Estimating and Extrapolating Survival Using a State-Transition Modeling Approach: A Practical Application in Multiple Myeloma.

OBJECTIVES: State-transition models (STMs) applied in oncology have given limited considerations to modeling postprogression survival data. This study presents an application of an STM focusing on methods to evaluate the postprogression transition and its impact on survival predictions. METHODS: Data from the lenalidomide plus dexamethasone arm of the ASPIRE trial was used to estimate transition rates for an STM. The model accounted for the competing risk between the progression and preprogression death events and included an explicit structural link between the time to progression and subsequent death. The modeled transition rates were used to simulate individual disease trajectories in a discrete event simulation framework, based on which progression-free survival and overall survival over a 30-year time horizon were estimated. Survival predictions were compared with the observed trial data, matched external data, and estimates obtained from a more conventional partitioned survival analysis approach. RESULTS: The rates of progression and preprogression death were modeled using piecewise exponential functions. The rate of postprogression mortality was modeled using an exponential function accounting for the nonlinear effect of the time to progression. The STM provided survival estimates that closely fitted the trial data and gave more plausible long-term survival predictions than the best-fitting Weibull model applied in a partitioned survival analysis. CONCLUSIONS: The fit of the STM suggested that the modeled transition rates accurately captured the underlying disease process over the modeled time horizon. The considerations of this study may apply to other settings and facilitate a wider use of STMs in oncology.

Burden of Treatment-Induced Peripheral Neuropathy in Patients with Multiple Myeloma in Sweden.

INTRODUCTION: Treatment-induced peripheral neuropathy (TIPN) is a complication of multiple myeloma (MM) treatment. OBJECTIVE: This real-world, retrospective study used electronic medical record (EMR) data from 3 Swedish clinics to assess the occurrence and economic burden of TIPN in patients with MM. METHODS: Eligible patients had an MM diagnosis in the Swedish Cancer Registry between 2006 and 2015 and initiated treatment during that period. Follow-up was until last EMR visit, death, or study end (April 2017). The current analyses included patients receiving bortezomib, lenalidomide, carfilzomib, or thalidomide at any treatment line. To discern healthcare resource utilization (HCRU) and costs associated with TIPN from other causes, patients with TIPN were matched with those without on baseline characteristics, treatment, and line of therapy. All analyses were descriptive. RESULTS: Overall, 457 patients were included; 102 (22%) experienced TIPN. Patients experiencing TIPN during first-line treatment mostly received bortezomib-based regimens (n = 48/57 [84%]); those with TIPN during second- and third/fourth-line treatment mostly received lenalidomide/thalidomide-based regimens (19/31 [61%], 8/14 [57%], respectively). Patients with TIPN had higher HCRU/costs than those without TIPN (mean differences in hospital outpatient visits: 5.2, p = 0.0031; total costs per patient-year: EUR 17,183, p = 0.0007). CONCLUSIONS: Effective MM treatments associated with a reduced incidence of TIPN could result in decreased healthcare expenditure.

Drug survival of second biological DMARD therapy in patients with rheumatoid arthritis: a retrospective non-interventional cohort analysis.

