Population Norms for the EQ-5D-5L, PROPr and SF-6D in Hungary.

OBJECTIVES: This study aimed to develop population norms for three preference-accompanied measures [EQ-5D-5L, Patient-Reported Outcomes Measurement Information System (PROMIS)-preference scoring system (PROPr) and Short-Form Six-Dimension (SF-6D)] in Hungary. METHODS: In November 2020, an online cross-sectional survey was conducted among a representative sample of the Hungarian adult general population (n = 1631). Respondents completed the Hungarian versions of the EQ-5D-5L, PROMIS-29+2 version 2.1 and 36-item Short Form Survey version 1 (SF-36v1). The association of utilities with sociodemographic and health-related characteristics of respondents was analysed using multivariate regressions. RESULTS: The proportion of respondents reporting problems ranged from 8 to 44% (self-care to pain/discomfort) on the EQ-5D-5L, 39-94% (physical function to sleep) on PROPr and 38-87% (role limitations to vitality) on the SF-6D. Problems related to physical function, self-care, usual activities/role limitations and pain increased with age, while mental health problems decreased in all three measures. In almost all corresponding domains, respondents indicated the fewest problems on the EQ-5D-5L and the most problems on the SF-6D. The mean EQ-5D-5L, PROPr and SF-6D utilities were 0.900, 0.535 and 0.755, respectively. Female gender (PROPr, SF-6D), a lower level of education (EQ-5D-5L, PROPr), being unemployed or a disability pensioner (EQ-5D-5L), being underweight or obese (SF-6D), lack of physical exercise (all) and polypharmacy (all) were associated with significantly lower utilities. PROPr yielded the lowest and EQ-5D-5L the highest mean utilities in 28 of 30 chronic health conditions. CONCLUSIONS: This study presents the first set of Hungarian population norms for the EQ-5D-5L, PROPr and SF-6D. Our findings can serve as reference values in clinical trials and observational studies and contribute to the monitoring of population health and the assessment of disease burden in Hungary.

Hungarian population norms for the 15D generic preference-accompanied health status measure.

OBJECTIVES: 15D is a generic preference-accompanied health status measure covering a wide range of health areas, including sensory functions. The aim of this study was to establish population norms for the 15D instrument in Hungary. METHODS: 2000 members of the Hungarian adult general population participated in an online cross-sectional survey in August 2021. The sample was broadly representative in terms of gender, age groups, highest level of education, geographical region, and settlement type. Index values were derived using the Norwegian 15D value set. In addition to providing population norms, mean index values were computed for 32 physical and 24 mental health condition groups. RESULTS: Most respondents (78.7%) reported problems in at least one 15D domain. The most problems were reported with sleeping (50.7%), followed by vitality (49.2%), distress (43.6%), discomfort and symptoms (31.2%), depression (31.1%), sexual activities (29.6%), breathing (28.1%), and vision (27.8%). The mean 15D index value was 0.810. With advancing age categories, the 15D index values showed an inverse U-shaped curve. Generally, mean index values in respondents with mental health conditions were lower [range 0.299 (post-traumatic stress disorder) to 0.757 (smoking addiction)] than those of respondents with physical conditions [range 0.557 (liver cirrhosis) to 0.764 (allergies)]. CONCLUSIONS: This study provided 15D population norms of the Hungarian general population; furthermore, this is the first study to provide population norms for the 15D in any country. The values established in this study can serve as benchmarks for evaluating efficacy outcomes in clinical trials, quantifying disease burden and identifying unmet needs.

Real-World Experience with Cemiplimab Treatment for Advanced Cutaneous Squamous Cell Carcinoma-A Retrospective Single-Center Study.

