Impact of the 2018 Japan Floods on methotrexate and anti-rheumatic drug prescriptions: A longitudinal analysis of the Japanese National Database

Impact of the 2018 Japan Floods on methotrexate and anti-rheumatic drug prescriptions: A longitudinal analysis of the Japanese National Database | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL This is a preprint and has not been peer reviewed. Data may be preliminary. 17 January 2025 V1 Latest version Share on Impact of the 2018 Japan Floods on methotrexate and anti-rheumatic drug prescriptions: A longitudinal analysis of the Japanese National Database Authors : Genki Kidoguchi 0009-0001-0558-8814 [email protected] , Shuhei Yoshida , Tomohiro Sugimoto , Shintaro Hirata 0000-0002-2474-9943 , and Masatoshi Matsumoto Authors Info & Affiliations https://doi.org/10.22541/au.173711171.12516474/v1 264 views 136 downloads Contents Abstract Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract Aim: Most rheumatic diseases are caused by a complex interplay of genetic, physical, and environmental factors. Large-scale disasters affect all of these factors; however, their impact on rheumatic diseases are unknown. We aimed to investigate changes in anti-rheumatic drug prescriptions among victims and non-victims following the 2018 Japan flood. Methods: In this retrospective cohort study, we used data from the Japanese National Database of Health Insurance Claims, which included information on all drugs prescribed by physicians. We included all cases of prescription at medical institutions in disaster-stricken areas between July 2017 and June 2019. The newly initiated prescription of methotrexate (MTX, 2 mg tablets or capsules), which has been exclusively approved for rheumatoid arthritis, juvenile idiopathic arthritis, or psoriatic arthritis/ psoriasis in Japan, as well as those for other anti-rheumatic drugs within the first year after the disaster were evaluated for government-certified disaster victims and non-victims. Results: The number of individuals who had not been prescribed MTX before the disaster was 4,973,401, including 31, 006 victims. Among them, 14,908 (including 110 victims) had a history of MTX prescription after the disaster. In the MTX-naïve group, new MTX prescriptions within one year after the disaster were significantly more frequent in victims compared to non-victims (age- and sex-adjusted hazard ratio: 1.83; 95% confidence interval: 1.37–2.46). Similarly, a non-significant increase in prescriptions for conventional synthetic/biological disease-modifying anti-rheumatic drugs was observed. Conclusions: Victims of the 2018 Japan flood were more likely to be prescribed MTX for the first time. Introduction Most rheumatic diseases result from a complex interplay of genetic, physical, psychological, and environmental factors. For instance, rheumatoid arthritis (RA) is associated with viral and bacterial infections, changes in gut microbes, poor oral hygiene, obesity, and psychological stress. [1, 2] Currently, global climate change is the cause of unprecedented large-scale natural disasters. These affect various aspects of human health through environmental, physical, and psychological factors, as well as healthcare delivery systems. Previous studies have demonstrated increased initiation of specific medications among victims with cognitive decline, sleep disorders, irritable bowel syndrome, and migraine. [3-6] Based on these findings, examining new prescriptions of anti-rheumatic drugs before and after a natural disaster may reflect the impact of disasters on rheumatic diseases. However, no large-scale studies have examined disaster-related changes in new anti-rheumatic drug prescriptions. In recent years, Japan has experienced a series of large-scale disasters, including the Great East Japan Earthquake. Therefore, clinicians must recognise how disasters affect rheumatic diseases through changes in medication prescriptions. Studies examining disaster-related changes in medication prescriptions have been limited to patients with RA. A previous study investigated the association between the Great East Japan Earthquake and RA activity in a cohort of 53 patients and revealed exacerbation of disease activity following the disaster. [7] Another study observed the influence of natural disasters such as earthquakes, typhoons, and heavy rains on 192 RA patients, and reported the deterioration of physical function one and six months after the disaster. [8] However, these were small-scale and case-based studies performed without a control group, and thus could not establish causal relationships between disasters and changes in rheumatic diseases. Therefore, the present study examined changes in anti-rheumatic drug prescriptions using population-based large-scale cohort data. We hypothesised that natural disasters affect rheumatic diseases and lead to increased prescriptions of anti-rheumatic drugs. The data used in this study corresponded to the census data of national health insurance claims and were analysed one year before and after the 2018 Japan Floods. In the analysis, we compared new prescriptions