BACKGROUND: Since persistence to first biological disease modifying anti-rheumatic drugs (bDMARDs) is far from ideal in rheumatoid arthritis (RA) patients, many do receive a second and/or third bDMARD treatment. However, little is known about treatment persistence of the second-line bDMARD and it is specifically unknown whether the mode of action of such a treatment is associated with different persistence rates. We aimed to assess discontinuation-, re-initiation- or continuation-rates of a 2nd bDMARD therapy as well as switching-rates to a third biological DMARD (3rd bDMARD) therapy in RA patients. METHOD: Analysis was based on German claims data (2010-2013). Patients were included if they had received at least one prescription for an anti-TNF and at least one follow-up prescription of a 2nd bDMARD different from the first anti-TNF. Patient follow-up started on the date of the first prescription for the 2nd bDMARD and lasted for 12 months or until a patient's death. RESULTS: 2667 RA patients received at least one anti-TNF prescription. Of these, 451 patients received a second bDMARD (340 anti-TNF, mean age 52.6 years; 111 non-anti-TNF, mean age 55.9 years). During the follow-up, 28.8% vs. 11.7% of the 2nd anti-TNF vs. non-anti-TNF patients (p < 0.001) switched to a 3rd bDMARD; 14.1% vs. 19.8% (p = 0.179) discontinued without re-start; 3.8% vs.1.8% (p = 0.387) re-started and 53.5 vs. 66.7% (p < 0.050) continued therapy. Patients in the non-anti-TNF group demonstrated longer drug survival (295 days) than patients in the anti-TNF group (264 days; p = 0.016). Independent variables associated with earlier discontinuation (including re-start) or switch were prescription of an anti-TNF as 2nd bDMARD (HR = 1.512) and a higher comorbidity level (CCI, HR = 1.112), whereas previous painkiller medication (HR = 0.629) was associated with later discontinuation or switch. CONCLUSIONS: Only 56.8% of RA patients continued 2nd bDMARD treatment after 12 months; 60% if re-start was included. Non-anti-TNF patients had a higher probability of continuing 2nd bDMARD therapy.

Which factors enhance positive drug reimbursement recommendation in Scotland? A retrospective analysis 2006-2013.

OBJECTIVES: To identify the factors that influence the Scottish Medicines Consortium (SMC) in deciding whether to accept pharmaceutical technologies for use within the Scottish health care system. METHODS: A database of SMC submissions between 2006 and 2013 was created, containing a range of clinical, economic, and other factors extracted from published health technology assessment reports. A binomial outcome variable was used, defined as the decision to "accept for use" or "not recommend" a technology. Univariate and multivariate analyses were conducted to assess the impact by means of odds ratios (ORs) of the submitted evidence on the recommendation decision. RESULTS: Out of 463 applications, 265 were accepted for use (57%) and 198 (43%) were not recommended for use within National Health Service Scotland. Univariate analyses showed that 13 variables significantly affected the SMC decision. Of these 13 variables, 7 variables were shown to have a meaningful impact in the multivariate analysis. Four of these concerned the outcome of cost-effectiveness analyses; the fact that a submission was supported by a cost-minimization analysis was the strongest positive variable (OR = 10.30) and a submission showing a product not being cost-effective (i.e., incremental cost-effectiveness ratio above £30,000/quality-adjusted life-year gained) was the strongest negative predictor (OR = 0.47). The other variables concerned whether the submission was related to a product indicated for a nervous system disease (OR = 0.41), whether it was indicated for nonchronic use (OR = 1.66), and whether the submission was performed by a big company (OR = 2.83). CONCLUSIONS: This study demonstrated that the outcome of cost-effectiveness analyses is an important factor affecting the SMC's reimbursement recommendation decision.

A European chart review study on early rheumatoid arthritis treatment patterns, clinical outcomes, and healthcare utilization.

This retrospective medical chart review aimed to provide a current, real-world overview of biologic usage in patients with rheumatoid arthritis (RA) in Germany, Spain, and the UK, and estimate clinical and healthcare utilization outcomes associated with early versus late treatment. Adults (≥18 years) with a confirmed RA diagnosis between January 2008 and December 2010, who received biologic treatment for ≥3 months and had ≥12 months of follow-up were included. Early treatment was receipt of biologic agent ≤1 year after RA diagnosis. Outcomes included 28-joint disease activity score (DAS28) reduction of ≥1.2 from biologic start and remission (DAS28 < 2.6). Time to outcome was evaluated using Kaplan-Meier curves and log-rank tests. Of 328 patients enrolled (Germany [n = 111], Spain [n = 106], UK [n = 111]), 58.2 % received early biologic (Germany: 55.0 %, UK: 55.9 %, Spain: 64.2 %; p = 0.321). First-line biologics were more frequent in Spain (26.4 %) and Germany (19.8 %) versus the UK (7.2 %; p < 0.001). Late-treated patients were hospitalized more often than early-treated patients (10.5 vs 2.9 % [p = 0.006] for 9.0 vs 5.4 mean inpatient days [p = 0.408]). DAS28 was 5.1 at biologic initiation (n = 310); 73.5 % of patients had a DAS28 decrease of ≥1.2 and 44.5 % achieved remission. More patients had DAS28 decrease of ≥1.2 (79.2 vs 65.9 %; p = 0.009) and remission (51.1 vs 35.6 %; p = 0.007) with early versus late treatment, with a significant difference in Kaplan-Meier curves when indexing on time since diagnosis (p < 0.001) and biologic start (p = 0.024). In RA patients receiving biologic therapy, over half received biologic therapy early. Early initiation was associated with improved clinical outcomes and reduced hospitalization rates versus late treatment.

