Choi HI, Moon JR, Lee SH, Cha JM. Advanced therapies in patients with inflammatory bowel disease: A nationwide population-based cohort study. World J Gastroenterol 2026; 32(44): 121290 [DOI: 10.3748/wjg.121290]
Corresponding Author of This Article
Jae Myung Cha, MD, Doctor, Department of Internal Medicine, Kyung Hee University Hospital at Gangdong, 892 Dongnam-ro, Gangdong-gu, Seoul 05278, South Korea. drcha@khu.ac.kr
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Gastroenterology & Hepatology
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Choi HI, Moon JR, Lee SH, Cha JM. Advanced therapies in patients with inflammatory bowel disease: A nationwide population-based cohort study. World J Gastroenterol 2026; 32(44): 121290 [DOI: 10.3748/wjg.121290]
Author contributions: Cha JM conceived and design the research plan ideas; Choi HI, Moon JR, Lee SH, and Cha JM performed data acquisition and interpretation of the study; Lee SH and Cha JM analyzed the statistical data of the study; Choi HI and Cha JM drafted and revised the manuscript; all the authors approved the final manuscript.
AI contribution statement: Portions of this manuscript were edited using ChatGPT to check specific English expressions for language refinement and proofreading. AI tools were not used to generate original scientific data, perform independent analyses, or draw scientific conclusions. The authors carefully review and verified all AI-assisted outputs and take full responsibility for the integrity and scientific content of the manuscript.
Supported by BongHwa Scholarship Foundation to the Korean Association for the Study of Intestinal Diseases for 2024.
Institutional review board statement: The study protocol was approved by the Institutional Review Board of Kyung Hee University Hospital in Gangdong (KHNMC IRB No. 2024-05-011).
Informed consent statement: Because all patient data in the Health Insurance Review and Assessment claims database are anonymized, informed consent was not required.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
STROBE statement: The authors have read the STROBE Statement—a checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-a checklist of items.
Data sharing statement: The data reported in this study are available from the corresponding author upon reasonable request.
Corresponding author: Jae Myung Cha, MD, Doctor, Department of Internal Medicine, Kyung Hee University Hospital at Gangdong, 892 Dongnam-ro, Gangdong-gu, Seoul 05278, South Korea. drcha@khu.ac.kr
Received: March 23, 2026 Revised: June 12, 2026 Accepted: July 2, 2026 Published online: November 28, 2026 Processing time: 193 Days and 19.4 Hours
Abstract
BACKGROUND
Patients with inflammatory bowel disease (IBD) often require the sequential use of advanced therapies (ATs) with different mechanism of action. However, real-world data on treatment sequencing, persistence, and treatment pathways of ATs in patients with IBD remain limited.
AIM
To better understand the treatment sequence, persistence, and treatment pathways of ATs in Korean patients with IBD.
METHODS
We performed a nationwide, population-based study of patients newly diagnosed with IBD between 2010 and 2022, after excluding prevalent cases between 2010 and 2011. Among patients who initiated ATs, time to initiation, treatment pathways from first- to fourth-line therapy, and persistence of first-line ATs were analyzed and compared between patients with Crohn’s disease (CD) and ulcerative colitis (UC).
RESULTS
Among patients receiving ATs (CD: n = 6758; UC: n = 4447), anti-tumor necrosis factor therapy was initiated more frequently in patients with CD than in those with UC (40.7% vs 11.2%; P < 0.0001). Infliximab was the most commonly used first-line agent (n = 6885), with greater use in CD than in UC (65.1% vs 55.9%), whereas vedolizumab was more frequently used in UC (13.4% vs 2.5%) and ustekinumab in CD (9.5% vs 3.6%) (all P < 0.0001). The median time to initiating first-line therapy was shorter in patients with CD compared with those with UC. Persistence on infliximab (1037 days vs 516 days), adalimumab (1135 days vs 698 days), ustekinumab (458 days vs 56 days) (all P < 0.0001), and vedolizumab (359 days vs 281 days; P = 0.0057) was longer in patients with CD than in those with UC.
CONCLUSION
The treatment patterns of ATs for IBD differed substantially between CD and UC. These findings highlight the distinct real-world treatment sequencing and durability between IBD subtypes and underscore the need for optimized, disease-specific therapeutic strategies.
