2024 Volume 47 Issue 1 Pages 232-239
Biologics are essential for treating inflammatory bowel disease (IBD); however, only a few studies have validated cost-effective treatment options and patient factors for biologic use using real-world data from Japanese patients with IBD. Here, we aimed to provide pharmacoeconomic evidence to support clinical decisions for IBD treatment using biologics. We assessed 183 cases (127 patients) of IBD treated with biologics between November 2004 and September 2021. Data on patient background, treatment other than biologics, treatment-related medical costs, and effectiveness index (ratio of the C-reactive protein-negative period to drug survival time) were analyzed using univariate and multivariate logistic regression analyses. Drug survival was determined using Kaplan–Meier survival curve analysis. The outcomes were to validate a novel assessment index and elucidate the following aspects using this index: the effectiveness–cost relationship of long-term biologic use in IBD and cost-effectiveness-associated patient factors. Body mass index ≥25 kg/m2 and duration of hypoalbuminemia during drug survival correlated significantly with the therapeutic effectiveness of biologics. There were no significant differences in surgical, granulocyte apheresis, or adverse-event costs per drug survival time. Biologic costs were significantly higher in the group showing lower effectiveness than in the group showing higher effectiveness. These findings hold major pharmacoeconomic implications for not only improving therapeutic outcomes through the amelioration of low albumin levels and obesity but also potentially reducing healthcare expenditure related to the use of biotherapeutics. To our knowledge, this is the first pharmacoeconomic study based on real-world data from Japanese patients with IBD receiving long-term biologic therapy.
Inflammatory bowel disease (IBD) is a chronic, idiopathic inflammatory disease of the intestinal tract that persists with relapse. It is classified into ulcerative colitis (UC) and Crohn’s disease (CD). IBD is an intractable disease that often develops in young individuals and considerably reduces patients’ QOL owing to protracted symptoms such as abdominal pain and diarrhea. In Japan, the number of patients with UC (incidence) in 2013 and 2021 was estimated to be 160000 (0.1%) and 220000 (0.17%), respectively, and that of patients with CD (incidence) in 2013 and 2021 was 40000 (0.027%) and 70000 (0.055%), respectively; these figures are increasing annually.1,2) Clinical practice guidelines emphasize the importance of biologics, especially for patients with moderate-to-severe IBD. Biologics are superior to conventional therapeutic agents in terms of inducing and maintaining remission.2–4) The effectiveness and safety of different biologics have been compared recently.5) Some studies have assessed real-world drug survival (DS) rates, long-term effectiveness, and safety of biologics.6,7) The DS time is the duration of treatment with a drug, where a high value indicates high overall acceptability, including the effectiveness and safety of the drug. Therefore, DS studies are useful for evaluating long-term treatments for chronic diseases in specialties such as rheumatology, dermatology, and gastroenterology. They are also suitable for analyzing real-world situations that are difficult to evaluate in randomized controlled trials. In particular, exploring factors that extend the duration of DS to better reflect the effectiveness of treatment is valuable to both patients and healthcare providers, as these factors directly contribute to long-term effectiveness. Furthermore, evaluating the cost-effectiveness of a drug is crucial for the maintenance of public healthcare insurance systems. However, some limitations have been identified regarding the use of DS alone as an evaluation index; thus, it is necessary to devise methods to improve the accuracy of DS alone as an evaluation index.8)
As biologics are generally expensive, their use must be efficient.9–11) Predicting biologics suitable for patients is important to prolong the maintenance period of remission.12–15) Additionally, maintaining remission in working-age patients (accounting for most patients with IBD) and preventing worsening of the condition will help improve the overall productivity of a society.16–19) Thus, evaluating real-world data on biologic use against IBD from a pharmacoeconomic perspective is important to develop IBD treatment strategies. However, there are no studies on the real-world use of biologics for IBD treatment in Japan with the aim of assessing the cost-effectiveness of treatment options or identifying important patient factors.
