Does Etanercept Biosimilar Prescription in a Rheumatology Center Bend the Medication Cost Curve?

OBJECTIVE: The market entry of biosimilars is expected to bring budgetary relief. Our objective was to determine how the introduction of biosimilars influences medication costs in patients with rheumatoid arthritis (RA) and which patients gain access to biologics due to the availability of biosimilars. METHODS: Using hospital data of patients with RA between 2014 and 2018, an interrupted time series was performed. The interruption in the time series was placed at June 2016 (i.e., the introduction of the etanercept biosimilar). The changes in trends for rheumatic medication costs before and after the interruption were measured. Secondary analyses focused on explaining these trends. RESULTS: In the first quarter after the interruption, there was a decrease in total costs for biologic users of -€63,020 (95% CI -€96,487 to -€29,553, P = 0.001). The postinterruption trend did not differ from the preinterruption trend (95% CI -€6695 to €6715, P = 0.998) and after 3 quarters, the medication costs were back at the interruption level. After the interruption, the average cost per biologic user decreased by -€370 (95% CI -€602 to -€138, P = 0.005), followed by a quarterly decrease (relative to the preinterruption trend; 95% CI -€86 to -€14, P = 0.010), bending the average cost curve. The percentage of patients being treated with biologics increased in postinterruption by 0.50 percentage points quarterly (95% CI 0.38-0.62, P < 0.001). Also, the average age at the start of the first biologic increased after the interruption (P = 0.057). CONCLUSION: The average cost per patient treated with biologics decreased after the introduction of biosimilars with a persistent trend. However, the budgetary relief due to market entry of biosimilars vanished quickly due to an increase in patients treated with biologics.

Tailored, Therapist-Guided Internet-Based Cognitive Behavioral Therapy Compared to Care as Usual for Patients With Rheumatoid Arthritis: Economic Evaluation of a Randomized Controlled Trial.

BACKGROUND: Internet-based cognitive behavioral therapy can aid patients with rheumatoid arthritis with elevated levels of distress to enhance their quality of life. However, implementation is currently lacking and there is little evidence available on the (cost-) effectiveness of different treatment strategies. OBJECTIVE: Cost-benefit ratios are necessary for informing stakeholders and motivating them to implement effective treatment strategies for improving health-related quality of life (HRQoL) of patients with rheumatoid arthritis. A cost-effectiveness study from a societal perspective was conducted alongside a randomized controlled trial on a tailored, therapist-guided internet-based cognitive behavioral therapy (ICBT) intervention for patients with rheumatoid arthritis with elevated levels of distress as an addition to care as usual (CAU). METHODS: Data were collected at baseline or preintervention, 6 months or postintervention, and every 3 months thereafter during the 1-year follow-up. Effects were measured in terms of quality-adjusted life years (QALYs) and costs from a societal perspective, including health care sector costs (health care use, medication, and intervention costs), patient travel costs for health care use, and costs associated with loss of labor. RESULTS: The intervention improved the quality of life compared with only CAU (Δ QALYs=0.059), but at a higher cost (Δ=€4211). However, this increased cost substantially reduced when medication costs were left out of the equation (Δ=€1863). Of all, 93% (930/1000) of the simulated incremental cost-effectiveness ratios were in the north-east quadrant, indicating a high probability that the intervention was effective in improving HRQoL, but at a greater monetary cost for society compared with only CAU. CONCLUSIONS: A tailored and guided ICBT intervention as an addition to CAU for patients with rheumatoid arthritis with elevated levels of distress was effective in improving quality of life. Consequently, implementation of ICBT into standard health care for patients with rheumatoid arthritis is recommended. However, further studies on cost reductions in this population are warranted. TRIAL REGISTRATION: Nederlands Trial Register NTR2100; http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2100 (Archived by WebCite at http://www.webcitation.org/724t9pvr2).

An Economic Evaluation of Stopping Versus Continuing Tumor Necrosis Factor Inhibitor Treatment in Rheumatoid Arthritis Patients With Disease Remission or Low Disease Activity: Results From a Pragmatic Open-Label Trial.