Core Tip: This nationwide Korean study demonstrates that advanced therapy use for inflammatory bowel disease shows distinct patterns between Crohn’s disease and ulcerative colitis. Anti-tumor necrosis factor agents, particularly infliximab, are the most common first-line treatments, with earlier initiation and longer persistence in Crohn’s disease. In contrast, vedolizumab is more frequently used for ulcerative colitis, and ustekinumab more commonly used for Crohn’s disease. Overall, treatment sequencing and durability differed significantly according to disease subtype, highlighting the importance of tailored, disease-specific therapeutic strategies in real-world clinical practice.
Citation: Choi HI, Moon JR, Lee SH, Cha JM. Advanced therapies in patients with inflammatory bowel disease: A nationwide population-based cohort study. World J Gastroenterol 2026; 32(44): 121290
The global incidence and prevalence of inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD), have progressively increased in both Western and Asian regions[1,2]. IBD management commonly follows a stepwise pharmacological approach, initiating with conventional agents such as 5-aminosalicylates, corticosteroids, and thiopurines, with subsequent escalation to advanced therapies (ATs), including biologics and small-molecule drugs[3,4]. The therapeutic landscape has expanded considerably, with a growing repertoire of ATs available, and therapeutic targets have evolved beyond symptom relief toward mucosal healing and histologic remission[5,6]. However, identifying the most appropriate AT strategy for individual patients remains challenging, given the heterogeneous and multifactorial nature of IBD pathogenesis.
In Asia, IBD presents with epidemiological and phenotypic features that differ significantly from those observed in Western populations[7]. Region-specific factors, including the endemic burden of infectious diseases such as tuberculosis and herpes zoster, socioeconomic conditions, and national reimbursement frameworks, are important determinants of AT selection and sequencing in Asia. While evidence from Western cohorts supports the early introduction of ATs[8], conventional or accelerated step-up strategies remain prevalent across Asia. Sankey diagrams offer an intuitive framework for visualizing real-world AT utilization patterns in populations with IBD. However, population-level data characterizing AT sequencing and selection in Asian IBD cohorts remain scarce, and treatment pathways are inherently shaped by country-specific healthcare infrastructure, drug availability, and reimbursement policies[9,10]. Siegel et al[9] delineated the treatment pathways for AT initiation in United States patients with IBD, while Matsuoka et al[10] showed the treatment pathways for ATs in Japanese patients with refractory UC. Both studies, however, were constrained in scope one by its focus on pre-biologic treatment sequences and the other by restriction to refractory UC population[9,10]. To address these gaps, we characterized the AT treatment pathways and, treatment patterns, and first-line persistence in Korean patients with IBD using nationwide population-based data.
MATERIALS AND METHODS
Data source
We conducted a retrospective, observational cohort study using administrative claims data from the Health Insurance Review and Assessment (HIRA) database, covering the period from 2010 to 2022. The HIRA serves as the national authority for reviewing and approving reimbursements for health insurance claims in South Korea for the entire Korean population under the National Health Insurance system[11-13]. The dataset provides anonymized individual-level information encompassing sociodemographic characteristics, health care service utilization (including diagnostic, procedual, and prescription records), principal diagnoses, and concurrent comorbidities. Disease classification within the HIRA database are recorded using the Korean Classification of Diseases, an adaptation of the International Classification of Diseases, 9th/10th Revision.
In South Korea, eligible patients with IBD may be registered in the Rare Intractable Disease (RID) program, entry into which requires fulfillment of strict and uniform diagnostic criteria[12,13]. Since 2009, RID-registered patients with IBD have benefited from a substantially reduced out-of-pocket co-payment of 10% for IBD-related medical costs[12,13]. RID enrollment is contingent on diagnostic verification by credentialed physicians at designated healthcare institutions, ensuring adherence to predetermined eligibility standards. Registration is formalized through disease-specific V codes V130 for CD and V131 for UC assigned only to patients who satisfy the requisite clinical criteria[14,15]. This structured verification process underpins the accuracy and reliability of the IBD-related claims data within the HIRA system. Given that all records in the HIRA database are fully de-identified at the source, the requirement for individual informed consent was waived, and the study was reviewed and approved by the Institutional Review Board of Kyung Hee University Hospital at Gangdong (KHNMC IRB No. 2024-05-011).
