Healthcare resource utilization and costs in patients with a newly confirmed diagnosis of lupus nephritis in the United States over a 5-year follow-up period.

BACKGROUND: We aimed to describe healthcare resource utilization (HCRU) and healthcare costs in patients with newly confirmed lupus nephritis (LN) in the United States over a 5-year follow-up period. METHODS: This retrospective, longitudinal cohort study (GSK Study 214102) utilized administrative claims data to identify individuals with a newly confirmed diagnosis of LN between August 01, 2011, and July 31, 2018, based on LN-specific International Classification of Diseases diagnosis codes. Index was the date of first LN-related diagnosis code claim. HCRU, healthcare costs, and incidence of systemic lupus erythematosus (SLE) flares were reported annually among eligible patients with at least 5 years continuous enrollment post-index. RESULTS: Of 2,159 patients with a newly confirmed diagnosis of LN meeting inclusion and exclusion criteria, 335 had at least 5 years continuous enrollment post-index. HCRU was greatest in the first year post-LN diagnosis across all categories (inpatient admission, emergency room [ER] visits, ambulatory visits, and pharmacy use), and trended lower, though remained substantial, in the 5-year follow-up period. Among patients with LN and HCRU, the mean (standard deviation [SD]) number of ER visits and inpatient admissions were 3.7 (4.6) and 1.8 (1.5), respectively, in Year 1, which generally remained stable in Years 2-5; the mean (SD) number of ambulatory visits and pharmacy fills were 35.8 (25.1) and 62.9 (43.8), respectively, in Year 1, and remained similar for Years 2-5. Most patients (≥ 91.6%) had ≥ 1 SLE flare in each of the 5 years of follow-up. The proportion of patients who experienced a severe SLE flare was higher in Year 1 (31.6%) than subsequent years (14.3-18.5%). Total costs (medical and pharmacy; mean [SD]) were higher in Year 1 ($44,205 [71,532]) than subsequent years ($29,444 [52,310]-$32,222 [58,216]), driven mainly by inpatient admissions (Year 1: $21,181 [58,886]; subsequent years: $7,406 [23,331]-$9,389 [29,283]). CONCLUSIONS: Patients with a newly confirmed diagnosis of LN have substantial HCRU and healthcare costs, particularly in the year post-diagnosis, largely driven by inpatient costs. This highlights the need for improved disease management to prevent renal damage, improve patient outcomes, and reduce costs among patients with renal involvement.

Economic Evaluation of Lupus Nephritis in the Systemic Lupus International Collaborating Clinics Inception Cohort Using a Multistate Model Approach.

OBJECTIVE: Little is known about the long-term costs of lupus nephritis (LN). The costs were compared between patients with and without LN using multistate modeling. METHODS: Patients from 32 centers in 11 countries were enrolled in the Systemic Lupus International Collaborating Clinics inception cohort within 15 months of diagnosis and provided annual data on renal function, hospitalizations, medications, dialysis, and selected procedures. LN was diagnosed by renal biopsy or the American College of Rheumatology classification criteria. Renal function was assessed annually using the estimated glomerular filtration rate (GFR) or estimated proteinuria. A multistate model was used to predict 10-year cumulative costs by multiplying annual costs associated with each renal state by the expected state duration. RESULTS: A total of 1,545 patients participated; 89.3% were women, the mean ± age at diagnosis was 35.2 ± 13.4 years, 49% were white, and the mean followup duration was 6.3 ± 3.3 years. LN developed in 39.4% of these patients by the end of followup. Ten-year cumulative costs were greater in those with LN and an estimated glomerular filtration rate (GFR) <30 ml/minute ($310,579 2015 Canadian dollars versus $19,987 if no LN and estimated GFR >60 ml/minute) or with LN and estimated proteinuria >3 gm/day ($84,040 versus $20,499 if no LN and estimated proteinuria <0.25 gm/day). CONCLUSION: Patients with estimated GFR <30 ml/minute incurred 10-year costs 15-fold higher than those with normal estimated GFR. By estimating the expected duration in each renal state and incorporating associated annual costs, disease severity at presentation can be used to anticipate future health care costs. This is critical knowledge for cost-effectiveness evaluations of novel therapies.