Carfilzomib, daratumumab, and dexamethasone (KdD) vs. lenalidomide-sparing pomalidomide-containing triplet regimens for relapsed/refractory multiple myeloma: an indirect treatment comparison.

Nearly all patients with multiple myeloma eventually relapse or become refractory to treatment. Lenalidomide is increasingly administered in the frontline until disease progression or intolerance to therapy, resulting in the need for highly effective, lenalidomide-sparing options. In this study, carfilzomib plus daratumumab and dexamethasone were evaluated against lenalidomide-sparing, pomalidomide-containing triplets using matching-adjusted indirect comparison in the absence of head-to-head data. The analyses utilized long-term follow-up data from the CANDOR study (NCT03158688). Treatment with carfilzomib, daratumumab, and dexamethasone resulted in significantly longer progression-free survival (hazard ratio 0.60 [95% confidence interval: 0.37, 0.88])vs. pomalidomide plus bortezomib and dexamethasone, and numerically longer progression-free survival (hazard ratio 0.77 [95% confidence interval: 0.50, 1.08]) vs. daratumumab plus pomalidomide and dexamethasone in patients with relapsed/refractory multiple myeloma and previous lenalidomide exposure, the majority of whom were lenalidomide refractory. Carfilzomib plus daratumumab and dexamethasone offers a highly effective, lenalidomide-sparing treatment option for this population.

Characteristics and Outcomes of Patients With Relapsed/Refractory Multiple Myeloma After Exposure to Lenalidomide in First Line of Therapy: A Single Center Database Review in Greece.

BACKGROUND: The increasing use of lenalidomide (Len) in first-line (1L) therapy of multiple myeloma (MM) has led to a significant proportion of patients becoming Len-refractory following 1L treatment. However, there are limited real-world data on treatment strategies and outcomes of patients who become Len-refractory following 1L therapy. PATIENTS AND METHODS: This real-world retrospective cohort study analyzed Len-refractory and non-Len-refractory patients who received 1L Len and initiated second-line (2L) therapy at a Greek MM center. The Len-exposed cohort (n = 249) included 55.4% Len-refractory patients after 1L. RESULTS: Compared to non-Len-refractory patients, Len-refractory patients more frequently had high-risk cytogenetics and Revised-International Staging System-3 disease stage at diagnosis, and had shorter progression-free survival (PFS) following 1L therapy. Len-refractory versus non-Len-refractory patients more frequently received triplets (59% vs. 40%), anti-CD38 agents (20% vs. 9%) and pomalidomide (22% vs. 13%). The overall response rate was 53% for Len-refractory patients and 64% for non-Len-refractory patients in 2L therapy; median PFS was 10.7 vs. 18.3 months, respectively. Median overall survival (OS) was shorter for Len-refractory patients vs non-Len-refractory patients (23.8 vs. 53.6 months). Len refractoriness was an independent prognostic factor for both PFS and OS in Len-exposed patients. CONCLUSION: In this real-world Len-exposed cohort, Len-refractory patients receiving 1L Len experienced poorer survival outcomes than non-Len-refractory patients, highlighting the unmet need in this patient population which has driven the development of novel therapies.

Time trends and forecasts of body mass index from repeated cross-sectional data: a different approach.

