Health Assessment Questionnaire Progression Research Articles

Disease Activity Indices in Rheumatoid Arthritis: Comparative Performance to Detect Changes in Function, IL-6 Levels, and Radiographic Progression.

Objective: To compare the capacity of various disease activity indices to evaluate changes in function, IL-6 levels, and radiographic progression in early and established rheumatoid arthritis (RA).Methods: Secondary data analysis of a clinical trial assessing the efficacy of tocilizumab in patients with established RA (ACT-RAY) and a longitudinal prospective register of early arthritis (PEARL). Targeted outcomes were changes in physical function, measured with the health assessment questionnaire (HAQ), IL-6 serum levels, and radiographic progression. The “Hospital Universitario La Princesa Index” (HUPI), DAS28 using erythrocyte sedimentation rate and SDAI were the disease activity indices compared. Models adjusted for age and sex were fitted for each outcome and index and ranked based on the R2 parameter and the quasi-likelihood under the independence model criterion.Results: Data from 8,090 visits (550 patients) from ACT-RAY and 775 visits (534 patients) from PEARL were analyzed. The best performing models for HAQ were the HUPI (R2 = 0.351) and SDAI ones (R2 = 0.329). For serum IL-6 levels, the SDAI (R2 = 0.208) followed by the HUPI model (R2 = 0.205). For radiographic progression in ACT-RAY, the HUPI (R2 = 0.034) and the DAS28 models (R2 = 0.026) performed best whereas the DAS28 (R2 = 0.030) and HUPI models (R2 = 0.023) did so in PEARL.Conclusions: HUPI outperformed other indices identifying changes in HAQ and radiographic progression and performed similarly to SDAI for IL-6 serum levels.

PMS31 - Quantifying the Importance of Model Parameters and Structural Assumptions on the Value of Treatments for Rheumatoid Arthritis Using Metamodeling

Our aim was to quantify the relative importance of model parameters and model structures on the cost-effectiveness estimates of biologic disease modifying anti-rheumatic drugs (bDMARDs) vs conventional DMARDs (cDMARDs) for treatment of patients with moderate to severe rheumatoid arthritis with inadequate response to cDMARDs. We used the Innovation and Value Initiative’s open-source rheumatoid arthritis individual patient simulation to simulate outcomes. 1,000 sets of parameter values were sampled in a probabilistic sensitivity analysis (PSA) and 32 model structures were simulated. For each parameter set and model structure, 1,000 patients were simulated to calculate the mean incremental net monetary benefit (iNMB). The simulated mean iNMB was regressed on values of the model parameters and characteristics of the model structures using linear regression models. The absolute values of the coefficients of standardized variables were used to rank the model inputs by their relative importance. Structural assumptions related to treatment switching, long-term progression of the Health Assessment Questionnaire (HAQ) score, utility, and the effect of treatment on HAQ had large impacts on the iNMB. For example, models that use a latent class growth model to simulate HAQ progression for patients using cDMARDs were predicted to increase the iNMB by around $45,000 relative to models that assumed a linear rate of progression. Standardized input parameters with the largest coefficients in absolute value included the extent to which the HAQ score rebounded after treatment failure and the impact of changes in the HAQ score on mortality. Cost-effectiveness estimates for rheumatoid arthritis vary due to both parameter and structural uncertainty. New studies are needed to improve the quality of parameter estimates; consensus-driven approaches such as Delphi panels can help determine appropriate model structures. Research should prioritize the most sensitive model parameters and debates should focus on the structural assumptions most likely to influence results.

