2025 Volume 48 Issue 1 Pages 33-38
Using a large health insurance database in Japan, we examined the real-world usage of budesonide enteric-coated capsules (BUD) in treating Crohn’s disease. We analyzed data from the Japan Medical Data Center claims database for Crohn’s disease patients prescribed BUD from April 2016 to March 2021, focusing on prescription status, adverse events (AEs), monitoring tests, and concomitant medications over 2 years following BUD initiation. Patients were categorized into two groups based on BUD usage duration: ≤1 year and >1 year. Of the 7364 registered patients, 1049 (14.2%) were prescribed BUD. Among the 562 followed for 2 years, 505 (89.9%) used BUD for ≤1 year and 57 (10.1%) for >1 year. Over 70% of the patients used at least one biologic, and more than 20% used at least two. The proportions of new thiopurine initiation were 22 and 9% in the ≤1-year and >1-year groups, respectively (p = 0.0181). We did not identify any obvious increase in AEs from long-term BUD use within the confines of our study design. However, regardless of prescription duration, over half of the patients lacked hepatitis B virus screening, glycated hemoglobin measurement, adrenal function quantification, or bone densitometry. Usage of strong CYP3A4 inhibitors was more frequent among patients in the BUD >1-year group. This study revealed that numerous Japanese patients received long-term BUD prescriptions. Although no apparent increase in AEs from long-term BUD was detected, we identified inadequate monitoring of AEs and drug interactions, as well as insufficient use of steroid-sparing agents.
Crohn’s disease (CD) is a granulomatous inflammatory disease that primarily affects young individuals and is characterized by edema and ulceration, mainly in the small and large intestines, as well as intestinal stenosis and fistulas. Despite the unknown etiology of CD and the lack of curative therapy, recent scientific and medical technological advances have led to a better understanding of CD’s pathogenesis. This has resulted in the development of various molecular-targeted agents and novel drug-delivery systems.1) The treatment for CD can be divided into two major categories: remission-induction therapy and remission-maintenance therapy. The mainstay of treatment is anti-inflammatory and immunomodulatory therapies, combined with enteral nutrition. Drugs with potent anti-inflammatory and immunosuppressive effects have been used for remission induction therapy. Prednisolone, a systemic corticosteroid, has been used for a long time because of its high efficacy in inducing remission in patients with inflammatory bowel disease (IBD). However, steroids cause various side effects, including osteoporosis, diabetes, immunosuppression, hypertension, etc.2,3)
In November 2016, budesonide enteric-coated capsules (BUD), containing budesonide (a corticosteroid) granules coated with a methacrylate copolymer that dissolves at pH ≥5.5, were launched for CD treatment in Japan. The BUD formulation enables the localized release of budesonide, primarily in the ileum and ascending colon, where CD is most intense, and the pH is >5.5. The local release of budesonide induces strong local anti-inflammatory action; after absorption, rapid metabolism by enzymes such as CYP3A4, primarily in the liver, results in a low bioavailability of approximately 10–20%, which reduces systemic side effects.4–6) However, clinical studies in Japan have shown a decrease in plasma and urinary cortisol levels,7) and the BUD package insert in Japan states that the clinical necessity of this drug should be reviewed after the first 8 weeks of administration, without indefinite administration8) as there are reports of adrenal insufficiency with extended usage of BUD.9) Similar to systemic steroid therapy, long-term BUD use is not recommended in either Japanese or international guidelines.2,3) Furthermore, appropriate monitoring of side effects, including hepatitis B virus (HBV) screening, adrenal function evaluation, glycated hemoglobin (HbA1c) measurement, and bone mineral density testing is necessary. In addition, the risk of systemic side effects secondary to the inhibition of budesonide metabolism by concomitant use of CYP3A4 inhibitors has been reported.10–12) However, the actual conditions under which these drugs are used in combination with BUD and their impact on side effects remain unclear. Furthermore, the possibility that the BUD release site is altered by the concomitant use of proton-pump inhibitors (PPI) or vonoprazan, which are potent inhibitors of gastric acid secretion, has not been ruled out. Therefore, the prescription status and safety of BUD and concomitant medications should be examined to ensure appropriate use of BUD.
This study aimed to investigate the actual use of BUD capsules in Japan using information obtained from a large insurance claims database to evaluate the prescribing patterns of BUD, including the duration of use, dosage, and combination with other medications, and to assess the safety of BUD.
