Persistence of advanced therapies in patients with inflammatory bowel disease: retrospective cohort study using a large healthcare claims database in Japan

Katsuyoshi Matsuoka; Ko Nakajo; Shiho Kawamura; Yongjing Zhang; Hsingwen Chung; Bryan Wahking; Jin Yu Tan; Hong Qiu

doi:10.5217/ir.2024.00118

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Original Article Persistence of advanced therapies in patients with inflammatory bowel disease: retrospective cohort study using a large healthcare claims database in Japan: Katsuyoshi Matsuoka^1,*, Ko Nakajo^2,*, Shiho Kawamura³, Yongjing Zhang⁴, Hsingwen Chung⁵, Bryan Wahking³, Jin Yu Tan³, Hong Qiu^6,; DOI: https://doi.org/10.5217/ir.2024.00118
Published online: January 2, 2025

¹Division of Gastroenterology and Hepatology, Department of Internal Medicine, Sakura Medical Center, Toho University, Sakura, Japan

²Office of the Chief Medical Officer, Johnson & Johnson, Tokyo, Japan

³Johnson & Johnson International, Singapore

⁴Office of the Chief Medical Officer, Johnson & Johnson, Shanghai, China

⁵Office of the Chief Medical Officer, Johnson & Johnson, Raritan, NJ, USA

⁶Office of the Chief Medical Officer, Johnson & Johnson, Raritan, NJ, USA

Correspondence to Hong Qiu, Johnson & Johnson, 1125 TrentonHarbourton Road, Titusville, NJ 08560, USA. E-mail: hqiu@its.jnj.com

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

• Received: July 22, 2024 • Revised: September 24, 2024 • Accepted: October 8, 2024

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
There are few studies that comprehensively report real-world persistence for first-line advanced therapies used to treat inflammatory bowel disease. We aimed to describe persistence of first-line advanced therapies among incident biologic or Janus kinase inhibitor users with inflammatory bowel disease.
Methods
Retrospective cohort study using the Japan Medical Data Center database from January 1, 2010, until September 30, 2022. Patients aged ≥15 years with relevant diagnostic and treatment codes were included. All eligible patients were observed until study end (September 30, 2022), death, or disenrollment, whichever occurred first.
Results
Among 1,115 patients with Crohn’s disease included in the analysis, 41.4% initiated adalimumab, 37.4% infliximab, 18.1% ustekinumab, and 3.0% vedolizumab. Median age was 31.2–34.8 years, 72.8% to 85.9% were male. Persistence at 12 months was 84.7% for adalimumab, 87.7% for infliximab, 91.3% for ustekinumab, and 53.1% for vedolizumab. Persistence at 24 months was 76.3%, 76.8%, 80.4%, and 28.6%, respectively. Among 1,942 patients with ulcerative colitis, 24.8% initiated adalimumab, 33.6% infliximab, 11.2% golimumab, 17.5% vedolizumab, 5.6% ustekinumab, and 7.3% tofacitinib. Mean age was 38.2–40.4 years, 57.4% to 65.8% were male. Persistence at 12 months was 57.6% for adalimumab, 87.7% for infliximab, 54.9% for golimumab, 69.7% for vedolizumab, and 84.0% for ustekinumab. At month 24, persistence for ustekinumab was 75.0%, versus 42.9%–59.4% for other treatments.
Conclusions
Index treatment with ustekinumab resulted in high persistence through 24 months after initiation in patients with Crohn’s disease or ulcerative colitis. Our study provides insights into the real-world usage of advanced treatments for patients with IBD in Japan.
Keywords: Crohn disease; Inflammatory bowel disease; Persistence; Ulcerative colitis; Ustekinumab

INTRODUCTION

Inflammatory bowel disease (IBD) is estimated to impact 4.9 million persons globally [1]. Crohn’s disease (CD) and ulcerative colitis (UC) are the major types of IBD, and are idiopathic, intractable, chronic inflammatory diseases affecting the gastrointestinal tract. UC is characterized by inflammation and ulceration of the mucosa and sub-mucosa of the rectum and colon, whereas CD causes transmural lesions that can affect any part of the gastrointestinal tract [2,3]. Symptoms include diarrhea, abdominal pain, rectal bleeding, fever and weight loss, fatigue, and extraintestinal manifestations that may involve joints, skin, or the eye. Both diseases tend to wax and wane, and disease flares can be associated with substantial morbidity, sometimes requiring hospitalization or surgical intervention [2,3].

Treatment aims to induce disease remission and prevent relapse and complications using long-term maintenance therapy. The treatment paradigm for IBD has undergone fundamental changes since the availability of biologic therapy and small molecules, collectively referred to as advanced therapy. Advanced therapies comprise biologics that target tumor necrosis factor-α (TNF-α) (infliximab, adalimumab, certolizumab, golimumab), integrins (vedolizumab, natalizumab), and interleukins (ustekinumab, risankizumab, mirikizumab), and small molecules such as Janus kinase (JAK) inhibitors (tofacitinib and filgotinib for UC, upadacitinib for UC and CD), and sphingosine-1-phosphate receptor modulators (ozanimod, UC only) [4]. The early use of advanced therapies has been shown to improve clinical outcomes in IBD, although most evidence currently exists for their benefit in CD rather than UC [5,6].

The global prevalence of IBD in 2019 was estimated at 59 per 100,000 population with marked geographical variability [7]. The highest prevalence is observed in North America (210 per 100,000 population), Western Europe (188 per 100,000), Central Europe (160 per 100,000), and Australasia (156 per 100,000) [7]. Previously uncommon in Asia, Africa, and South America, the incidence of IBD is increasing rapidly in these regions [7,8]. Geographic variability exists in terms of age of onset, sex distribution, and clinical course, possibly due to regional prevalence of genetic polymorphisms or differences in environmental risk factors [9]. In Japan, the period prevalence for CD and UC from 2010 to 2019 ranged from 40 to 57 per 100,000 and from 158 to 266, respectively [10-12]. While still lower than in Western countries, IBD prevalence is increasing rapidly [11-13].

Long-term treatment of IBD is frequently required to maintain remission. Commonly reported reasons for drug discontinuation are poor efficacy (loss or lack of response), and adverse events [14,15]. As a result, persistence to treatment is frequently used as an indicator of efficacy, tolerability, and patient satisfaction with treatment. Persistence refers to the number of days patients continue to take the prescribed medication without exceeding a permissible gap [16].

Seven biologics and four JAK/integrin inhibitors are approved and reimbursed for the management of IBD in Japan as of January 2024. The Japanese IBD management guideline does not provide an explicit positioning of these treatment options, and at the time of our study, there were few reported studies that assessed real-world treatment patterns of newer drug classes for IBD in Japanese patients [17]. To address this evidence gap, we aimed to describe persistence to first and second line advanced therapy among patients in Japan with CD or UC using real-world data from a nationally representative employment claims database. These data can help guide treatment selection for patients with IBD initiating treatment with advanced therapies.

