Introduction
The main goals of ulcerative colitis therapy are to relieve the symptoms of ulcerative colitis, to avoid complications and thus to maintain the patient’s quality of life. A distinction is made between therapy of acute attacks and long-term therapy. An important pillar of the therapy is also the psychosomatic care of the patient. All the options available today for the treatment of ulcerative colitis are only symptomatic, i.e. they cannot fight the actual cause of the disease and cure it.
Therapy according to the guideline
In acute phases, i.e. acute inflammation, the therapy can be escalated depending on the severity of the disease. In the case of a minor relapse, therapy with mesalazine is recommended first, which is also used in lower doses in remission therapy. It can be taken in the form of tablets or, in the case of local inflammation of the rectum, given as suppositories or foam.
If mesalazine alone and even with increased dosage is not effective, systemic therapy with corticosteroids in the form of tablets should be started according to the guidelines. Drug of choice is prednisolone for 8-12 weeks. If it is a very severe form of ulcerative colitis, the therapy should be carried out in a hospital.
The corticosteroids can be administered in hospital through a venous access, which makes them more effective than in tablet form. If this therapy is not sufficiently effective, immunosuppressive drugs such as Ciclospoprin A, Azathioprin or Tacrolimus (reserve medication) can be given instead. In addition, antibodies such as Infliximab are also available as an alternative.
If the course of ulcerative colitis is so severe that immunosuppressive drugs or antibodies are necessary, the guideline recommends surgical therapy in the form of proctocolectomy. This means that the entire colon and rectum is removed, which cures ulcerative colitis. Drug therapy of ulcerative colitis is based on two pillars.
Firstly, therapy in acute attacks and secondly, long-term therapy in intervals to maintain remission. Various drugs are available for this purpose. 1. salicylates (5-amino-salicylate5-ASA): Mesalazine, for example, belongs to this group of drugs.
This anti-inflammatory drug can be administered orally in the form of a tablet or rectally through the anus (suppositories). In left-sided ulcerative colitis, the rectal administration of a klysma or rectal foam is sufficient. In the case of an inflammation that also affects the transverse colon (transverse colon) and the ascending part of the colon (ascending colon), salicylates must be administered orally.
Salicylates are used both in acute therapy and in remission maintenance. The dose of sulfalazine depends on the severity of the attack. This drug works by shutting down the body’s immune system, so it is considered an immunosuppressive drug.
It works so effectively in ulcerative colitis because of the overactivity of certain components of the immune system. This is why it is the drug of choice in remission maintenance, i.e. between the individual attacks in which the patient is actually free of symptoms. This is intended to delay the next relapse longer.
If a severe relapse is present, the sulfasalazine can be replaced or supplemented by other immunosuppressive drugs (e.g. azathioprine or ciclosporin). In addition, parenteral nutrition must often be administered in such a case, as the patient can no longer take food in the normal way. It must be taken into account that, if necessary, electrolytes, protein or blood must also be supplied parenterally.
If no or only an unsatisfactory improvement can be achieved after 3 days even after regular treatment of such a relapse, the patient must undergo surgery. 2. glucocorticoids (cortisone): This well-tried medication has an excellent anti-inflammatory effect and is often used when salicylates are not effective enough. Glycocorticoids are not preferred for long-term therapy because they have lasting side effects (e.g. osteoporosis).
However, some patients, such as those who have a persistent disease activity of ulcerative colitis, require long-term treatment with low-dose glycocorticoids.The most popular glycocorticoid is budesonide, because it is broken down particularly quickly in the liver, so it has fewer side effects despite good effects in the intestines. They can be administered rectally, orally and also intravenously during therapy. It is important at the end of treatment with corticoids to “sneak them out”, i.e. not to stop the medication abruptly, but to regulate the dose in a controlled manner by reducing the dosage of the menstrual drug.
3) Immunosuppressive drugs: In a therapy-refractory course of ulcerative colitis, immunosuppressive drugs can be used so that the glycocorticoids, which are richer in side effects, can be avoided. These drugs work by shutting down the body’s immune system. It works so effectively in ulcerative colitis because of the overactivity of certain components of the immune system.
