Health economic evaluation of self-injection of biologics in patients with rheumatoid arthritis using a Japanese real-world web-based survey

Health economic evaluation of self-injection of biologics in patients with rheumatoid arthritis using a Japanese real-world web-based survey | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Health economic evaluation of self-injection of biologics in patients with rheumatoid arthritis using a Japanese real-world web-based survey Kazuhiko Takahata, Yui Maeda, Eiichi Tanaka, Ryoko Sakai, Manabu Akazawa This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6034350/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 21 May, 2025 Read the published version in BMC Health Services Research → Version 1 posted 8 You are reading this latest preprint version Abstract Background Biological disease-modifying antirheumatic drugs (bDMARDs) have dramatically improved the quality of life of patients with rheumatoid arthritis (RA); however, concerns regarding their high cost persist. Self-injection (SI) may reduce medical expenses by decreasing the frequency of hospital visits. In this study, we compared the health economic costs of patients with RA who selected SI of bDMARDs and those who did not. Methods In this cross-sectional study, we analyzed data from January 2024 using a web-based self-report survey provided by Medilead, Inc. This study included patients with RA who were divided into the SI and non-SI groups. We calculated per visit and total annual out-of-pocket medical expenses for each group. Results Among 326 patients with RA, 79 (24.2%; female: 64.6%; mean age: 60.2 years) were treated with bDMARDs. Of these, 65 patients (82.3%) selected SI, and 14 (17.7%) selected non-SI administration. The non-SI group had a higher median frequency of hospital visits than the SI group (12 vs. 6 visits per year). The median out-of-pocket medical expense per visit was higher in the SI group (155.17 USD/visit) than in the non-SI group (86.21 USD/visit). However, the SI group had lower total annual out-of-pocket medical expenses than the non-SI group (948.42 USD/year vs. 1,071.72 USD/year, respectively). Conclusion Over 80% of patients with RA selected SI to administer bDMARDs, and their total annual out-of-pocket medical expenses were lower than those of patients who selected non-SI owing to the reduced frequency of hospital visits. The results of our study may provide useful insights into the selection of self-injectable bDMARDs for therapeutic decision-making based on out-of-pocket medical expenses. rheumatoid arthritis self-injection biological disease-modifying antirheumatic drugs health economic evaluation real-world web-based survey out-of-pocket medical expenses Figures Figure 1 Figure 2 Figure 3 Background Rheumatoid arthritis (RA) is a chronic inflammatory disease. In the last 20 years, the use of biological disease-modifying antirheumatic drugs (bDMARDs) has led to clinical, structural, and functional remission of RA. In Japan, as of January 2025, 12 bDMARDs (infliximab [IFX], infliximab biosimilar [IFX-BS], etanercept [ETN], etanercept biosimilar [ETN-BS], adalimumab [ADA], adalimumab biosimilar [ADA-BS], golimumab [GOL], certolizumab pegol [CZP], ozoralizumab, tocilizumab [TCZ], sarilumab [SAR], and abatacept [ABT]) were approved for RA, with 10 bDMARDs, except for IFX and IFX-BS, approved for self-injection (SI). Although bDMARDs can substantially improve the quality of life of patients, there are concerns regarding their high costs [ 1 , 2 ]. SI enables patients or caregivers to administer medication at home and has the potential to reduce the following costs during hospital visits: (i) direct healthcare costs, such as medical and drug costs [ 3 ]; (ii) direct non-healthcare costs, such as travel costs [ 4 ]; and (iii) indirect costs, such as the loss of patients’ or caregivers’ work productivity. For example, from a societal perspective, self-injected subcutaneous depot medroxyprogesterone acetate (DMPA) was found to avert more pregnancies and cost less than health-worker-administered intramuscular DMPA [ 4 ]. In patients with inflammatory bowel disease, the annual cost of maintenance treatment with self-injected subcutaneous vedolizumab is 15.0% lower than that of maintenance treatment with health-worker-administered intramuscular vedolizumab [ 3 ]. Previous studies evaluating the health economics of RA treatment have focused primarily on the cost-effectiveness of bDMARDs [ 5 – 7 ], with only a few studies exploring the health and economic benefits of SI. Accordingly, we hypothesized that SI would provide economic health benefits to patients with RA. In this study, we aimed to compare health-related costs between patients with RA who selected SI and those who did not. Methods Study design This cross-sectional study used a web-based self-reported questionnaire for Japanese patients with RA. The participants were patients registered in Medilead, Inc. (Tokyo, Japan) [ 8 – 10 ]. Meadilead Inc. comprises the general Japanese population who agreed to participate in surveys such as questionnaires and interviews. Approximately 4.2 million individuals are registered with Meadilead, Inc. Among all the registrants, eligible participants completed self-reported questionnaires (Supplementary material – Study Questionnaire). This study included 326 participants who were previously diagnosed with RA by a medical doctor. The web-based survey was conducted from January 15, 2024, to January 31, 2024, and the patients responded to the questionnaire only once. We did not collect identifiable information such as names or addresses; all data were anonymized. This study was approved by the Meiji Pharmaceutical University Research Ethics Committee in April 2022 (Approval No. 202144). Informed consent was obtained from respondents using a web form at the beginning of the survey. Study participants Participants who responded that RA was their primary disease and were using disease-modifying antirheumatic drugs (DMARDs; lobenzarit, auranofin, salazosulfapyridine, iguratimod, tacrolimus hydrate, leflunomide, bucillamine, methotrexate, actarit, penicillamine, mizoribine, IFX, IFX-BS, ETN, ETN-BS, ADA, ADA-BS, GOL, CZP, TCZ, SAR, ABT, tofacitinib citrate, baricitinib, peficitinib hydrobromide, filgotinib maleate, or upadacitinib hydrate) were identified as the DMARDs group. In the DMARDs group, we identified users of at least one self-injectable bDMARDs (ETN, ETN-BS, ADA, ADA-BS, GOL, CZP, TCZ, SAR, and ABT) and categorized them into the bDMARDs group. In the bDMARDs group, patients who selected SI were categorized into the SI group, whereas the remaining patients were assigned to the non-SI group. TCZ and ABT are available as self-injectable subcutaneous and hospital-based intravenous (IV) infusion formulations. In this study, regardless of the formulation used, patients were classified into SI or non-SI groups based on their self-reported method of administration (i.e., whether they selected SI) for subcutaneous (SC) bDMARDs. Accordingly, even if TCZ or ABT was administered intravenously at a medical facility, patients who self-injected any bDMARDs subcutaneously were classified into the SI group. Therefore, IV formulations of TCZ and ABT may have been included in the aggregated bDMARDs data for both the SI and non-SI groups (Tables 1 and 2 ). Table 1 Patients’ characteristics bDMARDs group (n = 79) SI group (n = 65) non-SI group (n = 14) Female 51 (64.6%) 42 (64.6%) 9 (64.3%) Age (Mean ± SD, year) 60.2 ± 12.2 59.3 ± 11.5 67.0 ± 13.5 Disease duration of RA (Mean ± SD, year) 13.1 ± 9.9 13.2 ± 10.3 11.3 ± 8.3 Comorbidities Hypertension 14 (17.7%) 12 (18.5%) 2 (14.3%) Dyslipidemia 11 (13.9%) 8 (12.3%) 3 (21.4%) Diabetes mellitus 6 (7.6%) 5 (7.7%) 1 (7.1%) Depression 4 (5.1%) 3 (4.6%) 1 (7.1%) Respiratory disease 4 (5.1%) 3 (4.6%) 1 (7.1%) J-HAQ (Mean ± SD) 0.62 ± 0.72 0.61 ± 0.71 0.63 ± 0.75 Employment status Permanent employment 22 (27.8%) 21 (32.3%) 1 (7.1%) Temporary employment 16 (20.3%) 13 (20.0%) 3 (21.4%) Unemployed 41 (51.9%) 31 (47.7%) 10 (71.4%) WPAI (Median [IQR], %) Absenteeism 0 (0‒0) (n = 38) 0 (0‒0) (n = 34) 0 (0‒0) (n = 4) Presenteeism 15 (0‒37.5) (n = 32) 10 (0–40) (n = 29) 20 (0–30) (n = 3) Overall work impairment 0 (0‒0) (n = 32) 0 (0‒0) (n = 29) 0 (0‒0) (n = 3) Daily activity impairment 20 (0‒40) (n = 79) 20 (10‒45) (n = 65) 20 (0‒32.5) (n = 14) Annual income (Median [IQR], USD) Individual 12068.97 (5172.41‒24137.93) 12068.97 (5172.41‒24137.93) 12068.97 (5172.41‒24034.48) Household 31034.48 (18965.52‒51724.14) 31034.48 (18965.52‒51724.14) 27586.21 (15103.45‒44827.59) Coinsurance (Median [IQR], %) 30 (20‒30) 30 (20‒30) 20 (15‒30) bDMARDs ETN (including biosimilar) 29 (36.7%) 26 (40.0%) 3 (21.4%) TCZ 22 (27.8%) 16 (24.6%) 6 (42.9%) ADA (including biosimilar) 12 (15.2%) 10 (15.4%) 2 (14.3%) ABT 12 (15.2%) 8 (12.3%) 4 (28.6%) GOL 10 (12.7%) 6 (9.2%) 4 (28.6%) SAR 7 (8.9%) 4 (6.2%) 3 (21.4%) CZP 5 (6.3%) 4 (6.2%) 1 (7.1%) Medical department Rheumatology 40 (50.6%) 36 (55.4%) 4 (28.6%) Orthopedic surgery 27 (34.2%) 18 (27.7%) 9 (64.3%) Internal medicine 13 (16.5%) 11 (16.9%) 2 (14.3%) Collagen diseases 11 (13.9%) 9 (13.8%) 2 (14.3%) bDMARDs, biological disease-modifying antirheumatic drugs; SI, self-injection; SD, standard deviation; IQR, interquartile range; RA, rheumatoid arthritis; J-HAQ, Japanese Health Assessment Questionnaire; WPAI, work productivity and activity impairment; ETN, etanercept; TCZ, tocilizumab; ADA, adalimumab; ABT, abatacept; GOL, golimumab; SAR, sarilumab; CZP, certolizumab pegol. Note: Intravenous (IV) formulations of tocilizumab and abatacept may be included in the aggregated bDMARDs data. Table 2. Usage proportion of bDMARDs in each medical department Medical department ETN (including biosimilar) TCZ ADA (including biosimilar) ABT GOL SAR CZP Rheumatology (n = 40) Orthopedic surgery (n = 27) Internal medicine (n = 14) Collagen diseases (n = 11) 14 (35%) 12 (44.4%) 7 (50.0%) 4 (36.4%) 9 (22.5%) 9 (33.3%) 5 (35.7%) 3 (27.3%) 7 (17.5%) 5 (18.5%) 3 (21.4%) 4 (36.4%) 7 (17.5%) 3 (11.1%) 1 (7.1%) 3 (27.3%) 5 (12.5%) 4 (14.8%) 2 (14.3%) 2 (18.2%) 4 (10.0%) 2 (7.4%) 2 (14.3%) 3 (27.3%) 3 (7.5%) 1 (3.7%) 2 (14.3%) 1 (9.1%) Patients who visited multiple medical departments were counted in each department they visited. bDMARDs, biological disease-modifying antirheumatic drugs; ETN, etanercept; TCZ, tocilizumab; ADA, adalimumab; ABT, abatacept; GOL, golimumab; SAR, sarilumab; CZP, certolizumab pegol. Note: Intravenous (IV) formulations of tocilizumab and abatacept may be included in the aggregated bDMARDs data. Survey variables Patient characteristics at the time of survey implementation, including sex, age, duration of RA, comorbidities, Japanese Health Assessment Questionnaire [ 11 ], employment status, annual income, coinsurance, work productivity and activity impairment (WPAI) questionnaire, class of bDMARDs used, medical departments visited (rheumatology, orthopedic surgery, internal medicine, and collagen diseases), and the percentage of those who used bDMARDs in each department were collected. Comorbidities were defined as conditions for which hospitalization or outpatient visits occurred within the past year, excluding RA. The WPAI-RA questionnaire comprises six questions as follows [ 12 ]. (Q1) Are you currently employed (working for pay)? (Q2) During the past 7 days, how many hours did you miss from work because of problems associated with RA? (Q3) During the past 7 days, how many hours did you miss from work because of any other reason, such as annual leave, holidays, time off to participate in this study? (Q4) During the past 7 days, how many hours did you actually work? (Q5) During the past 7 days, how much did your health problems affect your productivity while you were working? and (Q6) During the past 7 days, how much did your health problems affect your ability to do your regular daily activities other than work at a job? The answers for Q2, Q3, and Q4 are indicated by time (hours), and those for Q5 and Q6 are indicated by scores (0–10). A score of 0 means that health problems had no effect on the patient’s work/daily activities, and a score of 10 means that health problems completely prevented the patient from work/daily activities. We calculated productivity loss as follows: absenteeism (%) = Q2/(Q2 + Q4); presenteeism (%) = Q5/10×100; overall work impairment (%) = Q2/(Q2 + Q4) + (1 − Q2/(Q2 + Q4))×(Q5/10)×100; daily activity impairment (%) = Q6/10×100. Higher percentages indicate that there was greater work and daily activity impairment and lower productivity. We collected data on travel time to the hospital, time off for hospital visits, chaperones for hospital visits, out-of-pocket medical expenses per visit, travel costs, and the frequency of hospital visits. We calculated the total annual out-of-pocket medical expenses and limited societal perspective medical expenses. The total annual out-of-pocket medical expenses were calculated using the following formula (1 USD = 145 JPY in 2024): [The median out-of-pocket expenses per visit (direct healthcare costs) + the median traveling costs per visit (direct non-healthcare costs)] × median frequency of hospital visits (number of visits). The limited annual societal perspective medical expenses were calculated based on the following steps (1 USD = 145 JPY in 2024): (1) For patients whose out-of-pocket payment amounts and co-payments (e.g., 10%, 20%, 30%) were available, we calculated medical expenses per visit from the public healthcare payer’s perspective using the following formula: The medical expenses per visit from the public health care payer’s perspective = Out-of-pocket expenses ÷ Co-payment For example, if a patient paid 155.17 USD per visit with a 30% co-payment, the total cost was estimated to be 517.23 USD. (2) We then calculated the median values for medical expenses per visit, traveling costs, and annual