Articles

Enbrel for Stroke and Alzheimer’s

A recent article in the LA times tells of a husband’s quest to find a treatment for his wife’s Alzheimer’s disease. This is a narrative that journalists know and love – the brave patient or loved-one who won’t accept the nihilism of the medical establishment, who finds a maverick doctor willing to buck the system.

The article itself at least was not gushing, it tended toward a neutral tone, but such articles do tend to instill in the public a very counterproductive attitude toward science and medicine. I would have preferred an exposé of a dubious clinic exploiting desperate patients by peddling false hope. That is a narrative in which journalists rarely engage.

The story revolves around Dr. Edward Tobinick and his practice of perispinal etanercept (Enbrel) for a long and apparently growing list of conditions. Enbrel is an FDA-approved drug for the treatment of severe rheumatoid arthritis. It works by inhibiting tumor necrosis factor (TNF), which is a group of cytokines that are part of the immune system and cause cell death. Enbrel, therefore, can be a powerful anti-inflammatory drug. Tobinick is using Enbrel for many off-label indications, one of which is Alzheimer’s disease (the focus of the LA Times story).

The Dubious Health Clinic
Before I go into the details of Tobinick’s claims, let’s review the typical features of what we commonly call the “quack clinic” or the dubious health clinic. I wrote about this in 2009, and listed the following features:

- The clinic often has an impressive name, such as “The Institute Of,” but lacks any formal affiliation with an established institution, like a university or hospital, and was founded and may even continue to be operated by one person.

- The clinic claims to treat or cure one or more diseases that is currently believed to be incurable. Their claims sound too good to be true.

- There is only one clinic in the world that can perform their special procedure or that uses their proprietary treatment. Sometimes the treatment offered is new and experimental.

- The clinic claims to cure a variety of diseases, all with different causes and pathophysiology, with a single treatment – the “one cure for all diseases” approach.

- The clinic is often located in a country with little or no regulation.

- The clinic claims that it is the victim of repression. Typically they will say that either Big Pharma, the medical establishment, the insurance industry – or some other convenient villain – is trying to suppress their revolutionary treatment. Alternatively, the “medical establishment” is simply closed-minded to their paradigm-shifting ideas.

- Testimonials are used to promote the treatments offered by the clinic, but they have not published appropriate research in legitimate peer-reviewed journals.

- When challenged by professional organizations, the clinic defends itself by appealing to politicians, using the testimonies of previous patients who believe they have been helped by the clinic and the accusation of a conspiracy of those trying to protect their monopoly.

The Institute of Neurological Recovery
Now let’s take a look at Tobinick’s clinic. It has an impressive name – a one-man institute. The website proclaims:

The Institute of Neurological Recovery (INR®) is pleased to provide this introduction to its pioneering medical concepts, research, and treatment programs. INR designates a group of separate medical practices that utilize innovative, patented, off-label medical treatments developed by Edward Tobinick M.D. These treatment methods are designed to target a number of neuroinflammatory conditions with unmet medical need.

Many of the features of a dubious clinic are right there – the impressive name, claim to treat many conditions with one treatment, emphasis on how innovative the treatments are. The website also claims that his treatments are patented.

This is an interesting side issue, worthy of its own post. There has been a surge in the US in recent years in medical procedure patents. However, the first (and I think only) infringement lawsuit lost its case. Medical procedure patents are generally opposed by medical organizations as counterproductive profiteering and are banned in 80 countries. They are still legal in the US but there has been a number of legislative efforts recently to limit or ban them.

The patented procedure (even if not enforced) seems like just another way to market the uniqueness of the treatments offered by the dubious clinic.

The list of conditions for which Tobinick claims or even has patented use of Enbrel include Alzheimer’s, stroke, traumatic brain injury, Parkinson’s disease, carpal tunnel syndrome, brain tumor, spinal cord injury, and back pain. That’s quite impressive for a doctor who isn’t even a neurologist. Tobinick is an internist who, prior to curing a long list of neurological diseases, specialized in laser hair removal.

The LA Times reports:

But his claims about the back treatment led to an investigation by the California Medical Board, which placed him on probation for unprofessional conduct and made him take classes in prescribing practices and ethics.

Tobinick has since moved his clinic to Florida, which is a very quack-friendly state.  Its “health care freedom” law effectively shields dubious practitioners from pesky medical boards.

