Healthcare utilization and cost of systemic lupus erythematosus in a US managed care health plan

Figures & data

Figure 1. Study design.

Table 1. Algorithms for assigning patients to categories for disease severity and flare severity.

Algorithm for determining SLE disease severity

Mild disease

Did not meet the criteria for moderate or severe disease.

Patients who died and had less than 1 month (30 days) of enrollment in the time period (follow-up, year 1, or year 2) were classified as having died with short enrollment rather than being assigned an SLE disease severity level.

Moderate disease

• Had no filled prescriptions for cyclophosphamide or rituximab or oral corticosteroid with ≥60 mg/day of prednisone equivalent dose and no claims with a diagnosis of a ‘severe’ condition; AND

• Met one or both of the following any time during the follow-up period:

• Had ≥1 non-laboratory claims with a diagnosis of a condition listed as ‘moderate ‘, where the diagnosis occurs in any position on the claim; OR

• Had ≥1 filled prescription for an oral corticosteroid with a prednisone-equivalent dose of ≥7.5 mg/day and <60 mg/day or for an immunosuppressive agent (other than cyclophosphamide).

Moderate conditions: acute pancreatitis, chorioretinitis, demyelinating syndrome/acute inflammatory demyelinating polyradiculoneuropathy, episcleritis/scleritis, hemolytic anemia, hepatitis (non-viral), ischemic necrosis of bone, nephritis, renal impairment other than nephritis or end stage renal disease, lupus enterititis/colitis, mononeuropathy/polyneuropathy, myelopathy, myocarditis, pericarditis, pleurisy/pleural effusion, pseudotumor cerebri, seizure, uveitis vasculitis (excluding aortitis)

Severe disease

• Had ≥1 filled prescriptions for cyclophosphamide or rituximab or oral corticosteroid with a prednisone equivalent dose of ≥60 mg/day; OR

• Had ≥1 non-laboratory claims with a diagnosis listed as ‘severe’, where the diagnosis occurs in any position on the claim.

Severe conditions: acute confusional state/psychosis, aortitis, arterial/venous thrombosis, aseptic meningitis, cardiac tamponade, cranial neuropathy, intestinal pseudo-obstruction, end stage renal disease, optic neuritis, pulmonary hemorrhage, stroke/TIA.

Algorithm for determining SLE flare severity

Mild flare

Initiation of any of the following:

• hydroxychloroquine or another anti-malarial,

• an oral corticosteroid with prednisone-equivalent dose of ≤7.5 mg/day

• non-immunosuppressive therapy (NSAIDS, androgens).

Treatment was considered to be ‘initiated’ if there were no filled prescriptions for that class of medication in the 60 days prior to the medication fill.

Length of flare: 30 days. However, if a flare of higher severity (moderate or severe) occurs during that 30 days, the length of the flare was limited to the time between the start of the mild flare and the start of the higher-severity flare.

Moderate flare

a. Initiation of any of the following:

• an oral corticosteroid with prednisone-equivalent dose >7.5 mg/day but ≤40 mg/day,

• immunosuppressive therapy, with the exception of cyclophosphamide.

Treatment was considered to be ‘initiated’ if there were no filled prescriptions for that class of medication in the 60 days prior to the medication fill. For oral corticosteroids, if the patient had a prior fill within 60 days, treatment was considered initiated if the prior fill was for a prednisone-equivalent dose less than or equal to 7.5 mg/day.

OR

b. A claim for an emergency room visit with a primary diagnosis of SLE (710.0x) with no inpatient admission within 1 day;

OR

c. A claim for an emergency room or office visit with a primary or secondary diagnosis for a specified SLE-related condition. If the diagnosis occurred during an office visit, the condition was required to be new, defined as no claims with this diagnosis during the previous 60 days. If the condition occurred in an emergency room visit, no inpatient admission within 1 day following the emergency room visit was allowed.

Length of flare: 30 days. However, if a severe flare occurred during that 30 days, the length of the flare was limited to the time between the start of the moderate flare and the start of the higher-severity flare. If the flare was initiated by a hospitalization, or a hospitalization occurred during the middle of the flare, and the hospitalization lasts beyond the 30 days, the length of the flare was still set at 30 days.

Severe flare

a. Initiation of any of the following:

• an oral corticosteroid with prednisone-equivalent dose >40 mg/day,

• cyclophosphamide.

