New CGRP-blocking MIGRAINE Drugs increase risk of worsening, gangrene, autonecrosis, amputation in Raynauds
In 2016, I published a few small books on migraine (and fibromyalgia) excerpted from the 4th Edition of Inflammation Mastery. The e-book on migraine is cheaper and more powerful than a corporate mocha
When the new-generation anti-CGRP migraine drugs were released in 2018, I predicted in my videos and blogs that these drugs would cause an increase in cardio-vascular complications such as stroke and other types of ischemia (lack of blood flow).
This was a "Captain Obvious" prediction given that CGRP is cardioprotective, and that these drugs target CGRP, thus negating one of the body's endogenous protective mechanisms.
“CGRP” is “calcitonin gene related peptide” which is a signalling molecule involved in the pain of migraine. The simple-minded drug approach is to target this intermediate messeger to stop the pain of migraine, while allowing the disease to continue and thereby leave patients dependent on the drug.
However, CGRP also helps keep blood flowing through arteries, so —obviously— targeting this artery-opening molecule with a pharmaceutical antibody will lead to a relative closing of arteries and stopping of blood flow.
The obvious expectation is that blocking CGRP would lead to more strokes, heart attacks, hypertension, organ/limb ischemia and amputation.
A new publication from the American Medical Association (JAMA Network Open 2021 Apr) shows significant risk for “worsening” all the way to loss of fingers (“digital amputation”) but the journal described these as “rare” and “uncommon” when in fact 1-per-20 patients (more than 5% of total) will be adversely affected. Furthermore, these anti-CGRP drugs are nearly worthless in relation to their high cost. As I said in 2018 (article included below), “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.”
Sure enough, stroke/ischemia/amputation are being reported. Also clear is the fact that the JAMA journals are now nothing more that tabloid advertisements for drug sales. The attached report from JAMA states that the adverse effects are "uncommon" but >5% is 1-per-20 "ranging from worsening RP to gangrene and autonecrosis that required distal digit amputation."
Any doctor in practice facing 1-per-20 patients worsening, having a stroke, or having their fingers amputated would be run out of business and run out of town.
These anti-CGRP drugs actually increase the risk of Raynaud’s phenomenon: “The other 4 patients (44.4%) were newly diagnosed with RP after administration of CGRP antagonists.” See the full text in the PDF below; this is a small and limited study but the implications are massive in 1) the quantity of patients affected and 2) the gravity of those consequences. I do not agree with their conclusions that are tryinig to minimize the scope and gravity of these problems, especially for a class of drugs that fail >80% of the time and which cost US$7,000 - US$8,500 per year.
The e-book on migraine is cheaper and more powerful than a corporate mocha.
CGRP Blockade for Migraine: Some Day We Will Look Back and Laugh (or Cry)
linkedin.com/pulse/cgrp-blockade-migraine-some-day-we-look-back-laugh-alex published on September 25, 2018
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) :
"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 .
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):
Blood pressure reduction
Promotion of wound-healing
Modulation (biphasic) of gastrointestinal motility
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 . 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 ; 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.
"Down there speaks everything, there is everything misheard. If one announces 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:  Cohen J. Migraine Breakthrough: Not So Fast. Forbes 2018 Jun 6 forbes.com/sites/joshuacohen/2018/06/06/migraine-breakthrough-not-so-fast  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  Pain Revolution https://www.amazon.com/dp/B01AR3NX0S/ or in slightly cheaper grayscale as Brain Inflammation https://www.amazon.com/dp/B01EQ9KMH6  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
Dr Alex Kennerly Vasquez (introduction; brief Bio-CV) writes and teaches for an international audience on various topics ranging from leadership to nutrition to functional inflammology. Major books include Inflammation Mastery, 4th Edition (full-color printing, 1182 pages, equivalent to 25 typical books [averaging 60,000 words each]), which was also published in two separate volumes as Textbook of Clinical Nutrition and Functional Medicine (Volume 1: Chapters 1-4; Volume 2: Chapter 5—Clinical Protocols for Diabetes, Hypertension, Migraine, Fibromyalgia, Rheumatoid Arthritis, Psoriasis, Vasculitis, Dermatomyositis and most other major inflammatory/autoimmune disorders); several sections have been excerpted including Antiviral Strategies and Immune Nutrition (ISBN 1502894890) (aka, Antiviral Nutrition [available as PDF download] and Brain Inflammation in Chronic Pain, Migraine, and Fibromyalgia. Dr Vasquez’s books are available internationally via bookstores such as BookDepository, Amazon.com, Barnes and Noble, ThriftBooks, AbeBooks, BetterWorldBooks, WaterStonesBooks and his new Telegram channel is https://t.me/DrAlexVasquez.