Heparin for the Treatment of Refractory Ulcerative Colitis: Results of a Controlled Trial

A trial of heparin in ulcerative colitis has been completed. Read about the results . (I am proud to have participated in that trial.) I previously wrote about findings at previous DDW meetings. Here is an overview and several abstracts about heparin in IBD that provide background information: Heparin in UC or Crohn’s?

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 colitisGastroenterology 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.


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.

Concerns Regarding the Use of Nonprescription Drugs in Crohn’s and UC

The nature of Crohn’s and Colitis is not known. I think this is one cause of patients using nonprescription drugs, often misnamed nutritional supplements. A reader of the IBDList asked my opinion of Salmon Oil after reading the article on this page regarding Purepa. My reply was really a discussionof these unregulated drugs, Concerns Regarding the Use of Nonprescription Drugs in Crohn’s and UC.

A reader asked:

Dear Dr. Holland:

As the mother of a 22-year old son with Crohn’s, I have valued your input on the IBDList for the past year. Today was my first visit to your IBD page.

In addition to being on Asacol, I have had my son on a variety of other natural “remedies” including cat’s claw, aloe vera capsules, vitamins and salmon oil.  After reading your article about Purepa, I am anxious for him to give it a try.  Do you feel this would have a greater benefit than the salmon oil capsules?  If so, do you know if it is yet available in the U.S. (the article you referred to was published in 1996).

Thank you in advance for this information. I appreciate everything you do to further the quest for a cure for Crohn’sand UC.

P.S.  My son is currently a patient at the Univ. of Iowa Hospitals (Center for Digestive Diseases). Do you feel they have an adequate “handle” on IBD? Are you taking new patients?


U of Iowa is well respected.  An important question in getting a handle on the case is to be sure they know your son is on a number of non-prescribed medications.  There is a misconception that many share that natural remedies are not medications.  Consider this:  A drug is a substance which is taken to affect a patient’s metabolism in some desireable way.  These natural products really are being used as medications by many.  The trouble doctors have in dealing with them is that there is in general no safety or efficacy data available to base any recommendation upon.  The drug companies that sell these materials have lobbied congress and have gotten laws passed that have prohibited regulation of themselves.  They also have a fig leaf of a regulation that says as long as they just say the magic words “nutritional supplement”they can market to the public without any regulatory oversight.

There is another misconception that natural substances are safe. There are tragedies in the medical literature of liver failure causing death in several children due to daily administration of certain herbal teas.  The teas were known to be hepatotoxic, but the labelling didnot include this (didn’t have to, it was a nutritional supplement). There are a number of natural substances that are known to be toxic insufficient doses.  Nicotine, caffeine, digitalis, aspirin, strychnine,castor oil, ipecac, poppy juice, to name a few.  (The last exampleis particularly instructive. Poppies are a source of opiates which causedwell documented toxicity to Dorothy, Toto, and the Cowardly Lion. The Tin Man and Scarecrow were spared, due to a difference in metabolism.) There are cases of death due to contaminated tryptophan.  Just because something comes in pill form does not mean it is as safe as people have come to expect from pills from regulated drug companies.

You may be aware that the risk of drug interactions goes up with thenumber of drugs taken.  With your son being on four different additionalmedications than prescribed there is the potential of drug interactions.

So, what are the drugs you are giving your child doing?  I don’tknow.  Indeed, I know that no one can know.  The products describedare all complex.  Aside from the vitamins, their manufacture is notregulated.  Fish oils can be a source of dioxins.  I wonder ifany of the nonprescription drugs your son is on have been through any regularmonitoring of known or likely contaminants.  The medical literaturealso contains articles showing that the unregulated drugs are sometimesmisidentified by the manufacturer.

I try to limit my advice to matters for which there is some sort ofexperience with the substance at hand which can predict how a patient willdo.  The need for the evidence to be predictive is what patients reallywant.  It is expected that a doctor could explain what the expectedeffect would be, what the side effects would be, and the chance of eitherhappening.  For the majority of unregulated drugs, the evidence forthe medicines marketed as nutritional supplements is anecdotal, which doesnot help one make predictions as to how a patient will respond.

All that said, what can I say about your particular questions?  Well, I do not have data on efficacy or side effects of Salmon oil in Crohn’s. Thus, prediction of relative effects is not possible.  (I even donot know if Purepa is whole fish extract or part fish extract.  Asa licensed drug, processing must adhere to Italian good manufacturing practicesand will therefore be consistent lot to lot.)  I also do not knowwhat interactions would develop, if any, with the other medications heis on.  As to Purepa, note that the patients in the study were selectedwith criteria that predicted a high chance of relapse.  The singlestudy thus applies to patients with the same clinical features.  Itis probably generalizable to patients outside Italy, though the fact thatItalians eat more olive oil is one reason that studies in other countrieswould be good.  Whether the drug would be beneficial to patients witha lower risk of relapse is not known.