The cost of care of systemic lupus erythematosus (SLE) in the UK: annual direct costs for adult SLE patients with active autoantibody-positive disease.

OBJECTIVES: The aim of the Systemic LUpus Erythematosus Cost of Care In Europe (LUCIE) study was to evaluate the annual direct medical costs of managing adults with active autoantibody-positive disease on medication for SLE in secondary care. This paper presents the UK analyses only. METHODS: A cost-of-illness study was conducted from the perspective of the National Health Service. Health resource utilization data were retrieved over a two-year period from four centres in England and unit cost data were taken from published sources. RESULTS: At baseline, 86 patients were included, 38 (44.2%) had severe SLE and 48 (55.8%) had non-severe SLE. The mean (SD) SELENA-SLEDAI score was 7.7 (5.7). The mean (SD) annual direct medical cost of was estimated at £3231 (£2333) per patient and was 2.2 times higher in patients with severe SLE compared with patients with non-severe SLE (p < 0.001). Multivariate model analyses showed that renal disease involvement (p = 0.0016) and severe flares (p = 0.0001) were associated with higher annual direct costs. CONCLUSIONS: Improvement of the overall stability of SLE and early intervention to minimize the impact of renal disease may be two approaches to mitigate the long-term direct cost of managing SLE patients in the UK.

A cost-utility analysis of alternative drug regimens for newly diagnosed severe lupus nephritis patients in Thailand.

OBJECTIVE: The aim of this study was to assess the value of four drug regimens for newly diagnosed severe LN from a societal perspective. METHODS: A model-based cost-utility analysis was devised to measure lifetime costs and health outcomes. Current treatment options consisting of different combinations of i.v. CYC, AZA and MMF were compared with a baseline regimen of i.v. CYC in both the induction and maintenance phases. Resource use and costs were derived from medical records reviews and databases. Event rates were elicited from randomized controlled trials. Relative treatment effects were obtained from meta-analyses. Health utilities were obtained from a real cohort of patients to estimate the outcome of quality-adjusted life years. RESULTS: It was found that a treatment regimen that combined i.v. CYC in the induction phase with AZA in the maintenance phase was cost saving compared with the baseline regimen. Treatment with i.v. CYC in the induction phase and MMF in the maintenance phase and treatment with MMF in the induction phase and a reduced dose of the same in the maintenance phase turned out to be a negatively dominated regimen. CONCLUSION: In the Thai context, the combination of i.v. CYC for the induction phase followed by AZA for the maintenance phase should be considered as the first-line therapy for newly diagnosed severe LN, as it seems to be the most cost-saving regimen.

Medical costs and healthcare resource use in patients with lupus nephritis and neuropsychiatric lupus in an insured population.

OBJECTIVE: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that can affect multiple organ systems, including the kidneys (lupus nephritis) and the central nervous system (neuropsychiatric lupus, or NPSLE). The healthcare costs and resource utilization associated with treating lupus nephritis and NPSLE in a large US managed care plan were studied. METHODS: SLE subjects ≥18 years of age and with claims-based evidence of nephritis or neuropsychiatric conditions were identified from a health plan database. An index date was set as a randomly drawn date from all qualifying claims during 2003-2008 for study subjects. Subjects were matched on the basis of demographic and clinical characteristics to unaffected controls. Costs and resource use were determined during a fixed 12-month post-index period. RESULTS: Nine hundred and seven lupus nephritis subjects were matched to controls, and 1062 subjects with NPSLE were matched to controls. Mean overall post-index healthcare costs were significantly higher among subjects with lupus nephritis in comparison to matched controls ($33,472 vs $5347, p < 0.001). Similarly, mean overall post-index healthcare costs were significantly higher among subjects with NPSLE compared to controls ($30,341 vs $4646, p < 0.001). Subjects with lupus nephritis or NPSLE had higher mean post-index numbers of ambulatory visits, specialist visits, emergency department visits and inpatient hospital stays, compared to controls (all p < 0.001). LIMITATIONS: Additional research, such as medical chart review, could provide validation for the claims-based identification of lupus nephritis and NPSLE subjects. Also, indirect costs were not evaluated in this study. CONCLUSION: Subjects with lupus nephritis or NPSLE have high costs and resource use, compared to unaffected controls.

