Rheumatoid Arthritis: Marra CA

Bansback N, Marra CA. · No affiliation provided · Arthritis Rheum. · Pubmed #19248126 No free full text.

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Bansback NJ, Anis AH, Marra CA. · No affiliation provided · J Rheumatol. · Pubmed #18671320 links to  free full text

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Marra CA, Esdaile JM, Sun H, Anis AH. · No affiliation provided · J Rheumatol. · Pubmed #11128654 No free full text.

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Bansback N, Marra CA, Finckh A, Anis A. · Centre for Health Evaluation and Outcome Sciences, St Paul's Hospital, BC, Canada. · Best Pract Res Clin Rheumatol. · Pubmed #19233048 No free full text.

Abstract: Recent years have witnessed a shift in the therapeutic approach for patients with early rheumatoid arthritis (RA). The focus of interest has been the improved outcomes achieved through the use of early aggressive disease-modifying therapy, including the use of biologic agents. Such strategies have acquisition costs which typically exceed those of older anti-rheumatic strategies. However, improved outcomes might lead to fewer hospitalizations and physician visits and improved employability, leading to future cost savings. This is in addition to the health benefits which patients value as improvements in quality of life. With many services competing to spend often limited health-care budgets, information on the relative benefits and costs of new approaches for treating RA can be useful in deciding on efficient allocation and treatment decisions.

Reynolds J, Shojania K, Marra CA. · Division of Rheumatology, Faculty of Medicine, University of British Columbia, Vancouver, Canada · Pharmacotherapy. · Pubmed #18041889 No free full text.

Abstract: Rheumatoid arthritis is a chronic autoimmune disease that often leads to functional disability and reduced quality of life. The pathogenesis of synovial inflammation that is associated with this disease is thought to result from T-cell activation. To become fully activated, T cells require an antigen-specific signal through the T-cell receptor and a second signal through a costimulatory receptor. Abatacept is the first drug in a new class of disease-modifying antirheumatic drugs (DMARDs) known as selective costimulation modulators. Costimulation modulators block the second signal and decrease T-cell activation. Abatacept has been approved by the United States Food and Drug Administration for reducing signs and symptoms, inducing major clinical response, slowing the progression of structural damage, and improving physical function in adults with moderate-to-severe active rheumatoid arthritis who have had an inadequate response to at least one other DMARD, such as methotrexate or tumor necrosis factor (TNF)-alpha inhibitors. Randomized controlled trials have shown that abatacept improves both clinical outcomes and health-related quality of life in patients who have had an inadequate response to other DMARDs. Abatacept has been shown to be well tolerated. In clinical trials, however, abatacept treatment was associated with a higher rate of infections compared with placebo. This finding was compounded when abatacept was used with TNF-alpha inhibitors; thus, this combination should be avoided. Abatacept appears to be a useful treatment option for patients with rheumatoid arthritis who have previously failed other DMARDs. However, additional clinical trials evaluating its long-term effect on patient safety and disease outcomes are needed.

Tan MC, Regier DA, Esdaile JM, Lynd LD, Anis AH, Marra CA. · Vancouver Coastal Health Research Institute, Vancouver, British Columbia, Canada. · Arthritis Rheum. · Pubmed #16874788 links to  free full text

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Bansback NJ, Regier DA, Ara R, Brennan A, Shojania K, Esdaile JM, Anis AH, Marra CA. · Health Economics and Decision Science, School of Health and Related Research, University of Sheffield, Sheffield, UK. · Drugs. · Pubmed #15733011 No free full text.

