Long-term Healthcare Resource Utilization and Costs among Patients with Myasthenia Gravis: A Swedish Nationwide Population-based Study.

INTRODUCTION: Health care costs and societal impact of myasthenia gravis (MG), a potentially life-threatening rare, chronic neuromuscular disease are sparsely studied. We assessed healthcare resource utilization (HCRU) and associated costs among patients with newly diagnosed (ND) and pre-existing (PE) MG in Sweden. METHODS: This observational, retrospective cohort study used data from four linkable Swedish nationwide population-based registries. Adult MG patients receiving pharmacological treatment for MG and having ≥ 24-month follow-up during the period 1/1/2010 to 12/31/2017 were included. RESULTS: A total of 1,275 patients were included in the analysis, of which 554 patients were categorized into the ND MG group and 721 into the PE MG group. Mean (±SD) age was 61.3 (±17.4) years and 52.3% were female. In first year post-diagnosis, ND patients had significantly higher utilization of acetylcholinesterase inhibitors (96.0% vs 83.9%), corticosteroids (59.6% vs 45.8%), thymectomy (12.1% vs 0.7%) and plasma exchange (3.8% vs 0.6%); had higher all-cause (70.9% vs 35.8%) and MG-related (62.5% vs 18.4%) hospitalization rates with 11 more hospitalization days (all p<0.01) and an increased risk of hospitalization (odds ratio [95% CI] = 4.4 [3.43, 5.64]) than PE MG. In year 1 post-diagnosis, ND MG patients incurred €7302 (p<0.01) higher total all-cause costs than PE MG, of which 84% were estimated to be MG-related and the majority (86%) were related to inpatient care. These results remained significant also after controlling for baseline demographics and comorbidities (p<0.01). In year 2 post-diagnosis, the all-cause medical costs decreased by ~55% for ND MG from year 1 and were comparable with PE MG. CONCLUSION: In this population-based study, MG patients required significantly more healthcare resources in year 1 post-diagnosis than PE MG primarily due to more pharmacological treatments, thymectomies and associated hospitalizations. These findings highlight the need to better understand potential factors including disease characteristics associated with increased health resource use and costs and need for more efficacious treatments early in the disease course.

Clinical characteristics and outcomes in risk-stratified patients with smoldering multiple myeloma: data from the Czech Republic Registry of Monoclonal Gammopathies.

Smoldering multiple myeloma (SMM) is an asymptomatic precursor to active multiple myeloma (MM). The aim of this study was to report clinical characteristics and outcomes of patients with SMM stratified based on their risk of progression to MM using the Mayo 20/2/20 criteria. Data were leveraged from the Czech Myeloma Group Registry of Monoclonal Gammopathies (RMG). Key outcomes included progression-free survival from SMM diagnosis to active MM diagnosis or death (PFS), progression-free survival from SMM diagnosis to progression on first line (1 L) MM treatment or death (PFS2), and overall survival (OS). Of 498 patients, 174 (34.9%) were classified as high risk and 324 (65.1%) as non-high risk. Median follow-up was approximately 65 months. During follow-up, more patients in the high-risk vs non-high-risk group received 1 L MM treatment (76.4% vs 46.6%, p < 0.001). PFS, PFS2, and OS were significantly shorter in high-risk vs non-high-risk patients (13.2 vs 56.6 months, p < 0.001; 49.9 vs 84.9 months, p < 0.001; 93.2 vs 131.1 months, p = 0.012, respectively). The results of this study add to the growing body of evidence that patients with high-risk vs non-high-risk SMM have significantly worse outcomes, including OS.

Patient Characteristics, Treatment Patterns, and Outcomes in Triple-Class Exposed Relapsed/Refractory Multiple Myeloma Patients, a Retrospective Observational Study Using Czech Registry Data.

