Advances in Treating Gastro-oesophageal Reflux Disease – What Role for Medical Devices?

Gastro-oesophageal reflux disease (GERD) is, as the term suggests, a reflux of the gastric content into the oesophagus which brings with it a detectable impairment in the quality of life in those patients who suffer regular relapse. Indeed, clinical GERD is diagnosed when a patient suffers two or more episodes of pyrosis, heartburn or other GERD symptoms in a week. This medical condition which already afflicts millions of people in the West has been shown by a number of epidemiological studies to have increasing rates of prevalence and incidence. In the USA, more than 15 million Americans are thought to suffer from daily heartburn, around 30 million experience such symptoms once a week and as many as 48% of the adult population is thought to experience heartburn at least once a month. When heartburn is considered as a key diagnostic indicator of GERD the situation is considered less severe in Europe with most recent studies having demonstrated a prevalence of 38% in Northern Europe and up to 9% in Italy, with the latter figure providing an indication of the situation in Southern Europe. Although the prevalence of GERD is reported to be lower in Asian countries, recent epidemiological data suggest that the incidence of the disease is increasing, especially in Japan. Endoscopic studies show that the overall prevalence of reflux oesophagitis (a complication of GERD) among the adult population in Japan is in the region of 14-16%. What these epidemiological findings serve to illustrate is the growing need for effective therapies to treat this condition and there is an increasing clarity in the view that drug treatment needs to sit alongside minimally invasive surgical techniques which tackle control of the disease rather than control of the symptoms.

Proton pump inhibitors (PPIs) have been shown to be effective in their ability to improve symptoms and quality of life but treatment costs are high and there are doubts amongst clinicians relating to the benefits of long term drug treatment. Allied with these concerns is a growing consensus of an increasingly urgent need to control recurring symptoms of GERD which are associated with complications such as oesophageal adenocarcinoma. Alternatives to drug treatment are required both from the health economic perspective and the lack of response of some patients to drug treatment. Medical device companies have for some time noted the potential for treatment of GERD with device alternatives which can be used in minimally invasive laparoscopic techniques. The most common approaches to GERD treatment outside of drug treatment are:

Endoscopic Suturing or endoluminal gastroplication (ELGP)

The Bard EndoCinch endoscopic suturing device was the first such device to be granted FDA approval and the first, therefore, to be used in human patients. The procedure is performed on an outpatient procedure and generally requires in the region of 45-60 minutes to complete. The procedure requires the use of two endoscopes and an orooesophageal overtube with the patient undergoing sedation. Following placement of the overtube, a suture capsule system attached to an endoscope is advanced through the overtube to the oesophagogastric junction (OGJ). A plication (folding of tissue at the OGJ) site 1-2 cm distal to the OGJ is then chosen and suction is applied to draw tissue into a suction chamber. A needle-directed suture is deployed through the tissue and captured in the device. The endoscope is then removed, the suture reloaded, the device reinserted, and the steps repeated adjacent to the first location. The original repetitive knot-tying procedure has been replaced by a more rapid anchoring system. This then completes the performance of one plication. Generally, 2 or 3 plications are created, although the optimal orientation and number of plications remain unknown. Bard have supplemented their information on clinical trial data with findings showing the economic benefits of the gastroplication techniques. Chen et al (Chen, YK et al. One-year follow-up of endoluminal gastroplication: clinical and economic outcomes of the U.S. multicenter trial. Gastrointest Endosc 2002; 55) reported that in 183 patients studied 12 months post ELGP there were reported significant improvements in heartburn and regurgitation. Additionally, Chen et al reported that substantial cost-savings were made due to the elimination or reduction of GERD prescriptions for the patients treated. These savings were especially seen for spending on PPIs (p>0.0001). Pre-ELGP annual drug costs were $2,379 compared to $351 at 12 months following ELGP (p<0.0001), for an average annual drug cost-saving of $2,028.

A recent variation of the endoscopic suturing system was designed to fixate gastric tissue just distal to the OGJ. The Plicator system from NDO Surgical consists of a reusable endoscopic plication system (EPS) instrument, single-use suture-based implant and helical tissue retractor. The EPS instrument consists of a control handle that retroflexes the distal end and opens and closes the 2 arms of the "operating" device located at the tip of the instrument, and 2 channels for passage of the tissue retractor and an endoscope. Just as with the EndoCinch device the procedure requires that the patient undergoes mild sedation and is administered analgesics prior to passing the EPS and endoscope assembly into the stomach. Retroflexion of the endoscope and distal tip of the EPS is followed by opening of the arms of the EPS distal tip. Within about 1 cm of the OGJ, the tissue retractor is advanced deeply into the gastric wall and then retracted back into the arms of the EPS. Finally, the EPS arms are closed and the full- thickness suture implant is deployed. The Plicator procedure takes approximately 20 minutes to perform.

