Robert Kavitt, MD, discusses Eosinophilic Esophagitis and where are we at with regards to this in 2014.
[MUSIC PLAYING] ROBERT KAVITT: Just a brief remark on an important part of the disclosure slide. There are no medical therapies for use in eosinophilic esophagitis that are FDA approved. So, where are we at in 2014? We have important treatment options for our patients with use in eosinophilic esophagitis, but this emphasizes that there's a lot of work that needs to be done. So, to begin here with endoscopic images of a patient of mine with EOE. This is a patient in his 20s who presented to the emergency room with our complaints of dysphagia, and had a food impaction with broccoli at that time. As you can see here, the classic endoscopic findings of esophageal rings, as well as linear furrowing in the esophagus. So, we know that 10 to 15% of adults who undergo an upper endoscopy to evaluate symptoms of dysphagia, are ultimately diagnosed with eosinophilic esophagitis. In fact, there are some patients who may not even have classic endoscopic findings of EOE, but if a patient has dysphagia of unknown etiology, it's important that if we have any level of suspicion that we take biopsies to look for this. We know that a third, to over half of adults, with eosinophilic esophagitis develop a food impaction necessitating endoscopic bolus removal. Which is further evidence why it's important that we treat our patients to both clinical and histologic remission in order to prevent the further development of stricturing disease, and avoid such impactions from occurring. So I'd like to begin by defining EOE, talking about PPI responsive esophageal eosinophilia, a new subset of disease that we're aware of now, in the past couple of years, that it's important to recognize and treat appropriately. Looking at highlighting what the treatment options are available for our patients at this point in time, and then highlighting from some abstracts from Digestive Disease Week, and looking at what the latest research is telling us. So the 2011 EOE guidelines published in the allergy literature highlight a definition for EOE that holds true today. EOE represents a chronic immune antigen mediated esophageal disease, characterized clinically by symptoms related to esophageal dysfunction, and histologically by eosinophil predominant inflammation. A new subset of disease, PPI responsive esophageal eosinophilia, or PPIREE, has really been recognized over the past couple years now. There was a nice review article published last year that showed that there are significant benefits from treating patients with this condition, with PPIs. So, patients who have this subset of disease, who are adults, generally been found in the literature ranging from 25 to 80% of those patients will have clinical remission from being given PPIs. And they went from a third to 61% of patients we found to have histologic remission. The guidelines that were published by the ACG in 2013, regarding the management of EOE, highlight this algorithm, and being able to allow us to identify patients who have the subset of disease. So patients come in, they have esophageal eosinophilia on biopsy. As long as we are able to assess and rule out other causes of esophageal eosinophilia, we need to treat these patients with a high dose proton pump inhibitor twice daily for an eight-week course, and then have them undergo a repeat endoscopy with biopsies. If that esophageal eosinophilia resolves, we categorize them as having this subset of PPIREE. If the esophagitis eosinophilia does not resolve, we consider them as having EOE and treat them accordingly. So what treatment options are available for our patients? We can start with topical steroids. Again, none are FDA approved at this time for the treatment of EOE. But the guidelines highlight the use of fluticasone metered-dose inhaler. And there's a range of doses that are used in the literature-- anywhere from 880 to 1760 micrograms per day, in a divided dose from a swallowed inhaler. As well as the option of oral viscous budesonide, that generally studies highlight in adults using two milligrams per day, in a divided dose. We also options that are usually preferred for dietary therapy. Either an elemental diet, or now, more likely, a six-food elimination diet. So we found that most cases of eosinophilic esophagitis are due to food allergies. That can be a response to either soy, egg, milk, wheat, nuts, or seafood. Patients will undergo serial endoscopy after avoiding these six foods for several weeks, and then gradually add back one to two foods at a time until we're able to determine what that dietary trigger is. Generally, patients will have to undergo somewhere between 6 and 10 endoscopies until the results are known. So this is a major cost, and a major time commitment on behalf of our patients. However, ultimately many patients do prefer this, because they're usually able to avoid the use of long-term corticosteroids as a result. The goal of the six-food elimination diet is to induce clinical and histological remission, and to maintain remission by avoiding the dietary trigger. The most common dietary triggers are wheat in 60% percent of patients, and milk 50% of patients. And, ultimately, about 15% of patients have been shown to have more than one food trigger as the etiology of their eosinophilic esophagitis. Unfortunately, skin protesting does not accurately predict what the allergen is in most of our patients. Only about 13% of patients have been found to undergo skin protesting, and have that accurately identify what food trigger is determined by serial endoscopy with biopsy. And then, finally we have endoscopic treatments available. It's been debated, in the literature, whether or not we should be dilating patients with eosinophilic esophagitis. Generally, conservative dilation in patients who have structuring disease that persists, despite medical and dietary therapy, as well as a symptomatic esophageal stenosis, can have benefit from esophageal dilation. Until 2008, it was generally consider that these patients were at a higher risk of perforation than the general population. But now, with more recent, larger case series, we find that as long as conservative dilation is performed, that that risk is not as significant as once thought. So now that we've laid the groundwork, I'd like to highlight research that has been presented