A systematic literature review of incidence, mortality, and relapse of patients diagnosed with chronic graft versus host disease.

INTRODUCTION: Chronic graft-versus-host disease (chronic GVHD) is a leading cause of late death and contributes significantly to morbidity following hematopoietic stem cell transplantation. This study aims to provide a systematic literature review on incidence, mortality, and relapse of chronic GVHD patients. Areas covered: The authors searched for English-language articles published between 2007 and 2017 using PubMed. Studies that applied the 2005 or 2015 NIH Consensus Criteria for the diagnosis and staging of chronic GVHD, and had a cohort size of at least 100 patients were included. Expert opinion: The authors found a wide variation of incidence rates, which can be explained by heterogeneity in the characteristics of study samples and applied transplantation protocols. Chronic GVHD was associated with higher non-relapse mortality (NRM), superior overall survival (OS) and lower risk of relapse. Studies indicated an increased risk for NRM and worse OS in the presence of more severe disease. Future therapies should focus to reach a delicate balance between controlling disease severity among patients diagnosed with chronic GVHD and preserving the graft versus tumor effect which goes along with chronic GVHD and results in improved OS and decreased relapse rate. Nonetheless, factors predicting disease severity still need to be further understood.

Humanistic burden of patients with chronic graft-versus-host disease - systematic literature review of health-related quality of life and functional status.

INTRODUCTION: Chronic graft-versus-host disease (GVHD) is a serious complication of allogeneic hematopoietic stem cell transplantation (HSCT). This study aims to provide a systematic overview of evidence on the health-related quality of life (HRQoL) and functional capacity of HSCT patients with National Institutes of Health (NIH)-defined chronic GVHD. Areas covered: English-language articles published between 2007 and 2017 were searched using PubMed. Studies that used the 2005 or 2015 NIH consensus criteria for the diagnosis and staging of chronic GVHD and had a cohort size of at least 100 patients were included. Expert opinion: Disease severity and organ involvement were the most important predictors of HRQoL and functionality in chronic GVHD patients. Further, identified predictors of HRQoL were nutrition status and functional capacity, while functional status was also associated with disease symptoms, nutrition status, age, and survival. Data regarding the effect of symptom bother on HRQoL were limited. Our findings confirm that the management of chronic GVHD should focus on improving not only clinical outcomes but also on HRQoL and functional capacity. Therefore, to evaluate new treatment options it is recommended to include patient relevant endpoints into prospective studies. This study also highlights the importance of nonpharmacological aspects in the management of chronic GVHD.

Improvement of fatigue, physical functioning, and well-being among patients with severe impairment at baseline receiving ibrutinib in combination with bendamustine and rituximab for relapsed chronic lymphocytic leukemia/small lymphocytic lymphoma in the HELIOS study.

Health-related quality of life (HRQoL) is an important endpoint, especially in clinical trials for malignancies with a long course of disease, such as chronic lymphocytic leukemia (CLL). Patient-reported outcomes were examined in the randomized, double-blind, placebo-controlled HELIOS study to assess the impact of treatment with the Bruton's tyrosine kinase inhibitor ibrutinib, added to bendamustine plus rituximab (BR) background therapy. Measures included FACIT-Fatigue, EORTC QLQ-C30, QLQ-CLL16, and EQ-5D-5L. Of 578 patients enrolled, 540 (93%) provided FACIT-Fatigue responses at baseline. Most had only a moderate degree of impairment at baseline; mean values did not appear to change over time in either treatment arm, suggesting that adding ibrutinib to BR did not impact health-related quality of life. However, post-hoc analyses showed that subgroups of patients with the worst fatigue, physical functional status, and well-being at baseline had greater improvements in these outcomes with ibrutinib plus BR treatment versus placebo.

Indirect Treatment Comparisons of Ibrutinib Versus Physician's Choice and Idelalisib Plus Ofatumumab in Patients With Previously Treated Chronic Lymphocytic Leukemia.