OBJECTIVE: To evaluate, from a societal perspective, the incremental cost-effectiveness of withdrawing tumor necrosis factor inhibitor (TNFi) treatment compared to continuation of these drugs within a 1-year, randomized trial among rheumatoid arthritis patients with longstanding, stable disease activity or remission. METHODS: Data were collected from a pragmatic, open-label trial. Cost-utility analysis was performed using the nonparametric bootstrapping method, and a cost-effectiveness acceptability curve was constructed using the net-monetary benefit framework, where a willingness-to-accept threshold (WTA) was defined as the minimal cost saved that a patient accepted for each quality-adjusted life year (QALY) lost. RESULTS: A total of 531 patients were randomized to the stop group and 286 patients to the continuation group. Withdrawal of TNFi treatment resulted in a >60% reduction of the total drug cost, but led to an increase of ∼30% in other health care expenditures. Compared to continuation, stopping TNFi resulted in a mean yearly cost saving of €7,133 (95% confidence interval [95% CI] €6,071, €8,234]) and was associated with a mean loss of QALYs of 0.02 (95% CI 0.002, 0.040). Mean saved cost per QALY lost and per extra flare incurred in the stop group compared to the continuation group was €368,269 (95% CI €155,132, €1,675,909) and €17,670 (95% CI €13,650, €22,721), respectively. At a WTA of €98,438 per QALY lost, the probability that stopping TNFi treatment is cost-effective was 100%. CONCLUSION: Although an official WTA is not defined, the mean saved cost of €368,269 per QALY lost seems acceptable in The Netherlands, given existing data on willingness to pay.

Implementation of the EULAR cardiovascular risk management guideline in patients with rheumatoid arthritis: results of a successful collaboration between primary and secondary care.

The updated European League Against Rheumatism (EULAR) guideline recommends cardiovascular disease (CVD) risk assessment at least once every 5 years in all patients with rheumatoid arthritis (RA). This viewpoint starts with a literature overview of studies that investigated the level of CVD risk factor (CVD-RF) screening in patients with RA in general practices or in outpatient clinics. These studies indicate that CVD-RF screening in patients with RA is marginally applied in clinical practice, in primary as well as secondary care. Therefore, the second part of this viewpoint describes an example of the successful implementation of the EULAR cardiovascular disease risk management (CVRM) guideline in patients with RA in a region in the south of the Netherlands where rheumatologists and general practitioners (GPs) closely collaborate to manage the cardiovascular risk of patients with RA. The different components of this collaboration and the responsibilities of respectively primary and secondary care professionals are described. Within this collaboration, lipid profile was used as an indicator to assess whether CVD-RF screening was performed in the previous 5 years. In 72% (n=454) of the 628 patients with RA, a lipid profile was determined in the previous 5 years. As part of routine quality control, a reminder was sent to the GP in case a patient with RA was not screened. After sending the reminder letter, in 88% of all patients with RA, CVD risk assessment was performed. This collaboration can be seen as good practice to provide care in line with the EULAR guideline.

Impact of Stopping Tumor Necrosis Factor Inhibitors on Rheumatoid Arthritis Patients' Burden of Disease.

OBJECTIVE: To determine the impact of stopping tumor necrosis factor inhibitor (TNFi) treatment on patient-reported outcomes (PROs) of physical and mental health status, health utility, pain, disability, and fatigue in patients with established rheumatoid arthritis (RA). METHODS: In the pragmatic, 12-month POET trial, 817 RA patients with ≥6 months of remission or stable low disease activity were randomized 2:1 to stopping or continuing TNFi. In case of flare, TNFi was restarted at the discretion of the rheumatologist. PROs were assessed every 3 months. RESULTS: TNFi was restarted within 12 months in 252 of 531 patients (47.5%) in the stop group. At 3 months, mean PRO scores were significantly worse in the stop group, and a larger proportion of patients experienced a minimum clinically important difference (MCID) on all PROs. Effect sizes (ES) were strongest for health utility (ES -0.24) and pain (ES -0.30). Mean scores improved again after this point, but disability scores remained significantly different at 12 months. After 12 months, the relative risk of experiencing an MCID ranged from 1.16 for mental health status to 1.58 for fatigue. Mean PRO scores for patients restarting TNFi within 6 months were no longer significantly different from those that did not restart TNFi at 12 months. CONCLUSION: Stopping TNFi had a significant negative short-term impact on a broad range of PROs. Long-term negative consequences appeared to be limited, and outcomes in patients needing to restart TNFi within the first 6 months tended to be restored at 12 months.

Tailored Therapist-guided Internet-based Cognitive-behavioural Treatment for Psoriasis and Rheumatoid Arthritis: Two Case Reports.

