The US Merative™ MarketScan® insurance claims database has been extensively used in previous real-world studies in patients with rheumatologic diseases [21,22,23], including axSpA [24,25,26,27], to explore various research questions, for example involving treatment patterns, HCRU utilization, and comorbidities. This observational, retrospective study using US Merative™ MarketScan® insurance claims data of more than 97,000 individuals with axSpA and an initial back pain diagnosis over a 15-year period provides insights into the significant challenge of delayed diagnosis of axSpA in the US, while also corroborating established literature.

Diagnostic delay remains a key challenge for patients with axSpA in the US. In this study, the mean (SD) time to diagnosis was 4.5 (2.8) years and 29.0% of patients had a total time to diagnosis ≥ 6 years. Patients underwent numerous consultations for back pain throughout the pre-diagnostic patient journey; 55.9% of patients had more than ten back pain consultations in total, throughout their diagnostic journey. On average, patients in this study saw 4.6 HCPs per year and 20.7 HCPs overall for back pain-related outpatient visits, which is similar to the global average of three HCPs per year as reported in a survey by the International Map of Axial Spondyloarthritis (IMAS) initiative [10]. These findings corroborate the results in existing literature that patients with axSpA in the US tend to see several HCPs for back pain prior to diagnosis [12]. This study also demonstrated that the burden of diagnostic delay is substantial and that associated costs are high. The results presented here are unlikely to have been influenced by selection bias due to the 5-year minimum look-back period, as demonstrated by the sensitivity analysis results. Despite the change in patient numbers, there were no significant differences between the main cohort with a minimum of 5 years of continuous data and the two cohorts in the sensitivity analysis.

The average patient-reported time to diagnosis in a recent survey of patients with axSpA in the US was 8.8 years [10], and an IMAS survey reported a global mean delay of 7.4 years (9.0 years in North America) [28], compared with 4.5 years reported in this study. The average time to diagnosis observed in this study was likely shorter than that reported in the patient surveys, as claims data capture the time from initial back pain diagnosis to axSpA diagnosis to compose the patient diagnostic journey, while surveys reflect time from symptom onset and may be prone to patient recall bias. A previous study using MarketScan® data reported that median time from back pain diagnosis to rheumatology referral was less than 1 year [7], which is significantly shorter than the durations reported in the current study. However, the inclusion and exclusion criteria and back pain codes applied to that study were not comparable to the current study, limiting the comparisons that may be drawn.

A large number of patients were diagnosed by HCPs other than rheumatologists in this study. Only 10.1% of patients consulted a rheumatologist during their diagnostic journey; among these patients, average secondary delay, defined as the time from the first rheumatology visit to axSpA diagnosis, was 1.7 years. In contrast, previous global studies have reported rheumatologists to be the most common diagnosing physicians [10, 29]. Patients with back pain in the US commonly receive care from providers other than rheumatologists; these providers may be unfamiliar with differentiating axSpA from other common causes of back pain. For this reason, misdiagnosis of axSpA may be common in a substantial proportion of patients in the US. Primary care providers are often considered to be the “gatekeepers” for patients with back pain and can play a crucial role in increasing referrals to rheumatologists for suspected axSpA. These findings highlight the need for improved referral pathways to rheumatology, clearer diagnostic pipelines, and improved awareness and recognition of axSpA within the field [17]. Awareness of the signs and symptoms of axSpA is not only required among primary care providers, but also with physiotherapists, chiropractors, and orthopedic surgeons who also see these patients.

The disease burden of axSpA is worsened by the delayed diagnosis of the disease, necessitating multiple specialist visits, diagnostic tests and procedures, and pharmacy prescriptions. Over two-thirds of patients studied here were prescribed opioids, over half were prescribed steroids, and close to half were prescribed antidepressants and anxiolytics between the time from the earliest back pain diagnosis to axSpA diagnosis. The use of steroids and opioids is not recommended in axSpA [30], and these data therefore suggest that patients may have experienced suboptimal treatment and management of their symptoms due to the lack of a prompt axSpA diagnosis. It should be noted, however, that these data are based on all-cause (not back pain-related) pharmacy claims.

