Scheme of drug therapy for nonspecific ulcerative colitis in children. IBD: Ulcerative colitis. What the patient needs to know

For citation: Khalif I.L. Surgical treatment and biological therapy for ulcerative colitis // RMJ. 2013. No. 31. S. 1632

Introduction Ulcerative colitis (UC) is an autoimmune disease characterized by prolonged inflammation of the mucous membrane of the rectum and colon. UC is characterized by episodic exacerbations with symptoms characterized by frequent liquid stools mixed with blood in combination with imperative urges and tenesmus. Disease activity can vary from complete remission to a fulminant form with systemic toxic manifestations. Although the exact pathogenesis of UC is not yet well understood, the best-described theory is that the gut flora triggers an aberrant gut immune response and subsequent inflammation in genetically predisposed individuals.

Ulcerative colitis (UC) is an autoimmune disease characterized by prolonged inflammation of the mucous membrane of the rectum and colon. UC is characterized by episodic exacerbations with symptoms characterized by frequent liquid stools mixed with blood in combination with imperative urges and tenesmus. Disease activity can vary from complete remission to a fulminant form with systemic toxic manifestations. Although the exact pathogenesis of UC is not yet well understood, the best-described theory is that the gut flora triggers an aberrant gut immune response and subsequent inflammation in genetically predisposed individuals.
Medical treatment of UC is aimed at controlling symptoms and resolving the underlying inflammatory process. Traditional treatments for UC include drugs such as 5-aminosalicylates (5-ASA), corticosteroids and immunosuppressants, incl. purine and cyclosporine antimetabolites. Treatment regimens are selected taking into account the severity of UC, which is defined as mild, moderate or severe based on clinical and laboratory parameters, and the prevalence of the disease (total, left-sided colitis, proctitis or proctosigmoiditis).
Principles of therapy
The main objectives of drug therapy for UC are the induction of remission and its maintenance for a long period. Drug therapy reduces the risk of long-term complications and improves the quality of life of patients by reducing the number of relapses, which occur in 67% of patients at least once every 10 years.
However, about 20% of patients with UC have chronic active disease, often requiring multiple courses of systemic steroids, with subsequent recurrence of symptoms with steroid dose reduction or shortly after steroid withdrawal. Such patients are considered steroid dependent. Steroid dependence is associated with serious complications, which for a significant part of patients become an indication for surgery.
Since 2005, drug therapy for UC has entered the era of biologics with the FDA approval of infliximab, a monoclonal antibody directed against tumor necrosis factor-α (TNF-α). Biologics have revolutionized the treatment of patients with UC and made it possible to control the disease in patients with intolerance and/or ineffectiveness of conventional therapy. Currently, 2 biological drugs for the treatment of UC are registered in Russia: infliximab and golimumab.
Infliximab, which is an antibody to TNF-α, reduces the signs and symptoms of the disease, induces clinical remission and healing of the intestinal mucosa, facilitates the cessation of corticosteroid use in patients with moderate to severe active UC who have not achieved an adequate response to corticosteroid therapy or immunomodulators or there is intolerance, or medical contraindications to therapy.
The first controlled trial of this drug in patients with UC included patients with moderate to severe UC. This study described a high rate of response to treatment, but the follow-up period was short. In the active UC trials (ACT I and ACT II), 364 patients with moderate to severe UC and treatment failure (but not requiring hospitalization) were randomized to either placebo or infliximab. Both doses of infliximab (5 mg/kg and 10 mg/kg) resulted in a significant clinical response at 8 weeks. (68.4 and 61.5%, respectively, compared with 37.2% in the placebo group (p<0,01) в АСТ I, и 64,5 и 69,2% соответственно по сравнению с 29,3% в группе плацебо (р <0,001) АСТ II). Частота клинической ремиссии в обеих группах инфликсимаба на 8 нед. колебалась от 27,5 до 38,8% в обоих исследованиях по сравнению с частотой плацебо-индуцированной ремиссии 14,9% (ACT I) и 5,7% (АСТ II). Частота заживления слизистой оболочки и бесстероидной ремиссии была также выше в обеих группах инфликсимаба в этих исследованиях. W.J. Sandborn et al. описали частоту колэктомий в наблюдательных исследованиях АСТ I и АСТ II . Общая частота колэктомий на 54 нед. составила 10% у пациентов, получавших инфликсимаб, по сравнению с 17% у пациентов, получавших плацебо. Исследования ACT I и АСТ II предоставили важные данные в поддержку использования инфликсимаба у пациентов со среднетяжелым и тяжелым ЯК, которые не ответили на другие методы терапевтического лечения, такие как стероиды, иммуномодуляторы и месалазин .
