Rheumatoid Arthritis: Clarke AE

Bernatsky S, Clarke AE, Suissa S. · Division of Clinical Epidemiology, McGill University Health Centre, Montreal, QC, Canada. · Arch Intern Med. · Pubmed #18299492 links to  free full text

Abstract: BACKGROUND: Rheumatoid arthritis is a severe inflammatory polyarthritis that requires long-term treatment with disease-modifying antirheumatic drugs. There is increasing concern about the influence of rheumatoid arthritis therapy on the risk for hematologic malignant neoplasms. METHODS: We used a case-control design nested in a cohort of 23,810 patients with rheumatoid arthritis assembled from administrative databases covering the population of Quebec, Canada. The study was carried out from January 1, 1980, through December 31, 2003. Case patients having hematologic malignant neoplasms were ascertained from physician billing and hospitalization records; each case patient was matched for age and sex with 10 control subjects. Adjusting for clinical variables and concomitant medications, we used conditional logistic regression to analyze potential associations between disease-modifying antirheumatic drug exposures and risk for hematologic malignant neoplasms. We estimated rate ratios attributable to each disease-modifying antirheumatic drug exposure. RESULTS: During the study, hematologic malignant neoplasms developed in 619 patients, including lymphomas in 346 patients, leukemia in 178 patients, and multiple myelomas in 95 patients. The unadjusted rate ratios for hematologic malignant neoplasms after drug exposures were as follows: methotrexate, 1.18 (95% confidence interval [CI], 0.99-1.40); azathioprine, 1.44 (95% CI, 1.01-2.03); and cyclophosphamide, 2.21 (95% CI, 1.52-3.20). Because biologic agents first appeared in the Régie d'Assurance Maladie du Quebec formulary in 2002, there were few exposures to these drugs. Adjusted estimates suggested that hematologic cancer risk was most elevated after exposure to cyclophosphamide (rate ratio, 1.84; 95% CI, 1.24-2.73). For lymphomas only, the adjusted rate ratio after cyclophosphamide exposure was 2.12 (95% CI, 1.33-3.54). CONCLUSIONS: In this large cohort of patients with rheumatoid arthritis, the greatest relative risk for hematologic malignant neoplasms was noted after use of cyclophosphamide. Assessments of risk related to newer and emerging therapies should carefully consider previous and concomitant medication exposures.

Marra CA, Marion SA, Guh DP, Najafzadeh M, Wolfe F, Esdaile JM, Clarke AE, Gignac MA, Anis AH. · Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia, Canada. · J Clin Epidemiol. · Pubmed #17493521 No free full text.

Abstract: BACKGROUND: There is evidence that utility elicitation methods used in the calculation of quality-adjusted life years (QALYs) yield different results. It is not clear how these differences impact economic evaluations. METHODS: Using a mathematical model incorporating data on efficacy, costs, and utility values, we simulated the experiences of 100,000 hypothetical rheumatoid arthritis patients over 10 years (50,000 exposed to infliximab plus methotrexate [MTX] and 50,000 exposed to MTX alone). QALYs, were derived from the Health Utilities Index 2 and 3 (HUI2 and HUI3), the Short Form 6-D (SF-6D), and the Euroqol 5-D (EQ-5D). Incremental cost-utility ratios were determined using each instrument to calculate QALYs and the results were compared using cost-effectiveness acceptability curves. RESULTS: Using the different utility measurement methods, the mean difference in QALYs between the infliximab plus MTX and MTX groups ranged from a high of 1.95 QALYs (95% CI=1.93-1.97) using the HUI3 to 0.89 QALYs (95% CI=0.88-0.91) using the SF-6D. Adopting the commonly cited value of society's willingness to pay for a QALY of $50,000, 91% of the simulations favored the cost utility of infliximab plus MTX when using the HUI3 to calculate QALYs. However, when using the EQ-5D, HUI2, or the SF-6D utility values to calculate QALYS, the proportion of simulations that favored the cost utility of infliximab were 63%, 45%, and 12%, respectively. CONCLUSION: Depending on the method for determining utility values used in the calculation of QALYs, very different incremental cost-utility ratios are generated.