PURPOSE: Treatment options for patients with relapsed or refractory chronic lymphocytic leukemia (R/R CLL) are limited. Until recently, few effective treatment options existed, and even with the advent of new agents, studies evaluating comparative efficacy are scarce. In the Ibrutinib Versus Ofatumumab in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia (RESONATE) Phase III study, ibrutinib, an oral, once-a-day, first-in-class covalent Bruton tyrosine kinase inhibitor, improved progression-free survival (PFS) and overall survival (OS) compared with ofatumumab (PFS hazard ratio [HR] = 0.106 and OS HR = 0.369 [adjusted for crossover] at a median of 16 months' follow-up). We sought to establish the relative efficacy of ibrutinib versus other treatment options for patients with R/R CLL using indirect comparison methods. METHODS: A systematic literature review was conducted to identify clinical trials sharing a common treatment arm with the RESONATE Phase III trial such that a network meta-analysis or indirect treatment comparisons (ITCs) could be conducted. Two trials were identified, each using the same comparator (ofatumumab) as the RESONATE study. Two pairwise ITCs were conducted using the Bucher method to establish the relative treatment efficacy of ibrutinib versus (1) idelalisib plus ofatumumab in the first study and (2) physician's choice, defined as a mix of therapies commonly used in R/R CLL, in the second study. Odds ratios for these ITCs were calculated for overall response rate (ORR) and HRs for PFS and OS. FINDINGS: A strong and consistent trend of superiority for ibrutinib was observed via these ITC models with idelalisib plus ofatumumab and physician's choice for ORR, PFS, and OS. Ibrutinib revealed prolonged PFS and OS versus comparators (PFS HR = 0.06; 95% CI, 0.04-0.11; and OS HR = 0.25; 95% CI, 0.12-0.54), physician's choice (PFS HR = 0.41; 95% CI, 0.25-0.66; and OS HR = 0.50; 95% CI, 0.23-1.08), and idelalisib plus ofatumumab. These findings were robust and continued to favor ibrutinib when adjusting (where appropriate) for underlying differences in patient population between the trials. Some trial differences were not accounted for in the models and thus some limitations remain; however, consistency of results supports the overall findings. IMPLICATIONS: In a randomized Phase III study, ibrutinib significantly improved ORR, PFS, and OS in patients with R/R CLL versus ofatumumab. In ITC models that used ofatumumab as the common comparator, ibrutinib appears to have higher ORR and longer PFS and OS versus both idelalisib plus ofatumumab and physician's choice. In the absence of head-to-head studies and taking into consideration inherent limitations of ITCs, these models provide useful estimates of comparative efficacy.

Thromboembolism prophylaxis in medical inpatients: effect on outcomes and costs.

OBJECTIVES: To evaluate the real-world use of venous thromboembolism (VTE) prophylaxis among medical inpatients and the impact of VTE prophylaxis on outcomes and cost. STUDY DESIGN: Retrospective analysis of patientlevel administrative claims data for medical inpatients at risk of VTE and linked outpatient data. METHODS: Data were analyzed from patients admitted to the hospital from 2005 to 2007 (calendar years) with a primary diagnosis of chronic heart failure, thromboembolic stroke, severe lung disease, acute infection, or cancer (index hospitalization), according to whether they received VTE prophylaxis or not. The number of VTE events, time to VTE event, length of hospital stay, and number of major or minor bleeding events were analyzed from the index date until the end of follow-up (180 days postdischarge) or death. RESULTS: Overall, 7127 of 13,293 patients (53.6%) received VTE prophylaxis. Prophylaxis significantly reduced the incidence of VTE compared with no prophylaxis (0.06% vs 3.44%, respectively; P <.00001) and increased the median time to VTE (182 vs 27 days, respectively). Prophylaxis also significantly reduced the incidence of VTE in the 180 days postdischarge. Readmission rates were similar between groups. Major bleeding occurred in 1.57% of patients receiving low molecular weight heparin + warfarin versus <.6% receiving any other form of prophylaxis. The development of VTE or major or minor bleeding events significantly increased total medical costs versus no VTE events (P <.0001) or no bleeding events (P <.0003). CONCLUSIONS: This real-world analysis showed that thromboprophylaxis was underutilized in medical patients, even though the clinical and economic impact of VTE was significant.

