Current treatments for Inflammatoty Bowel Disease

Hi again!

This week we will learn a little bit more about Inflammatory Bowel Disease (IBD) management and the different therapeutic options available for these diseases. 

Treatment for Crohn's Disease and Ulcerative Colitis (the two main forms of IBD) depends on how severe the symptoms are, and how much of the gut is affected. There is no standard treatment that will work for all patients. Each patient’s situation is different and treatment must be followed for each circumstance. 

Treatment for IBD can include the use of medication, alterations in diet and nutrition, and sometimes surgical procedures to repair or remove affected portions of the gastrointesitnal tract.

Initially, the aim of treatment is to reduce inflammation in the gut to bring relief from symptoms and induce remission (a phase without symptoms). We should remember that there is no cure for IBD, so the purpose of the treatment is to alleviate the symptoms and allow the patient to have a life as normal as possible. Once the condition is under control, the doctor will usually continue to prescribe drugs to maintain remission and prevent relapse – this is called maintenance treatment.

In some cases, if medical treatment is not effective, then surgery may be required. 

MEDICATION

Medication treating IBD is designed to suppress the immune system’s abnormal inflammatory response that is causing the symptoms. Suppressing inflammation not only offers relief from common symptoms like fever, diarrhea, and pain, it also allows the intestinal tissues to heal. Why many of the drugs used to help control IBD are anti-inflammatory drugs.  These include steroids, 5ASAs, immunosuppressants such as azathioprine, methotrexate and ciclosporin, and biological drugs like infliximab and adalimumab. Other drugs used for IBD include antiobiotics such as metronidazole and ciprofloxacin, and symptomatic drugs such as antidiarrheals and bulking agents. 

In addition to controlling and suppressing symptoms (inducing remission), medication can also be used to decrease the frequency of symptom flare ups (maintaining remission). With proper treatment over time, periods of remission can be extended and periods of symptom flare ups can be reduced. 

Several types of medication are being used to treat IBD today. Among the different drugs we can find:

