Patient Demographics and Characteristics
In total, 675 patients met the inclusion criteria (Fig. 1). Demographics, patient and clinical characteristics—including comorbidities—overall and by clinical and diagnosis subgroups, are presented in Table 1. The mean [standard deviation (SD)] age was 62 (17) years; 79% of the population were women. Most patients were white (85%) and lived in the south of England (65%), and half (50%) were overweight (body mass index > 25 kg/m2).
Comorbidities and manifestations of SSc were frequent in the overall population (Table 1). Raynaud’s phenomenon was recorded in 58% of patients. Gastroesophageal reflux disease (GERD) was recorded in 48% of patients, and anemia was recorded in 28%. Most patients (60%) were hospitalized at least once in the year before diagnosis. Only 16% of patients had a computed tomography (CT) scan at diagnosis.
Clinical Subgroup Analysis
Within the overall patient population, 127 patients (19%) were included in the SSc-ILD subgroup and 477 (71%) in the SSc-OOI subgroup (Table 1). The SSc-ILD-OOI subgroup contained 103 patients (15%). Patients with both ILD and OOI comprised 81% of the SSc-ILD subgroup and 22% of the SSc-OOI subgroup. Of 675 patients with SSc, 174 (26%) had neither ILD nor OOI.
GERD was reported more frequently in patients with SSc-ILD or SSc-OOI than in the overall population of patients with SSc. PAH was more common in patients with SSc-ILD than in patients with SSc or SSc-OOI. A higher proportion of the SSc-ILD subgroup presented with Raynaud’s phenomenon compared with the overall SSc population and the SSc-OOI subgroup (Table 1).
Diagnosis Subgroup Analysis
Of all patients (N = 675) diagnosed with SSc, 485 (72%) had their diagnosis recorded in primary care, 264 (39%) had their diagnosis recorded in secondary care, and 74 (11%) had their diagnosis recorded in both (Table 1). A smaller proportion of patients in the primary setting subgroup were hospitalized in the year prior to diagnosis (n = 213, 44%), compared with the secondary (n = 257, 97%) and both settings (n = 68, 92%) subgroups.
In the primary and secondary setting subgroups, the most commonly reported comorbidities were Raynaud’s phenomenon, GERD, and anemia. In the both settings subgroup, Raynaud’s phenomenon, GERD, and PAH were the most commonly reported comorbidities.
Pharmacotherapies Prescribed in Primary Care
Similar proportions of patients in each subgroup were prescribed pharmacotherapies (by treatment type), in both the clinical and diagnosis subgroup analyses (Table 2). In the 90 days prior to diagnosis, 345 patients (51%) did not receive pharmacotherapy in primary care. Glucocorticoids and calcium channel blockers were the most commonly prescribed pharmacotherapies, both before and after SSc diagnosis. In the 12 months after recorded diagnosis, 41% of patients were prescribed glucocorticoids. All types of glucocorticoids were prescribed more frequently after diagnosis, compared with before (Supplementary Table S3). In contrast, the recorded use of mycophenolate mofetil following SSc diagnosis was low (fewer than 5 patients in total).
Healthcare Resource Utilization
The rate of healthcare resource usage (GP visits, outpatient and inpatient stays, A&E attendances) among patients with SSc-ILD, OOI, or both was consistently higher than in patients with only SSc (Table 3). Patients with SSc-ILD and SSc-ILD-OOI had the highest rates of inpatient stays (2.7 and 2.8, respectively), outpatient visits (9.5 and 9.7), A&E attendances (0.8 and 0.8), and GP visits (16.2 and 16.9) per person-year.
Patients with a recorded diagnosis in secondary care, or secondary and primary care had higher HCRU rates than patients with a diagnosis in primary care.
Age-weighted median [interquartile range (IQR)] healthcare costs per patient-year in the clinical subgroup analysis were higher for patients with SSc-ILD [£6375 (£3451–£15,041)] or SSc-ILD and OOI [£6632 (£4023–£17,009)] than for patients with SSc-OOI [£4084 (£1454–£10,105)] or SSc only [£1496 (£664–£2817)] (Fig. 2a). Results were similar for crude data.
Each patient with SSc-ILD had, on average, 10 outpatient visits per year, at a total yearly median cost of £813. In comparison, patients with SSc-OOI averaged seven outpatient visits at a total yearly median cost of £608 (Tables S4 and S5).
Results of sensitivity analyses showed that healthcare costs were consistently the highest for patients with SSc-ILD (with or without OOI), after excluding patients with cardiovascular disease (CVD; defined as angina, AF, and CHD) (Fig. 2b), as well as among patients who died during follow-up (Fig. 2c) and those with anemia (Fig. 2d). Overall, median age-weighted healthcare costs were higher in patients with CVD [£5507 (£1660–£14,886)], anemia [£5915 (£2368–£14,259)], and in those who died [£9751 (£4550–£26,645)] compared with patients who did not have CVD [£2874 (£1060–£7316)], anemia [£2321 (£888–£6447)], or did not die [£2068 (£936–£5201)] (Fig. 2).
An investigation into potential predictors of total healthcare costs in the overall population, using a multivariate generalized linear model, showed a significant association between costs and older age at diagnosis, a diagnosis of anemia, and the total number of comorbidities based on incremental increases in the Charslon Comorbidity index (all p < 0.0001).
Inpatient Stays and Costs
Inpatient stays were the main contributor to healthcare costs in the entire cohort of patients with SSc [median (IQR)], £1627 (£109–6023); Table S5] and across all clinical subgroups except for the SSc-only subgroup, in which outpatient stays were the major cost contributor. This was true for patients with CVD and SSc, and patients with SSc only. In patients with age-weighted annual costs of ≥ £15,000 (n = 77), inpatient stays were still the main contributor to overall cost, including in patients (n = 6) with SSc only (Table S5E). Of all 790 inpatient attendances, 414 (52%) were day admissions, 287 (36%) were non-elective admissions, and 89 (11%) were ordinary elective admissions (pre-planned with a duration of more than 1 day). The proportions of the different admission types were consistent across all clinical subgroups (data not shown).
The median length of inpatient stay was less than 1 day, indicating that most patients who were hospitalized left the same day (Table 4). This was consistent across diagnostic and clinical subgroups. The median duration of elective stays was 5 days (IQR 3–7), as was the median duration of non-elective stays (IQR 3–11). These findings were also consistent across all clinical subgroups (data not shown). Based on grouping of attendances according to HRG subchapter codes, the main drivers of inpatient costs appeared to be related to connective tissue disorders (23%), the respiratory system (13%), cardiac surgery and primary cardiac conditions (13%), the digestive system (10%), and the vascular system (7%).