Radiofrequency Energy Delivery

Temperature-controlled delivery of radiofrequency (RF) energy has been used for many years to ablate a variety of tissue targets and to tighten or shrink tissue. The delivery of RF energy to the OGJ for the treatment of GERD as demonstrated with the Stretta device from Curon Medical requires a specially designed catheter and RF generator. The product has a catheter which consists of a 30 Fr bougie tip with a balloon-basket assembly and 4 thermocouple-controlled nickel-titanium needle electrodes positioned radially around the balloon. After the induction of moderate sedation and analgesia and the determination of the distance of the squamocolumnar junction relative to the incisors endoscopically, the RF delivery catheter is passed transorally to the region of the OGJ where the balloon is partially inflated. Needles are then deployed, and RF energy delivered according to a computer-based temperature-controlled algorithm while the mucosa is cooled by saline irrigation via the catheter. Numerous sets of thermal lesions are created at predetermined levels extending above and below the squamocolumnar junction. The procedure generally takes about 45 minutes to perform. The efficacy of the Stretta procedure has been reported in clinical trials data but clinicians have voiced concerns over the safety of the procedure. Modifications after complications in early procedures have resulted in lower complication rates associated with the procedure as it is currently performed.

Endoscopic Injection

This technique involves augmenting soft tissue by the injection or implantation of a number of biocompatible materials around the lower oesophageal sphincter. The first of these types of products receiving FDA approval for treating GERD is the Enteryx solution from Boston Scientific. Enteryx is an injectable solution of 8% ethylene vinyl alcohol copolymer dissolved in dimethyl sulfoxide and mixed with tantalum to make it radio-opaque and allow fluoroscopic visualisation to accurately place the injection at the lower oesophageal sphincter. When the Enteryx solution makes contact with polar physiologic fluid, the dimethyl sulfoxide diffuses away and the hydrophobic copolymer precipitates and forms a spongy solid mass. Using a sclerotherapy-type needle, the Enteryx material combined with tantalum is injected circumferentially at or just above the squamocolumnar junction under fluoroscopic visualization. This procedure takes approximately 30 minutes to perform.

Enteryx is likely to face competition from both Medtronic with its Gatekeeper product and from Artes Medical which has developed ArteFlux, an injectable bulking agent for soft tissue engineering for the treatment of GERD. ArteFlux technology is based on a patented injectable microsphere platform technology. An ArteFlux injection consists of a combination of precision-filtered absolutely round and smooth PMMA microspheres (125 microns in diameter) suspended in ultra- purified bovine collagen. ArteFlux is injected into the submucosal space of the lower oesophageal sphincter region, and the increased sphincter pressure can prevent or reduce acid reflux. Artes Medical is buoyed by the results of preclinical trials and is seeking cooperation from strategic corporate partners to conduct U.S. clinical trials with ArteFlux.

Where do we go from here?

The treatment of GERD using the devices mentioned is not assured. To date, there are no key studies which directly compare any of the techniques against existing antisecretory medications or antireflux surgery. As a consequence, “physician switching” is not yet at a level which elevates the market opportunities for the companies selling these offerings to the heights they would like.

As well as the dearth of good data on comparison with other treatments, efficacy has mostly been assessed over short periods and in some cases is considered unimpressive (Romagnuolo J, Can J Gastroenterol 2004 Sep;18(9):573-7).

However, these “shortcomings” should not detract from an assessment of the potential that medical device options present to physicians treating GERD sufferers. It certainly does not deter the likes of major companies such as Medtronic and Boston Scientific from looking at GERD not only from the viewpoint of treatment but also from the diagnostic side as evidenced by discussions these companies are reported to have had with innovative players looking at gastrointestinal diagnostics which measure pH in the oesophagus. The attractiveness of offering both a GERD diagnostic and a treatment option is not difficult to envisage.

While not yet a multibillion dollar market opportunity, medical device associated treatments have the potential within the next 3 years to at least carve deeply into the market for GERD therapies. In the USA alone the drug treatment for this condition represents a $9.3bn opportunity. Making the case for cost effectiveness of medical device alternative treatment is a crucial way forward for the companies mentioned in this article and for those considering involvement. Additionally the efficacy of the treatment must be measured and proven against alternative treatment options, especially in comparison to antireflux surgery.

Author: Dr. Akmal Bhatti, Director