The simple answer, therefore, is “I do not know.”  The reason forwriting all of the above is to explain the underlying concerns that I asa physician have that causes me to say “I do not know”.  As a fellowprescriber of medications I urge you to consider the risks and benefitsof your recommendations.  Also, I hope that you are keeping recordsof clinical response and medications (including dose and regimen and lot/batchnumber).  These records would be valuable for determining likely candidatemedications relating to clinical response, good or bad.

I hope for the best in your son’s case.

What does one do to get off prednisone?

Often patients are on steroids for some time. What is the protocol for stopping steroids?

Prednisone is a drug often used in IBD. What does one do to get off prednisone?

Usually, prednisone can be tapered rapidly down to 10 mg/day andthen more slowly tapered to none in normal people. In patients withIBD, tapering faster than 10 or 5 mg per month can induce a flare. IBD patients also tend to flare when their dose gets down to 10 to 30mg/day, usually 15 to 20 mg/day. I find it interesting that the doseis very consistent for a given patient, so a patient’s previous taperexperience is quite helpful. When one gets to the wall, tapering at2.5 mg/day each 2 to 4 weeks is usually done, and often the dose hasto go back a step up during the taper.

Steroid tapering is unpleasant, and the symptoms of the taper canfeel just like IBD. Malaise and joint pains are quite common. Thisis worrysome to both doctor and patient. After a few tries attapering and failure but no overt signs of IBD relapse, a decision ismade that it is steroid withdrawal, courage develops and one pushesthrough, usually with success.

All the above is for people not under certain stresses. Theadrenals put out about 35 mg/day of cortisol, which is about the sameas 10 mg/day of prednisone. Under stress, the doses needed arehigher. Someone who has been on prednisone for a time who is tapereddown to 10 mg/day, then gets pneumonia will need supplemementalsteroids until the infection is cleared. Even after being taperedoff steroids, for a year afterwards patients may need supplementalsteroids during times of metabolic stress.

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

Comments about non-injected vitamin B12

B12 is available in nasal form. How does that compare with classically injected B12?

The uselessness of sublingual Vitamin B12?

In the past I criticized the use of sublingual vitamin B12. Now there is nasal B12 available. A recent article in Gastroenterology[1] showed that nasal B12 is effective in treatment of B12 deficiency, using a dose of1.5 mg per day. 

Patients with Crohn’s disease often have involvement of the last part of the small intestine, which is known as the terminal ileum. That part of the intestine is responsible for absorption of vitamin B12. Vitamin B12 is a large molecule that will not cross any part of your body unless it is specifically brought across by a transport system. For B12 this requiresa system that involves a special protein made in the stomach, called intrinsicfactor, and the transport system in the terminal ileum which brings B12 into the body when it is bound with intrinsic factor. 

What is interesting is that there is a second way to absorb B12 that does not depend on the usual route. This pathway was described years ago, but requires high dose of B12, about one mg per day. I suspect that the B12 given nasally is eventually swallowed and absorbed by the intestinal route.

Interesting that now B12 is available in these formulations. While true that one gets away without a shot, the dose is about 300 times what is given orally. I imagine that 350 to 475 mg of vitamin B12 a year adds up in cost, and it may indeed be cheaper to just get a yearly shot of 1 mg of B12. Add to that the cost of testing to see if the oral or nasal B12 is getting in the system, and I wonder about the cost.

Patients with Crohn’s are at risk for B12 deficiency. Blood counts should be done regularly. In the future, as folate is added to the diet, looking for large blood cells as a clue to B12 deficiency will no longer work, so B12 levels will need to be every few years or so to detect the developmentof B12 deficiency in patients.

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

  1. Slot, WB and Merkus, FW and Van Deventer, SJ and Tytgat, GN. Normalization of plasma vitamin B12 concentration by intranasal hydroxocobalamin in vitamin B12-deficient patients. Gastroenterology 1997 Aug; 113(2):430-433.

How do doctors deal with patients who have incurable disease?

Ever wonder if your doc gets frustrated over not being able to cure incurable disease. Do you worry that you are only darkening the door of your physician, sorry to trouble them over something they cannot cure anyway? A reader asked, and I answeredHow do doctors deal with patients who have incurable disease?

A reader asked:

I’m truly curious as to how doctors deal with the frustration ofdealing with people they can’t, despite their best efforts, cure. I’m wellaware that my doctors are doing their best and that there isn’t a cureor quick fix — I wonder if they know I know that (and of course, I dotell them). Nonetheless, sometimes I hate to even darken their doors withyet another complication or flare-up — perhaps because I am so fond ofthem and appreciative of their efforts. I sometimes think we patients –with all our kvetching — would benefit from an understanding of our physicianson this human level. It’s not a topic I’ve ever seen or heard addressed.

Oh, yes, this is a common question of Doctors. Well, I think it is. I actually haven’t canvassed my fellow physicians on this one, but I have had friends ask me. 

