Treatment of inflammatory bowel disease

Treatment of inflammatory bowel disease in children is similar to that in adults and should comply with modern principles of evidence-based medicine. The tactics of treating inflammatory bowel disease differ from that in adults only in terms of individual doses and some other restrictions. To date, a relatively small number of controlled studies have been published, and therefore the strategy for treating inflammatory bowel disease in children is based on the results obtained in treating adults. Doses are calculated based on body weight, with the exception of methotrexate, the dose of which is calculated based on body surface area. The maximum dose corresponds to the recommended dose in adults.

Treatment goals for inflammatory bowel disease

Achieving remission, bringing physical and neuropsychic development into line with age norms, preventing unwanted side effects and complications.

Drug treatment of inflammatory bowel disease

Medicines can be used both as monotherapy and in various combinations according to individual needs. It has been shown that the simultaneous administration of systemic glucocorticosteroids and 5-aminosalicylic acid (5-ASA) or salazosulfapyridine preparations does not have any particular advantages over glucocorticosteroid monotherapy.

Taking into account the significantly lower frequency of side effects of 5-ASA (mesalazine) preparations, their administration is preferable. The dose of 5-ASA should be 50-60 mg/kg of body weight per day, the maximum is 4.5 g per day.

Glucocorticosteroids are indicated for patients in whom the use of 5-ASA and SASP does not provide the necessary effect, as well as for patients with lesions of the upper gastrointestinal tract (from the esophagus to the jejunum), extraintestinal symptoms. The course of inflammatory bowel diseases in children is usually more severe, which is associated with a high percentage of steroid-dependent patients.

Given the severe side effects of systemic glucocorticosteroids, researchers have high hopes for the topical glucocorticoid budesonide (budenofalk). About 90% of the drug is metabolized during the first pass through the liver, which is why the frequency of side effects is significantly lower (= 2.4 times). Budesonide is indicated for patients with mild and moderate forms of the disease in the acute phase, as well as for patients with lesions of the distal ileum and ascending colon. The optimal dose of budesonide is 9 mg per day.

In patients with chronic continuous inflammatory bowel disease, additional use of azathioprine or its active metabolite 6-mercaptopurine (6-MP) can help reduce the dose of glucocorticosteroids by an average of 60%. Fistulas close in 40% of cases against the background of using the listed drugs. The recommended dose of azathioprine is 2.5 mg / kg, 6-MP - 1-1.5 mg / kg per day. Side effects occur quite often, include fever, pancreatitis, dyspeptic disorders, increased frequency of infectious diseases. Pancreatitis is a contraindication to the use of azathioprine. The occurrence of these side effects can be avoided by gradually increasing the dose (half the dose is prescribed in the first 4 weeks of treatment), as well as subject to regular monitoring of laboratory parameters and thiopurine methyltransferase activity. Patients with low enzyme activity have an increased risk of side effects.

The effect of treatment is noted already in the first 2-4 months, in some cases after 6 months.

The use of antibiotics in the treatment of inflammatory bowel diseases is based on the assumption that some bacterial antigens act as a trigger for pathological immune defense of the intestinal mucosa. However, to date there are no research results confirming the role of antibiotics in achieving remission or reducing the activity of inflammatory bowel diseases. Only metronidazole at a dose of 20 mg/kg per day has been proven more effective than placebo in patients with Crohn's disease; the drug is highly effective in the treatment of perianal fistulas.

Cyclosporine A is not considered a drug suitable for long-term treatment; it is prescribed during exacerbations during the period of accumulation of azathioprine concentrations.

Of interest are reports of local use of tacrolimus in the form of ointment in children with lesions of the oral cavity and perianal region refractory to other drugs.

Methotrexate is considered the drug of choice when glucocorticosteroids are ineffective or there are severe side effects to treatment. It is administered subcutaneously at a dose of 15 mg/kg once a week.

