If you have reached this post, maybe you have been recently diagnosed with inflammatory bowel disease or know someone who has been. They are very common: over two million people in Europe live with an IBD, being Crohn's disease and Ulcerative colitis the most widely spread.
The principal characteristic of IBD conditions is the swelling of the digestive tract, which is a result of the wrong activity of the immune system. However, why does this happen? Under normal circumstances, the immune system is the one in charge of protecting our body against pathogens or any foreign and harmful substance. It is one of the more complex systems of our body and involves many different organs, cells, molecules and pathways. Some alterations could lead to its malfunction and this is what occurs in patients with IBD. The wrong activity of some of those processes lead the cells of their immune system to react against the intestine. In the end, this causes the inflammation of the patient’s bowel.
The IBD treatments work targeting the cells, communication molecules or pathways of activation of the immune system, inhibiting the processes at different levels to diminish the swelling.
For the moment, as chronic diseases, the first aim is to mitigate the symptoms. Once the condition is controlled, the next step is to maintain that relief and to monitor the disease for the prevention of future complications. The administration of treatments typically occurs over long periods, so it has to comply also with the lifestyle of the patient.
Today, we want to talk about the primary treatments used for IBD to familiarise yourself with them. However, before we begin, please keep in mind that we are not giving medical advice and you should always check with your doctor.
We start our list with the four types of therapies that doctors have traditionally used to treat these conditions: the first generation of IBD drugs.
They work reducing the number of bacteria, which consequently reduce the response of the immune system too. These are the only treatments that don’t act directly into the immune system but targeting the agents that induce its activation, the bacteria. Antibiotics perform well with Crohn’s disease patients because they mitigate the symptoms of infections characteristics of this condition, like fistulae (an abnormal passage between two regions of the intestine or between the gut and another region). However, they are in general not very useful for those patients with ulcerative colitis.
Antibiotics are generally used only for short periods because of its side-effects: its persistent use could also affect beneficial gut bacteria, causing further digestive problems. Besides, their overuse is linked to the appearance of resistant bacteria, a serious concern for world health.
Aminosalicylates are a type of drugs chemically related to aspirins; they are anti-inflammatories, which means that they limit the inflammatory response. Specifically, aminosalicylates act locally in the lining of the digestive tract targeting the genes involved in the inflammation. They regulate their expression which, as a result, reduce the production of pro-inflammatory proteins like cytokines and other molecules.
In general, Aminosalicylates are very well tolerated. They are effective in 50% of patients with Ulcerative colitis, but they don't perform well in patients with Crohn’s disease.
This treatment is based on hormones that have anti-inflammatory properties so as the aminosalicylates they work limiting the inflammation. They target cells involved in that response of the immune system like epithelial cells and T-lymphocytes. They have two actions; they firstly control the effects of the cytokines by blocking the responses of the cell to them. Secondly, they reduce the production of those proteins while increases the anti-inflammatory protein production.
These drugs can act very fast in the human body, and they perform well with both ulcerative colitis and Crohn’s disease. Thus, they have become the first line therapy for patients with CD and the second line for the other half of patients with UC that didn't respond well to aminosalicylates. However, due to their side-effects, the percentage of withdrawal is very high, and corticoids only achieve a long-standing remission in 20% of patients. During the last few years, there has been a movement among the medical community to decrease the duration of these treatments. Some doctors think that sometimes it is too long and unnecessary for the patients. They are at large becoming less recommended.
- Chemical Immunomodulators:
The previous mentioned aminosalicylates and corticosterois are immunomodulators too because they act modifying the activity of the immune system. However, historically this name was also used to categorize a group of IBD treatments. This group includes compounds that act at a cellular level targeting the blood’s white cells. They block their action, and since they are one of the principal cells of the immune system, they effectively reduce the inflammatory response. However, sometimes they could eventually kill those white cells, causing adverse effects that complicate the treatment.
The immunomodulators are an excellent option to maintain the release of the disease because patients can take them for extended periods. However, to induce the release, they have to be taken with other medications. Commonly, patients start with immunomodulators and corticosteroids at the same time, and once the first ones begin to take effect, they withdraw from corticosteroids.
A benefit of these treatments is that they were one of the firsts used to treat IBD, and thus they have been used during years. This has allowed the study of their effects on different patients with different courses of the disease. Now, thanks to that information, this treatment is more controlled and individualised than others.
Those are the four therapies that are regularly used for IBD. Sadly, they still leave a significant number of IBD patients insufficiently treated, so researches keep looking to find alternatives. In the last few decades, a better understanding of IBD has led to the development of second and third generation therapeutic agents:
Biological drugs are made from molecules that appear in living organisms, such as proteins or genes. For the treatment of IBD, they are in general proteins known as antibodies. They are tools used by white cells to block the entry of pathogens. They bind specifically to other proteins of microorganisms impeding their function. As well as they do it with those proteins, we can develop antibodies that block specific molecules that are involved in causing the inflammation, such as cytokines. However, it has to be taken into account that, as cytokines are key to the immune cells to communicate during infections, they also bring the risk of increasing the susceptibility to pathogens.
One example of this type of treatment are the antibodies against TNFα (a specialised protein that plays a role in increasing or decreasing inflammation) that can induce and maintain remission in 40% of IBD patients. Besides, in those failing anti-TNFα therapies, another example is the anti-α4β7 integrins antibody that shows to induce and sustain the remission of the diseases in the 15-20% of patients. In general, they are a good option for patients that didn’t respond well to the previous treatments mentioned, or they need to withdraw from corticosteroid treatments.
- JAK Inhibitors:
JAK inhibitors are an innovative third generation of treatments. JAK molecules are proteins involved in the intracellular process of activation of immune cells. Thus, JAK inhibitors block the inner pathways of reactions that lead to inflammation and control them in a very effective way as recent studies have demonstrated. Nowadays, there is only one JAK-based treatment available, and it is useful just for UC patients: Tofacitinib. It has demonstrated a broader clinical effect than biological therapy.
Although this last treatment is promising, its broad action limits its clinical use. Researchers are looking for a way to limit their effect to the target cells and avoid other interferences with the rest of the essential pathways of the organism. Our research project, New Deal, focuses precisely on this point. We aim to design a novel therapy that targets JAK inhibition in a more specific way.
Moreover, we are not alone in our search: nowadays there are a lot of international researches looking for improvements in IBD treatments. The therapies are gradually becoming less invasive and more effective. Together with the advances in medicine, now the diagnosis is more accurate allowing treatments to be more individualised.
Together, we are working on a better future for people who suffer IBD. If you suffer from IBD and have tried any of these treatments, feel free to share your experience with us, leaving us a comment below!