FormalPara Key Summary Points

Why carry out this study?

The management of geriatric patients with rheumatoid arthritis (RA) above the age of 75 poses a forthcoming quandary for  Western nations.

On the basis of the cancer and major adverse cardiovascular events (MACE) risk associated with Janus kinase (JAK) inhibitors, both the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have proffered advisories concerning the utilization of JAK inhibitors, specifically in patients aged over 65 years.

What was learned from the study?

Discontinuations attributed to infection were infrequent among patients younger than 65 years (1.8%) but increased to 9.1% in patients aged 65 years and older, and further rose to 13.2% among patients aged 75 years and older.

Drug retention rates for JAK inhibitors and anti-interleukin-6 receptor (IL-6R) antibodies were highest in the younger population (< 65 years), and both JAK inhibitors and abatacept showed high retention rates in the 65–74-year-old group.

While direct comparisons with the ORAL Surveillance study cannot be made, the increased occurrence of cancers and MACE with JAK inhibitors was not evident in the current study.

The fact that the medications with the highest retention rates differed between those aged 65–74 and those aged 75 and older is also important for future clinical research, and these two age cohorts need to be considered separately.

The use of abatacept or anti-IL-6R antibodies may be preferable for patients over 75 years of age.

Introduction

Japan has the oldest population in the world, becoming an aging society in 1970, an aged society in 1994, and a super-aged society in 2007. The percentage of Japanese citizens aged 65 or older exceeded 29% in 2020 and is expected to reach 35% in the next 20 years or less [1]. This implies an aging of patients as well as healthy individuals, and thus the aging of patients with rheumatoid arthritis (RA) is also being faced in Japan.

The treatment of elderly patients with RA presents various therapeutic challenges. Deterioration of musculoskeletal function (known as sarcopenia) as well as decreased medication adherence and retention due to cognitive decline are major concerns among them [2]. Moreover, age-related decline in kidney, liver, and heart functions, along with diminishing muscle strength, adds to the complexities of treating elderly patients with RA. Adverse events are inevitably more likely to occur, resulting in lower medication adherence rates [3, 4]. On the other hand, the goal of rheumatoid arthritis (RA) treatment, as stated in the European League Against Rheumatism (EULAR) treatment recommendations, is to attain remission or low disease activity, regardless of the patient’s age, including older individuals [5]. Additionally, addressing the medical care of elderly patients with RA stands as a paramount concern, given its potential to bolster the overall healthy life span of this demographic, consequently mitigating the decline in the labor force and curbing the escalating expenditures in healthcare. While we have previously investigated the continuation rates of biologics in elderly patients, it is important to note that these prior studies had limitations. Specifically, the enrolled patient numbers were insufficient to draw meaningful conclusions regarding patients over 75 years of age, and we were unable to include patients treated with Janus kinase (JAK) inhibitors in those earlier analyses [6].

The World Health Organization (WHO) defines the elderly as those aged 65 years and older. However, recent data on the physical and mental aging of the Japanese elderly indicate that the majority of people between the ages of 65 and 74 are physically and mentally healthy and able to engage in active social activities. The global trend of uniformly treating those aged 65 and older as elderly is no longer realistic in light of the current situation [7]. Therefore, the treatment of patients with RA aged 65–74 and those aged 75 and older should be considered separately [8]. Although the aging of the population in Western countries is relatively slow compared with that of Japan, the treatment of elderly patients with RA over the age of 75 is a future challenge that Western countries also face. In this context, Japan can offer valuable insights and serve as an exemplary case for addressing this issue.

In theory, biologics do not suppress signals other than those of their target molecules and are largely unaffected by hepatic or renal impairment. Given their remarkable balance between efficacy and safety, biologics emerge as a viable and promising treatment option for elderly patients [9]. On the other hand, the ORAL Surveillance study has raised concerns about the risk of malignancy and major adverse cardiovascular events (MACE) with JAK inhibitors, and therefore the Food and Drug Administration (FDA) and European Medicines Agency (EMA) have issued warnings about the use of JAK inhibitors, particularly in patients over 65 years of age [10, 11]. Nevertheless, the findings from the ORAL Surveillance study raise significant clinical inquiries and warrant further investigation [12]. The study documented an elevated risk among North Americans, yet further investigations are imperative to ascertain whether this risk disparity extends to other racial groups. Additionally, comparisons with tumor necrosis factor (TNF) inhibitors and other drugs are necessary to contextualize the findings comprehensively.