BACKGROUND: The systemic treatment of advanced cutaneous squamous cell carcinoma (cSCC) has seen significant developments in recent years. The anti-PD1 inhibitor cemiplimab has demonstrated efficacy in clinical trials, but real-world data are still limited. Here, we aimed to evaluate the efficacy and the safety of cemiplimab in a real-world clinical setting. METHODS: A retrospective analysis was carried out for all patients who received at least two doses of cemiplimab at our department between February 2020 and January 2023. Progression-free survival (PFS), overall survival (OS), the objective response rate (ORR), the disease control rate (DCR) and adverse events (AEs) were evaluated. RESULTS: Twenty-five patients were included with a median age of 78 (65-82) years. The median treatment duration was 48 (16-72) weeks. Five (20%) patients were immunocompromised. Sixteen patients (64%) developed AEs, including 36% serious AEs (SAEs) of grade ≥ 3. Six patients (24%) were withdrawn from treatment due to the occurrence of AEs. Among the 25 patients, 52% showed an objective response (3 complete and 10 partial responses), 76% had controlled disease and 24% experienced progression. Among the five immunocompromised patients, the ORR was 60%, while the DCR was 80%. CONCLUSIONS: This retrospective real-world study revealed that locally advanced or metastatic cSCC could be effectively treated with cemiplimab even in elderly, polymorbid and immunocompromised patients.

Anti-PD-1 Monotherapy in Advanced Melanoma-Real-World Data from a 77-Month-Long Retrospective Observational Study.

Real-world evidence plays an important role in the assessment of efficacy and safety of novel therapies. The increasing use of immune checkpoint inhibitors (ICIs) in patients with advanced melanoma has led to notably improved clinical outcomes, while they are also associated with immune-related adverse events (irAEs). The majority of the available data are based on clinical trials, where the investigated subjects often do not adequately represent the general patient population of the everyday practice. Although there is a niche of objective biomarkers for the future treatment response of ICIs, certain studies suggest that irAEs may be predictive. The aim of this study was to carry out a retrospective analysis of treatment data from patients with advanced melanoma, treated with a single anti-PD-1 agent (pembrolizumab or nivolumab) during a 77-month-long period. Treatment efficacy and occurrence of adverse events were analyzed to identify potential predictive markers. Primary and secondary endpoints were the overall survival (OS) and progression-free survival (PFS). In our cohort, we demonstrated that the occurrence of more than one irAE showed a correlation with response to PD-1 ICI therapy and improved the OS and PFS. Our study suggests, that the grade of toxicity of the irAE may affect the survival rate.

Narrow Vagina as a Predictor of Obstructive Voiding Dysfunction after Transobturator Sling Surgery.

BACKGROUND: Voiding dysfunction (VD) is a potential complication after female midurethral sling operations. OBJECTIVES: Our goal was to assess the rate of obstructive VD after -transobturator tension-free tape (TOT) procedures and to find perioperative risk factors (RFs) predicting postoperative voiding problems. METHODS: We have retrospectively evaluated the perioperative data of 397 women who underwent TOT operations. Significant post-void residual (PVR) (>50 mL) was considered as the primary (objective) end point of the study, the voiding difficulty as the secondary (subjective) 1. First univariate analysis and then multivariate logistic regression were performed, with a 5% significance level. RESULTS: Significant PVR was present in 51 (12.8%) women; catheterization was needed in 21 (5.3%) and reoperation in 3 (0.8%) cases. Seventy women (17.6%) experienced postoperative voiding difficulty. Narrow vagina (<2 cm), older age >70 years, and preoperative voiding difficulty were independent RFs for significant PVR (odds ratio: 5.07, 2.14, 5.38, respectively, p < 0.05). Preoperative overactive bladder syndrome and previous pelvic organ prolapse surgery were considered independent RFs for postoperative voiding difficulty. CONCLUSIONS: Older age, narrow vagina, or preoperative voiding difficulty increases the chance for significant postoperative PVR. These patients should be chosen and counseled appropriately.

Anti-Interleukin-17 Therapy of Severe Psoriatic Patients Results in an Improvement of Serum Lipid and Inflammatory Parameters' Levels, but Has No Effect on Body Composition Parameters.