METHODS

1. Data Source

The Japan Medical Data Center (JMDC) database consists of data from employee health insurance and contains claims data from 14 million individuals in Japan [18]. Members are non-government employees aged 18–65 years and their dependants of all ages up to 75 years. Data captured by JMDC include membership status of the insured individuals, demographic information, inpatient and outpatient episodes including diagnoses as International Classification of Disease 10 (ICD-10) codes, procedures, and dispensed prescriptions in Anatomical Therapeutic Chemical format. The data from an insured employee or their dependent can be followed longitudinally even if they transfer hospitals or visit multiple facilities [19].

2. Study Design, Objectives, and Population

The primary objective of this retrospective cohort study was to describe persistence of the index (or first-line) biologic treatment (anti-TNF-α, integrin, and interleukin antagonists) or JAK inhibitor treatment among incident users with CD or UC in Japan. All treatments were prescribed in routine clinical care and all visits were captured as a part of normal clinical practice.

Patients in the JMDC with a diagnosis of CD or UC, and who received any advanced treatment between January 1, 2010, and September 30, 2022, were included. Patients were identified using previously validated algorithms based on ICD-10 codes (K50 for CD, K51 for UC) and prescription codes for each disease within ± 30 days from the first diagnosis (Supplementary Table 1) [20,21]. Individuals with codes in the same month for both CD and UC, or for Behcet’s disease (M35), were excluded. Eligible patients were ≥ 15 years of age, had at least 6 months of enrolment in the database prior to the index date (defined as the baseline period), and were prescribed only one index biologic or JAK inhibitor treatment for first-line treatment. All eligible patients were observed until the end of the study period (September 30, 2022), death or disenrollment from the JMDC, whichever occurred first. Patients whose insurance enrolment ceased during the study period were censored at the last date of enrolment.

Advanced therapies of interest were adalimumab, infliximab (only intravenous route approved), vedolizumab, ustekinumab, golimumab (only for UC), and tofacitinib (only for UC). Filgotinib, a JAK inhibitor, was approved for use in UC in April 2022 and was only included as second line treatment due to the limited follow-up period available. The first identified biologic or JAK inhibitor treatment at or after the diagnosis of IBD was considered as the index treatment in patients who had no prior biologic or JAK inhibitor treatment within the previous 6 months. The index date was the date of initiation of the index treatment.

The database contained anonymized data and was licensed from JMDC Co., Ltd. by Janssen Research & Development, LLC. Patient information was linked via anonymized patient identifiers assigned in the database. Based on the Ethical Guidelines on Biomedical Research Involving Human Subjects (Ministry of Education, Culture, Sports, Science and Technology, and Ministry of Health, Labour and Welfare of Japan) ethics committee review and obtaining written informed consent were not required. The study was approved by the sponsor’s internal approval committee in accordance with Japanese ethical and legal guidelines.

3. Variables and Outcomes

Patient demographic information (age and sex) and clinical characteristics (previous IBD medications, comorbidities, inpatient/outpatient status at the index date, and hospitalizations during the baseline period) were collected. Comorbidities were identified using ICD-10 codes and were assessed using the Charlson Comorbidity Index during the baseline period. Inpatient status at the index date was defined as either an inpatient or Diagnosis Procedure Combination claim. The latter is the Japanese classification for inpatients in the acute phase of illness. Concomitant use of immune modulators or steroids was defined as prescriptions occurring in the same month (± 30 days) as the advanced therapies.

Persistence at 6, 12, 18, and 24 months was evaluated in patients who were enrolled in the database continuously for those periods after initiating the target biologics. Persistence was defined as continuous treatment over each follow-up period (i.e., 6, 12, 18, or 24 months after the index date), without the presence of a treatment gap defined as 1.5 times the number of days covered by the last prescription. Expected days of supply for infusions were based on maintenance dosing according to the drug label (Supplementary Table 2). Switching was defined as a prescription for an advanced therapy, other than the index treatment, before the end of the pre-defined treatment gap for the index treatment.

Discontinuation was defined as a presence of treatment gap that was not accompanied by a switch to another biologic. The date of discontinuation was the last day supply of the last prescription.

Persistence at 12 months stratified by inpatient/outpatient status at the index date was assessed. Additionally, corticosteroid-free persistence was assessed in patients who used corticosteroids during the baseline period and was defined as the proportion of patients who were persistent at 12 months, and who had at least 180 consecutive days with no prescription for corticosteroids up to the end of a 12-month observation period.

The proportion of days covered (PDC) was used to assess the extent to which a patient acts in accordance with the prescribed interval and dose of a dosing regimen. PDC was calculated as the number of days covered by prescriptions for an advanced treatment over 12 or 24 months, divided by the number of days in the 12-month or 24-month period from the index date, multiplied by 100. The proportion of those who achieved PDC ≥ 80% was reported.

Treatment sequences during first and second lines were described. Second-line treatments were those either switched to during the gap period or started after discontinuation of the index treatment.

4. Statistical Analysis

Frequencies and percentages were used to describe categorical variables, and counts, means, medians, standard deviations, and interquartile ranges for continuous variables. The Kaplan-Meier method was used to describe the risk of discontinuation and switching for each advanced treatment group. In view of the different periods of availability between therapies according to their introduction to the Japanese market, we conducted a sensitivity analysis of drug persistence in patients who initiated biologic treatment during or after year 2020, the year ustekinumab was approved for use in UC in Japan. All analyses were performed using SAS Enterprise Guide 8.3 (SAS Institute Inc., Cary, NC, USA).

RESULTS

1. Crohn’s Disease

There were 1,115 patients with CD who met eligibility criteria and were included in the analysis cohort (Fig. 1). Of these patients, 41.4% (n = 462) were initiated on adalimumab, 37.4% (n = 417) on infliximab, 18.1% (n = 202) on ustekinumab, and 3.0% (n = 34) on vedolizumab. The median number of days from the first diagnosis of CD until initiation of an advanced treatment in the respective groups was 172 days, 77 days, 224 days, and 477 days (Table 1).

The mean age of patients was similar in each treatment group, ranging from 31.2 to 34.8 years, and 72.8% to 85.9% were male. A majority (87.3% to 94.1%) of patients had used non-biological therapies during the 6-month baseline period; 79.4% to 85.1% used 5-aminosalicylates, 13.4% to 22.3% used immune modulators, and 29.3% to 47.5% used corticosteroids. The percentage of patients who had a hospitalization for any cause during the baseline period was 16.9% in the adalimumab group, 55.9% in the infliximab group, 29.7% in the ustekinumab group, and 26.5% in the vedolizumab group. Concomitant corticosteroids were used by 42.4% to 50.5% of patients and concomitant immune modulators by 27.7% to 47.1%. The percentage of patients who had inpatient status at the index date was highest in the infliximab group (57.6% vs. 28.4% and 28.7% in the other groups) (Table 1).