Should mycophenolate mofetil replace cyclophosphamide as first-line therapy for severe lupus nephritis?

Available treatments for severe (class III, IV, and V) lupus nephritis (LN) have expanded greatly over the last 40 years. In the 1970s and 1980s, cyclophosphamide (CYC), in combination with glucocorticoids, gained favor as induction and maintenance therapy for severe LN. However, the adverse event profile of CYC led to the search for other medications for severe LN. Beginning in the late 1990 s, mycophenolate mofetil (MMF) was introduced as induction and maintenance therapy for severe LN. This review discusses the clinical trial results, pharmacology, cost-effectiveness, and adverse effect profiles of CYC compared to MMF for induction and maintenance therapy for severe LN. The authors conclude that MMF should be considered first-line induction and maintenance treatment therapy for severe LN, although CYC may have a place under specific clinical and economic circumstances.

A structured literature review of the direct costs of adult systemic lupus erythematosus in the US.

OBJECTIVE: A structured review of the literature was undertaken to examine the direct costs of adult systemic lupus erythematosus (SLE) in a US population. METHODS: English-language studies published from January 2000 to April 2010 were systematically reviewed from both Medline's PubMed and the Cochrane databases. Studies were included if they reported direct medical costs of SLE among adults in the US. RESULTS: Seven studies published since January 2000 that reported direct medical costs associated with SLE in the US were identified. Studies examined main cost categories of inpatient, outpatient, and pharmacy services; each contributed substantially to total costs. Wide SDs were reported, consistent with variability in disease manifestation. Mean annual direct costs of SLE patients ranged from $13,735-$20,926; the costs of those with and without nephritis ranged from $29,034-$62,651 and $12,273-$16,575, respectively. Across studies of a general SLE population, pharmaceutical costs composed 19-30% of total expenditures, with inpatient costs accounting for 16-50% and outpatient costs accounting for 24-56% of overall costs. Methodologies varied across studies, with patient self-reported resource utilization generating the lowest estimates versus claims-based analyses; Medicaid claims analyses generated lower incremental cost estimates for SLE patients versus control patients compared to estimates based on commercial claims analysis. CONCLUSION: SLE is associated with substantial annual direct cost burden in the US; however, little research has been done examining costs associated with specific treatments or cost variation by disease severity and disease manifestations. Future research elucidating the causes in variation of costs will help in the appraisal of emerging therapies and in developing clinical management strategies.

Healthcare cost and loss of productivity in a Canadian population of patients with and without lupus nephritis.

