A switch from originator-adalimumab to the biosimilar SB5 in patients with Crohn's disease: an analysis of two propensity score-matched cohorts.

BACKGROUND/AIMS: Originator-adalimumab, an established treatment for patients with Crohn's disease (CD), showed no difference in efficacy or adverse events versus adalimumab biosimilar SB5 (SB5-adalimumab) over 10 weeks (W) of treatment. To understand the long-term effectiveness of SB5-adalimumab in CD, patients switched from originator-adalimumab to SB5-adalimumab were compared with patients remaining on originator-adalimumab over 104 W. METHODS: Data on patients aged ≥18 years, diagnosed with CD and treated at ISCARE, were collected prospectively from July 2018 to January 2021. Primary outcome: clinical disease activity at W52, measured by Harvey-Bradshaw index (HBI). Secondary outcomes: C-reactive protein (CRP), faecal calprotectin (FC) and adalimumab concentrations at W10, 26, 52 and 104, and treatment persistence. To ensure comparable cohorts, patients were propensity score (PS)-matched for age, gender and disease activity. RESULTS: After matching, 54 patients remained per cohort. At W52, mean (SD) HBI score was 3.2 (2.5) for originator-adalimumab and 4.0 [3.6] for SB5-adalimumab (difference [95% CI] -0.78 [-2.8, 1.3]; n = 18/cohort); no clinically meaningful differences in CRP, FC or drug concentrations were noted. Kaplan-Meier's estimates (95% CI) of remaining on treatment were originator-adalimumab: 0.870 (0.785-0.965) versus SB5-adalimumab: 0.648 (0.533-0.789) at W52 and significantly lower for SB5-adalimumab versus originator-adalimumab (p < .001) over 104 W. Local skin reaction events/pain was the main reason for treatment discontinuation in the SB5-adalimumab cohort (n = 20/54 [37%]). CONCLUSIONS: These long-term results of CD patients receiving originator-adalimumab or following nonmedical switch to SB5-adalimumab show similar therapeutic effects on clinical disease activity, biological parameters and pharmacokinetic profile in both cohorts from 52 to 104 W. A separation in persistence was observed beyond W26, mainly due to differences in local reactions at the injection site.

Serum levels of matrix metalloproteinases 2 and 9 and TGFBR2 gene screening in patients with ascending aortic dilatation.

Development of ascending aortic dilatation (AAD) in about 10 % of patients operated for aortic valve disease (AVD) is probably based on intrinsic pathology of the aortic wall. This may involve an abnormality in the process of extracellular matrix remodelling. The present study evaluated the serum levels of specific metalloproteinases (MMP-2 and MMP-9) and investigated the gene for transforming growth factor receptor 2 (TGFBR2) in 28 patients with AVD associated with AAD (mean age 60.6 years), in 29 patients (68.9 years) with AVD without AAD, and in 30 healthy controls (45.3 years). The serum levels of MMPs were determined by ELISA. Further, we focused on genetic screening of the TGFBR2 gene. Plasma MMP-2 concentrations were significantly higher in the groups of patients compared to the controls: median 1315.0 (mean 1265.2 ± SD 391.3) in AVD with AAD, 1240.0 (1327.8 ± 352.5) in AVD without AAD versus 902.5 (872.3 ± 166.2) ng/ml in the healthy controls, in both cases P < 0.001. The serum levels of MMP-9 were significantly higher in AVD with AAD patients [107.0 (202.3 ± 313.0)] and in AVD without AAD patients [107.0 (185.8 ± 264.3)] compared to the healthy controls [14.5 (21.2 ± 24.8) ng/ml], in both cases P < 0.001. No significant correlation was observed between plasma MMP-2 and MMP-9 and ascending aorta diameter. Genetic screening did not reveal any variation in the TGFBR2 gene in the patients. Measurement of MMP levels is a simple and relatively rapid laboratory test that could be used as a biochemical indicator when evaluated in combination with imaging techniques.

The Framingham risk function underestimated absolute coronary heart disease risk in Czech men.