1) Persistence

The mean (median) follow-up period was 3.2 (2.5) years per patient. Persistence of index adalimumab, infliximab, and ustekinumab was high at all time points (Table 2). Persistence at 12 months was 84.7% for adalimumab, 87.7% for infliximab, 91.3% for ustekinumab, and 53.1% for vedolizumab. Persistence at 24 months was 76.3% for adalimumab, 76.8% for infliximab, 80.4% for ustekinumab, and 28.6% for vedolizumab. Estimates of persistence were highest at all timepoints for ustekinumab and were lowest at all time points for vedolizumab. The percentage of patients who continued on the index biologic until study end was 40.7% for adalimumab, 43.2% for infliximab, 50.0% for ustekinumab, and 38.2% for vedolizumab. In the sensitivity analysis of persistence in patients who commenced treatment during or after 2020, persistence at each time point was generally similar to the main analysis, with high rates of persistence observed in users of infliximab and ustekinumab, although there was little numerical difference between infliximab and ustekinumab at any time point (Supplementary Table 3).

Persistence at 6, 12, 18, and 24 months by hospital admission status on the index date is provided in Supplementary Table 4. Persistence at 12 months among patients who had inpatient status at the index date was 83.2% for adalimumab, 90.5% for infliximab, 91.3% for ustekinumab, and 25.0% for vedolizumab (Fig. 2A).

There were 295 patients continuously enrolled for at least 12 months who were prescribed corticosteroids within 30 days prior to the index date. Among these, 210 (71.2%) were 12-month persistent patients who remained corticosteroid-free for at least 180 consecutive days prior to month 12. The percentage of previous corticosteroid users who became corticosteroid-free was 68.3% (86/126) in the adalimumab group, 83.9% (78/93) in the infliximab group, 65.2% (43/66) in the ustekinumab group, and 30.0% (3/10) in the vedolizumab group.

The percentage of continuously enrolled patients with PDC ≥ 80% at 12 months was 88.3% for adalimumab, 91.3% for infliximab, 92.4% for ustekinumab, and 65.6% for vedolizumab. The percentage with PDC ≥ 80% at 24 months was 79.1%, 81.1%, 85.0%, and 28.63%, respectively.

2) Risk of Discontinuation/Switching

The survival probability was highest for ustekinumab and lowest for vedolizumab in terms of the risk of discontinuation or switching from the index treatment over the study period (Fig. 3).

3) Second Line Treatment

A total of 237 patients (21.0%) with CD initiated on a biologic moved to second line treatment over the study period; including 22.3% (n = 103) of those initiated on adalimumab, 23.3% (n = 97) initiated on infliximab, 10.9% (n = 22) initiated on ustekinumab, and 44.1% (n = 15) initiated on vedolizumab. The median time from first to second line treatment was 470 days, 357 days, 642 days, and 678 days in the respective groups. Demographic and clinical characteristics of patients who received second line treatment were similar to first line (Supplementary Table 5). The percentage of patients who had a hospital admission within 6 months prior to commencing second line treatment was 18.9% in the adalimumab group, 49.2% in the infliximab group, 27.3% in the ustekinumab group, and 18.8% in the vedolizumab group. The most frequently prescribed second line treatment was ustekinumab (112/237 patients). Few patients (n = 47, 4.2%) moved to third-line treatment (Fig. 4). Rates of persistence with second line treatment were similar to first line treatment (Supplementary Table 6). Persistence with second line treatment in continuously enrolled patients at 24 months was 60.0% for adalimumab, 85% for infliximab, 85.4% for ustekinumab, and 50.0% for vedolizumab.

2. Ulcerative Colitis

There were 1,942 patients with UC who met eligibility criteria during the study period (Fig. 1). Of these patients, 24.8% (n = 482) were initiated on adalimumab, 33.6% (n = 653) on infliximab, 11.2% (n = 218) on golimumab, 17.5% (n = 340) on vedolizumab, 5.6% (n = 108) on ustekinumab, and 7.3% (n = 141) on tofacitinib. The median number of days from the first diagnosis of UC until initiation of an advanced treatment in the respective groups was similar and ranged between 477 to 650 days (Table 3).

The mean age of patients was similar in each treatment group, ranging from 38.2 to 40.4 years, and 57.4% to 65.8% were male. A majority (96.7% to 99.5%) of patients had used non-biological therapies during the 6-month baseline period; 88.8% to 93.4% used 5-aminosalicylates, 38.0% to 48.8% used immune modulators, and 50.9% to 75.5% used corticosteroids. The percentage of patients who had a hospitalization for any cause during the baseline period was 54.5% in the infliximab group, versus 10.6% to 21.1% in the other group. Concomitant corticosteroids were used by 45.4% to 74.1% of patients, and concomitant immune modulators by 33.3% to 63.2%. The percentage of patients who had inpatient status at the index date was highest in the infliximab group (57.0% vs. 14.2% to 23.0% in the other groups) (Table 3).

1) Persistence

Persistence at 12 months was 57.6% for adalimumab, 62.9% for infliximab, 54.9% for golimumab, 69.7% for vedolizumab, 84.0% for ustekinumab and 61.6% for tofacitinib (Table 2). Persistence decreased over time but was highest for ustekinumab at all time points until month 24 (75.0%), versus 42.9% to 59.4% for other treatments. The percentage of patients who continued on the index biologic until study end was 23.7% for adalimumab, 26.2% for infliximab, 23.9% for golimumab, 43.8% for vedolizumab, 55.6% for ustekinumab, and 34.8% for tofacitinib.

In the sensitivity analysis of persistence in patients who initiated treatment during or after 2020, persistence rates were very similar to the main analysis and were highest for ustekinumab at all time points (Supplementary Table 3).

Persistence at 6, 12, 18, and 24 months by hospital admission status on the index date is provided in Supplementary Table 4. Persistence at 12 months among patients who had inpatient status at the index date was 57.0% for adalimumab, 61.1% for infliximab, 47.4% for golimumab, 55.6% for vedolizumab, 83.3% for ustekinumab and 63.2% for tofacitinib (Fig. 2B).

There were 1,115 patients continuously enrolled for at least 12 months who were prescribed corticosteroids within 30 days prior to the index date. Among these, 496 (44.5%) were 12-month persistent patients who had remained corticosteroid-free for at least 180 consecutive days prior to month 12. The percentage of previous corticosteroid users who became corticosteroid-free was 42.1% (106/252) in the adalimumab group, 52.0% (194/373) in the infliximab group, 47.1% (48/102) in the golimumab group, 56.5% (91/161) in the vedolizumab group, 62.9% (22/35) in the ustekinumab group, and 58.3% (35/60) in the tofacitinib group.

