Assessing the Costs of Neuropsychiatric Disease in the Systemic Lupus International Collaborating Clinics Cohort Using Multistate Modeling.

OBJECTIVE: To estimate direct and indirect costs associated with neuropsychiatric (NP) events in the Systemic Lupus International Collaborating Clinics inception cohort. METHODS: NP events were documented annually using American College of Rheumatology definitions for NP events and attributed to systemic lupus erythematosus (SLE) or non-SLE causes. Patients were stratified into 1 of 3 NP states (no, resolved, or new/ongoing NP event). Change in NP status was characterized by interstate transition rates using multistate modeling. Annual direct costs and indirect costs were based on health care use and impaired productivity over the preceding year. Annual costs associated with NP states and NP events were calculated by averaging all observations in each state and adjusted through random-effects regressions. Five- and 10-year costs for NP states were predicted by multiplying adjusted annual costs per state by expected state duration, forecasted using multistate modeling. RESULTS: A total of 1,697 patients (49% White race/ethnicity) were followed for a mean of 9.6 years. NP events (n = 1,971) occurred in 956 patients, 32% attributed to SLE. For SLE and non-SLE NP events, predicted annual, 5-, and 10-year direct costs and indirect costs were higher in new/ongoing versus no events. Direct costs were 1.5-fold higher and indirect costs 1.3-fold higher in new/ongoing versus no events. Indirect costs exceeded direct costs 3.0 to 5.2 fold. Among frequent SLE NP events, new/ongoing seizure disorder and cerebrovascular disease accounted for the largest increases in annual direct costs. For non-SLE NP events, new/ongoing polyneuropathy accounted for the largest increase in annual direct costs, and new/ongoing headache and mood disorder for the largest increases in indirect costs. CONCLUSION: Patients with new/ongoing SLE or non-SLE NP events incurred higher direct and indirect costs.

Economic Evaluation of Damage Accrual in an International Systemic Lupus Erythematosus Inception Cohort Using a Multistate Model Approach.

OBJECTIVE: There is a paucity of data regarding health care costs associated with damage accrual in systemic lupus erythematosus. The present study was undertaken to describe costs associated with damage states across the disease course using multistate modeling. METHODS: Patients from 33 centers in 11 countries were enrolled in the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort within 15 months of diagnosis. Annual data on demographics, disease activity, damage (SLICC/American College of Rheumatology Damage Index [SDI]), hospitalizations, medications, dialysis, and selected procedures were collected. Ten-year cumulative costs (Canadian dollars) were estimated by multiplying annual costs associated with each SDI state by the expected state duration using a multistate model. RESULTS: A total of 1,687 patients participated; 88.7% were female, 49.0% were white, mean ± SD age at diagnosis was 34.6 ± 13.3 years, and mean time to follow-up was 8.9 years (range 0.6-18.5 years). Mean annual costs were higher for those with higher SDI scores as follows: $22,006 (Canadian) (95% confidence interval [95% CI] $16,662, $27,350) for SDI scores ≥5 versus $1,833 (95% CI $1,134, $2,532) for SDI scores of 0. Similarly, 10-year cumulative costs were higher for those with higher SDI scores at the beginning of the 10-year interval as follows: $189,073 (Canadian) (95% CI $142,318, $235,827) for SDI scores ≥5 versus $21,713 (95% CI $13,639, $29,788) for SDI scores of 0. CONCLUSION: Patients with the highest SDI scores incur 10-year cumulative costs that are ~9-fold higher than those with the lowest SDI scores. By estimating the damage trajectory and incorporating annual costs, data on damage can be used to estimate future costs, which is critical knowledge for evaluating the cost-effectiveness of novel therapies.

Canadian Rheumatology Association Recommendations for the Assessment and Monitoring of Systemic Lupus Erythematosus.