Given this context, the optimization of medical care for elderly patients with RA requires a strategic approach, aiming to maximize therapeutic efficacy through the prudent application of molecular targeted therapies. Hence, this study involved examining the 3-year retention rates of each biologic or targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD) in Japan, while also assessing their suitable application within different age groups.

Methods

Patients and Study Design

This study was conducted as part of the FIRST Registry [13,14,15,16], which involved several institutions centered on the University of Occupational and Environmental Health, Japan. Participating institutions included Wakamatsu Hospital, Tobata General Hospital, Kitakyushu General Hospital, and Shimonoseki Saiseikai Hospital. The study included patients who met the classification and diagnostic criteria for RA and were initiated on molecular targeted therapies [17, 18]. To mitigate the impact of temporal variations, b/tsDMARDs were compared over a specific period from July 2013 to October 2019. This timeframe was chosen to ensure that all classes of drugs, including JAK inhibitors, were available on the market simultaneously, minimizing any discrepancies arising from different time periods. No exclusion criteria were applied, and continuous monitoring was carried out for all patients. The bDMARDs used in this study included TNF inhibitors (infliximab, infliximab biosimilar, etanercept, adalimumab, golimumab, and certolizumab pegol), anti-interleukin-6 receptor (IL-6R) antibodies (tocilizumab and sarilumab), and abatacept. In addition, the tsDMARDs included in the study were tofacitinib and baricitinib. All drugs were used within the health insurance coverage and administered at approved doses and intervals in Japan. This study was approved by the ethics review board of the University of Occupational and Environmental Health, Japan (UOEHCRB21-068). Informed consent was obtained from patients while utilizing anonymized data.

Primary Outcomes

The primary endpoint of this study was to assess the 3-year retention rate of each b/tsDMARDs by generation and identify any differences in retention rates among these drugs. Reasons for treatment discontinuation were also collected as part of the study. In this study, “drug continuation” was defined as patients who maintained treatment with the drug at its prescribed dosage. On the other hand, “drug discontinuation” was defined as cases where the drug was discontinued because of insufficient efficacy or the occurrence of adverse events. Patients who chose to discontinue the drugs or reduce the dosage as a result of maintaining remission or low disease activity were treated as censored. The reasons for discontinuation were collected and based on information documented in the patient charts.

Propensity Score (PS)-Based Inverse Probability of Treatment Weighting (IPTW)

To adjust for differences in baseline patient characteristics among the groups, PS-based IPTW was utilized, as previously described [19]. In brief, propensity scores were calculated and then used to weight the data. The weights were determined by the ratio of patients receiving TNF inhibitors to all patients divided by the propensity score in the TNF inhibitors group, and the ratio of patients receiving anti-IL-6R antibodies, cytotoxic T lymphocyte antigen 4 immunoglobulin fusion proteins (CTLA4-Ig), and JAK inhibitors to all patients divided by 1 minus the propensity score in patients treated with anti-IL-6R antibodies, CTLA4-Ig, and JAK inhibitors. This weighting coefficient helped to stabilize the analysis. In this study, for covariate adjustment in the three groups of patients treated with TNF inhibitors, abatacept (ABA), or tocilizumab (TCZ), age, disease duration, gender, history of bDMARD use, MTX dose, glucocorticoid dose, tender joint count, swollen joint count, patient global assessment, evaluator global assessment, Health Assessment Questionnaire-Disability Index, C-reactive protein level, erythrocyte sedimentation rate, rheumatoid factor level, anti-citrullinated protein (CCP) antibody level, and matrix metalloproteinase-3 (MMP-3) level were used as baseline covariates, and generalized propensity scores were estimated using multinomial logistic regression. Since the covariates including the time-dependent covariates were adjusted using IPTW based on generalized propensity scores, the proportional hazards assumption holds.

Other Statistical Analyses

Patient characteristics are expressed as mean ± standard deviation, median (interquartile range), or number (%) of patients. Analysis of variance was employed for normally distributed continuous variables, the Kruskal–Wallis test for non-normally distributed continuous variables, and the chi-square test for categorical variables to assess differences among the groups. Retention rates were analyzed using the Kaplan–Meier method, and p values were calculated using the Cox proportional hazards model. All reported p values are two-sided and were not adjusted for multiple testing. The level of significance was p < 0.05. All analyses were conducted using JMP version 14.0 (SAS Institute Inc., Cary, NC) and SPSS software version 25.0 (SPSS Inc., Chicago, IL).

