors were carefully considered in interpreting the overall findings and in assessing the strength of the evidence synthesized in this review.

Discussion

CD is a chronic inflammatory disorder that often necessitates complex therapeutic strategies. While the advent of immunobiological agents, such as IFX, has significantly transformed management (3), surgical intervention, particularly laparoscopic ileocecal resection, remains a safe and effective approach for many patients, especially those with complicated disease phenotypes (17). The findings of this SR contribute to the growing body of evidence challenging the conventional step-up paradigm, suggesting that ileocolic resection should not be viewed solely as a last-resort intervention following medical therapy failure, but rather as a legitimate first-line treatment option for a carefully selected subgroup of patients. This paradigm shift is increasingly recognized in international guidelines, which emphasize that in cases of localized ileocecal disease, particularly when stricturing complications are present, early surgical intervention may represent a valid primary alternative to biologic therapy (18).

Several factors have been linked to clinical treatment failure, including stricturing disease, fistulizing behavior, ileocolic involvement, early age at diagnosis, and delayed initiation of appropriate therapy. In such cases, early surgical intervention has been shown to offer benefits, including improved control of inflammation and reduced rates of disease recurrence (19).

A central aspect of shared decision-making is the precise identification of patients most likely to benefit from early surgery. Features such as a stricturing phenotype, fistulizing complications, and extensive ileocolic involvement are strong predictors of medical therapy failure. They may help identify individuals who could derive greater benefit from upfront resection (20). Crucially, the choice between surgery and biologics extends beyond differences in clinical remission rates. Patient-reported outcomes, including quality of life, fatigue, treatment burden associated with lifelong medication, and fear of disease recurrence, are key determinants of treatment preference. Data from the LIR!C trial (5) suggest that, despite differing complication profiles between the two approaches, quality-of-life outcomes can be comparable, emphasizing that the perceived burden of each treatment modality is highly individualized and must be carefully considered during patient consultations (21,22).

Although this does not necessarily pertain to disease location, all included studies specifically addressed cases with ileal or ileocecal involvement, consistent with the scope of this review. In some studies, resection was indicated primarily for patients with stenosing or penetrating phenotypes, whereas in others, surgery was performed earlier, before the development of severe complications. Across studies, disease phenotype, whether inflammatory, stenosing, or fistulizing, has emerged as a key prognostic factor, directly impacting the risk of recurrence and the likelihood of treatment failure (11,23). The strength of this SR lies in the inclusion of the studies that compared both groups, early surgical intervention versus biological therapy for ileocecal CD, which provides the highest-quality evidence directly comparing surgical and medical approaches (5,11). Although overall data support surgery as a valid first-line therapeutic option for selected patients, we highlight that the comparisons were with groups of patients receiving anti-tumor necrosis factor (anti-TNF) therapy, with no data on other biological agents and small molecules.

Our data also support the observed trend that the introduction of biological agents has reduced the overall need for surgery. A meta-analysis of population-based studies conducted before 2000 reported a 10-year surgical risk of 46.6% among patients with CD, whereas a cohort from 2000 to 2017 showed a decline to 29.9% (4). Nevertheless, the need for surgical intervention in CD patients persists. Long-term data (5,11) further underscore the significance of the surgical approach. During extended follow-up, nearly half of the patients initially managed with IFX required surgical resection within a median of 17 months, indicating that biological therapy may not provide a durable solution for limited ileal disease. In contrast, no patient in the surgical arm required a second resection during long-term follow-up.

Postoperative endoscopic surveillance is increasingly recognized as a critical component in the management of CD following ileocolic resection. According to the 2017 American Gastroenterological Association (AGA) guideline (24), postoperative endoscopic monitoring should be performed 6 to 12 months after surgery to detect early recurrence, even in asymptomatic patients, because early endoscopic lesions often precede clinical relapse. Early detection through colonoscopy enables the initiation or escalation of therapy at an earlier stage, which has been associated with improved mucosal healing and a reduced risk of surgical re-resection. Endoscopic remission, a key parameter in the assessment of CD, was inconsistently evaluated across studies, a methodological limitation that affects data comparability.

Our review also identified predictors of clinical treatment failure, including stricturing disease, fistulizing behavior, ileocolic involvement, early age at diagnosis, and delayed therapy initiation, which help explain why certain patients derive greater benefit from early surgery. Importantly, treatment decisions should also consider patient-reported outcomes, such as quality of life, work absenteeism, and associated costs. Surgery was associated with significantly lower long-term costs while maintaining comparable quality-of-life outcomes, despite a higher risk of acute complications (5,11).

Study limitations

The limitations of this review largely reflect the nature of the available evidence. The study methodological heterogeneity, mostly retrospective, with variable follow-up durations and differing outcome measures, posed challenges in generating robust conclusions. For instance, endoscopic remission, a key parameter in evaluating CD, was not consistently assessed across studies, a methodological limitation that affects data comparability. Furthermore, the limited studies that directly compare surgical and medical management predominantly focus on older anti-TNF agents. The absence of comparative data involving newer biologic agents (e.g., vedolizumab, ustekinumab) and small-molecule therapies (e.g., tofacitinib, upadacitinib) represents a significant gap in the literature and, consequently, a limitation of this SR, demanding caution when generalizing our findings to the current treatment landscape.

Despite these constraints, the findings support an individualized, shared decision-making approach to managing limited ileal CD. Early surgical intervention, particularly ileocolic resection, should be regarded as a safe and effective therapeutic alternative option rather than merely a last resort, especially for patients with phenotypes predictive of medical treatment failure. Treatment decisions should be made collaboratively with the patient, taking into account their risk profile, disease characteristics, and personal preferences.

Conclusions

The recurrence rate of CD after intestinal resection varies and is influenced by factors such as smoking, penetrating disease phenotype, emergency surgery, and involvement of the upper GI tract (24). Although biologic therapy, when it is a first choice, is associated with fewer complications, the requirement for additional medical treatment remains similar when compared to early surgical intervention. Pediatric patients demonstrate a higher risk of early postoperative recurrence. Intestinal resection for ileocecal or isolated ileal CD represents an effective alternative to initial biologic therapy, particularly in cases complicated by strictures or other disease-related complications. These findings indicate that early surgical intervention may offer significant clinical benefits, challenging the prevailing paradigm that prioritizes biologic therapy exclusively. Therefore, the therapeutic decision must be individualized, considering disease phenotype (e.g., stricturing vs. inflammatory), risk profile, and patient preference. Long-term, randomized studies are necessary to further validate these observations, ideally including comparisons with newer classes of biologic and small-molecule therapies.

Acknowledgments

We thank Prof. Tristan Torriani for the English editing of this manuscript. We want to thank Ana Paula de Morais for her assistance in searching for articles in the databases.

Footnote

Reporting Checklist: The authors have completed the PRISMA reporting checklist. Available at https://tgh.amegroups.com/article/view/10.21037/tgh-25-131/rc

Peer Review File: Available at https://tgh.amegroups.com/article/view/10.21037/tgh-25-131/prf

Funding: This work was supported by the National Council for Scientific and Technological Development (CNPq) (No. #302557/2021-0 to R.F.L.) and by the Fund to support teaching, research, and extension of the University of Campinas (FAEPEX) (No. #39/2024 to L.M.G.).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tgh.amegroups.com/article/view/10.21037/tgh-25-131/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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