OBJECTIVE: To develop recommendations for the assessment of people with systemic lupus erythematosus (SLE) in Canada. METHODS: Recommendations were developed using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach. The Canadian SLE Working Group (panel of Canadian rheumatologists and a patient representative from Canadian Arthritis Patient Alliance) was created. Questions for recommendation development were identified based on the results of a previous survey of SLE practice patterns of members of the Canadian Rheumatology Association. Systematic literature reviews of randomized trials and observational studies were conducted. Evidence to Decision tables were prepared and presented to the panel at 2 face-to-face meetings and online. RESULTS: There are 15 recommendations for assessing and monitoring SLE, with varying applicability to adult and pediatric patients. Three recommendations focus on diagnosis, disease activity, and damage assessment, suggesting the use of a validated disease activity score per visit and annual damage score. Strong recommendations were made for cardiovascular risk assessment and measuring anti-Ro and anti-La antibodies in the peripartum period and conditional recommendations for osteoporosis and osteonecrosis. Two conditional recommendations were made for peripartum assessments, 1 for cervical cancer screening and 2 for hepatitis B and C screening. A strong recommendation was made for annual influenza vaccination. CONCLUSION: These are considered the first guidelines using the GRADE method for the monitoring of SLE. Existing evidence is largely of low to moderate quality, resulting in more conditional than strong recommendations. Additional rigorous studies and special attention to pediatric SLE populations and patient preferences are needed.

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.

Rheumatoid arthritis prevalence in Quebec.

BACKGROUND: To estimate rheumatoid arthritis (RA) prevalence in Quebec using administrative health data, comparing across regions. METHODS: Cases of RA were ascertained from physician billing and hospitalization data, 1992-2008. We used three case definitions: 1) ≥ 2 billing diagnoses, submitted by any physician, ≥ 2 months apart, but within 2 years; 2) ≥ 1 diagnosis, by a rheumatologist; 3) ≥1 hospitalization diagnosis (all based on ICD-9 code 714, and ICD-10 code M05). We combined data across these three case definitions, using Bayesian hierarchical latent class models to estimate RA prevalence, adjusting for the imperfect sensitivity and specificity of the data. We compared urban versus rural regions. RESULTS: Using our case definitions and no adjustment for error, we defined 75,760 cases for an over-all RA prevalence of 9.9 per thousand residents. After adjusting for the imperfect sensitivity and specificity of our case definition algorithms, we estimated Quebec RA prevalence at 5.6 per 1000 females and 4.1 per 1000 males. The adjusted RA prevalence estimates for older females were the highest for any demographic group (9.9 cases per 1,000), and were similar in rural and urban regions. In younger males and females, and in older males, RA prevalence estimates were lower in rural versus urban areas. CONCLUSIONS: Without adjustment for error inherent in administrative databases, RA prevalence in Quebec was approximately 1%, while adjusted estimates are approximately half that. The lower prevalence in rural areas, seen for most demographic groups, may suggest either true regional variations in RA risk, or under-ascertainment of cases in rural Quebec.

American College of Rheumatology criteria at inception, and accrual over 5 years in the SLICC inception cohort.

OBJECTIVE: To determine the frequency of each American College of Rheumatology (ACR) criterion met at time of enrollment, and the increase in each of the criteria over 5 years. METHODS: In 2000 the Systemic Lupus International Collaborating Clinics (SLICC) recruited an international inception cohort of patients with systemic lupus erythematosus (SLE; ≥ 4 ACR criteria) who were followed at yearly intervals according to a standard protocol. Descriptive statistics were used to assess the total and cumulative number of ACR criteria met at each visit. Regression models were done to compare the increase of individual and cumulative criteria as a function of race/ethnicity group, and sex. RESULTS: In all, 768 patients have been followed for a minimum of 5 years. Overall, 59.1% of the patients had an increase in the number of ACR criteria they met over the 5-year period. The mean number of ACR criteria met at enrollment was 5.04 ± 1.13 and at year 5 was 6.03 ± 1.42. At enrollment, nonwhite patients had a higher number of ACR criteria (5.19 ± 1.23) than white patients. The total number of criteria increased in both white and nonwhite ethnicities, but increased more among whites. Males had a slightly lower number of criteria at enrollment compared to females and males accrued fewer criteria at 5 years. CONCLUSION: In this international inception cohort of SLE patients with at least 4 ACR criteria at entry, there was an accumulation of ACR criteria over the following 5 years. The distribution of criteria both at inception and over 5 years is affected by sex and ethnicity.

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.

The 1000 Canadian faces of lupus: determinants of disease outcome in a large multiethnic cohort.

