Colitis bleeding won’t stop

Prednisone Didn’t Clear Colitis — Time for Biologics?

Q1. My son has been diagnosed with colitis and had a nasty flare. He was diagnosed in February, and it was managed through Asacol (mesalamine). However, two weeks ago he was bleeding and going to the bathroom 16 to 17 times a day. A colonoscopy was done and his colon was totally inflamed; it was no longer just the lower part of his colon. He was placed on 40 mg of prednisone and Asacol (12 per day). He has been on this for nine days. He now goes to the bathroom seven times a day, still with some blood. He says he is feeling better, is no longer nauseous and is even working out again. We are supposed to start tapering him off next week but he still is bleeding. He is supposed to start on 35 mg of prednisone and continue to taper. What are your thoughts on this treatment? I am so worried about this. I am also worried as he plays college baseball and plans to play this fall which I feel is foolish. I don’t feel this disease is under control at all! Please help us!

Most patients with severely active ulcerative colitis will respond to prednisone. Those who do not, like your son, will need alternative medications. One alternative is infliximab (Remicade), which is approved for ulcerative colitis treatment and very often helps dramatically. Infliximab is in a class of medications known as biologics and it works by blocking tumor necrosis factor, or TNF, a protein that causes increased inflammation.

Your son will most likely need something like infliximab to induce remission before he is able to play baseball at a competitive level. Prednisone cannot be taken for long periods of time because of serious side effects. So even if this drug eventually helps him, a long-term medication like infliximab should be considered.

Q2. I have heard that Remicade can only be taken for six years. Is this true? If yes, why? If no, are there any limitations on this or any other drug for GI disorders?

No, there is no time limit on the use of Remicade in ulcerative colitis. In general, there are no time limitations on any drug we use for inflammatory bowel disease.

However, the longer you take Remicade, the higher your risk is of developing complications, like opportunistic infections. Other drugs, such as the 5-aminosalicylic acid compounds, are much safer and much less expensive than Remicade. If you can be treated with these medications instead of Remicade, you are better off.

You can find more information on ulcerative colitis treatment in Everyday Health’s Ulcerative Colitis Center, as well as information on planning your colitis treatment strategy, the risks and benefits of colitis drugs, ways to cope with side effects of drugs, and alternative therapies for colitis.

Q3. I have had ulcerative colitis for over 19 years; now I am 34. I’m female. I have tried Asacol (mesalamine), which I am still taking, but I can’t get and stay in remission. I have also tried Colazal (balsalazide), Imuran (azathioprine), Rowasa (mesalamine) and prednisone. Do you have to take any pills with Remicade (infliximab) or just through your IV? I am running out of options. Can it be taken long-term?

All patients with ulcerative colitis should be on a 5-ASA product, like Asacol, and I would recommend that you stay on it.

Remicade need not be given with any additional pills, but many physicians use azathioprine (Imuran) or 6-mercaptopurine (Purinethol) during the first few months of Remicade to diminish your immune system’s response to Remicade. When your body produces antibodies in a mistaken attempt to “fight off” the Remicade, there’s a risk of lower response rate and infusion reactions.

Yes, Remicade can be taken long-term to maintain remission.

Q4. I have a drain in an abscess cavity with a connecting fistula between the cavity and my anal canal. How likely would it be for a fistula to form from the anal canal to the vagina, and what would the symptoms be? Nothing has worked to close the perianal fistula — I’ve tried Remicade, 6-MP, an advancement flap, and plugs.

Fistulas are abnormal communications or passages from the gastrointestinal tract to the skin or other organs, such as the vagina, and they are characteristic of Crohn’s disease. Passage of stool and gas through the vagina or urethra are symptoms you would expect if there were a fistula to the vagina or the bladder from the anal canal.

Surgical drainage of any abscess is an important first step in the management of fistulas, but a combination of medical and surgical therapy usually works best. It seems as though you could benefit from another opinion from experienced physicians, preferably at a major medical center where there are experts in gastrointestinal conditions like Crohn’s and colitis.

Q5. My son (age 17) was diagnosed with ulcerative colitis in December 2004. At that time, he was having diarrhea 10 to 12 times a day. For the past year, he has been on prednisone, which helped. He was finally able to get off it (had trouble with weaning as symptoms came back full force). He is still having somewhat loose and unformed stools about four to five times a day. I feel that he is still not in remission, and I’m wondering what the next step would be to help him. Or will his stools always be this way? Am I expecting too much for him to have formed stools only once a day?