Fautrel B, Clarke AE, Guillemin F, Adam V, St-Pierre Y, Panaritis T, Fortin PR, Menard HA, Donaldson C, Penrod JR. · Department of Rheumatology, University of Paris VI-Pierre et Marie Curie, Hospital Pitié-Salpêtrière, Paris, France. · Med Decis Making. · Pubmed #17409364 No free full text.

Abstract: 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.

Bernatsky S, Duffy C, Malleson P, Feldman DE, St Pierre Y, Clarke AE. · Montreal General Hospital, Montreal, Quebec, Canada. · Arthritis Rheum. · Pubmed #17266088 links to  free full text

Abstract: OBJECTIVE: Juvenile idiopathic arthritis (JIA) is a potentially devastating chronic pediatric disease. Although high costs have been well described in adult arthritis, little is known about the economic impact of JIA. Our objective was to describe direct medical costs for children with JIA compared with controls. METHODS: Consecutive clinic attendees (n = 155) with JIA were enrolled from 2 tertiary referral pediatric centers. Outpatient clinic controls without JIA (n = 181) were recruited at the respective centers. Data on direct medical costs were obtained at 3-month intervals. Average annualized direct medical costs were calculated, expressed in 2005 Canadian dollars. RESULTS: The total difference in annualized average direct medical costs for children with JIA versus controls was $1,686 (95% confidence interval $875, $2,500). JIA subjects had substantially higher costs concerning medication use, visits to specialists and allied health care professionals, and diagnostic tests. Multiple linear regression models for the JIA sample revealed that higher active joint count was independently associated with greater total direct medical costs. Also, JIA type was a predictor of greater direct costs, with higher costs for patients with polyarthritis (rheumatoid factor positive or negative) or systemic JIA. CONCLUSION: The economic impact of JIA is substantial, and higher active joint count is independently associated with greater costs. This may be of particular significance given the emergence of new, costly medications for use in JIA. Insights into the relationship between disease activity and cost in JIA should assist policy makers regarding resource allocation in the setting of competing demands. Ultimately, decisions regarding access to therapies should be considered in terms of overall cost-benefit ratios.

Callaghan R, Prabu A, Allan RB, Clarke AE, Sutcliffe N, Pierre YS, Gordon C, Bowman SJ, Anonymous00062. · Rheumatology Department, Division of Immunity and Infection, The University of Birmingham, UK. · Rheumatology (Oxford). · Pubmed #16728437 links to  free full text

Abstract: OBJECTIVES: To analyse the healthcare usage, direct healthcare costs and predictors of cost in primary Sjögren's syndrome (PSS) in the UK and to compare the findings with the data from healthy control groups and rheumatoid arthritis (RA) patients. METHODS: A total of 129 patients with PSS (American-European criteria), 91 with RA and 92 controls, were included in the study. All groups were age-matched females and all completed questionnaires on health status (SF-36) and healthcare utilization (economic component of the Stanford Health Assessment Questionnaire). Annual direct healthcare costs were calculated (and expressed in 2004 UK pound sterling) and predictors of costs for each patient group were determined by regression analyses. Age, health status, disease duration and anti-Ro/La antibody positivity were used as potential predictor variables. RESULTS: Mean age was similar in the PSS (59.2 yrs, S.D. 11.6), RA (60.3 yrs, S.D. 10.5) and control groups (57.7 yrs, S.D. 12.5). The mean disease duration was 5.4 yrs (S.D. 4.8) in the PSS group and 13.4 yrs (S.D. 11.4) in the RA group. The mean annual total direct cost per patient [95% confidence interval (CI)] was 2188 pounds sterling (1831 and 2546 pounds sterling) in the PSS group, 2693 pounds sterling(2069 and 3428 pounds sterling) in the RA group and 949 pounds sterling (741 and 1156 pounds sterling) in the control group. The costs in the PSS group were greater than for the RA and control groups for visits to all healthcare professionals (total) as well as visits to the dentist, dental hospital and ophthalmologist. The costs in the PSS and RA groups were higher than in controls for diagnostic tests and visits to hospital and the accident and emergency (A&E) department. The PSS group also incurred higher costs than controls, but lower costs than the RA group, for visits to a rheumatologist, urine and blood tests, assistive devices and drug therapy. Regression analysis identified the SF-36 physical function subscale as the best predictor of costs in PSS patients as well as controls and the mental health subscale in RA patients. CONCLUSION: This is the first study to evaluate direct healthcare costs in patients with PSS. PSS has a significant impact on the healthcare system, similar to that of RA, by more than doubling costs compared with control patients.