Patient data were obtained from the Japan Medical Data Center (JMDC) claims database, which was provided by JMDC, Inc., Tokyo, Japan. The database contains fully anonymized accumulated receipts (inpatient, outpatient, and dispensing) and medical examination data of insured persons younger than 75 years. As of 2024, there are approximately 17 million registered users, which includes nearly 14% of the Japanese population.13)
Study Population and Data CollectionData from patients with CD who were prescribed BUD from April 2016 to March 2021 were analyzed. BUD was launched in Japan in November 2016; therefore, all patients in this study were considered new BUD users (Supplementary Tables 1 and 2). The observation period for this study was defined as 2 years from the initial prescription of BUD; therefore, we included patients for whom BUD was prescribed in March 2019. The following information was obtained: patient background (age at the time of initial BUD prescription, sex, and number of beds at the prescribing institution to investigate whether there were differences in prescription trends based on the size of the hospital), duration from CD diagnosis to BUD initiation, duration of BUD prescription, IBD medications used at the time of BUD initiation (Supplementary Table 2), IBD medications used during the observation period, and history of intestinal resection and endoscopic papillary balloon dilatation. To confirm the status of testing for steroid-related side effects, we examined tests for HBV surface antigen (HBsAg), HBV surface antibody (HBsAb), HBV core antibody (HBcAb), and HBV-DNA measurements undertaken 3 months before and after BUD initiation; plasma cortisol and ACTH levels; HbA1c; and bone mineral density measurements during the observation period. Additionally, we investigated the initiation of hepatitis B medications, diabetes medications, and bisphosphonates (Supplementary Table 3) during the observation period. We defined novel initiation of these medications if they were not prescribed within 3 months of BUD initiation and were prescribed only after BUD initiation. Patients with new-onset adrenal insufficiency or Cushing’s syndrome (Supplementary Table 2) during the observation period were investigated if undiagnosed prior to BUD initiation and diagnosed only after BUD initiation. Furthermore, to investigate the impact of BUD on blood pressure, we examined the prescription status of antihypertensive medications14) (Supplementary Table 4) at the initiation and cessation of BUD therapy.
The prescription status of concomitant medications that could cause drug interactions was investigated. The target drugs included CYP3A4 inhibitors (Supplementary Table 5)15) and PPI/vonoprazan (Supplementary Table 6). We defined concomitant use as a prescription that overlapped with the duration of BUD therapy. The Anatomical Therapeutic Chemical (ATC) code was used to extract medications, and the name of each disease or condition was assigned according to the International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10) codes. The ATC and ICD-10 codes are shown in Supplementary Tables 1–6.
OutcomesThe primary endpoint was the duration of the BUD prescription. Adrenal insufficiency has been reported in a case of CD after 3 years of continuous BUD use and in a case of autoimmune hepatitis after 5-month continuous BUD use.16) Furthermore, a cumulative BUD dose of 2500 mg for microscopic colitis (approximately 0.8 years at the maximum daily dose of 9 mg) is the cutoff value for bone density loss.17) Therefore, we considered that prescriptions of BUD for more than 1 year were sufficiently indicative of long-term BUD use and classified patients into two groups by the duration of BUD prescription for more than 1 year and less than 1 year. Secondary endpoints were set to compare patient background, total BUD dosage, concomitant medication status, occurrence of side effects, and the various tests that were performed.
Statistical AnalysisUsing JMP ver. 16.2.0 (SAS Institute, Inc., Cary, NC, U.S.A.). The Mann–Whitney U test was used for age comparison, the chi-square test for the number of facility beds, and Fisher’s exact test for other items. Statistical significance was set at p ≤ 0.05.
Ethics ApprovalThis study was approved by the Institutional Review Committee of the Faculty of Pharmaceutical Sciences at Hokkaido University (2022-004).
The Japanese Ministry of Health, Labor, and Welfare (JMHLW) has designated CD as an intractable disease and issued certificates to patients with CD who met the diagnostic criteria. In 2021, the JMHLW issued certificates to 48320 patients with CD.18) In the JMDC database between April 2016 and March 2021, the number of patients registered with CD (ICD-10 K5019–21)) was 7364 (15.2% of the number of recipient certificates issued for CD in 2021), of which 1049 (14.2%) had a BUD prescription. Of all CD patients who were prescribed BUD, 562 were prescribed BUD by March 2019 and were followed up for 2 years; Of these, 507 (89.9%) were prescribed BUD for less than 1 year, 55 (10.1%) for more than 1 year, and 400 (71.2%) for more than 8 weeks, which is the standard prescription duration specified on the package insert (Fig. 1). The median total dose of BUD during the observation period was 662 (9–3150) and 3450 (1599–6570) mg for the ≤1-year and >1-year groups, respectively; for 63 patients (11.2%, data not shown), the total dose exceeded 2500 mg, which is the reported cutoff value for osteoporosis risk.17) There was no statistically significant intergroup difference in sex, age, duration from CD diagnosis to BUD initiation, or number of beds at the prescribing institution at the time of initial prescription (Table 1). For the 178 patients diagnosed with CD after the launch of BUD in November 2016, treatment was initiated early, with a median of 56 d from diagnosis.