Here, we aimed to provide evidence to support clinical decisions for treating IBD using biologics. To this end, we validated the utility of a novel effectiveness index, which assigns weight to the simple DS value, in conjunction with the addition of C-reactive protein (CRP) levels, an indicator of inflammatory symptoms. Subsequently, we conducted a pharmacoeconomic assessment of long-term biological therapy based on this index as well as various treatment costs, including drug expenses, required treatment costs, and associated expenditures.
This study was approved by the Institutional Review Board of the Centre for Clinical Research of Yamaguchi University Hospital and was conducted in accordance with the Ethical Guidelines for Medical and Health Research Involving Human Subjects (Approval Number: H2022-110, September 21, 2022). As this study was retrospective and observational in nature, obtaining informed consent from individual patients was not required.
Study PopulationThis study involved patients with IBD treated with (1) a monoclonal antibody against tumor necrosis factor-α (TNF-mab; e.g., infliximab, adalimumab, and golimumab); (2) a monoclonal antibody against interleukin (IL)-12/23p40 (IL12/23p40-mab; e.g., ustekinumab); or (3) an integrin α4β7 (integrin α4β7-mab) monoclonal antibody (e.g., vedolizumab), from November 2004 to September 2021, at the Department of Gastroenterology, Yamaguchi University Hospital, Japan. The package inserts for most biologics used for treating IBD in Japan state that the therapeutic effect is commonly achieved within 12–20 weeks of initiation, and if a therapeutic response is not achieved by then, discontinuation of the treatment should be considered. Therefore, as of September 2021, patients who had been treated with biologics for ≤6 months and were scheduled to continue treatment were excluded because the effects of biologics could not be determined. Nonetheless, all patients who discontinued treatment within ≤6 months as of September 2021 were included. Additionally, patients whose reason for discontinuing the administration of biologics at our hospital was non-medical (e.g., transfer to another hospital because of relocation) were excluded because treatment continuity could not be evaluated medically.
A gastroenterologist diagnosed IBD based on clinical, endoscopic, and histological tests. In Japan, patients receiving biologics for the treatment of IBD must meet the following criteria: a moderate-to-severe case where clear clinical IBD symptoms persist despite appropriate treatment with nutritional therapy and other drugs (such as 5-aminosalicylic acid, steroids, and azathioprine). All patients enrolled in this study met these criteria.
Patient CharacteristicsData on patient characteristics were collected from medical records; these included factors that might affect the therapeutic effects of biologics on IBD, such as age at diagnosis, sex, body mass index (BMI), smoking habits, history of IBD-related surgery, development of CD or UC, naïve or non-naïve status for biologic use, years from the initial diagnosis to the first administration of biologics, serum albumin level, and steroid history during biologic administration. All biologics used in this study were originator products, and no biosimilars were included. Based on the medication history, patients who were receiving biologics for the first time were categorized as naïve, whereas those who had received biologics at least once previously were categorized as non-naïve.
Non-biological TherapyWe investigated the duration of combination therapy for IBD including a biologic. This combination therapy included 5-aminosalicylic acid, immunosuppressants (azathioprine and tacrolimus), enteral nutrition, and granulocyte apheresis (GCAP), which are indicated for IBD treatment during biologic administration.