Results

Patient Disposition

A total of 2292 patients were encompassed within the scope of this analysis. The utilization of molecular targeted therapies exhibited significant variability across different age groups, wherein TNF inhibitors emerged as the prevailing choice (43.5%) for patients below the age of 65, while JAK inhibitors were administered to 17.1% of the patient population (Fig. 1). Conversely, there was a notable escalation in the utilization of CTLA4-Ig among individuals within the age range of 65–74 years. Furthermore, in the subset of patients aged 75 years and above, the percentage of JAK inhibitors employed experienced a decline (7.8%), while abatacept emerged as the prevailing choice (39.2%). On the other hand, anti-IL-6R antibodies were administered to approximately 25% of individuals across all age groups, and the utilization rate remained consistent irrespective of age.

Fig. 1
figure 1

Patient disposition. bDMARDs biologic disease-modifying anti-rheumatic drug, tsDMARDs targeted synthetic disease-modifying anti-rheumatic drugs, TNFi tumor necrosis factor inhibitors, Anti IL-6R anti-IL-6 receptor antibodies, CTLA-4 Ig cytotoxic T lymphocyte antigen 4 immunoglobulin, JAKi Janus kinase inhibitors

Full size image

Table 1 shows the patient profiles corresponding to each age group. Within these generational patient backgrounds, notable variations were observed not only in terms of age but also across several clinical factors. For instance, it is well established that the male-to-female ratio tends to shift towards a higher proportion of male patients among elderly patients with RA. In the present study, it was observed that among patients below 65 years of age, women accounted for 84.5% of the population, whereas among those aged 75 years and above, women constituted 77.6% (p < 0.001) [20]. As a fundamental principle, the participating centers in this study adhered to the EULAR treatment recommendations for RA and employed methotrexate (MTX) as a therapeutic approach in phase I, unless contraindications were present. However, only 53.2% of patients aged 75 years or older received MTX treatment.

Table 1 Baseline demographic and clinical characteristics of the included patients
Full size table

Comparison of Retention Rate Among b/tsDARDs

The long-term retention rate serves as an indicator, reflecting the balance between the safety and efficacy of the drug over an extended period. Taking into account the significant discrepancies in patient backgrounds observed across different drugs (Supplementary Tables 1, 2, and 3), all subsequent analyses were carried out following the adjustment of potential patient selection bias using the PS-based IPTW approach (Tables 2, 3, and 4). Initially, we investigated the 3-year persistence rate specifically for patients aged 50 years or older. The analysis revealed that the persistence rate for TNF inhibitors was lower compared to other preparations. However, there were no significant differences in the persistence rate among anti-IL-6R antibodies, CTLA4-Ig, and JAK inhibitors, as demonstrated in Fig. 2a. However, when comparing the 3-year retention rates of each molecular targeted therapy across different age groups, notable variations were observed (Fig. 2b). In the younger age group (< 65 years), JAK inhibitors and anti-IL-6R antibodies exhibited higher persistence rates compared to the other two therapies (p < 0.001). Conversely, among individuals aged 65–74 years, higher retention rates were observed for JAK inhibitors and CTLA4-Ig (p < 0.001). Furthermore, among those aged 75 years and older, CTLA4-Ig and anti-IL-6R antibodies agents demonstrated higher continuation rates (p < 0.001).

Table 2 Characteristics of patients under 65 years of age in adjusted data using PS-IPTW
Full size table
Table 3 Characteristics of patients aged 65–74 years in adjusted data using PS-IPTW
Full size table
Table 4 Characteristics of patients aged 75 years and older in adjusted data using PS-IPTW
Full size table
Fig. 2
figure 2

Drug retention rates and factors influencing discontinuation. a Retention rates in patients aged 50 and above. b Retention rates across different generations. c Reasons for drug discontinuation across different generations. TNFi tumor necrosis factor inhibitors, Anti IL-6R anti-IL-6 receptor antibodies, CTLA-4 Ig cytotoxic T lymphocyte antigen 4 immunoglobulin, JAKi Janus kinase inhibitors, AEs adverse events

