When I finally go into histologic remission, I will throw a party... that day will be worth celebrating. So what do I mean by histologic remission? I mean that I would like to have biopsy-confirmed results showing my gut has been healed by the motley collection of pills and injections that I find myself currently taking for Crohn's. There are several types of medications that are prescribed to treat Crohn's disease (therapy options range from corticosteriods to so-called "antimetabolites"* to new biologic therapies*... and even antibiotics*), and they range in their efficacy and mechanisms of action.
In my personal experience thus far, I haven't found the right medication(s) to significantly impact the colonoscopic or pathologic results in my gut, but there has been one medication in particular that has improved my more quality-of-life-type symptoms (e.g. fevers and malaise)... prednisone. At this point, I have heard a few gastroenterologists say that cortiosteroids (prednisone is one particular example of this class of medications) make Crohn's patients feel better, but don't actually get them better. What this means is that while steroids are good at suppressing systemic (whole body) inflammation, they are potentially less good at actually healing the mucosa (lining) of the gut. So even though the quality of life of a Crohn's patient on corticosteroids might be significantly improved, if that same patient were to get several gut biopsies, there might still be extensive evidence of active disease.
Pathologic features of Crohn's
In order to make a diagnosis of Crohn's disease, usually some kind of endoscopic examination will need to be done. This can be in the form of a colonoscopy or upper endoscopy, and often both. During that exam, if the gross pathology (evidence of the disease that can be seen with the naked eye or, in this case, camera) is suggestive of inflammation, the gastroenterologist can take a few biopsy specimens for further analysis under a microscope. A gut with Crohn's disease will have some key features if examined under magnification... the microscopic architectural features will be disorganized and high levels of certain inflammatory cells will be present (Geboes and Dalle. 2002). The inflammatory features on biopsy can sometimes be telltale for Crohn's (this situation will often include "granulomatous" inflammation), but in many cases the inflammatory process in the bowel can be non-specific and, thus, not itself diagnostic.
So, the ultimate goal for a Crohn's patient would be to achieve remission of the disease from an endoscopic and histologic standpoint... although symptomatic remission is what is most commonly achieved and, in a sense, is most important. If a repeat colonoscopy is done when symptoms are under control, confirmation of gut healing by pathologic examination would be the best way to show that disease activity is absent or very low... and that the medications have done their job.
Prednisone & the power to heal?
Published studies seem to show poor colonic mucosal healing with corticosteroid use in patients with Crohn's disease (Landi et al. 1992., Oliason et al. 1990.). Landi and colleagues gave high-dose prednisolone (the dose was 1 mg/kg/day, and prednisolone is an active corticosteroid that is essentially what prednisone gets converted into inside your body) to 147 patients with acute attacks of colonic or ileocolonic Crohn's disease. After 5 weeks, they found that 136 of these patients had achieved clinical remission, but 96 still had lesions on endoscopy. The study by Oliason and colleages was much smaller, having only 8 patients with ileal Crohn's disease... thus, I will consider these results as more of a case study than a controlled trial. With 20-30 mg/kg/day doses of prednisolone for 6-9 weeks, the patients had significant improvement in activity indices, but essentially no improvement in ileal inflammation. However, there was one study that showed rectal biopsy normalization in patients taking a combination of prednisolone and sulphasalazine; although the results with prednisolone on its own were less striking (Schmitz-Moorman et al. 1988.). This study suggested there was a good relationship between Crohn's Disease Activity Index score and histologic improvement in their subjects. Taken together, it seems that symptomatic relief with corticosteroid medications is much greater than the impact that steroids have on gut pathology.
Prednisone: commentary on the benefits and risks
My husband and I actually got into a heated debate about this topic, so I am going to try to summarize both of our viewpoints on this subject (while hopefully not completely botching his opinion). I want to leave my commentary for this post open to different viewpoints on this subject.
First the setup to the debate: While short courses of corticosteroids can be fine, long-term corticosteroid use is considered relatively dangerous. These drugs have a whole host fairly common, and fairly unpleasant, side effects, including weight gain, insomnia, bone loss, muscle loss, diabetes, and on and on. I currently have a bit of a moon face from the several months of prednisone.
