AGA’s 2018 Presidential Plenary session was packed, and excitement in the room was palpable! On the stage sat Sheila Crowe, our outgoing president, with David Lieberman, our incoming president. Our new logo was proudly and prominently displayed. In addition to expert presentations on eosinophilic esophagitis, colon cancer and inflammatory bowel disease, several abstracts were highlighted.
Dr. Stuart Jon Spechler of Baylor University Medical Center in Dallas, Texas, reported on a study titled “A VA Cooperative, Randomized Trial of Medical and Surgical Treatments for Patients With Heartburn That Is Refractory to Proton Pump Inhibitors.” At 10 U.S. Veterans Affairs medical centers, patients with heartburn refractory to proton pump inhibitor (PPI) treatment underwent comprehensive work-ups (including endoscopy with esophageal biopsy and esophageal manometry) to exclude non–gastroesophageal reflux disease (GERD) disorders. Remaining patients had esophageal multichannel intraluminal impedance-pH monitoring, and those with reflux hypersensitivity (normal acid reflux but symptoms associated with reflux episodes) or persistently abnormal acid reflux were randomized to laparoscopic Nissen fundoplication, active medical therapy (omeprazole 20 mg twice a day [BID] plus baclofen/desipramine for baclofen failures), or placebo (omeprazole 20 mg BID plus placebo/baclofen plus placebo/desipramine). The primary outcome was an improvement of 50 percent or more in GERD health-related quality of life at one year. Among 366 patients enrolled, 288 (78.7 percent) were excluded by prerandomization procedures! The remaining 78 patients (21.3 percent) with verified, reflux-related, PPI-refractory heartburn were randomized to surgery (27 participants), active medical therapy (25 participants), or placebo (25 participants). At one year, the success rate for surgery (66.7 percent) was significantly better than active medical (28.0 percent; P = .007) and placebo (11.5 percent; P < .0001). Active medical therapy and placebo success rates did not differ significantly. These findings demonstrate that careful work-up will reveal non-GERD disorders in most patients with PPI-refractory heartburn; however, for those with reflux-related heartburn, surgery is significantly better than medical therapy. The demonstration that active medical therapy was not significantly superior to placebo will come as no surprise to gastroenterologists who deal with this issue daily in their practices! I believe this report will have substantial impact on how we manage PPI-refractory heartburn.
The demonstration that active medical therapy was not significantly superior to placebo will come as no surprise to gastroenterologists who deal with this issue daily in their practices.
Dr. Christophe Cellier of the Hospital European Georges Pompidou in Paris, France, presented an abstract titled “AMG-714 (Anti-IL-15 MAB) Halts the Progression of Aberrant Intraepithelial Lymphocytes in Refractory Celiac Disease Type II (RCD-II): A Phase 2B, Randomized, Double-Blind, Placebo-Controlled Study Evaluating AMG714 in Adult Patients With RCDII/PRE-EATL.” Type 2 refractory celiac disease (RCD-II; also known as preenteropathy-associated T-cell lymphoma) progresses to enteropathy-associated T-cell lymphoma (EATL) in 50 percent of cases. No approved treatment currently exists for EATL, which has a five-year survival rate of only about 45 percent. Interleukin 15 (IL-15) plays a major role in preventing death of the aberrant intraepithelial lymphocytes (IELs) that define RCD-II. Consequently, an IL-15 antibody might prevent progression to EATL by enabling death of IELs. Thirteen patients randomized to AMG- 714 and 6 to placebo were treated for 10 weeks, and intestinal biopsies were performed before and after treatment. Although AMG-714 did not result in a significant reduction in intestinal aberrant IEL counts (the primary end point), the therapy did have significant effects in reducing T-cell receptor (TCR) clonality and improving symptoms of diarrhea. Adverse events occurred in five out of 13 study volunteers (38 percent) treated with AMG-714. This was a small study conducted in a very ill patient population, and it is unclear whether the demonstrated reduction in TCR clonality will halt the progression of EATL. On a positive note, however, these very ill patients did achieve significant symptomatic improvement. It remains unclear whether the benefits of AMG-714 outweigh its associated risks.
Finally, Dr. Tom Holvoet of Ghent University Hospital in Ghent, Belgium, presented an abstract titled “Fecal Microbiota Transplantation in Irritable Bowel Syndrome With Predominant Abdominal Bloating: Results From a Double Blind, Placebo-Controlled Clinical Trial.” In an earlier pilot study, study investigators demonstrated a beneficial effect of fecal microbiota transplant (FMT) in patients with irritable bowel syndrome (IBS) and associated severe bloating. This abstract describes the follow-up trial. A total of 64 patients with IBS were randomized to receive FMT with donor stool (42 patients; two stool donors used) or placebo (22 patients; given their own stool) delivered via nasojejunal tube. The primary end point was abdominal bloating and overall IBS-related symptoms at 12 weeks. In the active treatment group, 49 percent of study participants reported relief of general IBS-related symptoms (especially abdominal bloating) compared with 29 percent of study participants in the placebo group (P = .004). Unfortunately, only 27 percent of the active treatment group reported persistent symptom relief at one year. Analyses of the fecal microbiota that resulted in symptomatic improvement are being conducted. It is conceivable that a capsule containing those specific microbiota could be developed to induce and maintain symptomatic remission in patients with IBS and severe bloating. We eagerly await these results!
Dr. Souza has received consultant fees and research support from Ironwood Pharmaceuticals. Dr. Souza is the AGA Institute Council chair and a member of the OESO Permanent Scientific Committee, Section of Basic Sciences, and the WGO Clinical Research Committee.