Ulcerative Colitis Blog

Once a new diagnosis of UC is made there are several available treatment options ranging from no treatment at all to various medical therapies to surgical resection of the colon.

The mainstay of medical treatment for mild to moderate UC is the 5-aminosalicylic acid (5ASA) class of medications, including sulfasalazine, mesalamine and balsalazide. While all of these medications have similar efficacy, sulfasalazine has a higher rate of dose dependent side effects including nausea, vomiting, and headache. Sulfasalazine and balsalazide are only available in pill form for oral delivery, while mesalamine is available in pill form, as well as suppository and enema formulations. Side effects of mesalamine include diarrhea and rare kidney toxicity.

The 5ASA’s are anti-inflammatory drugs that block several important immune response pathways. They seem to work both locally, by direct effects on the intestinal cells, and systemically, once absorbed in to the circulation. While chemically similar to acetylsalicylic acid (aspirin), 5ASA has different effects on the gastrointestinal tract and immune system. Most notably, aspirin exacerbates UC in some cases.

Several clinical trials have shown that there is a dose dependent effect of the 5ASA’s. A high dose is more effective at inducing remission, while a lower dose is effective at maintaining remission. Distal UC, affecting the left colon (descending, sigmoid, or rectum) may be treated with 5ASA in suppository or enema formulations. Enemas reach the entire left colon, but suppositories only treat the rectum. These rectal formulations may be effective on their own, but response is even better when paired with oral 5ASA therapy.

The potential role of 5ASA as a chemopreventive (see posting 8/23) against colon cancer in UC makes its long term use a compelling, though unproven, consideration.

The inflammatory bowel diseases, Crohn's disease and ulcerative colitis, are chronic, relapsing disorders characterized by periods of quiescence and recurrent inflammation. The overall goal of treatment is to halt the inflammatory process and keep it at bay long-term. Treatment for UC consists of medication therapy and, in some patients, surgery if the disease proves to be refractory to medical management. Because UC affects people differently, a variety of factors are taken into consideration when creating an individual treatment plan for each patient. The following provides a brief overview of the key aspects physicians consider when choosing therapies.

1. Phase of Disease
Based upon the relapsing and remitting nature of IBD, disease activity and treatment is divided into 2 phases: Induction of Remission and Maintenance of Remission.

1) Induction of remission: When a person has signs or symptoms of active disease (either at diagnosis or during relapse), potent medications are used to decrease inflammation as quickly as possible and induce remission. As an analogy, you can liken the inflammation of IBD to a bonfire and the medications used to induce remission are akin to buckets of water being dumped over the flames to stamp out the fire. Examples of medications commonly used to induce remission are steroids, infliximab, and cyclosporine.

2) Maintenance of remission: As UC is a chronic disease, medications are required to maintain remission of disease once an acute flare has been controlled. These may be the same medications used to induce remission, or others which are selected due to lower toxicity long-term. Examples of medications used for maintenance of remission are: 5-ASA drugs (sulfasalazine, mesalamine), azathioprine, 6-mercaptopurine, and infliximab.

2. Extent and Severity of Disease

1) Extent of disease: UC universally involves the rectum and may extend to involve part or the entire colon. If only a limited portion is involved at the end of the colon/rectum the disease is termed “proctosigmoiditis”; if the disease progresses and affects the entire colon it is called “pancolitis”. The extent of disease guides the choice of medication in that disease limited to the very bottom of the rectum may be effectively treated with enema preparations, as opposed to more extensive disease which requires the use of oral medicines.

2) Severity of disease: The severity of UC varies among individuals and can change over the course of a person’s disease. Typically, disease severity is categorized as mild, moderate, or severe. The severity of disease may alter the choice of medications used to treat UC as more severe disease is treated with medications of greater potency.

3. History of Disease
Choice of medication may also be affected by the duration of disease and number of relapses/flares a patient has experienced. Medications used on initial presentation of disease may be changed later in the course depending on the number and intensity of relapses.

4. Other Considerations
Outside of specific disease characteristics, other considerations for choice of medical therapy may be impacted by patient drug allergies, tolerability, and cost.

The use of a class of steroids known as “corticosteroids,” is common for the induction of disease remission in IBD. This form of steroid is different from the anabolic type of steroids which receive media attention regarding use among athletes. Corticosteroids have a variety of anti-inflammatory effects which make them useful in the short-term to aid in achieving control of disease. Corticosteroids are produced in topical, oral, and intravenous formulations which can be administered depending on the severity and locations of a patient's disease.