Cost effectiveness of rivaroxaban versus enoxaparin for prevention of post-surgical venous thromboembolism from a U.S. payer's perspective.

BACKGROUND: Major orthopaedic surgery, such as total hip replacement (THR) and total knee replacement (TKR), is associated with an increased risk of venous thromboembolism (VTE). OBJECTIVE: Clinical trials have demonstrated the efficacy of rivaroxaban, a once-daily, orally administered Factor Xa inhibitor, for the prevention of VTE in patients undergoing THR or TKR. This analysis evaluated the cost effectiveness of rivaroxaban compared with enoxaparin, from a U.S. payer's perspective. METHODS: A decision-analytic model was developed to compare the costs and outcomes associated with rivaroxaban and enoxaparin for the prevention of VTE. The model replicated short-term clinical outcomes from the phase III RECORD trials. RECORD1 and RECORD2 compared rivaroxaban 10 mg daily (qd), given for 35 days, with enoxaparin 40 mg qd, given for 35 days or 10 to 14 days, respectively, in patients undergoing THR. RECORD3 compared 10 mg of rivaroxaban qd for 10 to 14 days versus 40 mg of enoxaparin qd for 10 to 14 days in patients undergoing TKR. The decision-analytic model also included data on long-term complications and sequelae as captured in observational studies and databases. It also included direct year 2010 medical costs over 1-year and 5-year time horizons. A series of sensitivity analyses were performed to determine the impact of different factors on the results of the model. Results of the cost-effectiveness analysis were reported in terms of symptomatic VTE events avoided. RESULTS: Rivaroxaban was associated with cost savings of $US 511.93 per patient and prevented an average of 0.0145 symptomatic VTE events per patient in the THR population, compared with enoxaparin. For a TKR population, 10 to 14 days of rivaroxaban prophylaxis was associated with cost savings of $US 465.74 and prevented an average 0.0193 symptomatic VTE events per patient. Sensitivity analysis suggested that the results of the model were robust, with cost savings ranging from $US 133.96-629.57 in the THR population and $US 293.01-848.68 in the TKR population, depending on the variables used. Sensitivity analysis also suggested that the economic profile of rivaroxaban is improved when the time horizon of the model is extended from 1 year to 5 years. A probabilistic sensitivity analysis confirmed the findings of baseline results, showing that rivaroxaban was less costly and more effective in all model simulations for both populations. CONCLUSIONS: This decision-analytic model analysis, from the U.S. payer's perspective, concluded that rivaroxaban may be cost saving in both the THR and the TKR populations, when compared with enoxaparin in the U.S.

Risk of venous thromboembolism and benefits of prophylaxis use in hospitalized medically ill US patients up to 180 days post-hospital discharge.

BACKGROUND: To assess the incidence of venous thromboembolism (VTE) and bleeding events with or without thromboprophylaxis and the associated costs in a cohort of medically ill patients in both in-hospital and outpatient settings. METHODS: A large hospital drug database and linked outpatient files were used to identify patients eligible for this analysis, based on demographic and clinical characteristics. RESULTS: Among 11,135 patients identified, 1592 (14.30%) were admitted with chronic heart failure, 1684 (15.12%) with thromboembolic stroke, 3834 (34.43%) with severe lung disease, 1658 (14.89%) with acute infection, and 2367 (21.26%) with cancer. Of the 11,135 patients, 5932 received anticoagulant therapy at some point during their hospitalization and until 30 days after discharge. VTE events occurred in 1.30% of patients who received anticoagulant prophylaxis versus 2.99% of patients who did not. Risk-adjusted total healthcare costs for patients with a VTE or major or minor bleeding event were significantly higher than for those without events (VTE: $52,157 ± 24,389 vs $24,164 ± 11,418; major bleeding: $33,656 ± 18,196 vs $24,765 ± 11,974; minor bleeding: $33,690 ± 14,398 vs $23,610 ± 11,873). In a multivariate analysis, appropriate anticoagulant prophylaxis use was significantly associated with a reduced risk of clinical VTE, compared with no anticoagulant use (hazard ratio: 0.37). Patients admitted with thromboembolic stroke were less likely to have a VTE than patients admitted with cancer (hazard ratio: 0.42). CONCLUSIONS: In this analysis, VTE and major bleeding event rates were lower for patients who received prophylaxis compared with those who did not. Prophylaxis use was associated with lower healthcare costs.