BACKGROUND: Psoriasis is frequently accompanied by metabolic syndrome. Effect of anti-tumor necrosis factor therapies on increases in body weight is well-known. Data on the effects of interleukin-17 inhibitors are limited. Authors determined the effect of anti-interleukin-17 therapies on the body composition and serum lipid and inflammatory parameters among severe psoriatic patients. METHODS: Thirty-five severe psoriatic patients were enrolled. Twenty-two received secukinumab and 13 received ixekizumab as their 2nd-or 3rd-line biological treatment. Before treatment initiation and 6 months later, laboratory examinations measuring metabolic and inflammatory panels and body composition analyses were performed. RESULTS: After 6 months, a significant reduction was observed in psoriasis area severity index (p < 0.001) from 18 to 0, in c-reactive protein (p < 0.001) from 6.6 to 4.00 mg/L, in low-density lipoprotein-cholesterol (p = 0.004) from 3.69 to 3.19 mmol/L, and an improvement in high-density lipoprotein-cholesterol (p = 0.022) from 1.31 to 1.40 mmol/L. Median baseline body mass index was 32.80 kg/m2. The body composition parameters did not show any significant changes. CONCLUSIONS: Anti-interleukin-17 therapy of severe psoriatic patients does not cause significant changes in body composition parameters. Improvements in the lipid and inflammatory parameters might have a beneficial effect on patients' cardiometabolic status. This effect might be detectable in high-risk obese psoriatic patients.

The relationship between IL-6 and thrombocytosis accompanying gastrointestinal tumours.

INTRODUCTION: Several reports have stated that thrombocytosis is associated with worse survival and higher rate of metastasis in solid tumours. A study in ovarian tumours implicated IL-6 produced by tumour cells as a key mechanistic factor. AIM: To evaluate the relevance of this paraneoplastic pathway in gastrointestinal cancer. MATERIAL AND METHODS: After excluding thromboembolic and inflammatory disorders, 161 patients were enrolled who had been operated due to various gastrointestinal cancer at the 1st Department of Surgery at the Semmelweis University between 2015 and 2017. Platelet counts and serum IL-6 levels were determined from preoperative blood samples. Thrombocytosis was defined as the upper limit of normal platelet count, e.g. 400 × 103/µl. RESULTS: A weak but significantly positive correlation was found between elevated platelet counts and serum IL-6 (correlation coefficient: R = 0.214, p = 0.006), which became more pronounced in colon and oesophageal cancer if evaluated in the different tumour types (R = 0.292 and R = 0.419, respectively). However, using a multivariant linear regression model (R 2 = 0.47) corrected with haemoglobin, white blood cell count, and advanced disease stage, the analysis showed no significant correlation between serum IL-6 and platelet counts. CONCLUSIONS: In gastrointestinal cancer our study did not support the paracrine-mediated paraneoplastic pathway described in ovarian tumors. Thrombocytosis showed significant correlation with white blood cells instead of serum IL-6, which implies that the inflammatory process may influence both parameters. Further studies are needed on larger patient cohorts.

Productivity Loss in Patients With Chronic Diseases: A Pooled Economic Analysis of Hungarian Cost-of-Illness Studies.

OBJECTIVES: To assess productivity loss (PL) variations across a set of chronic diseases and analyze significant PL drivers (demographics, health status, healthcare resource use) in Hungary. METHODS: Data from 11 cost-of-illness studies (psoriasis, dementia, systemic sclerosis, multiple sclerosis, benign prostatic hyperplasia, Parkinson's disease, psoriatic arthritis, rheumatoid arthritis, schizophrenia, epilepsy, and diabetes) were pooled, and patient-level data were analyzed. A weighted multiple linear regression analysis was run to identify significant PL indicators. All costs were adjusted to 2018 euro rates and PL was further presented as a proportion of gross domestic product/capita, facilitating results comparability and transferability. RESULTS: The dataset comprised 1888 patients from 11 chronic diseases. The average indirect cost/(gross domestic product/capita) ratio was highest in schizophrenia (72.4%) and rheumatoid arthritis (71.3%) and lowest in benign prostatic hyperplasia (1.6%). Correlation results infer that a higher EuroQol 5-dimension 3-level index score was significantly associated with lower PL. The number of hospital admissions was the main contributor toward increasing PL among resource use indicators. Age and sex showed inconsistent and insignificant correlations with PL. In regression analysis, a better EuroQol 5-dimension 3-level index score and higher education were consistently associated with decreasing PL in all models. CONCLUSIONS: This article will enable health decision makers to understand the importance of adopting a societal perspective for chronic disease reimbursement decisions. The correlation between PL and health status supports that timely started effective treatments may prevent patients from losing their workability.