OBJECTIVES: The aim was to validate the Framingham coronary heart disease (CHD) risk function with the formula by Wilson et al. (1998) in Czech men. METHODS: The validation was performed within the 20-year primary prevention study of atherosclerotic risk factors (STULONG) including 1417 middle-aged men from the Czech Republic (Prague). A total of 646 men examined in 1979-1988, and followed-up for ten years, were included into the validation study. The calibration and discrimination ability of the Framingham risk function in the Czech population were explored. RESULTS: The estimated 10-year risk of CHD by the Framingham risk function was 12.8% in 646 men, significantly higher than the observed risk (16.4 %), p = 0.013. The trend in the 10-year incidence of CHD was significantly increasing with quintiles of the estimated risk, p < 0.001. After the recalibration of the Framingham risk function, there was an insignificant difference between the estimated (18.2%) and observed (16.4%) risks of CHD, p = 0.320. The Framingham risk function classified men into those with and without CHD in the 10-year period with accuracy over 60%. CONCLUSIONS: Unlike some validation studies from Western Europe, the Framingham risk function significantly underestimated the 10-year CHD risk in the Czech Republic. In agreement with these studies, the incidence of CHD was significantly increasing across quintiles of the estimated risk.

[Primary prevention of ischemic heart disease in middle-aged men living in Prague: results of twenty-year research]. / Primární prevence ischemické choroby srdecní u muzu stredního veku v Praze: výsledky dvacetiletého sledování.

INTRODUCTION: Ischemic Heart Disease (IHD) represents the most frequent cause of mortality and morbidity in the Czech Republic. The aim of this study is to analyze long-term mortality of cardiovascular disease (CVD), identify its predictors and verify the validity of Framingham risk function for Czech patients. DESIGN AND METHODS: The twenty-year study (STULONG) of primary prevention of risk factors of atherosclerosis in 1419 men aged 38 to 53 years living in Prague was started in 1975. RESULTS: CVD mortality analysis showed a higher risk of death for heavy smokers vs. non-smokers or light smokers (p < 0.0001), hypertensive patients vs. patients with normal blood pressure (p < 0.0001), men with hypercholesterolemia vs. men with normal cholesterol level (p = 0.0432), and a lower risk for university graduates vs. men with elementary education (p = 0.0006). Between 1980 and 1984, age-specific CVD mortality rates of men from STULONG study were higher (p = 0.0132) than national CVD mortality rates; between 1985 and 1994, they were insignificantly lower. Framingham risk function underestimated absolute ten-year risk of IHD in all risk quintiles (p < 0.0001) with discrimination of 63%. CONCLUSION: CVD mortality observed within STULONG study was significantly affected by known risk factors (hypertension, smoking, hypercholesterolemia, lower education); Framingham risk function underestimated absolute ten-year risk of IHD.

Primary prevention of coronary artery disease among middle aged men in Prague: twenty-year follow-up results.

BACKGROUND: Coronary artery disease (CAD) represents the most common cause of morbidity and mortality in the Czech Republic. The aim of this study is to analyze long-term cardiovascular diseases (CVD) mortality, identify predictors of outcome and to validate the Framingham risk function in men from the Czech Republic. DESIGN AND METHODS: A 20-year primary prevention study of atherosclerosis risk factors in 1417 men from Prague aged 38-53 years was launched in 1975 (STULONG). RESULTS: When analyzing CVD mortality, heavy smokers had hazard higher than non-smokers and light smokers (p < 0.0001); hypertensives higher than normotensives (p < 0.0001); men with hypercholesterolemia higher than those with normal cholesterol (p = 0.0432), and university-educated men lower than elementary-educated men (p = 0.0006). In 1980-1984, the age specific mortality from CVD in men from STULONG was higher (p = 0.0132) than in the Czech Republic, in 1985-1994 insignificantly lower. The Framingham risk function underestimated the absolute 10-year risk of CAD across the quintile of the risk (p < 0.0001), with 63% discrimination. CONCLUSION: In STULONG, the mortality from CVD was significantly associated with known risk factors (hypertension, smoking, hypercholesterolemia, education); the Framingham risk function underestimated the absolute 10-year risk of CAD.

State of the art coronary heart disease risk estimations based on the Framingham heart study.

