Альманах клинической медицины. 2018; 46: 445-463
Социально-демографическая характеристика, особенности течения и варианты лечения воспалительных заболеваний кишечника в России. Результаты двух многоцентровых исследований
https://doi.org/10.18786/2072-0505-2018-46-5-445-463Аннотация
Актуальность. Эпидемиологические исследования, проводимые в разных странах, выявили ряд закономерностей, позволяющих прогнозировать проблемы, связанные с распространением воспалительных заболеваний кишечника (ВЗК), их тяжестью, затратами здравоохранения. Цель – представить сравнительные результаты двух первых крупных эпидемиологических исследований ВЗК в Российской Федерации (РФ): ESCApе и ESCApе-2. Материал и методы. Два многоцентровых наблюдательных поперечных (одномоментных) когортных исследования проводились по сходному дизайну с интервалом в 3 года. Цель исследований была общая: определить социально-демографические и клинические особенности течения язвенного колита (ЯК) и болезни Крона (БК) в РФ, а также варианты лечебной тактики. В исследовании ESCApе (2010–2011) участвовали 20 гастроэнтерологических центров из 17 регионов РФ, в ESCApе-2 (2013–2014) – 8 центров из 7 регионов РФ. Результаты. В исследование ESCApе были включены 1797 больных (1254 с ЯК и 543 с БК), в ESCApе-2 – 1000 больных (667 с ЯК и 333 с БК). Демографическая и социальная характеристика больных. В обоих исследованиях получено примерно равное соотношение мужчин и женщин как при ЯК, так и при БК. Возрастные характеристики больных также практически совпадали: для ЯК медиана составила 38 лет в ESCApе и 40 лет в ESCApе-2, для БК – 36 и 35 лет соответственно. В ESCApе основной пик начала ЯК приходился на возраст от 21 до 40 лет, а при БК он сдвигался к более молодому возрасту (22,5% заболели до 20 лет) и отмечен в трех возрастных группах (до 20 лет, 21–30 и 31–40). Статистически значимые различия между БК и ЯК были только в возрастном интервале 11–20 лет (22,5 против 13,6%, p < 0,01). В ESCApе-2 медиана начала заболевания для ЯК и для БК составила около 30 лет. В обоих исследованиях соотношение больных ВЗК – городских и сельских жителей – равнялось 4:1. В ESCApе доля курящих при БК была почти вдвое выше, чем при ЯК (15,6 и 8,8% соответственно, p < 0,001), аналогичная тенденция отмечена и в ESCApе-2 (15 и 7,3%, p < 0,001). Социально-экономическая характеристика больных в обоих исследованиях была сходной: от 50 до 60% составили работающие пациенты (род занятий и уровень дохода не изучались), инвалидность по разным причинам имели 30,9% больных ЯК и 40,9% больных БК (в том числе инвалидность по основному заболеванию 12,6 и 14,9% соответственно) в ESCApе и 35,7 и 51,1% в ESCApе-2. Клиническая характеристика больных. Сроки установления диагноза от начала первых симптомов ЯК в обоих исследованиях совпали: в ESCApе медиана была 5 месяцев, в ESCApе-2 – 4 месяца. При БК эти показатели значительно различались – 12 против 1 месяца. По тяжести течения заболевания больные в ESCApе распределились следующим образом: легкий ЯК отмечен у 16%, средней тяжести – у 53%, тяжелый – у 31%, при БК – у 21, 44 и 35% соответственно. В ESCApе-2 больные с тяжелыми формами не были представлены, частота легкого и среднетяжелого ЯК составила 51,3 и 46,6% соответственно, БК – 52,3 и 47,3%. При анализе протяженности поражения при ЯК частота левосторонних форм была сопоставима (38% в ESCApе и 34% в ESCApе-2), в первом исследовании чаще отмечены проктиты (33 против 11%, p < 0,01), а во втором чаще встречался тотальный ЯК (29 против 55%, p < 0,02). По частоте основных локализаций БК статистически значимых различий между ESCApе и ESCApе-2 не установлено: терминальный илеит был у 31,3 и 35,4% больных соответственно, илеоколит – у 33,4 и 37,8%, колит – у 25,6 и 32,1%. В ESCApе частота поражения верхних отделов желудочно-кишечного тракта составила 4,4%, смешанного поражения – 5,3%. В обоих исследованиях внекишечные системные проявления чаще регистрировали при БК, чем при ЯК: в ESCApе в 33,1 и 23% соответственно (р < 0,05), в ESCApе-2 – в 41,7 и 29,4% (р < 0,05). Среди внекишечных проявлений преобладали периферические артропатии. Анкилозирующий спондилит встречался только при БК, первичный склерозирующий холангит – только при ЯК. Частота афтозного стоматита была статистически значимо выше при БК в обоих исследованиях. Для других внекишечных проявлений (поражение глаз, кожи) статистически значимых различий не отмечено. Характеристика лечения. Анализировали варианты лечения перед включением в исследование, а также терапию, назначенную больным на визите при включении в исследование. Оказалось, что в ESCApе большая часть пациентов перед включением в исследование вообще не получала никакой терапии: 49,1% при ЯК и 40,5% при БК. Через 3 года ситуация изменилась: в ESCApе-2 доля нелеченых больных снизилась в 2,5–3 раза (до 15,3% при ЯК и 14,4% при БК), что, вероятнее всего, стало следствием повышения образовательного уровня врачей. Основная масса пациентов до включения в оба исследования получала препараты 5-аминосалициловой кислоты (5-АСК) – от 40 до 70%. Перед включением во второе исследование