Actually it is quite easy. Starting out in medical school, one imaginesthat you will become a docto n sae lives. Then you got on the wards, andthe livess are not that easy to save. After the shock of realizing thatone is unable to cure everything, the young physician learns to do thebest they can. I think ther ismoreto it then just the best that you can.For myself, I have also found a way of looking at the issue that workswell for me. I have decided that my role is to give advice. This has mademe much more comfortable. My ego is no longer dependent on patients takingtheir medicines. Nor does my ego anymore depend on the virulence of someonespnuemocccus. By realizing that I give advice, I am in balance with my abilityto impact the world. When a patient is not able to follow my advice, Ino longer feel frustrated, I look for ways to give better advice. Whenthings do not work as planned, I recognize that information is imperfectand I look for more information in order to give better advice. When Idecide on what initial tests to do, I do not fear not getting every testpossible. I get sufficient tests to allow me to give reasonable adviceunder the circumstances.

Say someone has a terminal disease. I find out what last things theywant to do: such as get to their sons graduation. Then I give advice onhow to best achieve those goals. Sometimes the effort will need to be greatto get a few extra days, but it will be worth it. With Crohn’s, I knowwhat the odds and consequences are of different choices, so I give adviceon how to deal with problems as they occur. As advice depends on goals,it is a natural extension to involve my patients in the decision makingprocess, not to decide what is the correct thing to do, but to help meunderstand what different consequences mean to my patients, so that theadvice I give makes sense in the patient’s contest. So my measure of successis whether the advice caused the best possible outcome given the circumstances.

So the next time you worry you are darkening your docs door, remember that you are not there for a cure, you are there for advice. By having a physician that understands your situation and goals, and by providing feedback on how the disease and treatment are being tolerated, you will be able to get advice to help you deal with the situation at hand.

Best of Luck, 

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

You want to get Pregnant while on Azathioprine?

Many women with Crohn’s are on azathioprine, an immunosuppressant. What should you do if you want to get pregnant while on azathioprine?

The subject of pregnancy and inflammatory bowel disease has been writtenabout extensively. Treatments are changing, and one worries about the effecton the unborn child. One reader wrote the following:

Thanks for an informative web page. I also subscribe to the IBD list and appreciate your comments. I have looked through some old IBD posts and saw where you said taking Imuran when conceiving a child gave you the willies. I was diagnosed with Crohn’s in 1993. I am now 27 years old and my husband and I want a child. I have been taking Imuran (50 mg a day)since November 1994. My GI has reluctantly agreed to let me try to taperoff Imuran. He feels Imuran is the reason that I was finally able to taper off prednisone after 3 years. I have been on Pentasa since March 1994.My GI feels that I will have a flare up when I discontinue the Imuran andthat would be a greater risk to the baby than the risk of birth defectscaused by continuing to take Imuran. My OB says the Imuran is unsafe duringpregnancy. I also would like to breast feed and Imuran would make thatimpossible. I’ve been told by my GI and OB that Pentasa is safe during pregnancy.

The above situation is a real example of the problems that face onewho is contemplating pregnancy with Crohn’s. The physicians seem to begiving contradictory advice. Actually, each is concerned about the outcomefor the patient, and different factors come into play. 

While no one advocates the use of Azathioprine in pregnancy, the reportsof the outcomes for patients on azathioprine who get pregnant seem to beno worse than the results of patients with untreated Crohn’s. That is tosay, fetal loss is common in active Crohn’s and also when on azathioprine.The incidence of birth defects is not higher when on azathioprine. My interpretationof this is that if azathioprine causes birth defects in a given pregnancy,they are so severe that the fetus will not survive. There was some controversya while back on what the effect of pregnancy on Crohn’s is. I think theliterature pretty much now shows that people respond variably, but thatif Crohn’s is active at the time of conception that things will probablynot go well. 

All that said, most drugs used in treatment of IBD have been found tobe safe during pregnancy. Steroids are known to be safe, as is sulfasalazine.Mesalamine is probably safe during pregnancy. Flagyl is not to be used(though the data I recall are just scattered case reports, and the warningto not use it may not stand up in the future). 

Remember that many people were successfully treated with medicationsbefore azathioprine came into common use for Crohn’s disease. While azathioprinemay be used to get a patient off steroids, the situation generally is notthat steroids were ineffective, but that steroids were needed chronicallyand side effects were a concern. 

My feeling about this is that since pregnancy is self limited in duration,getting off azathioprine at worst will mean 12 to 16 months of steroids.If the Crohn’s can be controlled with other medications, then all the better.In general, I would advise patients on azathioprine to get off the azathioprineand start steroids, a form of mesalamine, or both depending on circumstances.Also, I generally advise Crohn’s patients to avoid anything with sucrosein it, since some studies in the past showed a 50% reduction in complicationsof Crohn’s when that was done. 

The above notwithstanding, there is the possibility that a particularcase of Crohn’s was so bad that even the thought of recurrence is painful.I could imagine someone who had multiple fistulas, obstructions, operationsand wound failure, was starting to get cataracts, and who only got outof a cycle of repeated hospitalizations when put on azathioprine. A casesuch as that might warrant the risk of azathioprine. 

I cannot tell what is the right choice, however. This will depend onhow the risks sound to you and many aspects of your views on life, death,having children, and dealing with birth defects. It is not your responsibilityto make the medical decisions, but the input to your physicians on howyou value the various outcomes will let your doctors, who have a sensefor the relative rates of occurrence of the above outcomes, give betteradvice on how to proceed. 

