A New Approach to Managing GORD

Until now, assessing the progress of treatment for Gastro-Oesaphageal Reflux  Disease (GORD) has relied primarily on an assessment of oesophageal healing. Documenting GORD therapy success is a difficult task, as mucosal damage does  not always correspond with the severity of symptoms.1 In addition, 70% of all  patients with GORD symptoms have endoscopic-negative GORD.2,3

Until now, assessing the progress of treatment for Gastro-Oesaphageal Reflux  Disease (GORD) has   relied primarily on an assessment of oesophageal healing.  Documenting GORD therapy success is a  difficult task, as mucosal damage does  not always correspond with the severity of symptoms.1 In addition, 70% of all  patients with GORD symptoms have endoscopic-negative GORD.2,3
 
To further complicate the GORD picture, Endoscopy-Negative Reflux Disease  (ENRD), Non-Erosive    Reflux Disease (NERD), functional heartburn or reflux-like  dyspepsia is often diagnosed, and most    patients with heartburn do not have  mucosal breaks. Moreover, diagnostic approaches vary between    primary and  secondary care.

In the absence of gold standard diagnostic testing for GORD, symptom assessment  and     understanding how symptoms impact on a patient’s quality of life is critical to  the successful     management of a patient. Recent research has suggested that the  symptom complex experienced by   GORD patients is much wider than previously  appreciated.

Besides heartburn, acid eructation, and pain on swallowing, a variety of other  GORD-related     symptoms are experienced, including nausea, diarrhoea or  constipation and sleep disturbance, as     well as other symptoms, such as respiratory  complaints. GORD is a condition of diverse and variable     symptoms, many of which  significantly impair quality of life.

 
The problem for gastroenterologists trying to build a complete picture of a patient’s  symptoms is that     patients may find it difficult to describe accurately all the  symptoms they are experiencing.     Consequently, they may not be treated  effectively. Even after successful acute treatment, the majority of     patients suffer a  recurrence of symptoms within six months. And, if the non-classic signs of GORD     are not seen, patients may be misdiagnosed. The broad spectrum of symptoms in  GORD patients     and the high prevalence of endoscopy-negative GORD highlight  the need for a robust, validated     approach to symptom assessment.
 
SIMPLE QUESTIONNAIRE

One such approach is ReQuest™, a simple and effective questionnaire, which  patients use to assess     themselves daily for a wide range of GORD symptoms. It  was created following discussions with     patients and physicians to identify the  spectrum of symptoms reported and establish how they were     described by GORD  patients. The questionnaire was also based on an evaluation of relevant medical     literature and clinical trial data.

ReQuest is divided into seven dimensions covering acid complaints, upper  abdominal/stomach     complaints, lower abdominal / digestive complaints, nausea,  sleep disturbances, general well-being     and other complaints. A short version of the  questionnaire, which can be completed in less than five     minutes, focuses solely on  these seven dimensions, while the full version, which takes approximately     20  minutes, is more wide-ranging.

Both tests have undergone extensive clinical trial evaluation and statistical analysis,  which has     confirmed their internal consistency, test-retest reliability, construct  validity, and responsiveness to     changes during treatment.4,5,6

ReQuest fulfils the criteria set by the regulatory authorities for a validated  symptom-based system for     use as the primary outcome measure in clinical trials of  GORD therapy. It has now been validated in     26 languages and tested in 20  countries.

REQUEST / LA CLASSIFICATION

The ReQuest / LA classification system is the first to effectively integrate a highly  sensitive patient     questionnaire (ReQuest) with an adaptation of the LA classification  for esophagitis. The new index     allows the combined assessment of symptom relief  and the healing of oesophageal lesions in     GORD.

The adapted LA classification (N = lesions not present, grade A–D) was paired  with a grading of     patients’ symptom burdens from 0–4 (0 = no disease, 1 = minor,  2 = tolerable, 3 = troublesome, 4 =     intense), as assessed by the rescaled subscale  of the established GORD symptom evaluation     instrument ReQuest.

By comparing both scales in a matrix, clinicians are able to quantify both aspects of  GORD and assign     an index to each patient. An index of 0N indicates optimal  treatment outcome, in other words complete     remission (relief from symptoms and  the healing of oesophageal lesions).

