TREATMENT OPTIONS FOR CROHNS DISEASE Warfare: Bio, or Chemical?

Treatment Options For Crohns Disease Tracy R Rider Nazarene Bible College

Treatment Options It is estimated that approximately 1,000,000 people in the United States alone have Inflammatory Bowel Disease (IBD), and half of these people have Crohns Disease (CD). Because there is no known cure for CD, patients who do not respond to one level of medication are forced to opt for increasingly riskier treatments in an attempt to find a method of putting and keeping their disease in remission. Helminth Therapy (TSO) and Remicade are both recent treatment options for CD, however TSO has been demonstrated to be both more effective and safer, making it a better option than Remicade. Understanding Crohns Disease According to the Crohns and Colitis Foundation of America (CCFA), while CD occurs more often among Jewish populations, it is indiscriminate of gender and age. It is often considered primarily a disease of adolescents and young adults because this is the period of life when it is typically diagnosed. CD has been identified in roughly 100,000 minors in the United States alone (CCFA, Disease, n.p.). The incidence of CD has increased dramatically each year, even when consideration is made to allow for newer and better diagnostic techniques (Ovamed, A New, n.p.). Crohns disease and Ulcerative Colitis (UC) together are the two diseases that make up IBD, an auto-immune disease involving inflammation of the gastrointestinal tract. While the cause is unknown, it is postulated that IBD is the result of an inappropriately vigorous immune response to contents of the intestinal lumen (Weinstock et al. 2004, 184). Unlike UC, which affects only the surface layer of the colon, CD involves all tissue layers and can affect any area of the tract from the anus to the mouth. It is a chronic disease, meaning that although it may go into remission for periods of time, symptoms flare unpredictably throughout ones lifetime.

Treatment Options Often debilitating, CD presents numerous symptoms and complications, all of which drastically affect the patients quality of life. Common symptoms of CD include gastrointestinal bleeding, loose and bloody stools, (sometimes as many as 25 per day), chronic abdominal pain and cramping, lethargy, nausea, vomiting, and anemia. Anemia adds symptoms such as dizziness, chills, and lack of ability to focus or concentrate. While CD has many symptoms, each person responds to Crohns in a unique way (CCFA, Disease, n.p.). Likewise, people respond differently to the various medications used for treatment. Common complications of CD include malnutrition, intestinal obstruction caused by swelling or built up scar tissue, gastrointestinal ulcers which, in about 30

percent of CD patients, also develop into fistulas connecting the intestine and other organs such as the bladder, vagina, or skin, which often cause infection (CCFA, Disease, n.p.). While many complications eventually require surgery, doctors now recognize that surgery should be considered a last-line treatment. This is because when the disease recurs, it generally attacks an old surgery site (Frank et al. 1993, 52). Even at initial diagnosis, the quality of life of a Crohns patient is changed forever as he realizes he must adjust to living with CD. Despite studies that have concluded that neither personality type nor poor emotional control are factors encouraging the onset of the disease, CD frequently creates feelings of helplessness and guilt as the patient blames himself for the erratic and uncontrollable flare-ups. Depression often follows as one experiences first-hand the losses associated with having a chronic illness (CCFA, Disease, n.p.). CD interferes with every area of ones life, affecting relationships, cost of living, and the ability to participate in many social and recreational activities. It makes it more difficult to find either health or life insurance

Treatment Options plans (Kalibjian 2003, 332-341). Even benefits and job security are threatened by a diagnosis of CD (Saibil 2003, 190-192). Understanding CD Treatments For the purpose of this paper, treatment options for CD are broken into two broad categories: first-line and last-line. First-line treatments are those that are considered conventional and pose minimal risk to the user. Their success in inducing and maintaining remission without essential combination with other drugs has been well-established over time. Their benefits far outweigh the potential risk of any minor side-effects that may be associated with them. Last-line treatments are those which must be taken in combination with first-line treatments, are

considered more risky and are only prescribed after first-line treatment options have been proven unsuccessful in controlling the symptoms. Remicade is such a last-line treatment. According to Remicade labeling, Remicade is an immune suppressing, biologic medication. It is used to treat moderate to severe active CD in those who have been unresponsive to conventional treatment measures. It works by blocking a substance in the body that causes inflammation when present in excess. It does not cure CD, but reduces symptoms and may induce remission. It is administered intravenously, over a two hour period (Centacor, Remicade, 27), followed by two hours of monitored recovery. Some of the newer medications, such as TSO, are placed in the last-line category because they have not yet been approved by the FDA for sale in the United States. The active ingredient of TSO is trichuris suis ova, or, the eggs of a parasitic helminth worm (Ovamed, A New, n.p.). Increased rates of IBD found in populations with little to no remaining exposure to helminths led researchers to propose that helminths may have a positive effect in controlling IBD (Weinstock et al. 2004, 184). Research has shown that TSO works as a result of a normal action of the