OBJECTIVE: To compare the healthcare cost and loss of productivity in patients with systemic lupus erythematosus (SLE) with (LN) and without lupus nephritis (lupus nephritis-negative, LNN). METHOD: Patients were classified into those with active (ALN and ALNN) and inactive disease (ILN and ILNN). Patients reported on visits to healthcare professionals and use of diagnostic tests, medications, assistive devices, alternative treatments, hospital emergency visits, surgical procedures, and hospitalizations as well as loss of productivity in the 4 weeks preceding enrollment. RESULTS: Enrollment was 141 patients, 79 with LN and 62 LNN. Patients with LN were more likely to visit rheumatologists and nephrologists, undergo diagnostic tests, and had higher costs for medications than patients who were LNN. The annual healthcare cost averaged $CAN 12,597 ± 9946 for patients with LN and $10,585 ± 13,149 for patients who were LNN, a difference of $2012 (95% CI -$2075, $6100). Patients with ALN had more diagnostic tests and surgical procedures, contributing to a significantly higher annual direct cost ($14,224 ± 10,265) compared to patients with ILN ($9142 ± 8419) and a difference of $5082 (95% CI $591, $9573). The healthcare cost was not different between patients with ALNN and patients with ILNN. In patients with LN and patients who were LNN, < 50% were employed and on average missed 6.5-9 days of work per month. The loss of productivity was significantly higher for caregivers of patients with LN than caregivers of patients who were LNN. CONCLUSION: Healthcare cost and loss of productivity were similar between patients with LN and patients who were LNN; the loss of productivity for caregivers is higher for patients with LN; and the healthcare cost is greater in ALN than in ILN.

Long-term medical costs and resource utilization in systemic lupus erythematosus and lupus nephritis: a five-year analysis of a large medicaid population.

OBJECTIVE: To estimate the long-term direct medical costs and health care utilization for patients with systemic lupus erythematosus (SLE) and a subset of SLE patients with nephritis. METHODS: Patients with newly active SLE were found in the MarketScan Medicaid Database (1999-2005), which includes all inpatient, outpatient, emergency department, and pharmaceutical claims for more than 10 million Medicaid beneficiaries. The date a patient became newly active was defined as the earliest observed SLE diagnosis code, with a 6-month clean period prior to the diagnosis. This method identified 2,298 patients with a consecutive followup of 5 years. A reference group of patients without SLE was constructed using propensity score matching. Nephritis was assessed based on diagnosis and procedure codes involving the kidney. RESULTS: Mean annual medical costs for SLE patients totaled $16,089 at year 1, which is significantly greater (by $6,831) than that for reference patients. Costs decreased slightly at year 2 but then increased yearly at an average rate of 16% through year 5, to $23,860. SLE patients without nephritis (n = 1,809) had costs $967-3,756 higher than the reference patients. SLE patients with nephritis (n = 489) had costs $13,228-34,907 greater than the reference group. Inpatient visits for the nephritis subgroup were 0.6-1.0 per capita, which are approximately twice the rate for all SLE patients and 3 to 4 times higher than the reference group. CONCLUSION: SLE is a costly condition to treat. Medical expenses incurred by SLE patients increase steadily over time, particularly for patients with nephritis.

Direct and indirect costs to employers of patients with systemic lupus erythematosus with and without nephritis.

OBJECTIVES: To estimate the medical- and productivity-related cost burden of systemic lupus erythematosus (SLE) and SLE with nephritis in an employee population. METHODS: Using administrative data, annual costs were calculated for SLE patients, a subset with nephritis, and a matched control group of patients without SLE. These costs were compared with the cost of other chronic conditions. RESULTS: Mean annual medical expenditures and short term disability costs for SLE patients were $12,238 and $1184 greater (2005 dollars), respectively, than those of controls. Mean medical expenditures for SLE/nephritis patients were $46,862 greater than for controls. When compared with other chronic health conditions faced by employees, SLE/nephritis was the most costly condition. CONCLUSIONS: SLE, particularly with nephritis, is associated with substantial costs. Therapies that can better manage SLE may provide opportunities for savings to employers.

Cost comparison between mycophenolate mofetil and cyclophosphamide-azathioprine in the treatment of lupus nephritis.