Antidrug antibody formation during tumor necrosis factor α inhibitor treatment of severe psoriatic patients in the real-life practice.

INTRODUCTION: Antidrug antibody (ADA) production may be the reason behind secondary inefficacy of anti-TNF-α therapy in psoriasis. AIM: To investigate the production of ADA, serum tumor necrosis factor α (TNF-α) and drug levels as predictors of clinical response in real-life circumstances. MATERIAL AND METHODS: Serum drug concentrations (TNFi), the presence of ADAs and serum TNF-α levels were measured in 158 patients by the ELISA method. Clinical response was evaluated by calculating PASI. Their correlation has been statistically analysed. RESULTS: In adalimumab and infliximab treated patients, ADA formation was observed in 18.4% and 33%, respectively, and the serum TNFi concentration was significantly higher in the ADA negative groups. In contrast there was no ADA formation detected among etanercept treated patients. The serum TNFi concentration was significantly lower among non-responders (n = 33). The serum TNF-α level was also measured and the correlation with the concentration of the serum TNFi level was analysed. Having evaluated the results of all patients together, the serum TNFi and TNF-α concentrations showed a significant negative correlation. However, when groups were analysed separately, in case of adalimumab, a significant negative correlation was detected between serum TNFi and TNF-α concentrations. With respect to infliximab, there was no significant correlation, and an inverse correlation was found in the etanercept group. The TNF-α levels and ADA positivity were significantly higher in non-responders. CONCLUSIONS: This study revealed the major role of ADAs against TNFi in case of secondary inefficacy in real-life circumstances. ADA levels show a stronger correlation with PASI failure than serum TNFi or TNF-α levels.

Patient and general population values for luminal and perianal fistulising Crohn's disease health states.

BACKGROUND: In patients with Crohn's disease (CD), luminal disease activity paralleled by perianal fistulas may seriously impair health-related quality of life (HRQoL). Health utility values are not available from patients with CD that reflect the health loss associated with both luminal and perianal CD. OBJECTIVE: To generate utilities for luminal and concomitant perianal fistulising CD health states directly from patients and from members of the general public. METHODS: A cross-sectional survey was undertaken enrolling CD patients and a convenience sample of members of the general population. Respondents were asked to evaluate four common CD heath states [severe luminal disease (sCD), mild luminal disease (mCD), severe luminal disease with active perianal fistulas (sPFCD), and mild luminal disease with active perianal fistulas (mPFCD)] by 10-year time trade-off (TTO). In addition, patients assessed their current HRQoL by the TTO method. RESULTS: Responses of 206 patients (40.8% with perianal fistulas) and 221 members of the general population were analysed. Mean ± SD utilities among patients for sPFCD, sCD, mPFCD and mCD states were 0.69 ± 0.33, 0.73 ± 0.31, 0.80 ± 0.29 and 0.87 ± 0.26. Corresponding values in the general public were: 0.59 ± 0.31, 0.65 ± 0.29, 0.80 ± 0.26 and 0.88 ± 0.25. Patients with active perianal fistulas, previous non-resection surgeries, and higher pain intensity scores valued their current health as worse (p < 0.05). CONCLUSIONS: TTO is a feasible method to assess HRQoL in patients with perianal fistulising disease, often not captured by health status questionnaires. Utilities from this study are intended to support the optimization of treatment-related decision making in patients with luminal disease paralleled by active perianal fistulas.

Cost-of-illness studies in nine Central and Eastern European countries.