PP36 Early Diagnosis And Treatment Of Psoriatic Arthritis

Introduction:Screening for psoriatic arthritis (PsA) is expected to identify patients at earlier stages of the disease. Early treatment is expected to slow disease progression and delay the need for biologic therapy. This study estimated the cost-effectiveness of screening tools for PsA in Canada.Methods:A Markov model was built to estimate the associated costs and quality-adjusted life-years (QALYs) of screening tools for PsA in patients using topical treatment for psoriasis. The screening tools included: the Toronto Psoriatic Arthritis Screening (ToPAS) questionnaire; the Psoriasis Epidemiology Screening Tool (PEST); the Psoriatic Arthritis Screening and Evaluation (PASE) questionnaire; and the Early ARthritis for Psoriatic patients (EARP) questionnaire. Health states were defined by disability levels, as measured by the Health Assessment Questionnaire (HAQ), and state transition was modeled according to annual disease progression. Screening was assumed to be effective during a 2-year sojourn period. Incremental cost-effectiveness ratios (ICERs) were estimated based on health-state specific costs and utilities. A probabilistic analysis was undertaken to account for parameter uncertainty. All results were compared with the commonly cited cost-effectiveness threshold of CAD 50,000 (USD 37, 600) per additional QALY.Results:Screening with the ToPAS questionnaire resulted in cost savings compared with no screening or the EARP questionnaire, with a total cost of CAD 30,706 (USD 23,090) and 17.29 QALYs. The PEST dominated the PASE questionnaire and was more costly and more effective than the ToPAS questionnaire, with an ICER of CAD 312,398 (USD 234,909). The results were most sensitive to test sensitivity and specificity, HAQ progression, and average HAQ score at diagnosis and the start of biologic therapy. A scenario analysis tested screening efficacy for a 1-year period before diagnosis, with the ToPAS questionnaire remaining the most cost-effective option.Conclusions:Screening was cost-effective compared with no screening at the commonly used cost-effectiveness threshold of CAD 50,000 (USD 37, 600). Value of information analyses will be useful for determining the need to collect further information around test accuracy parameters.

The Clinical and Cost Effectiveness of Apremilast for Treating Active Psoriatic Arthritis: A Critique of the Evidence.

As part of the National Institute for Health and Clinical Excellence (NICE) single technology appraisal (STA) process, the manufacturer of apremilast was invited to submit evidence for its clinical and cost effectiveness for the treatment of active psoriatic arthritis (PsA) for whom disease-modifying anti-rheumatic drugs (DMARDs) have been inadequately effective, not tolerated or contraindicated. The Centre for Reviews and Dissemination and Centre for Health Economics at the University of York were commissioned to act as the independent Evidence Review Group (ERG). This paper provides a description of the ERG review of the company's submission, the ERG report and submission and summarises the NICE Appraisal Committee's subsequent guidance (December 2015). In the company's initial submission, the base-case analysis resulted in an incremental cost-effectiveness ratio (ICER) of £14,683 per quality-adjusted life-year (QALY) gained for the sequence including apremilast (positioned before tumour necrosis factor [TNF]-α inhibitors) versus a comparator sequence without apremilast. However, the ERG considered that the base-case sequence proposed by the company represented a limited set of potentially relevant treatment sequences and positions for apremilast. The company's base-case results were therefore not a sufficient basis to inform the most efficient use and position of apremilast. The exploratory ERG analyses indicated that apremilast is more effective (i.e. produces higher health gains) when positioned after TNF-α inhibitor therapies. Furthermore, assumptions made regarding a potential beneficial effect of apremilast on long-term Health Assessment Questionnaire (HAQ) progression, which cannot be substantiated, have a very significant impact on results. The NICE Appraisal Committee (AC), when taking into account their preferred assumptions for HAQ progression for patients on treatment with apremilast, placebo response and monitoring costs for apremilast, concluded that the addition of apremilast resulted in cost savings but also a QALY loss. These cost savings were not high enough to compensate for the clinical effectiveness that would be lost. The AC thus decided that apremilast alone or in combination with DMARD therapy is not recommended for treating adults with active PsA that has not responded to prior DMARD therapy, or where such therapy is not tolerated.

Adalimumab, etanercept, infliximab, certolizumab pegol, golimumab, tocilizumab and abatacept for the treatment of rheumatoid arthritis not previously treated with disease-modifying antirheumatic drugs and after the failure of conventional disease-modifying antirheumatic drugs only: systematic review and economic evaluation.

Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with increasing disability, reduced quality of life and substantial costs (as a result of both intervention acquisition and hospitalisation). The objective was to assess the clinical effectiveness and cost-effectiveness of seven biologic disease-modifying antirheumatic drugs (bDMARDs) compared with each other and conventional disease-modifying antirheumatic drugs (cDMARDs). The decision problem was divided into those patients who were cDMARD naive and those who were cDMARD experienced; whether a patient had severe or moderate to severe disease; and whether or not an individual could tolerate methotrexate (MTX). The following databases were searched: MEDLINE from 1948 to July 2013; EMBASE from 1980 to July 2013; Cochrane Database of Systematic Reviews from 1996 to May 2013; Cochrane Central Register of Controlled Trials from 1898 to May 2013; Health Technology Assessment Database from 1995 to May 2013; Database of Abstracts of Reviews of Effects from 1995 to May 2013; Cumulative Index to Nursing and Allied Health Literature from 1982 to April 2013; and TOXLINE from 1840 to July 2013. Studies were eligible for inclusion if they evaluated the impact of a bDMARD used within licensed indications on an outcome of interest compared against an appropriate comparator in one of the stated population subgroups within a randomised controlled trial (RCT). Outcomes of interest included American College of Rheumatology (ACR) scores and European League Against Rheumatism (EULAR) response. Interrogation of Early Rheumatoid Arthritis Study (ERAS) data was undertaken to assess the Health Assessment Questionnaire (HAQ) progression while on cDMARDs. Network meta-analyses (NMAs) were undertaken for patients who were cDMARD naive and for those who were cDMARD experienced. These were undertaken separately for EULAR and ACR data. Sensitivity analyses were undertaken to explore the impact of including RCTs with a small proportion of bDMARD experienced patients and where MTX exposure was deemed insufficient. A mathematical model was constructed to simulate the experiences of hypothetical patients. The model was based on EULAR response as this is commonly used in clinical practice in England. Observational databases, published literature and NMA results were used to populate the model. The outcome measure was cost per quality-adjusted life-year (QALY) gained. Sixty RCTs met the review inclusion criteria for clinical effectiveness, 38 of these trials provided ACR and/or EULAR response data for the NMA. Fourteen additional trials contributed data to sensitivity analyses. There was uncertainty in the relative effectiveness of the interventions. It was not clear whether or not formal ranking of interventions would result in clinically meaningful differences. Results from the analysis of ERAS data indicated that historical assumptions regarding HAQ progression had been pessimistic. The typical incremental cost per QALY of bDMARDs compared with cDMARDs alone for those with severe RA is > £40,000. This increases for those who cannot tolerate MTX (£50,000) and is > £60,000 per QALY when bDMARDs were used prior to cDMARDs. Values for individuals with moderate to severe RA were higher than those with severe RA. Results produced using EULAR and ACR data were similar. The key parameter that affected the results is the assumed HAQ progression while on cDMARDs. When historic assumptions were used typical incremental cost per QALY values fell to £38,000 for those with severe disease who could tolerate MTX. bDMARDs appear to have cost per QALY values greater than the thresholds stated by the National Institute for Health and Care Excellence for interventions to be cost-effective. Future research priorities include: the evaluation of the long-term HAQ trajectory while on cDMARDs; the relationship between HAQ direct medical costs; and whether or not bDMARDs could be stopped once a patient has achieved a stated target (e.g. remission). This study is registered as PROSPERO CRD42012003386. The National Institute for Health Research Health Technology Assessment programme.

OP0127 Impact of Disease Activity and Treatment on Progression of Functional Limitation in RA

BackgroundFunctional limitation is a key outcome in rheumatoid arthritis and a key driver of the cost of RA in health economic models. Due to restrictive inclusion/exclusion criteria and short follow...