Best of luck in your efforts!

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

Sucrose Restriction in Crohn’s Disease

There were some papers in the past that found that sucrose restriction can prevent recurrences of Crohn’s.

Can reduction of sugar intake reduce the risk of complications of Crohn,s disease?

Since the mid 1970,s it has been known that patients with Crohn,s disease consume more sugar than patients with ulcerative colitis or normal subjects.  In this discussion, it is to be understood that sugar means the disaccharide sucrose, which is also commonly known as table sugar.  Initially, two studies from Germany showed that patients with Crohn,s eat more sucrose than healthy controls (23,28).  A number of studies since then have confirmed this finding (37).

The usual teaching is that this is due to patients changing dietary habits to accomidate their inability to tolerate many foods.  However, patients with ulcerative colitis who often have similar digestive complaints do not have increased sucrose intake (11,24,34,38).  Also, patients who have Crohn,s report that when they get sick their sucrose intake actually drops rather than increases.  Other studies show that symptoms are not changed when sucrose is restricted (1) and one study suggested that sucrose worsens symptoms (1).

Studies have been done to look at whether restriction of sucrose intake is of benefit in patients with Crohn,s.  In a study of 64 patients with Crohn,s (7), 32 patients were put on a diet which minimized sucrose and white flour, and substituted whole wheat and fruits.  While the experimental and control groups were in different clinics, the treated group had 80% less days in the hospital and only 1 patient required surgery compared to 5 in the control group.  (Interestingly, this experiment was done before the first epidemiological studies reported increased sucrose intake in Crohn,s patients).

In a larger study, results were not as beneficial (35).  190 patients treated with sugar restrictin compared to 162 treated with usual diet showed that 3.7% of treated patients needed surgery compared to 8.6% of controls and hospital admission rates were 9.5% in treated patients and 13% in controls.  These numbers did not reach statistical significance.

K. W. Heaton, one author of the 64 patient study described above (7), noted that in the 
larger study of 352, patients were British and were asked to consume fruits and vegetables, a decidedly unBritish activity.  Also, the control group showed a drop in sucrose consumption, which makes it possible that the control group was really a partially treated group.  Unfortunately, a subgroup analysis was not reported with controls who did not reduce their sucrose intake.

I regularly recommend that my patients reduce or eliminate sucrose in the diet.  I allow commercial bread, which does have some sugar added, but I advise that patients do not consume anything with obvious sugar in it or sprinkled on it and do not add sugar to drinks or when cooking.  (I suspect that fermentation will have consumed the sucrose in regular bread, but not sweet bread). I recommend that a safe substitute is honey, which is fructose.

Stephen Holland, M.D. 
University of Illinois College of Medicine at Urbana-Champaign. 
©1997, Stephen Holland.

This material was abstracted from the chapter “Dietary Factors in the Etiology of Crohn’s Disease written by K. W. Heaton, in Inflammatory Bowel disease edited by Gunnar Järnerot, Raven press 1987.

Selected References:

1. Brandes, J.W. and Lorenz-Meyer, H. Zuckerfreie Diät: eine neuer Perspektive zur Behanndlung des Morbus Crohn?  Eine randomsierte, kontrollierte Studi.  Z. Gastroenterol., 19:1-12, 1981.

7. KW Heaton, JR Thornton, PM Emmett.  Treatment of Crohn,s disease with an unrefined-carbohydrate, fiber-rich diet.  Br. Med. J.  2:764-766, 1979

11. G Järnerot, I Järnmark, K Nilsson.  Consumption of refined sugar by patients with Crohn,s disease, ulcerative colitis, or irritable bowel syndrome.  Scand. J. Gastroenterol.  18:999-1002, 1983.

23. GA Martine, JW Brandes.  Increased consumption of refined carbohydrates in patients with Crohn,s disease.  Klin. Wochenschr. 54:367-371, 1976.

24. GA Martin, A Stenner, WJ Brandes.  Diet and ulcerative colitis.  Br. Med J. 2:1401, 1978.

28. B. Miller, F Fervers, R Rohbeck, G. Strohmeyer.  Zuckerkonsum bei Patiententen mit Morbus CrohnVerh. Dtsch. Ges Inn Med.  82:922-924, 1976.

34. GB Porro, E Pnaza.  Smoking, sugar, and inflammatory bowel disease.  Br. Med. J. 291:971, 1985.

37. JR Thornton, PM Emmett, KW Heaton.  Diet and Crohn,s disease: characteristics of the pre-illness diet.  Br. Med. J. 2:762-764, 1979.

38. JR Thornton, PM Emmett, KW Heaton.  Diet and ulcerative colitis.  Br. Med. J. 1:293-294, 1980. 
 

©1997, Stephen Holland.

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An Interview with senators Kassebaum and Kennedy regarding the new health insurance bill.

Job lock is but one consequence of the current insurance system for people with chronic disease, such as ulcerative colitis and Crohn’s disease. Alaw was passed by congress a few years ago. Here is an interview with senators Kennedy and Kassebaum regarding this law that was aired on PBS in the past.