frequency of hospital visits among these patients. (3) Finally, we estimated the limited annual societal perspective medical expenses using the following formula: Limited annual societal perspective medical expenses = [The medical expenses per visit from the public healthcare payer’s perspective (Direct healthcare costs) + the median traveling costs per visit (Direct non-healthcare costs)] × median frequency of hospital visits (number of visits). In this study, “limited annual societal perspective medical expenses” were estimated by combining direct medical expenses (e.g., drug costs and consultation fees) with direct non-medical expenses, specifically traveling expenses related to hospital visits. This definition is based on internationally accepted frameworks for health economic evaluation, in which adopting a societal or quasi-societal perspective is recommended to include both direct medical and direct non-medical expenses. Although this study does not incorporate indirect costs such as productivity loss or informal care, we aimed to go beyond the payer’s perspective and partially capture the economic burden on patients. Given that SI can reduce the number of hospital visits, the inclusion of traveling costs was considered relevant for assessing the economic benefits of SI. In addition, we surveyed the level of satisfaction with SI (satisfaction, continuity, implementer, ease of use, reasons for not selecting SI, and the preferred method for future administration). Satisfaction with SI was determined based on five levels: “very satisfied,” “somewhat satisfied,” “neutral,” “somewhat dissatisfied,” and “very dissatisfied.” SI continuity was determined based on the following: “Patient would like to continue SI in the future,” “Patient would like to switch to other methods of administration,” and “Do not know.” The SI implementer was surveyed based on categories of “Yourself,” “Your family,” “Home health nurse,” and “Other person.” The ease of SI was determined based on five levels: “very easy,” “somewhat easy,” “neutral,” “somewhat difficult,” and “very difficult.” Reasons for not selecting SI were determined based on the following survey replies: “patient was unaware of SI”; “patient knew about SI but did not receive information from their doctor”; “patient has used SI in the past, but has now stopped doing so”; “patient has difficulty in SI due to deformed joints”; “patient does not have a good impression of SI”; and “other reasons.” Patients who selected multiple reasons were included. Outcomes The primary outcome was the total annual out-of-pocket medical expenses of patients with RA who selected the SI of bDMARDs and those who did not. As a secondary outcome, we compared the limited annual societal perspective medical expenses between patients with RA who selected the SI of bDMARDs and those who did not. Statistical analysis For the endpoints, the response data are summarized separately for the bDMARDs, SI, and non-SI groups. Summary statistics were calculated for continuous variables, and ratios were calculated for categorical variables. All analyses were performed using R software version 3.2.2. Results Patients’ characteristics This study included 326 patients previously diagnosed with RA by a medical doctor. Among them, 303 (92.9%) and 79 (24.2%) patients were assigned to the DMARDs and bDMARDs groups, respectively (Fig. 1 ). In the bDMARDs group, 65 patients (82.3%) selected SI (SI group), whereas 14 (17.7%) did not (non-SI group). No patient was undergoing monotherapy with bDMARDs. Patient characteristics are presented in Table 1 . The mean age of patients in the non-SI group was higher than that of patients in the SI group (67.0 ± 13.5 years vs. 59.3 ± 11.5 years, respectively). Thirty-four patients (52.3%) in the SI group had permanent or temporary employment, which was higher than that in the non-SI group (n = 4; 28.5%). In the SI group, the median (IQR) scores were as follows: absenteeism, 0% (0–0); presenteeism, 10% (0–40); overall work impairment, 0% (0–0); and daily activity impairment, 20% (10–45). Conversely, median (IQR) scores for the non-SI group were as follows: absenteeism, 0% (0–0); presenteeism, 20% (0–30); overall work impairment, 0% (0–0); and daily activity impairment, 20% (0–32.5). Utilization of bDMARDs The most frequently used bDMARDs were ETN in the SI group (n = 26; 40.0%) and TCZ in the non-SI group (n = 6; 42.9%) (Table 1 ). The medical departments with the highest proportion of hospital visits were rheumatology in the SI group (n = 36; 55.4%) and orthopedics in the non-SI group (n = 9; 64.3%) (Table 1 ). ETN, TCZ, and ADA were frequently used in all medical departments (Table 2 ). Total annual out-of-pocket and limited annual societal perspective medical expenses The SI group had higher median out-of-pocket medical expenses per visit than the non-SI group (155.17 USD/visit vs. 86.21 USD/visit, respectively) (Table 3 ). However, the SI group had lower total annual out-of-pocket medical expenses than the non-SI group (948.42 USD/year vs. USD 1,071.72 USD/year, respectively) (Fig. 2 ). Table 3 Out-of-pocket and public health care payer’s perspective medical expenses Perspective of the analysis Items bDMARDs group (n = 79) SI group (n = 65) non-SI group (n = 14) - Travel time to the hospital (Median [IQR], min) 15 (15‒45) 15 (15‒45) 15 (15‒45) Time off for hospital visits (Median [IQR], h/visit) 0 (0‒6) 0 (0‒6) 0 (0‒0) Chaperone for hospital visits 11 (13.9%) 11 (16.9%) 0 (0.0%) Out-of-pocket Medical expenses (Median [IQR], USD/visit) (Direct health care costs) 155.17 (86.21‒241.38) 155.17 (103.45‒241.38) 86.21 (17.24‒18,750) Traveling costs (Median [IQR], USD/visit) (Direct non-health care costs) 3.03 (0‒6.48) 2.90 (0-6.62) 3.10 (1.93–4.83) Frequency of hospital visits (Median [IQR], visit/year) (Number of visits) 6 (4‒12) 6 (4‒12) 12 (10.5‒12) Public health care payer’s perspective Medical expenses (Median [IQR], USD/visit) (Direct health care costs) 632.18 (459.77‒1034.48) (n = 69) 775.86 (517.24‒1077.59) (n = 58) 287.36 (258.62‒603.45) (n = 11) Traveling costs (Median [IQR], USD/visit) (Direct non-health care costs) 2.90 (0.38‒6.30) (n = 69) 2.83 (0.00‒6.20) (n = 58) 3.45 (2.76‒6.90) (n = 11) Frequency of hospital visits (Median [IQR], visit/year) (Number of visits) 6 (4‒12) (n = 69) 6 (4‒12) (n = 58) 12 (6‒12) (n = 11) bDMARDs, biological disease-modifying antirheumatic drugs; SI, self-injection; IQR, interquartile range. The median public healthcare payer’s perspective medical expenses per visit were higher in the SI group (775.86 USD/visit) than those in the non-SI group (287.36 USD/visit) (Table 3 ). The SI group had higher limited annual societal perspective medical expenses than the non-SI group (4,672.14 USD/year vs. 3,489.72 USD/year, respectively) (Fig. 3 ). Regarding the total annual out-of-pocket medical expenses and limited annual societal perspective medical expenses, the medical costs of the SI and non-SI groups were reversed. Fact-finding surveys of SI Considering satisfaction with SI, a total of 50 patients (76.9%) in the SI group responded “somewhat satisfied” or “very satisfied.” Fifty-two patients (80.0%) responded that they would like to continue SI in the future. Sixty-four patients (98.5%) self-administered the injections. Regarding the ease of use of SI, 56 patients (86.1%) responded that it was “very easy” or “somewhat easy” (Table 4 ). Table 4 Satisfaction, continuity, implementer, and ease of use of self-injection in the SI group Survey items SI group (n = 65) Level of satisfaction with SI Very satisfied 15 (23.1%) Somewhat satisfied 35 (53.8%) Neutral 10 (15.4%) Somewhat dissatisfied 5 (7.7%) Very dissatisfied 0 (0.0%) Continuity of SI Patient would like to continue SI in the future 52 (80.0%) Patient would like to switch to another method of administration 4 (6.2%) Do not know 9 (13.8%) SI implementer Yourself 64 (98.5%) Other person 1 (1.5%) Ease of SI use Very easy 29 (44.6%) Somewhat easy 27 (41.5%) Neutral 8 (12.3%) Somewhat difficult 1 (1.5%) Very difficult 0 (0.0%) SI, self-injection. In the non-SI group, 10 patients (71.4%) had a negative impression of SI. Among these, six patients (42.9%) did not select SI owing to “not having a good impression of SI”; of the remaining four (28.6%), one patient each selected “patients was unable to administer the injection by himself/herself due to a lack of strength, and patient was afraid to inject himself/herself,” “patient worried about forgetting to inject,” “patient disliked SI by himself/herself” and “patient was feeling anxious about SI”. In addition, one patient each selected “patient did not select SI according to the doctor’s instruction” and “patient did not need to select SI”. Furthermore, one patient each selected “patient has used SI in the past but has now stopped from doing so” and “patient has difficulty with SI due to deformed joints”. Three patients (21.4%) knew about SI but had not received information from their doctors (Table 5 ). Thirteen patients (92.9%) preferred to continue with their current method of administration and did not want to switch to SI. Table 5 Reasons for not selecting self-injection in the non-SI group Reasons for not selecting SI Non-SI group (n = 14) Patient does not have a good impression of SI 6 (42.9%) Other reasons 6 (42.9%) Patient was unable to administer the injection by himself/herself due to a lack of strength, and the patient was afraid to administer the injection himself/herself 1 (7.1%) Patient worried about forgetting to inject 1 (7.1%) Patient disliked SI by himself/herself 1 (7.1%) Patient was feeling anxious about SI 1 (7.1%) Patient did not select SI according to the doctor’s instruction 1 (7.1%) Patient did not need to select SI 1 (7.1%) Patient knew about SI but did not receive information from their doctor 3 (21.4%) Patient has used SI in the past but has now stopped from doing so 1 (7.1%) Patient has difficulty with SI due to deformed joints 1 (7.1%) SI, self-injection. Discussion In this study, we found that over 80% of patients with RA using bDMARDs selected SI. Although the SI group had higher out-of-pocket medical expenses per visit than the non-SI group, total annual out-of-pocket medical expenses decreased. While SI reduces the frequency of hospital visits, patients may be prescribed bDMARDs for several months in a single visit in anticipation of potential natural disasters or limited access to healthcare services. Healthcare providers must work with the government to devise easy-to-understand measures to inform residents of the relevance of stockpiling regular medications for disasters and conduct educational activities for chronic diseases [ 13 ]. Accordingly, the medication cost per visit may increase, contributing to higher direct medical costs and, consequently, greater overall societal costs. However, Japan's high-cost medical expense benefit system sets an upper limit on out-of-pocket payments based on individual income levels. This system may have contributed to keeping out-of-pocket payments relatively low in the SI group despite higher medical costs, potentially explaining the observed discrepancy. Based on these results, the medical expense evaluation of SI for patients with RA using biologics may vary depending on the analytical perspective. This study was limited to results based on a web-based patient survey and did not provide an appropriate health economic evaluation from the perspective of public healthcare payers. Therefore, future studies should consider large claims data to evaluate medical expenses associated with SI more accurately from the public healthcare payer’s perspective. The difference in the number of hospital visits between the SI and non-SI groups may be explained by differences in employment status according to age. In this study, the mean age of participants in the non-SI group was higher than that of participants in the SI group. Older outpatients reportedly prefer bDMARDs administration by medical staff at medical facilities, whereas younger patients prefer SI [ 14 ]. This may be because a lower proportion of older patients was employed, making it easier for them to secure time for hospital visits. In this study, the proportion of patients with permanent or temporary employment was lower in the non-SI group than in the SI group. Therefore, the non-SI group had more frequent total annual hospital visits than the SI group. Informal care is unpaid care provided by families or non-family volunteers to fulfill patients’ needs to accomplish activities of daily living (ADLs), such as bathing, dressing, and eating, or instrumental ADLs, such as shopping, cooking, and money management [ 15 ]. From a societal perspective, it is important to consider health economics, including informal care costs. A study conducted in the United Kingdom reported that caregivers of patients with moderate RA required time off work and reduced working hours to provide care [ 16 ]. In the present study, 11 patients (16.9%) in the SI group required chaperones for hospital visits (Table 3 ). We observed that SI reduced the frequency of hospital visits, which may have reduced the frequency of chaperone hospital visits. Additionally, the median travel time to the hospital per visit was only 15 min for the SI and non-SI groups. However, SI reduced economic losses by decreasing the frequency of hospital visits, resulting in reduced travel time. To evaluate the health and economic benefits of SI from a societal perspective, it is crucial to consider the economic losses incurred by caregivers and patient travel times to hospitals. The results of our study indicate that patients were satisfied with their current method of administration, which is consistent with the findings of a previous study [ 17 ]. Conversely, patients or their caregivers may experience anxiety or fear regarding SI [ 18 – 21 ]. Negative past experiences with SI can affect