Ulcerative Colitis Blog

A very common question from patients is whether they can stop taking their medications once they are feeling well? I hear this question most often from younger or recently diagnosed patients who do not understand or accept that UC is a chronic disease which requires lifelong therapy.

Some patients will do well off medication for a period of time, sometimes a long period of time, until symptoms return. Since UC is a relapsing disease, just as flares happen spontaneously, remission can occur and last for a while off medication.

It is important to think of UC as a disease, like diabetes or high blood pressure, which requires life long medication, but not necessarily life long symptoms. If medications are taken regularly patients will feel better, often completely normal. It is when medications are discontinued or taken sporadically because they are not given high priority or there is denial about having a chronic disease that symptoms can return.

A self-fulfilling process takes place in which patients who take their medications and make it a part of their daily schedule have the best chance of remaining well, while those who are not compliant because of an unwillingness to take pills or denial regarding the diagnosis of a chronic disease will inevitably become ill.

In a recent blog I touched on the role of probiotics in UC. Another burgeoning area of research is the utility of "prebiotics" in the treatment of UC. Prebiotics are non-digestible dietary carbohydrates (think fiber, bran, germinated barley) that help protect the normal bacteria of the colon, stimulate the growth/metabolism of colon cells, and aid in the production of protective mucus lining the colon. When these food products are ingested, bacteria in the colon ferment them to make chemicals called "short chain fatty acids" or SCFAs. Scientists believe that these SCFAs may have anti-inflammatory properties that can help reduce colon inflammation in UC.

At present, only a handful of studies examining prebiotics in UC have been performed in humans. In one study of patients with mild to moderate UC, consumption of germinated barley foodstuff showed a significant reduction in disease activity up to 24 weeks. Another investigation showed that UC patients in remission who consumed 20 grams of germinated barley foodstuff daily had improved clinical results and fewer relapses than patients who were not taking the prebiotic. No significant side effects were noted in either study.

While no studies have conclusively shown that any specific type of food causes or worsens UC, these investigations raise the interesting possibility that certain foods may be helpful in decreasing inflammation. There is no data to suggest that these food products can or should replace standard medicines; rather, they may serve as a helpful adjuvant in the management of UC.

Vaccine administration is a complex process with varying schedules. Since people move around so much today these vaccinations are often administered by multiple health care providers, so full records are often lacking. More people than ever are traveling to exotic locales which require special vaccination.

Vaccine administration in the immunocompromised patient can have severe consequences. A UC patient is considered immunocompromised if she has:

1) significant malnutrition OR is currently on or has received any of the following UC treatments within the past 3 months:
2) azathioprine,
3) 6-mercaptopurine
4) infliximab
5) >20mg/day prednisone

If you meet the criteria for immunocompromise the the following live bacterial and viral vaccines should be avoided since they may cause active.

Varicella
Zoster
MMR (measles, mumps, rubella)
BCG
Anthrax
Smallpox
Yellow fever
Adenovirus
Typhoid
Cholera
Tick-borne encephalitis

According to the US Centers for Disease Control (CDC) immunocompromised UC patients should receive immunizations for tetanus, diphtheria, pertussis, influenza and pneumococcus according to the same schedule as the general population. Young women can and should receive the new HPV vaccine. The Hepatitis A and B and meningococcal vaccines should be given as needed for travel or based upon expected exposure.

Travel to certain areas of the world, such as Africa, which requires a yellow fever vaccine, is contraindicated while immunocompromised. When it becomes apparent that you will be starting immunosuppression, it is important to discuss whether any of the live vaccines need to be administered prior to initiation to therapy. For example, a patient who has not ever had chicken pox would want to have the varicella vaccine prior to immunosuppression to avoid complications later on.

For more information see the CDC website at www.cdc.gov.

YS wrote in to the blog recently with questions regarding immunomodulators for UC.

