Psychometric evaluation of the hepatitis C virus patient-reported outcomes (HCV-PRO) instrument: validity, responsiveness, and identification of the minimally important difference in a phase 2 clinical trial.

PURPOSE: To describe the psychometric properties and identify the minimally important difference (MID) of the hepatitis C virus patient-reported outcomes (HCV-PRO) instrument. Chronic HCV infection and associated treatments negatively affect PROs of function and well-being. METHODS: In a phase 2 trial, HCV-infected patients received direct-acting antivirals (DAAs) for 12 weeks with peg-interferon/ribavirin (peg-IFN/RBV) for 48 weeks, or placebo plus peg-IFN/RBV. The HCV-PRO total score, SF-36 PCS and MCS scores, EQ-5D-3L, and EQ VAS were measured at baseline, week 8, end of DAA treatment (EODT), end of peg-IFN/RBV treatment (EOT), and posttreatment week 24 (SVR24). Convergent validity of the HCV-PRO was assessed by Pearson's correlation coefficients. Discriminant validity was assessed by analyzing mean HCV-PRO total scores by EQ-5D anxiety/depression and pain/discomfort domain scores (none vs. some) and presence/absence of depression or fatigue adverse events. MID was identified through effect size (ES) and receiver-operating characteristic (ROC) curve analyses (HCV-PRO response vs. SF-36 PCS/MCS and EQ VAS MID thresholds). RESULTS: In 74 patients (22 % female; 81 % White; 51 % ≥50 years), correlations (0.64-0.96) between HCV-PRO total scores, SF-36 PCS/MCS scores, and EQ VAS scores at all time points supported convergent validity. HCV-PRO total scores were reduced to 10-30 points in patients impaired by depression, pain, or fatigue symptoms. Impact of peg-IFN/RBV regimen on HCV-PRO ES increased over time (EODT -0.76; EOT -0.93). ES and ROC curve analyses indicated an MID of -10 points. CONCLUSION: The HCV-PRO was valid and responsive in the population studied. An MID of -10 points represented a threshold of clinical significance for the HCV-PRO.

Development and initial psychometric evaluation of the hepatitis C virus-patient-reported outcomes (HCV-PRO) instrument.

BACKGROUND: Chronic hepatitis C virus (HCV) infection is an important public health issue owing to its worldwide prevalence and its profound effects on patients' well-being and function. We developed a new patient self-report tool, the HCV patient-reported outcomes (HCV-PRO) instrument, to assess patients' function and well-being reflecting both HCV disease and treatment burdens. METHODS: Items were developed through a qualitative phase including scientific literature review, expert appraisal, and semi-structured patient interviews. The item pool was initially psychometrically tested in 60 adult HCV patients, 18 years of age or older at a university hepatology clinic. A final psychometric test was conducted in 241 members of the online Harris International Panel to examine scale reliability, confirm factor structure, and assess convergent and discriminant validity. RESULTS: A single-factor 16-item HCV-PRO instrument demonstrated good model fit. The HCV-PRO items and total score (range 0-100) showed excellent item response (few floor and ceiling effects) and reliability (alpha > 0.90). Convergent validity was established from moderate to high (r > 0.50) correlation with symptom burden, life satisfaction (ladder of life), and SF-36v2 scales scores. Mean HCV-PRO scores differentiated between currently treated patients, those previously treated, and patients never treated (p < 0.01), suggesting strong known-groups validity. CONCLUSIONS: The results provide initial evidence that the HCV-PRO can yield reliable and valid measurement of the effects of HCV and its treatment on the well-being and function of HCV-infected patients.

Economics of switching to second-line antiretroviral therapy with lopinavir/ritonavir in Africa: estimates based on DART trial results and costs for Uganda and Kenya.