OBJECTIVE: To compare the healthcare expenditure associated with mycophenolate mofetil (MMF)-based immunosuppression in contrast to conventional therapy in patients with lupus nephritis. METHODS: Our retrospective single-center study compared the major healthcare costs during the first 24 months of treatment incurred by immunosuppressive medications, hospitalization, and complications in patients with severe lupus nephritis who had been treated with prednisolone and either MMF or sequential cyclophosphamide induction followed by azathioprine maintenance (CTX-AZA). RESULTS: Forty-four patients were studied (22 in each group). Baseline demographic and clinical measures, and remission rates after treatment, were similar between the 2 groups. Immunosuppressive drug cost was 13.6-fold higher in the MMF group (US$4168.3+/-1176.5 per patient, compared with $285.0+/-70.6 in the CTX-AZA group, mean difference $3883.2+/-251.3; p<0.001). MMF treatment was associated with a lower incidence of infections (12.0 episodes/1000 patient-months, compared with 32.4 in the CTX-AZA group; p=0.035). Combined cost of hospitalization and treatment of infections was 82.5% lower in the MMF group (mean difference -2208.7+/-1700.6; p=0.120). Overall treatment expenditure on immunosuppressive drugs, hospitalization, and treatment of infections was 1.57-fold higher in the MMF group (mean US $4635.9 compared with $2961.5 in the CTX-AZA group; p<0.001). CONCLUSION: While the cost of MMF treatment for severe lupus nephritis is much higher compared with CTX-AZA, the increased drug cost is partially offset by savings from the reduced incidence of complications.

SLE patients with renal damage incur higher health care costs.

OBJECTIVES: To compare costs and quality of life (QoL) between SLE patients with and without renal damage. METHODS: Seven hundred and fifteen patients were surveyed semi-annually over 4 yrs on health care use and productivity loss and annually on QoL. Cumulative direct and indirect costs (2006 Canadian dollars) and QoL (average annual change in SF-36) were compared between patients with and without renal damage [Systemic Lupus International Collaborating Clinics/ACR Damage Index (SLICC/ACR DI)] using simultaneous regressions. RESULTS: At study conclusion, for patients with the renal subscale of the SLICC/ACR DI = 0 (n = 634), 1 (n = 54), 2 (n = 15) and 3 (n = 12), mean 4-yr cumulative direct costs per patient (95% CI) were $20,337 ($18,815, $21,858), $27,869 ($19,230, $36,509), $51,191 ($23,463, $78,919) and $99,544 ($57,102, $141,987), respectively. In a regression where the renal subscale of the SLICC/ACR DI was a single indicator variable, on average (95% CI), each unit increase in renal damage was associated with a 24% (15%, 33%) increase in direct costs. In a regression where each level in the renal subscale was an indicator variable, patients with end-stage renal disease incurred 103% (65%, 141%) higher direct costs than those without renal damage. Cumulative indirect costs and annual change in the SF-36 summary scores did not differ between patients. CONCLUSIONS: SLE patients with renal damage incurred higher direct costs, but did not experience a poorer QoL. QoL may be more influenced by concurrent renal activity than accumulated renal damage, which can occur at any time and patients may gradually habituate to their compromised health state.

Medical insurance, socioeconomic status, and age of onset of endstage renal disease in patients with lupus nephritis.

OBJECTIVE: Limited access to care may hasten progression to endstage renal disease (ESRD) in patients with lupus nephritis. We examined associations between type of medical insurance, socioeconomic status (SES), and age at onset of ESRD in a national, population-based cohort. METHODS: Using the United States Renal Data System, incident cases of ESRD due to lupus nephritis in the US from January 1, 1996, to June 30, 2004, were examined in this cross-sectional study (n = 7971). Age at onset of ESRD was compared among patients with different types of medical insurance and by SES. RESULTS: In each ethnic group, patients with private insurance were older at the onset of ESRD than those with no insurance or Medicaid. For example, whites with private insurance were on average 7.5 years older than those with no insurance and 8.2 years older than those with Medicaid. There were no differences in age at onset of ESRD between those with no insurance and those with Medicaid. SES, based on the socioeconomic characteristics of the patient's area of residence, was associated with age of onset of ESRD only in whites. CONCLUSION: Among patients with lupus nephritis who develop ESRD, those with private medical insurance are older when they begin ESRD treatment than those with Medicaid or no insurance. Given that medical insurance is unrelated to the age at onset of lupus nephritis, these findings suggest that progression to ESRD varies with medical insurance status, possibly because of differences in quality of care or access to care.