Effectiveness IndexDS was defined as the number of months from the initiation to discontinuation of biologic therapy at our hospital. DS alone has been found to be insufficient as an index for evaluating the effectiveness of biologics.8) Therefore, in this study, the ratio of the CRP-negative period to DS time was determined and used as the effectiveness index for biologics. Effectiveness index values above or below the median value were considered to indicate superior or inferior effects of biologics, respectively (Fig. 1). Among various effectiveness indexes, we considered the use of the CRP value as the primary effectiveness index in this study.20) This choice was based on the clear reflection of inflammatory conditions by CRP values, the wealth of information provided via retrospective data, its high accuracy, and its widespread use across many medical institutions. By comparing CRP data with supplementary evaluation indices, we validated the credibility of this metric as an effectiveness indicator. To evaluate the validity of the effectiveness index used, the following five items were investigated as supplementary evaluation indices: (1) white blood cell (WBC)-negative period, (2) steroid-free period, (3) non-hospitalization period, (4) Crohn’s disease activity index (CDAI)-negative period, and (5) partial Mayo score (PMS)-negative period. These assessment indices were adopted as primary or ancillary evaluation measures in this study, given their inclusion in the clinical guidelines for assessing clinical symptoms of IBD.1–4)
A conceptual diagram of the effectiveness measure for long-term use of biologics is shown. The effectiveness index was defined as the ratio of the CRP-negative period (the period during which clinical effectiveness was observed) to drug survival (the duration of biologic administration), with a higher ratio indicative of superior effectiveness and a lower ratio indicative of inferior effectiveness. Abbreviations: CRP, C-reactive protein.
DS has been investigated as a safety indicator for biologics administered to treat IBD. The month of discontinuation was determined as either the month of the last prescription or that of the visit immediately preceding the month in which treatment was switched to another biologic. In cases of biologic discontinuation, the causes for discontinuation were examined and the occurrence of adverse events necessitating treatment during biologic administration was assessed.
CostThe aggregate medical expenses per case were determined by combining the expenditures incurred for medications (specifically approved for the treatment of IBD in Japan) utilized for IBD management and the healthcare expenses associated with the overall IBD treatment process. This includes surgical expenses, GCAP costs, and costs associated with the management of adverse events linked to biologic treatments. Medical cost was defined as the monthly cost of biological treatment, estimated based on healthcare fees at the time of treatment.
Cost-Effectiveness AnalysisCost-effectiveness was analyzed in accordance with the “Guideline for Economic Evaluation of Healthcare Technologies in Japan” from the payer’s perspective and included direct healthcare costs only.21) Based on the effectiveness indexes of different biologics, we compared the monthly medical costs between the groups with excellent and inferior treatment effects.
Statistical AnalysesStatistical analyses were conducted using R version 4.1.2 (R Foundation for Statistical Computing, Vienna, Austria). The patients were grouped based on the effectiveness indexes determined in this study, and univariate analysis was then performed to ascertain the statistical significance of the investigated factors. The Fisher’s exact and Mann–Whitney U tests were performed for categorical and continuous variables, respectively. All factors investigated in this study were considered to be critical determinants influencing treatment effectiveness. Univariate analysis was conducted with all factors, and multivariate logistic regression analysis was further performed with factors considered to be of particular clinical significance. In addition, DS, an indicator used to evaluate drug safety, was studied via log-rank testing using Kaplan–Meier survival curve analysis. The threshold for a statistically significant difference was set at p < 0.05.
In this study, 183 cases (127 patients) were included (Fig. 2). The median ratio of the CRP-negative period to DS time (effectiveness index) was 0.64. Of the 183 cases included, 92 showed an effectiveness index of ≤0.64 (poor-response group) and 91 showed an effectiveness index of >0.64 (excellent-response group). The median index values of these two groups were 0.17 (interquartile range [IQR]: 0.00–0.42) and 0.88 (IQR: 0.76–0.98), respectively. In each group, the monthly costs of each biologic agent were delineated when administered continuously over a 1-year period at the standard dosage recommended in the respective pharmaceutical package inserts and the actual quantities (Table 1). To evaluate the validity of this index, the percentages of adverse events and several ratios (WBC-negative period/DS period, steroid-free period/DS period, non-hospitalization period/DS period, CDAI-negative period/CDAI-evaluation period, and PMS-negative period/PMS-evaluation period; expressed as median and interquartile range) were compared between the groups (Table 2). No significant difference was found in the incidence of adverse events between the groups. All five supplementary evaluation indexes showed a positive correlation with the effectiveness index established in this study, and four indexes significantly differed between the groups. Additionally, DS was significantly longer in patients with a higher effectiveness index than in those with a lower effectiveness index (p = 0.00002). In particular, the difference in the continuation rate after 1 year was remarkable (Fig. 3). Based on these results, it is reasonable to define the responses of patients with an effectiveness index above and below the median value as excellent and inferior, respectively.