Patients with IBD
Prevalent cases, individuals with any prior IBD diagnostic codes, were identified during a two-year washout window spanning January 2010 to December 2011 (screening period). An incident IBD case was defined as a first-time RID registration between January 2012 and December 2022 (study period) in adults aged at least 17 years, with no IBD claims during the screening period. The age threshold for adult patients was based on the age classification used in the Montreal classification of IBD. Eligible patients with IBD were identified from the RID and HIRA databases using disease-specific diagnostic and registration codes: K50 combined with V130 for CD, and K51 combined with V131 for UC. Because RID enrollment occurs at the point of diagnosis, the exclusion of all individuals registered during the screening period effectively ensured that only truly incident cases entered the study cohort. Patients carrying diagnostic codes for both UC and CD were excluded to maintain unambiguous disease classification. Additional exclusion criteria were attributable to other conditions, specifically, those with conventional IBD medications for < 90 days or those who used ATs prior to IBD diagnosis. In Korea, patients with IBD are generally managed using a step-up approach, beginning with conventional agents followed by ATs, and top-down approach, commencing with biologics, is not covered by the national insurance scheme.
Study design
This analysis was embedded within a nationwide population-based IBD cohort constructed from the HIRA database (2010-2022), focusing on patients who received at least one AT prescription. The index date was defined as the date of first IBD code for diagnosis. The AT-treated group was defined as patients who received one or more AT prescriptions, whereas comparator group included patients treated exclusively with conventional therapies. In the Korean reimbursement system, AT initiation typically leads to the completion of induction therapy because: (1) Reimbursement guidelines require response evaluation after induction; and (2) Switching AT agents results in permanent loss of coverage for the next treatment. First-line ATs refer to the first use of ATs following prior exposure to conventional medications, with its index date corresponding to the dispensing of that medication class. Time to the first AT was defined as the interval from the IBD index date to the date of the first prescription of ATs. First-line AT persistence was defined as uninterrupted use of the index AT without substitution or permanent discontinuation, capturing the duration for which a patient remained on the originally prescribed agent. As a claims-based study, we identified therapeutic failure/switching when the initial AT was replaced by a different agent. Given the varying dosing schedules of different ATs, we applied drug-specific grace periods based on their standard dosing intervals. A grace period beyond the expected next dose was allowed before considering discontinuation. The persistence of each AT was evaluated according to its own approved dosing regimen. For example, maintenance intervals for infliximab (every 8 weeks), adalimumab (every 2 weeks), and vedolizumab (every 8 weeks) were individually applied. Patients who discontinued before completing standard induction were excluded from the persistence analyses to avoid misclassification of short-term trial use. A treatment pathway was conceptualized as a patient’s longitudinal sequence of distinct AT exposures, delineated by each transition to a new ATs, with a treatment cycle representing a single dispensed prescription. Treatment pathways were rendered as Sankey diagrams to visually map the patient flow across treatment lines and identify the predominant therapeutic sequences.
All IBD medications were classified according to their mechanism of action as conventional treatments (non-ATs) or ATs. The conventional treatments category included 5-aminosalicylic acids (mesalamine, sulfasalazine, and olsalazine), immunomodulators (azathioprine, 6-mercaptopurine, and methotrexate), and systemic corticosteroids (betamethasone, cortisone, desoxycorticosterone, dexamethasone, hydrocortisone, methylprednisolone, paramethasone, prednisolone, prednisone, and triamcinolone), and budesonide. Topical corticosteroids, including eye drops, ointments, creams, jellies, and lotions, were excluded. Under Korean national reimbursement regulations, ATs are not approved for primary or top-down use in IBD, and patients are required to demonstrate prior exposure to conventional agents before AT coverage is granted. Consequently, AT initiation in this cohort was almost universally preceded by the conventional treatment. The eligible ATs included infliximab, adalimumab, golimumab, vedolizumab, ustekinumab, and tofacitinib. Other ATs, such as filgotinib, ozanimod and upadacitinib, were not included in the analysis, because they were not available during the study period. Patient distributions across sequential AT lines were quantified, with proportions reported for first- through fourth-line AT use following the initial AT exposure. Using ICD codes, comorbidities are defined as hypertension (I10-13, and I15), diabetes mellitus (E11-14), dyslipidemia (E78), congestive heart failure (I50), ischemic heart disease (I20-I25), cerebrovascular disease (I63-64), chronic obstructive pulmonary disease (J41-44), and end-stage renal disease (N18-19, Z49, Z94.0, Z99.2) (Supplementary Table 1)[11].