The percentage of continuously enrolled patients with PDC ≥ 80% at 12 months was 61.5% for adalimumab, 66.7% for infliximab, 64.1% for golimumab, 71.7% for vedolizumab, 88.3% for ustekinumab, and 64.0% for tofacitinib. The percentage with PDC ≥ 80% at 24 months was 52.6%, 53.5%, 49.7%, 65.0%, 79.2%, and 59.2%, respectively.

2) Risk of Discontinuation/Switching

The biologic survival probability was numerically higher for ustekinumab followed by vedolizumab in terms of the risk of discontinuation or switching from the index treatment over the study period (Fig. 5).

3) Second Line Treatment

A total of 694 patients (35.7%) with UC moved to second line treatment over the study period; including 39.8% (n = 192) of those initiated on adalimumab, 36.4% (n = 238) initiated on infliximab, 46.3% (n = 101) initiated on golimumab, 29.7% (n = 101) initiated on vedolizumab, 13.9% (n = 15) initiated on ustekinumab, and 33.3% (n = 47) initiated on tofacitinib. Demographic and clinical characteristics of patients who received second line treatment were similar to first line (Supplementary Table 7). The median time from first to second line treatment was 317 days, 143 days, 266.5 days, 308 days, 326 days, 180 days, and 714 days in the respective groups. The most frequently prescribed second line treatments were infliximab (129/694 patients), vedolizumab (125/694 patients), and ustekinumab (124/694 patients). There were 247 patients (20.7%) who changed to third-line treatment of whom 77 (31%) switched to ustekinumab (Fig. 6). Rates of persistence with second line treatment were similar to first-line treatment. Persistence with second line treatment decreased over time but was highest at all time points for ustekinumab. A 24-month persistence was 82.4% for ustekinumab versus 26.5% to 56.5% for the other treatments (Supplementary Table 6).

DISCUSSION

We evaluated real-world persistence of first- and second line advanced therapies for IBD in Japan using a nationwide claims database. To our knowledge, this is the first study investigating this outcome capturing all advanced therapies approved during the study period in Japan.

Our findings are consistent with reports from other countries; a study using claims databases in the United States found that persistence at 12 months was numerically higher for ustekinumab in both bio-naïve and bio-experienced patients with CD (87.2% and 86.3%, respectively) versus infliximab (79.0%, 77.4%), adalimumab (64.9%, 60.7%), and vedolizumab (78.9%, 80.8%) [22]. A population-based study using the National Health Insurance database in South Korea reported that in patients with CD, ustekinumab had a significantly lower risk for non-persistence than infliximab (adjusted hazard ratio [HR], 0.69; 95% confidence interval [CI], 0.47–1.00; P= 0.048), whereas no significant difference was noted between adalimumab or vedolizumab compared to infliximab. In this study, ustekinumab also had the highest persistence in second line (79.2% vs. 54.9% for vedolizumab, 70.9% for infliximab, and 73.6% for adalimumab) [23]. A study of patients with CD using linked administrative healthcare databases in Italy found that 12-month persistence in first line and second line was higher for ustekinumab than for vedolizumab, infliximab, or adalimumab. Compared to adalimumab, first-line infliximab and first-line ustekinumab were associated with a reduced probability of discontinuation (HR, 0.537; 95% CI, 0.412–0.701; P< 0.001 and HR, 0.057; 95% CI, 0.008–0.404; P= 0.004, respectively), while no difference was noted for vedolizumab compared to adalimumab [24]. A 12-month persistence in a population-based study in Australia was 80.0% for ustekinumab, 73.5% for vedolizumab, 68.1% for infliximab, and 64.2% for adalimumab in patients with CD [25].

We observed that persistence rates for all advanced therapies declined over time in patients with CD or UC in both first line and second line. While this is not a new finding, it highlights the ongoing challenges associated with long-term management of IBD. Patterns of persistence were similar for treatment used in second line. Although the sample size for each treatment option was small in second line, persistence was maintained at > 80% persistence at 24 months for infliximab and ustekinumab in patients with CD, and for ustekinumab in patients with UC.

Results from our study using the JMDC database are consistent with evidence from other reports using electronic health records in Japan. A retrospective review of electronic health records from 31 consecutive adult patients with UC treated with ustekinumab found that the probability of continuing ustekinumab treatment was 77.3% (95% CI, 64.0%–94.0%) at week 24, and 70.0% (95% CI, 56.0%–89.0%) at week 48 [26]. In a prospective study of patients with CD in Japan who initiated ustekinumab treatment, 80.4% (274/341) of patients continued ustekinumab treatment for at least 1 year [27]. The similarity of these results across different study designs supports the external validity of our findings. Similarly, persistence of first line adalimumab and infliximab was 57.6% and 62.9% respectively, in UC, which is similar to a real-world study in Japan using healthcare records conducted between 2013 and 2016 (50.6% for adalimumab and 63.3% for infliximab) [28].

Despite the similar results, caution is needed when comparing studies due to differences in the study period, the definition of persistence, therapies of interest, insurance coverage, as well as intrinsic factors such as racial difference in responsiveness to each medication. For example, in contrast to our results, persistence of vedolizumab was comparable to ustekinumab and infliximab in patients with CD in a U.S. claims-based study [22]. The available sample size of some advanced therapies including was small, such as vedolizumab in CD (n = 34), tofacitinib in UC (n = 41), and ustekinumab in UC (n = 108) due to their relatively recent approvals in Japan (2019, 2018, and 2020, respectively). Accumulated experience is needed to more accurately evaluate the persistence of these advanced therapies in Japan.

As is the case for other studies using claims data, clinical information such as disease severity, reasons underlying treatment choice, and reasons for discontinuation, including planned dose de-escalation, or switching were not available to us. For example, we observed that more patients initiated on infliximab were inpatients at the time of drug initiation versus other drugs, which could be a result of the trend to administer the first infusion in hospital or be due to more severe underlying disease. We leveraged information on inpatient/outpatient status at the index date as proxy of disease severity at the initiation of the first advanced treatment. Patterns of persistence in patients initiated as inpatients were similar to the main analysis. We also observed that the proportion of patients with UC using corticosteroids at baseline was lowest in those initiated on ustekinumab. Thus, we are unable to rule out that patients initiated on ustekinumab may have had milder disease than patients imitated on other advanced therapies. Our results would benefit from confirmation by studies using other data sources such as healthcare records that can account for disease severity and other valid clinical information at baseline.

Other potential study limitations include the relatively short follow-up period possible for recently approved treatments (vedolizumab for CD and ustekinumab for UC). Treatment utilization was not an objective of this study and the percentage of patients who underwent dose-escalation or shortening administration intervals is not known. We observed that the concomitant use of corticosteroids and immune modulators varied across the treatment groups. We cannot exclude the possibility that concurrent use of corticosteroids and immune modulators may have potentiated the therapeutic response to biologics.