of anti-rheumatic drugs between government-certified victims and non-victims. Materials and Methods Study design and data collection After obtaining permission to use the data from the Ministry of Health, Labor, and Welfare (Permission no. 12232), this retrospective cohort study used data from the Japanese National Database of Health Insurance Claims and Specific Health Checkups (NDB). The NDB is one of the several government-maintained nationwide healthcare-related databases in Japan, and includes information on all prescription drugs dispensed in the country because all Japanese residents are covered by public health insurance. Japan has a universal health insurance system, and the NDB contains all the health service claims made by every individual who visited any medical institution. Setting Between June 28 and July 8, 2018, western Japan experienced torrential rainfall that triggered landslides and led to overflowing rivers. In terms of their destructive magnitude, the 2018 Japan Floods were the second-largest water-related disaster in the recorded history of Japan, surpassed only by the 2011 Great East Japan Earthquake. The aftermath included 263 fatalities, 484 injuries, and 8 missing individuals. Furthermore, 6,783 homes were destroyed and another 44,327 were damaged. Hiroshima, Okayama, and Ehime are the prefectures that were hit the hardest, accounting for approximately 90% of the total deaths. The estimated cost of the damage reached approximately 12.66 billion US dollars (converted at a central rate of 1 dollar to 111.37 yen, based on the average rate in the Tokyo Market for July 2018). Hiroshima, Okayama, and Ehime prefectures were selected as target areas for the location of medical institutions. [9] The survey period was set between July 2017 and June 2019, which corresponds to a period of one year before and one year after the disaster. Participants The participants in this study were those individuals aged 20 years or older who visited medical institutions located in the three target prefectures and had health insurance claims issued during the specified survey period. Among the participants, those identified as disaster victims by the local government were labelled as such in this study. The remaining participants were categorised as non-victims and analysed separately. Since accurate identification of specific rheumatic diseases in the claims data was limited, we defined our study populations based on prescription patterns of disease- specific medications. We focused on methotrexate (MTX; 2 mg) prescriptions because this formulation is specifically indicated for rheumatic diseases in Japan, and as detailed in a later subsection (“Targeted drugs”), the majority of these prescriptions are considered to be for the treatment of RA. Two distinct groups were included in this study. The first group consisted of participants who had no history of MTX prescriptions before the disaster, enabling us to identify those who had been newly prescribed MTX after the disaster. The second group consisted of participants with a history of MTX prescription after the disaster who had not been prescribed any anti-rheumatic drugs before the disaster. This enabled us to identify those who were prescribed anti-rheumatic drugs in addition to MTX after the disaster. We excluded patients aged rare incidence of rheumatic diseases such as RA and psoriasis in the younger population. Definition of disaster victims During the 2018 Japan flood, the Japanese government announced that certified victims would be fully exempt from medical insurance co-payments (10–30% of the total medical expenses). [9] Therefore, we defined a “disaster victim” as a person listed as a government-certified disaster victim in health insurance claims issued after the disaster. However, people whose medical expenses had already been exempted by the government, such as those under public livelihood protection and atomic bomb survivors, were not eligible for disaster-related exemption; therefore, they were categorised as non-victims even if they were affected. Disaster victims were certified by the local government of their residential municipality. The criteria for a certified “disaster victim” fell into one of the following categories: (1) the residential house was completely or partially destroyed, burned down, flooded above the floor level, or similarly damaged, or (2) family member who had financially supported the person was killed or suffered severely, or was missing. The validity of this definition of “disaster victims” is supported by its use in multiple studies investigating the impact of this disaster on different diseases using the same dataset. [3-6] Targeted drugs Many anti-rheumatic drugs are covered by insurance and have indications for treating other diseases. In Japan, oral MTX is available in two formulations (2 mg and 2.5 mg), each indicated for different diseases. The 2.5 mg formulation is specifically indicated for trophoblastic diseases and chronic lymphocytic leukaemia, while the 2 mg formulation is exclusively approved for RA, juvenile idiopathic arthritis (JIA), and diseases related to psoriasis (Pso) such as PsA and pustular Pso. This study included participants aged ≥20 years; therefore, prescriptions of MTX for JIA were not included. Insurance coverage for MTX prescriptions for Pso in Japan commenced in December 2018. Additionally, even if MTX was used after the insurance coverage began, the proportion of prescriptions for Pso is expected to be much smaller than that for RA. This is attributed to the prevalence of RA in Japan, which is approximately 0.75%, whereas that of Pso is lower at 0.34%. [10, 11] Furthermore, MTX is prescribed as the initial treatment for 85% RA patients, while only 39.1% Pso patients receive it during their treatment course. [12, 13] Given the prevalence rates and the proportion of MTX prescribed for these conditions, it can be inferred that the majority of MTX prescriptions are for the treatment of RA. Additionally, we extracted data on non-MTX drugs used for the treatment of RA in Japan as of 2019: conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs; including salazosulfapyridine, iguratimod, tacrolimus, bucillamine, and mizoribine), biological DMARDs (bDMARDs; including infliximab, etanercept, adalimumab, certolizumab pegol, golimumab, abatacept, and tocilizumab), and glucocorticoids (oral and injectable formulations). Outcomes We examined new prescriptions of targeted drugs after the disaster to evaluate changes in anti-rheumatic drug use. We focused on new prescriptions rather than existing ones because the continuation or discontinuation of existing prescriptions could be influenced by various factors such as healthcare access during disasters, whereas new prescriptions reflect medical needs more directly. The month in which the new prescription of the targeted drug was issued to the participant was identified in the database. The primary outcome of this study was the occurrence of new MTX prescriptions during the one-year period after the disaster. To evaluate changes in medication use among MTX users, the secondary outcome was defined as the occurrence of prescriptions for csDMARDs, bDMARDs, and glucocorticoids at a dosage of 1 mg or more during the one-year period after the disaster among patients with a prior history of MTX prescription within one year before the disaster. Statistical analyses We performed a chi-square test to compare binary and categorical variables between the victim and non-victim groups. In accordance with the NDB Japan rule, data masking is applied when the number of observations is 10 or less. For the chi-square test in Table 1, we proceeded with the test because the expected value was above 10. Additionally, we analysed the differences in the incidence rates of MTX, DMARDs, and glucocorticoids between the two groups using the Kaplan–Meier method with the log-rank test. We employed the Cox proportional hazards model adjusted for sex and age to quantitatively measure the impact of the disaster on the probability of new MTX and other drug prescriptions after ensuring, with the Schoenfeld residuals method, that the proportional hazards assumption was met. The follow-up period was defined as up to one year after disaster onset or until the first prescription of MTX for primary outcomes, and up to one year after disaster onset or until the first prescription of other anti-rheumatic medications (bDMARDs, csDMARDs, or glucocorticoids) for secondary outcomes. Furthermore, analyses were conducted to verify whether there was an inherent likelihood of disaster victims receiving MTX prescriptions more frequently than non-victims did before the disaster. We conducted logistic regression analyses for each period before and after the disaster after adjusting for age and sex in order to examine the association between disaster status and the incidence of total MTX prescriptions. All statistical analyses were performed using STATA/MP software (version 17; Stata Corp, 2019). Two-sided p -values of Ethics Ethical approval was granted by the Ethics Committee for Epidemiological Research at Hiroshima University (Ref. no. E-1389). The study was performed in accordance with the principles laid down in the Declaration of Helsinki. Study population A total of 1,556,403,905 prescription receipts were identified, leading to the identification of 6,176,299 participants. Of these, 1,176,170 participants under the age of 20 years were excluded. This resulted in 5,000,129 individuals being deemed eligible, of whom 4,973,401 were MTX-naïve, having no prior history of MTX prescription before the disaster, while 14,908 were MTX users with a history of MTX prescription after the disaster (Figure 1). Baseline characteristics Baseline characteristics of the eligible participants are detailed in Supplementary Table 1. Overall MTX prescriptions were more frequent among disaster victims in the pre-disaster period. However, logistic regression analysis adjusted for age and sex revealed that the odds ratio for MTX prescriptions was 1.11 (95% confidence interval [CI]: 0.98–1.27) for the victims before the disaster and 1.21 (95% CI: 1.07–1.37) after the disaster (Figure 2), with