Plausibility and Evidence
When considering just the notion that Enbrel, a TNF inhibitor, might have a broad range of applications, this is entirely plausible. It is common for immunosuppressive drugs to gain an FDA approved indication for one specific condition, such as transplant rejection or rheumatoid arthritis, and then to be used off-label for many other autoimmune conditions.

This is very tricky, however, as the immune system is complex. There are different components to the immune system, and different aspects of immunity are involved in different auto-immune conditions. Therefore there is no one immunosuppressant drug or treatment for all auto-immune conditions.

When a new immune suppressing drug comes on the market it is common for it to be tried in a variety of conditions – but practice then follows evidence. Initially we might see some case reports, followed by a case series. If the drug shows promise, then a double-blind placebo-controlled trial would ultimately determine its effectiveness.

This is definitely a gray area of off-label use. How much evidence is necessary to justify an off-label use of a drug – and how far off label? Sometimes the popularity of a new off-label use of a drug gets ahead of the evidence. In most cases, however, eventually the research is done and practice conforms to the evidence.

The claims of Tobinick, however, are not in the gray area – they are leaps and bounds ahead of the evidence. Further, the conditions he claims to treat are not clearly immune-mediated diseases. It’s one thing to use an immune-suppressing drug to treat a disease that is known to be caused by immune activity, and probably the kind of immune activity suppressed by the drug.

Tobinick, however, is claiming that a wide range of neurological conditions not known to be immune mediated are treated by a specific immunosuppressant.

On his website he cites many studies, but none of them establish the effectiveness of Enbrel for any of the conditions he is treating. Most of them are simply identifying that TNF is increased in the condition. This is very weak evidence, however, as markers of immune activity are frequently increased in diseases that are not caused by immune activity. The immune system is very reactive – it reacts to disease with inflammation (often what we refer to as the cleanup crew). The inflammation is not causing the disease, it is simply the body’s reaction to it.

Tobinick has also started to publish case series – little more than retrospective case series reporting on his own patients.  This is weak evidence even when coming from an established researcher within their own area of expertise. It is all but worthless coming from a clinic like Tobinick’s.

This is where his lack of expertise is especially relevant. Such arguments are often portrayed as elitist, as if a mere internist cannot have a valuable insight into how to treat neurological disease. But medicine and research are complex and there are many pitfalls. Unless you have expertise dealing with strokes or dementia, including how to properly research these conditions, you are likely to fall for these pitfalls.

For example, in his recent case series he writes:

Significant improvement was noted irrespective of the length of time before treatment was initiated; there was evidence of a strong treatment effect even in the subgroup of patients treated more than 10 years after stroke and TBI.

This, if anything, is evidence that the observed treatment effect is mere placebo. It is very implausible that stroke or TBI deficits will be equally responsive to an anti-inflammatory treatment (or any treatment) regardless of time since the stroke or trauma.

Stroke researchers are also very familiar with what is known as the “cheerleader effect.” Take any patient with chronic deficits, give them any intervention and then encourage them to function better, and they will function better. This can result simply from trying harder, or even just the incidental physical therapy benefit of engaging in a treatment and being evaluated.

Unless all these factors are controlled for with proper blinding, no conclusions about the treatment effect are possible. Tobinick is providing the kind of evidence that is guaranteed to be positive, but not the kind of evidence that would determine if his treatments are effective or not.

Conclusion
If you strip away the gratuitous narrative in the LA Times story and just look at the facts presented, a very different narrative emerges. Ken Chiate brought his wife to Tobinick’s clinic for 165 injections of Enbrel over four years, at a cost of $800 each (that’s $132,000). During that time there were questionable subjective effects from the treatment, typical of placebo-only effects. Meanwhile his wife continued to relentlessly progress, as is typical of the disease, until she finally died in 2011.

According to the article, the treatments gave Chiate a sense of purpose and of hope – a false hope, it turned out. He still clings to the idea that Enbrel may be an effective treatment for Alzheimer’s disease – even though Tobinick himself has apparently moved on to treating stroke.

In my opinion, the story documents exploitation of a well-meaning and desperate husband at the hands of a dubious practitioner, practicing at the fringes of medical ethics and evidence, making bold claims without adequate justification. The story also documents the utter failure of the regulatory system to prevent (or even properly react to) such exploitation. Florida in particular appears to be a haven for such activity.