Due to the limited number of patients aged ≥ 65 years in the JMDC, we did not include this age-group and it is not known if our findings are relevant to older adults. Although we employed case identifications validated in Japan, the possibility of misclassification of patients remains.

In conclusion, this large real-world study that comprehensively assessed the persistence of advanced therapies showed that index treatment with ustekinumab results in high persistence through 24 months after initiation in patients with CD or UC. Our study provides insights into the real-world usage of advanced treatments for patients with IBD in Japan. A planned systematic literature review and meta-analysis is under preparation may provide additional evidence about persistence of different advanced therapies [29]. However, additional studies are needed to compare persistence or other measurements pertinent to drug tolerance and effectiveness of advanced therapies.

NOTES

Funding Source

This work was supported by Janssen Research & Development LLC (Titusville, NJ, USA).

Conflict of Interest

Matsuoka K has received a research grant from Janssen Pharmaceutical K.K. outside the scope of this work; has received scholarship grants from AbbVie, EA Pharma, JIMRO, Kissei, Kyorin, Mitsubishi Tanabe, Mochida, Nippon Kayaku; and has received honoraria from AbbVie, Celltrion Healthcare, EA Pharma, Eli Lilly, Gilead Sciences, Janssen Pharmaceutical K.K., JIMRO, Kissei, Kyorin, Mitsubishi Tanabe, Miyarisan, Mochida, Nippon Kayaku, Pfizer, Takeda, Zeria. Kawamura S, Zhang Y, Wahking B, Tan JY, and Qiu H are employees of Johnson & Johnson and hold stock/shares in Johnson & Johnson. Nakajo K and Chung H are employees of Johnson & Johnson.

Matsuoka K is an editorial board member of the journal but was not involved in the peer reviewer selection, evaluation, or decision process of this article. No other potential conflicts of interest relevant to this article were reported.

Data Availability Statement

T he dataset that was used is held by the Japan Medical Data Center (JMDC) (https://www.jmdc.co.jp/en/). Access to the data for research is available after filing a formal data access request with https://www.jmdc.co.jp/en/inquiry. Requestors need to accept the terms and conditions of the data request and may need to pay the corresponding data access fee.

Author Contributions

Conceptualization: Matsuoka K, Kawamura S, Zhang Y, Wahking B, Tan JY, Qiu H, Nakajo K. Data curation; Formal analysis: Chung H. Methodology: Matsuoka K, Kawamura S, Zhang Y, Qiu H, Nakajo K. Project administration: Nakajo K. Supervision: Qiu H. Visualization: Chung H, Nakajo K. Writing - original draft: Nakajo K. Writing - review and editing: Matsuoka K, Kawamura S, Zhang Y, Chung H, Wahking B, Tan JY, Qiu H, Nakajo K. Software; Validation: Chung H. All authors approved the final version of the article, including the authorship list.

Additional Contributions

The authors thank Joanne Wolter (independent on behalf of Epidemiology, Office of the Chief Medical Officer, Johnson and Johnson) for medical writing support and production assistance.

Supplementary Material

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

Supplementary Table 1.

Anatomical Therapeutic Chemical Classification Codes for Case Identification

ir-2024-00118-Supplementary-Table-1.pdf

Supplementary Table 2.

Approved Administration Interval and Treatment Gaps for Biologics

ir-2024-00118-Supplementary-Table-2.pdf

Supplementary Table 3.

Sensitivity Analysis: 6-, 12-, 18-, and 24-Month Persistence of the Index Biologic in Patients with Crohn’s Disease or Ulcerative Colitis Who Initiated Biologic Treatment during or after Year 2020

ir-2024-00118-Supplementary-Table-3.pdf

Supplementary Table 4.

At 6-, 12-, 18-, and 24-Month Persistence of the Index Biologic in Patients with Crohn’s Disease or Ulcerative Colitis by Hospital Admission Status on the Index Date

ir-2024-00118-Supplementary-Table-4.pdf

Supplementary Table 5.

Baseline Characteristics of Patients with a Confirmed Diagnosis of Crohn’s Disease by Second Line Treatment

ir-2024-00118-Supplementary-Table-5.pdf

Supplementary Table 6.

At 6-, 12-, 18-, and 24-Month Persistence of Second Line Treatment in Patients with Crohn’s Disease or Ulcerative Colitis

ir-2024-00118-Supplementary-Table-6.pdf

Supplementary Table 7.

Baseline Characteristics of Patients with a Confirmed Diagnosis of Ulcerative Colitis by Second Line Treatment

ir-2024-00118-Supplementary-Table-7.pdf

Fig. 1.

Patient selection. ICD-10, International Classification of Disease 10; CD, Crohn’s disease; UC, ulcerative colitis; JAK, Janus kinase.

Fig. 2.

A 12-month persistence of advanced therapies by hospital admission status on the index date: (A) Crohn’s disease and (B) ulcerative colitis. IP, inpatient; OP, outpatient.

Fig. 3.

Estimates for the likelihood of discontinuation or switching after initiation of the first advanced treatment for Crohn’s disease (Kaplan-Meier method). (A) Adalimumab persistence. (B) Ustekinumab persistence. (C) Infliximab persistence. (D) Vedolizumab persistence. X-axes show the number of patients at risk.

Fig. 4.

Sankey diagram of treatment sequence in patients with Crohn’s disease initiating advanced treatment.

Fig. 5.

Estimates for the likelihood of discontinuation or switching after initiation of the first advanced treatment for ulcerative colitis (Kaplan-Meier method). (A) Adalimumab persistence. (B) Ustekinumab persistence. (C) Infliximab persistence. (D) Vedolizumab persistence. (E) Golimumab persistence. (F) Tofacitinib persistence. X-axes show the number of patients at risk.

Fig. 6.

Sankey diagram of treatment sequence in patients with ulcerative colitis initiating advanced treatment.

Table 1.

