On January 11, 2012, the U.S. Food and Drug Administration's (FDA) Gastroenterology and Urology Devices Advisory Panel voted on the pre-market clearance of the LINX Anti-Reflux System. The nine panel members voted unanimously to affirm the device's efficacy, safety, and favorable risk-benefit ratio for pathologic gastroesophageal reflux disease (GERD), which is refractory to anti-reflux medications. The anti-reflux system consists of a string of magnetic beads, the attraction between which assists in the closure of the lower esophageal sphincter (LES), which acts as an anti-reflux device, and a string of magnetic beads, which can be opened to allow food to enter the stomach when the patient swallows.
■ Clinical Challenges Controlling GERD: PPI, Surgery, or Other? GERD is one of the most prevalent gastrointestinal diseases in the United States. In addition to painful symptoms, GERD can lead to esophageal mucosal damage, Barrett's esophagus, and can progress to adenocarcinoma. The current primary medical treatment is the daily administration of proton pump inhibitors (PPIs.) PPIs are effective for esophagitis, but are less effective in controlling reflux symptoms. Fundoplication, although effective in reestablishing a barrier against reflux, permanently alters the anatomy of the stomach and is associated with many side effects. New techniques have been explored over the years in the hope of enhancing the strength of the LES while avoiding the adverse consequences of fundoplication. These techniques include suturing of the flaccid lower esophageal sphincter and injection of polymers to alter LES compliance; unfortunately, few have received FDA marketing approval. In this context, the LINX Anti-Reflux System was developed, which can be placed laparoscopically above the patient's stomach, near the lower esophageal sphincter. The technology has attracted attention because of its short surgical time, the fact that patients can return to normal eating and activity within a week, and the fact that it can be removed laparoscopically. FDA Advisory Panel Opinion Clinical Trials Have "Hard Knocks," But No Flaws The feasibility study of the LINX system*** included 44 patients from four research institutions in Europe and the United States. At 1 and 2 years postoperatively, 85% and 90% of patients reported symptomatic improvement, respectively, and 90% and 86% reported complete cessation of PPI use. 43% of patients experienced early dysphagia, most of which resolved on their own within 90 days postoperatively, and one patient had the anti-reflux system removed laparoscopically due to persistent dysphagia. The pivotal study included 100 patients from 14 research institutions. Postoperatively, 92% of patients reported symptomatic improvement, 93% had their PPI dosage reduced by at least half, and 64% had normal or improved esophageal acid exposure. The incidence of serious adverse events was 6%: three patients had the antireflux system removed because of dysphagia; two were readmitted 7 days after surgery for nausea and vomiting; and one was admitted to the hospital with chest pain in the first 6 months after surgery, and the system was removed 1 year after surgery. The FDA advisory panel's debate on safety centered on dysphagia, which was reported in 68% of patients who had an antireflux system placed and was the most commonly reported complication. The panel's *** knowledge was that dysphagia symptoms are relatively mild and not a safety concern. Dr. Gould, of the Medical College of Wisconsin, Milwaukee, believes that if the Nissen fundoplication cohort is studied, some symptoms that are not very common with other treatments also occur, and therefore its safety should be viewed holistically. Dr. Schwaitzberg, of Harvard Medical School, described the design of the clinical studies as "flawed," although he agreed that "their demonstration of efficacy and low complication rates is quite good. Schwartzberg emphasized, "I would like to see studies that continue for at least 10 years after approval, and as an inserted medical device, we want to know the long-term outcomes." Panel statistician Dr. Afifi, of the University of California, Los Angeles, said he would like to see case-control studies. Dr. Faulx, Case Western Reserve University Medical Center, Ohio, commented that the LINX Anti-Reflux System is proving to be quite useful, with minimal risk, compared to the less-than-perfect current standard of care.