future SI experiences [ 18 ]. In our study, more than 70% of patients who did not select SI had a negative impression of it, and we observed a similar trend to that of Smith et al. This study showed that over 20% of patients who had not selected SI did not receive information from their doctors or were unaware of SI. These results indicate that providing appropriate information may encourage more patients to switch to SI. Herein, we detected differences in the distribution of medical departments between the SI and non-SI groups. Specifically, most patients in the SI group visited rheumatology departments (36 patients; 55.4%), whereas those in the non-SI group tended to visit orthopedic departments more frequently (9 patients; 64.3%). These differences may have influenced both the decision to use SI and the subsequent economic outcomes. Rheumatologists are generally well-experienced in bDMARDs therapy and are more likely to provide active guidance and information regarding SI. Conversely, orthopedic departments, even when rheumatology specialists are involved, typically focus on structural and procedural treatments of joints, and may provide less information or support related to self-injection. Such differences across medical departments may affect patients’ choices regarding the method of bDMARDs administration, ultimately leading to variations in visit frequency and healthcare costs. However, this study has some limitations that must be addressed. First, we used data from a web-based, self-reported survey, and the possibility of RA misclassification cannot be disregarded. Second, this study was limited to patients who could participate in a web-based survey and had relatively high information technology literacy and interest in their disease. Third, we could not assess clinical data on disease and physical activity. Fourth, because this study was based on only one survey, causal relationships could not be investigated. Fifth, this study was conducted without distinguishing between SI and intravenous formulations; therefore, for patients who selected TCZ and ABT as bDMARDs, the use of SI and intravenous formulations may have been included. Sixth, the term “negative impression” reflects a psychological reluctance or fear of SI; however, it remains unclear whether these impressions are associated with prior adverse experiences. Additionally, owing to the structure of the questionnaire, data on the types of bDMARDs previously used and whether they were administered via SI or non-SI methods were not collected. This limitation may have affected the interpretation of the patient’s attitudes toward SI. Finally, this study has the potential for recall bias owing to its reliance on self-reported data. Information such as the frequency of hospital visits over the past 12 months was collected using a web-based questionnaire, which may have led to variability in the accuracy of responses. However, the questionnaire employed a multiple-choice format rather than open-ended responses to minimize the respondent burden and reduce the impact of recall bias. Furthermore, patients with RA experiencing stable disease activity tend to attend regular follow-up visits once a month or every two months, which may lead to accurate recall. Conclusion Over 80% of patients with RA using bDMARDs selected SI, which lowered their total annual out-of-pocket medical expenses by reducing the frequency of hospital visits. The results of our study may provide useful insights into the selection of self-injectable bDMARDs for therapeutic decision-making based on out-of-pocket medical expenses. Abbreviations ABT abatacept ADA adalimumab ADA-BS adalimumab biosimilar ADLs activities of daily living bDMARDs biological disease-modifying antirheumatic drugs CZP certolizumab pegol DMARDs disease-modifying antirheumatic drugs DMPA depot medroxyprogesterone acetate ETN etanercept ETN-BS etanercept biosimilar GOL golimumab IFX infliximab IFX-BS infliximab biosimilar IQR interquartile range IV intravenous J-HAQ Japanese Health Assessment Questionnaire RA rheumatoid arthritis SAR sarilumab SC subcutaneous SI self-injection TCZ tocilizumab WPAI work productivity and activity impairment. Declarations Ethics approval and consent to participate This study was approved by the Meiji Pharmaceutical University Research Ethics Committee in April 2022 (Approval No. 202144). The study complied with principles for ethical research in the Declaration of Helsinki, and informed consent was obtained from all the participants using a web form at the beginning of the survey. Consent for publication Not applicable. Availability of data and materials The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. Competing interests K.T. is an employee of Kyowa Kirin Co., Ltd., and has received tuition support for part of his doctoral degree program from his company. E.T. has received lecture fees or consulting fees from AbbVie Japan GK, Asahi Kasei Corp., Astellas Pharma Inc., Ayumi Pharmaceutical Co., Boehringer Ingelheim Japan, Inc., Bristol Myers Squibb Co., Ltd., Chugai Pharmaceutical Co., Ltd., Daiichi-Sankyo, Inc., Eisai Co., Ltd., Eli Lilly Japan K.K., Gilead Sciences, Inc., GlaxoSmithKline K.K., Kyowa Pharma Chemical CO., Ltd., Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Co., Mochida Pharmaceutical CO., Ltd., Nippon Kayaku Co., Ltd., Pfizer Japan Inc., Takeda Pharmaceutical Co., Ltd., Teijin Pharma Ltd, and Viatris Japan. E.T. has received research funding from Pfizer Inc., UCB Japan Co., Ltd., and Mitsubishi Tanabe Pharma Corporation. R.S. has received consulting fees from Nippon Kayaku Co., Ltd. M.A. received lectures and consulting fees from Astellas Pharma Inc., Mitsubishi Tanabe Pharma Co., GlaxoSmithKline K.K., and Janssen Pharmaceutical K.K. Y.M. has no conflicts of interest Peer reviewers for this manuscript have no relevant financial or other relationships to disclose. Funding The authors received no funding for this study. Authors’ contributions K.T., E.T., R.S. and M.A. conceived the study. All authors contributed to study design and interpretation. Data analysis was performed by K.T. and Y.M. The first draft of the manuscript was written by K.T., and all authors commented on previous versions of the manuscript. All the authors have read and approved the final version of this manuscript. Acknowledgments We thank Medilead Inc. for conducting the online survey and Editage for the English language editing. Authors’ information Department of Public Health and Epidemiology, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose-shi, Tokyo, 204-8588, Japan Kazuhiko Takahata, Yui Maeda, Ryoko Sakai and Manabu Akazawa Department of Rheumatology, Tokyo Women’s Medical University School of Medicine, 8-1, Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan Eiichi Tanaka and Ryoko Sakai References Yamanaka H, Tanaka E, Nakajima A, Furuya T, Ikari K, Taniguchi A, et al. A large observational cohort study of rheumatoid arthritis, IORRA: Providing context for today's treatment options. Mod Rheumatol. 2020;30:1–6. Hresko A, Lin TC, Solomon DH. Medical care costs associated with rheumatoid arthritis in the US: A systematic literature review and meta-analysis. Arthritis Care Res (Hoboken). 2018;70:1431–8. Bergqvist V, Holmgren J, Klintman D, Marsal J. Real-world data on switching from intravenous to subcutaneous vedolizumab treatment in patients with inflammatory bowel disease. Aliment Pharmacol Ther. 2022;55:1389–401. Di Giorgio L, Mvundura M, Tumusiime J, Morozoff C, Cover J, Drake JK. Is contraceptive self-injection cost-effective compared to contraceptive injections from facility-based health workers? Evidence from Uganda. Contraception. 2018;98:396–404. Tanaka E, Inoue E, Yamaguchi R, Shimizu Y, Kobayashi A, Sugimoto N, et al. Pharmacoeconomic analysis of biological disease modifying antirheumatic drugs in patients with rheumatoid arthritis based on real-world data from the IORRA observational cohort study in Japan. Mod Rheumatol. 2017;27:227–36. Brown S, Everett CC, Naraghi K, Davies C, Dawkins B, Hulme C, et al. Alternative tumour necrosis factor inhibitors (TNFi) or abatacept or rituximab following failure of initial TNFi in rheumatoid arthritis: The SWITCH RCT. Health Technol Assess. 2018;22:1–280. Vanier A, Mariette X, Tubach F, Fautrel B, STRASS Study Group. Cost-effectiveness of TNF-blocker injection spacing for patients with established rheumatoid arthritis in remission: An economic evaluation from the spacing of TNF-blocker injections in rheumatoid arthritis trial. Value Health. 2017;20:577–85. Medilead. Inc. Research Panel MHP (Medilead Healthcare Panel). https://www.medi-l.com/ . Accessed 13 Feb 2025. Yamaguchi H, Iwasaki K, Shoji A, Kokubo K, Igarashi A. Health-related quality of life (QoL) in Japanese patients with cancer: a large-scale questionnaire survey using EQ-5D-5L. Ther Res. 2022;41:949–55. Masaki H, Ishizaki S, Uenishi T, Kokubo K, Igarashi A. A survey of the impact of COVID-19 on the visiting frequency of Japanese Patients with gastrointestinal diseases. Jpn Pharmacol Ther. 2021;49:17–39. Matsuda Y, Singh G, Yamanaka H, Tanaka E, Urano W, Taniguchi A, et al. Validation of a Japanese version of the Stanford Health Assessment Questionnaire in 3,763 patients with rheumatoid arthritis. Arthritis Rheum. 2003;49:784–8. Reilly MC, Zbrozek AS, Dukes EM. The validity and reproducibility of a work productivity and activity impairment instrument. PharmacoEconomics. 1993;4:353–65. Akira Mitoya RK, Taniguchi R, et al. Current status and influencing factors of the stockpiling of regular medicines for disasters in patients with chronic disease. Jpn J Soc Pharm. 2024;43:2–11. Chilton F, Collett RA. Treatment choices, preferences and decision-making by patients with rheumatoid arthritis. Musculoskelet Care. 2008;6:1–14. Joo H, Zhang P, Wang G. Cost of informal care for patients with cardiovascular disease or diabetes: Current evidence and research challenges. Qual Life Res. 2017;26:1379–86. Galloway J, Edwards J, Bhagat S, Parker B, Tan AL, Maxwell J, et al. Direct healthcare resource utilisation, health-related quality of life, and work productivity in patients with moderate rheumatoid arthritis: An observational study. BMC Musculoskelet Disord. 2021;22:277. Kishimoto M, Yamairi F, Sato N, Kobayashi J, Yamauchi S, Iwasaki T. Patient preference for treatment mode of biologics in rheumatoid arthritis: A 2020 web-based survey in Japan. Rheumatol Ther. 2021;8:1095–111. van den Bemt BJF, Gettings L, Domańska B, Bruggraber R, Mountian I, Kristensen LE. A portfolio of biologic self-injection devices in rheumatology: How patient involvement in device design can improve treatment experience. Drug Deliv. 2019;26:384–92. Keininger D, Coteur G. Assessment of self-injection experience in patients with rheumatoid arthritis: Psychometric validation of the Self-Injection Assessment Questionnaire (SIAQ). Health Qual Life Outcomes. 2011;9:2. Wei Y, Zhao J, Ming J, Zhang X, Chen Y. Patient preference for self-injection devices in rheumatoid arthritis: A discrete choice experiment in China. Patient Prefer Adherence. 2022;16:2387–98. Rekaya N, Vicik SM, Hulesch BT, McDonald LL. Enhancement of an auto-injector device for self-administration of etanercept in patients with rheumatoid arthritis confers emotional and functional benefits. Rheumatol Ther. 2020;7:537–52. Additional Declarations No competing interests reported. Supplementary Files surveyquestionnaireEnglishver..xlsx Cite Share Download PDF Status: Published Journal Publication published 21 May, 2025 Read the published version in BMC Health Services Research → Version 1 posted Editorial decision: Revision requested 30 Apr, 2025 Reviews received at journal 28 Apr, 2025 Reviews received at journal 19 Apr, 2025 Reviewers agreed at journal 15 Apr, 2025 Reviewers agreed at journal 13 Apr, 2025 Reviewers invited by journal 12 Apr, 2025 Submission checks completed at journal 11 Apr, 2025 First submitted to journal 10 Apr, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6034350","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":442379362,"identity":"447bdca1-baac-4351-bc22-52172bfe61b7","order_by":0,"name":"Kazuhiko Takahata","email":"","orcid":"","institution":"Meiji Pharmaceutical University","correspondingAuthor":false,"prefix":"","firstName":"Kazuhiko","middleName":"","lastName":"Takahata","suffix":""},{"id":442379363,"identity":"68ecdc87-c007-423c-b760-ae38f6a05e72","order_by":1,"name":"Yui Maeda","email":"","orcid":"","institution":"Meiji Pharmaceutical University","correspondingAuthor":false,"prefix":"","firstName":"Yui","middleName":"","lastName":"Maeda","suffix":""},{"id":442379364,"identity":"b5cc6887-835d-44d8-90bf-e09d51f8b358","order_by":2,"name":"Eiichi Tanaka","email":"","orcid":"","institution":"Tokyo Women’s Medical University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Eiichi","middleName":"","lastName":"Tanaka","suffix":""},{"id":442379365,"identity":"a83d71d9-574c-488f-9dd9-4d6af26a930c","order_by":3,"name":"Ryoko Sakai","email":"","orcid":"","institution":"Meiji Pharmaceutical University","correspondingAuthor":false,"prefix":"","firstName":"Ryoko","middleName":"","lastName":"Sakai","suffix":""},{"id":442379366,"identity":"239a3316-4fdb-4604-ac5c-756051bca879","order_by":4,"name":"Manabu Akazawa","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA+klEQVRIiWNgGAWjYFACNgjFDyIYG2CiPERokWwgWYvBARQteIBu+7HEjz9qDssbXztjwFy4wy5ft4H54QcGmTs4tZidSTssIXHssOG22zkGzDPPJFtuO8BmLMHA8wy3lgPpDRIGbLcZgVrMf/O2MRuYHWAwA/rlMG4t5583/0j4d9t+82ygLbxt9UAt7N/wa7mRdkziYNvtxA3SYC2HgVp4CNhy41maZWPf/+QZt9MKmGe2HTcwO8xTLJGAzy/n04xv/viWZts/O3kDc2FbtYHZ8faNHz724A4xJMBhwAymQWRizwFitLA/YEZwfhClZRSMglEwCkYGAABLy1iOA71XFQAAAABJRU5ErkJggg==","orcid":"","institution":"Meiji Pharmaceutical University","correspondingAuthor":true,"prefix":"","firstName":"Manabu","middleName":"","lastName":"Akazawa","suffix":""}],"badges":[],"createdAt":"2025-02-15 05:08:07","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6034350/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6034350/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12913-025-12908-1","type":"published","date":"2025-05-21T15:57:23+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":80797083,"identity":"ec12d76e-98f6-4131-8174-561e00949f04","added_by":"auto","created_at":"2025-04-17 07:52:00","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":150972,"visible":true,"origin":"","legend":"\u003cp\u003ePatient flowchart\u003c/p\u003e\n\u003cp\u003eRA, rheumatoid arthritis; DMARDs, disease-modifying antirheumatic drugs; bDMARDs, biological disease-modifying antirheumatic drugs; SI, self-injection.