The aim was to review the most interesting articles dealing with estimations of an individual's absolute coronary heart disease risk based on the Framingham heart study. Besides the Framingham coronary heart disease risk functions, results of validation studies of these Framingham risk functions are discussed. In general, the Framingham risk functions overestimated an individual's absolute risk in external (non-Framingham) populations with a lower occurrence of coronary heart disease compared with the Framingham population, and underestimated it in populations with a higher occurrence of coronary heart disease. Even if the calibration accuracy of the Framingham risk functions were not satisfying, the Framingham risk functions were able to rank individuals according to risk from low-risk to high-risk groups, with the discrimination ability of 60% and more.

Prediction of lung cancer mortality in four Central European countries, 1990-2009.

During the post-war decades the cancer mortality in Europe has undergone deep changes. In the 1980s, remarkable increases in lung cancer mortality in the Central and Eastern European area resulted in rates equaling or exceeding those in most Western countries. In the present work, the future development of the lung cancer epidemic has been assessed in four Central European countries (Austria, Czech Republic, Hungary, and Slovakia) for the period 1900-2009, taking into consideration previously observed lung cancer mortality trends (1960-1989), in the same countries. The estimation of the predicted mortality trends was based on log-linear Poisson regression age/period/cohort model, using GLIM for calculation. In the twenty-year period from 1985-1989 to 2005-2009, the age-adjusted (world standard) lung cancer mortality rates for men are predicted to increase in Hungary and Slovakia, and show little change in Austria and the Czech Republic. For women, approximately exponential increases in lung cancer mortality rates (both adjusted all-age, and age-specific at young adult ages up to 44 years) can be expected, with highest rates in Hungary, intermediate in the Czech Republic and Austria, and lowest in Slovakia. Lung cancer mortality in women is still much smaller than in men, however, rapidly increasing, with less variation in trends between countries than in men. The current and predicted high and/or increasing lung cancer mortality rates in the countries under study, presumed to be associated with elevated exposure to respiratory carcinogens, mainly cigarette smoke, in previous decades, underlines that the control of smoking continues to be a priority among approaches to cancer prevention.

Patterns of cigarette sales and lung cancer mortality in some central and eastern European countries, 1960-1989.

BACKGROUND: Remarkable increases in lung cancer risk recently have been observed in the Central and Eastern European (CEE) area. This study examines the patterns of lung cancer mortality rates and cigarette sales in 1960-1989 in seven CEE countries with a total population of 97.5 million and 43,000 deaths from lung cancer in the last year under study. METHODS: Trends in cigarette sales and mortality rates from lung cancer in seven CEE countries were compared for the years 1960-1989. RESULTS: Among males, recent lung cancer death rates were the highest in Europe, and trends by country largely reflected the varied prevalence and duration of smoking in previous decades. For females, lung cancer mortality rates were much lower, although there were exponential rate increases. In the more recent birth cohorts, there were some declines in mortality rates among males, but not among females. CONCLUSIONS: The rising cigarette consumption through the 1960s, 1970s, and, in some countries, the 1980s is accompanied in most of the countries by rising lung cancer mortality rates for young adults. This increasing cigarette consumption will determine future trends in lung cancer, which will increase well beyond the turn of the century and will continue longer for females than for males. This outlook underlines the urgent need for comprehensive lung cancer prevention with the concerted control of smoking as a priority. The role of cofactors and their interaction with smoking deserve further exploration.

Cancer, cardiovascular mortality, and diet in Italy and the Czech Republic.

A descriptive study aimed at comparing mortality and dietary patterns in Italy and the Czech Republic was conducted in the period 1970-1990. Mortality from all causes, all cancers, selected site specific cancers and cardiovascular diseases were found to be generally higher in the Czech Republic than in Italy. The North-South gradients observed within Italy have diminished in the course of the last twenty years, mostly due to a less contained decrease of the mortality from cardiovascular diseases and to a marked increase in cancer mortality for Southern regions compared to Central and Northern regions. The mediterranean diet with many health promoting, possibly protective components, mostly of vegetable origin, is consumed in most parts of Italy, particularly in the South. In contrast, a Central European diet abounding in animal products and lacking in fresh fruit and vegetables is generally followed in the Czech Republic. These differences in diet may play a role in the origin of the observed differences in mortality patterns. Some factors other than diet, such as smoking habits, alcohol consumption, endogenous factors, and occupation, that are not considered here, are known to be involved in the causation of some types of cancer. The results of this study are compatible with the hypothesis of a relevant role played by dietary and other life-style habits in the etiopathogenesis of neoplastic and cardiovascular diseases.