Cost and outcomes associated with rivaroxaban vs enoxaparin for the prevention of postsurgical venous thromboembolism from a US payer's perspective.

OBJECTIVE: The objective of this analysis was the evaluation of the outcomes and costs associated with rivaroxaban and enoxaparin for the prevention of postsurgical venous thromboembolism (VTE) in patients undergoing total hip replacement (THR) and total knee replacement (TKR) from the US payer perspective. METHODS: VTE event rates have been reported in three Phase III clinical trials that compared rivaroxaban and enoxaparin for VTE prevention after orthopedic surgery during the prophylaxis (≤35 days for THR patients and 10-14 days for TKR patients) and post-prophylaxis periods (≤90 days following surgery). These data were used in this decision-analytic model to estimate and compare health outcomes and costs associated with rivaroxaban and enoxaparin. The base-case analysis considered the number and costs of symptomatic VTE events during the prophylaxis period only. A 90-day horizon was considered in the sensitivity analysis. RESULTS: Following THR, when extended durations of prophylaxis (35 days) were compared, rivaroxaban was associated with lower costs than enoxaparin, with total saving costs of $695/patient. When an extended duration of rivaroxaban prophylaxis (35 days) was compared with a short duration (10-14 days) of enoxaparin prophylaxis, rivaroxaban was estimated to prevent 9.9 additional symptomatic VTE events per 1000 patients, while saving $244/patient (rate/1000 patients). In the TKR population, short duration of rivaroxaban prophylaxis was estimated to prevent 13.1 additional symptomatic VTE events per 1000 patients. It was also less costly than short duration enoxaparin prophylaxis, with a saving of $411/patient (rate/1000 patients). LIMITATIONS: Only statistically significant differences were captured in the base-case economic analysis, and, therefore, differences in pulmonary embolism (PE) and bleeding events were not captured. CONCLUSIONS: In this model, rivaroxaban reduced total treatment payer costs vs enoxaparin for the prevention of VTE in THR or TKR patients.

Economic impact of venous thromboembolism after hip and knee arthroplasty: potential impact of rivaroxaban.

The number of total hip and knee arthroplasties is increasing, with a consequent rise in the number of patients at risk of venous thromboembolism. Each such event is associated with the risk of morbidity and mortality, plus substantial healthcare costs. Consequently, the American College of Chest Physicians guidelines recommend low-molecular-weight heparins, fondaparinux or vitamin K antagonists (usually warfarin) after total hip and knee arthroplasty. However, such agents are also associated with healthcare costs for administration and monitoring. New oral anticoagulants in development may reduce post-arthroplasty symptomatic thromboembolic events and produce potential savings for the healthcare system. This brief article outlines such potential savings with rivaroxaban based on the results of the REgulation of Coagulation in ORthopaedic surgery to prevent Deep vein thrombosis and pulmonary embolism (RECORD) program.

An indirect comparison, via enoxaparin, of rivaroxaban with dabigatran in the prevention of venous thromboembolism after hip or knee replacement.