• Adalimumab or Humira: Adalimumab is also known as Humira or the biosimilars Amgevita, Hyrimoz, Imraldi, and Hulio. Adalimumab is available to treat moderate to severe active Crohn’s Disease in adults, and moderate to severe active Crohn’s in children and young people from 6-17 years of age. It is used when treatment with other Crohn's and Colitis medicines have not worked or when side effects have been severe. It is a biologic medicine made from a synthetic (man-made) antibody. It works by targeting a protein in the body called tumour necrosis factor-alpha (TNF-alpha). The body naturally produces TNF-alpha as part of its immune response, to help fight infections. Over-production of this protein is thought to be partly responsible for the ongoing inflammation in the gut of people with Crohn’s or Colitis. Adalimumab binds to the TNF-alpha, which reduces the inflammation and helps to relieve symptoms. It is known as an anti-TNF drug. Although not everyone responds to adalimumab, several large studies have shown that adalimumab can be effective in bringing about and maintaining remission in people with Crohn’s and Colitis. The aim of treatment is to reduce inflammation in the gut and bring about remission, maintain remission and improve quality of life by reducing or eliminating symptoms. Adalimumab is given as an injection under the skin (subcutaneous injection). It cannot be taken by mouth in tablet form, because it would be destroyed by the digestive system.
• Aminosalicylates (5-ASAs): 5-ASAs are often the first treatment option for mild to moderate flare-ups of Ulcerative Colitis. They may then be prescribed to maintain remission and help prevent flare-ups on a longer-term basis. There are several types of 5-ASA drugs, also often referred to by their various brand names: Salazopyrin, Mesalazine, Asacol, Ipocol, Octasa, Pentasa, Salofalk, Mezavant and Dipentum. 5-ASA drugs are chemically related to aspirin and work by reducing this inflammation, allowing damaged tissue to heal. 5-ASAs are an effective treatment option for Ulcerative Colitis, with seven in 10 people responding well to the medicine. 5-ASAs can be taken orally by swallowing a tablet, capsule or granule, or topically through the anus as a suppository or an enema. The best form for you will depend on how severe your condition is and how much of your colon is affected.
• Azathioprine and Mercaptopurine: These medicines are a common treatment for Crohn's Disease and Ulcerative Colitis, with around 6 out of 10 people with the conditions taking them at some point. Azathioprine or mercaptopurine may help to reduce or stop taking steroids without having another flare-up. If the patient has had two or more flare-ups in 12 months that needed treatment with steroids, or the inflammation in the gut hasn’t been controlled by aminosalicylates (5-ASAs) such as mesalazine or sulfasalazine, these medicines could help. Azathioprine and mercaptopurine are immunosuppressants. The immune system is important for fighting infections, but sometimes cells in the immune system attack the body’s own tissues and trigger inflammation like that in Crohn’s and Colitis. Azathioprine and mercaptopurine reduce inflammation in the gut by dampening down the immune system. However, this can mean the patient is more likely to get infections. These medicines don’t work for everyone. Both azathioprine and mercaptopurine are taken by mouth, usually once a day, and come as 25mg and 50mg tablets.
• Biologic Drugs: Deciding to take a biologic medicine can feel like a big step. But if the patient is not well and other treatments aren’t working, they can make a huge difference to his/her quality of life. Biologic medicines are treatments for people with moderate to severe Crohn’s Disease or Ulcerative Colitis. They may be an option when other drugs such as immunosuppressants (azathioprine, mercaptopurine, methotrexate) or steroids haven’t been effective, or side effects have been hard to manage. Biologic medicines are produced by biological rather than chemical processes. Living organisms, such as living cells, produce the active substance which is made of proteins. There are five different biologic medicines available to treat moderate to severe Crohn’s Disease or Ulcerative Colitis. These are infliximab, adalimumab (see above), golimumab, vedolizumab and ustekinumab. Adalimumab is the most common one, why it has been explained separately. Not all drugs are available to treat both conditions. For Crohn's Disease: Infliximab is available to treat active fistulising Crohn’s Disease that hasn’t responded to treatment. Adalimumab has also been used successfully to treat fistulas in people with Crohn’s who also have active inflammation. Vedolizumab is a treatment option only when infliximab or adalimumab haven’t been effective or there is a reason why the patient shouldn’t take these. Ustekinumab may be used where immunosuppressants or steroids haven’t worked, or an anti-TNF drug hasn’t been effective or has stopped working. For Ulcerative Colitis: Vedolizumab may be an option if other treatments such as steroids or immunosuppressants haven’t helped the condition. It may also be an option if infliximab, adalimumab or golimumab (anti-TNF drugs) haven’t worked. Biologic medicines act to block some parts of the immune system, they reduce the inflammation and so improve symptoms. They work in different ways: i) Blocking the activity of cytokines (TNF alpha or interleukins). Cytokines are specific proteins usually produced as a response to infection or injury. In Crohn’s and Colitis overproduction of these proteins is thought to be partly responsible for the inflammation in the gut. ii) Blocking white cells moving into the gut. White blood cells are made by the immune system to fight infection, but in Crohn’s and Colitis, overproduction of these cells leads to gut inflammation. All these drugs are taken either by injection under the skin or through a drip in the arm (IV infusion).