Therefore, this is also the drug of choice in remission maintenance, i.e. between the individual relapses in which the patient is actually free of symptoms. This is intended to delay the next relapse longer. For this purpose, the drug azathioprine is initially the therapy of choice.
Cyclosporine and possibly methotrexate are available as alternative drugs. Most immunosuppressive drugs have a slow onset of action, so that the time until the onset of action must be bridged with cortisone administration. But even these drugs often have side effects, so that the treated patients must be examined regularly by a doctor and regular blood count checks are necessary.
4. immunomodulators: Since 2006, the new drug Infliximab has also been approved for the treatment of ulcerative colitis. This antibody binds to TNF-?, an inflammation-mediating messenger substance, which is neutralized by the binding and TNF-? can no longer exert its effect.
A more recent approach in therapy is that probiotics can be used in addition or as an alternative to 5-ASA in order to maintain remission. This term refers to the intake of selected intestinal bacteria that support the healthy intestinal flora in fighting the disease. Bacteria from the E. coli Nissle strain are frequently used.
Such a therapy is only paid for by the health insurance companies if there is an intolerance to 5-ASA. In acute phases, mainly anti-inflammatory drugs are used. The most common drug used for this is prednisolone, which has a similar effect to cortisol.
Since the disease is limited to the intestine, the anti-inflammatory effect is not needed throughout the body and local application (for example as enema or rectal foam) can reduce the frequency and severity of side effects. In the case of a severe relapse, however, one switches to the intravenous administration of prednisolone. Humira® is the trade name for an antibody called Adalimumab.
Adalimumab belongs to the so-called biologicals, which are artificially produced proteins that can intervene in various processes of the immune system. Humira specifically inhibits TNF-alpha (tumor necrosis factor alpha), which is involved in inflammatory processes. By inhibiting TNF-alpha, it is hoped to reduce inflammatory activity during the acute severe flare of ulcerative colitis.
Currently, Humira is not yet explicitly recommended by the guideline, but studies have already shown that Humira can restore and maintain remission (no diarrhea and no inflammatory foci in colonoscopy). Humira can therefore be used in patients with a severe course of disease when corticosteroids and azathioprine have not shown sufficient effect. It is important to note that Humira has a number of contraindications for which it should not be used.
These include pregnancy, immunosuppressed patients, acute, symptomatic infections, chronic infections and especially tuberculosis, multiple sclerosis, cancer and moderate heart failure. Side effects of such a therapy can be symptoms of flu, a reduction in blood counts or the occurrence of an allergic reaction. Remicarde® (Infliximab) is an antibody and, like Humira, belongs to the group of TNF-alpha inhibitors.
It is used when cortcoid steroids and azathioprine were ineffective in a severe relapse of ulcerative colitis. However, one study showed that only 21% of the patients studied were in remission after 8 weeks of administration of Remicarde. The remaining patients still had inflammatory activity.The antibody therapy is considered safe and can be used as an escalation attempt despite a one-fifth chance of success, provided that the contraindications are strictly observed.
The contraindications apply to TNF-alpha inhibitors in general, so they are similar to those of Humira and are listed there. Remicarde differs significantly from Humira in that it consists partly of a mouse protein, whereas Humira consists only of human proteins. As a result, taking Remicarde can lead to allergic reactions to the mouse protein, such as skin rashes, itching or shortness of breath.
Therefore, the therapy should be carried out under medical supervision in order to be able to detect an allergic reaction or other side effects in a timely manner. Methotrexate belongs to the group of immunosuppressants and is a folic acid antagonist. The drug inhibits an important enzyme in DNA synthesis, which in turn inhibits DNA synthesis.
Due to its cytostatic effect, it is often used as a chemotherapeutic agent in cancer diseases. However, administration in ulcerative colitis is controversial according to the guideline, as it has not shown any advantage over a placebo preparation in randomized controlled trials, which are the gold standard of medical studies. One point of criticism of the studies is the relatively low dosage of the drug and it is discussed whether a higher dosage could achieve the desired effect. Due to these inconsistencies, methotrexate has not been recommended as a second drug for azathioprine intolerance.
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