A new drug for the treatment of inflammatory bowel diseases refractory to the standard treatment regimen is infliximab. The drug contains chimeric antibodies to tumor necrosis factor a, one of the most powerful proinflammatory cytokines. The effectiveness of this drug has been proven only in adult patients; experience with children is limited. In pediatric practice, the drug is only approved for the treatment of Crohn's disease.

In patients with lesions of the distal colon, local treatment is preferable to systemic therapy, since its effectiveness allows avoiding or reducing the severity of adverse reactions. Unfortunately, in pediatric practice, nonspecific ulcerative colitis is more often (up to 70-80%) represented by pancolitis, as a result of which local therapy must be combined with the administration of systemic drugs.

Complications and insufficient response to drug treatment are considered indications for surgical treatment.

Algorithm for choosing treatment for non-specific ulcerative colitis

Features of the disease	Treatment
Exacerbation	Mild exacerbation - mesalazine or sulfasalazine Moderate exacerbation - glucocorticosteroids, mesalazine or sulfasalazine Severe exacerbation - glucocorticosteroids, mesalazine or sulfasalazine, parenteral or enteral
Maintenance of remission	Mesalazine or sulfasalazine, diet rich in dietary fiber, compensation for vitamin and microelement deficiencies
Chronic active and complicated course, steroid dependence, maintenance of remission after treatment with cyclosporine or tacrolimus	Azathioprine

Age-specific dosages of essential drugs for nonspecific ulcerative colitis in children

Preparation	Dose
Prednisolone, etc.	1-2 mg/kg per day orally or intravenously (40-60 mg)
Sulfasalazine	25-75 mg/kg per day (4 g/day)
Mesalazine	30-60 mg/kg per day (4.8 g/day)
Azathioprine	1-2 mg/kg per day, subject to monitoring of the content of 6-MP metabolites in the blood serum
6-Mercaptopurine	1-1.5 mg/kg per day, subject to monitoring of the content of 6-MP metabolites in the blood serum
Cyclosporine	4-8 mg/kg per day orally or intravenously (serum content 200-250 mcg/ml)
Tacrolimus	0.15 mg/kg per day orally (serum content 10-15 mcg/ml)
Infliximab	5 mg/kg IV

Algorithm for choosing therapy for Crohn's disease

Features of the disease	Preparation
Exacerbation	GC topical (budesonide) and systemic (prednisolone), mesalazine or sulfosalazine. Immunosuppressants (azathioprine, 6-mercaptopurine). Elemental diet
Maintenance of remission	Mesalazine or sulfasalazine. Diet rich in dietary fiber, compensation for vitamin and microelement deficiencies, cholestyramine for chologenic diarrhea
Chronic active and complicated course	Azathioprine, antibodies to tumor necrosis factor A

Age-specific dosages of essential drugs for Crohn's disease in children

Preparation	Dose
Prednisolone, hydrocortisone	1-2 mg/kg per day orally or intravenously (40-60 mg)
Budesonide	9 mg - starting dose, 6 mg - maintenance dose
Sulfasalazine	25-75 mg/kg per day (4 g/day)
Mesalazine	30-60 mg/kg per day (4.8 g/day)
Metronidazole	10-20 mg/kg per day
Azathioprine	1-2 mg/kg per day, subject to monitoring of the content of 6-MP metabolites in the blood serum
6-Mercaptopurine	1-1.5 mg/kg per day, subject to monitoring of the content of 6-MP metabolites in the blood serum
Methotrexate	15 mg/m2 (25 mg/day)
Thalidomide	1-2 mg/kg (single dose at night)
Infliximab	5 mg/kg IV

Forecast

The prognosis for most forms of inflammatory bowel disease is unfavorable, especially in the case of complications (in nonspecific ulcerative colitis - toxic dilation or perforation of the colon, intestinal bleeding, sepsis, thrombosis and thromboembolism, colon cancer; in Crohn's disease - stenosis and strictures, fistulas, abscesses, sepsis, thrombosis and thromboembolism, colon cancer).