at Digestive Disease Week this year in oral presentations that can help to guide further therapy. So, there was a wonderful study that was presented by a European group, by a colleague from Spain. Long term efficacy of PPI therapy in patients with PPI responsive esophageal eosinophilia. And in this international, multi-centered trial, it was observational and retrospective in nature, and they found that after initial PPI response, acid suppression was progressively tapered based on symptoms, and maintained at the lowest dose possible with the target end point of maintaining clinical remission in patients with PPIREE. Follow-up endoscopy was performed at 12 months or longer, once patients were on a PPI maintenance dose. They found that 74% of patients with PPI responsive esophageal eosinophilia had a sustained remission on a maintenance-dose PPI. So this is important, and tells us that PPI responsiveness in this patient population is not transient. So PPIREE, as I said, has really been known-- we've only been aware of this, mostly, for about the past two years, and we don't have a long-term natural history course of knowledge about patients with this condition. So, it's important that we now recognize that, at least over the time period studied, that this is not a transient phenomenon. Secondly, two-thirds of patients with histological relapse had this histological relapse occur in the distal esophagus. And it was founded that this could be over overcome with PPI dose intensification, the increasing dose or increasing frequency of the dose of PPI, showing us the transient response to PPIs might be dose-dependent in nature. And ultimately, only 8% of patients-- only for patients-- who have an initial diagnosis with PPI responsive esophageal eosinophilia were reclassified as having eosinophilic esophagitis. So, it's important, and tells us that most of these patients that we initially diagnosed with this condition ultimately continue to have it over time. The second study that I wanted to highlight was, again from a multi-center European group, presented by a colleague from Germany. Two new budesonide formulations are highly efficient for the treatment of active EOE-- results from a randomized, double- blind, double-dummy, placebo-controlled trial. So the aim is to investigate the safety and efficacy of these two new budesonide formulations, in both an effervescent tablet and viscous suspension, at different doses. So 76 patients were randomized, to eosinophilic esophagitis to a two-week course of these formulations of budesonide, as well as to placebo. And as you can see here, the one milligram, twice-daily budesonide effervescent tablet had a histologic remission response of 100%, and had an excellent outcome from a higher dose as well as from a viscous suspension. Whereas no response was obviously seen among the placebo group. So, either formulation was highly effective and safe for the short-term treatment of EOE. However, we know that patients with EOE have this as a chronic condition, and likely lifelong. So, there's a lot more work that needs to be done to tell us if patients have EOE, and they're on corticosteroids, what duration of treatment should be pursued. I presented an oral presentation, a randomized, blinded, controlled trial comparing esophageal dilation to no dilation among adults with EOE, with the aim to determine if, and to what extent, dysphagia improves in response to initial dilation followed by standard therapies of PPI and fluticasone. So we started with 31 patients that were randomized to either dilation or no dilation. Patients were not told if they underwent dilation at the time of endoscopy. They were then given a proton pump inhibitor, as well as an inhaled corticosteroid that was swallowed. And we surveyed our patients at 30 days and 60 days status, post-endoscopy to determine their level of the dysphagia symptoms. And, as you can see here, at both 30 days in 60 days, patients had a statistically significant improvement in their dysphagia score, with a P value of less than 0.01. However, there was no significant difference that was found at each of those time points between the two groups, whether or not they underwent dilation. So, as dilation did not result in additional improvement in dysphagia score, compared to fluticasone and PPI alone, we've determined dilation does not appear to be a necessary initial treatment strategy. But it's important to note that our patient population in the study had really mild to moderate disease. And, really, a very low-level of significant stricturing in the esophagus in these patients. So, it's important to note with that caveat that in the specific patient population, dilation did not make a significant difference. And then, finally, a group from Mayo Clinic presented a study-- an evaluation of this newer technology, the cytosponge, and compare it to upper endoscopy. So, 20 patients with EOE swallowed this capsule containing the cytosponge that's attached to a string. That capsule quickly dissolves in the stomach, and then the string is pulled up through the esophagus, and cytology specimens are collected using this sponge. Patients then underwent an upper endoscopy two hours after undergoing the testing with the cytosponge. And the sponge is found to have the sensitivity of 63% for diagnosis of EOE. All patients did prefer this over undergoing an upper endoscopy. And I think that there is going to be an important role for future technologies such as this in assessing patients with EOE. And hopefully when patients undergo an elimination diet, may be able to have other technologies available to them than eating to undergo the time off of work, and the cost of sedation and endoscopy, and assessing their level of eosinophilia. So, where are we at in 2014? We need to be correctly looking for, and treating, patients with PPI responsive esophageal eosinophilia, in treating them differently than patients who have true EOE. We need to recognize that remodeling consequences of EOE exist, and that it's important that we treat our patients for the long-term in order to prevent further structuring disease, and prevent food impactions in the future. We need to recognize the important role that dietary therapy plays in the treatment of our patients, and the role that dilatation may or may not play in depending on the severity of the stricturing disease. Thank you.
