This study assessed prescription patterns, demographics, and clinical factors associated with the time to first DMARD prescription among adults with RA using large-scale real-world data. The prescription pattern indicated a substantial proportion of early initiation; however, a notable subgroup of patients experienced delayed initiation despite a confirmed diagnosis of RA. In this cohort, approximately 43% of patients initiated DMARD therapy more than 3 months after their RA diagnosis, with a mean delay of 18.18 months. Furthermore, approximately 29% of patients initiated DMARD treatment 12 months after RA diagnosis. The findings of this study highlight variations in DMARD initiation across variables, such as age, sex, race, ethnicity, marital status, geographic region, and comorbidity burden.

In this study, the large difference between the mean and median times to DMARD initiation suggests the presence of outliers. This is consistent with the observation that 29% of the cohort initiated treatment more than 1 year after diagnosis. Such delays reflect incomplete visit histories or care received outside the TriNetX network, as well as missing data that could inflate the mean [20, 21]. Nonetheless, both the mean and median values were reported to provide a clearer picture of the real-world time to treatment initiation in patients with RA.

Over the past two decades, a wide range of DMARDs have been approved for the management of RA. Conventional synthetic DMARDs, including methotrexate, hydroxychloroquine, sulfasalazine, and leflunomide, remain the first-line therapy due to their well-established efficacy, safety, and accessibility. Furthermore, the introduction of bDMARDs, starting with TNF inhibitors, such as etanercept, infliximab, and adalimumab, and the subsequent development of non-TNF biologics, such as abatacept, rituximab, and interleukin-6 receptor antagonists (tocilizumab and sarilumab), have significantly expanded the therapeutic landscape [1, 11]. Recently, targeted synthetic DMARDs, including JAK inhibitors such as tofacitinib (2012), baricitinib (2018), and upadacitinib (2019), have offered additional oral options with comparable efficacy, particularly for patients who have shown an inadequate response to conventional therapy or biologics [22].

Although the therapeutic landscape of RA has expanded considerably, the benefits of early intervention have not yet been fully utilized in clinical practice. In this study, approximately 43% of newly diagnosed patients in the EHR dataset (2012–2024) initiated DMARD treatment after 3 months, and 29% initiated treatment after 1 year. This overall pattern of delayed DMARD initiation has been documented previously. A study that evaluated DMARD initiation rates among 40,040 newly diagnosed patients with RA using Truven Health MarketScan commercial and Medicare claims databases between 2009 and 2013 found that only 55.5% of patients received therapy within 12 months of diagnosis [14]. Similarly, another study that examined DMARD initiation among 16,680 patients in the US military’s TRICARE program (2007–2012) found that only 35.6% initiated DMARD therapy 3 months after diagnosis [7]. In addition, analyses of Medicare data that evaluated the use of DMARD therapy among 33,373 older adults with a new RA diagnosis from 2008 to 2017 reported that only 28.9% initiated DMARD therapy [23]. Simultaneously, the findings of this study also indicate substitutional improvement in recent years; in this cohort, 57% of patients started DMARD within 3 months of diagnosis, 83% by 6 months, and over 90% by 5 years. This suggests that the early initiation of DMARD therapy has improved compared with earlier treatment years, even though opportunities to further reduce delays remain.

In this analysis, demographic and regional characteristics were strongly associated with the timing of DMARDs initiation. Increasing age was associated with earlier prescribing of DMARD therapy, with higher rates of initiation observed in older patients than in patients aged 18–29 years. These findings should be evaluated in the context of prior real-world evidence showing that older patients with RA, Medicare beneficiaries aged ≥ 65 years, were less likely to receive DMARD therapy following RA diagnosis [14]. Moreover, the higher comorbidity burden was found to be associated with faster initiation of DMARD therapy, which contrasts with prior reports suggesting that a greater comorbidity burden is typically linked to delayed treatment initiation [7, 23, 24]. A possible explanation is that patients with multiple chronic conditions may have more frequent interactions with healthcare providers, allowing for earlier recognition of RA and prompt initiation of therapy.

Despite the fact that female sex bears most of the RA burden, they frequently do not receive early DMARD treatment. In the adjusted model, female patients initiated DMARD therapy later than male patients, which is consistent with previous studies. A cohort study reported that female patients had a 6% lower rate of DMARD initiation [14]. Moreover, another study demonstrated that male patients had at least 11% higher odds of initiating DMARD ≤ 90 days than female patients [7]. Potential explanations include the under-recognition of inflammatory musculoskeletal symptoms, which are more likely to be attributed to nonspecific or chronic pain conditions [25], sex differences in referral patterns to rheumatological clinic disease assessment, and differences in disease assessment and treatment intensity [26]. Another potential explanation for the longer time to DMARD treatment initiation among female patients, particularly those of childbearing age, could include pregnancy planning, current pregnancy, or breastfeeding. However, these factors are not directly captured in the dataset and therefore cannot be confirmed, especially given that the majority of female patients in this cohort were middle-aged to older.

