Desire

The Nexium advertisement appeals to our desire for power. 

Appeals to desires are common in advertising because they work.[1] These appeals work despite the evidence that we normally do not give them much thoughtful attention. Lack of attention can allow these appeals to sneak into the brain under the radar of critical appraisal.[2] 

Unfair comparisons

The Nexium advertisement claims that "Nexium 40mg offers greater healing power that either omeprazole or lansoprazole". This claim is based on two unfair comparisons. 

One of the comparisons is esomeprazole (Nexium) 40mg vs omeprazole (Losec, Acimax, Probitor) 20mg. (The dose of omeprazole is only disclosed in the fine print.) 

Omeprazole is a proton pump inhibitor that has been used for years to treat peptic ulcers and gastro-oesophageal reflux disease by reducing gastric acid levels.  

Omeprazole 20mg contains about 10mg of S-omeprazole and 10mg of its mirror molecule: R-omeprazole. Both S and R-omeprazole are converted to the same active drug that reduces production of gastric acid by proton pumps. R-omeprazole is absorbed into the body less than S-omeprazole and removed faster, so it may be less effective than S-omeprazole. 

 Esomeprazole is just a different spelling for S-omeprazole. "Es" = "S-".  AstraZeneca are using a different spelling that makes it less obvious that esomeprazole is just half of their old drug omeprazole (Losec).

 It is no surprise that 40mg S-omeprazole in Nexium 40mg is more effective than the 10mg of S-omeprazole plus 10mg of R-omeprazole. However a larger dose of omeprazole would be just as "powerful" as esomeprazole (Nexium) 40mg. 

The other comparison is esomeprazole (Nexium) 40mg vs lansoprazole (Zoton) 30mg.  (Again the dose of lansoprazole is only disclosed in the fine print.)

The graph below suggests that the difference in the percentage healed at 8 week is too small to be clinically significant.[3]  Patients are unlikely to be able to detect a worthwhile difference in relief of symptoms.  

 Missing comparisons

The advertisement does not compare Nexium with other alternatives. The alternatives that should be considered include other proton pump inhibitors, other drugs and non-drug therapies.

The only trial comparing esomeprazole with pantoprazole that we are aware of was published in September 2003 so it is too recent to be mentioned in the advertisement.[4]  That trial suggests that esomeprazole 40mg is unlikely to have any clinically significant advantages over pantoprazole 40mg.  This is despite evidence that pantoprazole 40mg is not significantly better than omeprazole 20mg.[5]  Both can be true because there is little difference between proton pump inhibitors especially at higher doses.  This is because of the law of diminishing returns as shown in the graph below.

 We are not aware of any trials comparing esomeprazole with rabeprazole which is the only other proton pump inhibitor currently available in Australia.

Many people with gastro-oesophageal reflux disease can be adequately treated long term with lifestyle changes including elevation of the head of the bed plus antacids or H2 antagonists such as ranitidine (Multiple brands).[6] 

 Many people with peptic ulcers are better treated with H. pylori bacteria eradication therapy.

General Recommendation

There is no proven clinically significant efficacy or safety advantage of Nexium over fair comparison doses of other proton pump inhibitors.

When a proton pump inhibitor is appropriate, use whichever is the cheapest at the time in the lowest dose that controls the symptoms.

Current Recommendation for Australia

The table below includes all proton pump inhibitors listed in the Pharmaceutical Benefits Scheme Yellow Book effective from 1 August 2003 in order of the cost of a pack of 30 tablets or capsules.

As doses increase prices increase but differences in efficacy diminish.  The best value approach may be:

·        Commence therapy with lifestyle changes plus esomeprazole 20mg (Nexium). This will quickly control symptoms for most patients.[7]

·        If symptoms are not controlled try pantoprazole 40mg (Somac) before using esomeprazole 40mg (Nexium) as a last resort.

·        If symptoms are controlled then try lifestyle measures alone or add a H2 antagonist such as ranitidine (Multiple brands) or rabeprazole 10mg (Pariet) for maintenance.

 Further reading

Do Single Stereoisomer Drugs Provide Value?
Therapeutics Letter, issue 45, June - September 2002
http://www.ti.ubc.ca/pages/letter45.htm

 Jankowski J, Jones R, Delaney B, Dent J.
10-minute consultation: Gastro-oesophageal reflux disease.
BMJ. 2002 Oct 26;325(7370):945.
http://bmj.bmjjournals.com/cgi/content/full/325/7370/945

Feedback

(Feedback will be provided to AstraZeneca and to regulatory agencies. We will take feedback seriously for improving future editions of AdWatch.)

AdWatch is produced by Healthy Skepticism:  www.healthyskepticism.org