A real problem for patients with inflammatory bowel disease is the lossof the ability to get health insurance when changing jobs. This results in job lock for many. It also can be a disaster for children with IBD whocannot get health insuarnce at any new job. Recently a law was passed that would require insurance companies to provide insuranceif a person was previously insured. I get a newsletter about health issues,and am reprinting here an article I have recently received. It is an interviewwith senators Kassebaum and Kennedy.

Insurance companies are really not mean. They are simply responding to the competitive pressures that our laws have created. Suppose an insurance company wanted to be nice and just decided to insure people with chronic disease. Everyone with chronic disease would insure themselves with that company. Their rates would go up, the subscribers would leave, and the insurance company would be out of business. Thus, by being nice, they end up out of business, doing no one any good. This is an example where regulation works. By preventing all insurance companies from excluding people with previous health problems the competitive playing field is levelled, and no company can gain a competitive advantage by excluding people with preexisting illness who have previously been insured. Rates stay low, people stay insured.

There is also a long term benefit. The existance of this law makes it very desireable to stay insured. If you stay insured,chronic illness will not cause job lock or uninsurability. Under the currentsystem, if you do not get insurance and get a chronic illness you are notmuch worse off than if you are not insured at all. Insurance rates areawfully high, and many do not have insurance because of the cost. Withthe binefit of guaranteed future insurability the equation changes slightly,and more healthy people will want to be isnured to have the benefit ofthe law. With more healthy people participating, the premiums costs willbe pressured downward, and premiums can go further down as more participate.Where this settles will depend on the future premium rates and disposableincome, but it will push more people to be insured. I think this effectis not fully appreciated.

On the down side, the new law will not take effect for one year. 

Thanks to Steve Freedkin for keeping the List.Healthplan active. Seethe boxed text below for subscribing information.

Stephen Holland, M.D.

Here is the article:

Here is the article:

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Both Houses of Congress have approved new legislation that calls for”portable” health insurance, and guarantees that a “pre-existing”condition will be paid for, even if a worker changes jobs. Tax deductionsfor nursing home payments also made it into the legislation, but mentalhealth benefits did not.

CHARLAYNE HUNTER-GAULT: The new health legislation is first of its kindin a decade and will affect millions of Americans. Known as the HealthInsurance Portability and Accountability Act, the bill requires insurersto offer policies to workers who changed jobs, insures that workers wholose their jobs cannot be denied individual coverage, guarantees that workerswith pre-existing conditions cannot be denied coverage for more than 12months, gradually increases the tax deduction from 30 to 80 percent forthe self-employed who buy insurance, and allows individuals to deduct costsof nursing home and other long-term care.

For more on the legislation and its impact, we’re joined by the bill’sauthors. Sen. Nancy Kassebaum, Republican of Kansas, is the chair of theLabor & Human Resources Committee, and Sen. Edward Kennedy, Democratof Massachusetts, is the ranking member of the Committee. Thank you bothfor joining us. Sen. Kassebaum, just what is the significance of this bill?

SEN. NANCY KASSEBAUM, Chair, Labor & Human Resources Committee:It will enable, it’s estimated 25 million Americans, to feel more secureregarding their health insurance. If you lose — if you’re losing a jobor changing a job, you worry about whether you’ll be able to maintain healthinsurance. This guarantees that if you’ve been part of a health plan, youcannot then be terminated, and particularly due to any preexisting healthcondition.

CHARLAYNE HUNTER-GAULT: All right. I want to get into some of the specif-ics in a minute, but Sen. Kennedy, let me — do you have anything to addto what Sen. Kassebaum has said in terms of the significance?

SEN. EDWARD KENNEDY, (D) Massachusetts: Just really one point, and Ithink she has said it well with regards to portability and preexistingcondition, but I think the power of this legislation is relieving familiesof a lot of anxiety. A lot of parents have a child that has some difficulty,some disability, and the family worries what is going to happen to thatchild when he or she grows up, or that worker that might be laid off andis not as well or healthy, as robust as they might have been and is goingto be out there and unemployed and really wondering whether they’re intheir senior years are going to be able to get any kind of health insurance,or someone that would like to move to a job and have a much greater opportunityfor themselves and their family, and that says, no, I can’t do it, becauseI just don’t know about that health insurance because I have my wife issick or my husband is sick. That kind of anxiety is an enormous burdenon so many millions of American families, it’s a real one. You might notbe able to put it into dollar and cents, but it’s a real one. This billaddresses that degree of preexisting condition, and it gives assurancethat people will be able to continue their health insurance, and it meansthat they’ll be able to move from job to job and still carry the healthinsurance. That’s important.

CHARLAYNE HUNTER-GAULT: All right. Let’s go through some of the specificson it then. That is the first major thing about it, that it requires insur-ers to offer policies to workers who change jobs. Explain how that willwork, Sen. Kassebaum.

SEN. NANCY KASSEBAUM: Well, it’s just that if you’ve lost a job or changeda job and you have had health insurance, you can’t just walk off the streetand say, I want this job and I want health insurance. You have had to havebeen on a health care plan. But if you moved and changed jobs and yourCOBRA benefits have run out as well, then an employer must offer a healthinsur- ance plan. And you cannot be excluded because of a prior healthcondition.