Remission in ulcerative colitis can be maintained with anti-inflammatory medications that do not have steroids in them. The most commonly used medications are ones that have 5-aminosalicylic acid (5-ASA) in them, such as mesalamine (brand names are Asacol, Pentasa, Lialda, Rowasa or Canasa), balsalazide (Colazal) and olsalazine (Dipentum).

Other possibilities for steroid-free maintenance include 6-mercaptopurine, Imuran (azathioprine), methotrexate and Remicade (infliximab). With the right combination of medications, your son could have fewer bowel movements daily.

Learn more in the Everyday Health Ulcerative Colitis Center.



The colectomy rate in severe UC (30%-35%), as well as percentages of remission and response, have remained unchanged since the introduction of corticosteroids in UC treatment, and similar results have been reported in both clinical trials and in the clinical setting. The classic limit of 7-10 d for establishing the criteria of steroid resistance was based on the results of historical series showing that the median time of remission was 7.5 d and that prolonged administration beyond 10 d did not increase the percentage of remission.

However, some authors have argued in favor of a more conservative approach since a group of “slow responders” have been identified. These patients showed a partial response within 10 d of admission, defined as a decrease in stool frequency, with little or no blood. In the largest retrospective series of a single experienced hospital (149 episodes in 115 patients), 19% fulfilling this criteria entered into remission within the first 21 d of treatment. More importantly, the long-term follow-up of these “slow-responders” showed that none of them required colectomy within a median follow-up period of 49 mo. These data are in contrast with the high colectomy rate of corticoesteroid refractory patients one year after ciclosporin-induced remission when azathioprine is not administered to maintain it.

In contrast with this point of view, a more resolute approach is based on the results of several studies which have identified factors predictive of treatment failure soon after corticosteroid initiation. The study of Travis et al was a pioneer in this area, demonstrating a prospective day-by-day evolution, during the first days after admission, of several inflammatory parameters (C reactive protein (CRP), erythrocyte sedimentation rate (ESR), platelets, etc) and clinical symptoms (bowel movements, blood in stools, pulse rate, etc) in 51 consecutive episodes of severe UC. This study identified a turning point in the disease outcome on the third day of treatment, establishing a critical limit for deciding whether patients are responders or non-responders. Two simple parameters (stool frequency of > 8 per day or 3-8 bowel movements per day and CRP > 45 mg/dL on the third day of therapy) have a positive predictive value (PPV) of 85% for colectomy. Similar results (decreased CRP and Montreal classification of UC activity as independent predictive factors for response on the 3rd day of treatment) have been obtained in a recent validated prospective study published as an abstract form. Two additional studies retrospectively analyzed clinical and biochemical data at 1, 3 and 7 d, or within the first 3 d of medical therapy, to obtain predictive models of the likelihood of colectomy. In one of these, a value higher than 8 obtained by the formula stool frequency/d + 0.14 × CRP (mg/dL) calculated on the 3rd day after initiation of treatment had a PPV for colectomy of 72%. This study confirmed that a regression formula including the same simple parameters used in the Travis et al study allows prediction of treatment failure and colectomy in a high percentage of severe UC patients. These results were prospectively validated in the only randomized, placebo-controlled study assessing infliximab as rescue therapy in severe UC, showing that patients fulfilling an index criteria of fulminant colitis (value ≥ 8) in the placebo arm had a PPV for colectomy of 69%. In the other retrospective study, a risk score was proposed to identify patients who are at low, intermediate or high likelihood of not responding to intensive medical treatment, aiding in the early selection of patients for second-line medical therapy or colectomy. Multiple logistic regression analysis identified mean stool frequency (graded from 0 to 4 points) and colonic dilatation (4 points) within the first three days and hypoalbuminemia (1 point) on day 1 of treatment, as significantly predictive of the need for surgery within the hospitalization period. The risk score allowed the stratification of patients into those with low (11%; score 0-1), intermediate (45%; score 2-3) and high risk (85%; score ≥ 4) of not responding to medical therapy. With a cut-off of ≥ 4 points, the sensitivity and specificity in predicting non-response to medical therapy were 85% and 75% respectively.