Abstract: Rheumatoid arthritis (RA) is a chronic, progressive, inflammatory disease that affects approximately 0.5-1% of the adult population. The introduction of new disease-modifying antirheumatic drugs (DMARDs) such as leflunomide, anakinra and the tumour necrosis factor (TNF)-alpha antagonists (infliximab, etanercept and adalimumab) have transformed the management of RA. In particular, the last class of agents has generated substantial controversy. Costing between 16,000 US dollars and 20,000 US dollars per patient-year (2001 values), the potential greater efficacy of treatment with TNFalpha antagonists comes at much higher drug costs, making these agents natural candidates for cost-effectiveness analyses (CEAs).A MEDLINE search (until 31 January 2004) identified six original CEAs evaluating TNFalpha antagonists in RA. The aim of a CEA is to facilitate the allocation of scarce health resources and to inform policy decisions. However, to enhance the reliability and relevance of these analyses to policy makers, there must be similarity between the methodologies used. Recently, the OMERACT (Outcome Measures in Rheumatoid Arthritis Clinical Trials) group produced a document to define such a reference case; the OMERACT document was used as a foundation to structure comparisons and highlight discrepancies.The methodologies employed in each analysis differed; in particular, disparate time horizons, comparators, quantities of drug and treatment sequences prohibit the comparison of cost effectiveness between studies. Outcomes also differed between the analyses. Most reported health-related quality of life (HR-QOL) in quality-adjusted life-years (QALYs). The QALYs metric was based on preference scores that were typically derived from linear regressions using the Health Assessment Questionnaire (HAQ). However, models also used American College of Rheumatology (ACR) criteria, as well as the disease activity score (DAS). Common to all studies was the lack of data from long-term randomised studies where efficacy and resource consumption in comparison with standard care has been investigated. As such, investigators combined short-term randomised control trial data with that of a long-term observational cohort, and modelled cost effectiveness over an appropriate time horizon. In addition, most analyses lacked rigorous sensitivity analysis to examine the impact of uncertainty in the parameters.Those analyses that examined time horizons of 6 months and 1 year published incremental cost-effectiveness ratios (ICERs) of 34,800 US dollars per ACR 70% response criteria (ACR70) weighted response (duration 6 months, 1999 values) and 96,166 US dollars (duration 1 year, 2002 values). Analyses that modelled costs and health outcomes beyond the first year reported ICER estimates ranging between 26,800 US dollars (patients' lifetime, 1998 values) and 40,308 US dollars (10 years, 2002 values). In terms of HR-QOL, the analyses reported incremental QALYs that ranged from 0.116 (over 19 years) to 1.6 (over 10 years). Discounted costs of therapy ranged from 30,362 US dollars (10 years, 2002 values) to 93,000 US dollars (22 years, 1998 values), and comparator costs ranged from 22,593 US dollars (10 years, 2002 values) to 84,000 US dollars (22 years, 1998 values).

Nahar IK, Shojania K, Marra CA, Alamgir AH, Anis AH. · Division of Rheumatology, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada. · Ann Pharmacother. · Pubmed #12921510 No free full text.

Abstract: OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, safety, and pharmacoeconomic impact of infliximab in the treatment of Crohn's disease (CD) and rheumatoid arthritis (RA). DATA SOURCES: MEDLINE and Pre-MEDLINE (1966-June 2002) and manufacturer prescribing literature were employed to find English-language articles on infliximab. Additional studies and abstracts were identified from the bibliographies of reviewed literature and conference proceedings. STUDY SELECTION/DATA EXTRACTION: All articles identified from data sources were evaluated, and all information deemed relevant was included in this review. Information regarding basic pharmacology was collected from studies in animals. Pharmacokinetic data were collected from human trials. Safety data were extracted from clinical trials and postmarketing surveillance. Priority was given to randomized, double-blind, placebo-controlled studies for the assessment of efficacy. All available economic evaluations were included. DATA SYNTHESIS: Infliximab is a new monoclonal antibody that appears to work by a unique mechanism: inhibiting the action of tumor necrosis factor-alpha (TNF-alpha). Infliximab is administered by intravenous infusion. In clinical trials in CD, infliximab significantly decreased the CD activity index compared with placebo in treatment-resistant disease and significantly reduced the number of draining fistulas in fistulizing disease. In RA, when infliximab was added to methotrexate (MTX), it resulted in a significant improvement in most disease outcome measures when compared with MTX plus placebo. Few major adverse effects were reported in the clinical trials; however, serious adverse events, including malignancy and demyelination, have been reported in postmarketing surveillance. Also, increased susceptibility to infections (including tuberculosis) has been reported. CONCLUSIONS: Infliximab is an effective new agent for the treatment of CD and RA. Its apparent unique mechanism of action makes infliximab an important addition to therapy. Caution should be exercised when considering infliximab for individuals who have chronic or recurrent infections, mild congestive heart failure (New York Heart Association [NYHA] class I/II), nervous system disorders, or live or have lived in an area endemic for histoplasmosis. Infliximab is contraindicated for patients with a clinically important, active infection, moderate to severe congestive heart failure (NYHA class III/IV), or an allergy to mouse proteins or any of the ingredients in infliximab. Further long-term efficacy, safety, and economic data on infliximab are required. Also, for the treatment of RA, the burden of administering infliximab (as a 2-hour supervised infusion) has to be considered when choosing among anti-TNF-alpha medication (as the other 2 approved agents, etanercept and adalimumab, can be self-administered by subcutaneous injection).