Topical Corticosteroids
UC which is limited to the very bottom portion of the rectum is called ulcerative proctitis or proctosigmoiditis. Patients with mild-moderate forms of ulcerative proctitis limited to the rectum or distal portion of the colon may be candidates for topical corticosteroid therapy. Topical corticosteroids come in enema solution and foam preparations. During periods of active disease, enemas are typically administered at night. Patients should be instructed to use the washroom prior using enema preparations in an attempt to empty the rectum. Ideally, enemas should be retained on the rectum as long as possible (hours to overnight). Many patients note that the foam preparations are easier to retain due to the consistency of the medication. As disease activity subsides, the enemas can be spaced out and tapered. The corticosteroids applied topically are systemically absorbed to some degree, and can result in side effects similar to those of oral steroids. For this reason, they are not recommended for long-term use and topical 5-ASA preparations may supplant them.

Systemic Corticosteroids
For disease that involves more extensive portions of the colon (beyond the left side of the colon) or is of greater severity, oral and/or intravenous corticosteroids may aid in inducing remission of disease. Oral prednisone is commonly prescribed at diagnosis and during flares of disease to quickly abolish the cycle of inflammation. At maximum doses (typically 40mg daily), patients responsive to corticosteroids will note abrupt improvement in symptoms over a period of days to weeks. Once a patient feels well again (1-2 formed bowel movements per day, no blood, no urgency, no nighttime symptoms), the steroids can be gradually tapered. In instances where the colitis is severe, patients may fail to respond to oral steroids. For these forms of severe, acute disease, hospitalization with intravenous corticosteroids is recommended. The vast majority of patients receiving intravenous therapy will note an improvement in symptoms within 5-7 days; a transition is then made to oral steroids with eventual taper.

Side Effects
While corticosteroids have a variety of useful anti-inflammatory properties, the duration of their use is limited by toxicities which are time and dose dependent. As such, corticosteroids are indicated for a limited time (weeks to 3 months) to obtain disease control and then should be safely tapered; their use for maintenance of disease remission is not recommended. Many side effects are dose-dependent and reversible with the exception of osteoporosis, osteonecrosis, and cataracts which are irreversible.

1) High blood pressure - Corticosteroids cause sodium (salt) and water retention which results in swelling and can elevate blood pressure.

2) High blood glucose - Hyperglycemia (a high blood sugar) can occur with steroids. Signs and symptoms of high blood glucose include excessive thirst and urination as well as fatigue. Careful monitoring of blood glucose levels is necessary for diabetics with IBD who require steroid treatment. Other patients exhibiting signs and symptoms of hyperglycemia should have a blood glucose checked.

3) Low potassium levels - Low blood potassium levels can be associated with corticosteroid use and are manifested by musculoskeletal cramps, weakness, nausea, and vomiting

4) Osteoporosis - Long-term corticosteroid use (>3 months) impairs calcium metabolism and can weaken bone mineralization. Patient’s receiving corticosteroids for > 3 months should have a bone density scan performed to assess for changes in bone mineralization.

5) Osteonecrosis - Osteonecrosis is a form of irreversible bone injury resulting from loss of blood flow to bony tissue. It most commonly affects the hip, shoulder joints, leg and foot joints.

6)Cataracts - Cataracts are associated with long-term corticosteroids use. Patient’s utilizing recurrent courses of steroids should have routine eye exams.

7) Fluid retention - As noted above, corticosteroids result in salt and water retention which makes patient’s swell. Many people will note fullness in the cheeks as well as fluid around the ankles.

8) Skin changes - Corticosteroids may thin skin or result in striae, the technical name for stretch marks.

9) Increased appetite - Many patients note a dramatic increase in their appetite after starting steroids.

10) Irritability/Insomnia - High doses of corticosteroids often make people feel jittery or hyperactive. Sleep disturbances may be noted.

If mesalamine type medications fail to induce and maintain a remission of UC then other medications are required. Corticosteroids, such as prednisone, are able to induce remission, but are not appropriate for long-term maintenance of remission due to significant side effects such as osteoporosis, weight gain, acne, elevated sugars, exacerbation of psychiatric illness, and insomnia.