In a recent study by J.F. Colombel et al. studied the association between early mucosal healing (defined as Mayo endoscopy index at 8 weeks endoscopy) and clinical outcomes in patients in ACT I and ACT II. The authors note that a low endoscopic index at 8 weeks. was statistically significantly associated with a lower rate of colectomy at 54 weeks. observation (p = 0.0004; placebo p = 0.47) and better outcomes in terms of symptoms and steroid requirements at weeks 30 and 54 (p<0,0001 инфликсимаб, р<0,01 плацебо), особенно для тех пациентов, которые не достигли клинической ремиссии через 8 нед.
The recently published PURSUIT, a randomized, double-blind, placebo-controlled study, reported the results of a phase 2 and 3 clinical trial of a new drug, golimumab. Golimumab is an anti-TNF-α antibody and is a fully human antibody intended for subcutaneous administration (unlike infliximab, which is administered intravenously). The drug has previously been registered for the treatment of rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis. Since 2013, it has also been registered in Russia, Europe, and the United States for the treatment of UC.
The study included patients with moderate to severe forms of UC (Mayo index from 6 to 12, endoscopic index ≥2) with various duration of the disease, who had no response, there was an insufficient response or an escape response when using 5-ASA drugs, oral corticosteroids, azathioprine, 6-mercaptopurine or steroid dependence.
The 2nd phase of the clinical trial included 169 patients who were randomized into 4 groups: one received a placebo, the rest received the drug in various dosages: 100/50 mg, 200/100 mg, 400/200 mg. An additional group (122 patients) was included in the study for safety evaluation and pharmacokinetic analysis. At the conclusion of this phase of the study, 200/100 mg and 400/200 mg were selected as the prescribed doses. The 3rd phase included 744 patients who were randomized into 3 groups: placebo, 400/200 mg and 200/100 mg of the drug for 0 and 2 weeks. All 1064 patients entered the maintenance study with golimumab for 54 weeks.
The study showed that for 2 weeks. in the golimumab groups, there was a decrease in the level of C-reactive protein, while in the placebo group it rose (-6.53 mg/l, -6.70 mg/l and +1.3 mg/l, respectively). The clinical response in the golimumab groups was significantly higher than in the placebo group (51.8% - at a dose of 200/100 mg, 55.5% - at a dose of 400/200, 29.7% - in the placebo group, p<0,0001). Эффективность обеих доз была также показана и для других параметров оценки: клинической ремиссии, заживления слизистой и улучшения показателей по опроснику качества жизни Inflammatory Bowel Disease Questionnaire (IBDQ). В то же время статистически значимых различий эффективности между двумя группами голимумаба выявлено не было.
In the golimumab maintenance study, patients who responded to an induction course were randomized into 3 groups: placebo, 100 mg bid/4 weeks. and 50 mg 1 r. / 4 weeks. Patients who did not respond to the induction course or responded to placebo were included in the study but were not randomized. Patients who responded to placebo received placebo, the rest received a dose of 100 mg until evaluation at 12 weeks. If the condition did not improve by 16 weeks, patients were excluded from the study. Patients who relapsed during the study were excluded from the study based on the results of sigmoidoscopy if the endoscopic Mayo index increased by 2 or more.
The study showed that a clinical response lasting up to 54 weeks was observed in 49.7 and 47% of patients treated with golimumab 100 and 50 mg, respectively, and 31.2% in the placebo group (p<0,001 и р=0,01 соответственно). Клиническая ремиссия на 30 и 54 нед. наблюдалась у 27,8% пациентов, получавших 100 мг, по сравнению с 15,6% пациентов в группе плацебо (р=0,04). В группе пациентов, получавших 50 мг, полученные данные выше, чем аналогичные в группе плацебо, однако различия статистически не значимы (23,2 и 15,6% соответственно). Заживление слизистой оболочки наблюдалось у 42,4% пациентов в группе голимумаба 100 мг по сравнению с 26,6% в группе плацебо (р=0,002) на 30 и 54 нед. В группе голимумаба 50 мг частота заживления слизистой составила 41,7%. Ремиссии к концу исследования достигли 38,9% пациентов, получавших 100 мг, и 36,5% пациентов, получавших 50 мг, по сравнению с группой плацебо (24,1%). 54% пациентов получали кортикостероиды на начальном этапе исследования. Из них бесстероидной ремиссии к 54 нед. достигли 23,2% пациентов, получавших голимумаб 100 мг, 28,2% - 50 мг, 18,4% - плацебо.
With advances in the development of new targeted drugs, most patients with localized and advanced UC can be controlled with medical treatment, but 20-30% of patients still require surgery at some point in their lives.
The evolution of the surgical treatment of UC has improved the quality of life of patients requiring colectomy. Until the early 1980s. Colproctectomy with ileostomy was the "gold standard" of surgical treatment, despite the occasional use of ileorectal anastomosis. The permanent Kok ileostomy was proposed in the 1960s, but has not been universally adopted, despite a well-documented improvement in quality of life compared to quality of life after coproctectomy with conventional ileostomy. Over the past 20 years, reconstructive-plastic colproctectomy with ileo-anal reservoir anastomosis (IARA) has become the new "gold standard".