Full size image

To explore the factors contributing to discontinuation in each age group, an analysis was conducted of the reasons for discontinuation categorized by age. The findings indicated that ineffectiveness was the most prevalent reason for discontinuation across all age groups (Fig. 2c). However, the proportion of patients discontinuing or switching because of ineffectiveness varied among age groups. Specifically, in the younger age group (< 65 years), approximately 68.8% of patients experienced discontinuation or switch due to ineffectiveness, whereas this proportion decreased to around 50% for patients aged 65, and it remained at a similar level for those aged 75 and older. On the contrary, discontinuations attributed to infection were infrequent among patients younger than 65 years, accounting for only 1.8% of cases. However, the proportion increased to 9.1% in patients aged 65 years and older and further rose to 13.2% among patients aged 75 years and older. The findings of the ORAL Surveillance study have sparked concerns regarding the incidence of malignancies associated with JAK inhibitors. In the study, 2.9% of younger patients discontinued b/tsDMARDs because of malignancy. The proportion increased to 5.8% among patients aged 65 to 74 years and 5.5% among patients aged older than 75 years.

Proportion of Reasons for Discontinuation of b/tsDMARDs

As depicted in Fig. 2, the primary reasons for discontinuation of b/tsDMARDs were categorized as “insufficient efficacy,” “infection,” “allergic reaction,” and “cancers.” Consequently, our subsequent analysis focused on evaluating the incidence of these factors in each drug specifically among patients aged 50 years or older. This approach aligns with the age criteria employed in the ORAL Surveillance study. However, it is important to acknowledge that our results may not be directly comparable to those of the ORAL Surveillance study because of differences in study design and patient characteristics. Furthermore, we examined these incidences within different age groups to gain a comprehensive understanding of the associations. Among patients aged 50 years and older, the rates of discontinuation due to insufficient efficacy were the lowest for anti-IL-6R antibodies and JAK inhibitors. Similarly, the rates of discontinuation due to allergic reactions were the lowest for CTLA4-Ig and JAK inhibitors. However, the rates of infections and cancers were similar across all drugs (Fig. 3a–c).

Fig. 3
figure 3

Incident rates of drug discontinuation reasons. Incidence rates of a insufficient efficacy, b serious infection, c allergic reaction, or d cancers as a cause for drug discontinuation across different generations. Yr year, NMSC non-melanoma skin cancer, TNFi tumor necrosis factor inhibitors, Anti IL-6R anti-IL-6 receptor antibodies, CTLA-4 Ig cytotoxic T lymphocyte antigen 4 immunoglobulin, JAKi Janus kinase inhibitors

Full size image

However, distinct trends emerged when analyzed by age groups. The discontinuation rates due to insufficient efficacy consistently remained the lowest for JAK inhibitors across all age groups (Fig. 3a). Regarding discontinuations due to infection, they were comparable for all drugs in patients below 65 years of age, with minimal instances (Fig. 3b). However, a notable trend towards increased discontinuations due to infection was observed for JAK inhibitors and anti-IL-6R antibodies in patients aged 65 years and older (p = 0.13). Moreover, there was a significant rise in infections, particularly among patients aged 75 years and older who received JAK inhibitors (p = 0.01). On the contrary, CTLA4-Ig exhibited a lower rate of discontinuations due to infection across all age groups. Discontinuations attributed to allergic reactions, including injection site reactions, were primarily associated with TNF inhibitors, followed by anti-IL-6R antibodies. In contrast, allergic reactions were rarely observed with CTLA4-Ig and JAK inhibitors (Fig. 3c). This indicates that allergic reactions might contribute to the comparatively lower retention rate of TNF inhibitors in comparison to other drugs. Notably, this trend was more pronounced in older patients. No significant differences were found in the incidence of malignancies among all the various drugs.