BACKGROUND: Although novel therapies improved prognosis of multiple myeloma (MM) patients, clinical outcomes in the multi-refractory population are still poor. PATIENTS AND METHODS: We reviewed data from the Czech Registry of Monoclonal Gammopathies, identified and characterized triple-class exposed (3CE) relapsed/refractory MM patients, treatment patterns after 3CE, assessed overall survival (OS), progression-free survival (PFS), time to next treatment (TTNT), explored cohorts with and without triple- and penta-refractoriness. RESULTS: In 83 3CE patients who started subsequent therapies, the median OS was 14.2 months (95% CI, 8.5-19.9), PFS 6.2 months (95% CI, 3.9-8.5), and TTNT 7.2 months (95% CI, 4.6-9.8). Triple- and penta-class refractory patients had a significantly worse prognosis in all outcomes. Their life expectancy was shorter, the disease progression started earlier, and the TTNT was shorter, which increased likelihood of becoming refractory to more therapies. Time-to-event results from the first index date and all index dates analyses were very similar. CONCLUSION: Similar to previous studies from the US and Europe, our results show a high disease burden. Introduction of novel therapies, such as CAR-T cells, new bispecific and trispecific monoclonal antibodies, and other drugs, is expected to bring significant benefits to these patients.

Comparison of Healthcare Encounters and Drug Persistence in Patients With Pulmonary Arterial Hypertension Receiving Oral Selexipag, Inhaled Iloprost, or Parenteral Treprostinil: A Retrospective Database Analysis.

Background: Agents targeting the prostacyclin (PGI2) pathway are important in managing pulmonary arterial hypertension (PAH). No head-to-head clinical trials have compared outcomes between the 3 different PGI2-pathway drugs most commonly available in countries with advanced healthcare: oral selexipag, inhaled iloprost, and parenteral (subcutaneous or intravenous) treprostinil. Objectives: To conduct retrospective database analyses to describe characteristics of patients with PAH initiating therapy with these agents and compare the rate and risk of healthcare facility encounters and drug persistence. Methods: Data were obtained from the Optum™ Clinformatics® Data Mart and Truven™ Health Analytics® MarketScan® Commercial Claims and Encounters databases from July 1, 2008, to September 30, 2020 (Optum™), or October 31, 2020 (Truven™). Patients were categorized into index-drug cohorts based on first pharmacy claims for selexipag, inhaled iloprost, or parenteral treprostinil. Eligible patients were ≥18 years of age with ≥1 ICD-9-CM or ICD-10-CM diagnosis code indicating pulmonary hypertension and no diagnosis code suggesting Group 3-5 pulmonary hypertension. Rates of hospitalization (inpatient admissions), emergency room visits, or outpatient visits per person-year were calculated. Drug persistence was measured as time to discontinuation of index drug. Multivariable analyses were performed to compare outcomes with selexipag vs inhaled iloprost and parenteral treprostinil, adjusting for baseline characteristics using inverse probability of treatment weighting. Results: Overall, 583 patients were included in the Optum™ sample and 482 in the Truven™ sample. Mean (SD) age was 61.7 (14.5) and 49.3 (11.3) years, respectively; 74.4% and 75.7% of patients, respectively, were women. In the pooled samples, after adjustment for baseline characteristics, selexipag had a lower risk than inhaled iloprost or parenteral treprostinil for hospitalization (relative rate ratio [95% CI], 0.40 [0.22, 0.75], and 0.26 [0.17, 0.39]) and outpatient visits (0.66 [0.56, 0.78] and 0.76 [0.66, 0.88]). Trends toward lower risk of emergency room visits did not attain statistical significance. Drug discontinuation risk was 16% and 36% lower with selexipag vs parenteral treprostinil and inhaled iloprost, respectively. Conclusions: In real-world use, selexipag appears to be associated with lower rates of hospitalization and outpatient visits than inhaled iloprost or parenteral treprostinil. Further research is required to identify factors underlying these differences.

High risk of depression, anxiety, and an unfavorable complex comorbidity profile is associated with SLE: a nationwide patient-level study.

OBJECTIVES: The aim of this national population-based, retrospective database study is to compare the comorbidity profiles of systemic lupus erythematosus (SLE) patients and general population controls matched for age, gender, and region and assess the risk of depression or anxiety when controlled for age, gender and adjusted for the Charlson Comorbidity Index (CCI). METHODS: Claims data of 1051 patients diagnosed with SLE (full population between January 01, 2011, and December 31, 2014) from the Hungarian National Health Insurance Fund have been analyzed against matched controls (1:5 ratio) with a follow-up of 30 months. The first record of SLE diagnosis was considered the diagnosis date. The odds ratio (OR) and 99.9% confidence interval (CI) of having depression or anxiety among patients with SLE vs. controls have been assessed using logistic regression models. RESULTS: SLE patients report more comorbidities than the matched general population both in pre- and post-index periods (mean CCI 1.79 vs. 1.15 and 2.78 vs. 1.22 [both p<0.001], respectively). Both SLE patients and controls diagnosed with depression or anxiety had significantly higher CCI than those without comorbid depression or anxiety (p<0.001). However, SLE patients had a twofold higher risk of depression or anxiety than matched controls when controlled for age, gender, and adjusted for CCI. CONCLUSION: Our analysis indicates the enormity of comorbidity burden in SLE, especially that of anxiety and depression. The size and complexity of the comorbidity burden emphasizes the importance of early diagnosis and intervention with comprehensive modalities incorporating attention to comorbidities in SLE patients.

