Innovative approaches to biologic development on the trail of CT-P13: biosimilars, value-added medicines, and biobetters.

The biosimilar concept is now well established. Clinical data accumulated pre- and post-approval have supported biosimilar uptake, in turn stimulating competition in the biologics market and increasing patient access to biologics. Following technological advances, other innovative biologics, such as "biobetters" or "value-added medicines," are now reaching the market. These innovative biologics differ from the reference product by offering additional clinical or non-clinical benefits. We discuss these innovative biologics with reference to CT-P13, initially available as an intravenous (IV) biosimilar of reference infliximab. A subcutaneous (SC) formulation, CT-P13 SC, has now been developed. Relative to CT-P13 IV, CT-P13 SC offers clinical benefits in terms of pharmacokinetics, with comparable efficacy, safety, and immunogenicity, as well as increased convenience for patients and reduced demands on healthcare system resources. As was once the case for biosimilars, nomenclature and regulatory pathways for innovative biologics require clarification to support their uptake and ultimately benefit patients.

Does Including Pain, Fatigue, and Physical Function When Assessing Patients with Early Rheumatoid Arthritis Provide a Comprehensive Picture of Disease Burden?

OBJECTIVE: To explore the possibility of integrating patient-important outcomes like pain, fatigue, and physical function into the evaluation of disease status in early rheumatoid arthritis (ERA) without compromising correct disease activity measurement. METHODS: Patients from the 2-year Care in Early Rheumatoid Arthritis (CareRA) trial were included. Pain and fatigue (visual analog scales), Health Assessment Questionnaire (HAQ), standard components of disease activity [swollen/tender joint counts (SJC/TJC), C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR), physician (PhGH) and patient (PaGH) global health] were recorded at every visit (n = 10). Pearson correlation and exploratory factor analyses (EFA), using multiple imputation (15×) and outputation (1000×), were performed per timepoint and overall, on standard components of disease activity scores with and without pain, fatigue, and HAQ. Each of the 15,000 datasets was analyzed using EFA with principal component extraction and oblimin rotation to determine which variables belong together. RESULTS: We included 379 patients. EFA on standard composite score components extracted 2 factors with no substantial cross-loadings. Still, pain (0.83), fatigue (0.65), and HAQ (0.59) were strongly correlated with PaGH. When rerunning the EFA with the inclusion of pain, fatigue, and HAQ, the 2-factor model had substantial cross-loadings between factors. However, a 3-factor model was optimal, with Factor 1: patient assessment, Factor 2: clinical assessment (PhGH, SJC, and TJC), and Factor 3: laboratory assessment (ESR/CRP). CONCLUSION: PaGH, pain, fatigue, and physical function represent a separate aspect of the disease burden of patients with ERA, which could be further explored as a target for care apart from disease activity. [ClinicalTrials.gov: NCT01172639].

Two-year cost-effectiveness of different COBRA-like intensive remission induction schemes in early rheumatoid arthritis: a piggyback study on the pragmatic randomised controlled CareRA trial.

OBJECTIVES: To evaluate the cost-effectiveness of treat-to-target strategies among recently diagnosed patients with rheumatoid arthritis (RA) using methotrexate (MTX) and a step-down glucocorticoid (GC) scheme (COBRA Slim) compared with (1) this combination with either sulphasalazine (COBRA Classic) or leflunomide (COBRA Avant-Garde) in high-risk patients and (2) MTX without GCs (Tight-Step-Up, TSU) in low-risk patients. METHODS: The incremental cost-utility was calculated from a healthcare perspective in the intention-to-treat population (n=379) of the 2-year open-label pragmatic randomised controlled Care in early RA trial. Healthcare costs were collected prospectively through electronic trial records. Quality-adjusted life years (QALYs) were estimated using mapping algorithms for EuroQoL-5 Dimension. Multiple imputation was used to handle missing data and bootstrapping to calculate CIs. Robustness was tested with biological disease-modifying antirheumatic drugs at biosimilar prices. RESULTS: In the high-risk group, Classic (∆k€1.464, 95% CI -0.198 to 3.127) and Avant-Garde (∆k€0.636, 95% CI -0.987 to 2.258) were more expensive compared with Slim and QALYs were slightly worse for Classic (∆-0.002, 95% CI -0.086 to 0.082) and Avant-Garde (∆-0.009, 95% CI -0.102 to 0.084). This resulted in the domination of Classic and Avant-Garde by Slim. In the low-risk group, Slim was cheaper (∆k€-0.617, 95% CI -2.799 to 1.566) and QALYs were higher (∆0.141, 95% CI 0.008 to 0.274) compared with TSU, indicating Slim dominated. Results were robust against the price of biosimilars. CONCLUSIONS: The combination of MTX with a GC bridging scheme is less expensive with comparable health utility than more intensive step-down combination strategies or a conventional step-up approach 2 years after initial treatment. TRIAL REGISTRATION NUMBER: NCT01172639.

EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update.

OBJECTIVES: To provide an update of the European League Against Rheumatism (EULAR) rheumatoid arthritis (RA) management recommendations to account for the most recent developments in the field. METHODS: An international task force considered new evidence supporting or contradicting previous recommendations and novel therapies and strategic insights based on two systematic literature searches on efficacy and safety of disease-modifying antirheumatic drugs (DMARDs) since the last update (2016) until 2019. A predefined voting process was applied, current levels of evidence and strengths of recommendation were assigned and participants ultimately voted independently on their level of agreement with each of the items. RESULTS: The task force agreed on 5 overarching principles and 12 recommendations concerning use of conventional synthetic (cs) DMARDs (methotrexate (MTX), leflunomide, sulfasalazine); glucocorticoids (GCs); biological (b) DMARDs (tumour necrosis factor inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab), abatacept, rituximab, tocilizumab, sarilumab and biosimilar (bs) DMARDs) and targeted synthetic (ts) DMARDs (the Janus kinase (JAK) inhibitors tofacitinib, baricitinib, filgotinib, upadacitinib). Guidance on monotherapy, combination therapy, treatment strategies (treat-to-target) and tapering on sustained clinical remission is provided. Cost and sequencing of b/tsDMARDs are addressed. Initially, MTX plus GCs and upon insufficient response to this therapy within 3 to 6 months, stratification according to risk factors is recommended. With poor prognostic factors (presence of autoantibodies, high disease activity, early erosions or failure of two csDMARDs), any bDMARD or JAK inhibitor should be added to the csDMARD. If this fails, any other bDMARD (from another or the same class) or tsDMARD is recommended. On sustained remission, DMARDs may be tapered, but not be stopped. Levels of evidence and levels of agreement were mostly high. CONCLUSIONS: These updated EULAR recommendations provide consensus on the management of RA with respect to benefit, safety, preferences and cost.

A multi-criteria decision approach for ranking unmet needs in healthcare.

Early temporary reimbursement (ETR) schemes for new interventions targeting high unmet needs are increasingly applied in pharmaceutical policy. Crucial for these schemes is the assessment of unmet healthcare needs of patients and society. This study develops and tests a multi-criteria decision approach (MCDA) for assessing therapeutic and societal needs. The Belgian unmet needs commission, responsible for creating a list of unmet needs for the ETR programme, has tested this methodology to assess the needs in eight health conditions. For therapeutic need, three criteria were included (impact of the condition on quality of life and on life expectancy and inconvenience of current treatment); for societal need two criteria (condition-related healthcare expenditures per patient, prevalence). The results show that the proposed MCDA is feasible and acceptable for the unmet needs commission. Clear definitions of the criteria and regular repetition of these is needed to avoid variable interpretation of the criteria by the commission members. Quality assessment of the evidence is desired. Rankings resulting from the application have face validity. Considering therapeutic need separately from societal need is considered appropriate. Policy makers should consider the use of MCDA in assessing healthcare needs. MCDA improves the transparency and accountability of the decision making processes and is practical and feasible.

Illness Identity in Adults with a Chronic Illness.

The present study examines the concept of illness identity, the degree to which a chronic illness is integrated into one's identity, in adults with a chronic illness by validating a new self-report questionnaire, the Illness Identity Questionnaire (IIQ). Self-report questionnaires on illness identity, psychological, and physical functioning were assessed in two samples: adults with congenital heart disease (22-78 year old; n = 276) and with multisystem connective tissue disorders (systemic lupus erythematosus or systemic sclerosis; 17-81 year old; n = 241). The IIQ could differentiate four illness identity states (i.e., engulfment, rejection, acceptance, and enrichment) in both samples, based on exploratory and confirmatory factor analysis. All four subscales proved to be reliable. Rejection and engulfment were related to maladaptive psychological and physical functioning, whereas acceptance and enrichment were related to adaptive psychological and physical functioning. The present findings underscore the importance of the concept of illness identity. The IIQ, a self-report questionnaire, is introduced to measure four different illness identity states in adults with a chronic illness.