Abbreviations: DS, drug survival; IL-12, interleukin-12; TNF-α, tumor necrosis factor alpha.
| Biologic | Biologic cost (JPY)a)/month | Poor-response group | Excellent-response group |
|---|---|---|---|
| Number of used vials or syringes | |||
| IFX 100 mgb) | 141194–215390 | 3834 | 3991 |
| ADA 40 mg | 156666–183667 | 4730 | 5579 |
| UST 130 mg/45 mg | 302826–339896 | 63/450 | 55/414 |
| VED 300 mg | 182993–186382 | 139 | 188 |
| GOL 50 mg | 290155–316555 | 100 | 38 |
Abbreviations: ADA, adalimumab; GOL, golimumab; IFX, infliximab; UST, ustekinumab; VED, vedolizumab. a) Incorporating fluctuations in drug pricing. b) Used for patients weighing 60 kg.
| Poor-response group | Excellent-response group | p | |
|---|---|---|---|
| N = 92 | N = 91 | ||
| DS (Med [IQR]) | 19.91 (10.16–41.77) | 28.08 (17.19–70.31) | 0.007 |
| CRP-negative period/DS period (Med [IQR]) | 0.17 (0.00–0.42) | 0.88 (0.76–0.98) | <0.001 |
| Adverse events (%) | 12 (13.0) | 13 (14.3) | 0.833 |
| WBC-negative period/DS period (Med [IQR]) | 0.93 (0.76–1.00) | 1.00 (0.91–1.00) | <0.001 |
| Steroid-free period/DS period (Med [IQR]) | 0.89 (0.66–1.00) | 1.00 (0.88–1.00) | 0.003 |
| Non-hospitalization period/DS period (Med [IQR]) | 0.99 (0.94–1.00) | 1.00 (0.99–1.00) | <0.001 |
| CDAI-negative period/assessment period (Med [IQR]) | 0.99 (0.63–1.00) | 1.00 (0.96–1.00) | 0.031 |
| PMS-negative period/assessment period (Med [IQR]) | 0.15 (0.00–0.51) | 0.30 (0.00–1.00) | 0.205 |
Abbreviations: CDAI, Crohn’s disease activity index; CRP, C-reactive protein; DS, drug survival (months); IQR, interquartile range; Med, median; PMS, partial Mayo score; WBC, white blood cell.
The horizontal axis depicts the biologic drug survival time (years), and the vertical axis represents the persistence rate at drug survival (%). Longitudinal continuation rates were compared between the poor-response and excellent-response groups, categorized based on the long-term effectiveness of biologics.
No significant differences were observed in the duration of treatment with 5-aminosalicylic acid, immunosuppressants, enteral nutrition, or GCAP between the groups demonstrating superior and inferior effectiveness indexes for biologics (Table 3).
| Poor-response group | Excellent-response group | p | |
|---|---|---|---|
| N = 92 | N = 91 | ||
| 5-ASA dosing period/DS period (Med [IQR]) | 0.89 (0.00–1.00) | 0.82 (0.00–1.00) | 0.257 |
| Immunosuppressant dosing period/DS period (Med [IQR]) | 0.00 (0.00–0.00) | 0.00 (0.00–0.00) | 0.555 |
| Elemental diet dosing period/DS period (Med [IQR]) | 0.33 (0.00–0.98) | 0.22 (0.00–0.95) | 0.463 |
| GCAP-implementation period/DS period (Med [IQR]) | 0.00 (0.00–0.00) | 0.00 (0.00–0.00) | 0.449 |
Abbreviations: 5-ASA, 5-aminosalicylic acid; CRP, C-reactive protein; DS, drug survival (months); GCAP, granulocyte apheresis; IQR, interquartile range; Med, median.