w, week (s); y, year (s).
| ≤1 year | >1 year | Total patients | p-Value ( ≤ 1 year vs. >1 year) |
|
|---|---|---|---|---|
| n (%) | 505 (89.9) | 57 (10.1) | 562 | — |
| Man/woman | 389 (77.0)/116 (23.0) | 50 (87.7)/7 (12.3) | 439 (78.1)/123 (21.9) | 0.065a) |
| Age mean (±stdev) | 37.2 (±13.0) | 35.6 (±13.0) | 35.4 (±13.0) | 0.2391b) |
| Duration from CD diagnosis to BUD initiation median days (IQR) |
||||
| All patients (n = 562) | 1075 (222–2833) | 1135 (303–3197) | 1088 (236–2854) | 0.378b) |
| Patients diagnosed after BUD launch (n = 178) |
56 (19–211) | 48 (11–116) | 56 (17–207) | 0.3512b) |
| Number of beds n (%) | ||||
| 0–199 | 155 (30.7) | 15 (30.2) | 170 (30.2) | |
| 200–499 | 123 (24.4) | 22 (38.6) | 145 (25.8) | 0.0645c) |
| Over 500 | 227 (45.0) | 20 (35.1) | 247 (44.0) | |
Age: age of patients at the time of initiation of budesonide therapy; CD: Crohn’s disease; BUD: budesonide enteric-coated capsules; IQR: interquartile range; number of beds: number of beds of the hospitals in which budesonide was initiated; a) Fisher’s exact test, b) Mann–Whitney U-test, c) chi-squared test; p ≤ 0.05 indicated statistical significance.
Table 2 shows the concomitant use of IBD medications, episodes of bowel resection, and endoscopic balloon dilatation at the time of the initial BUD prescription and during the observation period. The proportion of patients in the >1-year BUD group who were using <20 mg prednisolone at BUD initiation was significantly higher than those in the ≤1-year group. We grouped 49 and 513 patients who were and were not using prednisolone at BUD initiation, respectively, and the proportion of patients who used BUD for >1 year was compared in these groups. In the group that used prednisolone, 10 patients (20.4%) used BUD for >1 year; this was significantly higher than the 47 patients (9.2%) who did not use prednisolone (p = 0.0224, Fisher’s exact test, data not shown).
| ≤1 year (n = 505) | >1 year (n = 57) | Total patients (n = 562) | p-Value (≤1 year vs. >1 year) |
|||||
|---|---|---|---|---|---|---|---|---|
| At BUD initiation, n (%) |
Observation period, n (%) |
At BUD initiation, n (%) |
Observation period, n (%) |
At BUD initiation, n (%) |
Observation period, n (%) |
At BUD initiation |
Observation period |
|
| 5-Aminosalicylates | 335 (66.3) | 412 (81.6) | 40 (70.2) | 47 (82.5) | 375 (66.7) | 459 (81.7) | 0.657 | 1 |
| SASP | 3 (0.6) | 5 (1.0) | 2 (3.5) | 3 (5.3) | 5 (0.9) | 8 (1.4) | 0.0828 | 0.2749 |
| Thiopurine | 113 (22.4) | 223 (44.2) | 13 (22.8) | 18 (31.6) | 126 (22.4) | 241 (42.9) | 1 | 0.0896 |
| Prednisolone | ||||||||
| <20 mg | 19 (3.8) | 101 (20.0) | 8 (14.0) | 13 (22.8) | 27 (4.8) | 114 (20.3) | 0.0033* | 1 |
| ≥20 mg | 20 (4.0) | 104 (20.6) | 2 (3.5) | 11 (19.3) | 22 (3.9) | 115 (20.5) | 1 | 0.6044 |
| Total prednisolone ≥1000 mg | — | 57 (11.3) | — | 7 (12.3) | — | 64 (11.4) | — | 0.8258 |
| Elemental diet | 240 (47.5) | 323 (64.0) | 31 (54.4) | 38 (66.7) | 271 (48.2) | 361 (64.2) | 0.332 | 0.7713 |
| Infliximab | 134 (26.5) | 188 (37.2) | 8 (14.0) | 11 (19.3) | 142 (25.3) | 199 (35.4) | 0.0523 | 0.0081* |
| Adalimumab | 69 (13.7) | 162 (32.1) | 8 (14.0) | 22 (38.6) | 77 (13.7) | 184 (32.7) | 1 | 0.3716 |
| Ustekinumab | 17 (3.4) | 120 (23.8) | 3 (5.3) | 22 (38.6) | 20 (3.6) | 142 (25.3) | 0.4441 | 0.0232* |
| Vedolizumab | 0 (0) | 14 (2.8) | 0 (0) | 3 (5.3) | 0 (0) | 17 (3.0) | — | 0.4011 |