The incidence of colectomy in UC varies across populations and over time. E. Langholz et al. published in 1994 that 25% of UC patients required colectomy within 10 years of diagnosis. A study of the American population of patients with UC showed that the incidence of colectomy did not change over the past 10 years, although it did not take into account the relationship between the use of immunomodulators and surgical treatment. In addition, many of the data were published before the advent of studies on the efficacy of infliximab in inducing and maintaining remission in UC. In addition, previous studies of the incidence of colectomy did not take into account the indications for surgical treatment.
A large retrospective study conducted in Canada aimed to compare the rates of emergency and elective colectomy between 1997 and 2009. The study included adult patients hospitalized for exacerbation of UC. 437 patients underwent colectomy, 338 patients did not require surgical treatment. Of all patients who underwent colectomy, in 53.1% of cases it was performed for emergency indications. The authors provide data that from 1997 to 2009, the performance of colectomy for UC decreased significantly (p<0,01) - с 5,4 до 2,3 на 100 тыс. пациенто-лет. За 13-летний период частота колэктомий существенно снизилась среди пациентов, которым она проводится в плановом порядке (в среднем на 7,4%), однако она остается одинаковой у пациентов с показаниями для экстренной операции. В этот период доля пациентов, госпитализированных с обострением ЯК и получавших терапию салицилатами и стероидами, оставалась стабильной, увеличивалось назначение азатиоприна и 6-меркаптопурина. С 2005 по 2009 г. увеличивалось назначение инфликсимаба. Общее снижение вероятности колэктомии составило 13% у пациентов, ответивших на консервативную терапию, по сравнению с теми, которым потребовалась колэктомия. Таким образом, авторы делают вывод о том, что снижение частоты колэктомий у пациентов с ЯК происходит за счет снижения частоты плановых операций, а это в свою очередь связано с более частым назначением иммуносупрессивной и биологической терапии .
Over the past 20 years, the new “gold standard” has become reconstructive-plastic colproctectomy with IARA, which was first described by A.G. Parks and R.G. Nichols in 1978. This procedure avoids a permanent stoma and maintains a natural bowel movement. The introduction of this technique, most often with the formation of a J-shaped reservoir, was a real breakthrough: such patients receive radical treatment without the need for a permanent stoma, which allows them to achieve a quality of life comparable to that in the general population. However, this procedure is technically difficult, recurrence of the disease is observed with a frequency of about 30%, the frequency of postoperative pelvic sepsis is in the range from 5 to 24%. Total colectomy with ileostomy can be considered the operation of choice at the first stage of the reconstructive operation, because. it is fairly safe and can be performed quickly by an experienced colorectal surgeon, allowing the patient to get rid of the colitis, stop taking the drugs, and return to optimal health.
Removal of the rectum and restoration of intestinal continuity with IARA is performed in the second stage when the patient is fully recovered, and removal of the temporary ileostomy may further reduce the risk of local sepsis secondary to anastomotic leak. In addition, the use of minimally invasive techniques can further reduce postoperative complications and improve patient satisfaction.
Although for all patients with UC, removal of the colon and rectum represents a definitive cure for the disease with resolution of symptoms, discontinuation of drug therapy, and no risk of malignancy associated with persistent inflammation, surgery is not without risk and can significantly affect the patient's quality of life, therefore traditionally considered a method of rescue when medical therapy is ineffective.
Complications of treatment
Treatment with anti-TNF drugs is relatively safe when used as directed. Adverse events (AEs) with the use of infliximab in the AST studies did not differ from the expected AEs, which are known from the experience in the treatment of Crohn's disease (CD). Similarly, no new AEs have been identified in studies with golimumab. However, as with other biological therapies, there is a risk of severe infections, demyelinating disease, and associated death. In a pooled analysis of 484 patients with UC who received infliximab in the ACT trials, 3.5% (17/484) of patients developed these complications.
In addition, despite the high efficacy of biological therapy in the treatment of UC, escalating conservative treatment until surgery is strictly necessary can be risky. Mortality within 3 years after elective colectomy for UC (3.7%) was shown to be significantly lower than after treatment without surgery (13.6%) or in case of emergency surgery (13.2%). In addition, a recent British study showed a significantly higher risk of serious complications during 5 years of follow-up in patients who received a longer course of medical therapy for acute severe UC attack before surgery, although it was assumed that the risks of elective surgery may be too high in current practice. .
