Shoot, Joe, Bob,

Thank you for the kind words, but it's not my star...  It's your star as well...  None of this would be possible without support from CH'ers like you who decided to try something new to control their CH. 

Without your support, based on first hand results as well as encouraging other CH'ers to try the anti-inflammatory regimen and taking the online survey... we wouldn't have the evidence needed to at least interest a few neurologists to give this regimen a try with their CH patients...

We're not home yet and there remain a couple important milestones we need to reach before we're firmly on the road to having this regimen added to the Standards of Care recommended treatments for CH and other trigeminal autonomic chephalalgias. 

We need to have the complete survey results published and I'm working on that...  We also need another independent gold standard RCT conducted on the efficacy of this regimen to verify our results. 

Obtaining these goals isn't going to be easy as you'll see below...  You'll also see what's been consuming much of my time when not responding to CH'ers questions about the anti-inflammatory regimen.

It's interesting to note after a nearly 3 year effort reviewing a number of related studies, it appears my theory on the mechanism of action responsible for the efficacy of the anti-inflammatory regimen in preventing CH is gaining strength... 

This theory involves the capacity of vitamin D3 and its metabolites to down-regulate or suppress the calcitonin gene-related peptide (CGRP) produced in the trigemial ganglion.  CGRP, an amino acid peptide, helps transmit pain, it's a vasodilator and it's involved in neurogenic inflammation which has a role in the pathophysiology of both cluster headache and migraine.

There are several studies that have found CGRP levels elevated during the active pain phase of CH and migraine...

The latest news on this theory is gaining acceptance albeit based on evidence from a pair of proof of concept studies also briefed at the AAN Annual Meeting in Philadelphia, PA. 

These RCTs involve the use of monoclonal antibodies to suppress CGRP and in the process, prevent frequent and recurrent migraine headaches.  These studies were lead by none other than doctors Peter Goadsby and David Dodick.

See: Multimedia File Viewing and Clickable Links are available for Registered Members only!!  You need to or

Multimedia File Viewing and Clickable Links are available for Registered Members only!!  You need to or

The first of these studies on LY2951742, a monoclonal CGRP antibody originally developed by Eli Lilly, was conducted by Dr. David Dodick, MD, the Mayo Clinic, along with Dr. Peter Goadsby and a cast of other noted neurologists.  It was sponsored by Arteaus Therapeutics.  Lilly just bought the patent back from Arteaus for an undisclosed sum based on the results of this pilot study...

During this study subjects with a history of 4-14 migraine headache days (MHD) per month received bi-weekly subcutaneous doses of LY2951742 (150mg) or placebo for 12 weeks in a double-blind fashion.

The primary endpoint was the mean change number of migraine headache days per 28-day period assessed at 12 weeks. Secondary endpoints were the change in headache days, migraine attacks and responder rate.

Key Results

    A total of 217 subjects were randomized and received LY2951742 (n=107) or placebo (n=110)

    The primary endpoint, mean change in MHD at 12 weeks when compared to baseline was -4.2 (62.5% decrease) vs. -3.0 (42.3% decrease) for LY2951742 and placebo respectively (p<0.003).

    LY2951742 was superior to placebo for all secondary endpoints including:
        Headache days -4.9 vs. -3.7 (p<0.0117),
        Migraine attacks -3.1 vs. -2.3 (p<0.0051), and
        Responder rate 70% vs. 45% (OR 2.88 [CI 1.78 to 4.69])

     An exploratory endpoint of complete responders (100% reduction in MHD) was 33.3% vs. 17.3% for LY2951742 and placebo respectively.

    Adverse events occurred more frequently with LY2951742 than placebo and included: injection site pain, upper respiratory tract infections, and abdominal pain.

Conclusions: Treatment with LY2951742 in subjects with a history of frequent migraine days provided a significant decrease in the number of migraine headache days, headache days and migraine attacks when compared with placebo. LY2951742 was efficacious and well tolerated.