| Any biologics | 220 (43.6) | 378 (74.9) | 19 (33.3) | 41 (71.9) | 239 (42.5) | 419 (74.6) | 0.7801 | 0.6321 |
| Multiple biologics | — | 102 (20.2) | — | 14 (24.6) | — | 116 (20.6) | — | 0.4893 |
| Enterectomy | — | 45 (8.9) | — | 6 (10.5) | — | 51 (9.1) | — | 0.6932 |
| EBD | — | 20 (4.0) | — | 5 (8.8) | — | 25 (4.4) | — | 0.1627 |
Fisher’s exact test was performed. *p ≤ 0.05 indicated statistical significance. The observation period refers to the 2-year span following the initiation of BUD treatment. IBD: inflammatory bowel disease; BUD: budesonide enteric-coated capsules; SASP: salazosulfapyridine; thiopurines, azathioprine, and 6-mercaptopurine; EBD: endoscopic balloon dilatation.
Among the IBD medications used during the entire study period, infliximab was used significantly more frequently in the BUD ≤1-year group, and ustekinumab was used significantly more frequently in the >1-year group. Although there was no significant intergroup difference, more than 70% of the participants used at least one 1 biologic, and more than 20% used at least two biologics during the observation period. In all, 20 patients (35%) in the >1-year BUD group received novel biologic treatment or changed biologics during BUD use, with a median time from BUD initiation of 152 (7–563) d. Although not statistically significant, thiopurine use tended to be lower among patients in the >1-year BUD group; the proportion of patients who were newly initiated on thiopurine after BUD initiation was 22% in the ≤1-year BUD group and 9% in the >1-year group; this proportion was significantly lower in the >1-year BUD group (p = 0.0181). No significant intergroup difference was observed in the number of bowel resections or endoscopic balloon dilatations performed during the observation period.
Implementation Status of Screening for Hepatitis Virus B Infection, Adrenal Insufficiency, Diabetes, and OsteoporosisThe results of HBV screening, adrenal function evaluation, HbA1c, and bone mineral density testing are shown in Table 3. Approximately 60% of the patients had neither HBsAg nor HBV DNA tested within 3 months before and after the initial prescription of BUD. More than 80% of the patients had not been tested for HBsAg, HBs antibody, HBc antibody, or HBV DNA, which are commonly used as initial screening items. During the observation period, cortisol and ACTH levels were measured in approximately 5% of participants in each group; HbA1c, an indicator of diabetes, was measured in 34%, and bone mineral density, which is useful for the diagnosis of osteoporosis, was measured in 6% of the participants. There was no significant intergroup difference in the proportion of patients who underwent each test.
| ≤1 year (n = 505), n (%) |
>1 year (n = 57), n (%) |
Total patients (n = 562), n (%) |
p-Value (≤1 year vs. >1 year) |
|
|---|---|---|---|---|
| HBsAg or HBV-DNA | 202 (40.0) | 19 (33.3) | 221 (39.3) | 0.3913* |
| HBsAg, HBsAb, HbcAb, or HBV-DNA | 78 (15.4) | 4 (7.0) | 82 (14.6) | 0.1117 |
| Cortisol | 24 (4.8) | 4 (7.0) | 28 (5.0) | 0.5139 |
| Adrenocorticotropic hormone | 19 (3.8) | 4 (7.0) | 23 (4.1) | 0.2773 |
| Glycated hemoglobin | 176 (34.9) | 15 (26.3) | 191 (34.0) | 0.2383 |
| Bone mineral density | 34 (5.5) | 6 (10.5) | 28 (6.0) | 0.1414 |
Fisher’s exact test was performed. *p ≤ 0.05 indicated statistical significance. HBsAg: hepatitis B virus surface antigen; HBsAb: hepatitis B virus surface antibody; HBcAb: hepatitis B virus core antibody; HBV-DNA: hepatitis B virus DNA.