Chronic somatic conditions, such as psoriasis, arthritis psoriatica and rheumatoid arthritis, have a large impact on patients' lives. Tailored therapist-guided internet-based cognitive-behavioural therapy (ICBT) has been shown to be effective in improving physical and psychological well-being in these patients. Two cases are presented here, in order to provide an in-depth illustration of the course and content of this novel treatment and to investigate the therapeutic alliance in an online treatment. After face-to-face intakes, both patients received therapist-guided ICBT tailored to their specific problems and treatment goals. The treatment resulted in improved physical and psychological well-being and these clinically significant improvements were maintained at 6-month follow-up. In addition, the therapeutic relationship was evaluated positively by both patients and increased further during treatment, indicating an adequate therapeutic working alliance in this online treatment. These case reports show that tailored ICBT may contribute to improved care for patients with chronic somatic conditions.

EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update.

Recent insights in rheumatoid arthritis (RA) necessitated updating the European League Against Rheumatism (EULAR) RA management recommendations. A large international Task Force based decisions on evidence from 3 systematic literature reviews, developing 4 overarching principles and 12 recommendations (vs 3 and 14, respectively, in 2013). The recommendations address conventional synthetic (cs) disease-modifying antirheumatic drugs (DMARDs) (methotrexate (MTX), leflunomide, sulfasalazine); glucocorticoids (GC); biological (b) DMARDs (tumour necrosis factor (TNF)-inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab), abatacept, rituximab, tocilizumab, clazakizumab, sarilumab and sirukumab and biosimilar (bs) DMARDs) and targeted synthetic (ts) DMARDs (Janus kinase (Jak) inhibitors tofacitinib, baricitinib). Monotherapy, combination therapy, treatment strategies (treat-to-target) and the targets of sustained clinical remission (as defined by the American College of Rheumatology-(ACR)-EULAR Boolean or index criteria) or low disease activity are discussed. Cost aspects were taken into consideration. As first strategy, the Task Force recommends MTX (rapid escalation to 25 mg/week) plus short-term GC, aiming at >50% improvement within 3 and target attainment within 6 months. If this fails stratification is recommended. Without unfavourable prognostic markers, switching to-or adding-another csDMARDs (plus short-term GC) is suggested. In the presence of unfavourable prognostic markers (autoantibodies, high disease activity, early erosions, failure of 2 csDMARDs), any bDMARD (current practice) or Jak-inhibitor should be added to the csDMARD. If this fails, any other bDMARD or tsDMARD is recommended. If a patient is in sustained remission, bDMARDs can be tapered. For each recommendation, levels of evidence and Task Force agreement are provided, both mostly very high. These recommendations intend informing rheumatologists, patients, national rheumatology societies, hospital officials, social security agencies and regulators about EULAR's most recent consensus on the management of RA, aimed at attaining best outcomes with current therapies.

Influence of route of administration/drug formulation and other factors on adherence to treatment in rheumatoid arthritis (pain related) and dyslipidemia (non-pain related).

OBJECTIVES: A comprehensive review was performed to investigate the effect of route of administration on medication adherence and persistence in rheumatoid arthritis (RA) and to compare adherence/persistence with oral medications between RA and a non-painful disease (dyslipidemia). RESEARCH DESIGN AND METHODS: Comprehensive database searches were performed to identify studies investigating medication adherence and/or persistence in adults with RA receiving conventional synthetic or biologic agents. Similar searches were performed for studies of patients with dyslipidemia receiving statins. Studies had to be published after 1998 in English and involve ≥6 months' follow up. MAIN OUTCOME MEASURES: Adherence and persistence were compared between the different routes of drug administration in RA, and between the two diseases for oral medications. RESULTS: A total of 35 and 28 papers underwent data extraction for RA and dyslipidemia, respectively. Within the constraints of the analysis, adherence and persistence rates appeared broadly similar for the different routes of drug administration in RA. Adherence to oral medications was also broadly similar across the two diseases, but persistence was lower in dyslipidemia. Poor adherence has clinical consequences in both diseases: greater disease activity and risk of flare in RA, and increased serum cholesterol levels and risk of heart and cerebrovascular disease in dyslipidemia. Over 1-3 years, poor adherence to biologic RA medications led to increased resource use and medical costs but lower total direct costs due to reduced biologic drug costs. Conversely, poor adherence to dyslipidemia medications resulted in increased total direct costs. In both diseases, adherence improved with patient education/support. CONCLUSIONS: The route of drug administration and the symptomatic (pain) nature of the disease do not appear to be dominant factors for drug adherence or persistence in RA. LIMITATION: The wide range of adherence and persistence values and definitions across studies made comparisons between drug formulations and diseases difficult.

