Failure of reflux inhibitors in clinical trials: bad drugs or wrong patients?

[Guest guest]

It would be interesting to know, perhaps in a poll, if you feel your PPI is

working for you.

Carolyn

 ______________________________________________________________________________\

_________________________________

Gut doi:10.1136/gutjnl-2011-301898  http://tinyurl.com/73gd5ao

* Recent advances in clinical practice

Failure of reflux inhibitors in clinical trials: bad drugs or wrong patients?

1. J Kahrilas1,

2. Guy Boeckxstaens2

+ Author Affiliations

1. 1Department of Medicine, The Feinberg School of Medicine, Northwestern

University, Chicago, Illinois, USA

2. 2Department of Gastroenterology, Translational Research Center for

Gastrointestinal Disorders, University Hospital Leuven/Catholic University

Leuven, Leuven,

Belgium

1. Correspondence to Dr J Kahrilas, Northwestern University, Feinberg

School of

Medicine, Division of Gastroenterology and Hepatology, Department of Medicine,

676 N St Clair Street,

14th Floor, Chicago, IL 60611, USA; p-kahrilas@...

1. Contributors Author contributions: PJK took the lead in determining the

design of

the review, analysing and interpreting the data and drafting and critically

reviewing the manuscript for important clinical and intellectual content. GEB

also had a major role in determining the design,

analysing and interpreting the data and drafting and critically

reviewing the manuscript for important clinical and intellectual

content. Both authors have approved the final draft of the manuscript.

Abstract

Treatment modalities for

gastro-oesophageal reflux disease (GORD) mirror the pathophysiology of

the disease. Since acid plays a key role in GORD-associated mucosal

lesions, proton pump inhibitors (PPIs) are the dominant GORD treatment,

being the most potent inhibitors of acid secretion

available. However, the clinical effectiveness of PPIs varies with the

specific symptoms being treated; they are more effective

for heartburn than for regurgitation than for extra-oesophageal

symptoms. An alternative therapeutic approach to GORD is to

prevent the most fundamental cause of reflux symptoms, reflux itself,

which most commonly occurs by transient lower oesophageal

sphincter relaxation (TLOSR). Among potential pharmaceutical agents

developed to target TLOSRs, the most advanced are GABAB (γ-aminobutyric acid)

agonists, which experimentally reduce the occurrence of TLOSRs by about 40% in

both animal and human studies. However, the effectiveness of GABAB agonists in

clinical trials of patients with GORD with an incomplete

response to PPI treatment has been modest. In part, this is probably

attributable to the

difficult problem of patient selection in these trials. Identifying

patients by partial response to PPI treatment results in a

heterogeneous population, including those with persistent weakly acidic

reflux, patients with visceral hypersensitivity and

those with functional heartburn, dyspepsia, or chest pain. From the

clinical data available, the best treatment results and, hence,

the patients most likely to benefit from reflux inhibitors, are those

with persistent reflux, most commonly manifest as

persistent regurgitation despite PPI treatment.

________________________________

[Guest guest]

Carolyn wrote:

>

> It would be interesting to know, perhaps in a poll, if you feel your

> PPI is working for you.

>

If working, or not, for what, heartburn (acid reflux), or spasms/NCCPs.

Yes/no for each.

If I see any responses from such a line of questions I will use them in

the medication report I am working on. I have gotten back to working on

it. I need the name of the PPI, H2 blocker, or what have you and did it

work or not, for which problems. Non specific answers don't help me much.

notan