Cancer and Cardiovascular Risk by b/tsDMARDs and Age Group

The findings from the ORAL Surveillance study have brought forth apprehensions about the occurrence of cancers and MACE linked to the utilization of JAK inhibitors. This study possesses a distinct patient background and study design when compared to the ORAL Surveillance study, making direct comparisons challenging. However, it remains a significant concern to assess the risks of malignancy and MACE in patients encountered in routine clinical practice. Subsequently, we proceeded to examine the incidence of cancers and MACE associated with the use of each molecular targeted therapy, with TNF inhibitors employed as the reference for comparative analysis. Figure 4a shows the hazard rates for the incidence of cancers in all patients, revealing no significant differences in the incidence of cancers among all drugs compared to TNF inhibitors. Furthermore, when examining participants aged 50 years or older, the trend remained consistent, with no noticeable increase in the incidence of cancers with JAK inhibitors or other molecular targeted therapies in this registry (Fig. 4b). This trend persisted even among participants aged 65 years and older, who were considered to be at a higher risk, as demonstrated in Fig. 4c.

Fig. 4
figure 4

Hazard ratios for cancers, excluding NMSC. Hazard ratios for cancers, excluding NMSC in a all patients, b patients aged 50 and above, c patients aged 65 and above. NMSC non-melanoma skin cancer, CI confidence interval, TNF tumor necrosis factor, JAK Janus kinase, Anti IL-6R anti-IL-6 receptor antibodies, CTLA-4 Ig cytotoxic T lymphocyte antigen 4 immunoglobulin

Full size image

In contrast, when the incidence of MACE was examined, the overall incidence in this study was very low. Specifically, it was 0.9% for TNF inhibitors, 0.2% for CTLA4-Ig, 0.5% for anti-IL-6R antibodies, and zero for JAK inhibitors over 3 years. The hazard rates also revealed no significant differences among all drugs, as indicated in Supplementary Fig. 1A. These findings remained consistent when analyzing the data for patients aged 50 years and older (Supplementary Fig. 1B) as well as those aged 65 years and older (Supplementary Fig. 1C).

Discussion

The purpose of this study was to examine drug retention rates for four classes of molecular targeted therapies for RA using a multicenter RA registry (FIRST Registry) to provide data to aid in the selection of the optimal medication for each age cohort. We have previously reported drug retention rates in the elderly, but few cases were over 75 years of age, and JAK inhibitors were not included in the study [6]. In this study, the aging of Japanese society made it possible to collect and accumulate data on patients with RA aged 75 years and older. Comparison of long-term drug retention rates for each drug among the elderly, especially those over 75 years of age, is likely to be valuable data, as there is little evidence to date.

First, differences in patient background revealed that the rate of concomitant usage of MTX varied widely by age cohort. MTX is considered the primary treatment strategy during phase I therapy in the EULAR treatment recommendations [5, 21]. In fact, MTX is superior to other csDMARDs in terms of both efficacy and safety in several clinical trials conducted to date [22]. On the other hand, MTX primarily undergoes metabolism in the kidneys and tends to accumulate in the body in the presence of renal dysfunction. This limitation restricts the use of MTX, and when the estimated glomerular filtration rate (eGFR) falls below 30 mL/min/1.73 m2, employing MTX becomes challenging. Aging represents the most prominent risk factor for the decline in renal function as it leads to a reduction in glomerular count, with approximately 40% of individuals aged over 65 years experiencing a decline to an eGFR of 60 mL/min/1.73 m2. Aging also leads to decreased immune response, risk of infection, and reduced lung or heart reserve, making adverse events more likely to be severe. In fact, a Japanese study of MTX-related deaths in patients with RA found that 64.6% of the 851 deaths were aged 70 years or older [23]. Against this background, the inability to use MTX in phase I or to combine MTX with molecular targeted agents in phase II and later is one of the factors that make the treatment of elderly patients with RA difficult.

Abatacept and anti-IL-6R antibodies demonstrated the highest drug retention rates in patients aged 75 years and older in this study. Anti-IL-6R antibodies are recognized as molecular targeted therapies with relatively low dependence on MTX for their efficacy, and their effectiveness can be maintained even without concurrent MTX therapy [24]. In other words, the higher compliance rate observed can be attributed to the avoidance of the aforementioned issue encountered in older patients with RA, specifically the challenge of using MTX concomitantly. The same is true for JAK inhibitors. Nonetheless, JAK inhibitors were frequently discontinued as a result of the occurrence of infections, leading to an inability to sustain the retention rate. This has been consistently observed in Japanese studies of JAK inhibitors [25]. On the other hand, abatacept is recognized for its reduced reliance on MTX to achieve efficacy, although not to the same extent as anti-IL-6R antibodies. Additionally, this study indicated that abatacept is discontinued less frequently as a result of the development of infections. The use of abatacept or anti-IL-6R antibodies may be preferable for patients over 75 years of age.

