Month: July 1999

A reader of an old internet mail list called The IBDList wrote:

So much about having these illnesses cannot be communicated to your own physician in a 15 minute or even a 2 hour appointment. I have an excellent gastroenterologist, but he is extrememly busy and, unless I am in extreme distress at the time, I always hesitate to take up his time. And, of course, some of it just isn’t discussed because it is part of the illness. How do you convey pain? Or extreme embarrassment?

That’s why the list is so important. Sometimes, you just feel likethere is no one to tell or understand. Family members and friends can try to understand (or not), but this goes on so long and is so personal thatyou begin to feel that you are just making people feel worse, so you stoptelling anyone.

When I see comments such as this I have mixed feelings. I want patients to be able to express themselves and talk about their problems. However,I understand that as much as one may try to understand a patients condition,there is a world of difference in understanding the condition and actuallyhave suffered the illness. The physicians role is to understand the patient,the disease, and the treatments well enough to give good advice. Thus,the patient may give enough information to allow the physician to givegood advice, but that may well not be enough for the patient in terms ofemotional support.

Since physicians are limited to understanding the disease through theirpatients, I think it is important for patients with chronic diseases toseek out support groups. Sharing one’s problems with someone who has beenthere is important. Unless your doc has IBD, you probably cannot get thatlevel of understanding. Perhaps, even if you have a doc who has IBD, itis still not the same, for docs know the disease well enough that thereis perhaps less fear of the unknown, even if it is a happy little delusion.

That said, lets use some common sense as well. If you ahve a doc whonever has the time, it may be time to help that physician by decreasingtheir workload. Another doc who has the time may be what you need. Oneof the marvelous things about medicine is the variety of people you meet- both physicians and patients. The variety of needs that patients haveusually can be met by some physician out there. Another use of supportgroups, getting insight on what each doc in the community is like. 

So, if you feel you are a burdeon to your doc, it may be that you need a new doc. But if it is a matter of not being able to really communicate your burdeons, a support group might be very important for you to join.

An online forum of support that I recommend is the IBDList. [The IBDList was a mail-list that was discontinued years ago. The reader is encouraged to browse the internet for one of the many resources now available, and especially to look the the CCFA for local support groups – Ed.]

Stephen Holland, M.D.
Section of Clinical Pharmacology
University of Illinois College of Medicine at Peoria

A reader of the IBDList asked recently if a new anti-inflammatory, Celebrex, would be useful in the treatment of Ulcerative Colitis.  The analogy of sulfasalazine, another drug with a salicylate component was offered as a rational to try it.

Crohn’s and UC are different from arthritis.  Some experience from the past is interesting in this regard.  A chemical in the body called arachidonic acid is converted by a series of enzymes into several chemicals that are part of the signaling system for inflammation. Two class of chemicals, prostaglandins and another, leukotrienes, are of particular interest inIBD.  It turns out that prostaglandins are blocked by drugs like aspirin,Motrin, Nuprin, and other similar drugs.  However, the mesalamine drugs (sulfasalazine, Pentasa, and others) block leukotrienes.

Clinical experience has shown that Motrin and its cousins can actually make UC and Crohn’s worse and cause flares, while mesalamine is beneficial. This clinical observation shows that leukotrienes are an important cause of inflammation in IBD, and prostaglandins are protective.

A new development in arthritis research is that prostaglandins are made by two enzymes, cyclooxygenase-1 and cyclooxygenase-2 (COX-1 and COX-2). It has been found that prostaglandins made by COX-1 protect the stomach from injury, while COX-2 products are important in arthritis inflammation. A new drug on the market, Celebrex, (a.k.a. celecoxib) blocks COX-2 but not COX-1.  It was predicted that this drug would be effective in arthritis and cause less injury to the stomach.  Animal studies and human studies have borne this out.

The natural question for IBD researchers – could a COX-2 inhibitor be beneficial in IBD.

To evaluate that question and not put patients at risk, Brian Reuter at the University of Calgary in Alberta, Canada, gave the drug L745337( a drug similar to celecoxib ) to rats which had colitis induced by an enema of TNBS.  (This is a standard animal model of colitis). The results of the experiment were that the colitis was much worse in the rats given the COX-2 inhibitor.  In fact, it was even worse than giving Naprosyn to the rats, which was also done in the experiment.  Additionally, giving etodolac, an NSAID which turns out to be somewhat more specific for COX-2 than the run of the mill NSAID, was almost as bad as the pure COX-2 inhibitor L745337.