BACKGROUND: Substantial immunological improvement has been reported for HIV-infected patients who switch from a failing regimen to a protease inhibitor regimen with Lopinavir/ritonavir (LPV/r). We use decision analysis modeling to estimate health and economic consequences expected from this switch. METHODS: A Markov model combined best evidence for CD4(+) T-cell response, infectious disease events, death rates, and quality of life for African populations with Kenyan and Ugandan data on drug and medical care costs. We estimate the incremental cost-effectiveness ratio of switching to an LPV/r-based regimen versus remaining on a failed first antiretroviral (ARV) regimen or discontinuing all ARV drugs. The model assumes concurrent use of cotrimoxazole, and 4% annual loss to follow-up. Local effects due to prevalence of malaria and tuberculosis are included in the model. Sensitivity analysis examines the effects of varying disease, ARV therapy and CD4(+) T-cell cost, and ART discontinuation assumptions. RESULTS: The base model estimates an improvement of 20 months in average survival for the LPV/r group. The respective LPV/r ICER for Kenya is $1483 per quality-adjusted life year (QALY) compared to $1673/QALY for Uganda. The ICERs increase to $1517 and $1707, respectively, if CD4(+) T-cell tests cost $25. The model comparing switching to LPV/r to discontinuing all ARV drugs decreases both costs and benefits proportionally for the treatment groups. CONCLUSION: The estimates are clearly below the most stringent World Health Organization benchmark for cost-effectiveness for Kenya and within the acceptable range of cost-effectiveness for Uganda. Thus, the switch to second-line therapy with LPV/r in these countries appears to be a cost-effective use of resources.

Economic modeling of the combined effects of HIV-disease, cholesterol and lipoatrophy based on ACTG 5142 trial data.

BACKGROUND: This study examines the cost and consequences of initiating an ARV regimen including Lopinavir/ritonavir (LPV/r) or Efavirenz (EFV), using data from a recent clinical trial in a previously published model of HIV-disease. METHODS: We populated the Markov model of HIV-disease with data from ACTG 5142 study to estimate the economic outcomes of starting ARV therapy with a PI-containing regimen as compared to an NNRTI-containing regimen, given their virologic and immunologic efficacy and effects on cholesterol and lipoatrophy. CNS toxicities and GI tolerability were not included in the model because of their transient nature or low cost remedies, and therefore lack of economic impact. CD4+ T-cell counts and the HIV-1 RNA (viral load) values from the study were used to assign a specific health state (HS) to each patient for each quarter year. The resulting frequencies used as "raw" data directly into the model obviate the reliance on statistical tests, and allow the model to reflect actual patient behavior in the clinical trial. An HS just below the last observed HS was used to replace a missing value. RESULTS: The modeled estimates (undiscounted) for the LPV/r-based regimen resulted in 1.41 quality-adjusted life months (QALMs) gained over a lifetime compared to the EFV-based regimen. The LPV/r-based regimen incurred $7,458 (1.8%) greater cost over a lifetime due to differences in drug costs and survival. The incremental cost effectiveness ratio using the discounted cost and QALYs was $88,829/QALY. Most of the higher costs accrue before the 7th year of treatment and were offset by subsequent savings. The estimates are highly sensitive to the effect of lipoatrophy on Health-related Quality of Life (HRQOL), but not to the effect of cholesterol levels. CONCLUSIONS: The cost effectiveness of ARV regimens may be strongly affected by enduring AEs, such as lipoatrophy. It is important to consider specific AE effects from all drugs in a regimen when ARVs are compared. TRIAL REGISTRATION: (ClinicalTrials.gov number, NCT00050895http://[ClinicalTrials.gov]).

Comparison of Markov model and discrete-event simulation techniques for HIV.

BACKGROUND: Markov models have been the standard framework for predicting long-term clinical and economic outcomes using the surrogate marker endpoints from clinical trials. However, they are complex, have intensive data requirements and are often difficult for decision makers to understand. Recent developments in modelling software have made it possible to use discrete-event simulation (DES) to model outcomes in HIV. Using published results from 48-week trial data as model inputs, Markov model and DES modelling approaches were compared in terms of clinical outcomes at 5 years and lifetime cost-effectiveness estimates. METHODS: A randomly selected cohort of 100 antiretroviral-naive patients with a mean baseline CD4+ T-cell count of 175 cells/mm3 treated with lopinavir/ritonavir was selected from Abbott study M97-720. Parameter estimates from this cohort were used to populate both a Markov and a DES model, and the long-term estimates for these cohorts were compared. The models were then modified using the relative risk of undetectable viral load as reported for atazanavir and lopinavir/ritonavir in the published BMS 008 study. This allowed us to compare the mean cost effectiveness of the models. The clinical outcomes included mean change in CD4+ T-cell count, and proportion of subjects with plasma HIV-1 RNA (viral load [VL]) <50 copies/mL, VL 50-400 copies/mL and VL >400 copies/mL. US wholesale acquisition costs (year 2007 values) were used in the mean cost-effectiveness analysis, and the cost and QALY data were discounted at 3%. RESULTS: The results show a slight predictive advantage of the DES model for clinical outcomes. The DES model could capture direct input of CD4+ T-cell count, and proportion of subjects with plasma HIV-1 RNA VL <50 copies/mL, VL 50-400 copies/mL and VL >400 copies/mL over a 48-week period, which the Markov model could not. The DES and Markov model estimates were similar to the actual clinical trial estimates for 1-year clinical results; however, the DES model predicted more detailed outcomes and had slightly better long-term (5-year) predictive validity than the Markov model. Similar cost estimates were derived from the Markov model and the DES. Both models predict cost savings at 5 and 10 years, and over a lifetime for the lopinavir/ritonavir treatment regimen as compared with an atazanavir regimen. CONCLUSION: The DES model predicts the course of a disease naturally, with few restrictions. This may give the model superior face validity with decision makers. Furthermore, this model automatically provides a probabilistic sensitivity analysis, which is cumbersome to perform with a Markov model. DES models allow inclusion of more variables without aggregation, which may improve model precision. The capacity of DES for additional data capture helps explain why this model consistently predicts better survival and thus greater savings than the Markov model. The DES model is better than the Markov model in isolating long-term implications of small but important differences in crucial input data.