CHARLAYNE HUNTER-GAULT: Mm-hmm.

SEN. NANCY KASSEBAUM: Also, someone can start to work and if they have,umm, a heart — a health condition, ulcers, heart condition, whatever isdetermined as a preexisting condition, after a year’s time, then they haveto not be excluded again from an employers health plan that he would beoffering employees, she would be offering employees.

CHARLAYNE HUNTER-GAULT: Now, on the first one, Sen. Kennedy, one thatrequires insurers to offer policies to workers who change jobs, who bearsthe cost of that? How does that work? SEN. EDWARD KENNEDY: The employeeand, therefore, this is — we have to see within the states, as the statesare going to have important responsibilities, that some of it’s sharedwith the federal government to make sure that the premiums are not goingto go up out of sight, and one of — that was one of the real differencesbetween the House and Senate bill under Sen. Kassebaum, our bill.

It meant that all insurance policies were going to be available to peoplethat were going to be moving out or have some preexisting condition, andthe House would have tried to put them all in one policy, which would havemeant that the premiums were absolutely up through the roof, and it madeit inaccessible for people, but I — if I could just get back to one point,you know, what happens so often in, in Main Street America, as these familieshave paid into insurance companies for a long period of time, for ten,for fifteen, or for eighteen years, and suddenly they find a husband ora wife, a preexisting condition.

They may develop cancer. You know, what happens in so many instances,they are cut off, they are terminated. That policy is ended, or if a childis very, very sick, that policy is ended. That happens, every communityin America, and this addresses that issue. 

C HARLAYNE HUNTER-GAULT: But explain to me this part, where it saysit guarantees that workers with preexisting conditions cannot be deniedcoverage for more than 12 months, why is that there, for more than 12 months?What exactly does that mean?

SEN. NANCY KASSEBAUM: That’s because, as I said earlier, if you havemoved to a job that is offering health coverage but you have a preexistingcondition, and you have not been covered before, that you cannot be –you cannot be denied for more than 12 months. During that time, you wouldbe urged to be a participant in the plan, but you may not have a preexistingcondition covered until the end of 12 months time. But that’s for someonewho has never been part of a health plan.

CHARLAYNE HUNTER-GAULT: Oh, I see.

SEN. NANCY KASSEBAUM: Let me just say too, umm, it’s like any otherhealth plan. I mean, this isn’t something new. We’re not dictating theterms of new health plan. It could be Blue Cross-Blue Shield, or whateveran employer is offering, so an employer may pay part of the benefits asthey do in, in many plans, or it would be employee contribution. That isto be determined. It’s just that they cannot be denied.

CHARLAYNE HUNTER-GAULT: Mm-hmm. Now what about — there’s also individ-uals can deduct costs of nursing home and long-term care. Now tell me aboutthe importance of that.

SEN. EDWARD KENNEDY: Well, I think as all of us know the growing numbersof elderly in our communities, in our homes, we’re blessed with the factthat our parents are living longer, and I think in an ideal world, we wouldlike to have them have the option of either remaining at home or in a communitysetting so that they can remain at home in a community setting, or in termsof having nursing home help and assistance.

The amount of resources in a family that’s extended in the final severalmonths of one’s life are really extraordinary. And what we have tried todo, this program, is to try and provide through the tax program help andassistance to those families both in terms of getting insurance and beingable to cover some of those extraordinary expenses. It’s one of the areasof greatest concern, I think first of all to the parent, because the parentknows that they are draining the family’s resources and of course, theson or daughter knows that because they are seeing that they have to wantthe best in terms of the parent, the best in the care, and they’re worriedbecause they’re sacrificing the children’s future education.

So this, again, provides enormous tension and anxiety for those families,and this provides some relief. It doesn’t do all of the kinds of thingswe’d like, and let me just finally say I would hope that we can build onthis in the next Congress. We didn’t achieve all we would have liked, orat least I would have liked to have seen, that President Clinton wouldhave liked to have seen in the last Congress, but we’ve made a great progressin this one, and I hope we can continue the bipartisan effort, and thatwe can continue to make progress —

CHARLAYNE HUNTER-GAULT: Sen. Kassebaum, let me just ask you about thepart about the self-employed, who can buy insurance now, or get an increasein tax deductions. Explain that one, briefly to me and the significance.

SEN. NANCY KASSEBAUM: Yes, and also let me say on the long-term healthinsurance credit, this was something that Sen. Dole added, and which wasunanimously supported in an effort to encourage people to take long-terminsurance. This has been very expensive, and this will be a tax creditdesigned to encourage that people take that type of insurance. The self-employment —

CHARLAYNE HUNTER-GAULT: Excuse me. How much of a tax credit?

SEN. NANCY KASSEBAUM: What is that amount? I can’t think of what itis.

SEN. EDWARD KENNEDY: Well, it’s a modest credit, and it builds up overa period of years.

CHARLAYNE HUNTER-GAULT: Right.