OBJECTIVE: To compare the efficacy, in the prevention of venous thromboembolism (VTE), and safety, of rivaroxaban and dabigatran relative to the common comparator enoxaparin. METHODS: Two randomized clinical trials of dabigatran, one after total hip replacement (THR), RE-NOVATE, and one after total knee replacement (TKR), RE-MODEL, were identified as using the same enoxaparin regimen (40 mg once daily given the evening before surgery) and being of comparable duration to two rivaroxaban trials, RECORD1 and RECORD3. Indirect comparisons were performed on both efficacy and safety endpoints. To enable comparisons, symptomatic VTE results were based on the total study duration period, i.e. including the follow-up period. Major bleeding included surgical-site bleeding events. RESULTS: After THR, rivaroxaban 10 mg once daily significantly reduced total VTE and symptomatic VTE relative to dabigatran 220 mg once daily (relative risk 0.34 and 0.19, respectively). After TKR, rivaroxaban significantly reduced total VTE versus dabigatran (relative risk 0.53); symptomatic VTE was not different between dabigatran and rivaroxaban. There was no significant difference in the rates of major bleeding for patients receiving rivaroxaban or dabigatran. CONCLUSIONS: Based on the indirect comparisons, rivaroxaban was estimated to be more efficacious than dabigatran in the prevention of total VTE after THR and TKR. Our analysis relied upon published data for dabigatran and did not have the advantages of more detailed comparative data obtained directly from a randomized trial, as was the case with rivaroxaban. Further comparative research may be of value, but until available our conclusions represent the best available evidence.

Clinical and cost outcomes of venous thromboembolism in Medicare patients undergoing total hip replacement or total knee replacement surgery.

BACKGROUND: Venous thromboembolism (VTE) occurs most often during hospitalization for major surgery or trauma but may also occur up to several months after surgery. Since the potential for VTE exists in a range of clinical settings, an assessment of its impact on overall outcomes and costs to the patient and to the healthcare system is warranted. OBJECTIVE: To evaluate the effects of VTE (deep vein thrombosis, pulmonary embolism, or both) occurring within the first 30 days of hospital discharge for total hip replacement (THR) or total knee replacement (TKR) surgery on inpatient costs, mortality, rehospitalization, and major bleeding within 1 year after initial hospitalization for THR or TKR surgery. METHODS: The Medicare Provider Analysis and Review (MEDPAR) file for calendar years 2005-2007 provided hospital discharge abstracts for the fee-for-service, acute-care hospitalizations of all Medicare recipients. All patients included in the analysis underwent THR (n = 51,108) or TKR (n = 115,627). VTE events were diagnosed within the first 30 days and within 1 year post discharge. Propensity score matching was used to control for differences in baseline characteristics in patients with and without VTE events. Total cost was measured as Medicare cost plus beneficiary out-of-pocket cost. RESULTS: VTE occurred in 0.74% of patients undergoing THR. For patients with VTE versus no VTE, mortality was higher (2.9% vs 0.4%, P < 0.001) and rehospitalization within 1 year was more frequent (51.9% vs 22.4%, P < 0.001), as were complications such as bleeding (11.2% vs 2.7%, P < 0.001). Risk-adjusted Medicare cost and total healthcare cost, including beneficiary cost share in 1 year, were significantly higher for VTE patients versus patients with no VTE ($18,929 vs $3763, P < 0.001). VTE occurred in 0.70% of patients undergoing TKR. For patients with VTE versus no VTE, mortality was higher (2.5% vs 0.15%, P < 0.001), and rehospitalization within 1 year was more frequent (48.7% vs 20.7%, P < 0.001), as were complications such as bleeding (13.7% vs 2.1%, P < 0.001). For TKR surgery, risk-adjusted total healthcare cost, including beneficiary cost share in 1 year, was significantly different for VTE versus no VTE ($17,996 vs $4358, P < 0.001). LIMITATIONS: Study limitations include a reliance on ICD-9-CM codes, which could be inaccurate, and the inability (1) to control for unmeasured confounders, such as surgeons' skills; (2) to include outpatient medical care costs; and (3) to ensure that all patients were enrolled continuously throughout the study period. CONCLUSIONS: VTE after THR or TKR is associated with higher mortality, rehospitalization, and bleeding within 1 year, compared with no VTE. Risk-adjusted total, Medicare, and beneficiary healthcare costs were significantly higher for both THR and TKR patients with VTE (P < 0.001).

Anticoagulation Bridging Therapy Patterns in Patients Undergoing Total Hip or Total Knee Replacement in a US Health Plan: Real-World Observations and Implications.