OBJECTIVE: To describe disease expression and damage accrual in systemic lupus erythematosus (SLE), and determine the influence of ethnicity and socioeconomic factors on damage accrual in a large multiethnic Canadian cohort. METHODS: Adults with SLE were enrolled in a multicenter cohort. Data on sociodemographic factors, diagnostic criteria, disease activity, autoantibodies, treatment, and damage were collected using standardized tools, and results were compared across ethnic groups. We analyzed baseline data, testing for differences in sociodemographic and clinical factors, between the different ethnic groups, in univariate analyses; significant variables from univariate analyses were included in multivariate regression models examining for differences between ethnic groups, related to damage scores. RESULTS: We studied 1416 patients, including 826 Caucasians, 249 Asians, 122 Afro-Caribbeans, and 73 Aboriginals. Although the overall number of American College of Rheumatology criteria in different ethnic groups was similar, there were differences in individual manifestations and autoantibody profiles. Asian and Afro-Caribbean patients had more frequent renal involvement and more exposure to immunosuppressives. Aboriginal patients had high frequencies of antiphospholipid antibodies and high rates of comorbidity, but disease manifestations similar to Caucasians. Asian patients had the youngest age at onset and the lowest damage scores. Aboriginals had the least education and lowest incomes. The final regression model (R2=0.27) for higher damage score included older age, longer disease duration, low income, prednisone treatment, higher disease activity, and cyclophosphamide treatment. CONCLUSION: There are differences in lupus phenotypes between ethnic populations. Although ethnicity was not found to be a significant independent predictor of damage accrual, low income was.

Costs of rheumatoid arthritis: new estimates from the human capital method and comparison to the willingness-to-pay method.

BACKGROUND: Individuals' valuation of changes in health states in monetary terms have been measured by examining changes in the direct and indirect costs of disease and by the willingness-to-pay (WTP) methodology. METHODS: In 2002, a 2-part study was conducted in Quebec. In one part of the study, 121 rheumatoid arthritis (RA) patients from the McGill University Health Centre were mailed the Stanford Cost Assessment Questionnaire, which enabled the elicitation of direct costs and indirect costs, according to the friction cost and the human capital methods. The other part was a phone survey conducted in a representative sample of the general population and in the same sample of patients, aiming to elicit the societal WTP for a complete cure of RA in the context of 2 different scenarios: a public coverage or private insurance. These estimates were then compared. RESULTS: Estimates of the cost of illness of RA ranged from 11,717 to 28,498 Canadian Dollars (CAD) depending on the method. These estimates are higher than those previously published in Canada from the 1990s, which is partly due to the recent and costly biological therapies and to a change in the measurement of productivity losses. These estimates are somewhat lower than the societal WTP elicited from the WTP survey, that is, 26,717 and 36,817 CAD per RA case, depending on the public or private health insurance context in which the cure would be available. CONCLUSION: Given that neither method is ideal, data from both methods would provide an important sensitivity analysis when monetary estimates of health state changes are required.

The systemic lupus erythematosus Tri-Nation study: cumulative indirect costs.

OBJECTIVE: We previously reported that patients with systemic lupus erythematosus (SLE) in the US incurred approximately 19% and 12% higher direct medical costs than patients in Canada and the UK, respectively, without experiencing superior outcomes expressed as disease damage or quality of life. In the present study, we compared cumulative indirect costs over 4 years in these patients. METHODS: A total of 715 patients with SLE (269 US, 231 Canada, 215 UK) were surveyed semiannually for 4 years on employment status and time lost from labor and nonlabor market activities. Cross-country comparisons of indirect costs were performed. RESULTS: In the US, Canada, and the UK, mean 4-year cumulative indirect costs (95% confidence interval [95% CI]) due to diminished labor market activity were $56,745 ($49,919, $63,571), $38,642 ($32,785, $44,500), and $42,213 ($35,859, $48,567), respectively, and cumulative indirect costs due to diminished nonlabor market activity were $5,249 ($2,766, $7,732), $5,455 ($3,290, $7,620), and $8,572 ($5,626, $11,518), respectively. Regression results showed that cumulative indirect costs (95% CI) due to diminished labor market activity in the US were $6,750 ($580, $12,910) greater than in Canada and $10,430 ($4,050, $16,800) greater than in the UK. Indirect costs due to diminished nonlabor market activity in the US were $280 (-$2,950, $3,520) less than in Canada and $2,010 (-$1,490, $5,510) less than in the UK, both results insignificant due to wide CIs. CONCLUSION: Despite American patients incurring greater direct medical costs than Canadian and British patients, they do not experience superior health outcomes in terms of less productivity loss in either labor market or nonlabor market activities.

Valuing a hypothetical cure for rheumatoid arthritis using the contingent valuation methodology: the patient perspective.