BACKGROUND: To date, a multi-country review evaluating the cost-of-illness (COI) studies from the Central and Eastern European (CEE) region has not yet been published. Our main objective was to provide a general description about published COI studies from CEE. METHODS: A systematic search was performed between 1 January 2006 and 1 June 2017 in Medline, EMBASE, The Cochrane Library, CINAHL, and Web of Science to identify all relevant COI studies from nine CEE countries. COI studies reporting costs without any restrictions by age, co-morbidities, or treatment were included. Methodology, publication standards, and cost results were analysed. RESULTS: We identified 58 studies providing 83 country-specific COI results: Austria (n = 9), Bulgaria (n = 16), Croatia (n = 3), the Czech Republic (n = 10), Hungary (n = 24), Poland (n = 11), Romania (n = 3), Slovakia (n = 3), and Slovenia (n = 4). Endocrine, nutritional, and metabolic diseases (18%), neoplasms (12%), infections (11%), and neurological disorders (11%) were the most frequently studied clinical areas, and multiple sclerosis was the most commonly studied disease. Overall, 57 (98%) of the studies explicitly stated the source of resource use data, 45 (78%) the study perspective, 34 (64%) the costing method, and 24 (58%) reported at least one unit costs. Regardless of methodological differences, a positive relationship was observed between costs of diseases and countries' per capita GDP. CONCLUSIONS: Cost-of-illness studies varied considerably in terms of methodology, publication practice, and clinical areas. Due to these heterogeneities, transferability of the COI results is limited across Central and Eastern European countries.

Long-Term Efficacy of Tumor Necrosis Factor Inhibitors for the Treatment of Methotrexate-Naïve Rheumatoid Arthritis: Systematic Literature Review and Meta-Analysis.

INTRODUCTION: Synthesis of evidence on the long-term use of first-line biologic therapy in patients with early rheumatoid arthritis (RA) is required. We compared the efficacy of up to 5 years' treatment with first-line tumor necrosis factor inhibitors (TNFis) versus other treatment strategies in this population. METHODS: Previous systematic reviews, PubMed and the Cochrane Central Register of Controlled Trials were searched for randomized controlled trials (RCTs) involving treatment of methotrexate-naïve RA patients with first-line TNFis. Literature was synthesized qualitatively, and a meta-analysis conducted to evaluate American College of Rheumatology (ACR) responses, clinical remission defined by any standard measure, and Health Assessment Questionnaire Disability Index (HAQ) at Years 2 and/or 5. RESULTS: Ten RCTs involving 4306 patients [first-line TNFi, n = 2234; other treatment strategies (control), n = 2072] were included in the meta-analysis. Three studies were double-blind for the first 2 years, while seven were partly/completely open label during this period. Five studies reported data at Year 5; all were open label at this time point. At Year 2, ACR50 response, ACR70 response and remission rates were significantly improved with first-line TNFi versus control in double-blind RCTs [log-odds ratio (OR) 0.32 [95% confidence interval (CI) 0.02, 0.62; p = 0.035], log-OR 0.48 (95% CI 0.20, 0.77; p = 0.001), and log-OR 0.44 (95% CI 0.13, 0.74; p = 0.005), respectively], but not in open-label studies. No significant between-group differences were observed in mean HAQ at Year 2 in double-blind or open-label RCTs or in ACR response or remission outcomes at Year 5. CONCLUSION: In double-blind studies, 2-year efficacy outcomes were significantly improved with first-line TNFi versus other treatment strategies in patients with MTX-naïve RA. No significant differences in these outcomes were observed when data from open-label RCTs were considered on their own. Further data on the efficacy of TNFi therapy over ≥ 2 years in patients with methotrexate-naïve RA are required. Plain language summary available for this article.

Validity of the EQ-5D-5L and EQ-5D-3L in patients with Crohn's disease.