Do Radiographic Joint Damage and Disease Activity Influence Functional Disability Through Different Mechanisms? Direct and Indirect Effects of Disease Activity in Established Rheumatoid Arthritis

To explore the relationship between rheumatoid arthritis (RA) disease activity and functional disability over time, considering indirect (predictive) and direct (concurrent) associations as well as the influence of radiographic joint damage and treatment strategy. Functional disability [Health Assessment Questionnaire (HAQ)], disease activity [28-joint Disease Activity Score (DAS28)], and radiographic joint damage [Sharp/van der Heijde score (SHS)] were measured in 4 consecutive randomized controlled trials with increasingly intensive (tight control) treatment strategies. Average followup time for the 3 cohorts was 97, 53, and 50 months, respectively. Next to current DAS28, the previous DAS28 was used to study the predictive effect of a change in DAS28 on progression of functional disability (HAQ). Finally, it was investigated whether SHS mediated the predictive effect of DAS28. In patients treated with intensive treatment strategies, the progression of HAQ over time was statistically significantly less (p < 0.0001). The predictive influence of DAS28 on HAQ progression increased over the duration of the disease. SHS was not found to influence HAQ progression and did not mediate the predictive effect of DAS28. In the less intensively treated patients, the direct effect of disease activity decreased with disease duration, and contrarily, SHS did influence HAQ progression, but was not found to (fully) mediate the predictive effect of DAS28. In patients with RA treated with modern treatment strategies, there is less functional decline over time. Further, disease activity does predict functional decline but joint damage does not. This might indicate that factors associated with cumulative disease activity but not visible on radiographs can influence functional decline in patients with RA. This further underlines the importance of disease activity as a treatment target in early RA and in established RA.

FRI0076 The effects of tight disease control of rheumatoid arthritis on HAQ

BackgroundTreat to Target (T2T) is the main strategy for the treatment of rheumatoid arthritis (RA). We need to control disease activity in order to sustain ADL in optimal status and...

SAT0113 Common trajectories of HAQ disability progression over 15-years in the early rheumatoid arthritis study and the norfolk arthritis register

BackgroundThe Health Assessment Questionnaire (HAQ) is the most widely used measure of function in studies of inflammatory polyarthritis (IP) and its subset rheumatoid arthritis (RA). Previous research has suggested the...

Golimumab for the Treatment of Rheumatoid Arthritis After the Failure of Previous Disease-Modifying Antirheumatic Drugs: A NICE Single Technology Appraisal

As part of the National Institute for Health and Clinical Excellence (NICE) single technology appraisal (STA) process, the manufacturer of golimumab (Simponi(®); Merck Sharp & Dohme, USA) was invited to submit evidence for its clinical and cost effectiveness for the treatment of rheumatoid arthritis (RA) after the failure of previous disease-modifying antirheumatic drugs (DMARDs). The School of Health and Related Research Technology Appraisal Group (ScHARR-TAG) at The University of Sheffield was commissioned to act as the independent Evidence Review Group (ERG). This article provides details of the manufacturer's initial submission, the ERG's clarification questions and the ERG report submitted to NICE. The decision made by NICE is provided alongside a brief comment on additional results produced from an additional analysis requested by NICE on behalf of the Committee. The ERG produced a critical review of the evidence for the clinical and cost effectiveness of the technology based on upon the manufacturer's submission to NICE. The clinical evidence was derived from three randomized controlled trials of golimumab in the treatment of moderate to severe RA: GO-FORWARD and Kay et al. (DMARD-experienced population) and GO-AFTER (tumour necrosis factor [TNF]-α inhibitor-experienced population). The ERG considered that the trials were of reasonable methodological quality and measured a clinically relevant range of outcomes. The trials for golimumab, as well as comparator treatments, were synthesized using mixed-treatment comparison methods for the DMARD-experienced population and an indirect comparison using the Bucher method for the TNF-α inhibitor-experienced population. The trials used were appropriate, although no definitive judgement regarding the comparative efficacy of golimumab with other biologics was possible. The manufacturer provided a DMARD-experienced population model and a TNF-α inhibitor-experienced population model. The models allowed sequences of treatments to be evaluated for each population, although a fully incremental analysis between the use of golimumab following DMARD failure and the use of golimumab following TNF-α inhibitor failure was not possible. Several limitations with the model were identified, and after a request from NICE and suspension of the appraisal, the manufacturer submitted sensitivity analyses with an additional American College of Rheumatology 70 % improvement criteria (ACR70) health state included, using SF-36 data directly from the GO-FORWARD study. The annual rate of the Health Assessment Questionnaire (HAQ) score increase for patients receiving palliative treatment was also changed from 0.09 to 0.06. The further analyses provided highlighted the particular sensitivity of the results to HAQ progression rates and the re-administration frequency for rituximab in the TNF-α inhibitor-experienced population. The Appraisal Committee concluded that golimumab should be recommended in combination with methotrexate as an option for patients with severe active RA who have failed on conventional DMARDs, or who have failed on a TNF-α inhibitor and are contraindicated to or withdrawn from rituximab.