Patient background factors (11 items) were compared between the groups showing superior and inferior effectiveness indexes for biologics. First, the univariate analysis revealed significant differences in four items, namely, BMI ≥25 kg/m2, steroid-use status, naïve or non-naïve status with respect to biologic use, and duration of low albumin levels during DS time. Subsequently, factors considered to be of particular clinical significance were incorporated in the multivariate logistic regression analysis. Two categories, namely, BMI ≥25 kg/m2 and duration of low albumin levels during DS time, were found to be significantly associated with the therapeutic effect of biologics (Table 4).
| Group | Poor-response group | Excellent-response group | Univariate analysis | Multivariate analysis | |||
|---|---|---|---|---|---|---|---|
| N = 92 | N = 91 | p | OR | 95% CI | p | ||
| Sex (%)a) | Female | 35 (38.0) | 31 (34.1) | 0.645 | 1.72 | 0.819–3.6 | 0.152 |
| Age at diagnosis, years (Med [IQR]) | 25.00 (19.00–35.00) | 27.00 (22.50–37.00) | 0.118 | ||||
| BMI ≥25 kg/m2 (%)a) | Obesity | 20 (21.7) | 9 (9.9) | 0.042 | 0.185 | 0.0704–0.488 | <0.001 |
| Smoking habit (%)a) | Present | 6 (6.5) | 11 (12.1) | 0.214 | 1.09 | 0.306–3.9 | 0.892 |
| History of IBD-related surgery (%) | Present | 37 (40.2) | 40 (44.0) | 0.655 | |||
| UC/CD (%)a) | CD | 66 (71.7) | 67 (73.6) | 0.869 | 0.902 | 0.371–2.19 | 0.82 |
| Use of steroids (%)a) | Present | 61 (66.3) | 42 (46.2) | 0.007 | 0.574 | 0.284–1.16 | 0.123 |
| Biologics (%)a) | IFX | 15 (16.3) | 12 (13.2) | 0.69 | 0.897 | 0.317–2.54 | 0.859 |
| ADA | 35 (38.0) | 39 (42.9) | |||||
| UST | 23 (25.0) | 22 (24.2) | |||||
| VED | 15 (16.3) | 17 (18.7) | |||||
| GOL | 4 (4.3) | 1 (1.1) | |||||
| Naïve/non-naïve (%)a) | Naïve | 45 (48.9) | 62 (68.1) | 0.011 | 1.56 | 0.774–3.16 | 0.213 |
| Years from diagnosis to biologic administration (median [IQR]) | 4.00 (1.00, 11.25) | 3.00 (1.00, 12.00) | 0.903 | ||||
| Period of low albumin levels/DS period (median [IQR])a) | 0.86 (0.35, 1.07) | 0.21 (0.02, 0.63) | <0.001 | 0.0566 | 0.0224–0.143 | <0.001 | |
Abbreviations: ADA, adalimumab; BMI, body mass index; CD, Crohn’s disease; CI, confidence interval; CRP, C-reactive protein; DS, drug survival (months); GOL, golimumab; IFX, infliximab; IQR, interquartile range; Med, median; OR, odds ratio; UC, ulcerative colitis; UST, ustekinumab; VED, vedolizumab. a) Test items in multivariate analysis.
Table 5 shows the comparisons of various medical costs between the groups with excellent and poor therapeutic responses to biologic treatment. No significant differences were found in the surgical, GCAP, or treatment costs for adverse events when normalized to DS time. Although the costs of biologics and non-biologics differed significantly, the cost of medicine (excluding biologics) differed by <2000 JPY/month. However, the cost of biologics was significantly lower in the group with superior effectiveness than in the group with inferior effectiveness, and this difference exceeded 50000 JPY/month on a per-patient basis. The cost difference was because the group showing inferior therapeutic effectiveness of biologics was significantly more likely to require a higher dose of biologics than the standard dose (median: 1.22-fold). Conversely, the group showing excellent therapeutic effects received biologics close to the standard dose (median: 0.95-fold).