Fautrel B, Clarke AE, Guillemin F, Adam V, St-Pierre Y, Panaritis T, Fortin PR, Menard HA, Donaldson C, Penrod JR. · Department of Rheumatology, Hospital Pitié-Salpêtrière, 83 bd de l'Hôpital, 75013 Paris, France. · J Rheumatol. · Pubmed #15742435 No free full text.

Abstract: 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.

Adam V, St-Pierre Y, Fautrel B, Clarke AE, Duffy CM, Penrod JR. · Division of Clinical Epidemiology, McGill University Health Centre, The Montreal General Hospital, Montreal, Canada. · J Rheumatol. · Pubmed #15693099 No free full text.

Abstract: OBJECTIVE: Adolescent arthritis or rheumatism (AAR) has been shown to influence the activities, mental health, and healthcare utilization of affected individuals. However, these effects have never been estimated in a population-based sample. We examined the association of AAR with health status, health services use, health behaviors, and activity limitations. We also investigated the effect of socioeconomic status and family background on respondents with AAR. METHODS: The 1996 National Population Health Survey is a nationally representative survey exploring the health status and behaviors of Canadians. Among the 26,012 individuals aged 12 to 19 with complete responses on the presence of chronic illnesses, the 213 self-reporting arthritis or rheumatism (AAR) were compared to: (1) all other adolescents as a single group; or (2) the group of 9161 adolescents reporting other chronic diseases (OCD) but not AAR, and the group of 16,638 adolescents without chronic disease (WCD). Between-group differences were examined for the following variables: health status; use of health services; presence of activity limitations in school, work, or at home; and school enrollment and work status. RESULTS: Compared to those without, respondents with AAR reported more diagnoses of non-AAR chronic illnesses. Depression among AAR individuals was more prevalent than among non-AAR individuals, as was suffering from moderate or severe pain. Those with AAR were more likely than WCD individuals to use physician services, hospital services, and pain relief medications. AAR patients were more likely to be limited in their activities, and less likely to be enrolled in school than OCD or WCD individuals. CONCLUSION: This study indicates a broad range of effects of AAR in a nationally representative sample. Arthritis or rheumatism affected measures of mental health, health service use, and the school, work, and home activities of affected individuals, compared to individuals without chronic disease or with other chronic disease.

Clarke AE, St-Pierre Y, Joseph L, Penrod J, Sibley JT, Haga M, Genant HK. · Department of Medicine, Montreal General Hospital, Quebec, Canada. · J Rheumatol. · Pubmed #11708412 No free full text.