Statistical analysis
Descriptive statistics for continuous variables are presented as means ± SDs, while categorical variables are summarized as frequencies and proportions. To compare the characteristics between the non-AT and AT groups, t-tests were used for continuous variables, and χ2 tests were used for binary and categorical variables. A two-tailed alpha level of 0.05 was applied as the threshold for statistical significance across all tests. Statistical analyses were performed using R software (version 4.2.3; R Foundation for Statistical Computing, Vienna, Austria). The statistical methods of this study were reviewed by Lee SH from Samsung Medical Center.
RESULTS
A total of 56335 incident IBD cases were identified after excluding prevalent cases (n = 26007), patients with no IBD medication use (n = 2793) or those with IBD medication use < 90 days (n = 6192). Table 1 shows the baseline characteristics of the patients with IBD according to type (CD, n = 16598; UC, n = 39737). The mean age was significantly lower in the CD group than in the UC group (30.2 years vs 42.3 years; P < 0.0001). A higher proportion of patients with CD were aged 18-40 years, whereas patients with UC were more commonly aged ≥ 41 years (P < 0.0001). Male were less prevalent among those with CD than among those with UC (P < 0.0001). The use of ATs was more frequent in patients with CD than in those with UC (40.7% vs 11.2%, P < 0.0001). Patients with CD were more likely to be treated in metropolitan areas than those with UC (P < 0.0001). Regarding comorbidities, liver disease, rheumatic disease, diabetes, hypertension, cardiovascular disease, and malignancy were significantly more common in patients with UC than in those with CD. However, there were no statistically significant differences in the prevalence of obesity, pulmonary disease, or renal disease between groups.
Table 1 Baseline characteristics of adult patients with newly diagnosed inflammatory bowel disease, mean ± SD/n (%).
Among patients who received ATs after diagnosis (CD, n = 6758; UC, n = 4447), the most commonly initiated first-line agents were anti-tumor necrosis factor (TNF) biologics (Table 2). Infliximab was used more frequently in patients with CD than in those with UC (65.1% vs 55.9%; P < 0.0001). Among non-anti-TNF biologics, vedolizumab was more often used for UC (13.4% vs 2.5%; P < 0.0001), whereas ustekinumab was more commonly used for CD (9.5% vs 3.6%; P < 0.0001). Golimumab and tofacitinib were administered only to patients with UC. The median time to initiation of first-line ATs was generally shorter in patients with CD than in those with UC (Table 2). For infliximab, the median time was 167 days in CD vs 348 days in UC (P < 0.0001) and 273 days vs 498 days for adalimumab (P < 0.0001). Similar patterns of earlier initiation in CD were observed for vedolizumab (551 days vs 830.5 days; P = 0.0074) and ustekinumab (651.5 days vs 997 days; P = 0.0057).
Table 2 Use of first-line advanced therapies in patients with inflammatory bowel disease, n (%).
Figure 1A presents the treatment pathways of ATs for IBD according to first- to fourth-line use. Infliximab was the most commonly prescribed first-line therapy (n = 6885). Adalimumab was used substantially as both a first (n = 2537)- and second-line (n = 1155) agent. Ustekinumab and vedolizumab were used across multiple treatment lines, reflecting their increasing integration in various clinical scenarios. Tofacitinib was generally reserved for subsequent lines of therapy due to safety considerations and treatment sequencing. Golimumab shows limited clinical application beyond early treatment lines. Figure 1B illustrates the AT treatment pathways for CD. Infliximab and adalimumab were the dominant first-line therapies; infliximab was used almost exclusively in the first-line setting (n = 4400), while adalimumab was commonly prescribed both as a first- (n = 1543) and second-line treatment (n = 615). Ustekinumab and vedolizumab were used flexibly across multiple lines, particularly as second- or third-line agents. Figure 1C depicts the treatment pathways for ATs in UC. Infliximab and adalimumab dominated the first-line treatment landscape, with infliximab being the most frequently prescribed first-line therapy (n = 2485) and adalimumab commonly used as both first- (n = 994) and second-line therapy (n = 540). Vedolizumab and ustekinumab were used across multiple lines, reflecting their flexibility and tolerability. Golimumab was used modestly, but was present across all lines. Tofacitinib was primarily reserved for later treatment lines, second (n = 44), third (n = 13), and fourth (n = 7), with minimal first-line use (n = 20).