\u003c/p\u003e","description":"","filename":"Figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6034350/v1/9981cee4cfb7df7d58deceaf.jpg"},{"id":80796786,"identity":"985eced6-1b33-44d7-a833-ae0a046e09dd","added_by":"auto","created_at":"2025-04-17 07:44:00","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":131313,"visible":true,"origin":"","legend":"\u003cp\u003eTotal annual out-of-pocket medical expenses\u003c/p\u003e\n\u003cp\u003ebDMARDs, biological disease-modifying antirheumatic drugs; SI, self-injection.\u003c/p\u003e","description":"","filename":"Figure2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6034350/v1/14366fa6370e6000f5341efb.jpg"},{"id":80796790,"identity":"3024a3e2-db87-4b73-8704-a9c08bcff833","added_by":"auto","created_at":"2025-04-17 07:44:00","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":141618,"visible":true,"origin":"","legend":"\u003cp\u003eLimited annual societal perspective medical expenses\u003c/p\u003e\n\u003cp\u003ebDMARDs, biological disease-modifying antirheumatic drugs; SI, self-injection.\u003c/p\u003e","description":"","filename":"Figure3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6034350/v1/97fccacba0fffb60aa2ae371.jpg"},{"id":83460603,"identity":"6e63bee0-04a6-4c34-9552-e3164d77bdc7","added_by":"auto","created_at":"2025-05-26 16:12:46","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1432216,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6034350/v1/108ae010-e9e6-470d-b32c-4d0838168bf5.pdf"},{"id":80796788,"identity":"2aedaec1-0588-4608-aecb-933a1c3fccd7","added_by":"auto","created_at":"2025-04-17 07:44:00","extension":"xlsx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":19346,"visible":true,"origin":"","legend":"","description":"","filename":"surveyquestionnaireEnglishver..xlsx","url":"https://assets-eu.researchsquare.com/files/rs-6034350/v1/e22bb1a8f54c5a7487bb9bae.xlsx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Health economic evaluation of self-injection of biologics in patients with rheumatoid arthritis using a Japanese real-world web-based survey","fulltext":[{"header":"Background","content":"\u003cp\u003eRheumatoid arthritis (RA) is a chronic inflammatory disease. In the last 20 years, the use of biological disease-modifying antirheumatic drugs (bDMARDs) has led to clinical, structural, and functional remission of RA. In Japan, as of January 2025, 12 bDMARDs (infliximab [IFX], infliximab biosimilar [IFX-BS], etanercept [ETN], etanercept biosimilar [ETN-BS], adalimumab [ADA], adalimumab biosimilar [ADA-BS], golimumab [GOL], certolizumab pegol [CZP], ozoralizumab, tocilizumab [TCZ], sarilumab [SAR], and abatacept [ABT]) were approved for RA, with 10 bDMARDs, except for IFX and IFX-BS, approved for self-injection (SI). Although bDMARDs can substantially improve the quality of life of patients, there are concerns regarding their high costs [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eSI enables patients or caregivers to administer medication at home and has the potential to reduce the following costs during hospital visits: (i) direct healthcare costs, such as medical and drug costs [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]; (ii) direct non-healthcare costs, such as travel costs [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]; and (iii) indirect costs, such as the loss of patients\u0026rsquo; or caregivers\u0026rsquo; work productivity. For example, from a societal perspective, self-injected subcutaneous depot medroxyprogesterone acetate (DMPA) was found to avert more pregnancies and cost less than health-worker-administered intramuscular DMPA [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. In patients with inflammatory bowel disease, the annual cost of maintenance treatment with self-injected subcutaneous vedolizumab is 15.0% lower than that of maintenance treatment with health-worker-administered intramuscular vedolizumab [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Previous studies evaluating the health economics of RA treatment have focused primarily on the cost-effectiveness of bDMARDs [\u003cspan additionalcitationids=\"CR6\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e], with only a few studies exploring the health and economic benefits of SI.\u003c/p\u003e \u003cp\u003eAccordingly, we hypothesized that SI would provide economic health benefits to patients with RA. In this study, we aimed to compare health-related costs between patients with RA who selected SI and those who did not.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy design\u003c/h2\u003e \u003cp\u003eThis cross-sectional study used a web-based self-reported questionnaire for Japanese patients with RA. The participants were patients registered in Medilead, Inc. (Tokyo, Japan) [\u003cspan additionalcitationids=\"CR9\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Meadilead Inc. comprises the general Japanese population who agreed to participate in surveys such as questionnaires and interviews. Approximately 4.2\u0026nbsp;million individuals are registered with Meadilead, Inc. Among all the registrants, eligible participants completed self-reported questionnaires (Supplementary material \u0026ndash; Study Questionnaire). This study included 326 participants who were previously diagnosed with RA by a medical doctor. The web-based survey was conducted from January 15, 2024, to January 31, 2024, and the patients responded to the questionnaire only once. We did not collect identifiable information such as names or addresses; all data were anonymized. This study was approved by the Meiji Pharmaceutical University Research Ethics Committee in April 2022 (Approval No. 202144). Informed consent was obtained from respondents using a web form at the beginning of the survey.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eStudy participants\u003c/h3\u003e\n\u003cp\u003eParticipants who responded that RA was their primary disease and were using disease-modifying antirheumatic drugs (DMARDs; lobenzarit, auranofin, salazosulfapyridine, iguratimod, tacrolimus hydrate, leflunomide, bucillamine, methotrexate, actarit, penicillamine, mizoribine, IFX, IFX-BS, ETN, ETN-BS, ADA, ADA-BS, GOL, CZP, TCZ, SAR, ABT, tofacitinib citrate, baricitinib, peficitinib hydrobromide, filgotinib maleate, or upadacitinib hydrate) were identified as the DMARDs group.\u003c/p\u003e \u003cp\u003eIn the DMARDs group, we identified users of at least one self-injectable bDMARDs (ETN, ETN-BS, ADA, ADA-BS, GOL, CZP, TCZ, SAR, and ABT) and categorized them into the bDMARDs group.\u003c/p\u003e \u003cp\u003eIn the bDMARDs group, patients who selected SI were categorized into the SI group, whereas the remaining patients were assigned to the non-SI group. TCZ and ABT are available as self-injectable subcutaneous and hospital-based intravenous (IV) infusion formulations. In this study, regardless of the formulation used, patients were classified into SI or non-SI groups based on their self-reported method of administration (i.e., whether they selected SI) for subcutaneous (SC) bDMARDs. Accordingly, even if TCZ or ABT was administered intravenously at a medical facility, patients who self-injected any bDMARDs subcutaneously were classified into the SI group. Therefore, IV formulations of TCZ and ABT may have been included in the aggregated bDMARDs data for both the SI and non-SI groups (Tables\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e and \u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePatients\u0026rsquo; characteristics\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ebDMARDs group (n\u0026thinsp;=\u0026thinsp;79)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSI group (n\u0026thinsp;=\u0026thinsp;65)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003enon-SI group (n\u0026thinsp;=\u0026thinsp;14)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e51 (64.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e42 (64.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e9 (64.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eAge (Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD, year)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e60.2\u0026thinsp;\u0026plusmn;\u0026thinsp;12.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e59.3\u0026thinsp;\u0026plusmn;\u0026thinsp;11.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e67.0\u0026thinsp;\u0026plusmn;\u0026thinsp;13.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eDisease duration of RA (Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD, year)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13.1\u0026thinsp;\u0026plusmn;\u0026thinsp;9.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13.2\u0026thinsp;\u0026plusmn;\u0026thinsp;10.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e11.3\u0026thinsp;\u0026plusmn;\u0026thinsp;8.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"4\" rowspan=\"5\"\u003e \u003cp\u003eComorbidities\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHypertension\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14 (17.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12 (18.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2 (14.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDyslipidemia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11 (13.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8 (12.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3 (21.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDiabetes mellitus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (7.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 (7.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1 (7.1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDepression\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (5.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 (4.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1 (7.1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRespiratory disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (5.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 (4.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1 (7.1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eJ-HAQ (Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.62\u0026thinsp;\u0026plusmn;\u0026thinsp;0.72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.61\u0026thinsp;\u0026plusmn;\u0026thinsp;0.71\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.63\u0026thinsp;\u0026plusmn;\u0026thinsp;0.75\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eEmployment status\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePermanent employment\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22 (27.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e21 (32.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1 (7.1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTemporary employment\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16 (20.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13 (20.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3 (21.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUnemployed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e41 (51.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e31 (47.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e10 (71.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003eWPAI\u003c/p\u003e \u003cp\u003e(Median [IQR], %)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAbsenteeism\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0‒0) (n\u0026thinsp;=\u0026thinsp;38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0‒0) (n\u0026thinsp;=\u0026thinsp;34)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0 (0‒0) (n\u0026thinsp;=\u0026thinsp;4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePresenteeism\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15 (0‒37.5) (n\u0026thinsp;=\u0026thinsp;32)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10 (0\u0026ndash;40) (n\u0026thinsp;=\u0026thinsp;29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e20 (0\u0026ndash;30) (n\u0026thinsp;=\u0026thinsp;3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOverall work impairment\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0‒0) (n\u0026thinsp;=\u0026thinsp;32)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0‒0) (n\u0026thinsp;=\u0026thinsp;29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0 (0‒0) (n\u0026thinsp;=\u0026thinsp;3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDaily activity impairment\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20 (0‒40) (n\u0026thinsp;=\u0026thinsp;79)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e20 (10‒45) (n\u0026thinsp;=\u0026thinsp;65)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e20 (0‒32.5) (n\u0026thinsp;=\u0026thinsp;14)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eAnnual income\u003c/p\u003e \u003cp\u003e(Median [IQR], USD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIndividual\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12068.97\u003c/p\u003e \u003cp\u003e(5172.41‒24137.93)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12068.97\u003c/p\u003e \u003cp\u003e(5172.41‒24137.93)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e12068.97\u003c/p\u003e \u003cp\u003e(5172.41‒24034.48)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHousehold\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e31034.48\u003c/p\u003e \u003cp\u003e(18965.52‒51724.14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e31034.48\u003c/p\u003e \u003cp\u003e(18965.52‒51724.14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e27586.21\u003c/p\u003e \u003cp\u003e(15103.45‒44827.59)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eCoinsurance (Median [IQR], %)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30 (20‒30)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e30 (20‒30)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e20 (15‒30)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"6\" rowspan=\"7\"\u003e \u003cp\u003ebDMARDs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eETN (including biosimilar)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e29 (36.