Clinical and economic burden of idiopathic pulmonary fibrosis: a retrospective cohort study

Idiopathic pulmonary fibrosis (IPF) is a chronic disease in which normal lung parenchyma is replaced with fibrotic tissue, leading to dyspnea, cough and impaired lung function [1]. IPF predominantly occurs in older adults [1] and the progressive nature of the disease results in a median survival time of approximately 3 years from diagnosis [2, 3]. Commonly reported comorbid conditions among IPF patients include pulmonary hypertension, gastroesophageal reflux disease, obesity, emphysema, cardiovascular conditions and obstructive sleep apnea [4, 5]. IPF itself and these common comorbidities significantly impair health-related quality of life among patients [6] and impose a substantial burden on health care resources [5].

Although data are limited, compared with patients without IPF, those with IPF require greater health care resource utilization, have a greater number of comorbidities [7, 8] and generate higher direct medical costs [7]. Consensus guidelines recommend lung transplantation and long-term oxygen as potential therapies for IPF [4]—both are costly treatments. The FDA recently approved pirfenidone and nintedanib for the treatment of IPF; how these therapies affect resource utilization and cost in a real-world setting is yet to be determined [9, 10].

IPF incidence rate and prevalence estimates vary across studies because of differences in design and data sources [11, 12]. The prevalence of IPF ranges from 0.7 – 6.4 per 100,000 individuals in Taiwan to 27.9–63.0 per 100,000 in the USA, while incidence has been reported as 0.6–1.4 and 8.8–17.4 per 100,000 person-years, in Taiwan and the USA, respectively [13]. Because the incidence and prevalence of IPF is greater among older citizens, with the US population aging [12–14], it is expected that the economic burden and health care resource utilization of IPF will likely increase in the foreseeable future. Thus, there is a desperate need for improved understanding of the burden of IPF on health care systems. In this study, we used a commercial insurance claims database to characterize the economic burden of IPF by investigating health care resource utilization and costs associated with patient management.

IPF is a severe, chronic condition that primarily affects patients older than 60 years of age, who often have other comorbidities and who require substantial health care resources. In this study, we used a large, de-identified insurance claims database to identify three annual cohorts of IPF patients. The heightened presence of chronic conditions and comorbidities in the population was reflected in the 10-year Charlson Comorbidity Index score of 3.2. Overall, IPF patients were found to be frequent health care service users, with nearly 19 outpatient visits per year. More than one-third of patients were hospitalized—and approximately 30 % visited the ED—at least once per year. During that time period, the provision of inpatient and outpatient care amounted to a total annual cost of approximately $60,000 per patient, with about one-third of this spent on respiratory-related care.

A high level of variability exists in epidemiologic reports of incidence and prevalence in IPF, most likely due to differences in diagnostic testing and case definition, as well as differences in study populations and study design [4, 5, 11]. However, it is generally agreed that prevalence is increasing due to the aging of the population and improved awareness and earlier diagnosis of the condition [13, 14]. In a recent review of 15 studies investigating IPF prevalence in the USA, the authors reported values from 14 to 27.9 cases per 100,000 population [16]. Other data confirm a higher prevalence among patients aged 75 years or older (67.4 per 100,000 persons) compared with people in the 18–34-year age range (0.8 per 100,000 persons) [12]. In our study, overall prevalence ranged from 19.8 to 28.8 per 100,000 insured persons and was lowest in 2011; when data were analyzed over the 5-year age group, prevalence was highest in patients aged 80 years or over (165.9–185.5 per 100,000 insured persons).

However, health care utilization and costs were similar across all 3 years. An increase in the total number of insured people (from 4.1 million in 2009 to 5.7 million in 2011)—the denominator—is likely to have contributed to the lower prevalence of IPF in 2011, since the numbers of IPF patients (the numerator) were similar over the 3-year period. In fact, the higher number of insured people in 2011 was composed of a large number of individuals from the youngest age group (unlikely to have IPF). The number of those aged between 12 and 44 years differed from 1.7 and 1.9 million in 2009 and 2010, to 2.5 million in 2011. Data from the Centers of Disease Control and Progression support our observation, and show that the proportion of uninsured adults aged 19–25 years fell from 35.6 % in the third quarter of 2010 to 27.0 % in the fourth quarter of 2012 [17]. In addition, an analysis of IPF in US Medicare beneficiaries aged 65 years or above between the years 2000–2011 revealed that the incidence of IPF remained stable (overall estimate 93.7 cases per 100,000 person-years), while the prevalence increased from 202.2 to 494.5 cases per 100,000 person-years over this period [18].