With regards to costs and HCRU, the majority of existing literature focuses on employment and work disability experienced by patients with axSpA. While delayed diagnosis of axSpA generally results in increased HCRU, there is limited data available to explore this phenomenon in the US [31, 32]. In the absence of a control group, the current study is unable to draw conclusions regarding the association of longer time to diagnosis with higher costs. Earlier diagnosis might be more cost-effective, but it may be offset by additional higher post-diagnosis costs due to costly treatment regimens.

Previous studies investigating the factors associated with time to diagnosis have reported that delays may be influenced by a lack of clear diagnostic criteria and difficulty distinguishing inflammatory back pain, a useful screening tool for axSpA, which enables the distinction from other forms of chronic back pain [17]. Women, patients with younger age at onset of symptoms, patients with a negative HLA-B27 status, and patients with certain peripheral or extra-musculoskeletal manifestations, such as psoriasis, have also been observed to experience a longer time to diagnosis [9, 33,34,35]. Identifying the patient characteristics that may be associated with time to diagnosis warrants further study, for example, through multivariate regression analyses, as this could provide targets for the improvement of the patient diagnostic journey for patients at risk of diagnostic delay. Of note, in this study, women were found to have a significantly longer diagnostic delay than men. This aligns with previous research, which shows that, despite women reporting higher disease activity and significantly greater pain and functional limitation with axSpA, they experience longer diagnostic delay than men with axSpA [36]. Factors affecting this may include differences in early presentation, as women are less often HLA-B27-positive, and more often have nr-axSpA without visible radiographic abnormalities, requiring additional imaging for diagnosis [1, 37]. Further research is crucial to understand the factors leading to the sex differences observed in time to diagnosis and to identify targets for the improvement of the patient diagnostic journey for women with axSpA.

There are some key strengths of this study that should be noted. This study utilized a large patient cohort, and relied on claims data rather than subjective patient-reported data. A sensitivity analysis was conducted to assess the robustness of the main analysis and the criteria applied for inclusion of patients, to determine any potential selection bias that might have been introduced due to the requirement of a minimum of 5 years of continuous medical and pharmacy coverage. Another strength was that patients with axSpA in this study were mostly comparable to those in published literature, although patients in this study were older on average at back pain diagnosis and axSpA diagnosis, which may limit generalizability [7, 10]. The average age of patient-reported symptom onset obtained from a previous survey in US patients was 26.4 years [10], which is considerably lower than the 48.8 years reported in this study, likely as a result of the differing methods employed to ascertain onset of back pain (diagnostic codes versus direct survey).

Limitations of this study include the fact that it assessed time from the earliest back pain diagnosis to axSpA diagnosis, rather than earliest back pain onset to axSpA diagnosis, hence time to diagnosis may have been underestimated. Patients may not seek healthcare immediately upon developing back pain, which may further contribute to this underestimation [38]. Additionally, the focus of this study is back pain symptom duration, and therefore patients with axSpA who presented with symptoms other than back pain may have been excluded. The impact of this limitation would be expected to be low, however, given that chronic back pain is one of the most common symptoms of axSpA [39]. Patients whose initial back pain was not definable and those without a back pain diagnosis code within the look-back period were excluded, which may have contributed to the underestimation of time to diagnosis as these patients’ back pain may have started years earlier. The analysis also excluded patients who were diagnosed with back pain during the look-back period but did not meet other inclusion criteria, also potentially contributing to the underestimation of the time to diagnosis. This study also makes no distinction between nr-axSpA and r-axSpA to assess differences in the time to diagnosis and the patient diagnostic journey; of note, differences have been reported in time to diagnosis between the two [8]. Furthermore, due to the use of claims data, this study cannot provide certainty on whether the earliest diagnosis or onset of back pain was recorded and reported in the database, which is a standard limitation of claims data. Long-term trends regarding the change in time to diagnosis over time are also not evaluated in this study. Claims data also do not capture the use of over-the-counter (OTC) medication, which may lead to an underestimation of NSAID use, for example, as some are available OTC. Potential regional influences on these findings were not explored, in part because there were no a priori reasons for differences by US region. The contributions of race, ethnicity, and other social determinants of health to time to diagnosis and access to care, which have previously been shown to have a considerable impact, were also not assessed in this analysis due to limited data availability [40,41,42]. Lastly, as the majority of patients were diagnosed by an HCP other than a rheumatologist, there may be a greater potential for diagnostic misclassification, which may affect the accuracy of the findings.