In this paper, we report a case study on a technical generalization of the Lee-Carter model, originally developed to project mortality, to forecast body mass index (BMI, kg/m2). We present the method on an annually repeated cross-sectional data set, the Dutch Health Survey, covering years between 1981 and 2008. We applied generalized additive models for location, scale and shape semi-parametric regression models to estimate the probability distribution of BMI for each combination of age, gender and year assuming that BMI follows a Box-Cox power exponential distribution. We modelled and extrapolated the distribution parameters as a function of age and calendar time using the Lee-Carter model. The projected parameters defined future BMI distributions from which we derived the prevalence of normal weight, overweight and obesity. Our analysis showed that important changes occurred not only in the location and scale of the BMI distribution but also in the shape of it. The BMI distribution became flatter and more shifted to the right. Assuming that past trends in the distribution of BMI will continue in the future, we predicted a stable or slow increase in the prevalence of overweight until 2020 among men and women. We conclude that our adaptation of the Lee-Carter model provides an insightful and flexible way of forecasting BMI and that ignoring changes in the shape of the BMI distribution would likely result in biased forecasts.

Cost-Effectiveness of Blinatumomab in Pediatric Patients with High-Risk First-Relapse B-Cell Precursor Acute Lymphoblastic Leukemia in France.

BACKGROUND: Based on the results of the phase III randomized 20120215 trial, the European Medicines Agency granted the approval of blinatumomab for the treatment of pediatric patients with high-risk first-relapsed Philadelphia chromosome-negative B-cell precursor acute lymphoblastic leukemia (ALL). In France, blinatumomab received reimbursement for this indication in May 2022. This analysis assessed the cost effectiveness of blinatumomab compared with high-risk consolidation chemotherapy (HC3) in this indication from a French healthcare and societal perspective. METHODS: A partitioned survival model with three health states (event-free, post-event and death) was developed to estimate life-years (LYs), quality-adjusted life-years (QALYs) and costs over a lifetime horizon. Patients who were alive after 5 years were considered to be cured. An excess mortality rate was applied to capture the late effects of cancer therapy. Utility values were based on the TOWER trial using French tariffs, and cost input data were identified from French national public health sources. The model was validated by clinical experts. RESULTS: Treatment with blinatumomab over HC3 was estimated to provide gains of 8.39 LYs and 7.16 QALYs. Total healthcare costs for blinatumomab and HC3 were estimated to be €154,326 and €102,028, respectively, resulting in an increment of €52,298. The incremental cost-effectiveness ratio was estimated to be €7308 per QALY gained from a healthcare perspective. Results were robust to sensitivity analyses, including analysis from the societal perspective. CONCLUSIONS: Blinatumomab administered as part of consolidation therapy in pediatric patients with high-risk first-relapsed ALL is cost effective compared with HC3 from the French healthcare and societal perspective.

Forecasting lifetime and aggregate long-term care spending: accounting for changing disability patterns.

OBJECTIVE: The impact population aging exerts on future levels of long-term care (LTC) spending is an urgent topic in which few studies have accounted for disability trends. We forecast individual lifetime and population aggregate annual LTC spending for the Dutch 55+ population to 2030 accounting for changing disability patterns. METHODS: Three levels of (dis)ability were distinguished: none, mild, and severe. Two-part models were used to estimate LTC spending as a function of age, sex, and disability status. A multistate life table model was used to forecast age-specific prevalence of disability and life expectancy (LE) in each disability state. Finally, 2-part model estimates and multistate projections were combined to obtain forecasts of LTC expenditures. RESULTS: LE is expected to increase, whereas life years in severe disability remain constant, resulting in a relative compression of severe disability. Mild disability life years increase, especially for women. Lifetime homecare spending--mainly determined by mild disability--increases, whereas institutional spending remains fairly constant due to stable LE with severe disability. Lifetime LTC expenditures, largely determined by institutional spending, are thus hardly influenced by increasing LE. Aggregate spending for the 55+ population is expected to rise by 56.0% in the period of 2007-2030. CONCLUSIONS: Longevity gains accompanied by a compression of severe disability will not seriously increase lifetime spending. The growth of the elderly cohort, however, will considerably increase aggregate spending. Stimulating a compression of disability is among the main solutions to alleviate the consequences of longevity gains and population aging to growth of LTC spending.

Mortality risk associated with disability: a population-based record linkage study.