The results of these studies are in agreement with previous observations showing that complete remission, which takes longer than response, is achieved, in the majority of steroid-sensitive cases, within 7 to 8 d of beginning corticosteroid treatment.

In conclusion, to evaluate steroid resistance, steroids must be intravenously administered, in the hospital setting, at a dose equivalent to 1 mg/kg per body weight of prednisone. The lack of response at day three of steroid treatment, as defined by well-established clinical parameters, suggests a high probability of colectomy and should be used in general as a limit point to define steroid resistance. Whether 3, 7 or 21 d are used as a limit marker for steroid resistance, judicious decisions by physicians, skilled in Inflammatory Bowel Disease management, should prevail. The risks and benefits of any decision have to be carefully weighed, taking into account that the priority in the management of severe UC is to save the patient and, if possible, the colon.

Current approaches to the management of new-onset ulcerative colitis

Nonadherence to 5-ASAs is particularly high with reported index medication compliance of 57.2% in one study.119 Greater risk of disease relapse has been seen in both nonadherent patients and in adherent patients whose mesalazine formulations were switched.122 Patients on single daily dose MMX mesalamine appear to have the lowest discontinuation risk and highest adherence rate.121 Over 75% of IBD patients are compliant with anti-TNF therapy. Factors predicting nonadherence for IFX or ADA include female sex, smoking, anxiety, moodiness, and treatment-related constraints.123 It has been reported that IBD patients may misperceive the risks and benefits of anti-TNF therapy, namely IFX; as per questionnaire results, a majority of IBD patients would be unwilling to accept treatment-related side effects if the remission rate at 1 year was <75%. Such perceptions appear to be independent of age and duration of disease.124 In one study, highest adherence rates were seen with immunomodulators.125

Medication compliance should be assessed during each patient evaluation, especially in the setting of quiescent disease. Stress and mental health-related disorders like anxiety and depression reflect health-related QOL in IBD patients and may affect compliance so should be addressed in conjunction with medical and/or surgical therapy.126 Development of a patient-administered tool to assist practitioners in evaluating noncompliance would be beneficial in the clinical setting.125 Web-based health care designs may improve patients’ knowledge and QOL in the setting of chronic disease and may encourage adherence through a model of continued care.127

Practitioners should have a heightened sensitivity for the aforementioned patient-centered issues. Individualized therapeutic approaches are required and must take into account extent and severity of inflammatory disease with additional considerations for such factors as medication administration (route, pill burden), financial costs, age, lifestyle, occupation, and fertility/pregnancy status among others. Careful provision of informed consent relating to IBD therapy includes discussion of available therapeutic options, risks associated with lack of or suboptimal treatment and/or noncompliance, and pharmacotherapeutic alternatives such as colectomy. The ability of patients to comprehend and procure information about their chronic disease state is paramount. Shared decision making is an optimal model in such medical treatment encounters and should thus be advocated.128


UC is a chronic inflammatory colonic disease with a relapsing and remitting course. Once the diagnosis is established, new-onset cases should be stratified into mild, moderate, or severe disease categories to guide initial therapy. In general, mild-to-moderate UC can be managed in the outpatient setting with 5-ASAs, mesalamine, and topical corticosteroids (combined topical and rectal therapy ideal) and with oral corticosteroids in unresponsive cases. Oral or IV corticosteroids in the short-term are used for moderate UC with consideration of long-term options such as biologic agents or immunomodulators. Patients with moderate UC, those recalcitrant to IV corticosteroids, or those with disease complications should be considered for a biologic agent or CsA; colectomy is also a rescue option for moderate-to-severe cases. Early surgical involvement is crucial, and colectomy may be life-saving in refractory or fulminant cases. Frequent assessments are needed to determine clinical response with intensification of therapy as needed to achieve disease control. Short-term treatment choices may be influenced by long-term management goals. Several new drugs have shown efficacy and safety for UC. Medication compliance and health-related QOL are important patient-centered issues. Future directions include continued drug development with longer-term safety and efficacy profiling and patient initiatives to encourage continued quality IBD care.


Dr Sunanda Kane is a consultant for AbbVie and Shire. Renée Marchioni Beery reports no conflicts of interest in this work.

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