Perception of Originator Biologics and Biosimilars: A Survey Among Belgian Rheumatoid Arthritis Patients and Rheumatologists.

BACKGROUND: Among patients and rheumatologists, current knowledge and perception of biosimilars in comparison with originator biologics is unknown. OBJECTIVES: The aim of this study was to investigate this knowledge and perception in Belgian rheumatologists and rheumatoid arthritis (RA) patients. METHODS: Anonymous web surveys were conducted in Belgian RA patients (n = 121) and rheumatologists (n = 41) during the period January-March 2016. The surveys covered topics on knowledge, similarity, price, preference, interchangeability, extrapolation and switching. Descriptive and statistical analyses of responses were performed. RESULTS: Familiarity with biosimilars was reported by 49% of patients, of whom 77% knew what biosimilars were. RA patients equally questioned the proven efficacy of originators and biosimilars in RA, as well as their side effects and suitability. Furthermore, RA patients questioned the safety of biosimilars more often than that of originators (35 vs. 20%, respectively; p = 0.0094). Rheumatologists, more so than patients, expressed concerns that there might be differences between originators and biosimilars in terms of quality, safety, and price (p = 0.0292, p < 0.0001, p = 0.0129, respectively). The opinions of rheumatologists on interchangeability and extrapolation of indications varied. The price of an originator contributed substantially to the medicine preference of rheumatologists (p = 0.0002), but not patients. CONCLUSION: Our study showed that rheumatologists, more so than patients, were convinced that there can be differences between originators and biosimilars. Despite safety being the major concern of patients, patients trusted their physician's decision to start on or switch to a biosimilar. The evolution of the uptake of biosimilars in Belgium might thus depend mainly on the perception of physicians.

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.

Accelerometry-Based Activity Recognition and Assessment in Rheumatic and Musculoskeletal Diseases.

One of the important aspects to be considered in rheumatic and musculoskeletal diseases is the patient's activity capacity (or performance), defined as the ability to perform a task. Currently, it is assessed by physicians or health professionals mainly by means of a patient-reported questionnaire, sometimes combined with the therapist's judgment on performance-based tasks. This work introduces an approach to assess the activity capacity at home in a more objective, yet interpretable way. It offers a pilot study on 28 patients suffering from axial spondyloarthritis (axSpA) to demonstrate its efficacy. Firstly, a protocol is introduced to recognize a limited set of six transition activities in the home environment using a single accelerometer. To this end, a hierarchical classifier with the rejection of non-informative activity segments has been developed drawing on both direct pattern recognition and statistical signal features. Secondly, the recognized activities should be assessed, similarly to the scoring performed by patients themselves. This is achieved through the interval coded scoring (ICS) system, a novel method to extract an interpretable scoring system from data. The activity recognition reaches an average accuracy of 93.5%; assessment is currently 64.3% accurate. These results indicate the potential of the approach; a next step should be its validation in a larger patient study.

Costs of drugs for treatment of rheumatic diseases.

The cost of drugs is becoming an issue worldwide, in particular for inflammatory rheumatic diseases. In the current review, an overview of the scene is given with a specific emphasis on accessibility for those patients in real need of the available expensive treatments. The authors propose 7 principles for discussion that need to be addressed and are a responsibility for all stakeholders in rheumatology.

Instrumented BASFI (iBASFI) Shows Promising Reliability and Validity in the Assessment of Activity Limitations in Axial Spondyloarthritis.