Cases were not identified in which a diagnosis of adrenal insufficiency was made following the initiation of BUD treatment or in which a diagnosis of Cushing’s syndrome was recorded following the initiation of BUD treatment.
Initiation of Antiviral Therapy for HBV, Diabetes, or OsteoporosisHBV medications were used in 2 cases: one before BUD use and the other more than 1.5 years after cessation of BUD therapy. There were four patients (all in the ≤1-year BUD group) who did not use any diabetes medications at least 3 months prior to BUD therapy initiation and were started on diabetes medications after BUD initiation. Bisphosphonates were started after BUD therapy initiation in six patients (1 in the >1-year BUD group and 5 in the ≤1-year BUD group).
Initiation or Increase in Antihypertensive MedicationsAntihypertensive medications were initiated in 6 cases (2 in the >1-year BUD group and 4 in the ≤1-year BUD group). Of the 32 cases (5 in the >1-year BUD group and 27 in the ≤1-year BUD group) who had been prescribed antihypertensive medications at the start of BUD therapy, 22 experienced no changes in medication or dosage (three in the >1-year BUD group and 19 in the ≤1-year BUD group). Three patients, all in the ≤1-year BUD group, had an increase in dosage; five had a reduction in dosage (1 in the >1-year BUD group and 4 in the ≤1-year BUD group); and two had a change in medication (1 in the >1-year BUD group and 1 in the ≤1-year BUD group) at the end of the BUD prescription period. While the impact of BUD on blood pressure in patients who started or increased their antihypertensive medication cannot be denied, no specific effects from the long-term use of BUD were identified.
Concomitant Use of CYP3A4 Inhibitors, PPI, or VonoprazanSignificantly more cases of concomitant use of a strong CYP3A4 inhibitor were observed in the >1-year BUD group. Among the CYP3A4 inhibitors used concomitantly with BUD, clarithromycin was the most common agent (34 cases), and azoles were used in eight cases. There was no significant difference between the ≤1- and >1-year BUD groups. PPI or vonoprazan was used in approximately 30% of the cases overall, without any significant intergroup difference (Table 4).
| ≤1 year, n (%) |
>1 year, n (%) |
Total patients, n (%) |
p-Value (≤1 year vs. >1 year) |
|
|---|---|---|---|---|
| Strong inhibitor of CYP3A4 | 19 (3.8) | 17 (29.8) | 36 (6.4) | <0.0001* |
| PPI | 130 (25.7) | 19 (33.3) | 149 (26.5) | 0.2671 |
| Vonoprazan | 37 (7.3) | 3 (5.3) | 40 (7.1) | 0.7866 |
The CYP3A4 inhibitors are listed in Supplementary Table 4. If the prescription period overlapped during budesonide therapy, the case was defined as “concomitant use.” Fisher’s exact test was performed. *p ≤ 0.05 indicated statistical significance. PPI: proton-pump inhibitor.
This study aimed to clarify the actual status of BUD use in Japan using data recorded between April 2016 and March 2021 in a large insurance medical database. As BUD was launched in Japan in November 2016 for CD, this study provides large-sample, reliable results that examine the status of BUD use after its launch in Japan.
BUD is a steroid formulation with fewer systemic side effects, and the safety of BUD use for 2 years has been reported to be superior to that of prednisolone.22) However, recent domestic and international guidelines do not recommend long-term use of BUDs or systemic steroids.2,3) Iatrogenic adrenal insufficiency has been reported in a case of CD after 3 years of continuous use and in a case of autoimmune hepatitis after 5 months of BUD use.9,16) A cumulative BUD dose of 2500 mg (approximately 0.8 years at the maximum daily dose of 9 mg) is the cutoff value for bone mineral density loss.17) To identify the characteristics of patients who had been prescribed BUD for a long period, we classified the participants into two groups: 505 patients who had been prescribed BUD for ≤1 year and 57 patients who had been prescribed BUD for >1 year. It has been suggested that many cases diagnosed with CD after the launch of BUD in November 2016 have been using the drug as an initial remission induction therapy, which is considered an appropriate use of the medication (Table 1). Although the package inserts of BUD state that the necessity of the drug should be reviewed after 8 weeks of administration and that the drug should not be continued carelessly,8) approximately 27% of the patients had been prescribed the drug for >6 months and 10% for >1 year, indicating the need for attention to proper use of the medication (Fig. 1).