Prognostic Value of EGFR Exon-20 Insertions in Czech Patients With Advanced Non-small Cell Lung Cancer.

BACKGROUND/AIM: Per literature, patients with epidermal growth factor receptor (EGFR) exon-20 insertions respond poorly to tyrosine kinase inhibitors (TKIs). This study analyzed real-world data to examine the prognostic and predictive value of these mutations. PATIENTS AND METHODS: We conducted a retrospective cohort study using Czech TULUNG Registry data, with data on multiple mutation types, collected in 2011-2020. RESULTS: We analyzed 554 (95.85%) patients with EGFR exon-19 deletions or exon-21 L858R substitutions and 24 (4.15%) patients with exon-20 insertions who received first-line high-value therapies. We summarized clinical characteristics and outcomes in all patients and by cohort. The risk of progression was statistically significantly higher (86%) in the exon-20 insertion cohort compared to the cohort with other mutations. Although not statistically significant, the risk of death was 44% higher in patients with exon-20 insertions. CONCLUSION: Advanced NSCLC patients with rare EGFR exon-20 insertions have a high risk of progression.

Burnout among Hungarian dentists / Kiégés a magyar fogorvosok körében.

Összefoglaló. Bevezetés: A kiégés jelensége fokozottan érinti az egészségügyi dolgozókat, a nagyfokú stressz, a folyamatos fizikai és emocionális megterhelés miatt. A kiégés mérését fogorvosok körében végeztük, mivel Magyarországon még nem készült csak fogorvosokat méro keresztmetszeti vizsgálat. Célkituzés: Elsodleges célunk a fogorvosi kiégés elofordulásának, súlyosságának mérése, a rizikófaktorok kiszurése volt. Másodlagos célul a kiégés veszélyére való figyelem felkeltését tuztük ki az érintett csoportban. Módszer: Az adatgyujtés a 'Maslach Burnout Inventory - Human Services Survey' 22 tételes magyar, validált változatával történt online formában. Eredmények: Online kérdoívünket 407 fogorvos töltötte ki. A következo eredményeket kaptuk: az emocionális kimerülés esetében a válaszadók 20%-a (81 fo) tartozik a magas kategóriába, a cinizmus dimenziójának esetében a válaszadók 17,5%-át (70 fo) jellemzi a magas pontszám. A teljesítményvesztés magas dimenziója a minta 75%-ában (302 fo) volt igazolható. Szignifikáns (p≤0,05) védofaktornak találtuk a harmonikus kollegiális viszonyt, a hobbi meglétét, a 2-4 óra napi munkát, a támogató otthoni és munkahelyi légkört, az egészségi probléma és a saját vállalkozás hiányát. Szignifikáns negatív eltérést 6-10 éve dolgozó férfiak körében találtunk. Következtetés: Az eredmények felhívják a figyelmet a legfontosabb protektív tényezokre, melyek segítségével csökkentheto a kiégés mértéke. Orv Hetil. 2021; 162(11): 419-424. INTRODUCTION: Burnout has an increased impact on healthcare workers due to severe stress, constant physical and emotional strain. Burnout was measured among dentists, as no such cross-sectional study has been made in Hungary. OBJECTIVE: Our primary goal was to measure the incidence and severity of dental burnout and to screen for the risk factors. Our secondary goal was to raise awareness of the risk of burnout in the affected group. METHOD: Data collection was performed online with the 22-item Hungarian validated version of Maslach Burnout Inventory - Human Services Survey. RESULTS: 407 dentists completed our online questionnaire. The following results were obtained: in the case of emotional exhaustion, 20% of the respondents belong to the high category, in the cynicism dimension, 17.5% of the respondents have high scores. The high dimension of performance loss is typical in 75% of the sample. We found that harmonious collegial relationships, the existence of a hobby, 2-4 hours of daily work, a supportive home and work atmosphere, the lack of health problems and self-employment are significant (p≤0.05) protective factors. Significant negative differences were found among men who had been working for 6-10 years. CONCLUSION: The results draw attention to the most important protective factors that can help reduce the rate of burnout. Orv Hetil. 2021; 162(11): 419-424.