no significant association between being a victim and receiving MTX prescriptions before the disaster. The number of participants included in the MTX-naïve group who had no prior history of MTX prescription was 4,973,401 out of the 6,176,299 registered participants in the NDB. Table 1 indicates the baseline characteristics of the participants before the disaster. In total, 52.4% of victims and 36.0% of non-victims were >65 years old, and the percentages of women among victims and non-victims were 56.4% and 53.5%, respectively. The number of participants included in the MTX user group who had a history of MTX prescriptions before the disaster was 14,908 out of the 6,176,229 participants in the NDB. A total of 67.3% of victims and 59.3% of non-victims were over 65 years of age, and the percentages of women were 71.8% and 73.3%, respectively. New prescription of MTX The incidence of new MTX prescriptions and Kaplan–Meier curves of the participants are shown in Table 2 and Figure 3, respectively. The results of log-rank tests showed that a new prescription of MTX within one year after the disaster occurred at a higher rate among disaster victims than among non-victims ( p <0.001). Supplementary Table 2 reveals the results of the risk evaluation of the new prescriptions for MTX using the Cox proportional hazards model. After being adjusted for age and sex, the hazard ratio (HR) of the disaster on the new MTX prescription was 1.83 (95% CI: 1.37–2.46), suggesting that the likelihood of new prescriptions of MTX rose as a consequence of the disaster. Secondary outcome Table 2 describes the prescription incidence and Figure 4 and Supplementary Figures 1–3 display the Kaplan–Meier curves for the MTX user group according to the use of medications: bDMARDs in Supplementary Figure 1, csDMARDs in Supplementary Figure 2, glucocorticoids (oral and injectable) in Supplementary Figure 3, and any other anti-rheumatic drugs in Figure 4. Although the log-rank test showed no significant difference between the two groups ( p =0.325) for any other anti-rheumatic drugs, as detailed in Figure 4, a non-significant increase was observed. Supplementary Table 3 displays the results of the risk evaluation of non-MTX drugs using the Cox proportional hazards model in the MTX user group. The results revealed no significant differences between the victim and non-victim groups ( p =0.369). After adjusting for age and sex, the HR of the disaster was 1.21 (95% CI: 0.80–1.82). Discussion In this population-based cohort study, we revealed that disaster victims were more likely to be newly prescribed MTX after a disaster than non-victims. This finding was robust even after adjusting for age and sex. This study provides the first evidence from large-scale prescription data about changes in anti-rheumatic drug prescriptions following a disaster. However, prescriptions of bDMARDs, csDMARDs, and glucocorticoids among pre-disaster MTX users did not increase after the disaster. Although MTX is widely accepted in Japan as the first-line treatment for RA, as is also the case in other countries, the 2 mg MTX tablet is also covered by the Japanese health insurance system for treating diseases other than RA, such as Pso and JIA. As mentioned in the “Targeted drugs” subheading of the Methods section, given the age restriction of our study population and the timing of insurance coverage for Pso, these prescriptions were specifically for rheumatic diseases,with RA likely accounting for the majority of them. Therefore, the increased rate of new MTX prescriptions among victims suggests that natural disasters may contribute to the development or exacerbation of rheumatic disease, particularly RA. To the best of our knowledge, this is the first study to evaluate changes in anti-rheumatic drug prescriptions among disaster victims and to compare new prescriptions of these drugs between certified victims and non-victims living in the affected areas. Taking into account the study design and the large-scale, population-based data, we believe that this study suggests a causal relationship between disasters and changes in anti-rheumatic drug prescriptions. Furthermore, these findings have significant implications for clinicians and policymakers, considering the increasing frequency of large-scale natural disasters globally. The inclusion of disasters as a potential risk factor for the development of rheumatic diseases in clinical practice guidelines serves as a reminder to clinicians of the potential increase in anti-rheumatic drug prescriptions following such events. Moreover, given the anticipated surge in demand for MTX and other anti-rheumatic drugs during and after disasters, the results will be useful for strategizing drug stockpiling in disaster-susceptible areas. Furthermore, another study that investigated the correlation between migraine episodes and natural disasters emphasised the criticality of pre-disaster preparedness.