Posted in: Health Fraud, Medical Ethics, Politics and Regulation

Leave a Comment (30) ↓

30 thoughts on “Enbrel for Stroke and Alzheimer’s

  1. windriven says:

    And let’s not forget that etanercept (who comes up with these names???) is not entirely benign.

    FDA placed a black box warning on etanercept as far back as 2008 due to a number of serious infections associated with the drug. FDA cautions that as immunosuppressants, TNF blockers may increase risk of various cancers, listeria, legionella, histoplasmosis, coccidioidomycosis, blastomycosis, aspergillosis, candidiasis, and other opportunistic infections.

  2. nickmPT says:

    I have a question regarding medical school. It seems that there are a decent number of these MD quack-types, how much critical thought/scientific appraisal is taught in med school beyond rote memorization? (I can understand that all schools are different, but there are accreditation standards…)

    And, perhaps it is just hearing more of the small number of negatives of the profession, while most are practicing scientifically.

  3. windriven says:

    @nickmPT

    “[H]ow much critical thought/scientific appraisal is taught in med school?”

    This is a particular irritation for me. But I don’t think that it is fair to blame medical school. Inculcation of the scientific method is a process that should begin early and one hopes would be complete by the time a baccalaureate degree is earned. Medical school is not the place to teach English composition, differential calculus or the rudiments of how science works; it is a place to teach the practice of medicine.

    That said, it is unconscionable and unethical for medical schools to embrace and even teach unscientific mumbo-jumbo through sCAM curricula and sCAM “Integrative Medicine” facilities. It is no different than teaching so-called intelligent design. Bullcrap is bullcrap whether the cowpie flops at some fundamentalist school in Lubbock or the halls of Yale Medical School.

  4. nickmPT says:

    @windriven

    I agree, I just think of the degree inflation and how many students are coming out of high school and/or undergrad with very little appraisal of critical thinking (including possible pre-med, pre-PT type students). Teaching to the test has also been a pitfall as well.

    Perhaps, I am just lamenting at the overall lack of critical thought at all levels of education which then allows this crap to flourish (I suppose manure is good for crop growth, eh?).

  5. windriven says:

    @nickmPT

    You would be appalled at some of the resumes that I receive from graduates of presumably good programs. Some can’t write a coherent paragraph and I wouldn’t guess for a moment that they could summarize the scientific method in a couple of sentences.

    I agree that grade and degree inflation are out of control. And I deeply share your lament of the near absence of critical thinking skills demanded throughout the educational process.

  6. Sawyer says:

    @nickmPT

    Not unique to med school either. I have a Bachelor’s and a Master’s in Mechanical Engineering from a top-tier US university. While engineering programs may do a better job than med school at teaching students how to apply existing knowledge to new challenges, they put very little time into covering the scientific method, logical fallacies, pseudoscience, or the history of scientific discovery. I really don’t know how you would squeeze all this stuff into an already dense curriculum, so maybe suggesting to students that they should spend time looking at supplemental sources like SBM is the only viable option.

  7. nickmPT says:

    @Sawyer

    I could understand that in a professional program the goal is applying the existing knowledge to a trade. Ultimately, teaching of critical thought needs to start far sooner, i.e. grade school.

    I was having a discussion with my great aunt last night. She told of a math teacher (pre-highschool) her children had. He did not care about the kids getting the right answer, he cared more about their thought process. He also did not want the parents to help with the homework as he wanted the children to struggle and challenge their minds. Finally, he sat down with each child and worked through the problem with them, recognizing where there frame of reference was and guiding them towards less wrong trains of thought. This takes patience, compassion, and hard-work. It breeds motivation, curiosity, and intelligence.

    As long as our education system is built on the goal of getting the correct answer rather than how to get there this kind of thing will be perpetuated and society will suffer.

  8. wertys says:

    Some Australian doctors at a new University research institute tried to bring this therapy to Australia. The story is told in this link
    http://www.smh.com.au/national/health/patients-left-in-limbo-as-alzheimers-trial-awaits-ethical-approval-20120817-24dwa.html

    It seems they weren’t aware of the need for ethics approval for unregistered use of drugs which is disappointing for the huge number of patients and donors who were left hanging…

  9. woody2 says:

    Thank you for tackling Tobinick’s shenanigans. I felt he deserved the SBM Quack Takedown several years ago when he started pushing perispinal etanercept for Alzheimer’s disease. I had no idea how many injections he was giving patients. I am surprised that there have not been procedural complications – perispinal injections are not without risk even if you don’t factor in the potential adverse effects of etanercept.