• Steroids: Steroids, also called corticosteroids, are a common medicine for Crohn’s Disease and Ulcerative Colitis, with 4 out of 5 people with the conditions taking them at some point. There are many different types of steroids (also known as corticosteroids) which can be taken in different ways. Oral steroids are taken by mouth and swallowed. They include: prednisolone (brand names Deltacortril®, Deltastab® and Dilacort®), prednisone hydrocortisone (Plenadren®), methylprednisolone (Medrone®), beclometasone dipropionate (Clipper®), budesonide (Entocort® and Budenofalk®), budesonide-MMX (Multi-Matrix system) (Cortiment®). Intravenous steroids are given directly into a vein (in hospital). They include: hydrocortisone and methylprednisolone. Topical steroids are given directly at the site of inflammation. Rectal steroids (suppositories, foam or liquid enemas) are a type of topical steroid. Steroids that come as a mouthwash (for treating mouth ulcers) are another type of topical steroid. Topical steroids include: hydrocortisone (Colifoam®), prednisolone (Predfoam®) and budesonide (Budenofalk®). Steroids are hormones that are produced naturally in the body. Steroids used to treat Crohn’s and Colitis are man-made versions of these hormones, but they are taken in higher doses than your body makes naturally. In these high doses, steroids reduce inflammation by decreasing the activity of the immune system. Steroids are effective as a short-term treatment during a flare-up to bring IBD into remission. Taking steroids for long periods of time or repeatedly will not help to control Crohn’s or Ulcerative Colitis and can cause unwanted side effects. Once in remission, the steroid treatment will gradually reduce and stop and the patient will be offered a different treatment to keep the symptoms under control.
• Tofacitinib: Tofacitinib is also known by the brand name Xeljanz. Tofacitinib is a type of drug called a Janus kinase (JAK) inhibitor. JAKs are enzymes that are involved in activating the body’s immune response, which causes the gut inflammation in Ulcerative Colitis. Tofacitinib blocks this process, and so reduces inflammation. Tofacitinib is a small molecule drug, which means that it’s less likely to stop working over time than biologic medicines such as infliximab, adalimumab, golimumab or vedolizumab. Biologics are larger molecules that the immune system sometimes recognises as a foreign substance and thinks is harmful. It then produces proteins called antibodies to the biologic medicine and these prevent it from working as well. Although tofacitinib doesn’t work for everyone, several large studies have shown that it can be effective in bringing about and maintaining remission in people with Ulcerative Colitis when other drugs haven’t been helpful. Two large studies found that eight weeks after starting treatment with tofacitinib around 3 out of 10 people noticed a positive difference and over half of those people were in remission. Tofacitinib is a tablet that is usually taken by mouth twice a day. 
• Antibiotics: Antibiotics kill or stop the growth of bacteria, and are often used in treating complications of Crohn's or Colitis such as abscesses and fistulas (abnormal connections between the bowel and the skin or other organs). They are also sometimes used in treating pouchitis, an inflammation of the ileo-anal pouch that sometimes follows surgery for Colitis.  Antibiotics are occasionally used as a treatment for other Crohn's or Colitis symptoms, often together with other drugs. This is because while the exact cause of Crohn's and Colitis  is still unknown, it is very likely that it involves an abnormal reaction of the immune system to intestinal bacteria. Antibiotics could potentially help control symptoms of Crohn's or Colitis  by reducing these bacteria, and may also have immunosuppressant effects. Research has shown that antibiotics have no consistent benefit for Colitis symptoms, so are not usually used. There is some evidence to suggest that they are effective in treating Crohn’s Disease, in particular Crohn’s Colitis (Crohn’s Disease in the colon). Antibiotics may also help prevent Crohn’s from coming back after surgery. Using antibiotics can sometimes lead to the development of Clostridium difficile (C. difficile) infection. Clostridium difficile are potentially dangerous bacteria that can cause diarrhoea and serious complications. People with Crohn’s and Colitis are at a higher risk of C. difficile infection, and so may need to take extra care with antibiotics. Metronidazole (Flagyl): this is the most commonly prescribed antibiotic for Crohn’s Disease. It is usually taken as a tablet, but it can be taken as a suppository or be given by injection. Side effects may include nausea, lack of appetite and a metallic taste in the mouth. More rarely, long-term use can cause nerve damage and a tingling in the hands and feet. It is best to avoid drinking alcohol while taking metronidazole and for at least two days following the last dose, as there can be an interaction. Ciprofloxacin: it is also used for the treatment of Crohn’s and has been found to be as effective as metronidazole, with fewer side effects. It is normally taken as a tablet, but can be given by injection. Common side effects include nausea and diarrhoea. Some people also experience tendon damage or photosensitivity (sensitivity to sunlight). Ciprofloxacin may also interact with some of the other medications used for IBD, such as ciclosporin, methotrexate and iron supplements.
• Proton-pump inhibitors: Some people who are taking oral corticosteroids may also be prescribed a proton-pump inhibitor (PPI), such as omeprazole or lansoprazole. This can help protect the stomach from the side effects of steroids, such as gastrointestinal bleeding or dyspepsia (indigestion), in people who are at high risk of these complications. Side effects of PPIs can include headache, diarrhoea, stomach pain, rashes, and swollen feet. More rarely, they can cause kidney problems or agranulocytosis, which is a lack of white blood cells. Proton-pump inhibitors may not be suitable if you are also taking the immunosuppressants methotrexate or tacrolimus, and are also not recommended for people with Microscopic Colitis - a form of IBD, different from Ulcerative Colitis or Crohn’s Disease, that affects the large bowel.