Baseline Characteristics of Patients with a Confirmed Diagnosis of Crohn’s Disease by Index Treatment

Characteristic	Adalimumab (n = 462)	Infliximab (n = 417)	Vedolizumab (n = 34)	Ustekinumab (n = 202)
Sex
Male	361 (78.1)	358 (85.9)	25 (73.5)	147 (72.8)
Female	101 (21.9)	59 (14.1)	9 (26.5)	55 (27.2)
Age (yr)
Mean ± SD	31.2 ± 12.3	32.0 ± 12.2	34.8 ± 13.9	34.2 ± 13.2
Median (IQR)	27 (21–40)	30 (22–41)	30 (18–53)	32 (97–48)
15–29	258 (55.8)	211 (50.6)	4 (11.8)	39 (19.3)
30–39	86 (18.6)	98 (23.5)	6 (17.6)	37 (18.3)
40–49	80 (17.3)	65 (15.6)	6 (17.6)	28 (13.9)
50–64	35 (7.6)	41 (9.8)	0	1 (0.5)
≥ 65	3 (0.6)	2 (0.5)	18 (52.9)	97 (48.0)
Charlson Comorbidity Index
Mean ± SD	0.80±1.10	0.66±1.00	0.88±1.20	0.91±1.40
Median (IQR)	0 (0–1)	0 (0–1)	1 (0–1)	1 (0–1)
0	232 (50.2)	234 (56.1)	15 (44.1)	94 (46.5)
1–2	203 (43.9)	164 (39.3)	16 (47.1)	90 (44.6)
3–5	24 (5.2)	16 (3.8)	3 (8.8)	17 (8.4)
>5	3 (0.6)	3 (0.7)	0	1 (0.5)
Non-biologic treatments during baseline
Yes	409 (88.5)	364 (87.3)	32 (94.1)	187 (92.6)
No	53 (11.5)	53 (12.7)	2 (5.9)	15 (7.4)
5-Aminosalicylates	383 (82.9)	349 (83.7)	27 (79.4)	172 (85.1)
Immune modulators	87 (18.8)	56 (13.4)	5 (14.7)	45 (22.3)
Corticosteroids	167 (36.1)	122 (29.3)	14 (41.2)	96 (47.5)
Usage of concomitant medication by type
Immune modulators	159 (34.4)	163 (39.1)	8 (47.1)	56 (27.7)
Corticosteroids	209 (45.2)	177 (42.4)	17 (50.0)	102 (50.5)
Hospitalization
Yes	78 (16.9)	233 (55.9)	9 (26.5)	60 (29.7)
No	384 (83.1)	184 (44.1)	25 (73.5)	142 (70.3)
Inpatient/outpatient at the index date
Inpatient	131 (28.4)	240 (57.6)	9 (26.5)	58 (28.7)
Outpatient	331 (71.6)	177 (42.4)	25 (73.5)	144 (71.3)
Disease duration (day)^a
Mean ± SD	425.8 ± 579.1	321.7 ± 531.4	612.5 ± 662.1	529.5 ± 699.5
Median (IQR)	172 (48–565)	77 (22–368)	477 (71–889)	224 (79–712)

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

^a Days from the first confirmed diagnosis to the index date.

SD, standard deviation: IQR, interquartile range.

Table 2.

At 6-, 12-, 18, and 24-Month Persistence of the Index Treatment in Patients with Crohn’s Disease or Ulcerative Colitis

Index treatment	6 mo persistence with ≥6 mo continuous observation		12 mo persistence with ≥12 mo continuous observation		18 mo persistence with ≥18 mo continuous observation		24 mo persistence with ≥24 mo continuous observation
Index treatment	No. (%)	Total	No. (%)	Total	No. (%)	Total	No. (%)	Total
Crohn’s disease
Adalimumab	398 (91.7)	434	348 (84.7)	411	291 (79.7)	365	241 (76.3)	316
Infliximab	369 (94.1)	392	321 (87.7)	366	260 (82.0)	317	215 (76.8)	280
Vedolizumab	25 (78.1)	32	17 (53.1)	32	9 (42.9)	21	4 (28.6)	14
Ustekinumab	178 (94.7)	188	157 (91.3)	172	120 (88.2)	136	86 (80.4)	107
Total	970 (92.7)	1,046	843 (85.9)	981	680 (81.0)	839	546 (76.2)	717
Ulcerative colitis
Adalimumab	312 (68.0)	459	250 (57.6)	434	197 (50.9)	387	156 (48.3)	323
Infliximab	467 (76.1)	614	363 (62.9)	577	275 (54.9)	501	216 (49.8)	434
Golimumab	153 (73.9)	207	107 (54.9)	195	83 (49.4)	168	63 (42.9)	147
Vedolizumab	268 (82.0)	327	207 (69.7)	297	145 (64.2)	226	95 (59.4)	160
Ustekinumab	98 (95.1)	103	79 (84.0)	94	40 (81.6)	49	18 (75.0)	24
Tofacitinib	94 (68.1)	138	77 (61.6)	125	47 (51.1)	92	34 (47.9)	71
Total	1,392 (75.3)	1,848	1,083 (62.9)	1,722	787 (55.3)	1,423	582 (50.2)	1,159

Table 3.

Baseline Characteristics of Patients with a Confirmed Diagnosis of Ulcerative Colitis by Index Treatment

Characteristic	Adalimumab (n=482)	Infliximab (n = 653)	Golimumab (n = 218)	Vedolizumab (n = 340)	Ustekinumab (n = 108)	Tofacitinib (n = 41)
Sex
Male	297 (61.6)	430 (65.8)	139 (63.8)	207 (60.9)	62 (57.4)	89 (63.1)
Female	185 (38.4)	223 (34.2)	79 (36.2)	133 (39.1)	46 (42.6)	52 (36.9)
Age (yr)
Mean ± SD	39.2 ± 13.4	39.0 ± 13.5	38.2 ± 14.2	40.4 ± 13.7	39.7 ± 12.8	39.6 ± 13.2
Median (IQR)	39 (28–50)	39 (28–49)	39 (26–49)	41 (29–51)	42 (28–50)	40 (29–49)
15–29	144 (29.9)	191 (29.2)	76 (34.9)	97 (28.5)	29 (26.9)	40 (28.4)
30–39	104 (21.6)	158 (24.2)	37 (17.0)	66 (19.4)	21 (19.4)	33 (23.4)
40–49	115 (23.9)	150 (23.0)	54 (24.8)	78 (22.9)	34 (31.5)	37 (26.2)
50–64	111 (23.0)	140 (21.4)	45 (20.6)	91 (26.8)	23 (21.3)	27 (19.1)
≥ 65	8 (1.7)	14 (2.1)	6 (2.8)	8 (2.4)	1 (0.9)	4 (2.8)
Charlson Comorbidity Index
Mean ± SD	0.86 ± 1.20	1.09 ± 1.50	0.83 ± 1.20	0.88 ± 1.40	0.93 ± 1.10	0.94 ± 1.60
Median (IQR)	1 (0–1)	1 (0–1)	0 (0–1)	0 (0–1)	1 (0–1)	0 (0–1)
0	229 (47.5)	268 (41.0)	111 (50.9)	178 (52.4)	46 (42.6)	71 (50.4)
1–2	216 (44.8)	321 (49.2)	94 (43.1)	129 (37.9)	53 (49.1)	56 (39.7)
3–5	33 (6.8)	50 (7.7)	9 (4.1)	28 (8.2)	9 (8.3)	10 (7.1)
>5	4 (0.8)	14 (2.1)	4 (1.8)	5 (1.5)	0	4 (2.8)
Non-biologic treatments during baseline
Yes	466 (96.7)	639 (97.9)	217 (99.5)	335 (98.5)	105 (97.2)	138 (97.9)
No	16 (3.3)	14 (2.1)	1 (0.5)	5 (1.5)	3 (2.8)	3 (2.1)
5-Aminosalicylates	430 (89.2)	610 (93.4)	202 (92.7)	302 (88.8)	97 (89.8)	127 (90.1)
Immune modulators	208 (43.2)	287 (44.0)	99 (45.4)	166 (48.8)	41 (38.0)	65 (46.1)
Corticosteroids	343 (71.2)	493 (75.5)	150 (68.8)	224 (65.9)	55 (50.9)	83 (58.9)
Usage of concomitant medication by type
Immune modulators	267 (55.4)	413 (63.2)	106 (48.6)	175 (51.5)	36 (33.3)	54 (38.3)
Corticosteroids	335 (69.5)	484 (74.1)	145 (66.5)	228 (67.1)	49 (45.4)	80 (56.7)
Hospitalizations
Yes	78 (16.2)	356 (54.5)	46 (21.1)	46 (13.5)	20 (18.5)	15 (10.6)
No	404 (83.8)	297 (45.5)	172 (78.9)	294 (86.5)	88 (81.5)	126 (89.4)
Inpatient/outpatient at the index date
Inpatient	111 (23.0)	372 (57.0)	43 (19.7)	60 (17.6)	20 (18.5)	20 (14.2)
Outpatient	371 (77.0)	281 (43.0)	175 (80.3)	280 (82.4)	88 (81.5)	121 (85.8)
Disease duration (day)^a
Mean ± SD	762.2 ± 702.1	700.9 ± 695.1	762.7 ± 704.5	878.3 ± 792.5	1,035.5 ± 958.3	875.7 ± 834.6
Median (IQR)	534 (262–1,061)	477 (212–993)	515 (276–978)	645 (289–1,240)	650 (301–1,524)	578 (299–1,170)

