GLG News by Michael Blume

Implications: This potential issue has been of concern since we changed to Propofol based anesthesia for all of our patients approximately five years ago.  We made this decision because it made endoscopic procedures significantly more tolerable (essentially painless, except for the bowel prep) for just about all of our patients, as well as, frankly, safer.  While many patients did well with standard conscious sedation using agents such as Sublimaze and Versed, others did not do as well.  Using an anesthesiologist benefited not only high risk patients, but also patients who had rather high sedation tolerances, who often were difficult to identify prior to performing the procedure. 

Analysis: Propofol, at least in the state where I practice, can only be administered by anesthesiologists, so had third party payers limited their coverage, it would have made giving Propofol to many of our patients more challenging.  It is not just high risk medical patients (i.e. ASA-3 or higher) patients who need both anesthesiologists and this drug, but also patients who have higher sedation requirements, many of whom are not readily identifiable before the procedure.  Limiting access to Propofol (or at least safely administered Propofol) would have the effect of potentially creating some adverse outcomes, or at the least, bad patient experiences, which would limit patients' willingness to undergo endoscopic procedures, including screening colonoscopies. 

This issue will likely arise again when there are Propofol like drugs available that can be safely administered by non-anesthesiologists, and when guidelines are in place to adequately credential physicians and/or facilities to administer the drug (be it some new drug, or Propofol itself), monitor patients who get the drug, as well as manage potential side effects, be they hemodynamic or airway related.

Implications: Patients with isolated proctitis remain a difficult to treat subpopulation of patients with UC.  Topical mesalamine is often efficacious, but is not always the preferred mode of administration for many patients.  As we have a variety of options as to which oral mesalamine preparation to use in our patients, seeing data on treating proctitis can be useful in making a decision as to which one to use.

Analysis: Treating patients with ulcerative proctitis with oral medications is often challenging, and may be problematic for a variety of reasons, including efficient delivery of the drug to the rectum.  It is often difficult to examine data on proctitis in evaluating efficacy studies when trying to distinguish between the numerous mesalamine preparations on the market.  This study does demonstrate some benefit to using Asacol in patients with proctitis.  It would be useful to have data concerning this from the other mesalamine preparations in which one could compare "apples to apples" and make an informed decision as to which drug to use.  Additionally, from a practical standpoint, one is often more interested in what percentage of patients are able to achieve and/or maintain clinical remission with mesalamine alone, without having to resort to an additional medication.

Implications: Which PPI to prescribe?  We already have a myriad of choices between brands, which in general, are all quite effective when used for the correct indications.  An oral suspension is useful in a patient who requires PPI therapy, but who is unable to swallow pills for a variety of reasons.  This scenario, however, represents a very small percentage of the large patient population who are on PPI's.  This formulation would be unlikely to dramatically affect prescribing habits for most physicians in the community.

Analysis: This particular formulation addresses a small niche in the PPI market.  Most patients are able to swallow pills, and if not, are able to use formulations or options already available, i.e, solutabs, etc.  There may be a convenience factor in having a premixed oral suspension rather than opening capsules and mixing with juice or applesause, etc, in certain settings, such as nursing homes, hospitals (again, only in patients who are unable to swallow pills), however how much it will be used in this very specific situation will, in the end, depend on cost related issues compared to present options.  While there may be a place for using Protonix oral suspension, it will likely be a small place, and it would be unlikely that this will have a significant impact on the overall PPI prescrbing habits of physicians prescribing in an ambulatory care setting.

Implications: The clinical outcome information in this report regarding decreasing colectomy rate is not particularly surprising, but the cost statements may be misleading.  One wonders if the increased health care costs in the colectomy group reflect that fact that the observation period was only twelve months, and is skewed because of issues involving the immediate post-op period.  One should be looking at cost related issues in the long run, and would expect that five years down the line, for example, given the costs involved with drug therapy and monitoring patients with IBD and the fact that colectomy in UC is curative, the costs in the colectomy group would be significantly lower.  Remicade has been an important addition in how we treat inflammatory bowel disease for some time, and has been FDA approved for use in UC for several years now. It has allowed us to not only get more patients into remission, but also keep patients in remission and decrease steroid usage.