• Allopurinol: it is a drug that is usually used to prevent gout, which is a type of arthritis. Allopurinol interacts with the metabolism of azathioprine and mercaptopurine, increasing the levels of these drugs in the blood stream. If taken at the same time as normal doses of azathioprine/mercaptopurine, dangerously high amounts of azathioprine/mercaptopurine appear in the blood, so should be avoided. However in some people, azathioprine or mercaptopurine is metabolised in a way that increases the risk of harm to the liver. In these cases you may be prescribed a very low dose of azathioprine or mercaptopurine combined with allopurinol, to redirect the drug metabolism to the normal pathway. This has to be done with great care and with frequent monitoring of blood tests.
• Antidiarrhoeals: Loperamide (Imodium, Arret), codeine phosphate and diphenoxylate (Lomotil) help to reduce diarrhoea, which is the passing of loose, watery stools. They work by changing the muscle contractions in the gut, so that food takes longer to pass through your system. This allows more time for the water produced by the digestive processes to be reabsorbed by the colon, and for the stools to become more firm and less urgent. Antidiarrhoeals should not be taken in the middle of a significant flare-up, as this can occasionally lead to a serious complication called toxic megacolon. They should also not been recommend that you do not take antidiarrhoeals when there is a significant narrowing of the bowel called a stricture. Abdominal cramps and constipation can be a side effect of antidiarrhoeals, and sometimes they can cause hard stools that are difficult or painful to pass.
• Antispasmodics: Antispasmodics such as mebeverine (Colofac), hyoscine butylbromide (Buscopan) and alverine citrate (Spasmonal) reduce painful gut cramps or spasms by relaxing the intestinal muscles. These medicines are most likely to be recommended for people with Irritable Bowel Syndrome, but they may also be helpful for the IBS-like symptoms sometimes experienced by people with Crohn's or Colitis.
• Painkillers: If an IBD patient needs to take over-the-counter painkillers for gut or joint pain, paracetamol is likely to be the safest option. It is best to avoid ibuprofen and diclofenac, which are non-steroidal anti-inflammatory drugs (NSAIDs). While they can be effective, there is evidence that they may make other IBD symptoms worse, or possibly trigger a flare-up. Some people may also be affected in the same way by aspirin. For severe acute pain or after an operation, opiates such as codeine may be prescribed. These can cause side effects such as nausea, constipation, sedation and altered mood. Opiates can also lead to dependence and addiction if used regularly.
• Bulking agents: Bulking agents or ‘bulk formers’ contain a water-absorbent plant fibre– usually ispaghula or stercula. Popular brands include Fybogel, Isogel and Normacol. These come as granules which, when taken  with plenty of water, swell up inside the bowel to thicken liquid faeces or soften hard stools. The fibre also provides bulk to help the bowel to work normally. Bulking agents can be particularly helpful in treating diarrhoea if ther has been a colectomy with ileo-rectal anastomosis, an operation to remove the colon in which the small intestine is joined to the rectum. However, they should be avoid if a stricture (narrowing) of the bowel exists.
• Bile salt binders: Bile salts are naturally released from the liver to help with digestion, and are then reabsorbed in the ileum (the lower part of the small intestine). If patient has undergone a surgery to remove the ileum, higher levels of bile salts can drain into the colon and cause watery diarrhoea. Bile salt binders such as colestyramine (Questran), colestipol (Colestid) and colesevelam combine with the bile salts and prevent them from reaching the colon. This helps reduce the diarrhoea. Colestryramine and colestipol are in powder form and can be mixed with water, juice or soft food. Colesevelam comes as a capsule, which some people find more convenient. Possible side effects include indigestion, abdominal bloating and discomfort, nausea and constipation. Bile salt binders can also affect how well other drugs are absorbed, so other drugs should be taken at least one hour before, or four hours after, the bile salt binder.
• Laxative: Constipation - passing stools fewer than three times per week, needing to strain, or passing hard stools - can also be a symptom of IBD. Laxatives help to relieve constipation, and also soften stools to make them easier to pass. Osmotic laxatives, such as Movicol and Laxido, which contain a compound known as macrogol, are usually considered the best type of laxative for people with IBD. Others such as lactulose and senna are sometimes used, particularly in young people. However, laxatives can also cause diarrhoea, wind and stomach cramps, especially at the start of treatment.
• Anti-foaming agents: People with Crohn's or Colitis often report feeling bloated or having excess gas. If this is a problem, an anti-foaming agent such as Simethicone, which disperses bubbles of trapped wind, may be helpful. Simethicone can be bought over-the-counter in products such as Wind-Eze tablets and WindSetler.
• Anti-sickness medication: Some medications for Crohn’s and Colitis, as well as he condition itself, can occasionally cause nausea and vomiting. People experiencing this may be prescribed anti-sickness medication such as metoclopramide, ondansetron or cyclizine. These may be given as tablets or intravenous infusion. Side effects of these drugs can include drowsiness, uncontrollable movements of the body, headaches, diarrhoea and constipation.