[Statistical modelling of lung cancer mortality in the Czech Republic 1960-1989]. / Statistické modelování úmrtnosti na rakovinu plic v Ceské republice v letech 1960-1989.

The author's aim is to analyze in more detail the temporal mortality trends from lung cancer in the Czech Republic in the age group from 35-69 years during 1960-1989, separately for men and women. Poisson's log-linear regression model revealed that the mortality in both sexes depended significantly on three time factors: age, year of birth and historical period. The dependence of mortality on the above factors was analyzed by Osmond-Gardner's method. The mortality increased in both sexes with age. The risk of death in male generations born between the beginning of the 19th century and the First World War declined, however, in generations born after 1915 it increased again with consecutive years of birth. In women the risk of death increased with the year of birth. The impact of five-year periods on mortality increased slowly, however, in women only from the first half of the seventies.

Statistical modelling and prediction of lung cancer mortality in the Czech and Slovak Republics, 1960-1999.

BACKGROUND: The aim of the study was to analyse the pattern of lung cancer mortality from 1960 to 1989 and to predict lung cancer mortality for 1990-1999 for males and females aged > or = 30 years in the Czech and Slovak Republics. METHOD: The mortality pattern of lung cancer was examined and predicted using republic-age-period-cohort models. RESULTS: Trends in lung cancer mortality were upward for both sexes over the study period. In the early 1960s, lung cancer mortality in Slovak males was much lower than that in Czech males, but since the late 1960s lung cancer mortality in males increased more rapidly in Slovakia than in the Czech Republic. It was predicted that mortality due to lung cancer in Slovak males would exceed that in Czech males during the last 5 years of the 20th century. Slovak female lung cancer mortality was lower than that for Czech females throughout the study period, and the trends in both republics were similar.

Regional and national variation in lung cancer mortality in Italy and Czechoslovakia.

In developed countries lung cancer mortality has been shown to be related to lifestyle, occupational and environmental aspects, diet, and other factors which may vary widely from one region to another. To investigate inter-area differences in lung cancer mortality and cigarette smoking a descriptive study has been carried out in three areas of Italy and two republics of Czechoslovakia. The highest death rates from lung cancer were found in the Czech Republic and Northern Italy, for both sexes. Analysis of age-specific rates by birth cohort, comparing all five areas, showed the greatest differences in trends between Slovakia and Northern Italy in men, and between the Czech Republic and Southern Italy in women. The lowest rates were observed in Southern Italy throughout the period under study, particularly among women. Making allowance for the latency period between the onset of exposure and the development of the disease, data on the occurrence of lung cancer could be interpreted looking at previous smoking habits. An imperfect overlap between the trend of cigarette smoking and the corresponding lung cancer mortality pattern was present in Northern and Southern Italy, a finding suggesting that even non-smoking-related factors could have played a significant role in lung cancer aetiology.

[Smoking and the development of lung cancer]. / Kourení a výskyt plicní rakoviny.

It is generally accepted that cigarette smoking is the most important lung cancer risk factor to which 80-90% of lung cancer mortality in advanced countries with a high tobacco consumption is ascribed. In the Czech Republic the increase of tobacco consumption since the end of the Second World War was arrested at the end of the sixties. Since the beginning of the seventies the cigarette consumption did not change substantially and varied close to 2500 cigarettes per inhabitant above 15 years. No reliable data are so far available in the Czech Republic on the development of the prevalence of smoking in different age groups of the population. According to several non-representative surveys in different districts it may be assumed that in men aged 25-64 years in the course of the last 20 years the ratio of male smokers declined probably, while it increased in female smokers. Due to the long "latency" between exposure to noxious substances and the manifestation of lung cancer which amounts to two, three or more decades, we have to evaluate the present mortality rate from lung cancer as a reflection of carcinogenic factors (above all cigarette smoking) in the more remote past. When evaluating the trend of mortality from lung cancer in the Czech Republic during 1953-1989, throughout that period the values were much higher in men that in women and the trend in the two sexes was quite different. In men the mortality rate from lung cancer increased in 1953-1967 to three times the initial value, while in women the levels remained low.(ABSTRACT TRUNCATED AT 250 WORDS)

The natural history of lung cancer estimated from the results of a randomized trial of screening.