In a study conducted at the State Scientific Center of Coloproctology, predictors of the effectiveness of conservative therapy were evaluated, and it was shown that the detection of deep ulcerative defects during colonoscopy before the start of biological therapy predicts the ineffectiveness of its continuation with a 78% probability. If it is not possible to achieve clinical remission after the second course of therapy, in such patients its continuation is not justified. The absence of clinical remission by the third course of therapy predicts the ineffectiveness of further therapy with 68% accuracy.
Surgical treatment of UC, despite the complete relief of the patient from the disease due to the removal of the inflammatory substrate - the colon, is also still associated with significant early and late postoperative complications, even taking into account the intensive development of surgical methods. For example, with anastomotic failure, pelvic sepsis, intestinal obstruction, inflammation of the reservoir, sexual dysfunction, decreased fertility in women. Sometimes repeated operations are necessary. A population-based study has shown that approximately 20% of patients undergoing IARA surgery require at least 1 additional operation, and 15% require at least 2 additional operations. Reservoir failure and the associated incidence of pelvic sepsis in a large series of patients is 5-15%; the frequency of late resections of the small intestine after IARA ranges from 12 to 35%. Reservoir is the most common delayed complication of IARA. Finally, the risk of delayed pouch failure has been described in various studies as ranging from 1% to 20%, with an overall incidence of pouch failure of less than 10% requiring ileostomy, pouch excision, and terminal ileostomy or pouch revision.
Colproctectomy with the formation of IARA has the most pronounced negative effect on fertility in women. In a Danish study of 290 UC patients and 661 healthy women, colectomy was shown to reduce fertility by 80% (p<0,0001) . P. Johnson et al. в своем исследовании приводят аналогичные данные . Уровень бесплодия у пациенток после ИАРА значительно выше, чем у тех, кому не проводилось хирургическое лечение (38,1% vs 13,3%, р<0,001). Разницы между уровнем фертильности до и после постановки диагноза выявлено не было (р=0,23). Напротив, снижение уровня фертильности после хирургического лечения по сравнению с таковым до него составило 98% (р<0,0001). Сходные результаты получены по вынашиванию беременности в исследовании 1454 пациенток в США .
Although reconstructive surgery does not rule out long-term complications such as urinary incontinence (10-60% of patients), pouchitis (about 50%), and sexual dysfunction (20-25%), and the incidence of pouch leaks requiring removal occurs in 5-15% of cases, most of these complications can be resolved with medical therapy, which explains the overall satisfaction in patients after IARA, which exceeds 90% in most cases.
A number of quality-of-life studies in patients with IARA show that the average level of quality of life in these patients is comparable to that in the general population. On the other hand, when assessing long-term outcomes within 10 years after IARA, 12.6% have anastomotic leaks. The frequency of a normally functioning reservoir after 5, 10 and 15 years was 92.3, 88.7 and 84.5%, respectively. The average GIQLI (Gastrointestinal Quality of Life Index) is 107.8, which is 10.8% lower than in the healthy population. A statistically significant negative correlation was found between quality of life and age over 50 years, pouchitis, perianal inflammation, and increased stool frequency (p<0,0001) .
Although surgery cures inflammation and reconstructive coloproctectomy with IARA maintains a normal anatomic passage for defecation, this intervention may lead to new symptoms such as diarrhea, nocturnal defecation, and in some patients does not eliminate the need for treatment. In several surgical groups of patients who were followed up for at least 5 years, up to 60% of them had stools more than 8 times a day, 55% of patients noted incontinence, 50% had nocturnal bowel movements. In addition to the fact that many patients have at least one nocturnal bowel movement, 30-40% of patients are forced to control food intake in order to avoid the urge to defecate.
A number of studies have shown that quality of life is directly related to functional outcomes. J.C. Coffey et al. found that, according to the Cleveland Quality of Life Index, the indicators differ in different groups of patients. 95.3% of patients are forced to adhere to restrictions and diet. All of these patients felt that such restrictions affected their quality of life. Late meals and drinking lead to diarrhea. The indicator of this index was higher in patients with UC compared with patients with familial adenomatosis (0.84 and 0.78, p=0.042). And this is primarily due to the fact that the frequency of stool in these patients before surgery was almost always lower than after it. In patients who became pregnant after IARA, the quality of life was also lower (0.7, p = 0.039) than in patients with UC, although the function of the reservoir was similar to that in other patients. I. Berndtsson and T. Oresland describe an improvement in the quality of life of patients after IARA, however, among the factors that reduce it, indicate the frequency of nocturnal defecation (40%), perianal manifestations (51%) and the use of antidiarrheal drugs (61%). In the German Quality of Life Study after IARA, the main patient complaints were fatigue and arthralgia compared with the general population (p<0,01). В исследовании было показано, что на общий индекс IBDQ влияет число операций по поводу осложнений, связанных с ИАРА, индекс госпитальной тревоги и депрессии ≥11. На IBDQB (Inflammatory Bowel Disease Questionnaire Bowel) влияет индекс PDAI (Pouch Disease Activity Score) ≥7, а на IBDQS (Inflammatory Bowel Disease Questionnaire Systemic) - число внекишечных проявлений .
