Cost effectiveness of etanercept (Enbrel) in combination with methotrexate in the treatment of active rheumatoid arthritis based on the TEMPO trial

OBJECTIVE: To estimate the cost effectiveness of combination treatment with etanercept plus methotrexate in comparison with monotherapies in patients with active rheumatoid arthritis (RA) using a new model that incorporates both functional status and disease activity. METHODS: Effectiveness data were based on a 2 year trial in 682 patients with active RA (TEMPO). Data on resource consumption and utility related to function and disease activity were obtained from a survey of 616 patients in Sweden. A Markov model was constructed with five states according to functional status (Health Assessment Questionnaire (HAQ)) subdivided into high and low disease activity. The cost for each quality adjusted life year (QALY) gained was estimated by Monte Carlo simulation. RESULTS: Disease activity had a highly significant effect on utilities, independently of HAQ. For resource consumption, only HAQ was a significant predictor, with the exception of sick leave. Compared with methotrexate alone, etanercept plus methotrexate over 2 years increased total costs by 14,221 euros and led to a QALY gain of 0.38. When treatment was continued for 10 years, incremental costs were 42,148 euros for a QALY gain of 0.91. The cost per QALY gained was 37,331 euros and 46,494 euros, respectively. The probability that the cost effectiveness ratio is below a threshold of 50,000 euros/QALY is 88%. CONCLUSION: Incorporating the influence of disease activity into this new model allows better assessment of the effects of anti-tumour necrosis factor treatment on patients' general wellbeing. In this analysis, the cost per QALY gained with combination treatment with etanercept plus methotrexate compared with methotrexate alone falls within the acceptable range.     

Modeling the progression of rheumatoid arthritis: a two-country model to estimate costs and consequences of rheumatoid arthritis

OBJECTIVE: Two simulation models were developed to analyze the cost-effectiveness of new treatments that affect the progression of rheumatoid arthritis (RA). METHODS: We used data from 2 cohorts of patients with early RA who had been followed up since disease onset (up to 15 years). In the Swedish study, 183 patients were followed up for a mean of 11.3 years. In the UK study, 916 patients were followed up for a mean of 7.8 years. Disease progression over 10 years was modeled as annual transitions between disease states, defined by Health Assessment Questionnaire (HAQ) scores. A regression model was used to estimate transition probabilities conditional on age, sex, and time since onset of disease, in order to allow simulation of different patient cohorts. Costs and utilities associated with different HAQ levels were based on data from the cohort studies and cross-sectional surveys. RESULTS: Costs increase and quality of life decreases as RA progresses. In Sweden, total annual costs range from 4,900 dollars to 33,000 dollars per patient, compared with 4,900 dollars to 14,600 dollars in the UK. Cumulative costs over 10 years for patients starting in disease state 1 (HAQ < 0.6) are 54,600 dollars in Sweden and 26,600 dollars in the UK. The cumulative numbers of quality-adjusted life-years (QALYs) are 5.5 and 5.6, respectively. Both costs and QALYs were discounted at 3%. CONCLUSION: The 2 models, which were based on different patient cohorts, reach a similar conclusion in terms of the effect of RA over 10 years. They appear to accurately capture disease progression and its effects and can therefore be useful in estimating the cost-effectiveness of new treatments in RA.     

Cost-utility and cost-effectiveness analyses of a long-term, high-intensity exercise program compared with conventional physical therapy in patients with rheumatoid arthritis