VALUABLE INSIGHTS

A recent randomised, double-blind study of 581 patients using ReQuest has  established that     pantoprazole is as effective as esomeprazole (both 40mg/day) over  12 weeks in achieving the     complete remission of erosive GORD. With respect to  endoscopically confirmed healing, pantoprazole     was superior to esomeprazole.

 
A second randomised, double-blind ReQuest study, this time of four weeks’  duration (561 patients),     again comparing pantoprazole and esomeprazole (both  40mg/day), demonstrated parity between the     two PPIs in terms of symptom relief  scores, but it also showed that the beneficial effects of     pantoprazole were sustained  for longer, with significantly fewer symptomatic relapses in the     seven- day  post- treatment phase.8

Professor K D Bardhan, consultant physician and gastroenterologist at the District  General Hospital,     Rotherham, in the UK, who was instrumental in developing the  ReQuest/ L A classification, says: ‘We     need a device that enables an accurate  assessment of treatment success in GORD patients that     combines the main  parameters of symptom relief and oesophageal healing. The new ReQuest / LA     classification enables a detailed clinical and treatment outcome assessment of  GORD patients at any     stage of their disease using a single and reliable global  measure. In my view, ReQuest / LA     classification represents a helpful step in the  right direction and provides a means of standardising     the assessment and reporting  of GORD clinical trials.’

An extensive ReQuest database, which provides information on patient  demographics, symptom     profiles and treatment outcomes, now exists for over  8,000 patients with GORD. Use of the combined     endpoint  ‘complete remission’,  evaluated using the ReQuest™/LA classification, will permit even     greater insights  by helping to analyse patient populations and shed light on the factors that dictate     whether a treatment works. Such a source of GORD treatment outcomes, during  various stages of the     disease, could be of major benefit to patients, physicians and  the organisations that fund healthcare     in the future.

REFERENCES

1.      Dent J, Brun J, Fendrick AM, Fennerty MB, Janssens J, Kahrilas PJ, Lauritsen K, Reynolds JC, Shaw M, Talley NJ on behalf of the Genval Workshop Group. ‘An evidence-based appraisal of reflux disease management – the Geneval Workshop Report’. Gut 1999;44 (Suppl 2):1–16
 
2.     Tack J, Fass R. ‘Review article: approaches to endoscopic-negative reflux disease: part of the GERD spectrum or a unique acid-related disorder?’. Aliment Pharmacol Ther 2004;19 (Suppl 1):28–34
 3.     Martinez SD, Malagon IB, Garewal HS, Cui H, Fass R. ‘Non-erosive reflux disease (NERD) – acid reflux and symptom patterns’. Aliment Pharmacol Ther 2003;17:537–45
4.     Bardhan KD, Stanghellini V, Armstrong D, Berghöfer P, Gatz G, Mönnikes H. ‘Evaluation of GERD symptoms during therapy. Part I. Development of the new GERD questionnaire ReQuest’. Digestion 2004;69:229–37
 5.     Mönnikes H, Bardhan KD, Stanghellini V, Berghöfer P, Bethke TD, Armstrong D. ‘Evaluation of GERD symptoms during therapy. Part II. Psychometric evaluation and validation of the new questionnaire ReQuest in erosive GERD’. Digestion 2004;69:238–44
 
6.     Bardhan KD, Stanghellini V, Armstrong D, Berghöfer P, Gatz G, Mönnikes H. ‘International validation of ReQuest in patients with endoscopy-negative gastro-esophageal reflux disease’. Aliment Pharmacol Ther 2004;20:891–98
7.     Bardhan KD, Achim A, Ridderman T, Sander P, Pfaffenberger B. ‘Achieving complete remission in patients with erosive gastroesophageal reflux disease (GERD): Pantoprazole is comparable with esomeprazole’. Gut 2005;53;(Suppl 7):A-106
8.     Glatzel D, Abdel-Qader M, Gatz G, Pfaffenberger B, Sander P.  ‘Pantoprazole 40mg is as effective as esomeprazole 40mg to relieve symptoms of gastroesophageal reflux disease (GERD) after four weeks of treatment and superior regarding preventing of symptomatic relapse’. Gut 2005;54; (Suppl 7):A-105
 
COMPANY PROFILE

ALTANA Pharma is the pharmaceutical division of ALTANA AG. The company  concentrates on innovative pharmaceutical products in therapeutics, imaging  (contrast media) and OTC medication. Therapeutics, the most important business  area, is based on prescription drugs for gastrointestinal and respiratory diseases.