  10. Zuppy says:

    Dr. Edward Tobnick, Dermatologist has created near 100 ‘testimonial videos’.

    The title is – RAPID RELIEF FOR ORTHOPEDIC SURGEON WITH SEVERE PAIN

    I invite you to view the video and discuss!

    Rapid Relief for Orthopedic Surgeon with severe pain

    http://www.youtube.com/watch?v=qFsPIAMLSjU

    nrimed·102 videos
    Subscribe 816
    5,182

    Uploaded on 25 Nov 2009

    Please see http://www.painbreakthrough.com.
    The Institute of Neurological Recovery Los Angeles and Newport Beach, California and Boca Raton, Florida.

  11. Zuppy says:

    more informantion on Dr. Edward Tobinick created video: RAPID RELIEF FOR ORTHOPEDIC SURGEON WITH SEVERE PAIN

    Uploaded on 25 Nov 2009

    Please see http://www.painbreakthrough.com.
    The Institute of Neurological Recovery Los Angeles and Newport Beach, California and Boca Raton, Florida.

    Orthopedic Surgeon responds within minutes to a single dose of perispinal etanercept for severe pain. Copyright 2010 INR®, all rights reserved. Perispinal etanercept is a patented treatment developed and invented at the Institute of Neurological Recovery, a private medical group, inc. in Los Angeles. This video was shot in July 2009. More complete information at http://www.painbreakthrough.com. See also Tobinick, E., Perispinal etanercept for neuroinflammatory disorders Drug Discovery Today 2009 Feb;14(3-4):168-77.

  12. windriven says:

    @Zuppy

    “I invite you to view the video and discuss!”

    Cool! I wonder if Tobnick learned that schtick from Benny Hinn?

    I especially liked the part where he asked the shill, I mean patient, whether he thought his relief might be from the placebo effect.

  13. windriven says:

    @Zuppy

    “The Institute of Neurological Recovery Los Angeles and Newport Beach, California and Boca Raton, Florida.”

    INR in Boca Raton. Mouth of the Rat. One couldn’t make this stuff up!

  14. windriven says:

    Hmmm…

    I did find one interesting citation on the IRP site:

    “Randomized, double-blind, placebo-controlled, dose-response, and preclinical safety study of transforaminal epidural etanercept for the treatment of sciatica.”

    Cohen SP, Bogduk N, Dragovich A, Buckenmaier CC 3rd, Griffith S, Kurihara C, Raymond J, Richter PJ, Williams N, Yaksh TL. Anesthesiology. 2009 May;110(5):1116-26.PMID:19387178.

    Anesthesiology is a first rate journal and Steven Cohen, MD is a well known pain researcher and a full professor at Johns Hopkins.

  15. windriven says:

    Forgot to add that the Cohen study I mentioned above is a small study (n=24).

  16. WilliamLawrenceUtridge says:

    @Zuppy:

    What’s your point? That anyone can claim anything on the internet and there is no quality control? That testimonials are worthless? The importance of clinical trials in creating evidence that can be relied upon, because it’s too easy to create fake testimonials or cherry-pick only those who believe they are improving? That testimonials are indistinguishable from advertising, and about as trustworthy?

    Certainly those are valid points I can agree with.

  17. Zuppy says:

    Oops, sorry, I added in the line “I invite you to view and discuss”

    I wanted the readership to view Tobinick’s video and comment!

  18. windriven says:

    Curiously, in a later study* Cohen et al found epidural etanercept inferior to epidural steroids for lumboscral radiculopathy. This was also a small study (n=84)

    *Ann Intern Med. 2012 Apr 17;156(8):551-9. doi: 10.1059/0003-4819-156-8-201204170-00002.

  19. windriven says:

    @WLU

    I believe that Zuppy was offering this video for ridicule.

  20. Zuppy says:

    windriven is correct!

  21. Chris says:

    windriven:

    INR in Boca Raton. Mouth of the Rat. One couldn’t make this stuff up!

    Actually raton (with an accent over the “o”) is mouse, so it is mouse mouth, a rat is “rata. In Venezuela* the Mighty Mouse cartoon I watched was called “Super Raton.” Anyway I read somewhere it is a Spanish colloquial description of a type of inlet with jagged rocks that nibble on ropes like micey teeth. It is a bit more creative than the description of a bay on Whidbey Island: Useless Bay.