PURPOSE: The EuroQol five-dimension questionnaire (EQ-5D) is the most commonly used instrument to obtain utility values for cost-effectiveness analyses of treatments for Crohn's disease (CD). We aimed to compare the measurement properties of the two adult versions of EQ-5D (EQ-5D-3L and EQ-5D-5L) in patients with CD. METHODS: Between 2016 and 2017, a multicentre cross-sectional survey was carried out. Consecutive outpatients with CD completed the 3L, 5L and EQ visual analogue scale (VAS). Disease severity was graded by the Crohn's Disease Activity Index (CDAI) and Perianal Disease Activity Index (PDAI). The 3L and 5L were compared in terms of feasibility, agreement, ceiling effect, redistribution properties, discriminatory power, convergent and known-groups validity. RESULTS: Two-hundred and six patients (54.9% male, mean age 35 ± 11 years) participated in the survey. For 3L, 25 unique health states were observed versus 59 for the 5L. The overall ceiling effect decreased from 29.6% (3L) to 25.5% (5L). Absolute discriminatory power improved (mean Shannon index 0.84 vs. 1.18). The 3L correlated stronger with EQ VAS and CDAI scores, whereas the 5L with PDAI. The 5L demonstrated a better known-groups validity on the basis of age, perianal fistulas, extraintestinal manifestations and disability. CONCLUSIONS: This is the first study to report the impact of CD on quality of life using the EQ-5D-5L questionnaire. The 5L seems to perform better than 3L in terms of feasibility, ceiling effect, discriminatory power and known-groups validity. Understanding the differences in psychometrics between the 3L and 5L is essential as they have substantial implications for financial decision-making about CD treatments.

EQ-5D studies in cardiovascular diseases in eight Central and Eastern European countries: a systematic review of the literature.

BACKGROUND: The measurement of health-related quality of life (HRQoL) by validated generic instruments, such as EQ-5D, has become an increasingly important tool for the assessment of health care in a wide range of diagnoses. AIM: We aimed to systematically review EQ-5D literature on cardiovascular diseases in eight Central and Eastern European (CEE) countries. METHODS: A structured literature search was conducted in MEDLINE, EMBASE, Web of Science, CINAHL, PsycINFO, Cochrane Library, and the EuroQol website up to November 2016. Original cardiovascular-related studies that reported EQ-5D results were included. RESULTS: Of the 36 papers, 17 reported EQ-5D index scores. Most studies were performed in Poland (n = 24, 67%). The most common diagnosis regarding the number of publications and population size was ischaemic heart disease (n = 13, N = 6394), followed by atrial fibrillation (n = 4, N = 1052). The average EQ-5D index scores ranged from 0.61 to 0.88 and from 0.66 to 0.95 for patients before and after cardiac procedure/surgery, respectively (including angioplasty, coronary artery bypass grafting, ablation, surgical correction of septal defects, transcatheter aortic valve implantation [TAVI]). In all studies baseline scores were lower than the repeated assessments after the procedure, with the most substantial improvement of 0.24 in high-risk elderly patients after TAVI. Studies which did not assess invasive treatment reported mean EQ-5D index scores ranging from 0.18 to 0.80. CONCLUSIONS: The number of cardiovascular-related studies reporting HRQoL using EQ-5D has consistently increased in CEE countries over the past decade and is outstanding compared with other clinical fields. The EQ-5D index and EQ VAS scores varied based on the disease severity, patient characteristics, and treatment protocol.

Subjective health expectations of patients with age-related macular degeneration treated with antiVEGF drugs.

BACKGROUND: Subjective expectations regarding future health may influence patients' judgement of current health and treatment effects, as well as adherence to therapies in chronic diseases. We aimed to explore subjective expectations on longevity and future health-related quality of life (HRQOL) of patients with age-related macular degeneration (AMD) treated with antiVEGF injections and analyse the influencing factors. METHODS: Consecutive AMD patients in two ophthalmology centres were included. Demographics, clinical characteristics and informal care utilisation were recorded. Current health was evaluated by the EQ-5D generic health status questionnaire and time trade-off (TTO) methods. Happiness was measured on a visual analogue scale (VAS). Subjective life-expectancy and expected EQ-5D status at ages 70, 80 and 90 were surveyed. T-test was applied to compare subgroups and Pearson correlations were performed to analyse relationships between variables. RESULTS: One hundred twenty two patients were involved (females 62%) with a mean (SD) age of 75.2 (7.9) years and disease duration of 2.9 (2.5) years. The majority were in AREDS-4 state, the better eye's ETDRS was 64.7 (15.4). EQ-5D and TTO revealed moderate deterioration of health (0.66 vs. 0.72, p = 0.131), happiness VAS was 6.3 (2.2). Correlation between EQ-5D and ETDRS was moderate (R = 0.242, p < 0.05) and having both versus one eye in AREDS-4 resulted lower TTO (0.68 vs. 0.83; p = 0.013). Subjective life-expectancy did not differ significantly from statistical life-expectancy and had no significant impact on TTO. The self-estimated mean EQ-5D score was 0.60, 0.40 and 0.24 for ages 70, 80 and 90 which is lower than the population norm of age-groups 65-74, 75-84 and 85+ (0.77, 0.63 and 0.63, respectively). Age, gender, current EQ-5D, need for informal care and happiness were deterministic factors of subjective health expectations. CONCLUSION: AMD patients with antiVEGF treatment have comparable HRQOL as the age-matched general public but expect a more severe deterioration of health with age. Older patients with worse HRQOL have worse subjective expectations. Exploring patients' health expectations provides an opportunity for ophthalmologists to correct misperceptions and improve the quality of AMD care. Further studies should provide evidences on the relationship between subjective expectations and actual health outcomes, and on its impact on patients' AMD-specific health behaviour.

