Survey of Pharmacist-Led Medication Guidance for Patients with Inflammatory Bowel Disease in Japan

Inflammatory bowel disease (IBD) is a collective term for ulcerative colitis (UC), in which inflammation is confined to the colon, and Crohn’s disease, in which inflammation occurs throughout the digestive tract, from the mouth to the anus [1]. Furthermore, UC is known to progress to colorectal cancer if not properly managed [2, 3]. The main therapeutic goal is to help patients achieve remission from an active state and maintain that for a long time using pharmacotherapy. The main drugs used are mesalamine (5-ASA), thiopurine, corticosteroids, and biologic agents.

Adherence to these medications is required in the management of IBD. In particular, high adherence to 5-ASA is important for disease control in UC, and it has been reported that adherence to medication is a greater contributor to disease maintenance than the dose of 5-ASA [4, 5]. However, the number of patients with mesalamine intolerance is increasing every year and polypharmacy has been reported as a risk factor for disease relapse in UC [6, 7]. Moreover, in cases of thiopurine preparations or immunosuppressive drugs, genetic testing for NUDT15 variants or screening tests need to be performed before administration. Pharmacists should check the findings of these tests for safe pharmacotherapy because the implementation rate of these screening tests is approximately 50–60% [8, 9]. If these tests are not implemented, pharmacists and physicians should collaborate to help prevent serious adverse events, such as leukopenia, alopecia, and hepatitis B reactivation [10‒12]. Pharmacist intervention in Korea or Australia contributes to improved clinical outcomes and prevention of adverse effects of thiopurine preparations, and pharmacists need to be increasingly involved [13, 14]. However, in Japan, community pharmacists are often involved in outpatient visits and hospital pharmacists are involved in inpatient stays, resulting in fragmentation of information owing to different affiliations and lack of centralized management.

In recent years, it has been reported that in patients with cancer, pharmacists can contribute to preventing the severity of adverse effects caused by anticancer drugs and improving patients’ quality of life through drug-pharmacy collaboration [15, 16]. Furthermore, it has been reported that pharmacists are expected to play a role in controlling pathological conditions, reducing severity, and improving medication adherence in chronic diseases [17]. In the treatment of IBD, a chronic inflammatory disease, it is expected that pharmacists can contribute to improving the quality of drug therapy by establishing pharmacy-pharmacy collaboration and improving medication adherence. However, the current status of collaboration between community pharmacies and hospital pharmacists in IBD therapy has not been reported to date. The purpose of this study was to investigate the actual situation of medication guidance for patients with IBD and the information needed in drug-pharmacy collaboration in order to establish a partnership between community pharmacies and hospital pharmacies.

This study comprised a knowledge test for IBD (Table 1) and a survey of medication guidance for IBD among pharmacists using questionnaires. When this protocol was initiated, a published knowledge test for IBD focused on pharmacists was unavailable. Therefore, this test was designed according to the National Pharmacist Examination or the package insert for IBD treatment drugs and guidelines for IBD [18]. The drafting of a knowledge test was piloted for validation among three pharmacists, and the final knowledge test was administered.

The survey items are presented in Table 2. The questions concerned the background of the pharmacists (questions 1–4), the actual status of medication guidance (questions 5–6), and cooperation between the medical staff and pharmacists (questions 7–9). These surveys were performed using web forms and disseminated through professional associations with information. The duration of the study was from November 01, 2021, to December 31, 2023. Three surveys were administered: November 24, 2021, to January 24, 2022; May 25 to August 25, 2022; and February 24 to May 24, 2023. The pharmacists were reminded every month.

Based on question 4, the respondents were classified as pharmacists who had experience or had no experience with medication guidance for IBD. Moreover, these pharmacists were further classified as community pharmacists or hospital pharmacists, according to their affiliation. Continuous parameters, including age and test scores, are described as mean and standard deviation. Qualitative parameters are expressed as numbers and percentages. These parameters were analyzed using Fisher’s exact test or t test for comparisons between the groups. In addition, multiple regression analysis was conducted with the knowledge test score as the objective variable and the pharmacists’ background characteristics (age, sex, affiliation, and experience with IBD medication guidance) as the explanatory variables. Statistical analysis was performed using the GraphPad Prism software 10.0.2 (GraphPad Software, Inc., Boston, MA, USA). In all analyses, differences were considered statistically significant at p < 0.05.