больные чаще получали глюкокортикостероиды (ГКС), иммуносупрессоры (ИС) и генно-инженерные биологические препараты (ГИБП), но значимых отличий от первого исследования не было. Среди препаратов, которые назначали на визите при включении в оба исследования, также преобладала 5-АСК (ее получали 80–90% больных ЯК и около 70% больных БК). В ESCApе-2 по сравнению с ESCApе отмечена тенденция к снижению частоты использования ГКС при ЯК и БК, но различия не были статистически значимы. Возможно, это связано с отсутствием тяжелых форм ВЗК в ESCApе-2. В ESCApе ИС использовали редко: у 14,4% больных ЯК и у 26,8% пациентов с БК, однако в ESCApе-2 частота их назначения увеличилась: до 35,9% при ЯК и до 55,1% при БК (р < 0,01 в обоих случаях). Как назначались ИС – в виде монотерапии или в комбинации с ГКС – неизвестно. Через 3 года частота назначения ГИБП также увеличилась, но статистически значимо только при БК: 28,3% в ESCApе-2 против 9,2% в ESCApе (р < 0,01). По данным ESCApе, стероидорезистентность при ЯК развивалась в 23%, а стероидозависимость – в 21% случаев, при БК – в 24 и 27% соответственно. В ESCApе-2 этот показатель не изучался. Заключение. В обоих исследованиях отмечен ряд закономерностей, совпадающих с мировыми тенденциями: половозрастной состав больных ЯК и БК, возраст начала заболевания, соотношение городских и сельских жителей, статус курения, частота и характер внекишечных проявлений. В РФ в отличие от европейских стран преобладают среднетяжелые и тяжелые формы ЯК со значительной протяженностью поражения. Низкую частоту легких и ограниченных форм ВЗК можно объяснить недостаточной диагностикой. Отмечена высокая доля больных, получающих 5-АСК, как при ЯК, так и при БК, несмотря на то что при БК эта группа препаратов демонстрирует низкую эффективность. Частота назначения ИС и ГИБП статистически значимо увеличилась во втором исследовании, вероятнее всего, благодаря системе образовательных мероприятий. Вместе с тем частота назначения ГИБП при ВЗК остается низкой, что, по-видимому, обусловлено недостаточной доступностью этой группы препаратов. Частота стероидорезистентности / стероидозависимости в сумме составляет практически половину случаев как при ЯК, так и при БК. В целом можно говорить о некоторых положительных сдвигах в лечении больных во втором исследовании по сравнению с первым, но проследить динамику изменений можно только при условии проведения аналогичных исследований с определенной периодичностью.
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Almanac of Clinical Medicine. 2018; 46: 445-463
Social and demographic characteristics, features of disease course and treatment options of inflammatory bowel disease in Russia: results of two multicenter studies
https://doi.org/10.18786/2072-0505-2018-46-5-445-463Abstract
Background: Epidemiological studies performed in different countries have identified a number of trends that allow to predict the problems related to the prevalence of inflammatory bowel diseases (IBD), their severity and healthcare resources utilization. Aim: To present comparative results of two large epidemiological studies of IBD in the Russian Federation (RF), i.e. ESCApe and ESCApe-2. Materials and methods: Two multicenter cross-sectional cohort studies with a similar design were performed at three-year interval. The studies had the common aim: to identify social and demographic and clinical particulars of ulcerative colitis (UC) and Crohn’s disease (CD) in RF, as well as treatment options. Twenty (20) centers of gastroenterology from 17 RF regions participated in the ESCApe (2010–2011) and 8 centers from 7 RF regions in the ESCApe-2 study (2013–2014). Results: The ESCApe study included 1797 patients (1254 UC and 543 CD), whereas the ESCApe-2 included 1000 patients (667 UC and 333 CD). Patient demographic and social characteristics: In both studies, female: male ratio was similar in UC and CD. Patients’ age was almost identical: in UC, median age was 38 years and 40 years in ESCApe and ESCApe-2, respectively; in CD the corresponding values were 36 and 35 years. In ESCApe, the peak UC onset was at the age of 21 to 40 years, whereas in CD it was shifted towards younger age (22.5% of the patients manifested before 20 years) and the peak incidence was in three age groups (below 20 years, 21 to 30 and 31 to 40 years). A statistically significant difference between CD and UC was found only in the age group of 11 to 20 years (22.5% vs. 13.6%, respectively, p < 0.01). In ESCApe-2, median age of disease onset in UC and CD was approximately 30 years. In both studies, urban:rural ratio for UC and CD was 4:1. In ESCApe, the proportion of current smokers among CD patients was almost two-fold higher than among those with UC (15.6 and 8.8%, respectively, p < 0.001); the same trend was found in ESCApe-2 (15 and 7.3%, p < 0.001). Socioeconomic characteristics of patients in both studies were similar: 50 to 60% were at work (professional occupation and income levels were not studied); in ESCApe 30.9% of UC patients and 40.9% of CD patients had legal disability due to various