Cost-utility analysis of abatacept in rheumatoid arthritis in Italy

Objective: a substantial number of patients with rheumatoid arthritis (RA) have an insufficient or unsustained response to Tumor Necrosis Factor-α antagonists (anti-TNFs). The aim of the present study was to estimate the cost-utility of abatacept, a new selective T-cell co-stimulation modulator, in patients with moderately to severely active RA and an insufficient response or intolerance to anti-TNFs in the Italian setting. Methods: a probabilistic patient level simulation model was developed to estimate long-term costs and health outcomes of abatacept versus anti-TNFs (etanercept, adalimumab, infliximab) in RA patients. The model predicted patients’ HAQ (Health Assessment Questionnaire) scores over time based on the initial response to treatment (% change in HAQ score at six months). Responding patients continued treatment with a reduced rate of HAQ progression until long-term treatment failure. Health-state utilities and use of health care resources (excluding RA therapies) were assumed to depend on HAQ scores. The model used data from a Phase III clinical trial of abatacept in patients with inadequate response to anti-TNFs (Abatacept Trial in Treatment of anti-TNF Inadequate Responders [ATTAIN]) and various secondary data sources. The study was performed using the National Health Service (NHS) perspective. Cost-utility of abatacept vs other anti-TNFs was derived in terms of incremental cost per quality-adjusted life-year (QALY) gained based on a lifetime horizon with costs expressed in Euros. Single-way sensitivity analyses were performed on key parameters. Costs and health effects were discounted at 3% annually. Results: abatacept therapy was estimated to yield 1.18 additional QALYs per patient (5.02 abatacept vs 3.84 anti-TNFs) at an incremental cost of € 21,996.41 based on a 20 years time horizon. Cost per QALY gained was € 18,567.24. These results were robust to variation of key model parameters and are well within the usual cost-utility acceptance ranges. Conclusions: This study shows that in Italy, compared to anti-TNFs, abatacept therapy is cost-effective in patients with moderately to severely active RA and with an insufficient response or intolerance to anti-TNFs.

Cost effectiveness of the determination of autoantibodies against cyclic citrullinated peptide in the early diagnosis of rheumatoid arthritis

Objective:To estimate the incremental cost-effectiveness ratio (ICER) of antibodies against cyclic citrullinated peptides (aCCP) in the early diagnosis of rheumatoid arthritis (RA).Methods:A Markov model was used to model 10-year progression...

Leukocyte protein calprotectin and outcome in rheumatoid arthritis

Objective: To determine if calprotectin is predictive for outcome in patients with rheumatoid arthritis (RA). Methods: Fifty six RA in-patients with variable disease duration were prospectively followed for five years. Clinical and laboratory data were collected to assess disease activity. Health Assessment Questionnaire (HAQ) and radiographic scores (of hands and wrists) as described by Larsen were used as outcome measures. Plasma calprotectin levels were determined with ELISA technique. Results: Significant correlations (r) were found cross-sectionally at follow-up between calprotectin concentration and other known parameters of disease activity and severity: CRP (r= 0.67), investigator's global assessment of disease activity (r= 0.57), Waaler titre (r= 0.50), HAQ score (r= 0.48) and number of swollen joints (r= 0.48). Calprotectin at baseline was not identified as an independent predictor for HAQ or radiographic progression in the multivariate analysis. Conclusion: The results confirm calprotectin as a good measure of disease activity and joint inflammation in RA. However, the level of calprotectin at baseline was not predictive for radiographic damage or functional impairment five years later.