In total, 378 of the 826 targeted pharmacists responded to the survey (response rate, 45.8%; Fig. 1), 108 of whom had no experience in IBD medication guidance. The pharmacists’ backgrounds are presented in Table 3. Regarding the affiliation of pharmacists with no experience in IBD medication guidance, 86 were community pharmacists and 22 were hospital pharmacists; regarding the affiliation of experienced pharmacists, 243 were community pharmacists and 27 were hospital pharmacists. Therefore, the two groups differed significantly in terms of affiliation (p = 0.01). However, no differences in age or gender were noted between the groups.

The score of pharmacists with no experience was 4.5 ± 1.7, whereas that of pharmacists with experience was 5.0 ± 2.0 (Fig. 2a), yielding a significant difference between the groups (p < 0.01). When each group was further classified according to affiliation, no differences in the test score between the affiliations were noted in the group with no experience in IBD medication guidance (Fig. 2b). In contrast, the scores of community and hospital pharmacists with experience in IBD medication guidance were 4.9 ± 1.9 and 6.4 ± 2.2, respectively, with a significant difference (p < 0.01; Fig. 2c). In addition, the multiple regression analysis identified the community pharmacy affiliation (p < 0.01) and having no experience in IBD medication guidance (p < 0.01) as factors that significantly contributed to low scores (Table 4). The percentages of correct answers are shown in Table 5. There were differences in responses regarding the maximum daily dose of mesalamine in question 3 (p < 0.01) and azathioprine dosage-related polymorphism in question 4 (p < 0.01) between the pharmacists with and those without experience in IBD medication guidance. However, the percentage of correct answers by hospital pharmacists with experience in IBD medication guidance was higher than that by community pharmacists with regard to azathioprine dosage-related polymorphism in question 4 (p < 0.01), screening for hepatitis B in question 7 (p < 0.01), bioavailability of budesonide in question 8 (p = 0.04), and contraindications for 6-mercaptopurine in question 10 (p = 0.02).

The status of implementation of medication guidance for patients with IBD is shown in Figure 3. The rates of implementation involving residual drug adjustment (p < 0.01), confirmation of symptoms (p < 0.01), prescription from other hospitals (p = 0.04), and therapeutic effects (p = 0.04) by community pharmacists were higher than those by hospital pharmacists. In addition, community pharmacists were more likely than hospital pharmacists to verbally confirm medication adherence and check the number of coadministered medications (Fig. 4).

The status of cooperation between community and hospital pharmacists is shown in Figure 5. Community pharmacists had a higher rate of initiating cooperation than hospital pharmacists in patients with conditions other than IBD (47.3 vs. 16.1%, p < 0.01). However, community pharmacists were less likely to initiate cooperation regarding patients with IBD (18.5%) (p < 0.01). Community and hospital pharmacists used tracing reports (81.1 and 62.5%, respectively) and personal medication handbooks (50.6 and 68.8%, respectively) as tools for cooperation.