OBJECTIVE: To estimate the cost utility and cost effectiveness of long-term, high-intensity exercise classes compared with usual care in rheumatoid arthritis (RA) patients. METHODS: RA patients (n = 300) were randomly assigned to either exercise classes or UC; followup lasted for 2 years. Outcome measures were quality-adjusted life years (QALYs) according to the EuroQol (EQ-5D), Short Form 6D (SF-6D), and a transformed visual analog scale (VAS) rating personal health; functional ability according to the Health Assessment Questionnaire (HAQ) and McMaster Toronto Arthritis Patient Preference Interview (MACTAR); and societal costs. RESULTS: QALYs in both randomization groups were similar according to the EQ-5D and SF-6D, but were in favor of usual care according to the VAS (annual difference 0.037 QALY; 95% confidence interval [95% CI] 0.002, 0.069). Functional ability was similar according to the HAQ, but in favor of the exercise classes according to the MACTAR (annual difference 2.9 QALY; 95% CI 0.9, 4.9). Annual medical costs of the exercise program were estimated at 780 per participating patient (1 approximately $1.05). The increase per patient in total medical costs of physical therapy was estimated at 430 (95% CI 318, 577), and the increase in total societal costs at 602 (95% CI -490, 1,664). For societal willingness-to-pay equal to 50,000 per QALY, usual care had better cost utility than exercise classes, and significantly so according to the VAS. CONCLUSION: From a societal perspective and without taking possible preventive health effects into account, long-term, high-intensity exercise classes provide insufficient improvement in the valuation of health to justify the additional costs.     

Modeling the progression of rheumatoid arthritis: A two‐country model to estimate costs and consequences of rheumatoid arthritis

Objective

Two simulation models were developed to analyze the cost‐effectiveness of new treatments that affect the progression of rheumatoid arthritis (RA).

Methods

We used data from 2 cohorts of patients with early RA who had been followed up since disease onset (up to 15 years). In the Swedish study, 183 patients were followed up for a mean of 11.3 years. In the UK study, 916 patients were followed up for a mean of 7.8 years. Disease progression over 10 years was modeled as annual transitions between disease states, defined by Health Assessment Questionnaire (HAQ) scores. A regression model was used to estimate transition probabilities conditional on age, sex, and time since onset of disease, in order to allow simulation of different patient cohorts. Costs and utilities associated with different HAQ levels were based on data from the cohort studies and cross‐sectional surveys.

Results

Costs increase and quality of life decreases as RA progresses. In Sweden, total annual costs range from $4,900 to $33,000 per patient, compared with $4,900 to $14,600 in the UK. Cumulative costs over 10 years for patients starting in disease state 1 (HAQ < 0.6) are $54,600 in Sweden and $26,600 in the UK. The cumulative numbers of quality‐adjusted life‐years (QALYs) are 5.5 and 5.6, respectively. Both costs and QALYs were discounted at 3%.

Conclusion

The 2 models, which were based on different patient cohorts, reach a similar conclusion in terms of the effect of RA over 10 years. They appear to accurately capture disease progression and its effects and can therefore be useful in estimating the cost‐effectiveness of new treatments in RA.

     

Cost‐utility and cost‐effectiveness analyses of a long‐term,high‐intensity exercise program compared with conventional physical therapy in patients with rheumatoid arthritis

Objective

To estimate the cost utility and cost effectiveness of long‐term, high‐intensity exercise classes compared with usual care in rheumatoid arthritis (RA) patients.

Methods

RA patients (n = 300) were randomly assigned to either exercise classes or UC; followup lasted for 2 years. Outcome measures were quality‐adjusted life years (QALYs) according to the EuroQol (EQ‐5D), Short Form 6D (SF‐6D), and a transformed visual analog scale (VAS) rating personal health; functional ability according to the Health Assessment Questionnaire (HAQ) and McMaster Toronto Arthritis Patient Preference Interview (MACTAR); and societal costs.

Results

QALYs in both randomization groups were similar according to the EQ‐5D and SF‐6D, but were in favor of usual care according to the VAS (annual difference 0.037 QALY; 95% confidence interval [95% CI] 0.002, 0.069). Functional ability was similar according to the HAQ, but in favor of the exercise classes according to the MACTAR (annual difference 2.9 QALY; 95% CI 0.9, 4.9). Annual medical costs of the exercise program were estimated at €780 per participating patient (€1 ≈ $1.05). The increase per patient in total medical costs of physical therapy was estimated at €430 (95% CI €318, 577), and the increase in total societal costs at €602 (95% CI €?490, 1,664). For societal willingness‐to‐pay equal to €50,000 per QALY, usual care had better cost utility than exercise classes, and significantly so according to the VAS.