Cost-Effectiveness of Cardiovascular Screening in Patients With Rheumatoid Arthritis.

OBJECTIVE: Early detection and preemptive treatment of patients at risk is of great importance in reducing the excess risk of cardiovascular (CV) disease in rheumatoid arthritis (RA). However, it is unclear how much screening is cost-effective in RA. The objective is to assess whether CV screening in RA proves to be cost-effective from a medical perspective, using different scenarios based on different guidelines. METHODS: A Markov chain model was used with a time horizon of 10 years. Parameter values were mainly obtained from literature and from RA patients screened for CV diseases at the Radboud University Medical Centre, Nijmegen, The Netherlands. The primary outcome was incremental cost-effectiveness expressed as costs per quality-adjusted life year (QALY) gained. Probabilistic sensitivity analysis was performed and described in willingness-to-pay curves; several scenarios were built. RESULTS: In the base case scenario, in 82% of the simulations, screening proved to be dominant compared to no screening. The mean QALY gain was 0.09 (95% percentile -0.07, 0.27), and the mean cost savings were €-1,057 (95% percentile -€2,825, €333). Different scenarios showed small differences in cost-effectiveness; the probability that screening is dominant remained high with the lowest probability being 50% for a very conservative scenario. CONCLUSION: Screening for CV events in RA patients was estimated to be cost-effective with high chances of being less expensive and more effective. These results support endorsement of screening for CV risk in patients with RA.

The Disease Activity Score (DAS) and the Disease Activity Score using 28 joint counts (DAS28) in the management of rheumatoid arthritis.

In rheumatoid arthritis (RA), disease activity cannot be measured in all individual patients according to a single variable. The Disease Activity Score (DAS) and the DAS28 have been developed to measure disease activity in RA both in daily clinical practice as well as in clinical trials on a group as well as individual level. The DAS/DAS28 is a continuous measure of RA disease activity that combines information from swollen joints, tender joints, acute phase response and general health. The DAS-based EULAR response criteria were primarily developed to be used in clinical trials. The EULAR response criteria classify individual patients as non-, moderate, or good responders, dependent on the magnitude of change and level of disease activity reached. In addition, already in the early nineties, cut points were developed to categorise patients in remission. The DAS28 is incorporated in several electronic patient records and web-based systems for monitoring purposes in daily clinical practice. In addition to this, it is being used in combination with patient-reported outcome measures (PROMs) to facilitate self-monitoring.

Cost-effectiveness of abatacept, rituximab, and TNFi treatment after previous failure with TNFi treatment in rheumatoid arthritis: a pragmatic multi-centre randomised trial.

INTRODUCTION: For patients with rheumatoid arthritis (RA) whose treatment with a tumour necrosis factor inhibitor (TNFi) is failing, several biological treatment options are available. Often, another TNFi or a biological with another mode of action is prescribed. The objective of this study was to compare the effectiveness and cost-effectiveness of three biologic treatments with different modes of action in patients with RA whose TNFi therapy is failing. METHODS: We conducted a pragmatic, 1-year randomised trial in a multicentre setting. Patients with active RA despite previous TNFi treatment were randomised to receive abatacept, rituximab or a different TNFi. The primary outcome (Disease Activity Score in 28 joints) and the secondary outcomes (Health Assessment Questionnaire Disability Index and 36-item Short Form Health Survey scores) were analysed using linear mixed models. Cost-effectiveness was analysed on the basis of incremental net monetary benefit, which was based on quality-adjusted life-years (calculated using EQ-5D scores), and all medication expenditures consumed in 1 year. All analyses were also corrected for possible confounders. RESULTS: Of 144 randomised patients, 5 were excluded and 139 started taking abatacept (43 patients), rituximab (46 patients) or a different TNFi (50 patients). There were no significant differences between the three groups with respect to multiple measures of RA outcomes. However, our analysis revealed that rituximab therapy is significantly more cost-effective than both abatacept and TNFi over a willingness-to-pay range of 0 to 80,000 euros. CONCLUSIONS: All three treatment options were similarly effective; however, when costs were factored into the treatment decision, rituximab was the best option available to patients whose first TNFi treatment failed. However, generalization of these costs to other countries should be undertaken carefully. TRIAL REGISTRATION: Netherlands Trial Register number NTR1605. Registered 24 December 2008.

