CGRP Blockade for Migraine: Some Day We Will Look Back and Laugh (or Cry)

 

• Science will be rewritten to promote pharmaceutical profits: Now that CGRP-blocking drugs are on the market, the pathophysiology of migraine has to be re-written in order to change the clinical paradigm to accommodate pharmaceutical profiting and the "need" for more medical services surrounding the prescription and laboratory monitoring for these drugs. For the few patients who both 1) can afford these drugs, and 2) benefit from these drugs, I truly wish them well and hope they experience no adverse effects. Unfortunately, these drugs do not address the underlying problems that cause migraine, but certainly acute pain relief has value independent from the delivery of optimal healthcare.

• Pharmaceutical cheerleaders gain high-profit headline-making employ: I will resist the temptation to embarrass individual people, many with high-profile professorships in esteemed (ie, corporate-friendly) institutions, by showcasing via cited quotations their lack of restraint in their paid and overzealous endorsements of these new drugs. "Breakthrough" is the term most commonly employed as they describe this "new horizon" now visible as these new drugs "shake the ground beneath our feet" and herald "a new age in migraine treatment."

• High cost: With annual cost-per-patient of US$7,000 - US$8,500, popular use of the new CGRP drugs will bankrupt most patients and most healthcare systems. Borrowing three sentences from Joshua Cohen's "Migraine Breakthrough: Not So Fast" published in Forbes (2018 Jun 6) [1]:

"Suppose all eligible patients were to receive Aimovig or one of its competitors for one year. This would amount to a pharmacy budget impact of $27.6 billion. One sixth of that figure - $4.6 billion - would be money worth spending on the new product, but $23 billion would effectively be wasted. And, $23 billion is approximately the entire federal budget allocated to healthcare services and treatment for people living with HIV in the U.S."

• Low Efficacy: In the real world, benefit of these new drugs is seen in one-per-six or up to one-per-ten migraine patients, ie, NNT=6 or NNT=10, which means that 83-90% of patients do not benefit. This is worse than the notably low response rate with triptan drugs, and is abysmally less efficient than nutritional treatments' NNT of <2.

• CGRP is the most powerful vasodilating mediator known. Blocking CGRP is quite likely if not assured to promote cardiovascular, renal, and gastrointestinal complications, among other problems such as delayed wound healing and alterations in gastrointestinal function. Blocking an endogenous vasodilator is effectively the same as inducing iatrogenic vasoconstriction, exactly as occurred with rofecoxib/Vioxx, which was also lauded as a “breakthrough” anti-inflammatory drug because it was considered “specific” for painful inflammation; a “specific” “breakthrough” that killed tens-hundreds of thousands of people before being withdrawn 5 years after it hit the market [2].

• Beneficial properties of CGRP: Here, I will make a quick list of the benefits of CGRP so that everyone can appreciate what it does and what blocking it is likely to induce (for the latter, just reverse each of the following):

1. Vasodilation

2. Blood pressure reduction

3. Cardioprotection

4. Promotion of wound-healing

5. Modulation (biphasic) of gastrointestinal motility

6. Enhancement of mitochondrial function (likewise with calcitonin)

• The violence of organized and systematic forgetting: In medicine and biomedical science, we commonly collectively forget major legitimate advances in our understanding of disease causation and cure, especially when our forgetting is convenient for gain of personal and professional power, prestige, and profit. What appears to matter most is that we regularly resign our knowledge and consciousness in service of paradigm.

     Personally, I don't care too much if CGRP-blocking drugs work or don't work; if anything, I actually hope that they do work for the patients who have not responded to the otherwise supremely safe and effective treatments I have outlined [3]. So, in summary and repetition, if anything I am in favor of these drugs, assuming (naively) that they might be used appropriately, which they will not be. Doctors are not trained in nutrition and even though they are increasingly trained in "systems biology", they are not trained in integrative and internventional nutrition as a therapeutic approach, despite the supporting science, clinical efficacy and enviable safety.

• We've been here before: Rofecoxib/Vioxx was shown to increase cardiovascular deaths several years before the drug was withdrawn [4]; the most aggressive advertising campaigns hitherto seen in medicine overran what medicine always says is its precautionary principle. So, here again I believe, we are overriding science in favor of another high-profit flash-in-the-pan. Only time will tell, and like I said, I hope I'm wrong, but I'm not: the mere fact of spending ~US$8,000 per patient-year at 17% effectiveness before metabolically corrective treatment has been used is already a losing game, even if zero cardiovascular risks are demonstrated. A few years from now, we will either look back and laugh at this ridiculous overexpenditure, or we'll be (de)crying in witness of yet another pharmacocentric profiteering scheme that hoodwinked patients and doctors into yet another round of iatrogenic injuries and deaths. 

"But down there- there speaks everything, there is everything misheard. If one announce one's wisdom with bells, the shopmen in the market-place will out-jingle it with pennies! Everything among them talks; no one knows any longer how to understand. Everything falls into the water; nothing falls any longer into deep wells. Everything among them talks, nothing succeeds any longer and accomplishes itself."

Nietzsche in "Thus Spoke Zarathustra"

 

Citations: [1] Cohen J. Migraine Breakthrough: Not So Fast. Forbes 2018 Jun 6 forbes.com/sites/joshuacohen/2018/06/06/migraine-breakthrough-not-so-fast [2] Cockburn A. When half a million Americans died and nobody noticed. The Week 2012 Apr theweek.co.uk/us/46535/when-half-million-americans-died-and-nobody-noticed. Topol EJ. Failing the public health--rofecoxib, Merck, and the FDA. N Engl J Med. 2004 Oct 21;351(17):1707-9 https://www.nejm.org/doi/full/10.1056/NEJMp048286 [3] Pain Revolution https://www.amazon.com/dp/B01AR3NX0S/ or in slightly cheaper grayscale as Brain Inflammation https://www.amazon.com/dp/B01EQ9KMH6 [4] Mukherjee D, Nissen SE, Topol EJ. Risk of cardiovascular events associated with selective COX-2 inhibitors. JAMA. 2001 Aug 22-29;286(8):954-9

​

Originally posted 25 Sep 2018: https://www.linkedin.com/pulse/cgrp-blockade-migraine-some-day-we-look-back-laugh-alex/?published=t

​