Conclusion

From a societal perspective and without taking possible preventive health effects into account, long‐term, high‐intensity exercise classes provide insufficient improvement in the valuation of health to justify the additional costs.

     

Cost effectiveness of adalimumab in the treatment of patients with moderate to severe rheumatoid arthritis in Sweden

BACKGROUND: Societal decision makers increasingly emphasise their need for evidence based economic analyses to make reimbursement decisions. OBJECTIVE: To analyse the cost utility of adalimumab, on both incremental cost and incremental quality adjusted life years (QALYs), versus traditional disease modifying antirheumatic drugs and the other tumour necrosis factor (TNF) antagonists suitable for submission to the Swedish LFN (Pharmaceutical Benefit Board). METHODS: Swedish unit costs and treatment guidelines from a lifetime perspective were implemented. A mathematical model, incorporating data from seven trials, simulated the experiences of 10 000 hypothetical patients with moderate to severe rheumatoid arthritis (RA). The primary outcome measure-QALYs-was derived from utility values calculated from a relationship between the Health Assessment Questionnaire (HAQ) Disability Index (DI) and Health Utility Index-III (HUI-3) from adalimumab trial results. The model followed the progression of HAQ-DI through a number of treatments in a sequence accounting for mortality, drug and monitoring costs, and other direct costs. RESULTS: When using ACR50 as a response threshold for determining successful treatment, adalimumab plus methotrexate showed the greatest number of QALYs gained (2.3 from one study and 2.1 from the pooled results of two trials). The etanercept plus methotrexate strategy yielded QALY gains similar to the pooled adalimumab results. Except for the infliximab strategy, the costs results were between 35 000 and 42 000, a range normally considered cost effective in other European countries. CONCLUSION: Adalimumab appears to be cost effective for the treatment of moderate to severe RA. The results suggest that adalimumab is at least as cost effective as other TNF antagonists.     

Assessing utility values in rheumatoid arthritis: a comparison between time trade-off and the EuroQol

OBJECTIVE: To compare the utility values and quality-adjusted life years (QALYs) obtained by the Time Trade-Off instrument (TTO) and the EuroQol-5D (EQ-5D) in patients with rheumatoid arthritis (RA); to analyze the association between utility values and Disease Activity Score 28 (DAS28) and Health Assessment Questionnaire (HAQ). METHODS: We conducted a longitudinal, prospective, 1-year study of RA patients selected randomly from 10 rheumatology clinics. TTO and EQ-5D were administered at 4 scheduled visits. RESULTS: The study sample comprised 300 RA patients (82% women, mean age 59 years, mean disease duration 10.3 years). A total of 260 patients completed both the TTO and the EQ-5D at baseline, and the mean +/- SD TTO scores were significantly higher than the EQ-5D scores (0.81 +/- 0.22 versus 0.53 +/- 0.35, P < 0.0001). The intraclass correlation coefficient (ICC) for the utility methods was 0.19. Data about changes in both TTO and EQ-5D scores during the study year were available in 163 patients. These changes tended to be larger in the TTO scores than the EQ-5D scores (mean +/- SD 0.05 +/- 0.25 versus -0.005 +/- 0.35, P = 0.054). The ICC for the mean changes in the utility scores was 0.24. Patients obtained a mean +/- SD of 0.04 +/- 0.20 QALYs based on TTO scores and 0.004 +/- 0.27 based on EQ-5D scores (P = 0.12). At baseline, the EQ-5D scores were highly correlated with the HAQ (r = -0.74) and moderately correlated with the DAS28 (r = -0.47), whereas the TTO correlated poorly with both the HAQ and DAS28. Correlation between the mean change in the EQ-5D and in the HAQ was moderate (r = -0.55). CONCLUSION: TTO and EQ-5D do not yield the same utility values. The results suggest that the EQ-5D is more representative of RA status than the TTO, a valuable conclusion when addressing economic evaluations in RA.     

Artritis reumatoide: ¿cuán cara es?