A US study assessed the risk of depression in patients with CD and UC after colectomy surgery. The study included 707 patients with CD and 530 with UC who underwent colectomy and had no signs of depression prior to surgery. The risk of developing depression within 5 years was detected in 16% of patients with CD and 11% with UC. There was no difference in the incidence of depression depending on the disease. Female gender, comorbidities, use of immunosuppressants, perianal manifestations, presence of a stoma, and early surgery within the first 3 years after diagnosis are risk factors for depression in patients with CD; female gender and comorbidities - in patients with UC.
At the same time, in another study from Canada, which compared 2 groups of children with UC (operated and non-operated), it was shown that the quality of life according to the IMPACT III and IBDQ questionnaires in operated patients is comparable to that of non-operated ones. Depression, fatigue, homeschooling, and drug use have been cited as contributing to quality of life.
Economic indicators
Due to the early onset and chronic nature of inflammatory bowel disease (IBD), patients can be expected to use significant healthcare resources. Cost analysis is complex because it is necessary to take into account the impact that therapy has on direct health care costs and indirect costs, both for patients and their families, and for the health care system. Surgery and hospitalizations account for the majority of the direct health care costs of IBD, on the other hand, treatment costs account for a quarter of the total direct medical costs. In addition, cost data are not uniform, as while 25% of patients account for 80% of total costs. It follows that the most effective cost-containment measure is one that reduces the number of hospitalizations and operations.
With improved response and remission using infliximab for induction and maintenance of patients with IBD, the clinical benefits are also likely to translate into cost benefits. The assessment of the economic component was carried out in a small study in the USA. S.D. Holubar et al. showed that 2-year health care costs were $10,328 for surgical UC patients and $6,586 for medical UC patients. Patients with ileostomies were more economically expensive than those with ileo-anal reservoirs. In a cohort of therapeutic patients, the extent of the disease, rather than the severity, is associated with high costs. However, in this study, drug treatment did not include biological therapy. Surprisingly, as a result of cost-benefit analysis, many researchers have suggested that the use of infliximab is associated with a fairly high increase in cost per quality of life per year. The expansion of infliximab use has not significantly affected the surgical management of patients with UC or CD, and the rate of non-surgical hospitalizations has actually increased. Further pharmacoeconomic analysis is needed to truly assess the impact of infliximab treatment on UC treatment costs.
Conclusion
Drug therapy for UC is rapidly developing, the introduction of modern biological preparations has led to significant changes in the traditional principles of patient management and to new opportunities for disease control. Infliximab and golimumab, anti-TNF-α antibodies with targeted immunosuppressive effects, can achieve clinical response, clinical remission, mucosal healing, and improved quality of life in patients with moderate to severe UC who cannot tolerate or are resistant to conventional therapy. In addition, infliximab, the first biological agent used in the treatment of UC, has been shown to significantly reduce the need for colectomy.
Surgery continues to play an important role in the treatment of UC, and its evolution has kept pace with advances in therapy. Reconstructive coproctectomy with IARA, stepwise interventions, and minimally invasive surgery are important treatment tools that can reduce postoperative complications and achieve excellent long-term outcomes in patients with UC.
Aggressive drug therapy is not without complications, while surgical treatment significantly affects the lifestyle of patients and in many cases reduces the quality of life. When choosing between modern methods of surgical and medical treatment, the doctor must ask himself the question: can he influence the course of the disease with the help of medication, and incl. biological therapy, does he have enough time and facilities for conservative therapy? It is important to understand that one should not deprive the patient of the chance to save the colon without using the possibilities of conservative therapy, but it is equally important to understand in a timely manner that the possibilities of drug treatment have been exhausted, and not to miss the moment when it is necessary to operate the patient in a timely manner, when the conditions for surgical intervention more favorable.