All these medications can be taken alone or in different combinations, which is called combination therapy.

COMBINATION THERAPY

In some circumstances, a health care provider may recommend adding an additional therapy that will work in combination with the initial therapy to increase its effectiveness.  For example, combination therapy could include the addition of a biologic to an immunomodulator.  As with all therapy, there are risks and benefits of combination therapy.  Combining therapies can increase the effectiveness of IBD treatment, but there may also be an increased risk of additional side effects and toxicity.  The health care provider will identify the treatment option that is most effective for each individual health care needs.

It is real important trying to keep medication to a minimun. However, this would depend on how the patient is responding to the different administered drugs. Sometimes, they end up with a bunch of pills that should be taken at different times, in different ways, different doses... Which can make their lifes even more difficult. 

Me, when I have a bunch of pills and can't remember which pills I have just taken

DIET AND NUTRITION

While IBD may not be the result of bad reactions to specific foods, paying special attention to diet may help reduce symptoms, replace lost nutrients, and promote healing.

For people diagnosed with IBD, it is essential to maintain good nutrition because IBD often reduces the appetite while increasing body’s energy needs. Additionally, common IBD symptoms like diarrhea can reduce the body’s ability to absorb protein, fat, carbohydrates, as well as water, vitamins, and minerals.

Many people who experience IBD flare ups find that soft, bland foods cause less discomfort than spicy or high-fat or high-fiber foods, depending on the case. While the diet can remain flexible and should include a variety of foods from all food groups, doctor will likely recommend restricting the intake of some foods. 

Sometimes it should be also necessary to follow some nutritional treatment and take some supplements. The most common are:

• Iron supplements and infusion: Many people with Crohn’s and Colitis are iron deficient, which can lead to anaemia, a lower level of haemoglobin in red blood cells. Iron deficiency can make you feel very tired, and supplements may be needed to increase iron levels. Side effects of oral iron supplements can include constipation, blackened stools and stomach pain. Some people with Crohn's or Colitis find that ferrous sulphate iron tablets make their symptoms worse. In these cases, a type of iron called ferric maltol may be better tolerated, as it tends to have fewer side effects. Ferric maltol (Feraccru) has been developed specifically for people with Crohn's or Colitis, and has been shown to be effective in treating iron deficiency in people who have not responded to traditional iron tablets. Feraccru is not currently available everywhere, and cannot be taken if you are in an Crohn's or Colitis flare-up or have a haemoglobin level that is less than 9.5 g/dL. For people who are severely anaemic or cannot tolerate iron tablets, iron infusions are sometimes recommended. This is a very quick way to get iron into the bloodstream, and is done at the hospital as an outpatient. For young people who cannot tolerate iron tablets, over-the-counter multivitamins containing iron and vitamins may be recommended.