| Poor-response group | Excellent-response group | p | |
|---|---|---|---|
| N = 92 | N = 91 | ||
| Total medical cost (JPY)/DS period (Med [IQR]) | 264359 (192689–406587) | 191810 (156335–286624) | <0.001 |
| Surgical cost (JPY)/DS period (Med [IQR]) | 0 (0–0) | 0 (0–0) | 0.062 |
| GCAP cost (JPY)/DS period (Med [IQR]) | 0 (0–0) | 0 (0–0) | 0.449 |
| Treatment cost for biologics-related adverse events (JPY)/DS period (Med [IQR]) | 0 (0–0) | 0 (0–0) | 0.76 |
| Medication cost (JPY)/DS period (Med [IQR]) | 255444 (182806–400896) | 189054 (154076–286624) | 0.001 |
| Medication cost excluding biologics (JPY)/DS period (Med [IQR]) | 10710 (6416–19479) | 8745 (670–15147) | 0.022 |
| Biologics cost (JPY)/DS period (Med [IQR]) | 229738 (166110–379560) | 178554 (145457–275669) | 0.002 |
| Actual biologic cost/biologic costs for standard dose (Med [IQR]) | 1.22 (0.93–1.36) | 0.95 (0.87–1.20) | 0.001 |
Abbreviations: CRP, C-reactive protein; DS, drug survival (months); GCAP, granulocyte apheresis; IQR, interquartile range; Med, median.
Cost-effectiveness was verified based on the cost data of the two groups, that is, the group showing an excellent effectiveness index (median; IQR: 0.88 [0.76–0.98]) and that showing an inferior effectiveness index (0.17 [0.00–0.42]). We found that the total monthly medical cost for the group with an inferior effectiveness index was 264359 (192689–406587) JPY, whereas that for the group with an excellent effectiveness index was 191810 (156335–286624) JPY. Thus, the group with an excellent effectiveness index was considered as the cost-saving group.
We evaluated the long-term effects of biologics used in the treatment of IBD using the ratio of the CRP-negative period to DS time. We then clarified patient background factors that affected the effectiveness of biologics and the relationship between effectiveness and medical costs. In patients with IBD receiving long-term biologics in Japan, the higher the effectiveness of the treatment, the greater the cost savings. Obesity and low albumin status were identified as factors influencing cost-effectiveness.
DS time is a comprehensive indicator of drug effectiveness and safety. Identifying treatment methods and patient background factors that prolong DS time has gained research traction.8) However, DS time may be influenced by various factors, including the effectiveness and safety profile of the biologic, availability of alternative treatment options, preferences of medical practitioners and patients, severity of the condition, occupation of the patients, and sociocultural factors. Therefore, DS time alone may not fully reflect the effects of drugs.8) Common indicators of the effectiveness of biologics for IBD include inflammatory markers such as CRP levels and WBC counts, along with CDAI, PMS, and steroid-free status. However, such evaluations are performed at certain time points, and although these markers are easy to use as short-term indicators of drug effectiveness, their use as long-term indicators is difficult. Therefore, to evaluate the percentage of time when inflammation subsided during the administration of biologics, we evaluated the ratio of the CRP-negative period to DS time as a long-term effectiveness index. To evaluate the validity of this effectiveness index, we examined supplementary indexes and found that the ratio of the CRP-negative period to DS time is a valid supplementary effectiveness index for determining the therapeutic effect of biologics. Therefore, this index, which is simply DS time weighted with a clinical symptom, showed high validity and can be used as a long-term effectiveness index for biologics in other IBD-related studies.