This study revealed that pharmacists’ awareness of IBD differed depending on their affiliation and experience in medication guidance for patients with IBD and demonstrated the necessity of information sharing between hospitals and community pharmacies. Hospital pharmacists had only a few opportunities to provide medication guidance to patients with IBD (Table 3). This limitation may be due to the fact that opportunities differ depending on whether hospitals can treat patients with IBD; community pharmacists have more opportunities to treat patients with IBD than hospital pharmacists because they are required to fill prescriptions from all medical institutions. We performed an IBD knowledge test to confirm pharmacists’ understanding of IBD management. There are some reports about knowledge assessment tools for patients with IBD [19‒22]. However, at the time of our study, there were no published pharmacist knowledge assessment tools other than a report on pharmacists’ assessment of their confidence in managing IBD [23]. Therefore, our knowledge test of pharmacists was designed following the National Pharmacist Examination or the package insert for IBD treatment drugs and guidelines for IBD [18]. In our IBD knowledge test, pharmacists with experience in providing medication guidance to patients with IBD achieved higher scores (Fig. 2a). Among them, hospital pharmacists scored higher than community pharmacists, indicating that affiliation and experience in medication guidance for IBD influenced their scores (Fig. 2c; Table 4). Our results are supported by those documented by Prasad et al. [24], who reported that pharmacists’ knowledge scores were associated with their experience of treating patients with IBD. However, the knowledge scores of hospital pharmacists tended to be higher than those of community pharmacists. Hospital pharmacists’ knowledge scores were higher than those of community pharmacists, possibly because the former have opportunities to interact with patients with IBD who are hospitalized for purposes other than IBD treatment while being on IBD medications. The maximum dose of mesalamine in question 3, bioavailability in question 8, and contraindications of 6-mercaptopurine in question 10 are information that can be obtained from the package insert; therefore, there may be a lack of knowledge about them, which should be resolved through workshops (Table 5). Furthermore, the genetic polymorphism tests related to azathioprine in question 4 and screening test for hepatitis B in question 7 are conducted in hospitals; thus, there are only a few opportunities for community pharmacists to learn about them. Azathioprine is metabolized by thiopurine S-methyltransferase, leading to the formation of 6-methyl mercaptopurine, which leads to hepatotoxicity or 6-thioguanine nucleotides, resulting in immunomodulation and myelotoxicity [10]. The dose modification of azathioprine based on thiopurine S-methyltransferase-deficient genetic variants is incorporated into clinical practice in Western countries. However, these genetic variants are rare in Asia [25‒27]. Recent reports show that the genetic variants of NUDT15 are related to azathioprine-induced severe leukopenia and alopecia in Asia [11]. Therefore, hospital pharmacists, in particular, need to confirm whether a genetic test for NUDT15 has been performed before administering azathioprine. The findings of the screening tests for hepatitis B infection should also be checked by hospital pharmacists. This confirmation should be provided in cooperation between physicians and hospital pharmacists to avoid missing these screening tests. Confirmation of medication adherence is often implemented by community pharmacists, and it is necessary to provide guidance to improve adherence in patients with poor medication adherence (Fig. 4). In fact, 29.7–49.8% of patients with IBD show low medication adherence in East Asia, and pharmacists should focus more on providing medication guidance via cooperation between community and hospital pharmacies [28‒31]. However, the rate of implementation of cooperation between community and hospital pharmacies for patients with IBD is currently lower than for those without IBD (Fig. 5). Therefore, to improve medication adherence, pharmacists should improve drug awareness of patients with IBD via medication guidance and provide information on medication adherence to physicians. Physicians may be able to achieve adherence maintenance by selecting drugs that are administered less frequently or have fewer daily tablets and referring patients who need medication management to pharmacists to improve adherence [32‒34].

Tracing reports and personal medication handbooks were the most useful tools for cooperation established between community and hospital pharmacies. Therefore, including information on medication knowledge, adherence, and concomitant medications from other hospitals in tracing reports may contribute to strengthening the cooperation between community and hospital pharmacies. In the field of oncology, feedback from pharmacies to hospitals contributes to symptom reduction by facilitating the early detection of adverse drug events [35, 36]. This study has some limitations. We did not investigate the details of medication guidance for patients with IBD. The actual status of medication guidance within individual facilities was not surveyed, and it needs to be examined in detail when promoting future implementation of cooperation between community and hospital pharmacies.

In conclusion, this study elucidated the actual status of medication guidance for patients with IBD and the means of cooperation between community and hospital pharmacies. We hope that the results of this study will promote cooperation between community and hospital pharmacies for IBD treatment.

We thank all the pharmacists who responded to our questionnaires. We would also like to thank Editage (www.editage.jp) for English language editing.

The study protocol and questionnaires complied with the tenets of the Declaration of Helsinki and its amendments and the ethical guidelines for medical and health research involving human participants. The study protocol was reviewed and approved by the Ethics Committee of the Hokkaido University of Science, Approval No. 21–19. Informed consent was not obtained directly in writing; the purpose of the study was indicated when the questionnaire was filled out, and the decision to participate was confirmed by checking a box on the interview form if consent was given. This method of consent was approved by the Ethics Committee of the Hokkaido University of Science, Approval No. 21–19.

The authors have no conflicts of interest to declare.

This study was not supported by any sponsor or funder.

K.I. and K.O. conceptualized the study. K.I. performed a formal analysis and wrote the original draft of the manuscript. K.I. and K.H. conducted the investigation. All authors contributed to the review and edit and approved the final version of the manuscript.

All data generated or analyzed during this study are included in this article. The data obtained in this study are available from the corresponding author on request.