Asthma Drug Worse Than Placebo, Symptoms Worsen on Withdrawal

Friday, May 30, 2008 by: Heidi Stevenson
Tags: asthma, health news, Natural News

(NewsTarget) Asthma symptoms worsen on withdrawal of the drug Accolate (zafirlukast). Benefits are seen for only the first five weeks, after which symptoms return to their original state within seven weeks. These eye-opening results were reported in a well-designed Australian study published by the Journal of Negative Results in BioMedicine.

The study documenting Accolate's ineffectiveness points out that the majority of prior studies "have been undertaken over short periods of six weeks [emphasis by study author] or less, which may not have allowed sufficient time for tolerance or tachyphylaxis to develop or be recognized." [Note: Tachyphylaxis refers to loss of effectiveness after removal of a drug.]

Accolate is prescribed primarily for long term use.

Side effects for Accolate include headaches, nausea, diarrhea, pneumonia, Churg-Strauss Syndrome (vasculitis of the lungs), hepatitis and other liver disease.

Thus, a drug that is prescribed for long term use was tested for no more than six weeks before approval by the FDA. It has the potential of destroying your liver or causing pneumonia. It offers no long term benefit. On withdrawal of the drug, the patient's condition gets worse.

The Journal of Negative Results in BioMedicine

The Journal of Negative Results in BioMedicine does the opposite of most medical journals. Rather than reporting almost exclusively on studies that had positive results -- in the sense that they're beneficial to pharmaceutical companies -- this one reports exclusively on studies with negative results. It fulfills a much needed function, since negative results are rarely published.

In honest science, results should be considered valuable, whether they are positive or negative. If the study is well done, then the information should be considered of interest, as it adds to the base of knowledge. Unfortunately, this is not usually the case. So, The Journal of Negative Results in BioMedicine helps fill the gap.

Study Methodology

Subjects

This was a double-blind placebo-controlled study. Group I consisted of 21 subjects who took only beta2-agonists to relieve asthma attacks. The 24 Group II subjects took both beta2-agonists to relieve asthma attacks and corticosteroids.

The two groups were similar demographically. Group I had an age range of 21-69, with median of age 41. 10 were female and 11 were male. Group II had an age range of 19-65, with median age of 42. 14 were female and 10 were male.

Both groups were randomized to determine which would receive Accolate and which would take placebo.

The subjects can be typified as suffering from moderately severe asthma. All were asthmatics who had not gained symptom relief from the use of beta2-agonists alone for at least one year or who took a moderate-to-high dose of inhaled corticosteroids, plus beta2-agonists, for at least four weeks prior to the trial. Things that excluded potential subjects were upper respiratory tract infection, changes in asthma medication during the previous 6 weeks, or usage of oral corticosteroids in the three months prior to the trial. Anyone who had taken any of the following drugs during the 6 weeks prior to screening was excluded: long-lasting beta2-agonist, anticholinergic, cromone, or theophylline. All subjects were volunteers.

Five of the 43 subjects who started did not complete the study. The number in each group at the start of the study was:

Group I:

* 14 subjects - Accolate

* 7 subjects - placebo

Group II:

* 16 subjects - Accolate

* 8 subjects - placebo

At the end, the number of remaining subjects was:

Group I:

* 12 subjects - Accolate

* 5 subjects - placebo

Group II:

* 15 subjects - Accolate

* 8 subjects - placebo

27 of the remaining subjects took Accolate and 13 took placebo.

Adverse events directly associated with lung function during the trial include upper respiratory tract infection, inability to withhold beta2-agonist medication for six hours before a lung function test, and lung function deteriorating too much to continue. All but one of these subjects took Accolate. During withdrawal of Accolate, one subject's asthma worsened so much that oral corticosteroids were required. Other adverse events included worsening rheumatoid arthritis and angina, both of which occurred in subjects who took placebo.

The trial lasted 14 weeks -- one screening week, 12 weeks of taking the drugs and one following week to see if there were any withdrawal effects. All subjects were given the same dose of Accolate or a placebo that looked identical and was dispensed in an identical package.

Study Measurements

Several measures were used throughout the study period. These included:

* Daily recording of symptoms by the subjects.

* Peak Expiratory Flow (PEF), which measures the maximum air flow at the beginning of forced expiration. This test was done every day before either the study medication (Accolate/placebo) or the beta2-agonist.

* Spirometry (breath measurement) after inhaling methacholine (FEV). This is a standard test for asthma.

* Profiles of sputum and blood.

Study Results

The study produced definitive results. Although there were initial improvements in symptoms in subjects taking Accolate, by five weeks the degree of improvement started to fall, by the end of week 11 dropping to the level at which they'd started. When the drug was withdrawn, symptoms worsened.

Results Before Withdrawal

Subjects who took Accolate had a significant increase in neutrophils after withdrawal. Neutrophils are blood cells that fight bacterial infections. Increases in them generally occur because of infection. The study's authors stated that the subjects did not exhibit any symptomatic deterioration related to this, but one must wonder if further investigations would have documented problems.

Sputum testing showed no difference between Accolate and placebo groups. Nitric oxide in exhalations was unchanged in the two groups. Spirometry did not result in any significant distinctions between Accolate and placebo.

The Peak Expiratory Flow test, which tests actual breathing function, was highly significant. Subjects who took Accolate had a distinct improvement through week five. However, by week six, they started to lose their gains, reaching the same level that they'd had on starting the trial.

Results After Withdrawal

Among subjects who took placebo, there was no drop-off of function after withdrawal. Among those who took Accolate, the authors stated that there were "significant physical deteriorations" after withdrawal. They continued, "There was a clear 'over-shoot' to worse than study entry values in essentially all lung function and clinical parameters."

What This Study Reveals

Obviously, this study demonstrates that Accolate does more harm than good. What little good it does is short-lived and paid for by worsening of the asthmatic condition. At this time, there is no information to indicate how severe the rebound is, since the implications of increased neutrophils are not known, nor is it known whether the worsening is permanent.

We do know, though, that the entire system of drug testing for FDA approval does not work. Had a longer term study been done on Accolate, then its lack of efficacy could have been discovered and it would never have made it to market. It was first approved in 1996. Now, in 2008 -- 12 years later --we're seeing a study that should have been required before approval.

What is revealed here is the utter corruption of the system of medication in the United States. Accolate is just one drug. We've recently seen that Vioxx had to kill over 60,000 people before the FDA took action. How many more people will be killed or maimed before this disaster ends?

References:

Journal of Negative Results in Biomedicine, "Tolerance and rebound with zafirlukast in patients with persistent asthma", David W Reid, Neil L Misson, Shashi Aggarwal, Philip J Thompson, David P Johns, E Haydn Walters, (http://www.jnrbm.com/content/7/1/3)

electronic Medicines Compendium, (http://emc.medicines.org.uk/emc/assets/c/htm...)

About the author

* Heidi Stevenson, BSc, DIHom, FBIH
* Fellow, British Institute of Homeopathy
* Gaia Health (http://www.gaia-health.com)
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* The author is a homeopath who became concerned with medically-induced harm as a result of her own experiences and those of family members. She says that allopathic medicine is the arena that best describes the motto, "Buyer beware."
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* Heidi Stevenson provides information about medically-induced disease and disability, along with incisive well-researched articles on major issues in the modern world, so members of the public can protect themselves.
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She can be reached through her website: www.gaia-health.com