The present article reviews the main methodological features of cost analyses and economic evaluations in rheumatoid arthritis (RA). The main studies on costs and economic evaluations of interventions are also described. The economic impact of RA is substantial and the disease results in an incremental cost with respect to the population without arthritis. The distribution of indirect costs varies from one study to another, similar to that of direct costs, although these costs are strongly affected by hospital admissions and medication. The introduction of biological agents represents a short-term increase in costs. The beneficial effect of these agents on the variables predicting the cost of RA (Health Assessment Questionnaire [HAQ] and disease activity score [DAS]) may result in long-term savings, which should be measured. Economic evaluations of interventions, especially those performed in the long term using pharmacoeconomic models, incorporate a high degree of uncertainty. Most economic evaluations of biological agents obtain incremental cost-benefit ratios with respect to standard treatments of approximately 50,000 euros for each qualityadjusted life year (QUALY) gained.     

Cost-effectiveness of biological therapy compared with methotrexate in the treatment for rheumatoid arthritis in Colombia

The objectives of the study are to develop a cost-effectiveness model comparing biological therapy (BT) with methotrexate (MTX) alone, in the treatment for rheumatoid arthritis (RA), combining clinical and quality-of-life data from international trials with local costs and local epidemiological data. We designed a six-month cycle Markov model with five functional states, based on Health Assessment Questionnaire, with patients initiating treatment in any of the predefined states, based on a sample of 150 local RA patients. Simulations ran for 10 and 20 years, and for the whole life span. Utilities, in quality-adjusted life years (QALY), were taken from international literature. Discount rate was 3 % for costs and utilities. We calculated direct and indirect costs using a combination of international and local data. Results are presented as incremental cost-effectiveness ratios (ICER). ICERs in euros per QALY were €143,072 for 10 years; €139,332 for 20 years; and €137,712 for the whole life span. Total costs with MTX were lower than with BT, despite higher out of pocket, productivity, and complication costs. Under conventional thresholds, and for the “average” RA patient, BT would not be cost-effective in Colombia. BT compared to MTX provides more QALYs, but at a high cost. When ICERs were estimated for Colombia, BT would not be cost-effective. We propose different thresholds for different conditions, perhaps prioritizing chronic diseases that lead to disability.     

Functional Health Assessment Questionnaire (HAQ) and Psychological HAQ Are Associated with and Predicted by Different Factors in Rheumatoid Arthritis

OBJECTIVE: To evaluate the association between clinical, demographic, and psychological factors and the functional Health Assessment Questionnaire (HAQ) and psychological HAQ (PSHAQ) in patients with rheumatoid arthritis (RA). METHODS: After a mean followup time of 7 years after diagnosis, 112 patients with RA were asked to fill out the HAQ and the PSHAQ. Several clinical variables [erythrocyte sedimentation rate (ESR), visual analog scale (VAS) pain, VAS general well-being, Thompson joint score, and morning stiffness] had been assessed at diagnosis and at followup. In addition, the Impact of Rheumatic diseases on General health and Lifestyle questionnaire, comprising different domains of psychological distress, was assessed at diagnosis. Spearman correlations were calculated to determine associations between functional HAQ and clinical and psychological variables at baseline and to determine the associations between clinical variables and the HAQ and PSHAQ score at followup. Univariate logistic regression analyses were performed to identify possible predictors at diagnosis for a worse HAQ score and PSHAQ score (score > 1) at followup. RESULTS: At followup the functional HAQ score was associated with all clinical variables, whereas the PSHAQ was only associated with more subjective patient related variables (VAS pain, VAS general well-being, and morning stiffness). The final model of the multivariate regression analyses to predict a worse HAQ score at followup only included worse functional ability [odds ratio (OR) 2.63, 95% confidence interval (CI) 1.30-5.32, p = 0.007]. Anxiety (OR 1.13, 95% CI 1.03-1.24, p = 0.007) and a lower ESR value (OR 0.98, 95% CI 0.96-1.00, p = 0.05) assessed at diagnosis were included into the final model as predictors for a high PSHAQ score. CONCLUSION: Overall, the HAQ score, reflecting limitations of daily functioning, is a good representation of disease activity at diagnosis and after a mean disease duration of 7 years, whereas PSHAQ is not.     