SEN. EDWARD KENNEDY: It’s not going to offset the types of costs butit’ll help relieve, I suppose, people probably 30, 35 percent of the kindsof burden that they would have for maintaining someone in, in a nursinghome.

CHARLAYNE HUNTER-GAULT: All right. Let’s go —

SEN. EDWARD KENNEDY: But it’s the beginning of a program. I think itcould be built over a period of time. It’s constrained really because ofthe cost of it, but it’s a down payment; it can be expanded; hopefully,it will over a period of time.

CHARLAYNE HUNTER-GAULT: All right. Sen. Kassebaum, for the self-employed,yes.

SEN. NANCY KASSEBAUM: If you’re self-employed, currently you’ve beenable to deduct 30 percent of your insurance costs. Umm, this will now enableyou to deduct 80 percent. Umm, this is to balance what an employer candeduct 100 percent of the costs that they have to cover employees, forinstance, and this will be a balancing of fairness to those who have –are self-employed.

SEN. EDWARD KENNEDY: See, this has the larger employers are able totake the whole deduction. The small employers are not individuals, andwhat happens is you find out that in small businesses, as well as individual,they pay about 35 or 40 percent higher premiums. So they don’t get thefavorable tax treatment, they’re paying more, and it’s, it’s amazing tome that smaller businesses are, or individual, self-starting companiesprovide the coverage that they do.

CHARLAYNE HUNTER-GAULT: I understand that the Senate has just passedthis bill, and the House earlier and just a few minutes ago the Senatepassed it 98 to nothing, so what does that mean in terms of — Sen. Kassebaum,there’s a wonderful smile on your face, listening to that news.

SEN. EDWARD KENNEDY: Well, she should — if I can take — before sheanswers, under Sen. Kassebaum’s leadership, it passed unanimously in theCommittee a year ago today, it passed unanimously on the floor, and nowshe’s got a unanimous win.

CHARLAYNE HUNTER-GAULT: All right. Congratulations. When does this gointo effect, Sen. Kassebaum?

SEN. NANCY KASSEBAUM: July 1st of 1997.

CHARLAYNE HUNTER-GAULT: In other words, a year from now?

SEN. NANCY KASSEBAUM: Yes.

CHARLAYNE HUNTER-GAULT: Now, Senator, you said a few moments ago thatthis bill obviously doesn’t do everything that you wanted it to do, itdoes little for the 40 million people who don’t have insurance, there’sno equivalent coverage for mental health. Is legislation to cover thoseand other things likely to happen in the future? I mean, is there now amood to move on, on health care reform?

SEN. NANCY KASSEBAUM: I’m sure there is, and Sen. Kennedy, of course,has been a real pioneer in that. I am retiring at the end of my term thisyear, and Sen. Kennedy will be here to carry on. Sen. Domenici just todayintroduced legislation regarding mental illness and coverage for such.Both Sen. Kennedy and I have joined as co-sponsors, and there’ll be a hearingon that bill in September. 

CHARLAYNE HUNTER-GAULT: Right.

SEN. NANCY KASSEBAUM: We’re also supportive of the 48-hour stay fornewborn mothers in the hospital, which Sen. Bradley has introduced, andwe are both supportive. So these are measures that are out there, I thinkdesigned to help in particular areas where there is a real need. And letme say on the legislation that we’re talking about that we’ve just passedand that’s upcoming, after having a clip of what you showed earlier, thisshows where bipartisanship can come together.

It’s not always easy, and we don’t always agree, and we can spend somecountless hours debating, but at the end of the day for the best interestof legislation that we felt was important, it did take bipartisanship,and that did come together, and I think that’s what made it successful.

CHARLAYNE HUNTER-GAULT: Great. Well, thank you both for joining us.

SEN. EDWARD KENNEDY: Could I just add — mental health has been thestepchild of our heath care system, so we hope we can make some progress.

CHARLAYNE HUNTER-GAULT: Thank you, Senator. Bye.

[END]

Fish Oil for the Treatment of Crohn’s Disease

Heard about fish oil? This ill defined substance has gotten play in the popular health literature, but now there has been a study in Crohn’s disease published in the New England Journal of Medicine . The study showed that the preparation, Purepa, is effective. It should be available in a few years in the US.

There has been a fair amount of interest in fish oil as an antiinflammatory medicine over the years. In part this is driven by fish oil being “natural”. The scientific reason is that oils in the diet are the building blocks for certain chemicals the body makes, some of which are immune modulators. Fish oils contains a group of oils known as omega-3 fatty acids (chemically a double bond is present 3 down from the end of the carbon chain of the fat molecule). These oils are able to prevent the production of certain inflammatory molecules in the human body.

Fish oil per se is not a defined substance. There is the matter of variation of the fish, whether the oils is taken from whole fish sqeezings or just the fillets, and what processing is done. The whole fish issue is important because toxins (or perhaps useful drugs) are concentrated in fish livers. Processing is important because of stability. As with all supplements marketed as foods, the natural food pushers do not want regulation to be exerted upon them as it would add all sorts of complexities to their lives. As I see it, if they are going to push their own products, the consumer should be assured that the manufacturer can trace the source of raw material, have a regular way of making the stuff, keeps records of quality control, and does assays of the important ingredient(s). Additionally, the studies, if any, used to support the use of natural products often are used to recommend products different from those in the study. With something as unregulated, unassayed, and undefined as health food store products, who knows whether the health food store drug will do any good.