In this case, use of the thiopurine drugs azathioprine (AZA) and 6-mercaptopurine (6-MP), is appropriate. Azathioprine is a pro-drug which the body immediately breaks down to 6-MP. Azathioprine is 50% 6-MP by weight, so the dose of azathioprine is twice 6-MP, but the two drugs are otherwise identical.

The mechanism of action is not fully understood, but AZA/6-MP are thought to block DNA synthesis and decrease the number and function of white blood cells. They can take one to three months to take effect, so they are not practical for induction of remission, but are effective at maintaining remission.

Your doctor may test you for thiopurine methyltransferase (TPMT) before starting AZA/6-MP. TPMT is one of the enzymes that metabolizes 6-MP. There are three levels of TPMT enzyme function: normal; intermediate; and low. These are based upon whether a person has two normal genes, one normal gene, or no normal genes for the enzyme, respectively. Patients with intermediate or low functioning TPMT have a higher risk of developing bone marrow suppression resulting in low white blood cell count and an increased risk of infection. They require lower doses of medication and closer monitoring of laboratory tests for side effects.

A test can be performed to measure the level of AZA/6-MP metabolites in the blood stream. Levels of 6-TG and 6-MMP are predictive of symptom response and toxicity and can be used to help guide dosing.

Next week I will review the adverse effects of AZA/6-MP, which needlessly frighten many patients.

In response to my last blog on steroid use in UC, a comment was posted regarding options for patients who experience recurrent symptoms while reducing steroid doses.

As a brief overview, patients with UC on steroid therapy fall into 1 of 3 categories:
1) Steroid responsive - Approximately 50-55% of UC patients enter into prolonged disease remission with steroids and are able to transition to stable maintenance therapies.
2) Steroid dependent - This group encompasses about 25-30% of patients who experience remission of disease with high steroid doses, but then have recurrent symptoms as the steroids are titrated to lower doses or within 6 months of finishing the first steroid course.
3) Steroid refractory - A smaller proportion of patients (15-25%) have severe colitis that fails to respond to the highest acceptable dosages of oral steroids.

The comment posted raises the question about alternative therapies for patients who have developed steroid dependent UC. A few notes on this topic:

5-ASA Medications (ie; mesalamine, balsalazide)
Based on current scientific literature, the use of oral 5-ASA medications, either alone or in combination with other therapies, has not been shown to have a significant beneficial effect in steroid-dependent UC. There is little data regarding the use of topical 5-ASA medications (enema/suppository) in limited rectal disease for steroid-dependent UC.

As such, if a patient experiences rectal bleeding from a limited segment of disease in the rectum while tapering steroids, a trial of topical therapy could be considered. This would not be of value for patients with more extensive disease.

Thiopurines (ie; azathioprine, 6-mercaptopurine)
Thiopurines are commonly used in steroid-dependent UC in an effort to maintain remission as steroids are tapered. Since they have shown success as steroid-sparing agents, their use has gained wide acceptance in clinical practice. In order to be effective, however, they should be administered at optimal doses of 2-3mg/kg body weight for azathioprine and 1-1.5mg/kg body weight for 6-mercaptopurine. In patients who have persistent symptoms despite a routine dosage of medication, levels of the drug can be measured in the blood to see if it is being metabolized effectively. If the levels are low, the medication dose may need to be increased to fully treat the inflammation.

Methotrexate
Current guidelines do not advocate the use of methotrexate in steroid-dependent UC; however, this is mostly based upon the fact that there is a paucity of well-designed studies investigating this drug in steroid-dependent UC. There is limited evidence that higher doses of oral methotrexate or the injectable formulation may benefit a subset of steroid-dependent UC patients who are intolerant of or fail treatment with thiopurines. The use of this medication may warrant further study for this indication.

Infliximab
Infliximab received FDA approval for the treatment of moderate-severe active UC in the last year or so. At least one study specifically examining its utility in steroid-dependent patients has suggested it is potentially beneficial. Infliximab is typically administered as a dose of 5mg/kg at 0, 2, and 6 weeks, then once every 8 weeks. In patients who have an inadequate or waning response, the dose of the medication can be increased to 10mg/kg and/or the dosing interval can be shortened to every 4-6 weeks. The efficacy of adalimumab in UC is under investigation.

Experimental therapies
Some medical centers offer experimental therapies for patients who are failing the currently accepted medical regimens. Before exploring such therapies, patients and physicians should have a thorough discussion about the state of the patient's overall health status, realistic expectations for the future, and risks vs. benefits.