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helminth in its host. Helminths thrive by diminishing the hosts immune system response to their presence, which has the effect of suppressing an over-active immune response that is characteristic in people with IBD (184). The production and administration of TSO as explained on the Ovamed website involves harvesting mature parasites from laboratory pigs, cleaning them, and raising them in vitro until they produce ova. The ova are gathered and retested for purity. Patients simply take the microscopic ova solution out of their refrigerator, mix it into a flavored solution, and drink it (Ovamed, A New, n.p.). Understanding Your Options: TSO More Effective than Remicade The effectiveness of a treatment, especially in severe illnesses such as CD, sometimes becomes a more significant determining factor in treatment choice than safety. For the patient searching for stabilization of both treatment and disease, short term and long term efficacy must be considered. Unarguably, the short-term recovery rate of Remicade was very positive. At week four on a 5 mg/kg dose, studies showed that 81% of Remicade users reported a response, and 48% of Remicade users reported remission. Fistula response was reported in 68% of users, with an average duration of response lasting 12 weeks. Closure of fistulas was seen in 52% of users. However, people who were unresponsive by week 14 generally remained unresponsive to Remicade, even at increased doses (Centacor, Remicade, 7-11). Long-term recovery rates, however, were less positive, revealing a dramatic decline in efficacy. At 54 weeks, the number of Remicade patients that remained in remission while receiving 5 mg/kg every eight weeks- the standard maintenance regime- was only 14% higher than placebo users, and fistula response was only 16% higher than placebo users. Not only do many users lose their response to Remicade, but patients who wish to use Remicade long-term must receive treatment at least every eight to 14 weeks, regardless of symptoms, in an attempt to avoid

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developing antibodies against the treatment (8-11). From this evidence it is safe to conclude that it is unproductive to adopt Remicade as a long-term maintenance program for CD. The effectiveness of TSO in short-term clinical studies revealed that, by the 12th week, 75.9% responded and 65.5% were in remission (Summers 2005, 90). Long-term recovery rates for TSO showed an increase, not decrease, in efficacy. Clinical studies demonstrate that by the 24th week of treatment, 79.3% experienced a response and 72.4% were in remission (90). Long-term reports by users indicate a recovery trend of periodic flares of step by step decreasing severity until remission is achieved (Detlev, 26 Sep. 2005, n.p.). Maintenance dosing is required by TSO users until the immune system can learn appropriate immune response to gastrointestinal reactors (Detlev, 10 Aug 2005, n.p.). However, the substantial and sustained improvement reported makes this therapy a viable option for treatment of CD (Summers 2005, 90), and is without doubt, a more effective choice than Remicade. Understanding Your Options: TSO Safer than Remicade Despite known side-effects such as respiratory infections coughing and stomach pain dyspnea, flushing, headache and rash, cases of anaphylactic-like reactions, including laryngeal/pharyngeal edema and severe bronchospasm, and seizure (Centacor, Remicade,1920 ), the FDA approved Remicade in October of 1998 (Tauber 2004, 3). Since its approval, Centacor, the producer of Remicade, has had to notify physicians of these safety alerts and update its warning labels several times. Centacor confirms reports of tuberculosis, sepsis, pneumonia and other serious infections, some ending in death (14-15). Malignancies, including non-Hodgkins lymphoma and Hodgkins disease (21), and [s]evere hepatic reactions, including liver failure, jaundice, hepatitis and cholestasis, [and] Autoimmune hepatitis, including cases that ended in death or necessitated liver transplantation, were