Assessment of fatigue in rheumatoid arthritis: a psychometric comparison of single-item, multiitem, and multidimensional measures.

OBJECTIVE: To compare the psychometric functioning of multidimensional disease-specific, multiitem generic, and single-item measures of fatigue in patients with rheumatoid arthritis (RA). METHODS: Confirmatory factor analysis (CFA) and longitudinal item response theory (IRT) modeling were used to evaluate the measurement structure and local reliability of the Bristol RA Fatigue Multi-Dimensional Questionnaire (BRAF-MDQ), the Medical Outcomes Study Short Form-36 (SF-36) vitality scale, and the BRAF Numerical Rating Scales (BRAF-NRS) in a sample of 588 patients with RA. RESULTS: A 1-factor CFA model yielded a similar fit to a 5-factor model with subscale-specific dimensions, and the items from the different instruments adequately fit the IRT model, suggesting essential unidimensionality in measurement. The SF-36 vitality scale outperformed the BRAF-MDQ at lower levels of fatigue, but was less precise at moderate to higher levels of fatigue. At these levels of fatigue, the living, cognition, and emotion subscales of the BRAF-MDQ provide additional precision. The BRAF-NRS showed a limited measurement range with its highest precision centered on average levels of fatigue. CONCLUSION: The different instruments appear to access a common underlying domain of fatigue severity, but differ considerably in their measurement precision along the continuum. The SF-36 vitality scale can be used to measure fatigue severity in samples with relatively mild fatigue. For samples expected to have higher levels of fatigue, the multidimensional BRAF-MDQ appears to be a better choice. The BRAF-NRS are not recommended if precise assessment is required, for instance in longitudinal settings.

The EULAR Study Group for Registers and Observational Drug Studies: comparability of the patient case mix in the European biologic disease modifying anti-rheumatic drug registers.

OBJECTIVE: Under the auspices of the European League Against Rheumatism (EULAR), a study group of investigators representing European biologic DMARD (bDMARD) registers was convened. The purpose of this initial assessment was to collect and compare a cross section of patient characteristics and collate information on the availability of potential confounders within these registers. METHODS: Baseline characteristics of patients starting their first bDMARD in an arbitrary year (2008) for the treatment of RA, including demographic and disease characteristics, bDMARD drug details and co-morbidities, were collected and compared across 14 European bDMARD registers. RESULTS: A total of 5320 patients were included. Half the registers had restricted recruitment to certain bDMARDs during the study year. All registers` collected data on age, gender, disease duration, seropositivity for IgM-RF and 28-joint DAS (DAS28). The mean DAS28 ranged from 4.2 to 6.6 and the mean HAQ from 0.8 to 1.9. Current smoking ranged from 9% to 34%. Nine registers reported co-morbidities with varying prevalence. CONCLUSION: In addition to demonstrating European-wide collaboration across rheumatology bDMARD registers, this assessment identified differences in prescribing patterns, recruitment strategies and data items collected. These differences need to be considered when applying strategies for combined analysis. The lack of a common data model across Europe calls for further work to harmonize data collection across registers.

Modelling outcomes of complex treatment strategies following a clinical guideline for treatment decisions in patients with rheumatoid arthritis.