These results lead me to recommend against giving Celebrex to anyone with IBD.  It is interesting that the more selective the drug was for COX-2, the worse the rats did.  Certainly, there are other models of IBD, and it is possible that human UC or Crohn’s will act differently at times than the animal models. However, I’d much rather see the animal studies before trying the drug in people.  This is also a good exampleof how animal studies are beneficial.

I have reported previously on the use of heparin in Ulcerative Colitis.  A trial of heparin versus placebo wasrecently done.  The study was organized by Dr. Korzenik, now at WashingtonUniversity School of Medicine in St. Louis, MO.  I ran one of thesites that participated in the study.  The results of the study wereeagerly awaited.  The results of the trial were recently reportedat a session of Digestive Disease Week, a major international meeting thatI attended in Orlando, Florida.  Following is the abstract as published,with notes afterwards that I added.  The short answer is that it works. Read on for details.
 

Korzenik J, Bitton A, Robert M, et al.: A multi-center, randomized, controlled trial of heparin for the treatment of ulcerative colitis. Gastroenterology 1999, 116:A752.

Background: A series of open-labeled trials suggest a benefit of heparinfor the treatment of Inflammatory Bowel Disease (IBD). No prospective randomizedcontrolled trials have been performed. We report the initial data obtainedfrom a large multicenter controlled trial of heparin therapy for the treatmentof moderate to sever ulcerative colitis (UC). Aims: To assess safety andefficacy of heparin in the treatment of active UC. Methods: Subjects wereenrolled with moderate to severe ulcerative colitis having four or morestools/day. Permissible concomitant medications included mesalamine, steroidsand azathioprine/6-MP for specified durations prior to enrollment. Subjectswere randomized (1:1) to saline injections or standard porcine heparininjections at 10,000 units subcutaneously (sq) bid for 6 weeks. In thoserandomized to heparin, the dose was adjusted by an unblinded observer to10,000 units sq tid for patients whose appt remained below the upper limitof normal. A subgroup (20%) of subjects randomized to placebo receivedtid saline injections. Randomization was stratified by extent of colitis(left sided vs pan – colitis) and by use of steroids. Patients were monitoredwith weekly aPTT and twice weekly CBC. Efficacy was determined by clinicalassessment of stool frequency, frequency of bloody stools, patient globalscale, physician global scale, sigmoidoscopic and histologic assessment(at week 0 and end of week 6). Failure was established by an increase inexisting medications or need for additional medication. Decrease of hematocritby 6 points or decrease of platelets below 100,000 was also criteria fordiscontinuation. Results: 70 subjects were enrolled at 9 sites. No severe adverse effects were observed in any subject. One subject was prematurely discontinued because of a decrease in hct of > 6 points but was in remissionat the time with no evidence of bleeding. Three patients noted a transient increase in rectal bleeding though not clinically significant and wereable to continue their involvement. One patient developed a psoriasiformrash at the injection sites. Enrollment has been completed, but the trialhas not yet been unblinded. Conclusions: 1) The use of heparin is safein the setting of moderate to severe ulcerative colitis. 2) Several subjects are completing their involvement at this time. Data for clinical efficacy will be reported after the trial is unblinded and will be available shortly.

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At the conference the results were further detailed.  The majorresult was that the remission rate was 42% for patients on heparin, 20%for control patients.  It should be noted that these patients wereall not responding to regular therapy, so heparin was started only latein the course of their UC flare.  There was no significant increasein bleeding rates.  Patients that did respond all started to respondby three weeks.  One issue that was discussed was that the heparinwas given subcutaneously rather than intravaneously.  This was done because it was an outpatient study.  Since heparin given subcutaneouslymay make different fractions of the heparin available differentially, itis possible that IV use is more effective.  Note, also, the placeboresponse rate.  20% is somewhat low for a placebo response rate, showingthat these were chronically ill patients.  Nonetheless, 20% of patientsdid go into remission with just another month of their treatment withoutheparin.  This shows the importance of a placebo controlled trial. Had the control group not been included a result of just 40% response mighthave been believed to be placebo alone.  The placebo group shows that the response was real.

The information here is from an oral presentation.  These results have not been published in a journal and have not been carefully reviewed by outside experts.  A number of the results described in preliminary form do not turn out to be true.  The usefullness of a preliminary report is for early distribution of results and for feedback to the author before publication.  Due care needs to be exercised when acting onpreliminary results.