Access to biologicals in Crohn's disease in ten European countries.

AIM: To analyze access (availability, affordability and acceptability) to biologicals for Crohn's disease (CD) in ten European countries and to explore the associations between these dimensions, the uptake of biologicals and economic development. METHODS: A questionnaire-based survey combined with desk research was carried out in May 2016. Gastroenterologists from the Czech Republic, France, Germany, Hungary, Latvia, Poland, Romania, Slovakia, Spain and Sweden were invited to participate and provide data on the availability of biologicals/biosimilars, reimbursement criteria, clinical practice and prices, and use of biologicals. An availability score was developed to evaluate the restrictiveness of eligibility and administrative criteria applied in the countries. Affordability was defined as the annual cost of treatment as a share of gross domestic product (GDP) per capita. Correlations with the uptake of biologicals, dimensions of access and GDP per capita were calculated. RESULTS: At the time of the survey, infliximab and adalimumab were reimbursed in all ten countries, and vedolizumab was reimbursed in five countries (France, Germany, Latvia, Slovakia, Sweden). Reimbursement criteria were the least strict in Sweden and Germany, and the strictest in Hungary, Poland and Slovakia. Between countries, the annual cost of different biological treatments differed 1.6-3.3-fold. Treatments were the most affordable in Sweden (13%-37% of the GDP per capita) and the least affordable in the Central and Eastern European countries, especially in Hungary (87%-124%) and Romania (141%-277%). Biosimilars made treatments more affordable by driving down the annual costs. The number of patients with CD on biologicals per 100000 population was strongly correlated with GDP per capita (0.91), although substantial differences were found in the uptake among countries with similar economic development. Correlation between the number of patients with CD on biologicals per 100000 population and the availability and affordability was also strong (-0.75, -0.69 respectively). CONCLUSION: Substantial inequalities in access to biologicals were largely associated with GDP. To explain differences in access among countries with similar development needs further research on acceptance.

Long-term costs and survival of prostate cancer: a population-based study.

PURPOSE: There is a rising interest in measuring the societal burden of malignancies including prostate cancer. However, population-based studies reporting incidence costs of prostate cancer in the long term are lacking in Europe. The objectives of the study are to analyse the long-term costs and survival of prostate cancer patients treated by radical prostatectomy (RP) or conservative management (nRP). METHODS: A retrospective claims data analysis of the National Health Insurance Found Administration of Hungary between 01.01.2002 and 31.10.2013 was carried out. Annual incidence costs related to prostate cancer and overall survival were calculated for a cohort of patients diagnosed between 2002 and 2005. RESULTS: Altogether 17,642 patients were selected; 2185 (12%) of them have undergone RP. The annual incidence rate ranged between 4177 and 4736 cases. Mean age of RP and nRP patients was 59.4 (SD 5.9) and 71.0 (8.4) years, respectively. The mean survival time of the RP patients was significantly longer compared to nRP patients both in the total sample (11.2 vs. 7.4 years; p < 0.001) and in the subgroup <70 years (11.3 vs. 8.8 years; p < 0.001). At the end of the 12-year follow-up, RP patients had a higher (0.83 vs. 0.68), while nRP patients had a slightly lower (0.35 vs. 38) probability of being alive compared with the age-matched general male population. The long-term cumulative costs of the RP and nRP patients amounted to €4448 and €8616. The main driver of the cost difference was the high drug costs in the nRP group. CONCLUSIONS: To our knowledge, this study applied the longest time-window in reporting population-based incidence costs in Europe. We found that not only RP patients lived longer but they had significantly lower total long-term costs than nRP patients. Therefore, radical prostatectomy is a cost-effective strategy in prostate cancer.