Impact of lipoatrophy on quality of life in HIV patients receiving anti-retroviral therapy.

Metabolic and morphological side-effects occur in HIV-infected individuals receiving anti-retroviral treatment (ART). Peripheral fat loss that occurs particularly in the face, limbs and/or buttocks is referred to as lipoatrophy and has been found to be highly stigmatizing and to adversely impact the health-related quality of life (HRQL). Consumer Health Sciences Survey data collected between November 2003 and January 2006 were utilized to evaluate the impact of lipoatrophy on the HRQL in HIV-infected individuals receiving ART. This was evaluated using analysis of variance with item scores and mental component summary (MCS) and physical component summary (PCS) scores from the Medical Outcomes Trust questionnaire, SF-8 as dependent variables and lipoatrophy as the independent variable controlling for baseline age, sex and ethnicity. Clinical meaningfulness (mean difference divided by population standard deviation, delta/sigma) of differences between the groups with and without lipoatrophy was also evaluated. A cohort of 1124 subjects with at least six months of ART was selected based on the availability of data on whether or not lipoatrophy was present. Subjects were primarily male (80%), between the ages of 30 and 60 years (90%), Hispanic (37%) and about 25% each of African American and White. Overall, prevalence of lipoatrophy in this cohort of HIV patients was 18.9%. Statistically significant (p<0.001) differences in quality of life (as measured by SF-8 individual item scores and MCS and PCS scores) were observed between the two groups. The differences between the groups in item and summary scores were clinically meaningful in the small to near medium range (0.28-0.43). HIV-infected patients already experience a considerable deficiency in HRQL compared to general population; this study demonstrates that lipoatrophy further enhances that negative impact on HRQL.

Impact of lipoatrophy on patient-reported outcomes in antiretroviral-experienced patients.

Lipoatrophy is a noteworthy adverse effect of antiretroviral therapy. A 2-part literature review was conducted to assess the impact of lipoatrophy in HIV-infected persons: the first reviewed the qualitative studies that reported lipoatrophy data, and the second reviewed the clinical studies that recorded patient-reported outcome end points. This literature review provided considerable evidence that lipoatrophy has a negative impact on the psychosocial well-being and health-related quality of life of HIV-infected persons receiving antiretroviral therapy. However, the patient-reported outcome measures used in clinical studies were not lipoatrophy-specific and had limited ability to show real changes in health status associated with lipoatrophy.

Cost effectiveness of lopinavir/ritonavir compared with atazanavir plus ritonavir in antiretroviral-experienced patients in the US.