The results from a randomized controlled trial of screening for lung cancer in Czechoslovakia have been used to estimate parameters of the natural history, using a model to simulate the disease process and the effects of screening. The results suggest that the period before clinical presentation during which lesions can be detected by screening is very short (seven to eight months). This implies that to detect three-quarters of all lung cancers by screening, two examinations per year are necessary, and that such a program would advance diagnosis by six months if there were complete participation. The results of the trial itself suggest that the benefit, in terms of a reduction in mortality from lung cancer, is likely to be very small.

Lung cancer and smoking in Finland and the Czech Republic. Recent trends and predictions.

Trends of mortality from lung cancer in 1953-1989, age-specific lung cancer death rates of five-year birth cohorts, and the cigarette consumption were compared in Finland and the Czech Republic. While the lung cancer mortality and the smoking habits were fairly similar in Finland and the Czech Republic in the 1950s and early 1960s, contrasting differences gradually developed over the subsequent three decades in favor of Finland. In the year 1989, the Czech lung cancer death rates were much higher than the Finnish rates: in males 75.8 vs. 48.1 per 100,000; in females 9.3 vs. 6.6 per 100,000 (adjusted to the world standard population). Results obtained by descriptive epidemiologic methods support the opinion that a major part of the positive changes in the lung cancer epidemic in Finland can be explained as a consequence of the comprehensive smoking control program introduced in this country, including a significant decline in tar yield of cigarettes. In view of a long latency period between exposure and the development of disease, a continuing upward trend in lung cancer mortality is to be expected in the Czech Republic, particularly in females, resulting in an increase in the gap between Czech and Finnish lung cancer mortality. To achieve in future a falling trend in lung cancer rates even in the Czech Republic, amendments in the smoking control system according to the recommendations of the World Health Organization and International Union against Cancer are of importance.

[Evaluation of epidemiologic studies using the EPI INFO program]. / Vyhodnocování epidemiologických studií programovým systémem EPI INFO.

The authors describe the EPI INFO system suitable for introducing on a personal computer, compatible with the standard IBM XT/AT. The system was elaborated by a group of workers from Centres of Disease Control in Alabama in 1988. The advantage of the system is in addition to ready availability (it is distributed on a non-commercial basis), in particular because it combines the advantages of the data base and statistical programme system. It makes it possible storage of data, their easy processing by classification and tabulation, evaluation by some statistical (parametric and non-parametric) tests and simple graphical presentation of results, e.g. in histograms or figures using columns. Moreover, it is possible to make in the EPI INFO system further modifications of the stored data and to combine groups of similar or different format. The system does not only create its own external data groups but makes also possible their conversion into other systems and conversely is able to create from external groups of data its own groups of data.

[Adverse trends in the development of mortality in lung cancer in the Czech Republic]. / Nepríznivý vývoj úmrtnosti na plicní rakovinu v Ceské republice.

The mortality from malignant tumours of the respiratory system in men in the Czech Republik increased steeply during 1950-1967 from the initial value of 22.3 per 100,000 men to more than triple, while in women the values persisted during this period with minor accidental deviations at a level of cca 5.7 per 100,000 women (with standardization for the world population). During the subsequent 20-year period there was a rising trend in both sexes; in 1987 the value for men was 77.4 per 100,000, for women 9.1 per 100,000. The age-specific mortality from malignant tumours of the respiratory system had in none of the evaluated age groups of men and women a declining trend, while in the USA and in Great Britain in younger men and in the group of youngest women a decline is recorded. The cigarette consumption in the Czech Republic after the Second World War increased steeply to the end of the sixties; in 1971-1987 it did not rise further and varied mostly within the range of 19 and 20 billion cigarettes per year, i. e. 2500 cigarettes per inhabitant above 15 years of age, regardless whether he smoked or not. To change the hitherto adverse development of mortality from malignant tumours of the respiratory system it is essential to reduce in the first place the intoxication of the population with carcinogens of tobacco smoke, by influencing smoking habits and by reducing carcinogenic substances in cigarettes and by some modifications of the working and living environment, by provision of an optimal content of probably protective substances in foods and some other measures.