The immunomodulators, azathioprine and 6-mercaptopurine (6-MP), are medications which have been widely used in both Crohn's disease and UC for many years. The medications work by inhibiting metabolism of nucleic acids and cell growth. Indications for starting immunomodulator therapy include disease refractory to maximal treatment with oral 5-ASA medications, topical 5-ASA and steroids, and high doses of prednisone, in those patients who are no so ill as to require hospitalization.

Immunomodulator therapy is often started at a dose of 25 to 50mg daily. The maximal doses of immunomodulators are often quoted as: 1.5mg/kg/day for 6-MP and 2.5mg/mg/day for azathioprine. Many physicians will perform a blood test to measure the level of an enzyme called TPMT that is required to metabolize the medications. Knowing this value can help physicians adjust a patient's dosage. It takes 6-8 weeks for these medications to build-up to a therapeutic level in the body. As such, a person must be stable enough to be able to wait through this time for the medications to take effect. Tests are available to monitor the level of the medication in a person's blood to help guide future dosing.

Potential side effects of immunomodulators include nausea, vomiting, bone marrow suppression (a low white blood cell count), pancreatitis, elevation of liver enzymes, and allergic reactions. Patients starting on these medicines are initially required to have blood tests performed every 2-4 weeks to survey for side effects. If lab tests remain stable for 2 months, they are then checked every 3-4 months for the duration of medication use.

Christine wrote into the blog with concerns pertaining to her young grandchild with colitis. The peak onset of IBD in children typically occurs between 10-15 years of age. Children with the onset of IBD at ages less than 5-8 years fall into a unique category of patients. Studies of these very young IBD patients (< 5-8 yrs) have shown that there is a predominance of colonic involvement of disease. Furthermore, distinguishing between Crohn's disease and UC can be particularly challenging in this age group. Fifteen to 30% are diagnosed with "indeterminate colitis," which is a form of IBD carrying features of both Crohn's and UC. Symptoms of UC in the very young are similar to those of older children and adults, consisting of diarrhea, blood in the stool, and abdominal pain. Just as in older patients, the disease course in the very young varies considerably. The unpredictable nature of IBD is perhaps one of the most frustrating aspects of the condition for both patients and physicians. The treatment goals are to induce remission of disease and find an acceptable maintenance agent to keep disease quiescent and minimize untoward side effects. Unfortunately, there is a paucity of data regarding response to therapy in this age group. Studies of colectomy rates in this age group have suggested that 5-20% will require removal of the colon in the first few years of disease.

Christine also commented on her own feelings of frustration and helplessness with respect to her grandchild's illness. When children have a chronic medical condition, it affects the entire family. Many parents describe feeling a loss of control over life when their child falls ill. As it is human nature to want to care for and protect young children, there is a strong emotional investment from the entire family unit. Christine notes in her email family disgareement regarding the course of her loved one's therapy. Finding ways to discuss these issues rationally in a non-confrontational manner is key. In these situations, bonding together in a cohesive, supportive manner is in the best interest in the child and family members.

If a UC patient does not improve on 5-ASA or immunosuppressant therapy with azathioprine/6-MP there are other available medical treatments to consider prior to surgery.

Infliximab is an antibody to tumor necrosis factor (TNF). The not so accurately named TNF, is integral to the development of inflammation in the intestine and throughout the body. Infliximab is administered as an intravenous infusion every 8 weeks. It is effective at reducing UC symptoms and the need for surgery. About 50% of patients who have failed to respond to azathioprine will benefit from infliximab compared to 25% who receive placebo. About one-third of the infliximab treated patients will have a remission of symptoms, twice the placebo response. If infliximab is ineffective, poorly tolerated, or unavailable then the patient would need to undergo surgery or enter into a clinical study.

Adalimumab is an antibody, similar to infliximab, which blocks the pro-inflammatory effects of TNF. It is administered as an intramuscular injection like an epinephrine pen every 1 or 2 weeks. Adalimumab has already been effective and approved for use in Crohn’s disease, rheumatoid arthritis, and psoriasis.

Next week I will review a few more drugs currently undergoing clinical trials for UC.