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e26 (40.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3 (21.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTCZ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22 (27.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e16 (24.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6 (42.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eADA (including biosimilar)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12 (15.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10 (15.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2 (14.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eABT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12 (15.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8 (12.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4 (28.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGOL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 (12.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6 (9.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4 (28.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSAR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (8.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (6.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3 (21.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCZP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (6.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (6.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1 (7.1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003eMedical department\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRheumatology\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e40 (50.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e36 (55.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4 (28.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOrthopedic surgery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27 (34.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e18 (27.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e9 (64.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eInternal medicine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13 (16.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11 (16.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2 (14.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCollagen diseases\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11 (13.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9 (13.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2 (14.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003ebDMARDs, biological disease-modifying antirheumatic drugs; SI, self-injection; SD, standard deviation; IQR, interquartile range; RA, rheumatoid arthritis; J-HAQ, Japanese Health Assessment Questionnaire; WPAI, work productivity and activity impairment; ETN, etanercept; TCZ, tocilizumab; ADA, adalimumab; ABT, abatacept; GOL, golimumab; SAR, sarilumab; CZP, certolizumab pegol.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e\u003cp\u003eNote: Intravenous (IV) formulations of tocilizumab and abatacept may be included in the aggregated bDMARDs data.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eTable 2. Usage proportion of bDMARDs in each medical department\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"970\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 217px;\"\u003e\n \u003cp\u003eMedical department\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 166px;\"\u003e\n \u003cp\u003eETN\u003c/p\u003e\n \u003cp\u003e(including biosimilar)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003eTCZ\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 166px;\"\u003e\n \u003cp\u003eADA\u003c/p\u003e\n \u003cp\u003e(including biosimilar)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003eABT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003eGOL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003eSAR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003eCZP\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 217px;\"\u003e\n \u003cp\u003eRheumatology (n = 40)\u003c/p\u003e\n \u003cp\u003eOrthopedic surgery (n = 27)\u003c/p\u003e\n \u003cp\u003eInternal medicine (n = 14)\u003c/p\u003e\n \u003cp\u003eCollagen diseases (n = 11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 166px;\"\u003e\n \u003cp\u003e14 (35%)\u003c/p\u003e\n \u003cp\u003e12 (44.4%)\u003c/p\u003e\n \u003cp\u003e7 (50.0%)\u003c/p\u003e\n \u003cp\u003e4 (36.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e9 (22.5%)\u003c/p\u003e\n \u003cp\u003e9 (33.3%)\u003c/p\u003e\n \u003cp\u003e5 (35.7%)\u003c/p\u003e\n \u003cp\u003e3 (27.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 166px;\"\u003e\n \u003cp\u003e7 (17.5%)\u003c/p\u003e\n \u003cp\u003e5 (18.5%)\u003c/p\u003e\n \u003cp\u003e3 (21.4%)\u003c/p\u003e\n \u003cp\u003e4 (36.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e7 (17.5%)\u003c/p\u003e\n \u003cp\u003e3 (11.1%)\u003c/p\u003e\n \u003cp\u003e1 (7.1%)\u003c/p\u003e\n \u003cp\u003e3 (27.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e5 (12.5%)\u003c/p\u003e\n \u003cp\u003e4 (14.8%)\u003c/p\u003e\n \u003cp\u003e2 (14.3%)\u003c/p\u003e\n \u003cp\u003e2 (18.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e4 (10.0%)\u003c/p\u003e\n \u003cp\u003e2 (7.4%)\u003c/p\u003e\n \u003cp\u003e2 (14.3%)\u003c/p\u003e\n \u003cp\u003e3 (27.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e3 (7.5%)\u003c/p\u003e\n \u003cp\u003e1 (3.7%)\u003c/p\u003e\n \u003cp\u003e2 (14.3%)\u003c/p\u003e\n \u003cp\u003e1 (9.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003ePatients who visited multiple medical departments were counted in each department they visited.\u003c/p\u003e\n\u003cp\u003ebDMARDs, biological disease-modifying antirheumatic drugs; ETN, etanercept; TCZ, tocilizumab; ADA, adalimumab; ABT, abatacept; GOL, golimumab; SAR, sarilumab; CZP, certolizumab pegol.\u003c/p\u003e\n\u003cp\u003eNote: Intravenous (IV) formulations of tocilizumab and abatacept may be included in the aggregated bDMARDs data.\u003c/p\u003e\n\u003ch3\u003eSurvey variables\u003c/h3\u003e\n\u003cp\u003ePatient characteristics at the time of survey implementation, including sex, age, duration of RA, comorbidities, Japanese Health Assessment Questionnaire [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e], employment status, annual income, coinsurance, work productivity and activity impairment (WPAI) questionnaire, class of bDMARDs used, medical departments visited (rheumatology, orthopedic surgery, internal medicine, and collagen diseases), and the percentage of those who used bDMARDs in each department were collected. Comorbidities were defined as conditions for which hospitalization or outpatient visits occurred within the past year, excluding RA. The WPAI-RA questionnaire comprises six questions as follows [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. (Q1) Are you currently employed (working for pay)? (Q2) During the past 7 days, how many hours did you miss from work because of problems associated with RA? (Q3) During the past 7 days, how many hours did you miss from work because of any other reason, such as annual leave, holidays, time off to participate in this study? (Q4) During the past 7 days, how many hours did you actually work? (Q5) During the past 7 days, how much did your health problems affect your productivity while you were working? and (Q6) During the past 7 days, how much did your health problems affect your ability to do your regular daily activities other than work at a job? The answers for Q2, Q3, and Q4 are indicated by time (hours), and those for Q5 and Q6 are indicated by scores (0\u0026ndash;10). A score of 0 means that health problems had no effect on the patient\u0026rsquo;s work/daily activities, and a score of 10 means that health problems completely prevented the patient from work/daily activities. We calculated productivity loss as follows: absenteeism (%)\u0026thinsp;=\u0026thinsp;Q2/(Q2\u0026thinsp;+\u0026thinsp;Q4); presenteeism (%)\u0026thinsp;=\u0026thinsp;Q5/10\u0026times;100; overall work impairment (%)\u0026thinsp;=\u0026thinsp;Q2/(Q2\u0026thinsp;+\u0026thinsp;Q4) + (1\u0026thinsp;\u0026minus;\u0026thinsp;Q2/(Q2\u0026thinsp;+\u0026thinsp;Q4))\u0026times;(Q5/10)\u0026times;100; daily activity impairment (%)\u0026thinsp;=\u0026thinsp;Q6/10\u0026times;100. Higher percentages indicate that there was greater work and daily activity impairment and lower productivity.\u003c/p\u003e \u003cp\u003eWe collected data on travel time to the hospital, time off for hospital visits, chaperones for hospital visits, out-of-pocket medical expenses per visit, travel costs, and the frequency of hospital visits. We calculated the total annual out-of-pocket medical expenses and limited societal perspective medical expenses. The total annual out-of-pocket medical expenses were calculated using the following formula (1 USD\u0026thinsp;=\u0026thinsp;145 JPY in 2024):\u003c/p\u003e \u003cp\u003e[The median out-of-pocket expenses per visit (direct healthcare costs)\u0026thinsp;+\u0026thinsp;the median traveling costs per visit (direct non-healthcare costs)] \u0026times; median frequency of hospital visits (number of visits).\u003c/p\u003e \u003cp\u003eThe limited annual societal perspective medical expenses were calculated based on the following steps (1 USD\u0026thinsp;=\u0026thinsp;145 JPY in 2024):\u003c/p\u003e \u003cp\u003e(1) For patients whose out-of-pocket payment amounts and co-payments (e.g., 10%, 20%, 30%) were available, we calculated medical expenses per visit from the public healthcare payer\u0026rsquo;s perspective using the following formula:\u003c/p\u003e \u003cp\u003eThe medical expenses per visit from the public health care payer\u0026rsquo;s perspective\u0026thinsp;=\u0026thinsp;Out-of-pocket expenses\u0026thinsp;\u0026divide;\u0026thinsp;Co-payment\u003c/p\u003e \u003cp\u003eFor example, if a patient paid 155.17 USD per visit with a 30% co-payment, the total cost was estimated to be 517.23 USD.\u003c/p\u003e \u003cp\u003e(2) We then calculated the median values for medical expenses per visit, traveling costs, and annual frequency of hospital visits among these patients.\u003c/p\u003e \u003cp\u003e(3) Finally, we estimated the limited annual societal perspective medical expenses using the following formula:\u003c/p\u003e \u003cp\u003eLimited annual societal perspective medical expenses = [The medical expenses per visit from the public healthcare payer\u0026rsquo;s perspective (Direct healthcare costs)\u0026thinsp;\u003cb\u003e+\u003c/b\u003e\u0026thinsp;the median traveling costs per visit (Direct non-healthcare costs)] \u003cb\u003e\u0026times;\u003c/b\u003e median frequency of hospital visits (number of visits).\u003c/p\u003e \u003cp\u003eIn this study, \u0026ldquo;limited annual societal perspective medical expenses\u0026rdquo; were estimated by combining direct medical expenses (e.g., drug costs and consultation fees) with direct non-medical expenses, specifically traveling expenses related to hospital visits. This definition is based on internationally accepted frameworks for health economic evaluation, in which adopting a societal or quasi-societal perspective is recommended to include both direct medical and direct non-medical expenses. Although this study does not incorporate indirect costs such as productivity loss or informal care, we aimed to go beyond the payer\u0026rsquo;s perspective and partially capture the economic burden on patients. Given that SI can reduce the number of hospital visits, the inclusion of traveling costs was considered relevant for assessing the economic benefits of SI.\u003c/p\u003e \u003cp\u003eIn addition, we surveyed the level of satisfaction with SI (satisfaction, continuity, implementer, ease of use, reasons for not selecting SI, and the preferred method for future administration). Satisfaction with SI was determined based on five levels: \u0026ldquo;very satisfied,\u0026rdquo; \u0026ldquo;somewhat satisfied,\u0026rdquo; \u0026ldquo;neutral,\u0026rdquo; \u0026ldquo;somewhat dissatisfied,\u0026rdquo; and \u0026ldquo;very dissatisfied.\u0026rdquo; SI continuity was determined based on the following: \u0026ldquo;Patient would like to continue SI in the future,\u0026rdquo; \u0026ldquo;Patient would like to switch to other methods of administration,\u0026rdquo; and \u0026ldquo;Do not know.\u0026rdquo;\u003c/p\u003e \u003cp\u003eThe SI implementer was surveyed based on categories of \u0026ldquo;Yourself,\u0026rdquo; \u0026ldquo;Your family,\u0026rdquo; \u0026ldquo;Home health nurse,\u0026rdquo; and \u0026ldquo;Other person.\u0026rdquo;\u003c/p\u003e \u003cp\u003eThe ease of SI was determined based on five levels: \u0026ldquo;very easy,\u0026rdquo; \u0026ldquo;somewhat easy,\u0026rdquo; \u0026ldquo;neutral,\u0026rdquo; \u0026ldquo;somewhat difficult,\u0026rdquo; and \u0026ldquo;very difficult.