Surgery
The goal of any treatment is to restore a patient's physical health and wellbeing. For patients who have exhausted all possible medications, surgery may be the only tenable option to give a patient his or her quality of life back. While the prospect of surgery is understandably daunting and procedures are not without the possibility of complications, surgical management eliminates the future risk of colon cancer and has the potential to restore quality of life. Any UC patient considering surgery should discuss with his/her doctor referral to a colorectal surgeon who is specifically experienced in the surgical management of IBD patients. More on issues surrounding surgery will be discussed in future blogs.

There are several notable side effects of the thiopurines [azathioprine (AZA)/ 6-mercaptopurine (6-MP)]. They can be classified as early or late onset.

The early reactions are allergic and affect about 5% of users. They include pancreatitis (inflammation of the pancreas), hepatitis (inflammation of the liver), fever, nausea, rash, and fatigue. Abrupt discontinuation of medication leads to complete resolution of symptoms.

Late onset, or dose dependent, reactions include decreased levels of white blood cells (leukopenia), red blood cells (anemia), and platelets (thrombocytopenia) due to suppression of the bone marrow and hepatitis. It is not clear if thiopurines increase the risk of lymphomas or other cancers. Several studies have produced conflicting results. Leukopenia causes an increased risk of infections and thrombocytopenia causes bruising and bleeding.

In order to minimize the risk of dose-dependent side effects, blood tests are performed regularly on patients using AZA/6-MP to evaluate bone marrow suppression and hepatitis. White blood cell count and liver enzymes are tested every 2-4 weeks during the first couple months of therapy and after dose increases, but once a steady dose is achieved testing is performed approximately every three months. If testing shows an abnormality then either the dosing is adjusted or the medicine is changed.

If the thiopurines are used appropriately and followed closely then they are very safe and effective medications for moderate to severe UC, but they cannot be safely taken without follow-up. Skipping blood tests can lead to life threatening complications.

A question was posted by Jack as to how to manage symptoms of ulcerative proctitis (UP) when titrating steroids. While I cannot provide advice specific to individual cases through this blog, there are some generalities regarding treatment of UP that can be discussed.

Treatment of active UP
UP refers to inflammation solely involving the rectum (up to 10-15cm from the anus). Because UP is limited to a very small portion at the end of the colon, suppository and enema therapy is usually first line. Rectal 5-ASA medications (mesalamine) are an appropriate choice when initiating therapy for UP. Suppositories supply medication to the last 10-15cm of the rectum, while enemas (liquid, gel, or foam) deliver medication further up the left colon. Most patients find the suppositories easiest to use. If symptoms persist after 4 weeks of daily rectal therapy, there may be benefit to adding oral 5-ASAs 2.4- 4.8 grams/day. Alternatively, some patients may benefit from adding or switching to a rectal steroid suppository or foam. It should be noted that rectal steroids are absorbed systemically and if used on a regular basis, one can develop steroid-related side effects. As such, rectal steroids are appropriate for inducing remission of disease, but their use as a maintenance agent should be avoided.

Oral steroids are reserved for patients not responding to rectally administered 5-ASAs/and or rectal steroids or to oral 5-ASA medicines. Treatment with prednisone 40mg daily usually results in quick resolution of symptoms. High doses of steroids are used for 1-2 weeks until symptoms improve and are then tapered 5-10 mg per week. The rate at which steroids are decreased depends on a patient's symptoms and overall clinical picture. Slowing the taper or decreasing by 2.5mg increments may help some patients. After decreasing doses, it may take time for the body to adjust. If oral steroids are used, it is recommended that patients continue their prior treatment (rectal 5-ASA/steroid +/- oral 5-ASA) in addition to the steroids. The goal is to use these medications to maintain remission once the prednisone is tapered off.

Treatment of UP refractory to 5-ASA medicines and oral steroids
When patients continue to experience symptoms despite the addition of oral steroids, there are a number of considerations:
1) Is there a gastrointestinal infection present resulting in symptoms?
2) Are patients taking non-steroidal medications like ibuprofen? These medications can worsen
IBD and patients are advised not to take them.
3) Did the symptoms worsen after the addition of a 5-ASA medicine? Some patients will have a
hypersensitivity reaction to this class of medicines which resolves when the medicine is
stopped. The symptoms of a hypersensitivity reaction are usually abdominal pain and
diarrhea.
4) Did the patient just stop smoking cigarettes? Smoking cessation has been associated with
UC.
5) Were the rectal therapies stopped or not been given consistently? Discontinuing rectal
therapies may make disease worsen.