We also evaluated the impact of the therapeutic effects of biologics on medical costs. Total healthcare costs normalized to DS time were significantly lower in the excellent-response group than in the poor-response group. Drug costs, especially biologic cost, had a marked impact on this difference, whereas the surgical and treatment costs for adverse events had a minor influence. A pharmacoeconomic study of biologic use in IBD treatment conducted in Croatia demonstrated that a crucial part of accurately capturing the cost of biologics is understanding that attenuating their effectiveness increases the cost of maintenance therapy.22) Our results indicate that patients who were less responsive to treatment with biologics used them at higher than standard doses, resulting in elevated medical costs. Enhancing the effectiveness of biologics for IBD treatment holds major implications for the well-being of individual patients and the clinical community and yields substantial pharmacoeconomic advantages. Additionally, the DS time was significantly prolonged in the group showing excellent effectiveness with biologics compared with that in the group showing inferior effectiveness. In particular, the difference in the continuation rate 1 year after the start of administration was significantly higher in the excellent-response group, indicating that this timing is a predictive indicator of the effectiveness of biologics. Furthermore, cases in which the discontinuation of biologics was due to diminishing effectiveness constituted a higher proportion (43.5%; n = 40) in the poor-response group than in the excellent-response group (9.9%; n = 9).
Both groups, divided according to their effectiveness indexes for biologic therapy, showed similar outcomes with both biologic and non-biologic treatments. Therefore, two variables (i.e., BMI ≥25 kg/m2 and duration of low albumin levels during DS time) detected as patient background factors may have influenced the superiority or inferiority of the therapeutic effects. In a previous study, adipose tissue was used as the main source of inflammatory mediators and interleukins, and the presence of low levels of chronic inflammation in the context of obesity suggested that the obese state may have weakened the therapeutic effectiveness of biologics.23) However, as the dose of biologics used (other than infliximab) is constant regardless of body weight, patients with a high BMI may have been administered insufficient doses relative to their body weight, compared to patients with a low BMI.
Although the association of IBD with low albumin levels is not as strong as that with CRP levels, low albumin levels can reflect severe inflammation.24–26) Additionally, hypoalbuminemia is the most important predictive factor of unsuccessful biologic therapy in IBD.26) Hypoalbuminemia in patients with IBD was also found to be strongly associated with the risk of losing response to anti-TNF-α therapy.27) Furthermore, only administering enteral nutrition to patients with IBD increased their serum albumin levels and alleviated their symptoms.28) An elemental nutrient (a type of enteral nutrient) promotes mucosal healing as the nutritional status improves and may enhance the therapeutic effect of biologics. However, depending on the patient’s preference, challenges may be experienced with continued use of a particular drug, and non-compliance with the prescription is a common issue.29,30)
In this study, we could not investigate the adherence rates for prescription drugs; however, the non-adherence rate of enteral nutrients may be high in patients with prolonged low albumin levels. Therefore, it is desirable to devise formulations that improve the adherence to enteral nutrients.29) The findings of this study regarding the predictors of the effectiveness of biologics are consistent with previous results. Additionally, we clarified the therapeutic effectiveness and pharmacoeconomic impact of biologics on IBD.
The following are the study’s limitations:
Within the framework of the Japanese medical insurance system, the copayment requirements for medical expenses vary with various factors, such as the patient’s age and annual income. Future studies should be conducted to verify whether copayments influence drug selection by prescribing physicians.
Biologics in IBD treatment are used as last-resort treatment options for patients with moderate-to-severe IBD, for whom conventional treatments are inadequate, and they have improved the QOL of many patients. However, the use of expensive biologics may significantly influence Japanese medical finances. To further advance pharmacoeconomic research in the field of IBD, it is desirable to develop a test method that can be used to evaluate the clinical symptoms and mucosal conditions of patients with IBD with higher sensitivity, specificity, and safety. A comprehensive clinical approach, such as the cost-effective use of biologics and lifestyle guidance for patients with IBD, might help improve the quality of medical care and soundness of medical finances.
In conclusion, to make long-term biologic therapy a cost-effective treatment, medical interventions, such as long-term correction of obesity and low albumin levels, could lead to the effective utilization of limited national medical funds, which has important pharmacoeconomic implications. To the best of our knowledge, this is the first real-world data-based pharmacoeconomic study in Japanese patients with IBD receiving long-term biologic therapy.
This work was supported by the Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research (Grant Number: JP23H05270).
The authors declare no conflict of interest.