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Art. 402 gr. l.f. N.Sh. Sharov.

WIRS: « Treatment of nonspecific ulcerative colitis.

Patients with exacerbation of NUC are subject to hospitalization, preferably in a specialized gastroenterological or coloproctological department. Bed rest is indicated in moderate and severe forms of the disease. However, long-term bed rest is inappropriate and adversely affects the physical and mental state of patients.

Treatment of nonspecific ulcerative colitis includes the following components:

Diet therapy

Preparations of basic and auxiliary therapy

· Infusion therapy for the purpose of detoxification, correction of protein and water-electrolyte balance, vitamins.

Sedative drugs (small tranquilizers: Elenium, Seduxen)

Antidiarrheal therapy: anticholinergic drugs / contraindicated in glaucoma / (tinctures and extracts of belladonna, solutan, platyfillin), codeine, astringents of plant origin (decoctions of pomegranate peels, acorn bark, infusions of bird cherry fruits, blueberries, serpentine rhizomes, sulfur cones alder).

Surgical treatment - is indicated in the development of complications and the absence of the effect of conservative therapy.

Diet therapy. One of the main directions in the treatment of nonspecific ulcerative colitis is the correction of adequate nutrition and diet therapy. At the height of the disease, diet No. 4 or 4b is prescribed. During the subsidence of acute phenomena - diarrhea, abdominal pain - the patient is transferred to an unwashed diet. It should be emphasized that prolonged adherence to a strict diet does not contribute to the restoration of the metabolism and strength of the patient, which was disturbed due to the disease. It is necessary to strive for the dishes to be varied and tasty. Low-fat meats are recommended, boiled or steamed, eggs, pureed cereals, fried white bread, dry biscuits. Walnuts must be included in the diet. In the acute stage of the disease, decoctions of wild rose, blueberries, pears and other sweet and ripe berries and fruits, as well as some juices (orange, tomato) are recommended.

The principles of rational nutrition should exclude fried, fatty, salty, spicy dishes. Also, the diet of a sick child should not include chocolate, legumes, mushrooms, fruits and vegetables that stimulate peristalsis (plums, kiwi, dried apricots, beets). During the period of exacerbation, the amount of fiber, sweets, juices is limited. With prolonged remission, the diet can be significantly expanded, but milk and dairy products are contraindicated throughout life.

Many patients with ulcerative colitis have intolerance to various foods, especially often milk and dairy products, so eliminating them from the diet can help improve. In the acute stage of the disease, abundant food is not digested and absorbed enough, so food should be given in small portions, but often. With diarrhea, the intervals between meals should not exceed 2.5 hours. Dinner is recommended no later than 21 hours.

In nonspecific ulcerative colitis, protein metabolism is especially affected, since the absorption of proteins in the intestine is sharply disrupted, their increased decay occurs and losses with liquid feces increase. Metabolic disturbances increase especially rapidly during an acute severe attack of the disease. In such cases, prescribe food containing an increased amount of protein (130 - 150 g per day). During a severe attack of nonspecific ulcerative colitis, the amount of fluid consumed inside is also reduced, focusing on the nature of the stool. If they are very watery and plentiful, limit to 5 glasses of liquid per day. Along with the fact that the diet should be high in protein, it should also be low in residue, that is, not contain coarse fiber.

In the event of acute toxic dilatation of the colon, you should stop eating during the day and prescribe parenteral nutrition.

Medical therapy.

Treatment of almost all forms of UC (with the exception of those complicated by perforation, toxic dilation, profuse bleeding) begins with conservative methods. The goal of any therapeutic effect is to stop inflammation, achieve remission and maintain it for the longest possible time.
Salazopreparations (sulfasalazine, salazopyrin, salazodimethoxine), 5-aminosalicylic acid preparations (mesalazine and its analogues under trade names - salofalk, mesacol, pentasa, etc.) and corticosteroid hormones are widely used to treat ulcerative colitis. These drugs are basic for the treatment of NUC. Adjuvant therapies include immunosuppressants, leukotriene B4 inhibitors, anesthetics, mast cell stabilizers, immunoglobulins, reparants, cytoprotectors, antibacterials, antioxidants, and nicotine.

basic therapy. As a rule, treatment begins with the appointment sulfasalazine or preparations 5-ASA(with the exception of severe and common forms of UC).

In 1942, the drug sulfasalazine was first used in patients with combined lesions of the intestines and large joints, which gave a pronounced positive effect: relief of arthralgia and hemocolitis. Sulfasalazine has been used in the treatment of non-specific ulcerative colitis to date. However, its use has been limited by a large number of side effects such as hemolytic anemia, neutropenia, drug-induced hepatitis, Stevens-Johnson syndrome, pericarditis, interstitial nephritis, pancreatitis. The frequency of side effects according to different authors ranges from 5 to 55%. The composition of sulfasalazine includes mesalazine (5-aminosalicylic acid), which has an anti-inflammatory effect, and sulfapyridine, which ensures the delivery of mesalazine to the large intestine, to the site of localization of the main inflammatory process in ulcerative colitis. Sulfapyridine contributes to the development of a large number of side effects.