Clinical characteristics of treatment-resistant depression in adults in Hungary: Real-world evidence from a 7-year-long retrospective data analysis.

PURPOSE: Treatment-resistant depression (TRD) is associated with a poor quality of life and high economic burden. This observational retrospective epidemiological study aimed to estimate the proportion of patients with TRD within a cohort of patients with major depressive disorder (MDD) in Hungary and examine the mortality and comorbidities of patients with and without TRD. PATIENTS AND METHODS: This study included patients with MDD who experienced onset of a new depressive episode between 01 January 2009 and 31 August 2015, using data from a nationwide, longitudinal database. RESULTS: Overall, 99,531 patients were included in the MDD cohort, of which 8,268 (8.3%) also met the criteria for TRD. The overall survival of non-TRD patients was longer than in TRD patients; the risk of mortality for TRD patients was significantly higher than of non-TRD patients (HR [CI] 1.381 [1.212-1.571]; p<0.001). Patients with TRD had a significantly higher probability of having "Neurotic, stress-related and somatoform disordersË®, autoimmune conditions, cardio- or cerebrovascular diseases, thyroid gland diseases and self-harming behaviour not resulting in death than non-TRD patients (for all comparisons, p values were less than 0.005). DISCUSSION: To our best knowledge, this is the first study to assess the frequency of TRD in Hungary. In a cohort of Hungarian MDD patients, we have found that the proportion of TRD (~8.3%) is comparable to those reported in previous studies with similar methodology from other countries. The majority of our other main findings (e.g. more frequent self-harming behaviour, increased risk of "Neurotic, stress-related and somatoform disordersË® and higher overall mortality in TRD subjects) are also in line with previous results from other countries. Taking the substantial proportion of patients with TRD into consideration, a more comprehensive and targeted treatment strategy would be required for these individuals.

Epidemiology, mortality and prevalence of colorectal cancer in ulcerative colitis patients between 2010-2016 in Hungary - a population-based study.

BACKGROUND: The incidence and prevalence of ulcerative colitis (UC) varies geographically. The risk of colorectal cancer (CRC) and possibly some other malignancies is increased among patients with UC. It is still debated if patients with UC are at a greater risk of dying compared with the general population. Our aim was to describe the epidemiology and mortality of the Hungarian UC population from 2010 to 2016 and to analyze the associated malignancies with a special focus on CRC. METHODS: This is an observational, descriptive, epidemiological study based on the National Health Insurance Fund social security databases from 2010 to 2016. All adult patients who had at least two events in outpatient care or at least two medication prescriptions, or at least one inpatient event with UC diagnosis were analyzed. Malignancies and CRC were defined using ICD-10 codes. We also evaluated the survival of patients suffering from UC compared with the general population using a 3 to 1 matched random sample (age, gender, geography) from the full population of Hungary. RESULTS: We found the annual prevalence of UC 0.24-0.34%. The incidence in 2015 was 21.7/100 000 inhabitants. Annual mortality rate was 0.019-0.023%. In this subpopulation, CRC was the most common cancer, followed by non-melanotic skin and prostate cancer. 8.5% of the UC incident subpopulation was diagnosed with CRC. 470 (33%) of the CRC patients died during the course of the study (25% of all deaths were due to CRC), the median survival was 9.6 years. UC patients had significantly worse survival than their matched controls (HR = 1.65, 95% CI: 1.56-1.75). SUMMARY: This is the first population-based study from Eastern Europe to estimate the different malignancies and mortality data amongst Hungarian ulcerative colitis patients. Our results revealed a significantly worse survival of patients suffering from UC compared to the general population.

Large-scale mortality gap between SLE and control population is associated with increased infection-related mortality in lupus.