Long-term followup of health status in patients with severe rheumatoid arthritis after high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation

OBJECTIVE: High-dose chemotherapy (HDC) followed by autologous hematopoietic stem cell transplantation (HSCT) is a new treatment for patients with severe, refractory rheumatoid arthritis (RA). The present study was undertaken to assess the health status of patients with severe RA over a long-term followup period after treatment with HDC + HSCT. METHODS: Health status and utility scores were assessed in 8 patients before and after treatment with HDC + HSCT. Patients were followed up for 5 years posttransplantation. Health status was assessed by the Health Assessment Questionnaire (HAQ), the RAND-36 version of the Short Form 36 (SF-36) health survey, and the Arthritis Impact Measurement Scales (AIMS). Utility scores were calculated using the EuroQol (EQ-5D) questionnaire and the SF-36-derived utility index (called the SF-6D), from which quality-adjusted life years (QALYs) were derived. RESULTS: Most measures of health status improved compared with baseline in the first 2 years posttransplantation, notably HAQ and AIMS scores and scores on the functional status, general health, and health change summary scales of the RAND-36 version of the SF-36. Utility scores derived from the EQ-5D questionnaire and the SF-6D also increased significantly after transplantation. This was reflected in the 0.28 QALYs gained compared with baseline. For a putative 50-year-old RA patient with a life expectancy of 20 years, a threshold analysis revealed that HDC + HSCT yielded more QALYs than conventional therapy when treatment-related mortality (TRM) was <2.8%. CONCLUSION: HDC + HSCT temporarily increased the functionality and health status of patients with severe, refractory RA. With a reported TRM of 1.3%, HDC + HSCT can be considered a realistic treatment option for patients with severe RA.     

Sources of discrepancy in patient and physician global assessments of rheumatoid arthritis disease activity

OBJECTIVE: To investigate discrepancy in the perception of rheumatoid arthritis (RA) disease activity between patient and physician, and its possible sources. METHODS: Eighty patients with RA rated their level of disease activity on a visual analog scale (VAS). Physician global assessment (MDGA) of disease activity was performed blinded to the patient evaluation except for the results of laboratory tests. A discrepancy score (DS) was calculated by subtracting MDGA from patient global assessment (PTGA), leading to definition of 3 groups of patients: (1) no discrepancy when PTGA and MDGA were within 1.0 or 3.0 cm of each other; (2) negative discrepancy when PTGA was under-rated relative to the physician; and (3) positive discrepancy when PTGA was over-rated relative to the physician. Age, sex, disease duration, education, income, residence area, employment, use of antirheumatic drugs, comorbidity, pain score, Health Assessment Questionnaire (HAQ) rating, tender (TJC) and swollen (SJC) joint count, and Disease Activity Score (DAS28) were recorded. RESULTS: Negative discrepancy was found in 27.5% (VAS 1 cm) and 8.7% (VAS 3 cm) of patients, positive discrepancy in 43.7% (VAS 1 cm) and 23.7% (VAS 3 cm), and no discrepancy in 28.7% (VAS 1 cm) and 67.5% (VAS 3 cm). Patients were predominantly older (mean age near 50 yrs), female, with long disease duration and low income. The negative discrepancy group had a lower level of education and higher C-reactive protein (p < 0.05). The positive discrepancy group presented a higher pain score, HAQ score, and TJC (p < 0.0001). The no-discrepancy group had lower SJC (p < 0.05). CONCLUSION: Our results indicate that for disease activity in patients with RA assessed on pain score, HAQ, and TJC, the only important feature that determined perception of their RA disease activity was education.     

Assessing utility values in rheumatoid arthritis: A comparison between time trade‐off and the EuroQol

Objective

To compare the utility values and quality‐adjusted life years (QALYs) obtained by the Time Trade‐Off instrument (TTO) and the EuroQol‐5D (EQ‐5D) in patients with rheumatoid arthritis (RA); to analyze the association between utility values and Disease Activity Score 28 (DAS28) and Health Assessment Questionnaire (HAQ).