Drug retention rates for JAK inhibitors and anti-IL-6R antibodies were highest among adults (< 64 years of age). Discontinuations due to insufficient effect were lowest for JAK inhibitors in all age cohorts. Previous clinical trials have shown the superiority of JAK inhibitors over TNF inhibitors or abatacept, but this study additionally demonstrated the superiority of JAK inhibitors in terms of long-term drug retention rates [26,27,28]. In younger patients, the occurrence of infections leading to drug discontinuation was similarly low across all drugs, which may explain the high continuation rate observed for JAK inhibitors. In addition, younger patients often exhibit greater social engagement and demand for deep clinical remission. Consequently, JAK inhibitors were considered more appropriate for these patients. However, it is important to note that even younger patients undergo the aging process. Consequently, regardless of age or gender, it is essential to implement routine monitoring during the course of treatment. This is especially vital for medications like baricitinib and filgotinib, which rely on renal excretion, necessitating regular assessment of renal function. If there is a decline in eGFR, dose adjustments should be considered. The significance of this monitoring becomes particularly pronounced when patients transition from a younger to an older age group. This study did not assess long-term safety over intervals as extensive as 10 years, highlighting the requirement for additional follow-up investigations.

In the 65–74-year-old group, drug retention rates were high for both JAK inhibitors and abatacept. It is interesting to note that the highest retention rates were observed for drugs with different characteristics: the more effective JAK inhibitor and the safer abatacept. A unique follow-up study conducted in Denmark has revealed that the younger an individual appears (cognitive age), the better their physical function is preserved, leading to an extension of life expectancy [29]. In other words, significant individual variations exist in cardiac, renal, and other physical functions among individuals aged 65–74, emphasizing the potential importance of appearing youthful in maintaining overall health. The fact that the medications with the highest retention rates differed between those aged 65–74 and those aged 75 and older is also important for future clinical research, and these two age cohorts need to be considered separately.

Finally, the results of the ORAL Surveillance study have raised concerns regarding the heightened incidence of cancers and MACE with JAK inhibitors [10, 12]. While it is important to note that direct comparisons with the ORAL Surveillance study cannot be made, this trend was not observed in the present study. The incidence of cancers per 100 person-years in the ORAL Surveillance study was 0.77 for TNF inhibitors and 1.13 for tofacitinib [10]. On the other hand, in our study, the incidence rate per 100 person-years for cancers in patients aged 50 years and older was 1.30 for TNF inhibitors and 0.93 for JAK inhibitors, suggesting that the overall incidence of cancers did not differ markedly between both cohorts. The different trends observed in this study may be due to ethnic differences.

In contrast, the ORAL Surveillance study reported an incidence of MACE per 100 patient-years as 0.73 for TNF inhibitors and 0.98 for tofacitinib. In comparison, our study revealed an incidence of MACE as 0.38 for TNF inhibitors and 0.0 for JAK inhibitors, indicating the incidence of MACE itself differs significantly from the ORAL Surveillance study. This is due not only to genetic predisposition but also to the fact that Japanese people tend to be leaner and have different dietary habits than Westerners. As an example, it is acknowledged that the occurrence of acute coronary syndromes is notably lower in Japanese populations compared to other regions worldwide [30,31,32]. Additionally, our registry employed CT and echocardiography as part of the screening process for cancers and MACE before initiating molecular targeted therapies, which may have impacted the study results [33]. In any case, the importance of pretreatment risk assessment remains unchanged, as emphasized by the recommendations of the FDA, EMA, and EULAR treatment guidelines.

Limitations of this study are as follows. First, the study is not a randomized prospective design, and IPTW may not be sufficient to eliminate unknown confounding factors. Second, no comparisons were made between different products of TNF inhibitors or JAK inhibitors. Third, data on rituximab, which is not approved in Japan, were scarce in this registry and were not included in this study. Furthermore, it is essential to underscore that our study is fundamentally distinct from the ORAL Surveillance study, which is a prospective study centered on patients at risk for cardiovascular events.

Conclusion

This study enabled a comparison of the drug retention rates of each b/tsDMARDs in different age cohorts and yielded critical evidence for informed shared decision-making. The results of this study in Japan, which boasts the world’s oldest population, offer valuable guidance for the future treatment of elderly patients with RA.