Figure 1 Treatment pathways of advanced therapies were visualized using Sankey diagrams.
A: Patients with inflammatory bowel disease; B: Patients with Crohn’s disease; C: Patients with ulcerative colitis.
The median persistence of anti-TNF biologics differed significantly between patients with CD and those with UC (Table 3). For infliximab and adalimumab, the median persistence was significantly longer in patients with CD than in those with UC (infliximab: 1037 days vs 516 days, P < 0.0001; adalimumab: 1135 days vs 698 days, P < 0.0001). Among the non-anti-TNF biologics, vedolizumab and ustekinumab also had significantly longer persistence in patients with CD than in those with UC (vedolizumab: 359 days vs 281 days, P = 0.0057; ustekinumab: 458 days vs 56 days, P < 0.0001).
Table 3 Persistency of advanced therapies in adult patients with inflammatory bowel disease after the initiation of first-line therapies, median (Q1-Q3).
Population-based data characterizing first-line AT selection, treatment persistence, and longitudinal treatment pathways in Asian patients with IBD remain scarce. The major clinical implication of this study is the comprehensive characterization of real-world AT utilization patterns and first-line persistence in a large Asian population with IBD, leveraging a nationwide administrative claims database with near-complete population coverage. Considering the differing epidemiologic and clinical characteristics, as well as health-insurance policies in Asia, our study provides region-specific evidence that complements Western data. Furthermore, by systematically comparing the timing of AT initiation and therapy persistence according to the disease type, drug class, and sequential lines of therapy, this study offers valuable insights applicable to real-world clinical decision-making in Asia.
The choice of first-line ATs in biologic-naive patients with IBD may be influenced by various clinical scenarios, and there is insufficient evidence to suggest an optimal biological therapy sequence[16]. Importantly, the choice of first-line ATs in Asian countries, including Korea, may differ from that in Western countries because of several region-specific factors, such as differing infectious risks and variations in reimbursement systems. Asian patients with IBD face a higher risk of certain infections, particularly tuberculosis and hepatitis B reactivation, which necessitates careful consideration when selecting anti-TNF agents[2,7,17]. This mandates tuberculosis screening before initiating anti-TNF therapy, and potentially influences the selection of gut-selective agents such as vedolizumab in high-risk patients[18]. The risk of herpes zoster is also notably elevated in Asian patients with IBD who are treated with anti-TNF agents and tofacitinib, which may affect treatment preferences[19,20]. Genetic and pharmacogenetic differences between Asian and Western populations may influence drug efficacy and safety profiles. Additionally, variations in healthcare reimbursement systems across Asian countries significantly affect drug accessibility and prescription patterns. In Korea, the HIRA system has specific approval criteria and sequential requirements for ATs use that differ from those in Western insurance models. In this context, the present study is meaningful as it provides insights into the selection of first-line ATs under real-world conditions in Korea. In this study, anti-TNF biologics were the most commonly used first-line ATs, with infliximab and adalimumab more frequently prescribed for CD than for UC. In contrast, vedolizumab was more frequently used for UC, and ustekinumab for CD. Notably, the median time to the initiation of first-line ATs was consistently shorter in CD than in UC across all agents. Our real-world data align with recent network meta-analyses, which suggest that anti-TNF agents, particularly infliximab, are the preferred first-line ATs for biologic-naive patients with IBD, and that vedolizumab has demonstrated comparable efficacy to infliximab in patients with UC but not in those with CD[21-25].
Recommendations regarding first-line ATs for IBD have been evolving, driven by updates in clinical guidelines, changes in reimbursement criteria, and the emergence of novel agents[26-28]. However, real-world data provide substantial clinical insights, reflecting not only guideline implementation in practice but also therapeutic decision-making influenced by regional factors, such as disease phenotype, medication access, and infection risk. Overall, this study suggests a predominance on anti-TNF agents (especially infliximab and adalimumab) in the early treatment lines, whereas ustekinumab, vedolizumab, and tofacitinib are more commonly introduced in later lines in Korea.