Cost-utility of biological treatment sequences for luminal Crohn's disease in Europe.

BACKGROUND: This study aims to compare the cost-effectiveness of treatment sequences with available biologics, including adalimumab (ADA), biosimilar infliximab (bsIFX), originator infliximab (IFX) and vedolizumab (VEDO) for luminal Crohn's disease in nine European countries. METHODS: A Markov-model was constructed to simulate five-year medical costs and quality-adjusted life years (QALYs). Data on clinical efficacy were obtained from randomised controlled trials. Country-specific unit costs, discount rates and a third-party payer perspective were applied. RESULTS: The bsIFX versus conventional therapy resulted in the most favourable incremental cost-utility ratios (ICURs) ranging from €34,580 (Hungary) to €77,062/QALY (Sweden). Compared to bsIFX, the bsIFX-ADA sequence was more cost-effective than the bsIFX-VEDO sequence with ICURs varying between €70,277 (France) and €162,069/QALY (Germany). The ICURs of the bsIFX-ADA-VEDO sequence versus the bsIFX-ADA strategy were between €206,266 (The Netherlands) and €363,232/QALY (Spain). CONCLUSION: We are the first to compare cost-effectiveness of multiple biological sequences for luminal Crohn's disease. Based on our findings, bsIFX can be recommended as a first-line treatment in patients unresponsive to conventional treatments. While biological sequences only slightly differ in their associated health gains, their costs vary greatly. The bsIFX-ADA-VEDO seems to be the most cost-effective sequence of the available biologics across Europe.

The Rituximab Biosimilar CT-P10 in Rheumatology and Cancer: A Budget Impact Analysis in 28 European Countries.

INTRODUCTION: New biosimilars of monoclonal antibodies are anticipated to bring significant cost savings and increase access to treatment. The rituximab biosimilar CT-P10 has recently been approved in Europe in all indications held by reference rituximab (RTX), including rheumatoid arthritis, non-Hodgkin's lymphoma, and chronic lymphocytic leukemia. We analyzed the budgetary impact of the introduction of CT-P10 into the European Union (EU) for use in patients with rheumatoid arthritis and cancer diagnoses, using a budget impact analysis model. METHODS: The model used a base case scenario in which the 1-year uptake of CT-P10 was estimated at 30%, and the cost of CT-P10 was assumed to be 70% of the cost of RTX. A second 1-year scenario was also modeled, in which the market share of CT-P10 was assumed to be 50% (scenario 2). Finally, 3-year time horizon outcomes were calculated, in which the market share of CT-P10 was assumed to be 30%, 40%, and 50% in the first, second, and third years, respectively. RESULTS: In the base case scenario, the introduction of CT-P10 was associated with projected savings of €90.04 million in the first year, which would allow 7531 additional patients to access rituximab treatment. This was equivalent to a 6.4% increase in the number of rituximab-treated patients. In scenario 2, budget savings were €150.10 million, with a total of 12,551 additional patients able to access rituximab, equivalent to a 10.7% increase. Over a 3-year time horizon, projected budget savings were approximately €570 million, equating to 47,695 additional patients able to access rituximab. CONCLUSIONS: The model predicted that the introduction of CT-P10 in the EU will be associated with significant budget savings, the reallocation of which will enable many more patients to access rituximab treatment. This is likely to have a significant impact on health gains at patient and societal levels. FUNDING: CELLTRION Healthcare Co., Ltd. sponsored the development and analysis of the budget impact analysis model.