Treatment Options reported (15). It is unknown whether the constant blood tests required of Remicade users are even a beneficial preventative measure against contracting these side-effects (Phelan and Wooltorton 2004, 1045). Moreover, the increased danger of contracting infectious disease while using Remicade makes surgery more risky than normal. In contrast to the many serious liabilities that accompany the use of Remicade, clinical TSO

studies failed to discover any risk at all to the user: There was no indication that the ova therapy made any patient more ill, and there were no side-effects or complications attributable to therapy. Patients developed no new symptoms (Summers 2005, 90). There is no risk to inadvertent exposure to the TSO either. TSO Met the requirements that it should, 1) produce self-limited colonization in humans, 2) have no potential to cause human disease, 3) not replicate in the host, 4) not be transmissible, and 5) be free of there contaminating agents or organisms (Ovamed A New 2005). The success and safety record of TSO is also indicated by the fact that the approval process has been started, and, while this treatment is not currently approved for sale in the United States, it is entirely legal for your physician to prescribe TSO, as many are already doing (Ovamed, A New, n.p.). Stress is known to cause an exacerbation in CD, making it important to consider not only the medical risks associated with a treatment, but also the emotional burden. Statistics above show that CD is often diagnosed in adolescence, a time in life which presents its own emotional burdens associated with simply growing up. If taking Remicade, the CD sufferer would likely be under considerable stress just worrying about potential side-effects. Not only would one have to keep track of all the changes in the signs and symptoms of the CD, but also any changes that may lead the doctor to suspect one or more of the complications that would contraindicate continuation of Remicade therapy. Remicade also requires a four hour absence from either work

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or school. It is realistic to suggest, therefore, that fears and frustrations associated with Remicade use may actually trigger or aggravate ones symptoms. In order to reduce these stresses, the FDA should be looking to approve a treatment, such as TSO, that will not cause any further difficulty to patients with CD. While those opting for TSO do not have to worry about physical side-effects, there may still be a fear of ingesting live parasite eggs. Ovamed reports that most patients overcome this aversion once they see the solution and cannot find any evidence of either eggs in the mixture, or worms in the stool (Ovamed, A New, n.p.). Conclusion Because TSO is clearly an effective and safe therapy for treating Crohns disease, patients should consider it a more viable option than the use of Remicade, which has been shown to be both less effective in the long run, and undeniably less safe. While the choices may seem scary, neither option is as scary as making no decision at all. Dr. Frank Saibil warns: When you need treatment and you avoid it, there is a significant risk that the disease or complication will get worse, and may even endanger your life (Saibil 2003, 104). Patients with Crohns need to understand the options they are presented with and take positive, reassured steps toward regaining command over an otherwise debilitating situation.

Treatment Options WORKS CITED

CCFA. Disease Information. Crohns and Colitis Foundation of America. 16 Oct. 2005 <http://www.ccfa.org/info/treatment/medications>. Centacor. Remicade/Infliximab Label FDA Medwatch (Dec 2004). 29 Oct. 2005 <http://www.fda.gov/medwatch/SAFETY/2004/Remicade_12-22-04_PI.pdf>. Detlev. Re: the future. Online posting. 26 Sep. 2005. Ovamed GmbH. 20 Oct. 2005 <http://www.ovamed.de/english/home/home.html>. Detlev. Re: Question for Detlev. Online posting. 10 Aug. 2005. Ovamed GmbH. 20 Oct. 2005 <http://www.ovamed.de/english/home/home.html>. Frank, Michael S., David J. Ott, and Fergus Shanahan. Crohns Disease: Choosing the Right Therapy. Patient Care 27(1993): 52. Kalibjian, Cliff. Straight From the Gut. Beijing: OReily, 2003. Ovamed. A New Approach to Therapy of Ulcerative Colitis and Crohns Disease. Ovamed GmbH 16 Oct 2005 <http://www.ovamed.de/english/home/home.html>. Phelan, Cynthia and Eric Wooltoron. Infliximab and Serious Hematologic Events. CMAJ: Canadian Medical Association Journal 171(2004): 1045. Saibil, Fred. Crohns Disease and Ulcerative Colitis, Everything You Need to Know. Buffalo: Firefly Books, 2003. Summers, R.W., D.E. Elliot, J.F. Urban, R. Thompson, and Joel Weinstock. Trichuris suis Therapy in Crohns Disease. Gut 10.1136 (2005): 87-90.

Treatment Options Tauber, William B. Serious Adverse Events Associated with Use of the Anti-TNF alpha Drugs. 2004 Power Point Presentation, 25 October 2005 slide 3. <http://www.fda.gov/cder/present/DIA2004/Tauber.ppt.>. Weinstock, Joel, R Summers, and D.E. Elliot. Helminths and Harmony. Gut (2004) 7-9.