    * And I wish I spoke Spanish better than I do. I rebelled against linguist father and took more math. Which, in retrospect, was better since engineering paid lots better than either of parents’ liberal art degrees.

  22. windriven says:

    @Chris

    Yo no quiero rata o raton! :-)

    How’s that for Spanglish? I know what it means but my Spanish isn’t good enough to say that I don’t care if it is a rat or a mouse. I even ran a plant in Reynosa for a while. So I have no excuse for my abysmal Spanish.

    Math, physics, all good. I took German in high school (it still charges back when I spend a few weeks in Germany) and managed to take no language classes at all in college.

    Interesting that you went with an engineering degree coming from a liberal arts household. I’d bet that isn’t all that common – especially for a female going to U in the 70′s (I hope I remember that correctly).

  23. Zuppy says:

    I must compliment Steven Novella on this review of the Los Angeles Times story. Excellent commentary, which cannily captures the claims and practices of one Dr. Edward Tobinick, a person ticks all the boxes as a dubious person, who presently runs three dubious clinics, where dermatology clinics double as neurological clinics……with the same dermatology doctors and staff, led by dermatologist Dr. Edward Tobinick. There is not one neurology trained doctor or staff at Tobinick’s clinics. At these dubious clinics, an Alzheimer’s or Stroke patient on initial consultation and administration of the off-label drug Enbrel (etanercept) can expect to pay circa $5000 on the day. A single dose of Enbrel cost circa $200. Steven’s commentary goes some way to shine a spotlight on one Dr. Edward Lewis Tobinick, dermatologist.

  24. Zuppy says:

    You want Institutes………Dr. Edward Tobinick, dermatologist gots Institutes.

    Tobinick’s dermatolgy practice is called: Institute of Laser Medicine http://www.universitylaser.com/

    also home of Institute of Neurological Recovery http://www.instituteofneurologicalrecovery.com/

    which was previously called Institute of Neurological Research. http://www.nrimed.com/

    INSTITUTE OF NEUROLOGICAL RECOVERY – A New Breakthrough for Stroke and Traumatic Brain Injury (TBI)
    http://www.strokebreakthrough.com/

    2300 Glades Road, Suite 305E
    Boca Raton, FL 33431

    361 Hospital Road, Suite 428
    Newport Beach, CA 92663

    100 UCLA Medical Plaza
    Suites 205-210
    Los Angeles, CA 90095

    (310) 824-6199

  25. Chris says:

    windriven, not being a liberal arts major was a goal of both myself and my brother. Part of it was seeing frustration in our parents. Though the fortunate part of being an Army brat was that moving around I was always the new kid, so I learned to ignore comments from certain people.

  26. Xplodyncow says:

    etanercept (who comes up with these names???)

    I might be wrong about this, but I believe it’s R&D that devises the generic name, and the syllables reflect the type of compound. For example (writes this non-scientist), drugs with a particular action on some specific part of the immune system all end in “-cept” (e.g., etanercept, abatacept) or “-mab” (e.g., adalimumab, certolizumab, golimumab, infliximab, rituximab, tocilizumab). Brand names, however, seem to be random combinations of letters invented by marketers.

  27. Zuppy says:

    Los Angeles Daily News 1987

    Warning: Fry Now, Pay Later Melanoma Is Caused By A Serious Sunburn From Childhood
    By JENNIFER LOWE, Los Angeles Daily News
    Posted: May 20, 1987

    “You can’t have people in not stay out of the sun,” said Dr. Edward L. Tobinick, a Beverly Hills dermatologist and medical director of the Skin Cancer Institute, a private skin-care clinic.

  28. Narad says:

    INR in Boca Raton. Mouth of the Rat. One couldn’t make this stuff up!

    Tobinick also has a house in Highland Beach. I recall that Florida’s homestead exemption, which shields one’s house from creditors, was cited as a reason for Boca long being Spam Central. It was also popular for pump-and-dump boiler rooms and, before that, swamp peddlers.

  29. norrisL says:

    As a 49 year old sufferer of early onset of dementia, this crap gets me really wound up, especially when I see that he had tried to do trials here in Australia. Grrrrrrrrrrr (angry noise)

Comments are closed.