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

^a Days from the first confirmed diagnosis to the index date.

SD, standard deviation; IQR, interquartile range.

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Persistence of advanced therapies in patients with inflammatory bowel disease: retrospective cohort study using a large healthcare claims database in Japan

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Persistence of advanced therapies in patients with inflammatory bowel disease: retrospective cohort study using a large healthcare claims database in Japan

Fig. 1. Patient selection. ICD-10, International Classification of Disease 10; CD, Crohn’s disease; UC, ulcerative colitis; JAK, Janus kinase.

Fig. 2. A 12-month persistence of advanced therapies by hospital admission status on the index date: (A) Crohn’s disease and (B) ulcerative colitis. IP, inpatient; OP, outpatient.

Fig. 3. Estimates for the likelihood of discontinuation or switching after initiation of the first advanced treatment for Crohn’s disease (Kaplan-Meier method). (A) Adalimumab persistence. (B) Ustekinumab persistence. (C) Infliximab persistence. (D) Vedolizumab persistence. X-axes show the number of patients at risk.

Fig. 4. Sankey diagram of treatment sequence in patients with Crohn’s disease initiating advanced treatment.

Fig. 5. Estimates for the likelihood of discontinuation or switching after initiation of the first advanced treatment for ulcerative colitis (Kaplan-Meier method). (A) Adalimumab persistence. (B) Ustekinumab persistence. (C) Infliximab persistence. (D) Vedolizumab persistence. (E) Golimumab persistence. (F) Tofacitinib persistence. X-axes show the number of patients at risk.

Fig. 6. Sankey diagram of treatment sequence in patients with ulcerative colitis initiating advanced treatment.

Fig. 1.

Fig. 2.

Fig. 3.

Fig. 4.

Fig. 5.

Fig. 6.

Persistence of advanced therapies in patients with inflammatory bowel disease: retrospective cohort study using a large healthcare claims database in Japan

Characteristic	Adalimumab (n = 462)	Infliximab (n = 417)	Vedolizumab (n = 34)	Ustekinumab (n = 202)
Sex
Male	361 (78.1)	358 (85.9)	25 (73.5)	147 (72.8)
Female	101 (21.9)	59 (14.1)	9 (26.5)	55 (27.2)
Age (yr)
Mean ± SD	31.2 ± 12.3	32.0 ± 12.2	34.8 ± 13.9	34.2 ± 13.2
Median (IQR)	27 (21–40)	30 (22–41)	30 (18–53)	32 (97–48)
15–29	258 (55.8)	211 (50.6)	4 (11.8)	39 (19.3)
30–39	86 (18.6)	98 (23.5)	6 (17.6)	37 (18.3)
40–49	80 (17.3)	65 (15.6)	6 (17.6)	28 (13.9)
50–64	35 (7.6)	41 (9.8)	0	1 (0.5)
≥ 65	3 (0.6)	2 (0.5)	18 (52.9)	97 (48.0)
Charlson Comorbidity Index
Mean ± SD	0.80±1.10	0.66±1.00	0.88±1.20	0.91±1.40
Median (IQR)	0 (0–1)	0 (0–1)	1 (0–1)	1 (0–1)
0	232 (50.2)	234 (56.1)	15 (44.1)	94 (46.5)
1–2	203 (43.9)	164 (39.3)	16 (47.1)	90 (44.6)
3–5	24 (5.2)	16 (3.8)	3 (8.8)	17 (8.4)
>5	3 (0.6)	3 (0.7)	0	1 (0.5)
Non-biologic treatments during baseline
Yes	409 (88.5)	364 (87.3)	32 (94.1)	187 (92.6)
No	53 (11.5)	53 (12.7)	2 (5.9)	15 (7.4)
5-Aminosalicylates	383 (82.9)	349 (83.7)	27 (79.4)	172 (85.1)
Immune modulators	87 (18.8)	56 (13.4)	5 (14.7)	45 (22.3)
Corticosteroids	167 (36.1)	122 (29.3)	14 (41.2)	96 (47.5)
Usage of concomitant medication by type
Immune modulators	159 (34.4)	163 (39.1)	8 (47.1)	56 (27.7)
Corticosteroids	209 (45.2)	177 (42.4)	17 (50.0)	102 (50.5)
Hospitalization
Yes	78 (16.9)	233 (55.9)	9 (26.5)	60 (29.7)
No	384 (83.1)	184 (44.1)	25 (73.5)	142 (70.3)
Inpatient/outpatient at the index date
Inpatient	131 (28.4)	240 (57.6)	9 (26.5)	58 (28.7)
Outpatient	331 (71.6)	177 (42.4)	25 (73.5)	144 (71.3)
Disease duration (day)^a
Mean ± SD	425.8 ± 579.1	321.7 ± 531.4	612.5 ± 662.1	529.5 ± 699.5
Median (IQR)	172 (48–565)	77 (22–368)	477 (71–889)	224 (79–712)