Numerous studies in the development of drugs containing mesalazine made it possible in the late 70s and early 80s to create drugs that do not contain sulfapyridine. This resulted in a significant reduction in side effects, which in turn allowed for higher doses of mesalazine and reduced the need for corticosteroids. Mesalazine is active in local contact with the intestinal mucosa and its therapeutic efficacy is correlated with the concentration in the intestinal lumen. These features of mesalazine made it possible to develop and successfully apply local therapy in the form of suppositories, microclysters both in the acute period and during maintenance therapy.

5-ASA preparations can be divided into 3 groups. The first group includes Sulfasalazine and Olsalazine, which are released under the action of the intestinal flora and act in the colon. The second group includes Mezakol, Salofalk, Rovaza. The release of these drugs depends on the pH of the medium and their action is localized in the terminal ileum and in the colon. The third group includes the drug Pentasa - which is released slowly and acts throughout the entire intestine:

The mechanism of action of 5-ASA preparations is based on the anti-inflammatory effect, which is realized through inhibition of the formation of prostaglandins, a decrease in the synthesis of cytokines: IL-1, IL-2, IL-6, tumor necrosis factor, inhibition of the lipoxygenase pathway of arachidonic acid metabolism, and a decrease in the production of free radicals.

Indications for the use of 5-ASA drugs: primary therapy for mild UC activity, primary therapy in combination with steroids for moderate and severe UC activity, maintenance therapy for UC

In our country, sulfasalazine, salofalk and pentasa are the most commonly used 5-ASA preparations. As noted earlier, sulfasalazine has been used in the treatment of UC for 60 years. The splitting of sulfasalazine into mesalazine and sulfapyridine depends on the composition of the intestinal flora and occurs only in the large intestine. With the localization of inflammation in the blind and ascending sections of the colon (in young children), the effectiveness of sulfasalazine is significantly reduced.

Salofalk - the active substance of this drug is mesalazine. The drug is a coated tablet, resistant to the action of gastric juice. Its feature is the absence of a sulfo component, which reduces the number of side effects. Activation of salofalk occurs when the acidity of the medium changes above 6. The place of action of salofalk is mainly in the terminal ileum and colon.

Pentasa - this drug has been introduced to the Russian market relatively recently. The active substance is also mesalazine, enclosed in microgranules that are resistant to the acidic environment of the stomach. Pentasa is released slowly, gradually along the intestine, starting from the duodenum. At the same time, changes in the level of intraluminal pH and acceleration of transit during diarrhea do not affect the release rate of the drug. Due to these features, Pentasa provides a high therapeutic concentration throughout the small and large intestine.

The modern medical field does not stand still and is constantly evolving. All this is required in order to simplify the treatment of various diseases, in particular, they include colitis. One of the most promising discoveries is monoclonal antibodies. They purposefully interact with inflammatory processes, providing the opportunity to obtain the maximum positive result.

The principle of treatment of colitis with monoclonal antibodies

Currently, monoclonal antibodies are used in the process of targeted therapy, due to the fact that the results of the study were the most positive with this treatment. Most often, this type of drug is used for colitis.

The principle of interaction of monoclonal antibodies is very simple: they recognize a certain kind of antigens and substances begin to attach to them. Thanks to this action, the immune system will quickly recognize the problem and begin to fight it. Simply put, such drugs provide an opportunity for the body to get rid of inflammatory processes on its own. Another advantage of these drugs for colitis is that they can only affect cells that have been pathologically altered, while healthy ones remain untouched.

Preparations with monoclonal antibodies against colitis

Regardless of the fact that monoclonal antibodies were invented not so long ago, the variety of medicines in which they are contained is very impressive. New drugs are being released all the time.

Currently, the most popular medications that contain monoclonal antibodies used for colitis are: Ustenkinumab, Alefacept, Trastuzumab, Clenoliximab, Ocreluzumab and others.

Undoubtedly, monoclonal antibodies, like a large number of other medications, have their own side effects. Mostly, patients who use this or that drug for colitis are treated with the appearance of allergic reactions, manifested in the form of itching and rash. Rarely observed accompaniment with nausea, gastrointestinal upset and vomiting.

In any case, before taking this or that medicine, you need to consult with the attending specialist, who will give you an appointment in accordance with the clinical picture for the use of the required medications.

Treatment of nonspecific ulcerative colitis depends on the localization of the pathological process in the intestine, its extent, the severity of attacks, the presence of local and systemic complications.

