Esomeprazole was clearly superior to PRA. Patients on esomeprazole reported a higher prevalence of overall satisfaction with the treatment, had more weeks of satisfactory symptom relief, a lower symptom score the last two weeks and preferred more often to continue the same treatment. This superiority of established pharmacological treatment over CAM explains the infrequent use of alternative medicine for reflux disease compared to the use for other disorders . However, it was not an ideal treatment. Delayed onset of effect and rapid relapse of symptoms were noted by one out of four and five patients respectively. Satisfactory relief of symptoms failed every 10th week, 15% asked for another drug and 15% preferred regular treatment.
PRA was less effective, but more than half of the patients were satisfied with the treatment and nearly half of them wanted to continue the treatment. The main advantage of PRA was a trend toward a faster acting effect. Disadvantages were rapid relapse of symptoms, intake of too many tablets, and some diarrhoea.
The placebo response in mild/moderate reflux disease is substantial. This study allows no comparisons with placebo, but PRA is probably more effective than placebo. Other raft-forming agents have shown an immediate reduction in gastro-oesophaeal reflux and increase in oesophageal pH, which is superior to that of omeprazole for 4 hours . PRA reduces reflux of both food and acid. The reduced reflux of food and not only acid shows the rafting properties of PRA, which seem to be at least as good as those of comparable anti-reflux agents . Two placebo-controlled clinical trials have proven a symptomatic effect of PRA above placebo [9, 11]. The placebo response rates vary a lot in clinical studies but are in most studies inferior to that of PRA in this study [1, 5]. Therefore, PRA seems to be an alternative for a minority of patients with mild/moderate reflux disease who prefer natural, locally acting, non-absorbable agents rather than ordinary pharmaceutical products.
Evidence Based Medicine has to become involved into CAM as long as our patients prefer, use and report effects of such products. We need knowledge, but unlike this trial, CAM-producers seldom support high quality research. This study indicates that alternative products could have a place in the therapeutic armamentarium.
Overall satisfaction was the main outcome in the trial. This outcome depends on factors like symptomatic effect, drug administration schedule (e.g. on-demand versus continuous treatment, or dosing once versus several times daily) number of tablets, drug formulation (e.g. small or large tablets, chewable tablets, or granules), taste, preference for natural or pharmaceutical products, age, disease under study, expectation and experience from previous treatment regimens etc. This study does not allow conclusions about all factors related to overall satisfaction. The most important predictor for overall satisfaction was treatment with esomeprazole. This is likely due to the efficient relief of symptoms, but not only. The convenient dosage schedule with one tablet a day, the rather long-lasting effect, the good tolerance and perhaps previous experience with acid secretion inhibitors might have contributed to overall satisfaction with esomeprazole. Symptom score last two weeks showed an insignificant trend toward prediction of overall satisfaction after correction for treatment group and indicates that symptom relief is not decisive for satisfaction.
Overall satisfaction increased with age. Since symptoms did not correlate with age, other factors such as habituation to and tolerance for minor complaints and gratitude for some symptom relief might increase with age and explain the increased satisfaction in the elderly.
Patient preference for continuing on-demand treatment was impressive and in accordance with other studies [6, 7]. On-demand treatment will necessarily result in more symptoms than continuous therapy does, but despite of more symptoms patients are nearly as satisfied with on-demand treatment as continuous treatment . Twelve patients (16%) wanted to switch to regular treatment after the trial. The perfect drug for on-demand treatment has an immediate, long-lasting and sufficient effect , which is not fulfilled by any of the actual drugs. A high symptom score at inclusion was the only predictor for continuous treatment, not the degree of symptoms at the end. Even with an ideal drug, it is likely that on-demand treatment is unacceptable for some patients since it implies relapses. Continuous treatment is probably preferable especially if symptoms during relapses are severe. It is therefore comprehensible that patients with a high symptom score at inclusion also perceive severe relapses and prefer regular dosing.
On-demand treatment is not a precise definition. The term includes treatment of actual symptoms as in this trial, treatment to prevent foreseeable symptoms, intermittent therapy defined as regular intake of drugs for a short period when needed, and threshold therapy in which the patients adjust the medication down to a dose and frequency that still maintains adequate control of symptoms . This trial, in which patients took one tablet when needed to relieve symptoms, gives no information about other on-demand dosage schedules. The intake of approximately one tablet of Eso 20 every other day indicates that the patients have taken the drugs as prescribed.