OBJECTIVE: The aim of the present study was to analyse the incidence, prevalence, mortality and cause of death data of adult SLE patients and matched controls in a full-populational, nationwide, retrospective study. METHODS: This non-interventional study was based on database research of the National Health Insurance Fund of Hungary. A total of 7888 patients were included in the analyses, within which two subgroups of incident patients were created: the 'All incident SLE patients' group consisted of all incident SLE patients (4503 patients), while the 'Treated SLE patients' group contained those who received relevant therapy in the first 6 months after diagnosis (2582 patients). RESULTS: The median age of the SLE population was found to be 46.5 years (women 85%). The incidence rate was 4.86 and 2.78 per 100 000 inhabitants in the 'All incident SLE patients' and 'Treated SLE patients' groups, respectively. The standardized mortality ratio was 1.63 and 2.09 in the 'All incident SLE patients' and 'Treated SLE patients' groups, respectively. Overall survival was significantly lower (P < 0.001) in both groups than in the general population, with hazard ratio = 2.17 in the 'All incident SLE patients' group and hazard ratio = 2.75 in the 'Treated SLE patients' group. There was no significant difference between SLE and control deaths regarding cerebrovascular conditions as the cause of death. Generally, cancer-related deaths were less common, while haematological cancer and infection-related deaths were more common in SLE patients. CONCLUSION: Infections, especially sepsis, had the largest positive effect on top of the extra mortality of SLE. This highlights that SLE patients are at increased risk of infection-related death.

Epidemiological data and utilization patterns of anti-TNF alpha therapy in the Hungarian ulcerative colitis population between 2012-2016.

Background: Anti-TNF therapy is efficacious in the maintenance of remission in ulcerative colitis (UC); however, long-term data on real-life use of these agents are lacking.Methods: This observational, retrospective, epidemiological study using the National Health Insurance Fund social security database aimed to understand patient characteristics and therapeutic patterns of anti-TNF therapy. Data of adult Hungarian, UC patients treated with anti-TNF agents (IFX-infliximab, ADA-adalimumab) between 2012 and 2016 were analyzed.Results: Five hundred and sixty-eight UC patients were identified. Approximately 70-80% of the patients reached maintenance therapy. A large proportion of patients stopped therapy after 10 to 12 months due to the reimbursement policy. Corticosteroid use decreased significantly after the initiation of biological therapy. The dose-escalation rate was 19.8% for ADA and 10.9% for IFX, respectively, and was performed earlier along the treatment timeline for patients on ADA. In the present study, the rate of primary non-response (PNR) was 11.6% and the rate of secondary loss of response (LOR) was 36.5%.Summary: Treatment length is in correspondence with the Hungarian reimbursement policies. The mandatory stop of treatment in the reimbursement policy is suboptimal in UC patients requiring biological therapy. The corticosteroid-sparing effect of biological therapy was demonstrated.

Anti-TNF dose escalation and drug sustainability in Crohn's disease: Data from the nationwide administrative database in Hungary.

BACKGROUND: A significant percentage of patients receiving anti-tumor necrosis factor alpha (anti-TNFα) agents lose clinical response over time. This study aims to provide representative real-world data on anti-TNFα drug sustainability, prevalence and predictors of anti-TNFα dose escalation. METHODS: In this nationwide, retrospective study, patients receiving infliximab or adalimumab therapy between 2013 and 2016 were included using the administrative claims database of the Hungarian National Health Insurance Fund. Demographic characteristics, drug sustainability, dose escalation, use of parallel medications were analyzed. RESULTS: 476 infliximab and 397 adalimumab patients were included. Dose escalation was observed in 7%, 9% and 22% of patients receiving originator/biosimilar infliximab and adalimumab during the complete follow-up, respectively. Dose escalation was associated with shorter disease duration (OR = 1.75, p = 0.026) and corticosteroid use. Drug retention rates were 62.7%, 72.3%, 75.4% after 1 year follow-up for Remicade®, Inflectra® and Humira®, which decreased to 38.3% and 52.1% for Remicade® and Humira® at 3 years. Drug sustainability was affected by steroid use prior biologic initiation in adalimumab treated patients (HR = 2.04, p < 0.001), while in infliximab treated patients dose escalation (HR = 0.51, p = 0.02) and gender (HR = 1.39, p = 0.033) were predictors of treatment discontinuation. CONCLUSION: Dose escalation rates were lower in this real-world administrative database study for both adalimumab and infliximab compared to published data. Drug retention rates were overall satisfactory, with no apparent difference between the legacy and biosimilar infliximab.