Abstract: OBJECTIVE: Few longitudinal data exist on the relationship between radiographic damage and self-reported functional disability and direct medical costs in rheumatoid arthritis (RA). We assessed these relationships. METHODS: One hundred thirty patients with RA (at time of the first available radiograph, mean age 56.6 yrs, 16.9% male, mean disease duration 16.8 yrs) were followed for up to 13.4 years. Semiannually, they reported on functional disability (0 = no difficulty, 3 = unable to do), global severity (0 = very well, 100 = very poor), pain (0 = no pain, 3 = severe pain), and health services utilization through completion of the Stanford Health Assessment Questionnaire (HAQ). Concurrent hand radiographs were scored for erosions and joint space narrowing using the Genant method and a single score summing both erosions and joint space narrowing for both hands was calculated (0 = no damage, 200 = maximum damage). The univariate association of functional disability, global severity, pain, or direct medical costs with concurrent radiographic damage was assessed through Spearman correlations and hierarchical regression models. The hierarchical models permit exploitation of the between-patient and within-patient variation present in our longitudinal data. RESULTS: At the time of the first available radiograph, mean (SD) levels of functional disability, global severity, and pain were 1.3 (0.7), 39.4 (21.0), and 1.1 (0.7), respectively. At entry into the study, the average radiograph score was 49.7 and upon leaving the study it was 66.9. Patients were followed an average of 6.7 years, with radiograph scores increasing at an average rate of 2.5 units/yr. The Spearman correlation [95% confidence interval (CI)] between average per-patient radiograph score and average per-patient HAQ disability index, average per-patient global severity, average per-patient pain score, and average per-patient direct medical costs was, respectively, 0.42 (0.26, 0.55), 0.23 (0.06, 0.39), 0.20 (0.03, 0.36), and 0.06 (-0.11, 0.23). The mean slope (95% CI) for disability on radiograph score was 0.0186 (0.0132, 0.0226), for severity on radiographs 0.1889 (0.1295, 0.2498), and for pain on radiographs 0.0057 (0.0027, 0.0084). As an example, over 10 years, a 25 unit (i.e., 50%) increase in radiograph scores would, on average, be associated with a 0.46 unit (i.e., 35%) increase in disability, a 4.72 unit (12%) increase in global severity score, and a 0.14 unit (13%) increase in pain, all expressed on the HAQ scales. There was little association between radiograph score and direct medical costs. CONCLUSION: A clinically meaningful association exists between radiographic damage and self-reported functional disability, suggesting that interventions that slow radiographic progression may improve the patient's health status. Such a relationship was not observed between radiographic damage and direct medical costs.

Clarke AE, Levinton C, Joseph L, Penrod J, Zowall H, Sibley JT, Grover SA, Esdaile JM. · Department of Medicine, Montreal General Hospital, McGill University, Quebec, Canada. · J Rheumatol. · Pubmed #10332970 No free full text.

Abstract: OBJECTIVE: With increasing interest in revising the mechanisms of health care funding, the ability to anticipate patients' medical expenditures as well as to identify potentially modifiable predictors would be informative for health care providers, payers, and policy makers. METHODS: Eight hundred fifty-eight patients with rheumatoid arthritis from 2 Canadian centers reported semi-annually on their health services utilization and health status for up to 12 years. Annual direct costs were calculated using 1994 Canadian prices. Regression models for the variation in total direct costs and the individual resource components (i.e., physicians, tests, medications, acute and non-acute hospital care) were estimated using previous values of age, sex, disease duration, education, methotrexate availability, employment status, global well being, pain, duration of morning stiffness, and functional disability as predictor variables. The models were developed using all available data except the last 2 observations (i.e., data collected on the last 2 self-report questionnaires) from each patient, which were reserved for model validation. The predictive abilities of the models were assessed by comparing the most recent costs with those predicted by the model using values of the predictor variables from the previous time period. Further, to assess whether the models conferred any advantage over cost estimates based only on previous costs, most recent observed costs were also compared with costs observed in the preceding time period. RESULTS: Self-reported indices of either global well being, pain, or functional disability predicted total direct costs as well as the costs of the 5 individual resource components. Being younger, female, disabled from the work force, having shorter disease duration, and receiving more formal education also predicted higher costs in at least on health resource category. However, being older predicted higher acute and non-acute care hospital costs. Regression models incorporating longitudinal data did not perform better than average costs in the preceding time period in predicting future short term costs. CONCLUSION: Global well being, pain, functional disability, and previous costs are the most important predictors of short term direct medical costs. Although we have demonstrated that regression models do not perform better than previous costs in predicting future short term costs, previous costs are a much less informative predictor than health status variables. Variables such as functional disability and pain identify potentially modifiable disease features and suggest interventions that may improve patient well being and reduce costs.