OBJECTIVE: A willingness-to-pay (WTP) survey measures the value of a given intervention in money terms. We examined the WTP of Canadian patients with rheumatoid arthritis (RA) for a hypothetical cure for RA under private and public scenarios. The validity of the survey was explored by studying the association between WTP and variables thought to be associated with WTP and randomly-varied variables of the survey materials. METHODS: A telephone survey was carried out in a sample of 121 patients with RA from 5 rheumatologists affiliated with the McGill University Health Centre. In advance, patients had been sent a 4-page brochure providing a comprehensive description of the disease (including photos or no photos). The hypothetical cure for RA was presented through 2 scenarios: a private insurance implying an annual premium and a public coverage requiring additional income taxes. The survey included questions related to their WTP, socioeconomic status (ability to pay), general health, opinion about the performance of the healthcare system, and their opinion about the difficulty of the survey. For elicitation of WTP, patients were randomized to one of 3 payment cards. Mailed questionnaires concerning RA health status were also completed. A series of univariate comparisons and multivariate ordered logit regressions were carried out to examine the association of WTP and patient and study variables. RESULTS: Patients were willing to pay annually significantly more for the private program (mean 1190 Canadian dollars) than for the public program (mean 502 Canadian dollars). Annual WTP was associated with age, household income, site of care (private program), private health insurance, opinion about the performance of the public healthcare system (public program), and presence of brochure photos. The payment card did not affect WTP for either program. CONCLUSION: The WTP survey was well understood and accepted by the patients with RA. Although measures of RA-specific health status (e.g., Health Assessment Questionnaire) were not found to be associated with WTP, many variables thought to be associated with WTP were found to be related in the expected directions. Since WTP for the private program was higher than that for the public program, our study design did not fully capture altruistic valuations of RA patients. Thus, our estimates represent a lower bound on patients' WTP for an RA cure.

Determinants of discordance between patients and physicians in their assessment of lupus disease activity.

OBJECTIVE: We evaluated different methods for quantifying patient-physician discordance and identified factors associated with discordance in the assessment of lupus disease activity. METHODS: Data from 208 female patients who had a comprehensive annual examination were extracted from the Montreal General Hospital Lupus Registry. Discordance was measured by the difference between the patient self-reported 10 cm visual analog scale (VAS) and the physician VAS for global disease activity (VASDIFF). Multiple linear regression was used to identify the correlates of discordance, e.g., SF-36TM scales, Systemic Lupus Activity Measure (SLAM) components, etc. Four regression models were estimated using: (1) all patients; (2) only patients who evaluated disease activity higher than their physician's assessment; (3) only patients who evaluated disease activity lower than their physician's assessment; and (4) all patients, with the absolute value of VASDIFF as the dependent variable. RESULTS: Of the 208 observations, 150 (72%) of the VASDIFF scores were within +/- 2.5 cm on a 10 cm scale, indicating absence of marked discordance; 43 (20.7%) were from patients overscoring and 15 (7.2%) from patients underscoring their physician by at least 2.5 cm. Higher SF-36 role physical score, more bodily pain, and lower role emotional score in addition to the SLAM-skin component were independently associated with higher discordance. SF-36 social function and mental health scores as well as SLAM-neurological and kidney components were correlated with discordance in some subanalyses. Bodily pain was the most important variable for predicting "clinically relevant" discordance, followed by SLAM-skin and kidney components. CONCLUSION: Discordance between patients and physicians may result from patients scoring their disease activity based on their psychological and physical well-being, whereas physicians score disease activity based on the clinical and physical signs and symptoms of lupus.

Counterbalancing patient demands with evidence: results from a pan-Canadian randomized clinical trial of brief supportive-expressive group psychotherapy for women with systemic lupus erythematosus.

OBJECTIVE: To evaluate the effect of Brief Supportive-Expressive Group Psychotherapy as an adjunct to standard medical care in reducing psychological distress, medical symptoms, and health care costs and improving quality of life in women with systemic lupus erythematosus (SLE). METHODS: A randomized clinical trial was conducted with 133 SLE female patients from 9 clinics across Canada. Clinical and psychosocial measures were taken at baseline, posttreatment, and 6 and 12 months posttreatment. Outcomes assessed were psychological distress, quality of life, disease activity, health service utilization, and diminished productivity. RESULTS: Intention-to-treat analyses revealed that there were no clinically important group differences on any of the outcome measures. CONCLUSION: Although both groups improved over time on several measures (e.g., decreases in psychological distress, stress, and emotion-oriented coping), these changes could not be attributed to the psychotherapeutic intervention. Thus, evidence does not support the referral of these patients to this type of intervention.