BACKGROUND: The necessity for anticoagulant bridging therapy after joint replacement surgery is widely understood, but treatment administration patterns in the prevention of venous thromboembolism (VTE) after total hip replacement (THR) or total knee replacement (TKR) surgery during the hospital stay have yet to be examined. OBJECTIVE: To investigate anticoagulation thromboprophylaxis patterns, especially the use of anticoagulant bridging therapy and/or nonbridged treatment strategies, in patients undergoing THR/TKR surgery. METHODS: This retrospective study was based on a large hospital database linked with outpatient claims from 2005 through 2007. The study population included 1770 patients who were admitted for either THR or TKR surgery and were aged ≥18 years on the date of the surgery, defined as the index date. Patients were required to have commercial insurance or Medicare coverage and be continuously enrolled in their health plan for at least 180 days before and 90 days after the index date. The data were analyzed retrospectively for risk-adjusted postsurgery VTE and major bleeding events among patients receiving anticoagulation thromboprophylaxis. Patterns of anticoagulant bridging therapy use were also assessed. A risk adjustment was performed using propensity score matching. RESULTS: Of 1770 eligible patients, 1551 (88%) received anticoagulant VTE prophylaxis; 264 (15%) received combination low-molecular-weight heparin and warfarin. Of these, 105 (40%) patients were switched between the 2 monotherapies, and 159 (60%) received bridged (overlapping) prophylaxis. The overall rates of VTE and bleeding events were significantly lower with bridged therapy than with nonbridged therapy (5.8% vs 18.4%, respectively, for VTE, P <.02; 2.3% vs 4.60% for major bleeding, P = .41; 1.15% vs 8.05% for minor bleeding, P <.03). CONCLUSION: Although existing guidelines recommend anticoagulant bridging therapy after THR or TKR surgery, the limited data regarding anticoagulant bridging practice patterns suggest that patients who undergo such surgery do not receive adequate anticoagulant thromboprophylaxis immediately after discharge. Our findings suggest that increased use of bridging therapy after THR or TKR surgery may help improve postsurgery patient outcomes by reducing VTE and bleeding rates.

Impact of postoperative venous thromboembolism on Medicare recipients undergoing total hip replacement or total knee replacement surgery.

PURPOSE: The impact of postoperative venous thromboembolism (VTE) during initial hospitalization for total hip replacement (THR) or total knee replacement (TKR) surgery was assessed. METHODS: Using Medicare Provider Analysis and Review files, patients who underwent THR, TKR, or hip fracture surgery from 2005 to 2007 were identified using appropriate procedure codes from the International Classification of Diseases, 9th Revision, Clinical Modification. Medicare managed care patients were excluded from the study. Eligible patients were classified as having had deep venous thrombosis (DVT), pulmonary embolism (PE), DVT and PE, or no VTE during their initial hospitalization. Risk adjustment was performed using propensity score matching. Medicare cost, cost to beneficiaries, and cost to primary payers were analyzed to determine risk-adjusted differences in outcome measures, including mortality, rehospitalization, bleeding, length of stay, and total health care expenditures related to VTE events. RESULTS: A total of 170,047 patients were identified. Postoperative VTE events occurred in 3,014 patients (1.77%) during their initial hospitalization. Risk-adjusted mortality rates were three to four times higher for patients with VTE compared with those without VTE. Patients with VTE were more likely to be rehospitalized and experience bleeding within 30 days. Risk-adjusted differences in annual mean cost, including Medicare cost and costs to beneficiaries and primary payers, were significantly greater for patients with VTE. CONCLUSION: Patients who developed VTE after THR or TKR had a higher likelihood of mortality, bleeding, and rehospitalization; were hospitalized longer; and incurred higher costs to Medicare, Medicare beneficiaries, and private payers compared with patients without VTE.

Analysis of venous thromboprophylaxis duration and outcomes in orthopedic patients.