Methods

We conducted a longitudinal, prospective, 1‐year study of RA patients selected randomly from 10 rheumatology clinics. TTO and EQ‐5D were administered at 4 scheduled visits.

Results

The study sample comprised 300 RA patients (82% women, mean age 59 years, mean disease duration 10.3 years). A total of 260 patients completed both the TTO and the EQ‐5D at baseline, and the mean ± SD TTO scores were significantly higher than the EQ‐5D scores (0.81 ± 0.22 versus 0.53 ± 0.35, P < 0.0001). The intraclass correlation coefficient (ICC) for the utility methods was 0.19. Data about changes in both TTO and EQ‐5D scores during the study year were available in 163 patients. These changes tended to be larger in the TTO scores than the EQ‐5D scores (mean ± SD 0.05 ± 0.25 versus ?0.005 ± 0.35, P = 0.054). The ICC for the mean changes in the utility scores was 0.24. Patients obtained a mean ± SD of 0.04 ± 0.20 QALYs based on TTO scores and 0.004 ± 0.27 based on EQ‐5D scores (P = 0.12). At baseline, the EQ‐5D scores were highly correlated with the HAQ (r = ?0.74) and moderately correlated with the DAS28 (r = ?0.47), whereas the TTO correlated poorly with both the HAQ and DAS28. Correlation between the mean change in the EQ‐5D and in the HAQ was moderate (r = ?0.55).

Conclusion

TTO and EQ‐5D do not yield the same utility values. The results suggest that the EQ‐5D is more representative of RA status than the TTO, a valuable conclusion when addressing economic evaluations in RA.

     

Association of anti-CCP positivity with serum ferritin and DAS-28

Antibodies to cyclic citrullinated peptides (anti-CCP) are highly specific for the diagnosis of rheumatoid arthritis (RA) with a marginal increased prediction of the disease. In this study, we aimed to investigate the relation of the presence of anti-CCP with clinical manifestations and disease activity in a cohort of RA patients. A total of 61 RA patients were included in this study. Data of disease-related parameters such as duration of disease, medications, degree of pain (visual analog scale, VAS), disease activity score 28 (DAS-28) and health assessment questionnaire (HAQ) were recorded. Laboratory workup included erythrocyte sedimentation rate (ESR), plasma C-reactive protein (CRP), rheumatoid factor (RF), anti-CCP, complete blood count and anemia parameters. Anti-CCP positivity was associated with higher scores of DAS-28, longer duration of morning stiffness, serum RF positivity and low levels of serum ferritin, while it was not associated with disease duration, VAS, HAQ, ESR, CRP and hemoglobin.     

Assessing the impact of rheumatoid arthritis on quality of life in a group of patients attending a rheumatology clinic in Sri Lanka

BackgroundRheumatoid arthritis (RA) has a worldwide distribution affecting 0.5–3% of the population. We used Stanford Health Assessment Questionnaire (HAQ) to assess the quality of life (QOL) in a sample of patients with RA. Disability assessment component of the HAQ; the HAQ-DI, assesses a patient's level of functional ability and has been validated and used in clinical trials extensively.ObjectiveTo find the impact of illness on quality of life, in a sample of patients with RA using HAQ, and to calculate the HAQ-DI. Additionally, to find the age distribution and relationship of HAQ-DI with VAS, DAS28 and duration of illness.MethodologyA self administered questionnaire was used in a random sample of 100 patients attending a rheumatology clinic. Statistical analysis was done using the SPSS statistical package version 17 (SPSS Institute, Chicago).ResultsWe had a 100% female population with mild disease [HAQ-DI (0–<1)] in 62% of patients, while severe disease (≥2 and ≤3) was found in 5%. RA prevalence was highest in 41–50 years group (mean age ± SD = 50.8 ± 11.5 years). VAS had a positive correlation with HAQ-DI. Relationship of HAQ-DI and DAS28 was not statistically significant (p = 0.72), although there was a positive correlation between DAS28 and HAQ-DI in disease duration more than 5 years group (r = 0.19). Mean HAQ score was the highest in more than 10 years disease duration population (p = 0.006).ConclusionIn a busy clinic setting, simple parameters like disease duration and VAS give an indication about the functional effect of illness on a patient's quality of life.     