Authors: David Dodick; Peter Goadsby; Egilius Spierings; Joel Scherer; Steven Sweeney; David Grayzel

The second study was conducted on ALD403 in a randomized, double blind, placebo-controlled trial. ALD403 is an anti-CGRP peptide antibody. The objective of this study was to evaluate the efficacy and safety of ALD403, a genetically engineered humanized anti-CGRP antibody (IgG1), for migraine prevention.

Calcitonin gene-related peptide (CGRP) is a small protein thought to have an integral role in the pathophysiology of migraine.

Patients with a history of 5-14 migraine days per month received a single intravenous dose of ALD403 1000 mg or placebo in a double-blind fashion. The primary endpoint was the mean change in frequency of migraine days from baseline to migraine days during weeks 5-8. Patients were followed for 24 weeks for additional safety and efficacy analyses

Key Results

    Of 174 patients randomized, 163 patients received either ALD403 (81) or placebo (82).

    The mean change in migraine days between weeks 5-8 and baseline was -5.6 days (66% decrease) for ALD403 vs. -4.6 days (52% decrease) for placebo (one-sided p = 0.03).

    Sixteen percent of patients receiving a single dose of ALD403 had no migraines for the full 12 weeks (p<0.001) vs. 0% for placebo.

    The proportion of patients with a 50% and 75% reduction in migraine days at 12 weeks for ALD403 and placebo was 60% vs 33% (p < 0.001) and 32% vs 9% (p < 0.001), respectively.

    ADL403 was well tolerated and there were no differences in the type or frequency of adverse events, vital signs, or laboratory safety data between the two treatment groups.

Conclusions: A single intravenous dose of ALD403 1000 mg was effective and well tolerated for the prevention of migraine in patients with a high monthly frequency of migraine days.

Authors: Peter Goadsby; David Dodick; Stephen Silberstein; Richard Lipton; Jes Olesen;

My comments:

It doesn't take a leap of faith to see either of these two monoclonal antibody preventatives for migraine being used for cluster headache...  The only real question is when and for how much...  2 to 5 years is a reasonably safe range estimate for FDA approval.

Cost is likely going to be a factor as will coverage under most healthcare insurance programs including Obamacare...

Neither study indicated the cost to treat migraineurs with either of these two monoclonal antibody preventatives... That said, Zenapax, (daclizumab), a monoclonal antibody used since 2000 to prevent rejection after organ transplants is $6,800 per treatment at a wholesale price for five doses.

With an estimated 36 million migraineurs in the US alone, the potential return for big pharma is staggering...  If only 10% of these migrainerus are treated at $5,000 per treatment, the potential gross revenue is $18 Billion dollars.

So where does this leave us as CH'ers...  Big Pharma and a gaggle of top gun neurologists are queuing up a pair of monoclonal antibody (MAB) migraine preventatives that will have a clear application for CH'ers...

LY2951742 - 33.3% of migraineurs treated with bi-weekly doses over 12 weeks experienced a complete remission of migraine symptoms vs 17.3% for the placebo.

ALD403 - 16% of migraineurs treated with a single intravenous infusion experienced a complete remission of migraine symptoms vs 0% for the placebo.

Vitamin D3 - The anti-inflammatory regimen with a minimum of 10,000 IU/day vitamin D3 costs roughly 35 cents a day. 83% of the CH'ers who use it experience a significant (70%) reduction in the frequency, severity and duration of their CH.  It also works effectively to prevent cluster headaches completely in an average of 12 days for 60% of CH'ers who use it.

At face value, the anti-inflammatory regimen is the hands down winner for CH'ers...  Although the number of users being tracked is roughly one tenth the number of CH'ers, better than 80% of migraineurs who use this regimen experience a complete remission of migraine headaches, typically in one month.

Unfortunately, the anti-inflammatory regimen results come from an uncontrolled survey conducted by me and not a gold standard RCT with random selection, double blinding and placebo controlled construct, conducted by a noted neurologist.   

We need one of these RCTs... but funding an RCT like this is a major problem as we're talking USP vitamin and mineral supplements so nothing can be patented.  Finding a noted neurologist willing to serve as the Principal Investigator is another problem...

If you eliminate big pharma as an RCT funding source, you're left with the nutraceutical companies, educational institutions and big government...

So now you know what's consuming my spare time...

Take care,

V/R, Batch