BACKGROUND: Venous thromboembolism (VTE) following total hip replacement (THR) and total knee replacement (TKR) surgery imposes significant health and economic burden. OBJECTIVE: To examine the impact of thromboprophylaxis duration on deep vein thrombosis (DVT), pulmonary embolism (PE), total VTE (DVT and PE), and bleeding events among THR/TKR patients. METHODS: A retrospective study (April 1, 2004, to December 31, 2006) was conducted using a US health plan claims database linked to an inpatient database containing medication use. Outcomes were compared using χ2 tests; predictors of outcomes were analyzed using multivariate logistic regression. RESULTS: Of 3497 patients, 3195 (91%) received thromboprophylaxis for =1 day postsurgery. Most patients (67%) received short-duration (1-14 days) rather than extended-duration (>14 days) thromboprophylaxis. The incidence of thromboembolic and bleeding events was higher in those who received short-duration thromboprophylaxis: DVT (2.84% vs 1.24%; P = .0038), PE (1.12% vs 0.19%; P = .0052), total VTE (3.96% vs 1.43%; P <.0001), and major bleeding (1.68% vs 0.38%; P = .0011). Multivariate logistic regressions (adjusted for observed demographic and clinical characteristics) revealed similar results. Baseline comorbidity score was significantly associated with major bleeding; most of the bleeding events in those who received short-duration thromboprophylaxis occurred within the first 14 days. CONCLUSIONS: In this database analysis of patients who had undergone THR/TKR surgery, a large proportion of patients did not receive the minimum duration of thromboprophylaxis recommended by the guidelines. Extended-duration thromboprophylaxis was associated with a significantly lower risk of DVT, PE, and VTE compared with short-duration thromboprophylaxis.

Validation of the Functional Assessment of Chronic Illness Therapy Fatigue Scale relative to other instrumentation in patients with rheumatoid arthritis.

OBJECTIVE: This study validated a brief measure of fatigue in rheumatoid arthritis (RA), the Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale. METHODS: The FACIT Fatigue was tested along with measures previously validated in RA: the Multidimensional Assessment of Fatigue (MAF) and Medical Outcomes Study Short-Form 36 (SF-36) Vitality. The sample included 636 patients with RA enrolled in a 24 week double blind, randomized clinical trial (RCT) of adalimumab versus placebo. RESULTS: The FACIT Fatigue showed good internal consistency (alpha = 0.86 to 0.87), strong association with SF-36 Vitality (r = 0.73 to 0.84) and MAF (r = -0.84 to -0.88), and the ability to differentiate patients according to clinical change using the American College of Rheumatology (ACR) response criteria (ACR 20/50/70). Psychometric performance of the FACIT Fatigue scale was comparable to that of the other 2 fatigue measures. A minimally important difference in FACIT Fatigue change score of 3-4 points was confirmed in a separate sample of 271 patients with RA enrolled in a second double blind RCT of adalimumab versus placebo. CONCLUSION: The FACIT Fatigue is a brief, valid measure for monitoring this important symptom and its effects on patients with RA.

Comparison of measured utility scores and imputed scores from the SF-36 in patients with rheumatoid arthritis.

PURPOSE: We sought to evaluate 3 methods for imputing utility-based outcomes from clinical trial data measured using the Medical Outcomes Study 36-Item Short Form (SF-36). SUBJECTS: Our subjects included 131 male and 505 female adults (mean age, 55.42 +/- 12.59 years) who were participating in a randomized clinical trial evaluating a new treatment of adults with rheumatoid arthritis (RA). MEASURES: Participants completed the SF-36, 2 versions of the Health Utilities Index (HUI-2 and HUI-3), the EuroQol EQ-5D, and the Health Assessment Questionnaire (HAQ). SF-36 scores were transformed to utility-based scores using 4 methods developed independently by Fryback, Nichol, and Brazier. RESULTS: All 4 imputed scores were significantly correlated with HUI-2, HUI-3, EQ-5D, and the disease-specific HAQ scores at baseline and at the end of the clinical trial period (P < 0.05). Changes in the imputed scores from baseline to end of study also were significantly correlated with corresponding changes in the measured utility scores and the HAQ score (P < 0.0001). For all imputed and measured scores, changes from baseline were associated with the clinical assessments, ACR20 and ACR50. The associations were stronger for the utility-based measures than the imputed indices. Both imputed and measured scores were sensitive to change in the clinical trial. However, mean scores for the HUI-3 and the Brazier VAS were significantly lower than for the other measures. CONCLUSION: Imputed utility-based score estimates are significantly correlated with measured utility outcomes. However, the imputed measures had more constrained variability, showed poorer correspondence to the ACR20 and ACR50 benchmarks, and predicted less than half of the variance in actual utility-based outcomes. Therefore, directly assessed, not imputed, utility-based measures should continue to be favored for cost-effectiveness analysis.