Zhang W, Bansback N, Guh D, Li X, Nosyk B, Marra CA, Anis AH. · Centre for Health Evaluation and Outcome Sciences, St. Paul's Hospital, Vancouver, British Columbia, Canada. · J Rheumatol. · Pubmed #18688916 No free full text.

Abstract: OBJECTIVE: To evaluate the shortterm effect of adalimumab on work productivity in patients with moderate to severe active rheumatoid arthritis (RA). METHODS: In a substudy of the Canadian Adalimumab Clinical Trial (CanAct), clinical, health status, and productivity outcomes were measured at baseline and 12 weeks. Patients were classified as responders and nonresponders by the 20% American College of Rheumatology (ACR20) improvement criterion and the minimum clinically important difference (MCID) of the Health Assessment Questionnaire (HAQ) score (0.22), respectively. The Health and Labour Questionnaire (HLQ) was used to measure productivity outcomes and costs. RESULTS: Included in the analysis were 389 patients completing both baseline and 12-week HLQ questionnaire. Absenteeism (a decrease of 0.5 workdays per 2 weeks) and unpaid work productivity (3.5 fewer hours unpaid help per 2 weeks) were improved significantly after 12 weeks. Improvements in productivity outcomes were associated with clinical response. Bootstrapping results suggest that responders achieved statistically significant improvement in presenteeism (ACR20) and unpaid work productivity (ACR20 and HAQ) versus nonresponders. The costs saved by responders were up to $155.04 per 2 weeks more than those by nonresponders. CONCLUSION: The costs of adalimumab were partially offset, even in the short term, by cost savings induced by clinical response among Canadian patients with moderate to severe RA. These findings complement results of other study analyses that demonstrate early and sustained benefits of adalimumab.

Marra CA, Esdaile JM, Guh D, Fisher JH, Chalmers A, Anis AH. · Department of Health Care and Epidemiology, Faculty of Medicine, University of British Columbia, and Centre for Health Evaluation and Outcomes Sciences, St. Paul's Hospital, Vancouver, Canada. · Arthritis Rheum. · Pubmed #11409664 links to  free full text

Abstract: OBJECTIVE: To determine factors associated with response or toxicity to cyclosporin A (CSA) in a population-based inception cohort with rheumatoid arthritis (RA). METHODS: Prospectively collected longitudinal measures including tender joint count (JC), duration of morning stiffness (MS), systolic and diastolic blood pressure (SBP, DBP), and serum creatinine (SCr) were modeled using generalized estimating equations. Survival methods were used to estimate CSA continuation time and its determinants. RESULTS: Of 133 patients (75% female, median RA duration 13 years), 37 discontinued CSA because of ineffectiveness (19) or because of toxicity (18) including increased SCr in 10, hypertension in 4, infections in 3, and gingival hyperplasia in 1. Patients remained on CSA a median of 75 months (95% confidence interval [CI] 38-112). Those receiving concomitant methotrexate (MTX) were more than 4 times as likely to continue on CSA therapy (hazard ratio 0.22, 95% CI 0.10-0.94). A lower final JC was predicted by a longer CSA treatment duration (relative risk [RR] 0.99 per month, 95% CI 0.98-0.99) and concomitant MTX therapy (RR 0.79, 95% CI 0.63-0.99); decreased MS was predicted only by longer CSA treatment duration (reduction of 2.0 minutes per month, 95% CI 1.1-3.0). Each previous disease-modifying antirheumatic drug (DMARD) exposure predicted a rise in SCr (35 micromole/liter, 95% CI 22-48), SBP (7.2 mm Hg, 95% CI 2.7-11.7), and DBP (3.8 mm Hg, 95% CI 3.0-6.4). CONCLUSIONS: Combination CSA/MTX prolongs therapy and reduces JC. Long-term CSA treatment was fairly well tolerated. Previous DMARD use appears to be a determinant for the development of toxicity.

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.