\u0026rdquo;\u003c/p\u003e \u003cp\u003eReasons for not selecting SI were determined based on the following survey replies: \u0026ldquo;patient was unaware of SI\u0026rdquo;; \u0026ldquo;patient knew about SI but did not receive information from their doctor\u0026rdquo;; \u0026ldquo;patient has used SI in the past, but has now stopped doing so\u0026rdquo;; \u0026ldquo;patient has difficulty in SI due to deformed joints\u0026rdquo;; \u0026ldquo;patient does not have a good impression of SI\u0026rdquo;; and \u0026ldquo;other reasons.\u0026rdquo; Patients who selected multiple reasons were included.\u003c/p\u003e\n\u003ch3\u003eOutcomes\u003c/h3\u003e\n\u003cp\u003eThe primary outcome was the total annual out-of-pocket medical expenses of patients with RA who selected the SI of bDMARDs and those who did not. As a secondary outcome, we compared the limited annual societal perspective medical expenses between patients with RA who selected the SI of bDMARDs and those who did not.\u003c/p\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eFor the endpoints, the response data are summarized separately for the bDMARDs, SI, and non-SI groups. Summary statistics were calculated for continuous variables, and ratios were calculated for categorical variables. All analyses were performed using R software version 3.2.2.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003ePatients\u0026rsquo; characteristics\u003c/h2\u003e \u003cp\u003eThis study included 326 patients previously diagnosed with RA by a medical doctor. Among them, 303 (92.9%) and 79 (24.2%) patients were assigned to the DMARDs and bDMARDs groups, respectively (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). In the bDMARDs group, 65 patients (82.3%) selected SI (SI group), whereas 14 (17.7%) did not (non-SI group). No patient was undergoing monotherapy with bDMARDs.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003ePatient characteristics are presented in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The mean age of patients in the non-SI group was higher than that of patients in the SI group (67.0\u0026thinsp;\u0026plusmn;\u0026thinsp;13.5 years vs. 59.3\u0026thinsp;\u0026plusmn;\u0026thinsp;11.5 years, respectively). Thirty-four patients (52.3%) in the SI group had permanent or temporary employment, which was higher than that in the non-SI group (n\u0026thinsp;=\u0026thinsp;4; 28.5%).\u003c/p\u003e \u003cp\u003eIn the SI group, the median (IQR) scores were as follows: absenteeism, 0% (0\u0026ndash;0); presenteeism, 10% (0\u0026ndash;40); overall work impairment, 0% (0\u0026ndash;0); and daily activity impairment, 20% (10\u0026ndash;45).\u003c/p\u003e \u003cp\u003eConversely, median (IQR) scores for the non-SI group were as follows: absenteeism, 0% (0\u0026ndash;0); presenteeism, 20% (0\u0026ndash;30); overall work impairment, 0% (0\u0026ndash;0); and daily activity impairment, 20% (0\u0026ndash;32.5).\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eUtilization of bDMARDs\u003c/h3\u003e\n\u003cp\u003eThe most frequently used bDMARDs were ETN in the SI group (n\u0026thinsp;=\u0026thinsp;26; 40.0%) and TCZ in the non-SI group (n\u0026thinsp;=\u0026thinsp;6; 42.9%) (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe medical departments with the highest proportion of hospital visits were rheumatology in the SI group (n\u0026thinsp;=\u0026thinsp;36; 55.4%) and orthopedics in the non-SI group (n\u0026thinsp;=\u0026thinsp;9; 64.3%) (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eETN, TCZ, and ADA were frequently used in all medical departments (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eTotal annual out-of-pocket and limited annual societal perspective medical expenses\u003c/h2\u003e \u003cp\u003eThe SI group had higher median out-of-pocket medical expenses per visit than the non-SI group (155.17 USD/visit vs. 86.21 USD/visit, respectively) (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). However, the SI group had lower total annual out-of-pocket medical expenses than the non-SI group (948.42 USD/year vs. USD 1,071.72 USD/year, respectively) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eOut-of-pocket and public health care payer\u0026rsquo;s perspective medical expenses\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePerspective of the analysis\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eItems\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ebDMARDs group\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;79)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSI group\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;65)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003enon-SI group\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;14)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTravel time to the hospital\u003c/p\u003e \u003cp\u003e(Median [IQR], min)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15\u003c/p\u003e \u003cp\u003e(15‒45)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15\u003c/p\u003e \u003cp\u003e(15‒45)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e15\u003c/p\u003e \u003cp\u003e(15‒45)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTime off for hospital visits\u003c/p\u003e \u003cp\u003e(Median [IQR], h/visit)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e(0‒6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e(0‒6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e(0‒0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eChaperone for hospital visits\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11\u003c/p\u003e \u003cp\u003e(13.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11\u003c/p\u003e \u003cp\u003e(16.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e(0.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eOut-of-pocket\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMedical expenses (Median [IQR], USD/visit)\u003c/p\u003e \u003cp\u003e(Direct health care costs)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e155.17\u003c/p\u003e \u003cp\u003e(86.21‒241.38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e155.17\u003c/p\u003e \u003cp\u003e(103.45‒241.38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e86.21\u003c/p\u003e \u003cp\u003e(17.24‒18,750)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTraveling costs (Median [IQR], USD/visit)\u003c/p\u003e \u003cp\u003e(Direct non-health care costs)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.03\u003c/p\u003e \u003cp\u003e(0‒6.48)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.90\u003c/p\u003e \u003cp\u003e(0-6.62)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.10\u003c/p\u003e \u003cp\u003e(1.93\u0026ndash;4.83)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFrequency of hospital visits\u003c/p\u003e \u003cp\u003e(Median [IQR], visit/year)\u003c/p\u003e \u003cp\u003e(Number of visits)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6\u003c/p\u003e \u003cp\u003e(4‒12)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6\u003c/p\u003e \u003cp\u003e(4‒12)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e12\u003c/p\u003e \u003cp\u003e(10.5‒12)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003ePublic health care payer\u0026rsquo;s perspective\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMedical expenses (Median [IQR], USD/visit)\u003c/p\u003e \u003cp\u003e(Direct health care costs)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e632.18\u003c/p\u003e \u003cp\u003e(459.77‒1034.48)\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;69)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e775.86\u003c/p\u003e \u003cp\u003e(517.24‒1077.59)\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;58)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e287.36\u003c/p\u003e \u003cp\u003e(258.62‒603.45)\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;11)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTraveling costs (Median [IQR], USD/visit)\u003c/p\u003e \u003cp\u003e(Direct non-health care costs)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.90\u003c/p\u003e \u003cp\u003e(0.38‒6.30)\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;69)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.83\u003c/p\u003e \u003cp\u003e(0.00‒6.20)\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;58)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.45\u003c/p\u003e \u003cp\u003e(2.76‒6.90)\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;11)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFrequency of hospital visits\u003c/p\u003e \u003cp\u003e(Median [IQR], visit/year)\u003c/p\u003e \u003cp\u003e(Number of visits)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6\u003c/p\u003e \u003cp\u003e(4‒12)\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;69)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6\u003c/p\u003e \u003cp\u003e(4‒12)\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;58)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e12\u003c/p\u003e \u003cp\u003e(6‒12)\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;11)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003ebDMARDs, biological disease-modifying antirheumatic drugs; SI, self-injection; IQR, interquartile range.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe median public healthcare payer\u0026rsquo;s perspective medical expenses per visit were higher in the SI group (775.86 USD/visit) than those in the non-SI group (287.36 USD/visit) (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). The SI group had higher limited annual societal perspective medical expenses than the non-SI group (4,672.14 USD/year vs. 3,489.72 USD/year, respectively) (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eRegarding the total annual out-of-pocket medical expenses and limited annual societal perspective medical expenses, the medical costs of the SI and non-SI groups were reversed.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eFact-finding surveys of SI\u003c/h2\u003e \u003cp\u003eConsidering satisfaction with SI, a total of 50 patients (76.9%) in the SI group responded \u0026ldquo;somewhat satisfied\u0026rdquo; or \u0026ldquo;very satisfied.\u0026rdquo; Fifty-two patients (80.0%) responded that they would like to continue SI in the future. Sixty-four patients (98.5%) self-administered the injections.\u003c/p\u003e \u003cp\u003eRegarding the ease of use of SI, 56 patients (86.1%) responded that it was \u0026ldquo;very easy\u0026rdquo; or \u0026ldquo;somewhat easy\u0026rdquo; (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eSatisfaction, continuity, implementer, and ease of use of self-injection in the SI group\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSurvey items\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSI group (n\u0026thinsp;=\u0026thinsp;65)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLevel of satisfaction with SI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eVery satisfied\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e15 (23.1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSomewhat satisfied\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e35 (53.8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNeutral\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e10 (15.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSomewhat dissatisfied\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5 (7.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eVery dissatisfied\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eContinuity of SI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePatient would like to continue SI in the future\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e52 (80.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePatient would like to switch to another method of administration\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4 (6.2%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDo not know\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e9 (13.8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSI implementer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYourself\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e64 (98.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOther person\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1 (1.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEase of SI use\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eVery easy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e29 (44.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSomewhat easy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e27 (41.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNeutral\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e8 (12.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSomewhat difficult\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1 (1.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eVery difficult\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"3\"\u003eSI, self-injection.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eIn the non-SI group, 10 patients (71.4%) had a negative impression of SI. Among these, six patients (42.9%) did not select SI owing to \u0026ldquo;not having a good impression of SI\u0026rdquo;; of the remaining four (28.6%), one patient each selected \u0026ldquo;patients was unable to administer the injection by himself/herself due to a lack of strength, and patient was afraid to inject himself/herself,\u0026rdquo; \u0026ldquo;patient worried about forgetting to inject,\u0026rdquo; \u0026ldquo;patient disliked SI by himself/herself\u0026rdquo; and \u0026ldquo;patient was feeling anxious about SI\u0026rdquo;. In addition, one patient each selected \u0026ldquo;patient did not select SI according to the doctor\u0026rsquo;s instruction\u0026rdquo; and \u0026ldquo;patient did not need to select SI\u0026rdquo;. Furthermore, one patient each selected \u0026ldquo;patient has used SI in the past but has now stopped from doing so\u0026rdquo; and \u0026ldquo;patient has difficulty with SI due to deformed joints\u0026rdquo;. Three patients (21.4%) knew about SI but had not received information from their doctors (Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e). Thirteen patients (92.9%) preferred to continue with their current method of administration and did not want to switch to SI.