Modified oral ondansetron regimen for cyclophosphamide-induced emesis in lupus nephritis.

OBJECTIVE: To evaluate the antiemetic efficacy of a modified regimen of oral ondansetron and dexamethasone in patients with lupus nephritis undergoing treatment with cyclophosphamide whose conventional antiemetic regimen had failed. DESIGN: A before-after prospective observational pilot project. SETTING: A federal research hospital. PATIENTS: Fourteen outpatients with lupus nephritis receiving intravenous cyclophosphamide 0.75-1.0 g/m2 had previously experienced chemotherapy-induced emetic events (vomiting or retching) while receiving a standard combination intravenous antiemetic regimen. The regimen consisted of four doses of thiethylperazine 10 mg and diphenhydramine 25 mg every 6 hours, and two doses of lorazepam 0.5 mg every 6 hours starting at 1 hour prior to cyclophosphamide. A subset of 8 patients previously completed a blinded study in which they received the intravenous formulation of ondansetron (4 doses of 4-16 mg q4h) administered orally beginning 30 minutes prior to the cyclophosphamide infusion. MAIN OUTCOME MEASURES: The number of emetic events and cost of drug administration were assessed for the modified ondansetron intervention and compared with those of the standard antiemetic regimen. The incidence of emetic events and visual analog nausea scores for the subset of eight patients were also evaluated. INTERVENTIONS: To account for the delayed onset of emesis associated with cyclophosphamide, patients received both ondansetron 8 mg orally every 4 hours (3 doses) and dexamethasone 10 mg orally (1 dose) beginning 4 hours after the cyclophosphamide infusion. This is different from the manufacturer's recommended dose schedule, in which ondansetron is administered prior to chemotherapy. RESULTS: No emetic events were observed following the administration of oral ondansetron/dexamethasone. The 95% confidence interval for the true rate of emesis was 0% to 19.3%. There was a significant difference in efficacy between ondansetron/dexamethasone and the triple antiemetic regimen (p < 0.0002). None of the patients experienced adverse effects while receiving the ondansetron/dexamethasone regimen. Cost comparisons (including admixture and nursing administration times) for standard combination therapy and oral ondansetron/dexamethasone were $109.09 and $70.24, respectively. No difference in emetic events or nausea ratings was observed between oral ondansetron/dexamethasone tablets and oral administration of ondansetron using the intravenous formula. CONCLUSIONS: This study suggests that a modified oral ondansetron/dexamethasone regimen is safe and efficacious, and costs less than alternative regimens to prevent cyclophosphamide-induced emesis in patients with lupus nephritis.

The economic impact of treatment of severe lupus nephritis with prednisone and intravenous cyclophosphamide.

OBJECTIVE: It has been reported that outcomes are improved in patients with severe lupus nephritis treated with combined prednisone and intravenous cyclophosphamide, compared with those treated with prednisone alone. These findings motivated this analysis of the economic impact of the combined therapy. METHODS: The annual expected incidence of severe lupus nephritis in the year 1988 in the US was estimated to be 1,130. A hypothetical patient cohort of this size was used as the model for the present analysis; the costs of treatment with prednisone alone and with combined prednisone and intravenous cyclophosphamide were calculated and compared. The analysis took into account the expected rate of renal failure with each therapeutic approach, as well as age, sex, and the economic value of working years gained. RESULTS: Although the treatment costs are higher for the combination therapy, the analysis revealed overall savings due to a reduced need for kidney dialysis or transplantation, and the economic value of working capacity gained. Savings attributable to patient care costs were $50.8 million; those attributable to working capacity gained were $42.3 million. CONCLUSION: This analysis indicates that over a 10-year period, as much as $93.1 million per annual cohort is saved by the use of combination therapy for the treatment of severe lupus nephritis.