Analysis: It would be hard to believe that in the long run, colectomy would not be cost effective vs continued medical therapy.  Colectomy might be more expensive in the short run (i.e. twelve months), but most likely not in the long run.  What is more important is that the drug has the potential to reduce disease related morbidity, improve quality of life, decrease steroid usage and morbidity, and have a positive effect on clinical outcomes. 

The larger issue is when to start the drug, and in whom, as initiating Remicade is a signficant  committment, and is certainly not without risks.   One is often dealing with young patients, often of child bearing age, and making a decision to use Remicade either for induction and/or maintenance has major implications.  One has to carefully weigh benefits and risks when deciding to use this drug.  That being said, the drug is effective, and if used appropriately, has the potential to significantly improve clinical outcomes.  In the next several years, we will have the choice of a number of biologic agents to utilize in our inflammatory bowel disease patients (Humira is already FDA approved for Crohns disease, for example), and understanding the best way to utilize these drugs will become increasingly important.

Implications: Constipation predominant IBS is an extremely common problem, which while not life threatening, interferes significantly with daily function in many people.  We have very few effective drugs (especially since Zelnorm was taken off of the market) for this condition.  Lubiprostone may be a welcome addition to what are limited therapeutic options, however its efficaciousness, while statistically better than placebo, is not overwhelming.  Its utility may be limited by its limited efficaciousness, pregnancy concerns (it is category C, and many patients with this disorder are young females), and cost.  It will probably have a place, however, in how we treat some patients with this disorder, either as a stand alone drug, or part of some type of combination regimen.

Analysis: IBS is probably the most common disorder treated by most gastroenterologists who are in a community based clinical practice.  Treating constipation predominant IBS is particularly difficult because we have very few drugs that are efficacious.  Removing Zelnorm from the market caused problems for many patients who were responding well to this drug, and for whom nothing else worked.  Having another drug, albeit not dramatically efficacious (17.9% response rate, while better than 10%, is not that dramatic), is welcome, and one wonders if this may be helpful in a subset of patients with this disorder, either as a stand alone drug or part of some combination of drugs. 

At 24 mcg twice daily (the approved dosage for idiopathic constipation), I have encountered some limited success in patients with difficult to treat chronic constipation.  The nausea associated with this drug has limited its tolerability.  This is likely dose related, and hopefully at 8 mcg, nausea will be less of a problem. 

The other concern with the drug is that it is pregnancy category C.  This is a disorder that often strikes women who are of child bearing age, and one needs to use it with caution in these patients.  One needs to combine this fact with the reality that IBS and idiopathic constipation, while uncomfortable and often painful conditions, are not life threatening conditions.  It is difficult to justify using a category C drug for a patient who might become pregnant for a condition that is not life threatening or associated with significant medical complications. 

Despite the above concerns, this drug has helped many patients with refractory idiopathic constipation (it is not a first line drug), and likely will help some patients with IBS-C.  Where it will fit in to how we treat patients with IBS-C remains to be seen.

Implications:

Some patients with bloating who have IBS may have some component of bacterial overgrowth, which may be responsive to a non-absorbable antibiotic, such as Xifaxan. Given how difficult is this disorder often to treat, this may be another therapeutic option on how to alleviate symptoms in some patients with this disorder.

Analysis: Would make the following comments:

1. Not all IBS patients are alike. The patients who may benefit may represent a subset of patients with IBS. Determining this is going to be mostly on clinical grounds, i.e. by taking a history, as in the community, Lactulose breath tests are not readily available in a community practice at this time. The decision to use Xifaxan will be made by starting that patient on empiric therapy, assuming it is likely in one's clinical judgement that that particular patient is likely to respond.

2. The dosage of Xifaxan used to treat bacterial overgrowth is significantly higher than the approved dosage used to treat traveler's diarrhea. It is often difficult to get third party payors to pay for an appropriate dosage at the present time, and this can limit one's ability to use what may be a very novel therapy. This most likely may not change until this indication becomes FDA approved.