• Vitamin B12 injections: Vitamin B12 performs several important functions in the body, including forming red blood cells and keeping the nervous system healthy. People with Crohn’s Disease who have had their ileum removed, or who have inflammation in that area, can have difficulties absorbing vitamin B12 from food. This can lead to vitamin B12 deficiency anaemia, which is usually treated with regular injections of the vitamin in a form called hydroxocobalamin.
• Calcium and Vitamin D supplements: People with IBD are at higher risk of developing thinner and weaker bones, especially if they are on steroid medication. You may be prescribed a calcium supplement with added vitamin D, such as Adcal-D3, to help protect your bones. Side effects of these supplements are rare, but may include constipation, skin rash, and hypercalcaemia (too much calcium in your blood) or hypercalciuria (too much calcium in your urine).
• Folic acid: patients taking immunosuppressant are likely to be prescribed folic acid to help reduce some of the possible side effects, such as nausea and vomiting. Usually it is taken once a week. However, a number of different regimes may be used. Folic acid and zinc and magnesium supplements are also sometimes needed in people who have had extensive surgery and are unable to absorb these nutrients fully.
• Probiotics: as we explained in our last post, probiotics are live microorganisms that aim to improve the health of your gut by helping to repopulate your gut with friendly bacteria. Probiotics can be added to drinks or yoghurts, or taken in capsule form. They generally produce fewer side effects than other treatments, but can occasionally cause bloating, wind, and in rarer cases, infections. A specific formulation of high-potency probiotics, previously found in VSL#3 but now sold as Vivomixx, has been shown to be effective in preventing pouchitis, and maintaining remission after antibiotic treatment.More research is needed to confirm this effect. Some small studies have found that certain high-potency probiotics may help people with Colitis stay in remission. But it is currently not recommended because other more effective options are available. As yet, there is no clear evidence that probiotics can help induce or maintain remission in people with Crohn’s Disease. Probiotics are not available on prescription, and can be expensive. If you do decide to take probiotics, try find one with lots of bacteria in them. High-potency probiotics like VSL#3 and Viviomixx have 450 billion bacteria with several strains, but probiotics sold in supermarkets typically only contain 10 billion bacteria and one strain. A lot of the bacteria can be destroyed by stomach acid, so the actual amount of bacteria reaching the bowel is not known.Probiotics containing live bacteria need to be stored in the fridge. Any probiotic that contains lactobacillus is derived from milk, and so many not be suitable for those with severe dairy intolerances.

• Enteral or parenteral nutrition: a special liquid diet taken by mouth or given via a feeding tube (enteral nutrition) or nutrients injected into a vein (parenteral nutrition) may be recommended for severe IBD flares. This can improve the overall strength and nutrition, and allow the bowel to rest, which can reduce inflammation.

SURGERY

Even with proper medication and diet, as many as two-thirds to three-quarters of people with IBD will require surgery at some point during their lives. While surgery does not cure IBD, it can conserve portions of your gastrointesinal tract and return you to the best possible quality of life.

Surgery becomes necessary when medications can no longer control symptoms, or if the patient develops a fistula, fissure, cancer or intestinal obstruction. Surgery often involves removal of the diseased segment of bowel (resection), the two ends of healthy bowel are then joined together (anastomosis). While these procedures may cause the symptoms to disappear for many years, IBD frequently recurs later in life.

Key things to know about Surgery:

• About 70% of people with Crohn’s disease eventually require surgery.
• In one-quarter to one-third of patients with ulcerative colitis, surgery will be necessary.
• Different types of procedures may be performed depending on the reason, severity of illness, and location of the disease.
• Approximately 30% of patients who have surgery for Crohn’s disease experience recurrence of their symptoms within three years and up to 60% will have recurrence within ten years.
• In ulcerative colitis, surgery involves the removal of the entire colon and rectum, with the creation of an ileostomy or external stoma (an opening on the abdomen through which wastes are emptied into a pouch, which is attached to the skin with adhesive).

As we have explained, the treatment should be completely personalized depending on every patient symptoms, severity and response to therapy. Different drugs combinations could be attemtped accompained by nutritional therapy to improve the quality of life of those living with IBD. Surgery is always the last option, only if everything else fails or if there is an emercency. 

I truly hope you have found this info useful and interesting. 

Have a nice day and see you soon!

Sonia