BACKGROUND: Management of rheumatoid arthritis (RA) is characterised by a sequence of disease-modifying antirheumatic drugs (DMARDs) and biological response modifiers (BRMs). In most of the Western countries, the drug sequences are determined based on disease activity and treatment history of the patients. A model for realistic patient outcomes should reflect the treatment pathways relevant for patients with specific characteristics. OBJECTIVE: This study aimed at developing a model that could simulate long-term patient outcomes and cost effectiveness of treatment strategies with and without inclusion of BRMs following a clinical guideline for treatment decisions. METHODS: Discrete event simulation taking into account patient characteristics and treatment history was used for model development. Treatment effect on disease activity, costs, health utilities and times to events were estimated using Dutch observational studies. Long-term progression of physical functioning was quantified using a linear mixed-effects model. Costs and health utilities were estimated using two-part models. The treatment strategy recommended by the Dutch Society for Rheumatology where both DMARDs and BRMs were available (Strategy 2) was compared with the treatment strategy without BRMs (Strategy 1). Ten thousand theoretical patients were tracked individually until death. In the probabilistic sensitivity analysis, Monte Carlo simulations were performed with 1,000 sets of parameters sampled from appropriate probability distributions. RESULTS: The simulated changes over time in disease activity and physical functioning were plausible. The incremental cost per quality-adjusted life-year gained of Strategy 2 compared with Strategy 1 was 124,011. At a willingness-to-pay threshold higher than 119,167, Strategy 2 dominated Strategy 1 in terms of cost effectiveness but the probability that the Strategy 2 is cost effective never exceeded 0.87. CONCLUSIONS: It is possible to model the outcomes of complex treatment strategies based on a clinical guideline for the management of RA. Following the Dutch guideline and using real-life data, inclusion of BRMs in the treatment strategy for RA appeared to be less favourable in our model than in most of the existing models that compared drug sequences independent of patient characteristics and used data from randomised controlled clinical trials. Despite complexity and demand for extensive data, our modelling approach can help to identify the knowledge gaps in clinical guidelines for RA management and priorities for future research.

Cardiovascular disease assessment in rheumatoid arthritis: a guide to translating knowledge of cardiovascular risk into clinical practice.

As physicians we like to have evidence for making decisions about interventions to improve health. The evidence vacuum in the field of cardiovascular disease (CVD) prevention and clinical outcome in patients with rheumatoid arthritis (RA) has received vigorous attention in the recent literature. There is broad agreement that a patient with RA fulfilling the criteria established for the general population on CVD risk reduction should receive proven interventions, including smoking cessation, weight reduction, blood pressure control and lipid-lowering therapy. In accordance with these recommendations, and despite all the uncertainties about CVD treatment threshold, targets and outcome results in RA, we firmly advocate that CVD risk should be assessed and acted on in patients with RA as recommended for the general population, even while educational CVD-preventive programmes are being developed and hard CVD end point studies are undertaken in this patient population. The initial strategies for implementing CVD risk evaluation will necessarily be modest at first. There are several possible strategies for collection of data that can be incorporated into the daily routine during rheumatology consultations at outpatient clinics. We recommend starting with these simple procedures: 1. CVD risk factor recording and evaluation using risk calculators available for the general population 2. Referral of patients with high CVD risk to a primary care physician or a cardiologist skilled in this subject for follow-up 3. Providing information about excess CVD risk and how to modify it to the patients as major stakeholders.

Burden of disease in treated rheumatoid arthritis patients: going beyond the joint.

OBJECTIVE: The disease burden in rheumatoid arthritis (RA) extends beyond the joint. This article evaluates the physical and psychosocial extra-articular burden of treated RA and relationships among diverse disease manifestations. METHODS: MEDLINE searches identified papers published in English from January 2003 to December 2012 that evaluated systemic complications and psychosocial aspects associated with RA. Preference was given to studies with randomized cohorts and large (>100) sample sizes. Of 378 articles identified in the initial search, 118 were selected for inclusion. RESULTS: RA is associated with multiple comorbidities and psychosocial impairments, including cardiovascular disease, osteoporosis, interstitial lung disease, infection, malignancies, fatigue, depression, cognitive dysfunction, reduced work performance, work disability, and decreased health-related quality of life. The etiology of the extra-articular burden may reflect the systemic inflammation and immune system alteration associated with RA, metabolic imbalances and side effects related to treatment, or the influence of comorbidities. Strategies that may help to reduce the extra-articular disease burden include personalized medicine and the potential introduction of treatments with new mechanisms of action. CONCLUSION: Despite improvements in treating joint disease, the extra-articular burden in RA remains substantial, encompassing multiple comorbidities and psychosocial impairments.

Treating to the target of remission in early rheumatoid arthritis is cost-effective: results of the DREAM registry.