The cost-effectiveness of etanercept and infliximab for the treatment of patients with psoriatic arthritis

OBJECTIVE: Tumour necrosis factor (TNF) antagonists have been shown to improve the outcomes in patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA). We assess the cost-effectiveness of two TNF antagonists and so-called 'palliative care' for the treatment of active PsA from the perspective of the UK National Health Service (NHS). METHODS: Bayesian statistical methods were used to synthesize evidence from three Phase III trials, identified through a systematic review, and estimate the relative efficacy of etanercept, infliximab and palliative care. A probabilistic decision analytic model was then used to compare these treatments after the failure of at least two conventional disease-modifying anti-rheumatic drugs (DMARDs), following the British Society for Rheumatology (BSR) guidelines for use. The primary outcome measure, quality-adjusted life years (QALYs), was derived from utility values estimated as a function of disability measured by the Health Assessment Questionnaire (HAQ). The deterioration experienced in HAQ at treatment withdrawal (rebound) was incorporated using alternative scenarios to represent best- and worst-case assumptions. The model was extended beyond the trial duration to a 10-yr and lifetime horizon, using available evidence and expert opinion-based assumptions on disease progression. Resource utilization was based on literature, national databases and expert opinion. Prices were obtained from routine NHS sources and published literature. RESULTS: At a 10-yr time horizon, the incremental cost-effectiveness ratio (ICER) for etanercept compared with palliative care was pound sterling26 361 per QALY gained for the best-case rebound scenario, which increased to pound sterling30 628 for the worst-case. The ICERs for infliximab compared with etanercept were pound sterling165 363 and pound sterling205 345 per QALY, respectively. These findings are mainly explained by the fact that infliximab has higher acquisition and administration costs without substantially superior effectiveness compared with etanercept. Results were sensitive to estimates of rebound assumptions at withdrawal and the time horizon. CONCLUSIONS: Only results for etanercept remained within the range of cost-effectiveness estimates considered to represent value for money in the NHS by the National Institute for Health and Clinical Excellence. Further research appears most valuable in relation to the short-term effectiveness, utility parameters and assumptions regarding the effect of rebound.     

Scores for functional disability in patients with rheumatoid arthritis are correlated at higher levels with pain scores than with radiographic scores

OBJECTIVE: To analyze correlations of functional disability scores with other measures of clinical status, in particular, Larsen radiographic scores and pain scores, in patients with rheumatoid arthritis (RA). METHODS: The functional capacity of 141 patients with RA (102 women, 39 men; median age 57 years; median disease duration 11.8 years; 83% rheumatoid factor positive) was assessed according to the Stanford Health Assessment Questionnaire (HAQ). Other variables studied included Larsen scores for radiographic damage of the small joints of the hands, wrists, and feet, pain scores by visual analog scale (VAS), Disease Activity Scores, general health scores by VAS, and Beck Depression Inventory (BDI) scores. RESULTS: The Spearman correlation coefficient comparing HAQ and Larsen scores was 0.277 (P = 0.001) and between HAQ and pain scores 0.652 (P < 0.001). In regression analysis, pain scores explained 41.4% of the variation in HAQ scores, normalized Larsen scores explained 7.3%, and BDI scores explained 5.5%; other variables were not significant in the model. CONCLUSION: Functional capacity scores of patients with RA are correlated at higher levels with pain scores than with radiographic scores of small joints.     