OBJECTIVES: We assessed the association between mortality and disability and quantified the effect of disability-associated risk factors. METHODS: We linked data from cross-sectional health surveys in the Netherlands to the population registry to create a large data set comprising baseline covariates and an indicator of death. We used Cox regression models to estimate the hazard ratio of disability on mortality. RESULTS: Among men, the unadjusted hazard ratio for activities of daily living, mobility, or mild disability defined by the Organization for Economic Co-operation and Development at age 55 years was 7.85 (95% confidence interval [CI] = 4.36, 14.13), 5.21 (95% CI = 3.19, 8.51), and 1.87 (95% CI = 1.58, 2.22), respectively. People with disability in activities of daily living and mobility had a 10-year shorter life expectancy than nondisabled people had, of which 6 years could be explained by differences in lifestyle, sociodemographics, and major chronic diseases. CONCLUSIONS: Disabled people face a higher mortality risk than nondisabled people do. Although the difference can be explained by diseases and other risk factors for those with mild disability, we cannot rule out that more severe disabilities have an independent effect on mortality.

The value of survival gains from therapeutic innovations for US patients with relapsed/refractory multiple myeloma.

AIMS: This study quantifies the value of survival gains attributable to novel treatments approved since 2003 for United States (US) patients with relapsed/refractory multiple myeloma (RRMM). METHODS: We estimated the increase in survival attributable to lenalidomide and bortezomib for multiple myeloma (MM) patients in the 1983-2013 Surveillance, Epidemiology, and End Results (SEER) registry. To estimate the survival benefit of treatments approved since 2015 (carfilzomib, elotuzomab, daratumumab, used in combination with lenalidomide and dexamethasone) we used clinical trial data to calibrate survival estimated using the SEER data. We then conducted an economic valuation of the estimated shift in survival curves for all therapies. Finally, we estimated the share of the value accruing to patients and manufacturers using treatment costs estimated from MarketScan data. RESULTS: The introduction of bortezomib in combination with dexamethasone (Vd) and lenalidomide in combination with dexamethasone (Rd) resulted in substantial survival gains and societal value for multiple myeloma patients, generating 1.7 additional life-years per RRMM patient. More recently, approved novel treatments have improved survival over effective treatments (i.e. Rd/Vd) by an additional 2.5 life-years - the monetary value of this incremental survival benefit far exceeds the incremental cost of treatment. At the patient level, the incremental benefit of Rd/Vd is $335,500 and with novel treatments is $565,000. Applying this benefit to all future cohorts of US RRMM patients translates into a value of at least $75 billion and $130 billion with Rd/Vd and the novel treatments, respectively. CONCLUSIONS: SEER registry data were only available through 2013. Therefore, survival gains for recently approved treatments were estimated based on clinical trials, rather than observed survival. Our valuation analysis does not capture sources of value aside from survival gains, for example, better quality of life, increased productivity, or the value of surviving until subsequent novel therapies become available. Substantial extensions in life expectancy in RRMM since 2003 translate into real economic value gained by society.

Cost-effectiveness of once weekly carfilzomib 70 mg/m2 plus dexamethasone in patients with relapsed and refractory multiple myeloma in the United States.

BACKGROUND: In the US, carfilzomib 70 mg/m2 once-weekly plus dexamethasone (Kd70 QW) was recently indicated for relapsed and/or refractory multiple myeloma. In current US clinical practice, most patients treated with Kd receive carfilzomib at a previously approved dose of 27 mg/m2 twice-weekly (Kd27 BIW). This analysis assessed the cost-effectiveness (CE) of Kd70 QW vs Kd27 BIW regimens which were compared in the randomized phase 3 ARROW trial. METHODS: Based on clinical outcomes (overall survival and utilities) from ARROW, a partitioned survival model was developed to estimate life years (LYs) and quality-adjusted life years (QALYs). Long-term survival was extrapolated using SEER registry data matched to ARROW patients. Costs were estimated using a US healthcare payer perspective. RESULTS: The analysis estimated that treatment with Kd70 QW vs Kd27 BIW resulted in an increase of 1.10 LYs, 0.91 QALYs, and additional lifetime costs of $74,858, yielding an incremental CE ratio (ratio of incremental costs to QALYs) of $82,257 per QALY gained. Results were robust to sensitivity and subgroup analyses. CONCLUSIONS: When compared with Kd27 BIW, Kd70 QW is the optimal dose that represents a cost-effective utilization of health care budget with incremental CE ratios well below the accepted willingness-to-pay thresholds in the US.