Index treatment	6 mo persistence with ≥6 mo continuous observation		12 mo persistence with ≥12 mo continuous observation		18 mo persistence with ≥18 mo continuous observation		24 mo persistence with ≥24 mo continuous observation
Index treatment	No. (%)	Total	No. (%)	Total	No. (%)	Total	No. (%)	Total
Crohn’s disease
Adalimumab	398 (91.7)	434	348 (84.7)	411	291 (79.7)	365	241 (76.3)	316
Infliximab	369 (94.1)	392	321 (87.7)	366	260 (82.0)	317	215 (76.8)	280
Vedolizumab	25 (78.1)	32	17 (53.1)	32	9 (42.9)	21	4 (28.6)	14
Ustekinumab	178 (94.7)	188	157 (91.3)	172	120 (88.2)	136	86 (80.4)	107
Total	970 (92.7)	1,046	843 (85.9)	981	680 (81.0)	839	546 (76.2)	717
Ulcerative colitis
Adalimumab	312 (68.0)	459	250 (57.6)	434	197 (50.9)	387	156 (48.3)	323
Infliximab	467 (76.1)	614	363 (62.9)	577	275 (54.9)	501	216 (49.8)	434
Golimumab	153 (73.9)	207	107 (54.9)	195	83 (49.4)	168	63 (42.9)	147
Vedolizumab	268 (82.0)	327	207 (69.7)	297	145 (64.2)	226	95 (59.4)	160
Ustekinumab	98 (95.1)	103	79 (84.0)	94	40 (81.6)	49	18 (75.0)	24
Tofacitinib	94 (68.1)	138	77 (61.6)	125	47 (51.1)	92	34 (47.9)	71
Total	1,392 (75.3)	1,848	1,083 (62.9)	1,722	787 (55.3)	1,423	582 (50.2)	1,159

Characteristic	Adalimumab (n=482)	Infliximab (n = 653)	Golimumab (n = 218)	Vedolizumab (n = 340)	Ustekinumab (n = 108)	Tofacitinib (n = 41)
Sex
Male	297 (61.6)	430 (65.8)	139 (63.8)	207 (60.9)	62 (57.4)	89 (63.1)
Female	185 (38.4)	223 (34.2)	79 (36.2)	133 (39.1)	46 (42.6)	52 (36.9)
Age (yr)
Mean ± SD	39.2 ± 13.4	39.0 ± 13.5	38.2 ± 14.2	40.4 ± 13.7	39.7 ± 12.8	39.6 ± 13.2
Median (IQR)	39 (28–50)	39 (28–49)	39 (26–49)	41 (29–51)	42 (28–50)	40 (29–49)
15–29	144 (29.9)	191 (29.2)	76 (34.9)	97 (28.5)	29 (26.9)	40 (28.4)
30–39	104 (21.6)	158 (24.2)	37 (17.0)	66 (19.4)	21 (19.4)	33 (23.4)
40–49	115 (23.9)	150 (23.0)	54 (24.8)	78 (22.9)	34 (31.5)	37 (26.2)
50–64	111 (23.0)	140 (21.4)	45 (20.6)	91 (26.8)	23 (21.3)	27 (19.1)
≥ 65	8 (1.7)	14 (2.1)	6 (2.8)	8 (2.4)	1 (0.9)	4 (2.8)
Charlson Comorbidity Index
Mean ± SD	0.86 ± 1.20	1.09 ± 1.50	0.83 ± 1.20	0.88 ± 1.40	0.93 ± 1.10	0.94 ± 1.60
Median (IQR)	1 (0–1)	1 (0–1)	0 (0–1)	0 (0–1)	1 (0–1)	0 (0–1)
0	229 (47.5)	268 (41.0)	111 (50.9)	178 (52.4)	46 (42.6)	71 (50.4)
1–2	216 (44.8)	321 (49.2)	94 (43.1)	129 (37.9)	53 (49.1)	56 (39.7)
3–5	33 (6.8)	50 (7.7)	9 (4.1)	28 (8.2)	9 (8.3)	10 (7.1)
>5	4 (0.8)	14 (2.1)	4 (1.8)	5 (1.5)	0	4 (2.8)
Non-biologic treatments during baseline
Yes	466 (96.7)	639 (97.9)	217 (99.5)	335 (98.5)	105 (97.2)	138 (97.9)
No	16 (3.3)	14 (2.1)	1 (0.5)	5 (1.5)	3 (2.8)	3 (2.1)
5-Aminosalicylates	430 (89.2)	610 (93.4)	202 (92.7)	302 (88.8)	97 (89.8)	127 (90.1)
Immune modulators	208 (43.2)	287 (44.0)	99 (45.4)	166 (48.8)	41 (38.0)	65 (46.1)
Corticosteroids	343 (71.2)	493 (75.5)	150 (68.8)	224 (65.9)	55 (50.9)	83 (58.9)
Usage of concomitant medication by type
Immune modulators	267 (55.4)	413 (63.2)	106 (48.6)	175 (51.5)	36 (33.3)	54 (38.3)
Corticosteroids	335 (69.5)	484 (74.1)	145 (66.5)	228 (67.1)	49 (45.4)	80 (56.7)
Hospitalizations
Yes	78 (16.2)	356 (54.5)	46 (21.1)	46 (13.5)	20 (18.5)	15 (10.6)
No	404 (83.8)	297 (45.5)	172 (78.9)	294 (86.5)	88 (81.5)	126 (89.4)
Inpatient/outpatient at the index date
Inpatient	111 (23.0)	372 (57.0)	43 (19.7)	60 (17.6)	20 (18.5)	20 (14.2)
Outpatient	371 (77.0)	281 (43.0)	175 (80.3)	280 (82.4)	88 (81.5)	121 (85.8)
Disease duration (day)^a
Mean ± SD	762.2 ± 702.1	700.9 ± 695.1	762.7 ± 704.5	878.3 ± 792.5	1,035.5 ± 958.3	875.7 ± 834.6
Median (IQR)	534 (262–1,061)	477 (212–993)	515 (276–978)	645 (289–1,240)	650 (301–1,524)	578 (299–1,170)

Table 1. Baseline Characteristics of Patients with a Confirmed Diagnosis of Crohn’s Disease by Index Treatment

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

Days from the first confirmed diagnosis to the index date.

SD, standard deviation: IQR, interquartile range.

Table 2. At 6-, 12-, 18, and 24-Month Persistence of the Index Treatment in Patients with Crohn’s Disease or Ulcerative Colitis

Table 3. Baseline Characteristics of Patients with a Confirmed Diagnosis of Ulcerative Colitis by Index Treatment

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

Days from the first confirmed diagnosis to the index date.

SD, standard deviation; IQR, interquartile range.