OBJECTIVE: To estimate the cost effectiveness and long-term combined effects of HIV disease and antiretroviral (ARV) therapy-related risk for coronary heart disease (CHD) on quality-adjusted survival and healthcare costs for ARV-experienced patients. METHODS: A previously validated Markov model was updated and supplemented with the Framingham CHD risk equation. The representative patient in the model was male, aged 37 years and had a baseline 10-year CHD risk of 4.6%. Patients started with either lopinavir/ritonavir (LPV/r) or ritonavir-boosted atazanavir (ATV+RTV) as the protease inhibitor (PI). The proportions of patients with viral suppression below 400 and 50 copies/mL, respectively, at week 48 reported in clinical trials were used to estimate the differences between these two therapies. The daily ARV costs were $US 24.60 for LPV/r capsules (2005 costs) and $US 26.54 for LPV/r tablets (2006 costs), $US 29.76 for ATV and $US 8.57 for ritonavir (2005 costs). Costs of other ARV drugs were taken from average wholesale drug reports for 2005. The cost of AIDS events was estimated from Medicaid billing databases and reflected a medical care system perspective and 2005 treatment costs. Cost-effectiveness calculations assumed a lifetime time horizon. The effects of different model assumptions were tested in a multiway sensitivity analysis by combining extreme values of parameters. RESULTS: The model estimated a clinical and economic advantage to using LPV/r over ATV+RTV, which varied depending upon the use of LPV/r capsules or tablets. Using LPV/r capsules was comparatively beneficial for ARV-experienced patients in quality-adjusted life-months (QALMs) of 4.6 (corrected for differences in CHD risk) compared with ATV+RTV. In addition, there were 5- and 10-year overall per-patient cost savings of $US 17,995 and $US 21,298, respectively. Estimates for the LPV/r tablet formulation approved in 2005 (assuming similar efficacy) improved cost savings over 5- and 10-year periods to $US 19,598 and $US 23,126 per patient, respectively, because of a drug price differential. Sensitivity analysis tested numerous assumptions about the model cost and efficacy parameters and found that the results were robust to most changes. Model limitations were the uncertainty associated with the model parameters used. CONCLUSION: LPV/r appears to be a highly cost-effective regimen relative to ATV+RTV for the treatment of HIV. The long-term CHD risk associated with LPV/r was minimal compared with the increased risk of AIDS/death and costs projected for a less efficacious PI-based regimen.

Cost effectiveness of lopinavir/ritonavir tablets compared with atazanavir plus ritonavir in antiretroviral-experienced patients in the UK, France, Italy and Spain.

BACKGROUND AND OBJECTIVE: Selection of antiretroviral therapy (ART) for antiretroviral-experienced patients should involve balancing multiple factors, including clinical efficacy, adverse-event risk, resistance concerns, cost effectiveness and expected budget impact. The efficacy of a regimen and its durability, as demonstrated in controlled clinical trials, must be considered in the light of short- and long-term economic impacts on the healthcare system. These impacts may vary based on drug costs, costs of reported adverse effects, the regimen's likelihood of contributing to viral resistance to second-line therapies and the marginal cost differences between other healthcare resources used over a patient's lifetime. Risk of coronary heart disease (CHD) may be of concern in the selection of ART, because differences in CHD risk factors have been reported for different regimens, and heart disease is both a deadly and costly condition. This study set out to estimate the long-term combined effects of HIV disease and antiretroviral-related risk for CHD on quality-adjusted survival and healthcare costs for antiretroviral-experienced patients in the UK, Spain, Italy and France. METHODS: A previously validated Markov model was updated with 2006 cost estimates for each of the four countries and supplemented with the Framingham CHD risk equation. In the model, the average patient was male, aged 37 years, with a baseline 10-year CHD risk of 4.6%. Patients started with either lopinavir/ritonavir (LPV/r) or ritonavir-boosted atazanavir (ATV+RTV) as the protease inhibitor (PI). Clinical trial results, local drug costs and AIDS and CHD cost estimates were used to estimate the differences between these two therapies. RESULTS: There was a significant advantage using LPV/r over ATV+RTV, which varied depending on the country's cost structure and assumptions related to drug efficacy. There was a comparative benefit for experienced patients in quality-adjusted life-months (QALM) of 4.6 (the net gain after subtracting quality-adjusted life-years [QALYs] lost owing to CHD risk). In addition, there were 5- and 10-year overall cost savings of between euro947 and euro6594 per patient after 5 years, and an impact ranging from a cost increase of euro308 (for France) to a cost saving of euro7388 (for Spain) at year 10. The lifetime incremental cost-effectiveness ratios ranged from dominant for Spain to euro11 856/QALY for Italy. CONCLUSION: LPV/r was a highly cost-effective regimen relative to ATV+RTV for the treatment of HIV for each of the four countries examined in this study. The effect of LPV/r on long-term CHD risk was minimal compared with the increased risk of AIDS/death projected for a less efficacious PI-based regimen. The cost of lipid-lowering drugs and treatment for CHD was insignificant compared with the overall cost savings from LPV/r therapy. The choice of regimen for antiretroviral-experienced patients should be based on a regimen's expected efficacy and durability for countries with similar cost structure to those examined here.

Cost-minimization comparison of darunavir plus ritonavir and lopinavir/ritonavir in HIV-1 infected treatment-naïve women of childbearing age.