There were 39 patients in each group. P = 0.006 for the comparison of the two groups by log-rank analysis.

With this background, now comes a drug which is a fish oil preparation. Researchers in Italy used a fish oil preparation called Purepa, manufactured in Sweden, and coated the capsules with an enteric coating called Eudragit NE 30D. It is well defined and manufactured with the care a drug company takes. A study in the New England Journal of Medicine (NEJM 334(24):1557-1560, 13 June 1996) reported that patients with Crohn’s disease had less relapses when taking the medicine than did those taking placebo. The study was well done. It used a group of patients randomly assigned to either drug or placebo. Patients were not able to tell which drug they were on. (Which also implies that enteric coated Purepa does not have the nasty fish taste which can make fish oil hard to take.) The patients who were asked to participate were known to have a high chance of flares of the disease, based on their having all been in remission less than 2 years, with serum alpha 1-acid glycoprotein concentration > 130, alpha 2-globulin > 0.9, or a sed rate > 40. The findings were remarkable. The patients on drug had a relapse rate of only 41% compared to controls who had a relapse rate of 74% over the one year of followup. Diarrhea was a side effect in 4 of 39 fish oil treated patients vs 1 of 39 placebo patients. The diarrhea did not resolve when the drug was stopped in experimental or control subjects. The dosage of fish oil was 9×500 mg capsules per day, = 4.5 grams of fish oil per day. Interestingly, all relapses occurred within 7 months in both groups. Also, the fish oil group had improvement in all three serum measurements made, while the placebo group all had worsening of the measures.

The problems with the study concern whether the drug will be effective in all patients with Crohn’s, or only those patients like those in the study. This is a real issue – Crohn’s disease is a heterogeneous group, and the Italian group that published this may have selected a subset of Crohn’s that would respond differently. Also, this study was done in Italy. The Italian diet differs from a typical American diet, not to mention Scottish, New Zealand, Chinese, Dutch, Polish, German, French, or any cuisine that you may wish to identify. Italians also are heterogeneous in their diet, varying greatly from North to South, and inland vs seacoast. The study did not subgroup its results by region of Italy where subjects were born or lived, which would have been interesting.

It looks like this will be effective, however. Given the safety of the preparation it will be a welcome addition to treatment of Crohn’s. The variation in fish oil preparations available, along with the history of previous negative studies with fish oils, leads me to conclude that until a particular preparation is studied it will not be possible to say whether any particular fish oil preparation will work in Crohn’s. It is interesting that both placebo group and Fish Oil group had no more relapses after 7 months. It would be nice to know if the changes in any of the blood measures predicted who would relapse. The relapse curves also raise the question whether patients only need to be on the drug for 7 months to get the full benefit.

Stephen Holland, M.D.
University of Illinois College of Medicine at Urbana-Champaign

cA2 in Crohn’s disease

What is the “cure” for Crohn’s that has been reported in the news? There have been reports of an antibody that can treat Crohn’s disease. While not a cure, it may represent a new treatment that will more rapidly bring flares of Crohn’s under control.

[ The IBDPage has been around for a long time. Remicade (infliximab | Janssen) was the first anti-TNF drug available. Take this post as an interesting post from long ago – Ed.]

cA2 in Crohn’s disease

A fair amount of press has recently been seen about a new cure for Crohn’s disease. Unfortunately, this was very poor reporting. The drug that has garnered all this attention was called cA2, and now is named Infliximab. This drug is an antibody that binds an immune chemical called TNF-alpha. Antibodies are large proteins that can only be administered intravenously.The reports at the Digestive disease week meeting in San Francisco lastMay (May 1996) basically showed that in patients with severe Crohn’s disease,65% percent had an excellent response to administration of cA2. Patientswith Ulcerative colitis were not helped. Patients relapsed as the drugwore off. 

Thus, while not a cure, cA2 will probably be an important drug in the treatmentof Crohn’s disease. It will probably find its role in the treatment ofpatients with Crohn’s who are hospitalized for a severe flare. In thesepatients, the drug will probably allow faster control of the inflammation.The patients will still be treated with steroids, but the cA2 will allowfaster discharge. Interestingly, a lot of patients getting the drug at this time are patients who have been maintained as an outpatient who havebeen doing poorly with chronic fistulas or inflammation that has nevercome under control.

One aspect which has cause a lot of excitement in the scientific communityabout this drug is that it is one of the first success stories for immunologyresearch predicting clinical results. TNF-alpha is an early player in theimmune response, so blocking it should be effective. However, studies ofUlcerative Colitis patients showed that they do not have elevated levelsof TNF-alpha, while Crohn’s patients do. Thus, the effectiveness of cA2in Crohn’s but not in UC confirmed the immune studies in those patients.The research into what causes the lack of response in 35% of the Crohn’spatients will be interesting to follow.

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