The main goals of conservative therapy:

• pain relief,
• prevention of disease recurrence
• prevention of the progression of the pathological process.

Ulcerative colitis of the distal intestines: proctitis and proctosigmoiditis are treated on an outpatient basis, as they have a milder course. Patients with total and left-sided lesions of the colon are shown to be treated in a hospital, since they have more pronounced clinical manifestations and there are large organic changes.

Nutrition of the sick

A diet for ulcerative colitis should spare the intestines, help increase its regenerative abilities, eliminate fermentation and putrefactive processes, and also regulate metabolism.

Sample menu for ulcerative colitis:

• Breakfast - rice or any other porridge with butter, steamed cutlet, tea;
• Second breakfast - about forty grams of boiled meat and berry jelly;
• Lunch - soup with meatballs, meat casserole, dried fruit compote;
• Dinner - mashed potatoes with fish cake, tea;
• Snack - baked apples.

Medical treatment

Treatment of ulcerative colitis of the intestine is carried out in three main directions:

• preventing or stopping internal bleeding;
• restoration of water-salt balance in the body;
• cessation of pathogenic effects on the intestinal mucosa.

Phytotherapy

Infusions of medicinal herbs have a mild restorative effect: they envelop the damaged intestinal mucosa, heal wounds, and stop bleeding. Herbal infusions and decoctions can replenish fluid loss in the body and restore water and electrolyte balance.

The main components of therapeutic herbal teas are:

1. The leaves and fruits of currants, raspberries and strawberries help the liver fight any acute inflammatory process in the body.
2. Dried blueberries cleanse the intestines of putrefactive microorganisms and help in the fight against cancer cells.
3. Nettle improves blood clotting, relieves inflammation, cleanses the intestines from decay and decay products.
4. Peppermint fights emotional lability, diarrhea, relieves inflammation and spasms, and has a pronounced antimicrobial effect.
5. Chamomile is a powerful herbal antibiotic that can also relieve spasms.
6. Yarrow stops diarrhea, has bactericidal properties and cleanses the intestines from pathogenic microorganisms.
7. St. John's wort stimulates intestinal motility and has an anti-inflammatory effect.

These herbs are used to treat ulcerative colitis in the form of infusions and decoctions. They are combined in fees or brewed separately.

• Dry leaves and raspberry branches are poured with boiling water and insisted for half an hour. Take a remedy of one hundred milliliters four times a day before meals.
• A collection of medicinal herbs is prepared as follows: centaury grass, sage leaves and chamomile flowers are mixed in a teaspoon. Then pour a glass of boiling water and leave for thirty minutes. Drink one tablespoon every two hours. Three months later, the intervals between doses of the infusion are lengthened. Such treatment is harmless and can last for a long time.
• Peppermint leaves are poured with boiling water and infused for twenty minutes. Take a glass twenty minutes before meals. The same effective remedy for colitis is an infusion of strawberry leaves, which is prepared similarly to this.
• Fifty grams of fresh pomegranate seeds are boiled over low heat for half an hour, pouring a glass of water. Take two tablespoons twice a day. Pomegranate decoction is a fairly effective remedy for allergic colitis.
• One hundred grams of yarrow herb is poured with a liter of boiling water and insisted for a day in a closed container. After straining, the infusion is boiled. Then add one tablespoon of alcohol and glycerin and mix well. Take the remedy thirty drops half an hour before meals for a month.
• Mixed in equal amounts of medicinal sage, peppermint, chamomile, St. John's wort and cumin. This mixture is placed in a thermos, poured with boiling water and left overnight. Starting from the next day, take the infusion regularly for half a cup three times a day for a month.

Folk remedies

• Dried watermelon peels in the amount of one hundred grams are poured with two glasses of boiling water and taken one hundred milliliters six times a day.
• Eight grams of propolis should be eaten daily to reduce the symptoms of colitis. It needs to be chewed on an empty stomach for a long time.
• Squeeze the juice from the onion and take it one teaspoon three times a day. This folk remedy is very effective in the treatment of ulcerative colitis.
• The whey obtained by squeezing the cheese is recommended to be taken twice a day.
• Walnut kernels are regularly eaten for three months. Positive results will become noticeable within a month from the start of treatment.
• How to cure ulcerative colitis with microclysters? For this, starch microclysters are shown, prepared by diluting five grams of starch in one hundred milliliters of cool water.
• Microclysters made from honey and chamomile, which are pre-brewed with boiling water, are considered effective. One enema requires fifty milliliters of solution. The duration of treatment is eight procedures.
• Viburnum berries are poured with boiling water and viburnum tea is drunk immediately before meals.