[14] In this study, no significant difference was found in the incidence of new prescriptions for bDMARDs, csDMARDs, and glucocorticoids between victims and non-victims among MTX users. However, a trend toward a higher prescription rate was observed in the victim group compared to the non-victim group. One potential explanation for the lack of significant differences is that the disaster may have disrupted the daily lives of victims. Under these circumstances, patients with MTX-treated rheumatic diseases such as RA and Pso may have been reluctant to undergo bDMARDs or csDMARD treatment for various reasons, including the need for an increased frequency of hospital visits to distant specialists; more psychological stress on the patients, and the risk of new side effects associated with new medications, which could potentially make their daily lives more difficult. Furthermore, the limited study period and number of MTX-treated patients with new non-MTX prescriptions may have reduced the statistical power to detect significant differences. Our results are consistent with the biological basis of rheumatic disease development and exacerbation. A previous study evaluated the levels of immunological cytokines in patients with RA and in healthy controls after exposure to mental stress. [15] It was reported that patients with RA exhibited elevated levels of inflammatory cytokines such as IL-1β, IL-6, IFN-γ, and TNFα in response to stress compared with healthy individuals. These inflammatory cytokines are involved in the development and exacerbation of rheumatic diseases. [16] Thus, it is reasonable that patients with rheumatic diseases may develop symptoms because of an increase in inflammatory cytokines following a disaster. This study had several limitations. First, although MTX 2mg prescriptions were specific to rheumatic diseases in Japan, we could not identify which rheumatic disease was being treated because the NDB lacks information about diagnoses and reasons for prescriptions. However, the unique prescription format for MTX 2mg in Japan, which is not found in other countries, allows for the extraction of prescriptions specifically for rheumatic diseases without relying on ICD-10 codes, thus ensuring considerable diagnostic accuracy in the identification of patients with rheumatic diseases. Second, the certification of victims considered in this study was conducted by local governments. However, it is possible that specific groups of individuals may not have sought official recognition as disaster victims despite being impacted by the disaster. Therefore, the “non-victims” in this study may have included a few actual victims, which may have lead to an underestimation regarding differences between victims and non-victims in our study. In addition, the quantitative measurement of mental and physical stress was not included in our data, although this variable could potentially influence the results of this study and should be included in future analyses. Third, we could not adjust for all confounding factors, including environmental factors, physical and psychological stress levels, as well as infectious and immunological conditions that might affect rheumatic diseases. Finally, the potential for an increase in MTX prescriptions among victims, caused by the exemption of out-of-pocket medication costs, warrants consideration. In Japan, drug prices are intrinsically lower than in other countries, [17] with co-payment rates of 10% for those aged ≥75 years, 20% for 70–74 years, and 30% for within the Japanese health insurance system ranges from -0.125 to -0.076. [18] Hence, the increase in healthcare demand due to the exemption from medical expenses is limited and is not considered to contribute to the rise in MTX prescriptions. In conclusion, this study indicated an increased incidence of newly prescribed MTX among the victims of the 2018 Japan Flood. Availability of data and material Data cannot be shared due to restrictions mandated by the Ministry of Health, Labour and Welfare. Funding This research was not supported by any specific grants from any funding agencies in the public, commercial, or not-for-profit sectors. Conflict of interest SH received speaker fees, consultancy fees, research grants, and honoraria from AbbVie, Asahi-Kasei Pharma, Astellas, AstraZeneca, Ashima, Bristol Myers Squibb, Boehringer Ingelheim, Chugai, Daiichi-Sankyo, Eisai, Gilead Sciences, Glaxo Smithkline, Eli Lilly, Janssen, Novartis, Nippon Shinyaku, Otsuka, Pfizer, Taisho, Tanabe-Mitsubishi, and UCB. Authors’ contributions GK contributed to conception, design, analysis, interpretation of data, and drafting of the manuscript. SY contributed to analysis, acquisition of data, interpretation of data, and critical revision of the manuscript. TS contributed to design and critical revision of the manuscript. 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Med Soc . 