OBJECTIVE: The Bath Ankylosing Spondylitis Functional Index (BASFI) is the most popular method to assess activity capacity in axial spondyloarthritis (axSpA), to our knowledge. It is endorsed by the Assessment of Spondyloarthritis international Society. But it may have recall bias or aberrant self-judgments in individual patients. Therefore, we aimed to (1) develop the instrumented BASFI (iBASFI) by adding a body-worn accelerometer with automated algorithms to performance-based measurements (PBM), (2) study the iBASFI's core psychometric properties, and (3) reduce the number of iBASFI items. METHODS: Twenty-eight patients with axSpA wore a 2-axial accelerometer while completing 12 PBM derived from the BASFI. A chronometer and both manual and "automated algorithm-based" acceleration segmentation identified movement time. Test-retest trials and methods (algorithm vs manual segmentation/chronometer/BASFI) were compared with ICC, standard error of measurement [percentage of movement time (SEM%)], and Spearman ρ correlation coefficients. Linear regression identified the optimal set of reliable iBASFI PBM. RESULTS: Good to excellent test-retest reliability was found for 8/12 iBASFI items (ICC range 0.812-0.997, SEM range 0.4-30.4%), typically with repeated and fast movements. Automated algorithms excellently mimicked manual segmentation (ICC range 0.900-0.998) and the chronometer (ICC range 0.878-0.998) for 10/12 iBASFI items. Construct validity compared with the BASFI was confirmed for 7/12 iBASFI items (δ range 0.504-0.755). Together, sit-to-stand speed test (stBeta 0.483), cervical rotation (stBeta -0.392), and height (stBeta -0.375) explained 59% of the variance in the BASFI (p < 0.01). CONCLUSION: The proof-of-concept iBASFI showed promising reliability and validity in measuring activity capacity. The number of the iBASFI's PBM may be minimized, but further validation in larger axSpA cohorts is needed before its clinical use.

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.

Physical activity assessment in patients with axial spondyloarthritis compared to healthy controls: a technology-based approach.

INTRODUCTION: Traditionally, assessment in axial Spondyloarthritis (aSpA) includes the evaluation of the capacity to execute tasks, conceptualized as physical function. The role of physical activity, defined as movement-related energy expenditure, is largely unknown and almost exclusively studied using patient-reported outcome measures. The aims of this observational cross-sectional study are to compare physical activity between patients with aSpA and healthy controls (HC) and to evaluate the contribution of disease activity to physical activity differences between groups. METHODS: Forty patients with aSpA were matched by age, gender, period of data acquisition in terms of days and season to 40 HC. Physical activity was measured during five consecutive days (three weekdays and two weekend days) using ambulatory monitoring (SenseWear Armband). Self-reported disease activity was measured by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Differences in physical activity between patients with aSpA and HC were examined with Wilcoxon signed-rank tests and a mixed linear model. Difference scores between patients and HC were correlated with disease activity. RESULTS: Average weekly physical activity level (Med(IQR); HC:1.54(1.41-1.73); aSpA:1.45(1.31-1.67),MET) and energy expenditure (HC:36.40(33.43-41.01); aSpA:34.55(31.08-39.41),MET.hrs/day) were significantly lower in patients with aSpA. Analyses across intensity levels revealed no significant differences between groups for inactivity and time spent at light or moderate physical activities. In contrast, weekly averages of vigorous (HC:4.02(1.20-12.60); aSpA:0.00(0.00-1.20),min/d), very vigorous physical activities (HC0.00(0.00-1.08); aSpA:0.00(0.00-0.00),mind/d) and moderate/(very)vigorous combined (HC2.41(1.62-3.48); aSpA:1.63(1.20-2.82),hrs/d) were significantly lower in patients with aSpA. Disease activity did not interact with differences in physical activity between patients with aSpA and HC, evidenced by non-significant and very low correlations (range: -0.06-0.17) between BASDAI and HC-aSpA patients' difference scores. CONCLUSIONS: Patients with aSpA exhibit lower physical activity compared to HC and these differences are independent of self-reported disease activity. Further research on PA in patients with aSpA should be prioritized.

Belgian rheumatologists' perception on eligibility of RA patients for anti-TNF treatment matches more closely Dutch rather than Belgian reimbursement criteria.

OBJECTIVES: To assess discrepancies between perception of Belgian rheumatologists on eligibility of RA patients for anti-TNF treatment and Belgian reimbursement criteria and to compare Belgian with Dutch criteria and UK guidelines. METHODS: Consecutive MTX-experienced patients with active RA were recruited from 25 private and academic rheumatology practices. Discrepancies between eligibility for anti-TNF treatment according to the rheumatologist and fulfillment of Belgian reimbursement criteria [HAQ > or =25%, tender joint count (TJC) and swollen joint count (SJC) > or =8; > or =1 erosion; failure of > or =2 DMARDs including MTX; no tuberculosis] were recorded. Reasons for failing the Belgian criteria and results of applying Dutch reimbursement criteria and UK guidelines on the dataset were analysed. RESULTS: Of 492 patients, rheumatologists considered 135 (27.4%) as eligible, whereas Belgian criteria were fulfilled for only 34 (6.9%). Positive predictive value (PPV) of rheumatologists' perception on eligibility for fulfillment of Belgian criteria was 22.9%, whereas negative predictive value (NPV) was 99.1%. The 104 patients (21.1%) considered eligible despite criteria not being fulfilled had significantly greater TJCs, SJCs, disease activity score (DAS28) and Rheumatoid Arthritis Disease Activity Index scores than the 385 patients (78.2%) in the no-discrepancy group. Number of swollen joints, HAQ and erosions mainly accounted for discrepancies. Of 492 patients, 263 (53.4%) qualified for Dutch criteria and 41 (8.3%) for UK guidelines. PPV of Belgian rheumatologists' perception was 72.6% for fulfilling Dutch criteria (NPV 49.6%) and 23.4% for UK guidelines (NPV 96.7%). CONCLUSIONS: Rheumatologists consider more RA patients eligible for anti-TNF treatment than would be reimbursed according to Belgian criteria. Dutch guidelines, based on DAS28, match more closely eligibility according to Belgian rheumatologists.

