A recent Washington Post article slamming pharmaceutical giant Pfizer for burying data on a potential link between their anti-inflammatory drug Enbrel and prevention of Alzheimer’s Disease (AD) has generated considerable controversy. The article contends that Pfizer, due to various business considerations, withheld key data that suggests Enbrel may “reduce the risk of Alzheimer’s disease by 64%”. In the context of an epidemic of Alzheimer’s disease, decades of intensive study and over 2000 clinical trials in the last twenty years which have produced zero effective treatments for this terrible disease, this allegation is shocking. “Why didn’t they tell the world?” the article asks right in the headline. The answer may surprise you and requires a little context.
Enbrel is an anti-inflammatory drug approved by the FDA to treat rheumatoid arthritis by blocking an inflammatory molecule (cytokine) called TNF-alpha. There is a hypothesis that chronic inflammation of the brain may be part of the sequence of events which produces Alzheimer’s disease, so various anti-inflammatory treatments have been studied to see if they influence cognitive symptoms – so far none has. In the mid-to-late 2000s, a couple of low-quality scientific papers suggested that treatment with Enbrel could rapidly reverse Alzheimer’s disease, in some cases “within minutes”! In my experience, claims like this are often artifacts (“if it sounds too good to be true…). Not surprisingly, these studies were not independently replicated, but still some people promoted this expensive and potentially dangerous off-label treatment with Enbrel for Alzheimer’s disease in the hopes of a cure. This is widely criticized as exploitation of desperate patients with a treatment which is, at best, unproven.
Never-the-less, interest in a more-rigorous assessment of Enbrel for Alzheimer’s disease persisted and Pfizer eventually funded a phase II clinical trial to assess its potential. This trial used standardized, rigorous diagnostic criteria to select patients and was randomized and double blinded. It did not detect any clear beneficial effects of the treatment. In some secondary analyses, the authors of this study thought there was a trend toward better outcomes in treated patients, but the control patients worsened much faster than is typical, so even these weak trends were likely artifacts. The study was published in the respected journal Neurology in May of 2015. Around the same time, the internal study described in the Post article was completed, surprisingly showing a massive effect. This study was not blinded, not randomized and did not use rigorous diagnostic criteria, but rather was mined from insurance claim data. This type of data is useful for generating new ideas but should be viewed as exploratory and not the equivalent of a randomized controlled trial. The Post article suggests that Pfizer failed to investigate potential links between decreasing inflammation in the body and the progression of AD, but barely mentioned that they funded a clinical trial. Moreover, the article criticizes Pfizer for failing to share this data, but it is also clear that the data was made available to some external researchers.
Despite the sensational headline, Pfizer’s decisions in this case make sense. Regardless of motivations, the better-quality study showed little clinical effect. The insurance-claims-based data was too strong to be believable, particularly since the drug does not appear to cross the blood brain barrier and without further verification the data was probably not publishable. And importantly, the risk of promoting further off-label use of this treatment is real. Additional potential risks of taking Enbrel include that it lowers the body’s immune response leading to a greater chance of infection and the expense of the treatment which may be thousands of dollars a month. It should be emphasized that there is presently a lack of concrete, scientifically accepted evidence indicating that Enbrel is a viable treatment for AD and due to this lack of evidence patients should not be advised to use Enbrel as a therapeutic or preventive measure outside of a clinical trial.
Rowland, Christopher. “Pfizer had clues its blockbuster drug could prevent Alzheimer’s. Why didn’t it tell the world?” The Washington Post. 04 June 2019. WP Company. 20 June 2019 https://www.washingtonpost.com/business/economy/pfizer-had-clues-its-blockbuster-drug-could-prevent-alzheimers-why-didnt-it-tell-the-world/2019/06/04/9092e08a-7a61-11e9-8bb7-0fc796cf2ec0_story.html?utm_term=.89675cddbdae.
Butchart, Joseph et al. “Etanercept in Alzheimer disease: A randomized, placebo-controlled, double-blind, phase 2 trial.” Neurology vol. 84,21 (2015): 2161-8. doi:10.1212/WNL.0000000000001617
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Novella, Steven. “Enbrel for Stroke and Alzheimer’s.” Science-Based Medicine. 8 May 2013. Science-Based Medicine. 20 June 2019 https://sciencebasedmedicine.org/enbrel-for-stroke-and-alzheimers/.