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eReasons for not selecting self-injection in the non-SI group\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eReasons for not selecting SI\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNon-SI group (n\u0026thinsp;=\u0026thinsp;14)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003ePatient does not have a good impression of SI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (42.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eOther reasons\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (42.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePatient was unable to administer the injection by himself/herself due to a lack of strength, and the patient was afraid to administer the injection himself/herself\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (7.1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePatient worried about forgetting to inject\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (7.1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePatient disliked SI by himself/herself\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (7.1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePatient was feeling anxious about SI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (7.1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePatient did not select SI according to the doctor\u0026rsquo;s instruction\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (7.1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePatient did not need to select SI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (7.1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003ePatient knew about SI but did not receive information from their doctor\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (21.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003ePatient has used SI in the past but has now stopped from doing so\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (7.1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003ePatient has difficulty with SI due to deformed joints\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (7.1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"3\"\u003eSI, self-injection.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this study, we found that over 80% of patients with RA using bDMARDs selected SI. Although the SI group had higher out-of-pocket medical expenses per visit than the non-SI group, total annual out-of-pocket medical expenses decreased. While SI reduces the frequency of hospital visits, patients may be prescribed bDMARDs for several months in a single visit in anticipation of potential natural disasters or limited access to healthcare services. Healthcare providers must work with the government to devise easy-to-understand measures to inform residents of the relevance of stockpiling regular medications for disasters and conduct educational activities for chronic diseases [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Accordingly, the medication cost per visit may increase, contributing to higher direct medical costs and, consequently, greater overall societal costs. However, Japan's high-cost medical expense benefit system sets an upper limit on out-of-pocket payments based on individual income levels. This system may have contributed to keeping out-of-pocket payments relatively low in the SI group despite higher medical costs, potentially explaining the observed discrepancy. Based on these results, the medical expense evaluation of SI for patients with RA using biologics may vary depending on the analytical perspective. This study was limited to results based on a web-based patient survey and did not provide an appropriate health economic evaluation from the perspective of public healthcare payers. Therefore, future studies should consider large claims data to evaluate medical expenses associated with SI more accurately from the public healthcare payer\u0026rsquo;s perspective.\u003c/p\u003e \u003cp\u003eThe difference in the number of hospital visits between the SI and non-SI groups may be explained by differences in employment status according to age. In this study, the mean age of participants in the non-SI group was higher than that of participants in the SI group. Older outpatients reportedly prefer bDMARDs administration by medical staff at medical facilities, whereas younger patients prefer SI [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. This may be because a lower proportion of older patients was employed, making it easier for them to secure time for hospital visits. In this study, the proportion of patients with permanent or temporary employment was lower in the non-SI group than in the SI group. Therefore, the non-SI group had more frequent total annual hospital visits than the SI group.\u003c/p\u003e \u003cp\u003eInformal care is unpaid care provided by families or non-family volunteers to fulfill patients\u0026rsquo; needs to accomplish activities of daily living (ADLs), such as bathing, dressing, and eating, or instrumental ADLs, such as shopping, cooking, and money management [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. From a societal perspective, it is important to consider health economics, including informal care costs. A study conducted in the United Kingdom reported that caregivers of patients with moderate RA required time off work and reduced working hours to provide care [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. In the present study, 11 patients (16.9%) in the SI group required chaperones for hospital visits (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). We observed that SI reduced the frequency of hospital visits, which may have reduced the frequency of chaperone hospital visits. Additionally, the median travel time to the hospital per visit was only 15 min for the SI and non-SI groups. However, SI reduced economic losses by decreasing the frequency of hospital visits, resulting in reduced travel time. To evaluate the health and economic benefits of SI from a societal perspective, it is crucial to consider the economic losses incurred by caregivers and patient travel times to hospitals.\u003c/p\u003e \u003cp\u003eThe results of our study indicate that patients were satisfied with their current method of administration, which is consistent with the findings of a previous study [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Conversely, patients or their caregivers may experience anxiety or fear regarding SI [\u003cspan additionalcitationids=\"CR19 CR20\" citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Negative past experiences with SI can affect future SI experiences [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. In our study, more than 70% of patients who did not select SI had a negative impression of it, and we observed a similar trend to that of Smith et al. This study showed that over 20% of patients who had not selected SI did not receive information from their doctors or were unaware of SI. These results indicate that providing appropriate information may encourage more patients to switch to SI.\u003c/p\u003e \u003cp\u003eHerein, we detected differences in the distribution of medical departments between the SI and non-SI groups. Specifically, most patients in the SI group visited rheumatology departments (36 patients; 55.4%), whereas those in the non-SI group tended to visit orthopedic departments more frequently (9 patients; 64.3%). These differences may have influenced both the decision to use SI and the subsequent economic outcomes. Rheumatologists are generally well-experienced in bDMARDs therapy and are more likely to provide active guidance and information regarding SI. Conversely, orthopedic departments, even when rheumatology specialists are involved, typically focus on structural and procedural treatments of joints, and may provide less information or support related to self-injection. Such differences across medical departments may affect patients\u0026rsquo; choices regarding the method of bDMARDs administration, ultimately leading to variations in visit frequency and healthcare costs.\u003c/p\u003e \u003cp\u003eHowever, this study has some limitations that must be addressed. First, we used data from a web-based, self-reported survey, and the possibility of RA misclassification cannot be disregarded. Second, this study was limited to patients who could participate in a web-based survey and had relatively high information technology literacy and interest in their disease. Third, we could not assess clinical data on disease and physical activity. Fourth, because this study was based on only one survey, causal relationships could not be investigated. Fifth, this study was conducted without distinguishing between SI and intravenous formulations; therefore, for patients who selected TCZ and ABT as bDMARDs, the use of SI and intravenous formulations may have been included. Sixth, the term \u0026ldquo;negative impression\u0026rdquo; reflects a psychological reluctance or fear of SI; however, it remains unclear whether these impressions are associated with prior adverse experiences. Additionally, owing to the structure of the questionnaire, data on the types of bDMARDs previously used and whether they were administered via SI or non-SI methods were not collected. This limitation may have affected the interpretation of the patient\u0026rsquo;s attitudes toward SI. Finally, this study has the potential for recall bias owing to its reliance on self-reported data. Information such as the frequency of hospital visits over the past 12 months was collected using a web-based questionnaire, which may have led to variability in the accuracy of responses. However, the questionnaire employed a multiple-choice format rather than open-ended responses to minimize the respondent burden and reduce the impact of recall bias. Furthermore, patients with RA experiencing stable disease activity tend to attend regular follow-up visits once a month or every two months, which may lead to accurate recall.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eOver 80% of patients with RA using bDMARDs selected SI, which lowered their total annual out-of-pocket medical expenses by reducing the frequency of hospital visits. The results of our study may provide useful insights into the selection of self-injectable bDMARDs for therapeutic decision-making based on out-of-pocket medical expenses.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eABT\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eabatacept\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eADA\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eadalimumab\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eADA-BS\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eadalimumab biosimilar\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eADLs\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eactivities of daily living\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003ebDMARDs\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ebiological disease-modifying antirheumatic drugs\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eCZP\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ecertolizumab pegol\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eDMARDs\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003edisease-modifying antirheumatic drugs\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eDMPA\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003edepot medroxyprogesterone acetate\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eETN\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eetanercept\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eETN-BS\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eetanercept biosimilar\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eGOL\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003egolimumab\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eIFX\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003einfliximab\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eIFX-BS\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003einfliximab biosimilar\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eIQR\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003einterquartile range\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eIV\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eintravenous\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eJ-HAQ\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eJapanese Health Assessment Questionnaire\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eRA\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003erheumatoid arthritis\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eSAR\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003esarilumab\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eSC\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003esubcutaneous\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eSI\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eself-injection\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eTCZ\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003etocilizumab\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eWPAI\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ework productivity and activity impairment.