With regard to treatment options, there is no one right answer. While there is insufficient evidence for the routine use of antibiotics in UP and UC, there are reported cases of people with refractory disease improving on antibiotics. As such, a trial of an antibiotic such as ciprofloxacin or metronidazole may not be unreasonable. For ex-smokers, anecdotes of using nicotine patches have suggested they may be of benefit in this subgroup. Finally, escalation of therapy to azathioprine/6-mercaptoputrine, cyclosporine, or infliximab may be considered.

The human gastrointestinal tract is a unique environment home to millions of bacteria. There is a great deal of interest in understanding the role these bacteria play in the GI tract and how they can be modulated to treat disease.

Probiotics are living organisms in food and dietary supplements which when ingested, improve the health of the host beyond their inherent, basic nutrition. Similar to the living bacterial cultures in yogurt, probiotics are ingestible cultures of organisms believed to have health benefits. Examples of probiotics include: Lactobacillus GG (LGG), Lactobacillus acidophilus, Saccharomyces boulardii, Bifidobacterium, and E. coli Nissle 1917. Studies in ulcerative colitis have shown that probiotics do not differ significantly from 5-ASA medications for remission of UC with regard to efficacy or safety. Whether they add an additional health benefit when used in conjunction with conventional therapy is an area of active investigation

Probiotics have been shown to have a definitive benefit in the treatment of chronic pouchitis for UC patients who have undergone colectomy with creation of an ileal pouch. A study of the probiotic VSL#3 showed that 90% of patients taking the probiotic had remission of symptoms after a year, compared to only 60% of patients who took a placebo. Other studies suggest that VSL#3 may be useful in preventing pouchitis in patient who undergo colectomy. Studies of Lactobacillus GG in pouchitis, however, did not active the demonstrate the beneficial results as VSL#3.

It should be noted that because probiotics are not a "drug" type therapy, their manufacturing and use is not overseen by governmental body such as the FDA. As such, there is diversity among probiotics in terms of the number of active organisms contained in each and their potential efficacy. Patients considering the use of probiotics are advised to speak with their doctors regarding the efficacy and choice of a probiotic for their condition.

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.

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.

Marylou wrote into the blog asking about medical treatment for ulcerative colitis that is no longer responding to imuran, prednisone, methotrexate, or sulfasalazine. For patients seeking the next line of medical therapy, the agents of choice would be the so-called "biologics" such as Remicade. Two studies called ACT 1 & ACT 2 (Active Ulcerative Colitis Trials) were published in 2005 examining the efficacy of Remicade as a maintenance therapy for UC patients losing response to their current medications. Of the 364 patients enrolled in the studies, 65-70% had a clinical response to Remicade as compared to 29-37% of those who received placebo. Remicade is given as a 2 hour infusion at an infusion clinic or hospital. Initially, a patient receives doses at 1,2, and 6 weeks to build up the medication in the body. Thereafter, it is typically given every 8 weeks.

Another drug in the same category as Remicade is Humira. Its mechanism of action is similar to Remicade, however, it is a "humanized form" (Remicade is made from a combination of mouse and human antibodies and Humira is made from human antibodies). Humira has usually been reserved as a second line agent for people who fail Remicade therapy. It is administered as an injection done under the skin every 2 weeks.

There are several new treatments for IBD that are in the process of being developed. Many large centers and those affiliated with university hospitals can provide patients an option to try new therapies through being in a clinical trial. Patients considering this avenue can contact regional centers to find out if they may qualify to participate in a study.

Marylou also asked about the prospect of surgery in UC. The indications for surgery would include disease refractory to medicines, acute massive bleeding that cannot be stopped, a sick colon that perforates (break open), or cancer. Historically, is has been quoted that 30% of patients who develop severe disease will ultimately require a colectomy. Advances in surgical techniques over the last several decades have provided surgeons with a way to reconnect the small bowel to the rectum after the colon is removed, so appropriate UC patients may not need to wear a permanent ostomy (bag for stool collection). Surgery is a viable and reasonable option for patients suffering from porly controlled disease or ill-toward effects of medications. Patients considering surgery should seek consultation with a colorectal surgeon who is familiar with surgical techniques in IBD patients.