Rashidi AA, Anis AH, Marra CA. · Centre for Clinical Epidemiology and Evaluation, Faculty of Pharmaceutical Sciences, University of British Columbia, Canada. · Health Qual Life Outcomes. · Pubmed #16626489 links to  free full text

Abstract: BACKGROUND: Assessment of Health Related Quality of Life (HRQL) has become increasingly important and various direct and indirect methods and instruments have been devised to measure it. In direct methods such as Visual Analog Scale (VAS) and Standard Gamble (SG), respondent both assesses and values health states therefore the final score reflects patient's preferences. In indirect methods such as multi-attribute health status classification systems, the patient provides the assessment of a health state and then a multi-attribute utility function is used for evaluation of the health state. Because these functions have been estimated using valuations of general population, the final score reflects community's preferences. The objective of this study is to assess the agreement between community preferences derived from the Health Utilities Index Mark 2 (HUI2) and Mark 3 (HUI3) systems, and patient preferences. METHODS: Visual analog scale (VAS) and HUI scores were obtained from a sample of 320 rheumatoid arthritis patients. VAS scores were adjusted for end-aversion bias and transformed to standard gamble (SG) utility scores using 8 different power conversion formulas reported in other studies. Individual level agreement between SG utilities and HUI2 and HUI3 utilities was assessed using the intraclass correlation coefficient (ICC). Group level agreement was assessed by comparing group means using the paired t-test. RESULTS: After examining all 8 different SG estimates, the ICC (95% confidence interval) between SG and HUI2 utilities ranged from 0.45 (0.36 to 0.54) to 0.55 (0.47 to 0.62). The ICC between SG and HUI3 utilities ranged from 0.45 (0.35 to 0.53) to 0.57 (0.49 to 0.64). The mean differences between SG and HUI2 utilities ranged from 0.10 (0.08 to 0.12) to 0.22 (0.20 to 0.24). The mean differences between SG and HUI3 utilities ranged from 0.18 (0.16 to 0.2) to 0.28 (0.26 to 0.3). CONCLUSION: At the individual level, patient and community preferences show moderate to strong agreement, but at the group level they have clinically important and statistically significant differences. Using different sources of preference might alter clinical and policy decisions that are based on methods that incorporate HRQL assessment. VAS-derived utility scores are not good substitutes for HUI scores.

Anis AH, Guh DP, Lacaille D, Marra CA, Rashidi AA, Li X, Esdaile JM. · Department of Health Care and Epidemiology, University of British Columbia, Vancouver, BC. · CMAJ. · Pubmed #16301701 links to  free full text

Abstract: BACKGROUND: Previous research has shown that patient cost-sharing leads to a reduction in overall health resource utilization. However, in Canada, where health care is provided free of charge except for prescription drugs, the converse may be true. We investigated the effect of prescription drug cost-sharing on overall health care utilization among elderly patients with rheumatoid arthritis. METHODS: Elderly patients (> or = 65 years) were selected from a population-based cohort with rheumatoid arthritis. Those who had paid the maximum amount of dispensing fees (200 dollars) for the calendar year (from 1997 to 2000) were included in the analysis for that year. We defined the period during which the annual maximum co-payment had not been reached as the "cost-sharing period" and the one beyond which the annual maximum co-payment had been reached as the "free period." We compared health services utilization patterns between these periods during the 4 study years, including the number of hospital admissions, the number of physician visits, the number of prescriptions filled and the number of prescriptions per physician visit. RESULTS: Overall, 2968 elderly patients reached the annual maximum cost-sharing amount at least once during the study periods. Across the 4 years, there were 0.38 more physician visits per month (p < 0.001), 0.50 fewer prescriptions filled per month (p = 0.001) and 0.52 fewer prescriptions filled per physician visit (p < 0.001) during the cost-sharing period than during the free period. Among patients who were admitted to the hospital at least once, there were 0.013 more admissions per month during the cost-sharing period than during the free period (p = 0.03). INTERPRETATION: In a predominantly publicly funded health care system, the implementation of cost-containment policies such as prescription drug cost-sharing may have the unintended effect of increasing overall health utilization among elderly patients with rheumatoid arthritis.

Marra CA, Rashidi AA, Guh D, Kopec JA, Abrahamowicz M, Esdaile JM, Brazier JE, Fortin PR, Anis AH. · Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, Canada. · Qual Life Res. · Pubmed #16047508 No free full text.