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the Meiji Pharmaceutical University Research Ethics Committee in April\u0026nbsp;2022 (Approval No. 202144). The study complied with principles\u0026nbsp;for ethical research in the Declaration of Helsinki, and informed consent was obtained from all the participants\u0026nbsp;using a web form at the beginning of the survey.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eK.T. is an employee of Kyowa Kirin Co., Ltd., and has received tuition support for part of his doctoral degree program from his company.\u003c/p\u003e\n\u003cp\u003eE.T. has received lecture fees or consulting fees from AbbVie Japan GK, Asahi Kasei Corp., Astellas Pharma Inc., Ayumi Pharmaceutical Co., Boehringer Ingelheim Japan, Inc., Bristol Myers Squibb Co., Ltd., Chugai Pharmaceutical Co., Ltd., Daiichi-Sankyo, Inc., Eisai Co., Ltd., Eli Lilly Japan K.K., Gilead Sciences, Inc., GlaxoSmithKline K.K., Kyowa Pharma Chemical CO., Ltd., Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Co., Mochida Pharmaceutical CO., Ltd., Nippon Kayaku Co., Ltd., Pfizer Japan Inc., Takeda Pharmaceutical Co., Ltd., Teijin Pharma Ltd, and Viatris Japan.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eE.T. has received research funding from Pfizer Inc., UCB Japan Co., Ltd., and Mitsubishi Tanabe Pharma Corporation.\u003c/p\u003e\n\u003cp\u003eR.S. has received consulting fees from Nippon Kayaku Co., Ltd.\u003c/p\u003e\n\u003cp\u003eM.A. received lectures and consulting fees from Astellas Pharma Inc., Mitsubishi Tanabe Pharma Co., GlaxoSmithKline K.K., and Janssen Pharmaceutical K.K.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eY.M. has no conflicts of interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePeer reviewers for this manuscript have no relevant financial or other relationships to disclose.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors received no funding for this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eK.T., E.T., R.S. and M.A. conceived the study. All authors contributed to study design and interpretation. Data analysis was performed by K.T. and Y.M. The first draft of the manuscript was written by K.T., and all authors commented on previous versions of the manuscript. All the authors have read and approved the final version of this manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe thank Medilead Inc. for conducting the online survey and\u0026nbsp;Editage\u0026nbsp;for the English language editing.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; information\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDepartment of Public Health and Epidemiology, Meiji Pharmaceutical University, 2-522-1 Noshio,\u0026nbsp;Kiyose-shi, Tokyo, 204-8588, Japan\u003c/p\u003e\n\u003cp\u003eKazuhiko Takahata, Yui Maeda, Ryoko Sakai and Manabu Akazawa\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Department of Rheumatology, Tokyo Women\u0026rsquo;s Medical University School of Medicine, 8-1, Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan\u003c/p\u003e\n\u003cp\u003eEiichi Tanaka and Ryoko Sakai\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eYamanaka H, Tanaka E, Nakajima A, Furuya T, Ikari K, Taniguchi A, et al. A large observational cohort study of rheumatoid arthritis, IORRA: Providing context for today's treatment options. Mod Rheumatol. 2020;30:1\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHresko A, Lin TC, Solomon DH. Medical care costs associated with rheumatoid arthritis in the US: A systematic literature review and meta-analysis. Arthritis Care Res (Hoboken). 2018;70:1431\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBergqvist V, Holmgren J, Klintman D, Marsal J. Real-world data on switching from intravenous to subcutaneous vedolizumab treatment in patients with inflammatory bowel disease. Aliment Pharmacol Ther. 2022;55:1389\u0026ndash;401.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDi Giorgio L, Mvundura M, Tumusiime J, Morozoff C, Cover J, Drake JK. Is contraceptive self-injection cost-effective compared to contraceptive injections from facility-based health workers? Evidence from Uganda. Contraception. 2018;98:396\u0026ndash;404.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTanaka E, Inoue E, Yamaguchi R, Shimizu Y, Kobayashi A, Sugimoto N, et al. Pharmacoeconomic analysis of biological disease modifying antirheumatic drugs in patients with rheumatoid arthritis based on real-world data from the IORRA observational cohort study in Japan. Mod Rheumatol. 2017;27:227\u0026ndash;36.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBrown S, Everett CC, Naraghi K, Davies C, Dawkins B, Hulme C, et al. Alternative tumour necrosis factor inhibitors (TNFi) or abatacept or rituximab following failure of initial TNFi in rheumatoid arthritis: The SWITCH RCT. Health Technol Assess. 2018;22:1\u0026ndash;280.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVanier A, Mariette X, Tubach F, Fautrel B, STRASS Study Group. Cost-effectiveness of TNF-blocker injection spacing for patients with established rheumatoid arthritis in remission: An economic evaluation from the spacing of TNF-blocker injections in rheumatoid arthritis trial. Value Health. 2017;20:577\u0026ndash;85.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMedilead. Inc. Research Panel MHP (Medilead Healthcare Panel). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.medi-l.com/\u003c/span\u003e\u003cspan address=\"https://www.medi-l.com/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. Accessed 13 Feb 2025.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYamaguchi H, Iwasaki K, Shoji A, Kokubo K, Igarashi A. Health-related quality of life (QoL) in Japanese patients with cancer: a large-scale questionnaire survey using EQ-5D-5L. Ther Res. 2022;41:949\u0026ndash;55.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMasaki H, Ishizaki S, Uenishi T, Kokubo K, Igarashi A. A survey of the impact of COVID-19 on the visiting frequency of Japanese Patients with gastrointestinal diseases. Jpn Pharmacol Ther. 2021;49:17\u0026ndash;39.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMatsuda Y, Singh G, Yamanaka H, Tanaka E, Urano W, Taniguchi A, et al. Validation of a Japanese version of the Stanford Health Assessment Questionnaire in 3,763 patients with rheumatoid arthritis. Arthritis Rheum. 2003;49:784\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eReilly MC, Zbrozek AS, Dukes EM. The validity and reproducibility of a work productivity and activity impairment instrument. PharmacoEconomics. 1993;4:353\u0026ndash;65.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAkira Mitoya RK, Taniguchi R, et al. Current status and influencing factors of the stockpiling of regular medicines for disasters in patients with chronic disease. Jpn J Soc Pharm. 2024;43:2\u0026ndash;11.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChilton F, Collett RA. Treatment choices, preferences and decision-making by patients with rheumatoid arthritis. Musculoskelet Care. 2008;6:1\u0026ndash;14.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJoo H, Zhang P, Wang G. Cost of informal care for patients with cardiovascular disease or diabetes: Current evidence and research challenges. Qual Life Res. 2017;26:1379\u0026ndash;86.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGalloway J, Edwards J, Bhagat S, Parker B, Tan AL, Maxwell J, et al. Direct healthcare resource utilisation, health-related quality of life, and work productivity in patients with moderate rheumatoid arthritis: An observational study. BMC Musculoskelet Disord. 2021;22:277.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKishimoto M, Yamairi F, Sato N, Kobayashi J, Yamauchi S, Iwasaki T. Patient preference for treatment mode of biologics in rheumatoid arthritis: A 2020 web-based survey in Japan. Rheumatol Ther. 2021;8:1095\u0026ndash;111.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003evan den Bemt BJF, Gettings L, Domańska B, Bruggraber R, Mountian I, Kristensen LE. A portfolio of biologic self-injection devices in rheumatology: How patient involvement in device design can improve treatment experience. Drug Deliv. 2019;26:384\u0026ndash;92.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKeininger D, Coteur G. Assessment of self-injection experience in patients with rheumatoid arthritis: Psychometric validation of the Self-Injection Assessment Questionnaire (SIAQ). Health Qual Life Outcomes. 2011;9:2.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWei Y, Zhao J, Ming J, Zhang X, Chen Y. Patient preference for self-injection devices in rheumatoid arthritis: A discrete choice experiment in China. Patient Prefer Adherence. 2022;16:2387\u0026ndash;98.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRekaya N, Vicik SM, Hulesch BT, McDonald LL. Enhancement of an auto-injector device for self-administration of etanercept in patients with rheumatoid arthritis confers emotional and functional benefits. Rheumatol Ther. 2020;7:537\u0026ndash;52.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-health-services-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bhsr","sideBox":"Learn more about [BMC Health Services Research](http://bmchealthservres.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/BHSR/default.aspx","title":"BMC Health Services Research","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"rheumatoid arthritis, self-injection, biological disease-modifying antirheumatic drugs, health economic evaluation, real-world web-based survey, out-of-pocket medical expenses","lastPublishedDoi":"10.21203/rs.3.rs-6034350/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6034350/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eBiological disease-modifying antirheumatic drugs (bDMARDs) have dramatically improved the quality of life of patients with rheumatoid arthritis (RA); however, concerns regarding their high cost persist. Self-injection (SI) may reduce medical expenses by decreasing the frequency of hospital visits. In this study, we compared the health economic costs of patients with RA who selected SI of bDMARDs and those who did not.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eIn this cross-sectional study, we analyzed data from January 2024 using a web-based self-report survey provided by Medilead, Inc. This study included patients with RA who were divided into the SI and non-SI groups. We calculated per visit and total annual out-of-pocket medical expenses for each group.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eAmong 326 patients with RA, 79 (24.2%; female: 64.6%; mean age: 60.2 years) were treated with bDMARDs. Of these, 65 patients (82.3%) selected SI, and 14 (17.7%) selected non-SI administration. The non-SI group had a higher median frequency of hospital visits than the SI group (12 vs. 6 visits per year). The median out-of-pocket medical expense per visit was higher in the SI group (155.17 USD/visit) than in the non-SI group (86.21 USD/visit). However, the SI group had lower total annual out-of-pocket medical expenses than the non-SI group (948.42 USD/year vs. 1,071.72 USD/year, respectively).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eOver 80% of patients with RA selected SI to administer bDMARDs, and their total annual out-of-pocket medical expenses were lower than those of patients who selected non-SI owing to the reduced frequency of hospital visits. The results of our study may provide useful insights into the selection of self-injectable bDMARDs for therapeutic decision-making based on out-of-pocket medical expenses.\u003c/p\u003e","manuscriptTitle":"Health economic evaluation of self-injection of biologics in patients with rheumatoid arthritis using a Japanese real-world web-based survey","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-04-17 07:35:55","doi":"10.21203/rs.3.rs-6034350/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-04-30T11:32:57+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-04-28T07:45:28+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-04-19T17:23:48+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"184506971685875422558424797755853087305","date":"2025-04-15T08:33:10+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"11359245315314535600724588452253581055","date":"2025-04-13T22:43:09+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-04-12T06:30:16+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-04-12T03:52:52+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Health Services Research","date":"2025-04-11T01:50:03+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-health-services-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bhsr","sideBox":"Learn more about [BMC Health Services Research](http://bmchealthservres.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/BHSR/default.aspx","title":"BMC Health Services Research","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"1c8da142-d15a-4662-a334-c7d87e22a44b","owner":[],"postedDate":"April 17th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-05-26T16:08:35+00:00","versionOfRecord":{"articleIdentity":"rs-6034350","link":"https://doi.org/10.1186/s12913-025-12908-1","journal":{"identity":"bmc-health-services-research","isVorOnly":false,"title":"BMC Health Services Research"},"publishedOn":"2025-05-21 15:57:23","publishedOnDateReadable":"May 21st, 2025"},"versionCreatedAt":"2025-04-17 07:35:55","video":"","vorDoi":"10.1186/s12913-025-12908-1","vorDoiUrl":"https://doi.org/10.1186/s12913-025-12908-1","workflowStages":[]},"version":"v1","identity":"rs-6034350","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6034350","identity":"rs-6034350","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}