Carfilzomib and dexamethasone versus eight cycles of bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma: an indirect comparison using data from the phase 3 ENDEAVOR and CASTOR trials.

In ENDEAVOR, carfilzomib and dexamethasone (Kd56) demonstrated significant improvement in progression-free survival (PFS) compared with bortezomib and dexamethasone (Vd). Both agents were administered until disease progression; the EU label for Vd, however, stipulates a maximum of eight treatment cycles. Here, matching-adjusted treatment comparison was used to compare efficacy of Kd56 with Vd, if Vd was administered for 8 cycles (Vd-8). Data from ENDEAVOR and CASTOR trials (which compared daratumumab, bortezomib, and dexamethasone with Vd-8) were used. Hazard ratios of PFS were estimated for Vd vs. Vd-8 and Kd vs. Vd-8. For cycles 1-8, risk reduction in PFS for Kd56 vs. Vd-8 was equal to that estimated in ENDEAVOR (HR: 0.53; 95% CI 0.44-0.65). Beyond eight cycles, risk reduction in PFS for Kd56 and Vd-8 was estimated to be 60% (HR: 0.40; 95% CI 0.26-0.63). The analysis suggested that PFS benefit of Kd56 over Vd increases when Vd is given for eight cycles only.

Letter--Value-Driven Treatment Decisions: Need of the Hour for Relapsed/Refractory Multiple Myeloma.

DISCLOSURES: No funding was involved in the writing of this letter. Medhekar, Sapra, Majer, Harrison, and Tekle are employees of and stockholders in Amgen.

Modeling Covariate-Adjusted Survival for Economic Evaluations in Oncology.

BACKGROUND AND OBJECTIVES: In economic evaluations in oncology, adjusted survival should be generated if imbalances in prognostic/predictive factors across treatment arms are present. To date, no formal guidance has been developed regarding how such adjustments should be made. We compared various covariate-adjusted survival modeling approaches, as applied to the ENDEAVOR trial in multiple myeloma that assessed carfilzomib plus dexamethasone (Cd) versus bortezomib plus dexamethasone (Vd). METHODS: Overall survival (OS) data and baseline characteristics were used for a subgroup (bortezomib-naïve/one prior therapy). Four adjusted survival modeling approaches were compared: propensity score weighting followed by fitting a Weibull model to the two arms of the balanced data (weighted data approach); fitting a multiple Weibull regression model including prognostic/predictive covariates to the two arms to predict survival using the mean value of each covariate and using the average of patient-specific survival predictions; and applying an adjusted hazard ratio (HR) derived from a Cox proportional hazard model to the baseline risk estimated for Vd. RESULTS: The mean OS estimated by the weighted data approach was 6.85 years (95% confidence interval [CI] 4.62-10.70) for Cd, 4.68 years (95% CI 3.46-6.74) for Vd, and 2.17 years (95% CI 0.18-5.06) for the difference. Although other approaches estimated similar differences, using the mean value of covariates appeared to yield skewed survival estimates (mean OS was 7.65 years for Cd and 5.40 years for Vd), using the average of individual predictions had limited external validity (implausible long-term OS predictions with > 10% of the Vd population alive after 30 years), and using the adjusted HR approach overestimated uncertainty (difference in mean OS was 2.03, 95% CI - 0.17 to 6.19). CONCLUSIONS: Adjusted survival modeling based on weighted or matched data approaches provides a flexible and robust method to correct for covariate imbalances in economic evaluations. The conclusions of our study may be generalizable to other settings. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT01568866 (ENDEAVOR trial).

[Impact of disease progression on health status, quality of life and costs in rheumatoid arthritis in Hungary]. / A betegségprogresszió hatása az egészségi állapotra, életminoségre és költségekre rheumatoid arthritisben Magyarországon.