From the perspective of AT treatment pathways, the current study showed that infliximab and adalimumab are the most frequently used first-line ATs in IBD, particularly in CD. Ustekinumab and vedolizumab were used across multiple treatment lines, whereas tofacitinib was primarily reserved for the later lines. AT persistence was substantially more prolonged in patients with CD than in those with UC, suggesting greater durability of the therapeutic response in this disease subtype. Our findings align with those of many Western studies, showing that first-line ATs continue to be predominantly centered on anti-TNF agents (e.g., infliximab and adalimumab)[29]. Recently, the use of non-anti-TNF therapies has been increasing in Western countries, not only as second-line options, but also as first-line treatments[30]. However, our data showed that the early use of non-anti-TNF therapies is relatively limited in Korea, with a stronger reliance on anti-TNF treatments. This may be explained by approval timelines, reimbursement policies, healthcare infrastructure, and drug accessibility, which appear to exert a stronger influence than in Western settings, potentially leading to slower diversification of treatment pathways in Korea. After failure of first-line anti-TNF agents, switching to non-anti-TNF agents rather than a second anti-TNF agent may be favored[31]. The optimal selection of first-line ATs is critical because the greater the number of therapy lines used, the lower the likelihood of achieving remission[32].
Existing evidence on AT persistence in IBD is inconsistent across studies, with findings frequently constrained by abbreviated observation periods, substantial heterogeneity in study populations, or the absence of head-to-head comparisons between CD and UC. In the present study, the median persistence of ATs was significantly longer in patients with CD than in those with UC. The persistence of infliximab, adalimumab, and ustekinumab was significantly longer in patients with CD than in those with UC (all P < 0.0001), as was that of vedolizumab (P = 0.0057). The median persistence of vedolizumab observed in our study may be attributed to its initial approval as a second-line therapy for IBD under the reimbursement system in Korea. Our results corroborate those of an Austrian single-center study that similarly observed superior first-line AT persistence in CD compared to UC[33]. However, the study was limited by its single-center design and included only anti-TNF agents, with limited data on other ATs. Given the higher risk of treatment non-persistence in UC, more careful selection of first-line ATs is warranted in patients with UC. In real-world registry data from the national Australian IBD study and a meta-analysis, 12-month persistence rates were higher with ustekinumab for CD and vedolizumab for UC than with anti-TNF agents[34,35]. However, these studies reported only 12-month outcomes and did not assess the median or long-term persistence of individual ATs, distinguishing them from the present study. In nationwide population-based data from Korea, 24-month persistence rates were higher for ustekinumab in CD and vedolizumab in UC than for other ATs[36]. Nationwide Japanese data also showed superior 12-month persistence with ustekinumab in CD, regardless of prior biologic exposure[37]. These findings suggest that disease phenotype may play a more prominent role in treatment persistence than previously recognized, particularly for non-anti-TNF agents.
Caution is required when interpreting the persistence of ATs in real-world observational studies. In Korea, tofacitinib was approved for medical insurance reimbursement for the treatment of UC on May 1, 2019. As the current study was only conducted until 2022, the tofacitinib persistence date may have reached the end of the study period without sufficient observations. Ustekinumab was approved for medical insurance reimbursement for CD on December 1, 2018, and for UC, it was approved as a second-line therapy on January 1, 2021, with approval expanded to first-line therapy on September 1, 2022. Therefore, the persistence data for ustekinumab may also reflect the influence of the reimbursement approval criteria rather than the actual difference between CD and UC, and there is a possibility that the end of the study period was reached without sufficient observations. Therefore, the persistence data for tofacitinib and ustekinumab in this study should be interpreted with caution.
The real-world treatment pathways of IBD vary by region and healthcare system. Siegel et al[9] analyzed the treatment pathways leading to AT initiation in patients with IBD in the United States using commercial insurance and Medicare data. Even in this setting, < 1% of patients with UC and < 5% of those with CD initiated ATs without prior conventional therapy. While the United States study focused on conventional treatment pathways leading to AT initiation, our study evaluated the treatment patterns of ATs following the initiation of first-line ATs, representing a key difference in study design. Similarly, in another large insurance claims database, only 14.4% of CD patients and 5.9% of UC patients had received ATs at a mean follow-up of 2.3 years after diagnosis[38]. Patients typically undergo four to six courses of conventional therapy before initiating first-line ATs. In a nationwide Canadian study, the mean times from diagnosis to initiation of the first AT were 644 and 978 days for CD and UC[39]. Notably, that study included only patients who had been exposed to at least two ATs, making a direct comparison with our findings difficult. In Japanese hospital-based claims data, similar patterns of prolonged corticosteroid use and delayed AT initiation were observed in patients with UC[40]. All data highlights the considerable delays in AT initiation, suggesting that the guideline-recommended strategy for the early use of ATs has yet to be fully implemented in real-world clinical settings.