Mapping the SF-12 to the HUI3 and VAS in a managed care population.

BACKGROUND: Transforming generic health-related quality of life (HRQOL) instruments to a summary utility index is useful for deriving quality-adjusted life years (QALY) in any cost/QALY analysis. OBJECTIVE: The purpose of this study was to investigate the role of the SF-12 in predicting utility scores derived from Health Utility Index (HUI3) and Visual Analog Scale (VAS). METHOD: Data were obtained from a survey of 6923 managed care patients in the United States, aged 18 to 93 years, selected by strata of medication usage (at least 1 medication in target year, 5 or more medications, target medications, and both). The SF-12 was used to assess self-reported HRQOL. Utility was measured by the HUI3 and a VAS. The SF-12 items were used to predict HUI3 and VAS scores using ordinary least square regressions, with sociodemographic covariates. A second model entered each SF-12 item as categorized responses. A third model used the Physical Composite and Mental Composite scores to predict HUI3 and VAS scores. RESULTS: The SF-12 items and sociodemographic covariates accounted for 35% to 55% of the variations in HUI3 and VAS scores, respectively. Age and most SF-12 items were significantly (P < 0.0001) associated with both utility scores in all 3 models. CONCLUSIONS: This research provides support that an algorithm can be derived from the SF-12 to estimate utility scores based on the HUI3 and VAS for studies in populations where utility has not or cannot be measured directly.

The cost-effectiveness of irbesartan in the treatment of hypertensive patients with type 2 diabetic nephropathy.

BACKGROUND: End-stage renal disease (ESRD)-related health care costs are substantial. Improving clinical outcomes in patients at risk of progression to ESRD could lead to considerable health care savings. OBJECTIVE: We estimated the cost-effectiveness of irbesartan compared with placebo or amlodipine in the treatment of patients with type 2 diabetes mellitus, hypertension, and overt nephropathy. METHODS: Three treatments for hypertension patients with type 2 diabetes mellitus and nephropathy were assessed: (1) irbesartan, (2) amlodipine, and (3) placebo. A Markov model was developed based on primary data from the Irbesartan in Diabetic Nephropathy Trial and the United States Renal Data System. Projected survival and costs were compared for each treatment at 3-, 10-, and 25-year time horizons. Different assumptions of treatment benefits and costs were tested with use of sensitivity analyses. RESULTS: At 10 and 25 years, the model projected irbesartan to be both the least costly and most effective (ie, demonstrating a survival advantage) strategy. At 25

Development of a new instrument for rheumatoid arthritis: the Cedars-Sinai Health-Related Quality of Life instrument (CSHQ-RA).

OBJECTIVE: To update and complement existing instruments, we developed a multidimensional disease-specific instrument, intended to reflect the impact of rheumatoid arthritis (RA) with modern treatment options on patient's Health-Related Quality of Life (HRQOL). METHODS: Items were developed from a systematic review of published HRQOL measures and transcripts of RA patient focus groups. Items were refined by an expert panel and administered to 350 patients for psychometric testing. RESULTS: The systematic review identified 228 potential items, and the focus group transcripts identified 96 additional items. Expert review and pilot testing resulted in an initial 58-item instrument. Twenty-six items were excluded due to floor/ceiling effects, poor response rates, or high item-item correlations. Factor analysis identified a 5-factor structure (eigenvalues >or=1). Multi-trait scaling performed on both completed surveys confirmed the 5 sub-scale structure (Cronbach's > 0.87). CONCLUSION: The CSHQ-RA consists of 33 items that address 5 HRQOL domains, each with high internal consistency. Additional testing will assess the instrument's validity and responsiveness.