For corticosteroids, if the patient had a prior fill within 60 days, treatment was considered initiated if the prior fill was for a dose less than or equal to 40 mg/day. For cyclophosphamide, each prescription was counted as a new prescription if the prior fill or administration was more than 100 days earlier;

OR

b. Admission for an inpatient hospital stay with a primary diagnosis of SLE (710.0x);

OR

c. Admission for an inpatient hospital stay with a primary diagnosis for a specified SLE-related condition.

For flares based upon a hospitalization, the start date of the flare was the date that the patient was admitted to the hospital, unless the patient was admitted to the emergency room (with any diagnosis) during the previous day; if patients had an emergency room admission the day prior to the hospitalization, the date of the emergency room admission was considered to be the start date of the flare. Note that only visits to an emergency room site were considered under this definition; visits to urgent care or outpatient clinics were not included.

Length of flare: 30 days.

For flares, specified SLE-related conditions included the conditions listed for the disease severity algorithm, plus the following conditions: arthritis/arthralgia, dry eye/tear film insufficiency, rash, low white blood cell count (leukopenia, neutropenia, lymphocytopenia), lymph node enlargement, myalgia/myositis, urticarial.

Figure 2. Derivation of the study cohort.

Table 2. Demographics and comorbidities of patient sample.

	Total (n = 2990)	Disease severity sub-group
		Mild (n = 789)	Moderate (n = 1558)	Severe (n = 643)
Demographics, n (%)
Male	253 (8.5)	58 (7.4)	131 (8.4)	64 (10.0)
Age
18–44	1469 (49.1)	392 (49.7)	766 (49.2)	311 (48.4)
45–64	1521 (50.9)	397 (50.3)	792 (50.8)	332 (51.6)
Region
Northeast	242 (8.1)	65 (8.2)	123 (7.9)	54 (8.4)
Midwest	711 (23.8)	200 (25.4)	350 (22.5)	161 (25.0)
South	1572 (52.6)	404 (51.2)	845 (54.2)	323 (50.2)
West	465 (15.6)	120 (15.2)	240 (15.4)	105 (16.3)
SLE-related comorbid conditions at baseline,* n (%)
Nephritis	228 (7.6)	10 (1.3)	134 (8.6)	84 (13.1)
Mononeuropathy/polyneuropathy	205 (6.9)	24 (3.0)	118 (7.6)	63 (9.8)
Other renal impairment	187 (6.3)	5 (0.6)	85 (5.5)	97 (15.1)
Lupus enteritis/colitis	117 (3.9)	18 (2.3)	62 (4.0)	37 (5.8)
Seizure	96 (3.2)	10 (1.3)	39 (2.5)	47 (7.3)
Pleurisy/pleural effusion	91 (3.0)	7 (0.9)	45 (2.9)	39 (6.1)
Arterial/venous thrombosis	87 (2.9)	9 (1.1)	18 (1.2)	60 (9.3)
Aortitis	80 (2.7)	8 (1.0)	23 (1.5)	49 (7.6)
Stroke/transient ischemic attack	63 (2.1)	3 (0.4)	22 (1.4)	38 (5.9)
Nephrotic syndrome	61 (2.0)	2 (0.3)	33 (2.1)	26 (4.0)

*SLE-related conditions found in ≥2% of patients in the cohort as a whole or in any severity sub-group are listed.

Table 3. Healthcare utilization and costs^a during the 2-year follow-up period.