Effectiveness of an integrated outpatient care programme compared with present-day standard care in early rheumatoid arthritis.

OBJECTIVES: To investigate the effectiveness of an integrated care programme in daily practice compared with present-day standard care for ambulatory early rheumatoid arthritis patients. METHODS: In this cross-sectional study, group A received programmed multidisciplinary outpatient care and group B standard rheumatologist-centred care. Demographics, disease duration, initial and actual treatment, disease activity (Disease Activity-28 Score), general health (Short Form-36 [SF-36]), functionality (Health Assessment Questionnaire [HAQ]), coping style (Utrecht's Coping List), illness perception (Dutch-Revised Illness Perception Questionnaire) and satisfaction about care were recorded. RESULTS: Eight-nine patients were included in group A and 102 in group B. Demographics, rheumatoid factor, antibodies against cyclic citrullinated peptides and disease duration were comparable. More patients in group A received initial combination therapy (35% versus 3%). Actual treatment regimens were comparable. More patients were in remission (69% versus 39%) or had low disease activity (80% versus 60%), mean HAQ-scores were lower (0.52 versus 0.80), more patients had no functional impairment (38% versus 15%) and SF-36 scores were higher in group A. Coping style and illness perception were similar, except for illness coherence. Satisfaction differed only for aspects typically favouring a care programme. Participation in a care programme independently predicted remission and absence of disability in a regression model, including gender and initial treatment as other predictors. CONCLUSION: Disease activity was better controlled and functionality and general health better preserved in patients following an outpatient care programme. This was partly due to the easier implementation of an intensive initial treatment strategy but apparently also to other aspects of organized pharmacological and non-pharmacological care, to be defined in randomized, controlled studies.

Cost-effectiveness of abatacept in patients with moderately to severely active rheumatoid arthritis and inadequate response to tumor necrosis factor-alpha antagonists.

OBJECTIVE: To assess cost-effectiveness of abatacept in patients with rheumatoid arthritis (RA) with inadequate response to tumor necrosis factor-alpha antagonists (anti-TNF). METHODS: We developed a simulation model to depict progression of disability [in terms of Health Assessment Questionnaire Disability Index (HAQ-DI)] in women aged 55-64 years with moderately to severely active RA and inadequate response to anti-TNF. At model entry, patients were assumed to receive either oral disease modifying antirheumatic drugs (DMARD) only or oral DMARD plus abatacept. Patients were then tracked from model entry until death. Future health-state utilities and medical-care costs (except study therapy) were estimated based on predicted values of the HAQ-DI. The model was estimated using data from a Phase III clinical trial of abatacept plus secondary sources. Cost-effectiveness was expressed in terms of incremental cost (2006 US$) per quality-adjusted life-year (QALY) gained alternatively over 10 years and a lifetime. Future costs and health effects were discounted at 3% annually. RESULTS: Over 10 years, abatacept would yield 1.0 additional QALY (undiscounted) per patient (4.0 vs 3.0 for oral DMARD) at an incremental (discounted) cost of $45,497 (100,648 vs $55,151) respectively; over a lifetime, corresponding figures were 1.6 QALY (5.8 vs 4.2) and $64,978 ($140,714 vs $82,489). Cost-effectiveness was [mean (95% CI)] $50,576 ($47,056, $54,944) per QALY gained over 10 years, and $45,979 ($42,678, $49,932) per QALY gained over a lifetime. Findings were robust in sensitivity analyses. CONCLUSION: Abatacept is cost-effective by current standards of medical practice in patients with moderately to severely active RA and inadequate response to an anti-TNF.