BACKGROUND: Guidelines from the Department of Health and Human Services in the US recommend ritonavir-boosted lopinavir (LPV/r) as a preferred protease inhibitor (PI) for HIV-positive antiretroviral-naїve pregnant women. These guidelines also cite ritonavir-boosted darunavir (DRV + RTV) as an alternative PI in this clinical scenario. The purpose of this analysis was to compare economic outcomes for regimens based on these two treatments. STUDY DESIGN: An existing discrete event simulation (DES) model was adapted to conduct a cost-minimization analysis comparing the two regimens in HIV-infected women of childbearing age (WOCBA), from the perspective of a healthcare payer in the US. METHODS: The DES model was used to represent disease states, health events, healthcare encounters, pregnancy, and treatment choices in HIV-infected WOCBA starting treatment with regimens based on either LPV/r or DRV + RTV. It also incorporated parameters for individual patient characteristics, and for antiretroviral (ARV) treatment effectiveness, treatment sequencing, clinical progression, and resource use. Potential events included scheduled physician visits; viral suppression; viral rebound; AIDS-related complications; CHD events; treatment discontinuation and switching; ARV treatment side-effects (SE); and death. The primary outcomes were discounted 5-year and 10-year healthcare costs. Alternative scenarios considered different rates of switching from DRV + RTV to LPV/r upon conception. RESULTS: Compared with DRV + RTV, LPV/r was associated with similar clinical outcomes while offering savings at the 5- and 10-year horizons (of $24,904 and $43,502 per patient, respectively), and in extensive sensitivity analyses. The main driver of the savings was the difference in cost between PIs. CONCLUSIONS: Starting HIV-infected ARV-treatment-naїve WOCBA on an LPV/r-based regimen is cost-saving and provides similar patient outcomes compared to a DRV + RTV-based regimen.

Lopinavir/ritonavir versus darunavir plus ritonavir for HIV infection: a cost-effectiveness analysis for the United States.

BACKGROUND: The ARTEMIS trial compared first-line antiretroviral therapy (ART) with lopinavir/ritonavir (LPV/r) to darunavir plus ritonavir (DRV + RTV) for HIV-1-infected subjects. In order to fully assess the implications of this study, economic modelling extrapolating over a longer term is required. OBJECTIVE: The aim of this study was to simulate the course of HIV and its management, including the multiple factors known to be of importance in ART. METHODS: A comprehensive discrete event simulation was created to represent, as realistically as possible, ART management and HIV outcomes. The model was focused on patients for whom clinicians believed that LPV/r or DRV + RTV were good options as a first regimen. Prognosis was determined by the impact of initial treatment on baseline CD4+ T-cell count and viral load, adherence, virological suppression/failure/rebound, acquired resistance mutations, and ensuing treatment changes. Inputs were taken from trial data (ARTEMIS), literature and, where necessary, stated assumptions. Clinical measures included AIDS events, side effects, time on sequential therapies, cardiovascular events, and expected life-years lost as a result of HIV infection. The model underwent face, technical and partial predictive validation. Treatment-naive individuals similar to those in the ARTEMIS trial were modelled over a lifetime, and outcomes with first-line DRV + RTV were compared with those with LPV/r, both paired with tenofovir and emtricitabine. Up to three regimen changes were permitted. Drug prices were based on wholesale acquisition cost. Outcomes were lifetime healthcare costs (in 2011 US dollars) from the US healthcare system perspective and quality-adjusted life-years (QALYs) (discounted at 3 % per annum). RESULTS: Choice of LPV/r over DRV + RTV as initial ART resulted in nearly identical clinical outcomes, but distinctly different economic consequences. Starting with an LPV/r regimen potentially results in approximately US$25,000 discounted lifetime savings. Accumulated QALYs for LPV/r and DRV + RTV were 12.130 and 12.083, respectively (a 19-day difference). In sensitivity analyses, net monetary benefit ranged from US$12,000 to US$31,000, favouring LPV/r (base case US$27,762). CONCLUSIONS: A comprehensive simulation of lifetime course of HIV in the USA indicated that using LPV/r as first-line therapy compared with DRV + RTV may result in cost savings, with similar clinical outcomes.

Broadening the perspective when assessing evidence on boosted protease inhibitor-based regimens for initial antiretroviral therapy.