Although the literature has reported racial disparities in the use of DMARDs and access to rheumatologic care, evidence on the timing of first DMARD prescription is mixed. Several observational studies have reported that patients from racial and ethnic minority groups are less likely to receive DMARD therapy sooner after RA diagnosis. A recent systematic review that evaluated access to bDMARDs reported that Black and Asian races were associated with a lower likelihood of access [27]. Furthermore, in a retrospective observational study, the authors found that Black and Hispanic ethnicity were associated with lower rates of DMARD initiation in the first 12 months of diagnosis compared to white patients (27% and 24%, respectively). However, the latter study reported no significant difference in the adjusted model [23]. Likewise, another study reported that African American patients with RA were 30% less likely to receive DMARDs therapy than white patients in an adjusted model [28]. It is important to highlight that in RA clinical trials, white participants consistently dominate enrollment (up to 79%), while Black and Hispanic participants each represent a small minority, up to 4.7% and 10%, respectively [29]. In the fully adjusted Cox proportional hazards model, both Hispanic and non-Hispanic ethnicities had 12–15% slower DMARD initiation. American Indian/Alaskan Native patients showed a 30% higher likelihood of earlier initiation than white patients, whereas other racial groups showed insignificant time associations. This may be driven by the fact that in this study, the model was adjusted for a wide range of confounders, such as age group, sex, ethnicity, marital status, geographic region, comorbidity burden as measured by the age-adjusted Charlson Comorbidity Index, and DMARD drug class. Nevertheless, this highlights the need for targeted efforts to reduce disparities and ensure equitable access to timely RA management.

In this study, patients residing in the Northeastern and Southern regions of the USA were more likely to experience treatment delays than those in the Midwestern regions compared to those in the West (20% and 5% slower initiation, respectively). Several US studies have documented regional differences in the quality and accessibility of RA care, supporting the geographic variations observed in this study. A study that examined variations in DMARD receipt among Medicare and Medicaid beneficiaries from 2006 to 2009 found that the use of bDMARDs varied significantly across the USA., even after adjusting for patients’ characteristics. The authors reported that patients residing in the Middle and South Atlantic regions were less likely to receive biologic treatment, highlighting structural inequities in RA care of 7% and 11%, respectively [30]. Similarly, a cohort study based on the Truven Health Analytics MarketScan Commercial Claims and Encounters database and Medicare Supplemental and Coordination of Benefits database from 2008 to 2014 reported significant variations in the proportion of patients with RA who received DMARD therapy within a year of diagnosis across US regions [31]. However, unlike this study, those studies were limited to Medicaid and Medicare beneficiaries, had a smaller sample size, and shorter follow-up times. It is important to note that, the regional variation in DMARD initiation may, in part, reflect differences in pre-authorization requirements across the USA; however, the information on prior authorization process was not available in the current data and therefore could not be assessed.

Despite therapeutic advances and guideline recommendations emphasizing early intervention [4, 11], several barriers continue to delay the timely initiation of DMARDs. High out-of-pocket costs and insurance restrictions remain significant obstacles to equitable access [32]. Delays related to comorbidity management or provider caution may further limit access to early treatment, particularly in high-risk and underserved populations [24]. Addressing these challenges through health policy reforms, education, and improved access to rheumatology care is essential to achieve treat-to-target goals in all patient populations.

This study has several limitations. First, the observational design limits the ability to establish a causal relationship between patient characteristics and treatment initiation due to unmeasured confounding factors that may influence both clinical decisions and outcomes. Second, although EHR data offer valuable real-world insights, they are subject to coding inaccuracies, misclassification bias, and variability in data completeness. Third, certain contextual factors, such as socioeconomic status, insurance type and restrictions, pre-authorization requirements, referral delays, and provider specialty, were not consistently available; hence, the provider- and system-level determinants of DMARD therapy timing were limited.

The strengths of this study include its use of a large, diverse, and nationally representative real-world cohort of adults with RA and data captured over a decade. The large sample size and diversity of the study population enhanced the statistical power and generalizability, allowing for a robust assessment of treatment patterns and predictors of DMARD timing across demographic, geographical, and clinical subgroups. Furthermore, the inclusion of comprehensive demographic and clinical covariates, such as age, sex, race, ethnicity, regional location, and comorbidity burden, provided a better understanding of real-world prescribing practices. This enabled a more meaningful interpretation of the factors associated with the timing of DMARD initiation and contributed evidence that may inform guideline implementation and health policy.

Future studies should build on these results by looking beyond the timing of treatment to assess the clinical outcomes and safety profiles associated with different DMARD classes. As the therapeutic landscape continues to change, real-world comparative analyses of new DMARD classes, such as Janus kinase (JAK) inhibitors, against established biological agents, such as adalimumab, will be essential for evaluating their effectiveness, safety, and recommended sequence of use in everyday practice. Importantly, the increasing availability and affordability of JAK inhibitors, coupled with their oral administration and ease of access, may facilitate earlier treatment initiation, particularly in populations facing barriers to bDMARD therapies. Exploring whether early initiation of targeted therapy leads to better long-term outcomes will provide evidence and guidance for personalized, cost-effective, and timely management of RA.