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Shifting Trends in Initial RA Treatment Approaches

A recent study by Sparks et al (Abstract #0509) reveals evolving trends in disease-modifying antirheumatic drug (DMARD) usage for rheumatoid arthritis (RA) over two decades in the United States. 

This retrospective analysis evaluated 407,728 DMARD initiation episodes among 229,365 unique patients from 2001 to 2021. The patient population was predominantly female (79.7%) with median age 50 (IQR 44-58 years). Twenty-two individual DMARDs were grouped into categories of conventional synthetics (csDMARDs), biologics (bDMARD), and targeted synthetics (tsDMARDs). Secondary analyses included an examination of trends in the first-line use of non-csDMARDs and the uptake of biosimilars.

Over the study period, significant shifts in DMARD utilization were observed. 

Use of csDMARD declined considerably (79.7% to 54.7%; p <0.001), while there were significant increases in bDMARDs (20.3% to 33.1%; p<0.001) and tsDMARDs (0.1% in 2014 to 12.2%; p<0.001). Notably, methotrexate use decreased by almost half from 2001 to 2021 (29% to 15%, p<0.001), suggesting a gradual shift from this gold standard therapy. Interestingly, although biosimilars were introduced during the study period, their uptake remained consistently low, possibly reflecting limited clinician familiarity, patient acceptance or lack of incentive to shift from established biologics. Within tsDMARDs, tofacitinib use peaked in 2019 but usage halved by 2021 (8.9% to 4.4%), while  upadacitinib use increased from 1.2% to 7.6% during the same period (p< 0.001).

As the therapeutic armamentarium for RA expands, this study provides valuable insights into current and emerging trends in initial RA treatment. While csDMARD such as methotrexate remain the gold standard of initial therapy, this data indicates a decline in their use, as bDMARDs and tsDMARDs gain traction. These findings suggest that clinicians are embracing more advanced therapies earlier in the treatment algorithm in this evolving therapeutic landscape. These trends may reflect a shift toward a more nuanced decision-making process that considers patient-specific needs, including safety and treatment convenience. However, of concern, these practices lack a robust evidence base and do not align with international guidance statements.

Earlier initiation of bDMARDs and tsDMARDs will undoubtedly introduce new challenges for rheumatologists, including navigating cost, long-term safety concerns and management of treatment failure. That said, earlier initiation of bDMARDs and tsDMARDs may potentially offer enhanced patient outcomes, but evidence if needed. Additionally, while the therapeutic armamentarium for RA has expanded significantly over recent years, it remains finite. Increased reliance on advanced therapies earlier in treatment could exacerbate this limitation, highlighting the need for strategic, evidence-based use.

The low uptake of biosimilars during the study was also notable, suggesting that efforts to improve awareness, affordability, and clinician and patient confidence are necessary to enhance their cost-saving potential. The adoption of cost-efficient alternatives is particularly important in the context of the evolving treatment landscape.

Ultimately, these findings emphasize the need for rigorous studies to evaluate the impact of early bDMARD and tsDMARD adoption on long-term disease outcomes, safety, and healthcare costs. This will inform evidence-based treatment decisions. As the field evolves, innovation must be balanced with evidence, to ensure the best possible outcomes for patients.

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