My opinion: Given all of the side effects, my opinion is that there must be some perceived health benefit of corticosteroids, beyond their ability to improve the quality of life for Crohn's patients, in order for them to be so widely prescribed for therapy. This benefit need not be a real benefit of actually suppressing the overactive, damaging inflammation in the gut, but could just be a perceived benefit by clinicians... i.e. because it is a known powerful immunosuppressive, it should, theoretically, impact the course of Crohn's disease. My point is not to say that quality of life issues aren't important or shouldn't be treated... very much the contrary. I know better than most how difficult it is to just go about normal life when running a fever or to the bathroom 10x per day. My argument is simply that corticosteroid should be used sparingly if they do not impact the course of the inflammatory bowel disease. The risks seem to outweigh the benefits of just making me "feel good".
I would analogize the situation to the use of opioid medications for pain. My perception (which may or may not be true) is that physicians have a bias toward underusing opiates to relieve pain. Clearly, this is because there are certainly dangerous side effects of these medications. But in addition, I think that the fact that opioids just relieve pain... and don't do anything to fix the underlying problem... is another reason why they may be cautiously prescribed. Here there is a clear dissociation: a drug that can improve quality of life in a patient with chronic pain, but doesn't do anything to treat the underlying pain mechanism. In my opinion, the cost-benefit calculus is shifted toward greater cost in this situation, where the benefit is one that only impacts quality of life for a risky medication.
Opiates are actually a great category of drug to talk about because an interesting counterpoint to the use of opiates for pain, is the use of opiates for diarrhea. The notable medication here is loperamide (i.e. Imodium), which is the same type of medication as an opiate used to treat pain... with the important caveat that it doesn't cross the blood-brain barrier (thus, no pain relief or risk of addiction). Similarly to opiates for pain, loperamide treats the symptoms of diarrhea, without healing the underlying cause of the diarrhea. However, in this situation, the medication (generally) carries minimal risk of adverse effects, so it is used quite widely. The cost-benefit analysis is heavily weighted toward the benefit of symptom relief, even if it will not impact the course of the illness.
My husband's opinion: I think he basically puts more weight on the improvement of quality-of-life-type symptoms, and, thus, his analysis of the costs versus benefits of prednisone (having seen my personal short-term response to it) is more favorable toward the benefits. Even if there is no mucosal healing that occurs, because it eliminates fevers and improves general wellbeing, short-term use is fine (don't know the tipping point when short term ends and long term begins though). Btw, he also thinks that opiates are under prescribed to treat pain... with which I do agree.
*The (very) basic run-down of Crohn's drugs (other than corticosteroids):
Antibiotics: Probably most everyone has been at least one, if not several, of these for various bacterial infections, so I don't need to be too detailed... but these medications either slow down the growth of or kill bacteria. In Crohn's, antibiotics such as flagyl or ciprofloxacin are sometimes prescribed with the idea that if you change the bacterial balance in the colon, it could help slow the inflammatory response.
Antimetabolites: Generally speaking, antimetabolites are medications that inhibit the use of a chemical in normal metabolism. For Crohn's disease, these medications include azathoprine, 6-mercaptopurine, and methotrexate and are drugs that impact the production of lymphocytes (white blood cells) in the bone marrow... the idea being if you have less lymphocytes around, they can't do as much damage to the GI tract.
Biologic therapies: These medications are the newer frontier of therapy for Crohn's disease. Biologics are components that are synthesized by biologic processes instead of a chemical ones, but this descriptor really says nothing about what the drugs do. Most of the current biologic therapies used for Crohn's are designed to bind to and inhibit TNF-alpha, a molecule that seems to be a be a bad actor in overaggressive inflammation. Trials for different kinds of biologic therapies are currently underway though.
Bibliography:
Geboes and Dalle. 2002. Influence of treatment on morphological features of mucosal inflammation. Gut 50(Suppl III):iii37-iii42.
Landi et al. 1992. Endoscopic monitoring of Crohn's disease treatment: a prospective, randomized clinical trial. The Groupe d'Etudes Therapeutiques des Affections Inflammatoires Digestives. Gastroenterology 102:1647-1653.
Oliason et al. 1990. Glucocorticoid treatment in ileal Crohn's disease: relief of symptoms but not of endoscopically viewed inflammation. Gut 31:325-328.
Schmitz-Moorman et al. 1988. Relationships
between drug regime and histology of rectal mucosa in CD. Pathology - Research and Practice 183:30–34.
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