BACKGROUND: Where health economic studies are frequently performed using modelling, with input from randomized controlled trials and best guesses, we used real-life data to analyse the cost-effectiveness and cost-utility of a treatment strategy aiming to the target of remission compared to usual care in early rheumatoid arthritis (RA). METHODS: We used real-life data from comparable cohorts in the Dutch Rheumatoid Arthritis Monitoring (DREAM) registry: the DREAM remission induction cohort (treat-to-target, T2T) and the Nijmegen early RA inception cohort (usual care, UC). Both cohorts were followed prospectively using the DREAM registry methodology. All patients fulfilled the American College of Rheumatology criteria for RA and were included in the cohort at the time of diagnosis. The T2T cohort was treated according to a protocolised strategy aiming at remission (Disease Activity Score in 28 joints (DAS28) < 2.6). The UC cohort was treated without DAS28-guided treatment decisions. EuroQol-5D utility scores were estimated from the Health Assessment Questionnaire. A health care perspective was adopted and direct medical costs were collected. The incremental cost effectiveness ratio (ICER) per patient in remission and incremental cost utility ratio (ICUR) per quality-adjusted life year (QALY) gained were calculated over two and three years of follow-up. RESULTS: Two year data were available for 261 T2T patients and 213 UC patients; an extended follow-up of three years was available for 127 and 180 patients, respectively. T2T produced higher remission percentages and a larger gain in QALYs than UC. The ICER was € 3,591 per patient in remission after two years and T2T was dominant after three years. The ICUR was € 19,410 per QALY after two years and T2T was dominant after three years. CONCLUSIONS: We can conclude that treating to the target of remission in early RA is cost-effective compared with UC. The data suggest that in the third year, T2T becomes cost-saving.

Development and evaluation of a crosswalk between the SF-36 physical functioning scale and Health Assessment Questionnaire disability index in rheumatoid arthritis.

BACKGROUND: The SF-36 physical functioning scale (PF-10) and the Health Assessment Questionnaire disability index (HAQ-DI) are the most frequently used instruments for measuring self-reported physical function in rheumatoid arthritis (RA). The objective of this study was to develop a crosswalk between scores on the PF-10 and HAQ-DI in RA. METHODS: Item response theory (IRT) methods were used to co-calibrate both scales using data from 1791 RA patients. The appropriateness of a Rasch-based crosswalk was evaluated by comparing it with crosswalks based on a two-parameter and a multi-dimensional IRT model. The accuracy of the final crosswalk was cross-validated using baseline (n = 532) and 6-month follow-up (n = 276) data from an independent cohort of early RA patients. RESULTS: The PF-10 and HAQ-DI adequately fit a unidimensional Rasch model. Both scales measured a wide range of functioning, although the HAQ-DI tended to better target lower levels of functioning. The Rasch-based crosswalk performed similarly to crosswalks based on the two-parameter and multidimensional IRT models. Agreement between predicted and observed scale scores in the cross-validation sample was acceptable for group-level comparisons. The longitudinal validity in discriminating between disease response states was similar between observed and predicted scores. CONCLUSION: The crosswalk developed in this study allows for converting scores from one scale to the other and can be used for group-level analyses in patients with RA.

The provisional ACR/EULAR definition of remission in RA: a comment on the patient global assessment criterion.

OBJECTIVES: The provisional ACR/European League Against Rheumatism (EULAR) definition of remission in RA requires a score of ≤1 on the patient global assessment (PGA, 0-10 scale). We explored the relation between the PGA criterion and the patient's clinical disease state in an observational dataset. METHODS: Data of 512 newly diagnosed RA patients of the Dutch Rheumatoid Arthritis Monitoring (DREAM) remission induction cohort were analysed. Both 28-joint counts and more comprehensive joint counts (tender joint count-53, swollen joint count-44) were used. RESULTS: ACR/EULAR remission was present in 20.1% of the patients when using 28-joint counts and in 17.4% of the patients when applying more comprehensive joint counts. In 108 patients, the PGA score was >1 despite fulfilment of the remaining criteria (TJC28, SJC28 and CRP in mg/dl ≤1). Residual disease activity was observed in 31.5% (34/108) and median (interquartile range) scores on PGA, pain and fatigue were 2.4 (1.8-4.0), 2.0 (1.1-3.0) and 2.7 (1.3-5.0), respectively. Applying more comprehensive joint counts showed comparable results. In 19.5% (100/512) of patients, disease activity was absent (TJC53 = 0, SJC44 = 0, and CRP ≤1). In 41% (n = 41) of these patients, the PGA score was >1. Receiver operating characteristic analysis showed moderate accuracy of the PGA to discriminate between fulfilment and no fulfilment of all remaining criteria. CONCLUSION: Frequently, patients did not meet the PGA criterion despite a good clinical disease state. Apparently the PGA is not solely influenced by RA disease activity. In patients with marked divergence between the PGA and objective clinical measurements, caution should be taken when applying the provisional ACR/EULAR definition of remission.