In terms of concomitant medications at the time of BUD initiation, prednisolone use was significantly higher in patients who used BUD for >1 year. Furthermore, when the duration of BUD prescription was compared by grouping patients who were using prednisolone, significantly more patients who were using prednisolone at the time of BUD initiation received BUD for a longer period than those who did not. This suggests that patients using prednisolone at the time of BUD initiation may include many steroid-dependent patients who relapse following steroid-dose reduction. The appropriate use of steroid-sparing agents such as thiopurines is recommended for steroid-dependent patients.2,3) Although a more appropriate use of thiopurines may be recommended for patients in the group prescribed BUD for >1 year, the rate of use was similar in the group prescribed BUD for ≤1 year. Patients with a long-term BUD prescription should be evaluated on a case-by-case basis to determine the appropriate use of steroid-sparing agents. In addition, more strategic measures should be taken from the start of BUD for patients who are using prednisolone at the time of BUD initiation. Observing other IBD medications used during the first 2 years of BUD therapy, approximately 70% of patients used some type of biologic, and approximately 20% used more than two biologics, regardless of the duration of BUD prescription. In addition, 35% of patients in the >1-year group either started a new biologic or switched to another while taking BUD for a median of 152 d. The reasons for changing biologic agents were not clear in this study, but many patients initiated new biologics during the long-term use of BUD. Therefore, the discontinuation of BUDs should be considered in some cases after careful consideration of the need for continued use.
BUD is a steroid recognized for its safety profile. Within our study, only a few cases exhibited potential side effects from BUD. Given the small number of cases, no significant trends in side effects were observed relative to the duration of the prescription. However, adverse events (AEs) during the long-term use of BUD have been reported.9,17,23) Therefore, appropriate monitoring is necessary. In this study, we investigated whether HBV screening, adrenal function tests, HbA1c levels, and bone densitometry were performed when BUD was used. However, the rate of implementation of these tests was low, regardless of the duration of the BUD prescription. This suggests that not all the AEs were detected.
The number of patients who received a strong CYP3A4 inhibitor was significantly higher in the group prescribed BUD for >1 year. Most of these drugs are clarithromycin and azole antifungal agents, and it is necessary to pay attention to the side effects caused by the increased action of BUD when used in combination, such as the exacerbation of infections due to the increased immunosuppressive effect of steroids.
Although existing studies have suggested that coadministration with omeprazole does not affect the absorption rate of enteric-coated BUD capsules,24) the specific site of dissolution has not been determined. Additionally, the effect of vonoprazan, a potassium-competitive acid blocker that is more potent in suppressing gastric pH than PPI,25) on BUD dissolution is yet to be studied. To address these gaps, the present study investigated the coadministration of PPIs and vonoprazan, revealing that these agents were used in combination in approximately 30% of cases. These findings underscore the need for further investigations into the efficacy of these combinations and their impact on BUD dissolution.
The limitations of this study include the lack of information on laboratory data and clinical symptoms, which makes detailed efficacy and safety evaluation difficult. Additionally, the lack of information on the course of the disease and medications used before 2016 may have affected the selection of therapeutic agents during the observation period of this study. Furthermore, JMDC claims database includes patients only under 75 years; however, CD is common in young people, we believe that the inclusion of a study population under 75 years of age would not be a major limitation to the generalizability of the results of this study, and the database does not contain information on human immunodeficiency virus (HIV)-positive patients. Some of the CYP3A4 inhibitors listed are HIV medications, and it is possible that actual concomitant use was not detected. Moreover, as drug administration was determined from prescriptions, its actual use could not be evaluated. Additionally, we identified patients using both the ICD-10 code and prescriptions for BUD formulations in this study. However, the reliability of this approach has not been validated.
Some patients were prescribed budesonide granule-filled capsules for long-term use, although these are recommended for short-term use. No apparent increase in AEs with long-term use of BUD was detected in this study; however, the results suggest that monitoring of side effects and drug interactions in long-term users is inadequate and that steroid-sparing agents may not be used appropriately.
This study was supported by JSPS KAKENHI (Grant Number: 21K14821).
The authors declare no conflict of interest.
This article contains supplementary materials.