The differences in the treatment patterns between CD and UC observed in our study may be explained by several clinical and demographic factors. Patients with CD are often younger at diagnosis and tend to have a more complicated disease course, including penetrating and stricturing phenotypes, which may necessitate earlier intensification with ATs[41]. Anti-TNF agents are frequently prioritized in CD to manage fistulizing disease and extra-intestinal manifestations, which are more prevalent in CD than in UC. Additionally, the potential for transmural inflammation and irreversible bowel damage in CD may drive early AT interventions. In contrast, patients with UC often present with less complicated disease at diagnosis and may achieve adequate disease control with conventional therapies before requiring treatment escalation to ATs[42]. The mucosa-limited nature of UC inflammation and the availability of effective conventional therapies may contribute to less use of ATs in patients with UC. These disease-specific characteristics, combined with reimbursement policies and physician treatment preferences, collectively shape the distinct treatment trajectories observed in patients with CD and UC in real-world practice.
This study has several limitations. First, a nationwide claims database with comprehensive population coverage was used in our study; however, our findings may not be generalizable to other populations, as the treatment pathways and persistence of ATs can depend on the natural history and severity of IBD, infection risk, and local reimbursement criteria. However, our results likely reflect the treatment pathway data for IBD medications in Korea. Second, owing to the retrospective study design and lack of propensity score matching, comparative analyses between CD and UC were limited. Nevertheless, we were able to provide substantial real-world information on treatment pathways and persistence of ATs in Asian patients with IBD. In addition, it was difficult to assess certain medical information, such as current medication use, because nationwide databases do not provide the same level of detail as hospital-based databases. However, hospital-based databases may be subject to reporting bias, because the use of ATs in patients with IBD is relatively uncommon and variable. Even in a nationwide database, the number of patients for some ATs was low in certain subgroups. Third, classification errors may exist in the claims-based data, as variables were defined based on operational definitions using diagnostic and prescription codes. However, patients with IBD are strictly managed within the Korean healthcare system, and ATs are typically prescribed in tertiary hospitals. Unlike other conditions with lower coding accuracy, an operational definition-based classification of IBD is expected to be reliable in Korea. Fourth, we used a pragmatic definition of AT exposure (≥ 1 prescription) for the AT group. However, the Korean reimbursement policies that discourage AT switching and mandate post-induction response evaluations promote high treatment persistence. The extended median treatment duration in our cohort supports the finding that early discontinuation is rare. Pediatric patients with IBD were excluded in this study. As the reimbursement criteria for pediatric and adult IBD differ in Korea, the treatment pathways may also differ. As the results of this study pertain to adults, further research is needed to evaluate the treatment patterns in pediatric IBD.
CONCLUSION
In patients with IBD, anti-TNF biologics are the most commonly and persistently used first-line ATs, with notable differences in selection and use of biologic agents between the two subtypes. Our data showed that the time interval from IBD diagnosis to AT initiation was prolonged, primarily because of the reimbursement policy requiring the mandatory use of conventional therapies before AT eligibility in Korea. This step-up approach mandated by the Korean healthcare system may delay access to ATs compared to settings, such as Western countries, where top-down strategies are available. Further research should explore the clinical drivers and long-term outcomes associated with the differential biologic agents’ use and treatment persistence in IBD, especially in Asian countries.
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Scientific quality: Grade B, Grade B, Grade B, Grade B
Novelty: Grade A, Grade A, Grade B, Grade B
Creativity or innovation: Grade B, Grade B, Grade B, Grade B
Scientific significance: Grade B, Grade B, Grade B, Grade B
P-Reviewer: Sassaki LY, Assistant Professor, MD, PhD, Brazil; Zheng YY, Associate Professor, Associate Research Scientist, Professor, China S-Editor: Fan M L-Editor: A P-Editor: Wang CH