The prevalence of IPF is usually reported as higher among males [19–21]; however, we observed no difference by gender. This is possibly due to more women accessing care, but we are unable to verify this supposition. In general, women are more likely to seek health care services than men [22–24], and women are more willing to look after themselves [23]. As in previously published studies, in which IPF prevalence has been reported to increase with age (and the highest rates observed in patients over 75 years old) [16], we observed an increase in IPF prevalence with age in this claims database, with a notable rise in those older than 65 years. We observed that most cases (39.7–42.3 %) derived from the southern area of the USA, a finding that reflects other real-world health care experiences. For example, data from Optum Payer lists, covering over 150 million individuals across all payer types, reveal that 33–46 % of claims are from the Southern area of the US, approximately double those coming from the West, Midwest, and Northeast states [25]. Given the consistency of these observations, we suggest that this phenomenon is likely due to distribution of the source population rather than regional differences in disease prevalence.

Few previous studies have reported on the economic burden of IPF. Most recently, Wu et al. [8] found that IPF patients were more likely to use health care resources than non-IPF patients (number of hospitalizations 0.63 vs. 0.31, emergency room visits 0.62 vs. 0.48 and outpatient visits 5.7 vs. 3.1 per person-year). Similarly, Collard et al. [7] reported that the all-cause hospital admission rate (0.5 per person-year) and outpatient visit rate (28.0 per person-year) for IPF patients were both nearly two-fold higher than in controls. Total direct costs for patients with IPF were approximately $26,000 per person-year. Differences in case-finding and expense-inclusion likely account for differences in cost between that and our study [16]. Rather than limiting expenses to those incurred for IPF alone, to help reflect the true cost of care for these patients, we included costs and health care utilization for any cause and, for other analyses, for any respiratory-related condition (including IPF, bronchitis, pneumonia, etc.). These data reflect actual patient care rather than a clinical trial situation. In clinical practice, patients are often given other diagnoses (e.g. myocardial ischemia, asthma, chronic obstructive pulmonary disease [COPD], obesity, ILD) and are evaluated by more than two practitioners before ultimately being correctly diagnosed with IPF. Some patients in our study may have been initially diagnosed with a condition other than IPF and had the diagnosis changed to IPF after additional evaluation.

Database analyses come with inherent limitations, and use of secondary data, without direct involvement of the patient or physician, may decrease confidence in the conclusions drawn [26, 27]. Insurance claims data depend on professional ICD coding, and, given the complexity of the disease process, it must be recognized that accurate diagnosis of IPF can be challenging [27, 28]. In the clinical setting, some cases may be misdiagnosed, and coding patterns may vary between professionals. In this study, the physician specialty for IPF care was pulmonologist in approximately 50 % of patients, and the other half were seen by a primary health care physician or a physician whose specialty was not recorded, for most of their IPF care visits. It is indeed likely that some patients whose practitioners were recorded as unknown may actually have seen a pulmonologist. Guidelines recommend high-resolution computed tomography (HRCT) of the lungs and/or surgical lung biopsy to diagnose IPF [4]. In this study, the lower than expected number of patients with a diagnostic test is a reflection of the cross-sectional study design; it is likely that patients had a HRCT scan conducted at the time of their diagnosis (e.g. diagnosed with IPF prior to 2009), but this may have been outside the study period.

Furthermore, approximately 50 % of IPF patients also had a diagnosis of COPD, including emphysema; whether these were incorrect diagnoses in patients who previously smoked (but did not have COPD) or correctly coded comorbid conditions cannot be determined from the available data. To help reduce the effect of coding inconsistencies, data on all-cause and respiratory-related conditions were considered. This included individuals with at least 1 inpatient claim or two outpatient claims with IPF as one of the diagnosis codes, in hopes of capturing all patients with IPF, including those who may have been misdiagnosed. To limit miscoding, patients who had a non-IPF ILD claim after the last IPF claim in that calendar year were excluded from the analysis. Similar criteria have been used in previous studies [7, 8, 18].

Because the ICD-9 code for IPF changed from 516.3 to 516.31 in 2012, the current analysis was limited to 2009–2011 to further limit possible coding errors. Other limitations include the cross-sectional study design and the fact that patients were not required to have IPF for the entire calendar year; thus, given that some patients may only have started to incur costs later in the year, the total economic burden of disease may be underestimated. A cross-sectional view of patients with IPF offers a true-to-life picture of what might be expected in any given year in which some patients are diagnosed early and others later in the year.

IPF presents a large burden on health care utilization resources. Additional research is needed to determine whether and how this burden might be reduced.