Several national and international guidelines recommend the use of antiretroviral therapy containing a protease inhibitor (PI) with ritonavir (RTV) boosting for human immunodeficiency virus (HIV)-infected treatment-naïve patients. RTV-boosted PIs such as lopinavir (LPV/r), atazanavir (ATV + RTV), darunavir (DRV + RTV), fosamprenavir (FPV + RTV), and saquinavir (SQV + RTV) are usually recommended in regimens for initial therapy. The guideline recommendations are generally based on the clinical efficacy of the regimens. A broadened perspective of assessing the evidence related to selection of a PI for optimal first-line therapy might consider additional factors for evaluation, such as effectiveness in actual clinical practice and cost-effectiveness of individual drugs in formulating recommendations. Among the guideline-recommended PIs, LPV/r is one of the earliest PIs approved, has been a well-recognized boosted PI for treatment-naïve patients in all guidelines, and demonstrates the most evidence on long-term clinical and economic effectiveness. Studies have shown its efficacy in various controlled and real-world settings in different populations, the relationship of adherence to virologic efficacy, and the implications of resistance when used in sequence with other PI regimens. In the absence of published evidence for other guideline-recommended PIs that will greatly facilitate a fully transparent, comparative effectiveness evaluation, the cumulative evidence from this broader perspective indicates all PIs should not be viewed as equally safe and effective across all patients for initial therapy, nor should any single PI within the class be considered preferred for all treatment-naïve patients.

Cost-effectiveness analysis of lopinavir/ritonavir and atazanavir+ritonavir regimens in the CASTLE study.

INTRODUCTION: The purpose of the study was to conduct a cost-effectiveness analysis and budget impact analysis comparing lopinavir with ritonavir (LPV/r) and atazanavir plus ritonavir (ATV+RTV) for antiretroviral-naïve patients with a baseline CD4+ T-cell distribution and total cholesterol (TC) profile as reported in the CASTLE study. METHODS: This decision analysis study used a previously published Markov model of HIV disease, incorporating coronary heart disease (CHD) events to compare the short- and long-term budget impacts and CHD consequences expected for the two regimens. RESULTS: Patients were assumed to have a baseline CHD risk of 4.6% (based on demographic data) and it was also assumed that 50% of the population in the CASTLE study were smokers. The CHD risk differences (based on percent of patients with TC >240 mg/dL) in favor of ATV+RTV resulted in an average improvement in life expectancy of 0.031 quality-adjusted life years (QALYs) (11 days), and an incremental cost-effectiveness ratio of $1,409,734/QALY. Use of the LPV/r regimen saved $24,518 and $36,651 at 5 and 10 years, respectively, with lifetime cost savings estimated at $38,490. A sensitivity analysis using a cohort of all smokers on antihypertensive medication estimated an average improvement in life expectancy of 31 quality-adjusted days in favor of ATV+RTV, and a cost-effectiveness ratio of $520,861/QALY: a ratio that is still above the acceptable limit within the US. CONCLUSION: The use of an LPV/r-based regimen in antiretroviral-naïve patients with a baseline CHD risk similar to patients in the CASTLE study appears to be a more cost-effective use of resources compared with an ATV+RTV-based regimen. The very small added CHD risk predicted by LPV/r treatment is more than offset by the substantial short- and long-term cost savings expected with the use of LPV/r in antiretroviral-naïve individuals with average to moderately elevated CHD risk.

Improvement and longterm maintenance of quality of life during treatment with adalimumab in severe rheumatoid arthritis.

OBJECTIVE: In patients with longstanding severe rheumatoid arthritis (RA) receiving chronic treatment with adalimumab, health related quality of life (HRQOL) was assessed using new instruments [Functional Assessment of Chronic Illness Therapy-Fatigue scale (FACIT-Fatigue) and Health Utilities Index Mark 3 (HUI3)] and a more conventional instrument [Medical Outcomes Study Short Form-36 Health Survey (SF-36)]. METHODS: Different measures for collecting patient-reported outcomes were applied simultaneously during the 3-year study period. Sociodemographic and medical history data were assessed at the baseline visit. Clinical examinations (e.g., joint examination and morning stiffness), disease assessments, and HRQOL data were recorded every 8 weeks. For dichotomous and categorical variables, absolute and relative frequencies were calculated. Metric measures were described using mean and standard deviation and/or standard error of the mean. HRQOL data were analyzed using observed cases. RESULTS: All assessed measures (FACIT-Fatigue, HUI3, SF-36) showed a rapid and statistically significant improvement from baseline following initiation of adalimumab therapy. This effect was maintained over the study period for a mean of 1.6 years in all applied measures. HRQOL data from all tested instruments were significantly correlated with each other. CONCLUSION: Chronic therapy with adalimumab improved measures of fatigue and HRQOL in patients with longstanding RA.