	Total (n = 2990)	Sub-group
		Mild (n = 789)	Moderate (n = 1558)	Severe (n = 643)
Healthcare services
Inpatient stays
≥1 stay, n (%)*	790 (26.4)	83 (10.5)	369 (23.7)	338 (52.6)
Mean (SD) number stays*	0.5 (1.2)	0.1 (0.4)	0.4 (0.9)	1.3 (2.0)
Mean (SD) cost, $/patient*	9248 (36,222)	1643 (7982)	5479 (18,376)	27,712 (69,023)
Office visits
≥1 visit, n (%)*	2982 (99.7)	782 (99.1)	1557 (99.9)	643 (100)
Mean (SD) number visits*	31.4 (25.0)	21.2 (17.4)	31.4 (23.0)	44.1 (31.1)
Mean (SD) cost, $/patient*	4660 (8787)	2688 (4771)	4299 (7431)	7954 (13,470)
Outpatient hospital visits
≥1 visit, n (%)*	2271 (76.0)	487 (61.7)	1206 (77.4)	578 (89.9)
Mean (SD) number visits *	6.6 (12.2)	2.9 (4.5)	5.6 (7.9)	13.5 (21.3)
Mean (SD) cost, $/patient*	7632 (37,101)	2343 (5358)	4428 (8590)	21,886 (77,017)
Emergency room visits
≥1 visit, n (%)*	1363 (45.6)	223 (28.3)	721 (46.3)	419 (65.2)
Mean (SD) number visits *	1.9 (5.5)	1.3 (4.7)	1.9 (5.8)	2.9 (5.5)
Mean (SD) cost, $/patient*	427 (1507)	173 (565)	363 (911)	894 (2805)
Laboratory services
≥1 service, n (%)*	2976 (99.5)	777 (98.5)	1556 (99.9)	643 (100)
Mean (SD) number services*	24.6 (19.4)	15.1 (10.8)	24.1 (16.4)	37.5 (26.1)
Mean (SD) cost, $/patient*	3411 (4676)	2007 (3157)	3074 (3307)	5950 (7341)
Other medical costs
Mean (SD) cost, $/patient*	988 (6882)	210 (970)	548 (2765)	3009 (13,983)
Pharmacotherapy
Prescription NSAIDs
n (%)*	1455 (48.7)	353 (44.7)	825 (53.0)	277 (43.1)
Mean (SD) number*	6.1 (7.1)	5.6 (6.5)	6.7 (7.7)	4.8 (5.4)
Oral or intravenous corticosteroids
n (%)*	2115 (70.7)	240 (30.4)	1317 (84.5)	558 (86.8)
Mean (SD) number*	7.5 (7.2)	3.7 (4.8)	7.5 (7.1)	9.2 (7.7)
Immunosuppressants
n (%)*	964 (32.2)	0 (0)	647 (41.5)	317 (49.3)
Mean (SD) number	11.3 (8.6)	0 (0)	11.5 (8.5)	11.0 (8.8)
Anti-malarial drugs
n (%)**	1995 (66.7)	520 (65.9)	1070 (68.7)	405 (63.0)
Mean (SD) number**	11.3 (7.2)	11.1 (7.0)	11.7 (7.4)	10.5 (6.9)
Rituximab
n (%)*	23 (0.8)	0 (0)	0 (0)	23 (3.6)
Mean (SD) number	4.8 (3.2)	0 (0)	0 (0)	4.8 (3.2)
Other biologics
n (%)**	88 (2.9)	10 (1.3)	55 (3.5)	23 (3.6)
Mean (SD) number	11.1 (8.4)	11.5 (9.6)	11.8 (8.3)	9.0 (8.0)

*p < 0.001 for differences among severity sub-groups; ** p < 0.05 for differences among severity sub-groups.

^a2008 USD.

Figure 3. Mean unadjusted per-patient medical, pharmacy, and total costs over the 2-year follow-up period (2008 USD). Costs were significantly different (p < 0.001) between disease severity groups.

Table 4.  Frequency of flares by disease severity and costs per flare (2008 USD) during the 2-year follow-up period.

Number (%) of patients with ≥1 flare
	Total (n = 2990)	Mild disease (n = 789)	Moderate disease (n = 1558)	Severe disease (n = 643)
≥1 Flare, n (%)
Any*	2860 (95.7)	677 (85.8)	1543 (99.0)	640 (99.5)
Mild Flare Severity	2137 (71.5)	547 (69.3)	1143 (73.4)	447 (69.5)
Moderate Flare Severity	2585 (86.5)	461 (58.4)	1510 (96.9)	614 (95.5)
Severe Flare Severity	596 (19.9)	11 (1.4)	194 (12.5)	391 (60.8)
Mean (SD) flares/patient*	6.7 (3.6)	4.8 (2.9)	7.0 (3.5)	8.1 (3.5)
Unadjusted cost of flares
	Total flares (n = 30,701)	Mild flares (n = 11,890)	typo- Moderate flares (n = 17,094)	Severe flares (n = 1717)
Total cost, $/flare
Mean (SD)	2163 (10,754)	909 (2584)	1539 (3263)	17,059 (40,988)
Median (range)	582 (0–797,011)	376 (0–171,577)	700 (0–109,443)	7172 (0–797,011)
Medical cost, $/flare
Mean (SD)	1719 (10,675)	541 (2453)	1065 (3120)	16,387 (40,876)
Median (range)	212 (0–797,011)	80 (0–169,125)	291 (0–107,774)	6535 (0–797,011)
Pharmacy cost, $/flare
Mean (SD)	444 (743)	368 (599)	474 (788)	673 (1046)
Median (range)	206 (0–25,952)	184 (0–14,029)	216 (0–25,952)	318 (0–10,014)

*p < 0.001 among severity sub-groups.