UNLABELLED: Rheumatoid arthritis (RA) is a chronic, progressive polyarthritis leading to substantial disability. Standardised data on consequences of disease progression are needed for clinical assessments and also for cost-effectiveness models. AIM: To analyse the impact of disease progression on health status, disease specific quality of life and costs in Hungary. METHODS: A cross-sectional survey was performed between April and August, 2004, involving consecutive RA patients of 6 hospital based rheumatology outpatient centres. Self-completed questionnaires were used to assess functional (HAQ) and health status (EQ-5D), quality of life (RAQoL). Disease activity (DAS) and costs were also surveyed, statistical analysis was performed. RESULTS: 255 patients were involved [mean age 55.5 +/- 12.3 years; disease duration 9.0 +/- 9.3 years; HAQ 1.38 +/- 0.76; EQ-5D 0.46 +/- 0.33; RAQoL 16.2 +/- 8.1; DAS 5.09 +/- 1.42; costs 1,043,163 (+/- 844,750) HUF/patient/year, conversion 1 Euro = 250 HUF]. Correlation was significant between the parameters ( p < 0.01): EQ-5D index = 1.014 - 0.25 x HAQ-0.041 x DAS; HAQ = 0.314 + 0.065 x RAQoL. Analysis by disease severity levels (HAQ groups 0.5 difference) revealed that health status worsens (mean EQ-5D: 0.784; 0.576; 0.504; 0.367; 0.211; 0.022) and costs increase (mean 628,280; 888,187; 953,759; 1,291,218; 1,346,112; 1,371,674 HUF/patient/year) with disease progression. Minimally important worsening of functional ability (0.25 HAQ increase) corresponds to -0.0705 EQ-5D and +1.884 RAQoL change. Lower health status difference (EQ-5D -0.05725) was calculated in patients with lower disease activity (DAS < 5.1). CONCLUSIONS: Correlation between disease progression, health status, quality of life and costs does not differ significantly from international results. The amount of costs is much lower in all disease severity levels than in developed European countries. Our study serves baseline data for health economic analysis in RA in Hungary.

Reframing the Value of Treatments for Relapsed/Refractory Multiple Myeloma.

DISCLOSURES: Ailawadhi reports research support from Pharmacyclics and consulting relationships with Takeda, Amgen, and Celgene. Jakubowiak reports consulting and advisory board relationships with AbbVie, Amgen, BMS, Celgene, Karyopharm, SkylineDX, and Takeda. Panjabi, Campioni, and Majer are employees of and stockholders in Amgen.

[Health care costs of acute myocardial infarction in Hungary, 2003-2005]. / Az akut myocardialis infarctus betegségterhe Magyarországon, 2003-2005.

BACKGROUND: The morbidity of acute myocardial infarction (AMI) is remarkable in Hungary, therefore understanding the disease burden more accurately is inevitable. AIM: We assessed the hospitalized AMI patient's burden on the financer both in active and chronic hospital care as well as outpatient visits and we estimated the size of indirect social costs. METHODS: We assessed the active and chronic hospital care costs of 'new' AMI patients having the event in May 2003. The costs were assessed in the subsequent 12 and 24 months to the event in the population over 25 with the morbidity from the database of the National Health Insurance Fund Administration (NHIFA). Data were collected by gender and age (age groups 25-44, 45-64, 65 and over). Costs of GPs, specialist visits, transportation and productivity losses were taken into account as other costs. RESULTS: Average health insurance costs of AMI's active hospital care in the first 12 months are generally higher in females as in males; 476.3 thousand HUF vs 391.1 thousand HUF (65 and over), 429.1 thousand HUF vs 389.4 thousand HUF (45-64) and 229.5 thousand HUF vs 240.6 thousand HUF (25-44). The burden in the chronic care is 15-40 thousand HUF per patient in the first year, which is similar to the active care costs in the 13-24th months after the AMI (22-54 thousand HUF). CONCLUSION: NHIFA was estimated to spend 4.4 billion HUF on direct health care on behalf of the nearly 12 thousand annual AMI patients in the first 12 months, 3.6 billion HUF on the active and 370 million on the chronic hospital care. Avoiding one AMI could save 345-565 thousand HUF (depending on gender and age) direct health care cost in the first 12 months. In our estimation the annual indirect costs of AMI exceed 840 million HUF (177 829 HUF/patient) in the working age group.