Discussion
This retrospective cohort study of commercially insured patients demonstrated that NIU is associated with substantial clinical and economic burden, particularly when UME is present. UME was associated with increased vision loss and NIU-related treatment use compared with NIU alone. This clinical burden translated to higher costs associated with UME compared with NIU alone, which were highest among patients with bilateral disease and those with blindness. Taken together, these findings suggest an unmet need for appropriate and effective management, particularly when UME is present.
NIU, and particularly UME, are not well-characterised in the real-world setting. One retrospective analysis of claims data estimated an annual NIU prevalence of 121 cases per 100 000 adults in the US, however, the prevalence of complications such as UME were not assessed.1 Other claims-based studies of NIU have omitted assessment of UME or its impact on real-world outcomes.7 14 Further, epidemiological literature has reported a wide range in the prevalence of UME among patients with uveitis, ranging from 9% to 70% depending on anatomical location.5 Of note, the 9.1% prevalence of UME found in the current study is expected to be under-reported, since current reimbursement practices may not include regular coding of UME based on the lack of FDA-approved treatments to manage UME. Therefore, consistent with previous studies, the number of patients identified with UME in the current study likely represents a lower bound estimate of the potential true NIU population affected by UME.
To our knowledge, this is the first study to evaluate the economic burden of UME specifically in the commercially insured US population. Patients with UME incurred $19 851 PPPY in mean all-cause healthcare costs compared with $16 188 PPPY among patients with NIU without UME, which is consistent with two prior cost estimates of NIU among privately insured patients in the US.7 14 Thorne et al estimated total direct healthcare costs of $12 940 (2012 USD) during a 1-year study period for patients with intermediate or posterior NIU or panuveitis,7 which, when inflated to 2020 USD ($16 182), is very similar to the current estimate for the NIU population. In a separate study by Chu et al, total monthly healthcare costs totalled $1 144–$2 689 (ie, $13 728–$32 268 annually; 2009 USD) for patients with chronic NIU treated with corticosteroids, immunosuppressants or biologicals.14 These costs are higher than the current estimates likely due to the fact that Chu et al focused only on treated patients. Of note, neither of these studies identified the proportion of patients with UME in their populations, which limits comparability with the current study. Based on the literature, the annual healthcare costs of UME observed in this study are within the range of or higher than those of other eye conditions, including DME ($11 290–$29 959 depending on insurance coverage),15 16 RVO ($3 285–$11 587 depending on type and insurance coverage)17 18 and macular degeneration ($334–$4 030 depending on type and treatment),19 emphasising the importance of the large economic burden of UME in the US.
The high healthcare costs observed in this study may have been driven by several factors, including the high frequency of bilateral disease among patients with UME (27.4%), especially among the subgroup with UME and LSI during the study period (50.1%). Indeed, bilateral disease was associated with the highest costs PPPY ($24 162) compared with unilateral ($17 361) or unspecified disease ($19 160). Additionally, increasing vision loss resulted in progressively higher medical costs, ranging from $11 054 among patients with no indicator of visual loss to $53 767 among those with blindness. Not only does vision loss result in substantial medical costs, it also negatively affects quality of life,20 21 increases the risk of physical and mental health comorbidities (eg, depression, stroke, premature death),22 and decreases work productivity,23 all of which contribute to the large burden of eye conditions like UME.
Pharmacy costs were also a driver of the high costs associated with UME, reflecting the increased rate of treatment among patients with UME compared with those with NIU without UME (64.6% vs 45.0%). Of note, from a clinical standpoint, all patients with active UME or NIU would be expected to be treated, however, treatment rates were measured among a representative sample of patients with UME or NIU at any time, which included both patients with active and resolved disease during the study period, who may or may not require treatment. The high rates of NIU treatment in addition to increased medical costs among patients with UME suggests a potential unmet need for targeted management of the condition in this patient population. Indeed, guidelines for the treatment of UME currently do not exist, and within existing guidelines for NIU, there is limited guidance regarding the management of UME.24 25 This observation reveals a lack of differentiation of UME in coding as a distinct entity by eye specialists, possibly due to the fact that no UME treatment is currently FDA-approved. Additionally, there is evidence that current NIU treatment options are suboptimal for UME. In a retrospective analysis of patients with UME from tertiary academic ocular inflammation centres in the US, the rate of improvement of UME-induced visual impairment was only 41% after 3 months of care, and nearly 50% of patients were still experiencing decreased visual acuity after 6 months despite treatment per best medical judgement at the time of the study period (1978–2007).26 Moreover, current systemic NIU treatment options are associated with systemic adverse events like diabetes, osteoporosis and hypertension, while local treatments are associated with a high risk of ocular complications (eg, cataracts, increased ocular pressure, glaucoma),2 27 which may further contribute to clinical burden and costs. Of note, a cross-sectional study of patients with NIU found that treatment with oral corticosteroids or immunosuppressants was associated with worse quality of life, emphasising the far-reaching clinical implications of these therapies.9 Taken together, these findings highlight the limitations of current treatment options for UME (none of which are approved by the FDA) and the need for more effective and safe therapies that specifically target UME and that may help to alleviate the associated clinical and economic burden.
Limitations
The findings of this study should be interpreted in the context of some limitations. Indicators of vision loss may be under-reported in claims data; however, it was assumed that these indicators were missing at random. Similarly, as there are currently no treatments approved for UME, recorded diagnoses of UME were expected to be under-reported in claims data; however, it was assumed that recorded UME diagnoses were missing at random. Due to the expected under-reporting of UME in claims data, it is possible that some patients with UME were classified in the NIU without UME cohort as it was not possible to identify these patients in the absence of a recorded UME diagnosis. This may have led to an underestimation of the cost difference observed between patients with and without UME found in this study. In addition, this analysis reflected the burden of NIU and UME from October 2015 to March 2020, which may change as the treatment landscape evolves. Further, since this study was conducted in a commercially insured population, the results may not be generalisable to those with other types of insurance (eg, Medicare, Medicaid) or no insurance coverage. Finally, as with all claims-based studies, there may have been billing inaccuracies or omissions in coded procedures, diagnoses and pharmacy claims.