Ted recently wrote into the blog querying the use of fecal biotherapy in UC and a common bacterial gastrointestinal infection known as Clostridium difficle (C. diff).Fecal biotherapy refers to the process of taking stool from a healthy donor and administering it to another individual either by colonoscopy, enema, or a tube inserted from the nose into the intestine. The concept behind this is that the gut theoretically becomes colonized with the bacteria from the healthy donor's stool in the hopes of healing a gastrointestinal malady. This is an extension of probiotic therapy discussed in prior blogs.

There have been at least 3 or 4 published studies regarding the use of fecal biotherapy in UC showing some degree of benefit. In these studies, patients with severe UC or UC losing response to other therapies were given retention enemas of stool from donors. On average, the enemas were administered daily for approximately 5 days. The authors of these studies have suggested that many patients had improved symptoms or achieved remission of UC for 6 months to 13 years. A few caveats to this research are that: 1) the numbers of patients studied were small, 2) none were randomized control trials (the "gold standard" study design for assessing efficacy of treatment), and 3) they are possibly limited by publication bias (ie; studies that show a positive treatment result get published and those that show a treatment doesn't work are less likely to get published).

As Ted noted, this has typically been reported as a last resort type of therapy. A major fear regarding the use of donated human feces is the potential for transmission of viral, bacterial, and parasitic infections among individuals. There are no guidelines as what kind of an individual is an appropriate donor. Furthermore, there is no consensus as to appropriate preparation and administration of fecal contents for biotherapy.

One of the major limitations of our understanding of the bacteria of the intestine has been our inability to grow many of the bacteria outside of the GI tract for experimentation. New molecular methods designed in the last few years, however, have provided scientists with the ability to identify different strains of bacteria in stool. The advent of these tools may help investigators understand more about how fecal biotherapy works and utilize these principles to design more mainstream therapy.

The following biologic therapies have recent or ongoing studies in UC. Some are more promising than others.

Basiliximab is an antibody which binds to the interleukin-2 (IL-2) receptor on activated white blood cells (T-lymphocytes). Antibody binding prevents IL-2 from binding to the receptor and activating the lymphocyte. This process impairs immune system responses. Basiliximab was initially studies in the late 1990s and approved for prevention of organ rejection after kidney transplant. A study of 20 patients with steroid resistant UC showed promising results after a single dose of Basiliximab. Thirteen of 20 patients were in remission after 24 weeks, while had undergone colectomy.

Visilizumab is an antibody to the CD3 antigen, a receptor intimately related to the immune response, with the ability to induce cell death (apoptosis) selectively in activated T cells. Preliminary studies were performed in bone marrow transplant. A single open label phase I (safety) study of 32 steroid refractory patients showed a possible benefit of therapy with an acceptable safety profile. Follow-up studies are currently underway.

Daclizumab is an antibody to the IL-2 receptor similar to basiliximab. It is also used for the prevention of acute rejection of transplanted kidneys. The only study in ulcerative colitis involved 159 patients with moderate disease and did not show a benefit over placebo.

Kevin wrote into the blog recently to share his experience with probiotics in UC:

"Just wanted to mention something that really has worked for me. I have pancolitis (entire colon affected). I seem to flare up every two years and need a round of steroids to get back in remission. This last time, I flared again when I had tapered down off the prednisone a bit. For me, what finally got me off the steroids was a probiotic (live bacteria and other helpful "bugs") called Primal defense. I have been almost as colitis free as before I was diagnosed. Primal defense is soil organisms, similar to what you would ingest if you ate fresh vegetables out of a garden. Apparently they crowd out the unhealthy bugs that tend to accumulate in the guts of IBD sufferers. I can't guarantee it will work for anyone else, but it sure did the trick for me. Of course, check with your GI Doc before trying anything. Most will say stuff like "well, at least it won't harm you."

As discussed in a prior blog, probiotics have been studied for use in UC and Crohn's disease. Thus far, probiotics have only shown definitive benefit for treatment of pouchitis. Results from studies evaluating the utility of probiotics for UC and Crohn's have shown equivocal results. That being said, certainly there are some individuals such as Kevin who have noted improvement which they attribute to the probiotic. For the most part, probiotics are felt to be safe and the majority of physicians are not opposed to patients using them. As not all formulations are the same, however, it is wise discuss probiotics with one's physician before selecting one to take.