What are the goals of treatment in reflux esophagitis?
J.E. Richter (Birmingham, Alabama)
The goals of treatment in gastroesophageal reflux disease (GERD) are the following:
- relieve the symptoms of GERD;
- heal and prevent the relapse of mucosal lesions (i.e., esophagitis);
- prevent the complications of long-term esophagitis, such as strictures ulcerations, bleeding and columnar metaplasia.
These goals are easy to establish, but efficacy of the therapies and scientific data supporting the obtainability of these goals decrease as we progress from controlling symptoms to preventing complications. Furthermore, these goals are set against a complex background - GERD is a chronic condition that tends to wax and wane in intensity and relapses are common.
Relief of symptoms
From the patient's viewpoint, relief of symptoms is the most important reason for seeking medical attention. Fortunately, the currently available medical and surgical therapies should allow this to be accomplished in all patients both acutely and long term. In patients presenting with reflux symptoms and no esophagitis, this is the only goal. In approximately 20-30% of patients, this may be accomplished by lifestyle changes, antacids or alginic acid , Whether the latter two drugs are better than
placebo is controversial, nevertheless this is a rather small point if patients obtain relief of their heartburn. Prokinetics drugs (bethanechol, metoclopramide, domperidone and cisapride) have been shown to produce greater relief of symptoms compared to placebo in controlled studies . Clinically, they are efficacious, but only in mild to moderate reflux disease. The cornerstone of medical therapy for GERD is the H2-blockers. All are equally effective when used at proper dosages, usually with a twice a day dosing regimen. Overall, 50-70% of symptomatic patients have complete or partial resolution of symptoms with H2-bIockers . Higher dosages of H2-blockers marginally improve on these results in patients with more severe symptoms. However, I believe the drug of choice in these latter patients are the proton pump inhibitors. Symptomatic responses with omeprazole are seen in 60-95% of cases . Unlike the H2-blockers where partial symptom relief is the rule, omeprazole usually totally relieves all symptoms allowing the patients to enjoy many previously prohibited foods and sleep without head elevation. To obtain this goal, some patients may require higher doses of omeprazole in the range of 40 to 80 mg per day. Long-term symptom relief is more problematic. Patients with mild symptoms will remain in remission with H2-blockers or cisapride, usually given b.i.d.. Those with severe symptomatic disease will require omeprazole or antireflux surgery.
Healing of esophagitis
Today most cases of acute reflux esophagitis can be healed. However, this frequently requires marked acid suppression for a prolonged period of time. The key to treating and healing reflux esophagitis is the initial esophagitis grade. The more severe the grade of esophagitis, the stronger the acid suppression and the longer the duration of therapy required to heal the mucosal lesions.
Antacids, alginic acids and most prokinetics drugs have no predicable reliability in healing even mild esophagitis [1,2]. Data with cisapride is more equivocal. European studies show healing of even severe esophagitis after 12 weeks of therapy, while studies in the United States show minimal efficacy primarily in grade II esophagitis . Recent reviews of the literature suggest that healing rates with H2-blockers rarely exceed 60% after 12 weeks of treatment, even when higher than standard dosages are used [3,4]. Healing rates differ considerably in individual trials and depend mostly on the degree of esophagitis before therapy. Savary grade I esophagitis is reported to heal in 75-90% of patients after most treatments while grade II heals only in 40-50% of patients during treatment with H2-blockers . Omeprazole has become the drug of choice for treating severe esophagitis or esophagitis unresponsive to H2-blockers . Five well-designed trials comparing omeprazole 20-60 mg/day with ranitidine 150 mg b.i.d. for healing grade II-IV esophagitis, have uniformly demonstrated significantly better results for the omeprazole treated groups. Healing at 4 weeks in the omeprazole groups ranged from 67-85% vs. 26-45% for ranitidine; healing at 8 weeks in the omeprazole groups ranged from 85-96% vs. 40-66% for ranitidine. Five studies of similar design have evaluated more than 300 patients with esophagitis unresponsive to H2-blockers and
uniformly found that omeprazole 40 mg/day will successfully heal nearly 90% of these patients within 12 weeks.
There is growing awareness that most patients with healed erosive-ulcerative esophagitis will relapse within 6 to 9 months after discontinuation of drug therapy. Therefore maintenance therapy is unanimously recommended, but its efficacy is yet to be conclusively proven. Recent studies suggest that cisapride 20 mg b.i.d. may be superior to placebo in keeping mild grade II esophagitis in remission for up to 6 months . H2-blockers are also likely to be effective for mild to moderate disease, but require full twice daily dosages regimens. Patients with severe esophagitis will require maintenance therapy with omeprazole. Most will require 20 mg/day, some may be controlled on 10 mg/day, while a smaller group will require at least 40 mg/day . Holiday therapy (3-4 days out of the week) does not seem to be effective.
Prevention of complications
Although it is logical and physiologically sensible, little data is available showing that aggressive medical therapy prevents the development of complicated GERD. Furthermore, many of our patients have well established complicated disease at the time of presentation, which may be beyond relief with either medical or surgical treatments.
Aggressive medical therapy can heal esophageal ulcers and prevent recurrent bleeding . Recent studies in our laboratory suggest that omeprazole can resolve many peptic strictures associated with esophagitis and keep these patients dysphagia free for up to 6 months . However, long-term studies are not available. Barrett's esophagus is more problematic and the major complication that should be prevented. Studies in dogs suggest that severe esophagitis often heals with the development of columnar metaplasia. However, esophagitis, in this animal model, heals with the persistence of squamous mucosa if acid reflux is markedly inhibited . This supports the use of aggressive acid suppression in patients with severe esophagitis, either high dose H2-blockers or omeprazole. Although formal studies are not available, the clinical experience of most gastroenterologists support these animal observations since Barrett's esophagus rarely develops de novo or progresses after effective control of esophagitis. Having said this, there is little convincing data that either omeprazole or surgery predictably produces regression of Barrett's esophagus once it is established.
7. Klinkenberg-Knol EC, Jansen JBMJ, tamers CBHW et al. Use of omeprazole in the management of reflux esophagitis resistant to H2 receptor antagonists. Scand J Gastroenterol 1989;24:(suppl 116):88-96.