reasons (including that related to UC and CD in 12,6 and 14.9%, respectively), whereas in ESCApe-2 the respective proportions were 35.7 and 51.1%. Clinical characteristics of patients: The time from the first UC symptoms to diagnosis was similar in both studies (median, 5 months in ESCApe and 4 months in ESCApe-2); in CD patients these parameters were significantly different in both studies (12 vs. 1 month). As for the severity of the disease, the UC patients in ESCApe had mild disease in 16%, moderate in 53%, and severe in 31%, whereas the respective proportions among the CD patients were 21, 44, and 35%. In ESCApe-2, there were no patients with severe disease; mild and moderate UC were diagnosed in 51.3 and 46.6% of the patients, respectively, and mild and moderate CD, in 52.3 and 47.3%. The frequency of left-side UC was similar: 38% in ESCApе and 34% in ESCApе-2. Proctitis was more frequent in the first study (33 vs. 11%, p < 0.01), and total UC was more frequent in the second study (29 vs. 55%, p < 0.02). There were no significant differences between ESCApe and ESCApe-2 in the main CD localizations: terminal ileitis was seen in 31.3 and 35.4% of the patients, respectively, ileocolitis in 33.4 and 37.8%, colitis in 25.6 and 32.1%. The upper gastrointestinal involvement In ESCApе was found 4.4%, and mixed involvement in 5.3%. In both studies, extra-intestinal manifestations were more frequent in CD, than in UC: in ESCApe, 33.1% and 23% (р < 0.05), and in ESCApe-2 in 41.7 and 29.4%, respectively (р < 0.05). Peripheral arthropathies were most frequent. Ankylosing spondylitis was found in CD only, and primary sclerosing cholangitis, only in UC. Aphthous stomatitis was significantly more prevalent in CD in both studies. There were no significant differences in all other extra-intestinal symptoms (eye and skin involvement). Treatment characteristics: Treatment options before the study entry, as well as at the study inclusion visit were analyzed. In ESCApe, the majority of the patients had not been given any treatment before the study entry (49.1% with UC and 40.5% with CD). Three years later the situation was changing: in ESCApe-2, the proportion of treatment-naïve patients was 2.5 to 3-fold lower (15.3% with UC and 14.4% with CD), which was most probably related to increasing awareness of physicians. Before the study entry, most patients (40 to 70%) had been treated with 5-aminosalicylic acid (5-ASA). Before the second study, the patients were more frequently treated with glucocorticosteroids (GCS), immunosuppressors and genetically engineered biological agents (GEBA), but with no significant differences from the first study. 5-ASA prevailed also among the agents that were administered during the inclusion visits in both studies (80 to 90% UC patients and about 70% of CD patients). Compared to ESCApe, in ESCApe-2 there was a trend towards lower rate of GCS administration in UC and CD, but the differences did not reach the significance level. It may be explained by the absence of severe IBD types in ESCApe-2. In ESCApe, immunosuppressors were rarely used (in 14.4% of the UC patients and in 26.8% of the CD patients); however, in ESCApe-2 there were administered more frequently: up to 35.9% of the UC patients and 55.1% of the CD patients (р < 0.01 for both cases). It was unknown if immunosuppressors were used as monotherapy or in combination with GCS. Three years later, the rate of GEBA administration was also higher, but this increase was significant only in CD: 28.3% in ESCApe-2 vs. 9.2% in ESCApe (р < 0.01). According to the results of ESCApe, in the UC patients steroid resistance was seen in 23% and steroid dependency in 21%, whereas in the CD patients these values were 24 and 27%, respectively. In ESCApe-2 these parameters were not assessed. Conclusion: Both studies showed a number of patterns coinciding with the world trends, such as age and gender distribution of UC and CD patients, age at manifestation, the proportion of urban to rural residents, smoking status, prevalence and types of extra-intestinal symptoms. Unlike in European countries, moderate and severe forms of UC with extensive involvement are prevalent in RF. Low prevalence of mild and limited types of IBD is to be explained by underdiagnosis. Of note is the high proportion of patients with UC and CD treated with 5-ASA, although in CD these agents have demonstrated low efficacy. The rates of immunosuppressors and GEBA administration significantly increased in the second study, most likely, due to the implementation of a system of educational measures. Nevertheless, the rate of GEBA use in IBD remains low, which is to be related to their insufficient availability. In total, steroid resistance / steroid dependency rate amount to almost half of UC and CD cases. In general, some positive changes in the patient management are obvious in the second study. However, monitoring these changes over time could only be possible if similar studies would be performed at regular intervals.
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