Cost effectiveness of losartan in patients with hypertension and LVH: an economic evaluation for Sweden of the LIFE trial

OBJECTIVE: Evaluate the cost effectiveness of losartan compared with atenolol from a Swedish national health system perspective. DESIGN: The Losartan Intervention For Endpoint reduction in hypertension study (LIFE) was a double-masked, randomized trial of losartan versus atenolol in 9193 patients with essential hypertension and left ventricular hypertrophy (LVH) ascertained by electrocardiography. Losartan reduced the primary composite end point of cardiovascular death, myocardial infarction (MI), or stroke by 13% (P = 0.021) and reduced the risk of stroke by 25% (P = 0.001), despite a comparable degree of blood pressure control. METHODS: Life years gained was estimated by combining the absolute risk reduction in stroke with the life years gained by preventing stroke. Quality-adjusted life years (QALYs) gained was estimated by combining the absolute risk reduction in stroke with the QALYs gained by preventing stroke. QALYs were estimated by weighting life years by health-related quality of life (QoL), as measured with visual analogue scale (VAS) data collected in the trial. Net costs were defined as the total of study medication cost, stroke-related costs, and costs of increased survival. Costs are in 2003 Swedish prices. All costs and effects were discounted at a 3% annual rate. RESULTS: Prevention of a stroke resulted in a gain of 5.7 life years and 4.3 QALYs. As a consequence, losartan treatment resulted in a per patient increase of 0.092 life years [95% confidence interval (CI): 0.038, 0.146] and 0.069 QALYs (95% CI: 0.028, 0.109) as compared with atenolol treatment. Losartan reduced direct stroke-related cost per patient by 1141 euros due to a lower cumulative incidence of stroke for losartan at 5.5 years (4.9%) as compared with atenolol (6.5%) (95% CI of difference: 0.7, 2.5). The reduction in stroke-related cost offset 80% of the added cost of losartan drug therapy. After inclusion of study medication cost, net cost per patient was 289 euros higher for losartan than atenolol. The net cost per QALY gained for losartan was 4188 euros (37,813 SEK), which is well within common Swedish benchmark upper values (200-500,000 SEK) for accepted cost-effective interventions. CONCLUSION: Based on the results from the LIFE trial, treatment with losartan compared with atenolol, in hypertensive patients with LVH, is a cost-effective intervention.     

A reappraisal of HAQ disability in rheumatoid arthritis

OBJECTIVE: To investigate the course of self-reported disability in rheumatoid arthritis (RA) using the major self-report measure of functional impairment, the Health Assessment Questionnaire (HAQ). METHODS: The course of HAQ disability was assessed in 32,525 observations (1,843 patients) in which the HAQ was administered. In addition, a subset of 2,189 visits from 50 patients, followed on average for 17 years, was studied to model the effect of disease duration on the course of HAQ disability in individual patients. Linear and fractional polynomial regression as well as smoothing algorithms were applied to the group of RA patients and then to the individual course of patients. RESULTS: Group linear and nonlinear models of the effect of disease duration on HAQ disability were found to have 3 characteristics: 1) HAQ disability scores are high at disease onset rather than gradually increasing; 2) HAQ disability increases very slowly over time (0.03 units per year); and 3) all such models fit very poorly, explaining only 5% of the variance in HAQ disability scores. However, application of nonlinear models to individual patient courses (as opposed to groups of patients) explains 37% of the HAQ disability score variation. In some patients, the course of HAQ disability was either 1) chaotic (scores change without any pattern) or 2) determinable, but unrelated to time. When covariates were added to the group model, however, the course of HAQ disability became clearer, and 51% of the variance in the disability score could be explained, statistically, by pain, depression, erythrocyte sedimentation rate, and disease duration. CONCLUSION: Individual RA patients have differing, characterizable courses: 1) nonlinear, 2) chaotic, or 3) non-time determined. The model that self-reported physical disability, as measured by the HAQ, occurs as a function of disease acting over time does not fit the data well and is an inadequate model. This discrepancy may also be the result of the patient's upward reappraisal of functional ability with increasing time. The predominant determinants of HAQ disability in RA are disease activity, pain, and psychosocial factors rather than structural abnormality. Although the HAQ is a useful clinical tool and a central measure of disease outcome, it measures both process and outcome, and usually more process than outcome. Individual patient models that include all that is known about the patient--the paradigm of clinical care-may be a more effective way to examine the course of RA than are conventional group-based models.