2000;10(2):115-138. doi:10.4091/iken1991.10.2_115 Table MTX-naïve MTX-user Victims Non-Victims p -value Victims Non-Victims p -value All participants, n 31,006 4,942,395 110 14,798 Age classification, n(%) 20–44 6,668 (21.5%) 1,710,176 (34.6%) p <0.001 a ( a ) 1,067 (7.2%) p =0.198 45–64 8,103 (26.1%) 1,451,712 (29.4%) b ( b ) 4,949 (33.4%) 65+ 16,235 (52.4%) 1,780,507 (36.0%) 74 (67.3%) 8,782 (59.3%) Sex, n(%) Male 13,528 (43.6%) 2,298,159 (46.5%) p <0.001 31 (28.2%) 3,948 (26.7%) p =0.723 Female 17,478 (56.4%) 2,644,236 (53.5%) 79 (71.8%) 10,850 (73.3%) Data were presented as n(%). a Values less than 10 that were masked owing to the NDB Japan rules. b Values over 10 that were masked due to NDB Japan rules MTX-naïve patients had no prior history of MTX prescription before the disaster, whereas MTX-user patients had a history of MTX prescription after the disaster and no history of other anti-rheumatic drugs prescription before the disaster Abbreviations: MTX, methotrexate Victims Non-Victims p -value MTX, n (%) 54(0.17%) 3811(0.08%) p <0.001 bDMARDs, n(%) a ( a ) 414(2.8%) p =0.093 csDMARDs. n(%) a ( a ) 1074(7.3%) p =0.467 Glucocorticoid, n(%) 13(11.8%) 1547(10,5%) p =0.641 Any of the anti-rheumatic drugs 23(20.9%) 2627(17.8%) p =0.388 Data were presented as n(%). a Values less than 10 that were masked owing to the NDB Japan rules. Abbreviations: MTX, methotrexate; DMARDs, disease-modifying anti-rheumatic drugs; bDMARDs, biological DMARDs; cDMARDs, conventional synthetic DMARDs. Figure legends Figure 1: Flowchart of eligible and ineligible participants The flowchart shows the selection of eligible and ineligible participants. MTX-naïve patients were those who had no prior history of MTX prescriptions before the disaster, while MTX users were those who had a history of MTX prescriptions after the disaster. MTX, methotrexate Figure 2: Time trend of adjusted OR of disaster victims for prescription of total MTX before and after the disaster This plot displays the adjusted OR for disaster victims regarding the association with total MTX prescriptions before and after the disaster. Pre-disaster users were included to evaluate trends prior to the disaster. The p -value for interaction indicates the association between the time variable (pre- or post-disaster) and disaster-affected status. OR, odds ratio; MTX, methotrexate Figure 3: Kaplan–Meier failure curves for the participants newly prescribed with MTX The Kaplan–Meier curve illustrates the incidence of new MTX prescriptions within a span of 12 months following the disaster for victims and non-victims. MTX, methotrexate Figure 4 : Kaplan–Meier failure curves for the participants newly prescribed with any other anti-rheumatic drugs The Kaplan–Meier curve depicts the incidence of new other anti-rheumatic drug prescriptions (csDMARDs, bDMARDs, and glucocorticoids) among MTX-treated participants within a span of 12 months following the disaster among victims and non-victims. csDMARDs, conventional synthetic disease-modifying anti-rheumatic drugs; bDMARDs, biological disease-modifying anti-rheumatic drugs; MTX, methotrexate Supplementary Figure 1: Kaplan–Meier failure curves for the participants newly prescribed with bDMARDs The Kaplan–Meier curve depicts the incidence of new bDMARDs prescription among MTX-treated participants within a span of 12 months following the disaster among victims and non-victims. bDMARDs, biological disease-modifying anti-rheumatic drugs; MTX, methotrexate Supplementary Figure 2: Kaplan–Meier failure curves for the participants newly prescribed with csDMARDs The Kaplan–Meier curve depicts the incidence of new csDMARDs prescription among MTX-treated participants within a span of 12 months following the disaster among victims and non-victims. csDMARDs, conventional synthetic disease-modifying anti-rheumatic drugs; MTX, methotrexate Supplementary Figure 3: Kaplan–Meier failure curves for the participants newly prescribed or injected with glucocorticoids The Kaplan–Meier curve depicts the incidence of new glucocorticoid prescription or injection among MTX-treated participants within a span of 12 months following the disaster among victims and non-victims. MTX, methotrexate Information & Authors Information Version history V1 Version 1 17 January 2025 Copyright This work is licensed under a Non Exclusive No Reuse License. Keywords epidemiology pharmacoepidemiology rheumatoid arthritis rheumatology Authors Affiliations Genki Kidoguchi 0009-0001-0558-8814 [email protected] Hiroshima University Hospital View all articles by this author Shuhei Yoshida Hiroshima University Hospital View all articles by this author Tomohiro Sugimoto Hiroshima University Hospital View all articles by this author Shintaro Hirata 0000-0002-2474-9943 Hiroshima University Hospital View all articles by this author Masatoshi Matsumoto Hiroshima University Hospital View all articles by this author Metrics & Citations Metrics Article Usage 264 views 136 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Genki Kidoguchi, Shuhei Yoshida, Tomohiro Sugimoto, et al. Impact of the 2018 Japan Floods on methotrexate and anti-rheumatic drug prescriptions: A longitudinal analysis of the Japanese National Database. Authorea . 17 January 2025. DOI: https://doi.org/10.22541/au.173711171.12516474/v1 If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download. For more information or tips please see 'Downloading to a citation manager' in the Help menu . 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