Abstract: BACKGROUND: Preference-based, generic measures are increasingly being used to measure quality of life and as sources for quality weights in the estimation of Quality Adjusted Life Years (QALYs) in rheumatoid arthritis (RA). However, among the most commonly used instruments (the Health Utilities Index 2 and 3 [HUI2 and HUI3], the EuroQoL-5D [EQ-5D], and the Short Form-6D [SF-6D], there has been little comparative research. Therefore, we examined the reliability and responsiveness of these measures and the Rheumatoid Arthritis Quality of Life (RAQoL) and the Health Assessment Questionnaire (HAQ) in a sample of RA patients. MAJOR FINDINGS: Test-retest reliability was acceptable for all of the instruments with the exception of the EQ-5D. Using two external criteria to define change (a patient transition question and categories of the patient global assessment of disease activity VAS), the RAQoL was the most responsive of the instruments. For the indirect utility instruments, the HUI3 and the SF-6D were the most responsive for measuring positive change. On average, for patients whose RA improved, the absolute change was highest for the HUI3. CONCLUSIONS: The HUI3 and the SF-6D appear to be the most responsive of the preference-based instruments in RA. However, differences in the magnitude of the absolute change scores have important implications for cost-effectiveness analyses.

Marra CA, Woolcott JC, Kopec JA, Shojania K, Offer R, Brazier JE, Esdaile JM, Anis AH. · Faculty of Pharmaceutical Sciences, University of British Columbia, Centre for Clinical Epidemiology and Evaluation, Vancouver Coastal Health Research Institute, 717-828 West 10th Ave, Vancouver, BC, Canada V6Z 1Y6. · Soc Sci Med. · Pubmed #15652688 No free full text.

Abstract: Rheumatoid arthritis (RA) is a common, chronic disease where health-related quality of life (HRQL) is one of the main goals of therapy. As such, instruments used to measure HRQL in RA must be able to discriminate across RA severity. The two basic categories of instruments used to measure HRQL are generic instruments and disease-specific instruments. Generic instruments can be further subdivided into preference-based measures which yield both single and multi-attribute utility values anchored at zero (death) and 1.00 (perfect health) as a measure of HRQL. The scores from these types of instruments can be integrated into cost-utility analyses as the weightings for quality adjusted life years. We assessed the construct validity of utility scores from four generic preference-based measures (the Health Utilities Index 2 and 3 (HUI2, HUI3), the EuroQol 5D (EQ-5D), and the Short Form 6-D (SF-6D) and disease specific measures (the Rheumatoid Arthritis Quality of Life Questionnaire (RAQoL) and the Health Assessment Questionnaire (HAQ)) in a sample of 313 RA patients in British Columbia, Canada. We also estimated the minimally important differences (MID) for each of the measures. Generally, as anticipated, the disease-specific measures were better able to discriminate across groups with higher RA severity; however, utility scores from each of the scales also appeared to discriminate well across RA severity categories. The MID values agreed with those previously reported in the literature for the HUI2, SF-6D and the HAQ and provided new information for the HUI3, EQ-5D and the RAQoL. We conclude that the all of the preference-based utility measures that were evaluated appear to adequately discriminate across levels of RA severity.

Marra CA, Esdaile JM, Guh D, Kopec JA, Brazier JE, Koehler BE, Chalmers A, Anis AH. · Department of Health Care and Epidemiology, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada. · Med Care. · Pubmed #15586840 No free full text.

Abstract: OBJECTIVES: Utility scores can be assessed indirectly using preference-based instruments and used as weightings for quality-adjusted life years in economic analyses. It is not clear whether available instruments yield similar results or what domains of health are contributing to the overall score in a sample of patients with rheumatoid arthritis (RA). SUBJECTS: Our study included 313 individuals with rheumatologist-confirmed RA. MEASURES: A self-completed survey that permitted scoring of 4 indirect utility instruments (the Health Utilities Index Mark 2 and 3 (HUI-2 and HUI-3), the EuroQoL (EQ-5D), and the Short Form 6D (SF-6D) was the basis of our study. RESULTS: Mean (standard deviation) global utility scores were 0.63 (0.24) for the SF-6D, 0.66 (0.13) for the EQ-5D, 0.71 (0.19) for the HUI-2, and 0.53 (0.29) for the HUI-3 (P = 0.02 by repeated-measures analysis of variance). The intraclass correlation across all the indices was 0.67 (95% confidence interval 0.62-0.71). Bland-Altman plots revealed that agreement among instruments was poor at lower utility values. In this elderly RA sample, all of the global utilities mostly measured functional ability and pain. CONCLUSIONS: There are significant differences in utilities obtained from different indirect methods. Agreement among the instruments was moderate but poorer at lower utilities. It is unlikely that these utility values, if used as the weightings for quality-adjusted life years, would result in comparable estimates.

Marra CA, Lynd LD, Esdaile JM, Kopec J, Anis AH. · Department of Health Care and Epidemiology, University of British Columbia, Vancouver, Canada. · Rheumatology (Oxford). · Pubmed #15292531 links to  free full text

Abstract: OBJECTIVE: Self-rated health (SRH) is an independent, strong predictor of morbidity and mortality. Socio-economic status (SES) is strongly associated with SRH. This study investigated the relationship between SES and SRH outcomes in a sample of patients with rheumatoid arthritis (RA) in Canada. METHODS: Both generic preference-based [Health Utilities Index Mark 3 (HUI3) and Short Form 6D (SF-6D)] and non-preference-based [disease-specific (Rheumatoid Arthritis Quality of Life, RAQoL) and a functional status (Health Assessment Questionnaire, HAQ)] SRH questionnaires were administered to 313 RA patients. Both proximate (education and annual household income) and contextual (neighbourhood income, education and unemployment) measures of SES were captured. Ordinary least squares (OLS) regression was used to adjust for RA severity while assessing the relationship between SRH and SES measures. Two-stage least-squares (TSLS) regression was used to determine if there was an inter-relationship between SES and SRH measures. RESULTS: The sample was well distributed across RA severity and SES measures. Contextual and proximate measures of SES were poorly correlated. Lower levels of proximate SES measures (but not contextual) were associated with poorer SRH outcomes. The OLS regressions showed significant associations between the HUI3 and the SF-6D overall scores and the HAQ for self-reported income. The RAQoL did not differ significantly across SES. TSLS regression confirmed the finding that self-reported income was similarly associated with the SRH measures. CONCLUSIONS: Even in a country with universal access to health-care, the impact of a chronic disease such as RA on SRH is associated with self-reported income. The finding that preference-based measures vary with income independently of RA severity could bias economic evaluation.

Marra CA, Esdaile JM, Anis AH. · Department of Health Care and Epidemiology, University of British Columbia, Vancouver, Canada. · J Rheumatol. · Pubmed #12465143 No free full text.

Abstract: OBJECTIVE: Thiopurine S-methyltransferase (TPMT), which catalyzes the inactivation of azathioprine (AZA), exhibits genetic polymorphism that results in dose related, serious toxicities (mainly hematological cytopenias) in 10-15% of individuals treated with AZA. Polymerase chain reaction (PCR) tests provide a sensitive, specific means of prospectively identifying these patients before AZA therapy and minimizing toxicity through dosage reduction. Our objective was to model the cost effectiveness of the 2 alternative AZA treatment strategies in rheumatologic conditions: (1) utilizing PCR to determine polymorphisms leading to TPMT deficiencies prior to AZA therapy with a reduction in dose; and (2) no testing. The analysis was conducted from a third party payer perspective over one year. METHODS: A decision analytic model was applied to map the costs and outcomes of patients under both strategies. Data applied to the model included the positive and negative predictive values of the PCR, the probabilities of adverse events due to AZA, and the costs associated with their management. Sources of data included published clinical trials, diagnostic test evaluations, surveillance trials, and economic evaluations. RESULTS: Dose related toxicities resulted in AZA discontinuation rates of 10-20%. The usual dosing strategy cost $677 Cdn per patient, whereas the genotype directed dosing strategy cost $663 Cdn per patient. In the genotype dosing strategy, the number needed to treat to avoid one adverse event over 6 months was 20. Thus, the genotype based dosing strategy dominated the usual dosing strategy. One-way sensitivity analyses revealed that the estimates were robust to ranges of +/- 30% for the costs, the properties of the PCR test, and the probability of adverse events. CONCLUSION: The introduction of PCR testing to identify TPMT polymorphisms prior to AZA treatment may represent good value in certain health care settings.