On Oct. 20, 2017 the FDA approved Shingrix, a killed herpes zoster (HZ) vaccine for adults over 50 years old.
It was approved in Canada a week earlier on Oct. 13, and there might be an important difference in the two countries.
Key Take Aways:
- This is a more potent, more durable non-live vaccine to prevent HZ.
- It is approved for adults 50 and older.
- It is a series of two shots.
- There may be issues with Medicare payment.
- There may be issues for CLL patients in the USA getting the new vaccine, as the CDC only recommends it for those with a normal immune system.
You can skip to my bottom line at the end of the article, or follow me as I take a deep dive in the details.
SHINGRIX is a sterile, non-live vaccine for intramuscular injection. It is not a live attenuated or weakened virus, so it can’t grow. That should be safe for us. In fact it should be strongly recommended, as shingles is such a scourge for so many of us.
The risk of developing HZ increases with age and appears to be related to a decline in specific immunity to the varicella zoster virus (VZV) that causes chickenpox and shingles. SHINGRIX has been proven to boost that specific immune response. That is the reason we believe that it provides protection against shingles.
Approvals, Dosing, Recommendations and Medicare:
Here is a link to the FDA approval:
Here is a link to the Canadian approval:
In Canada, the product monogram, the official document that describes the indications of the medication says “SHINGRIX is indicated for prevention of herpes zoster (HZ, or shingles) in adults 50 years of age or older”
In the USA, the package inset (PI) reads the same, namely “SHINGRIX is indicated for prevention of herpes zoster (HZ, or shingles) in adults 50 years of age or older”
The older live vaccine (Zostavax) is contra-indicated in CLL. It is approved for those with a normal immune system who are over 60 and is a single shot.
The new vaccine is approved for adults over 50. It consists of a series of two shots, between 2 and 6 months apart. And that might be the first problem because Medicare has never paid for two shots for the same disease in one year. But there is potentially a much bigger problem. This is taken from the CDC with my comments in italics.
“…the US Centers for Disease Control and Prevention’s (CDC) Advisory Committee on Immunization Practices (ACIP) voted in favor of three recommendations for the use of Shingrix (Zoster Vaccine Recombinant, Adjuvanted [adjuvants are chemicals added to boost immune response]) for the prevention of shingles (herpes zoster):
- Herpes Zoster subunit vaccine (Shingrix) is recommended for the prevention of herpes zoster and related complications for immunocompetent adults aged 50 years and older.
- Herpes Zoster subunit vaccine (Shingrix) is recommended for the prevention of herpes zoster and related complications for immunocompetent adults who previously received Zoster Vaccine Live (Zostavax). [In my opinion, this essentially says no one, even those who could get it safely, should bother with the old vaccine if they can safely wait until when the new one is available, hopefully early in 2018. Why get the older vaccine that might be risky for those around you with compromised immunity when the ACIP recommends that everyone be boosted with the new vaccine, even those who have received Zostavax].
- Herpes Zoster subunit vaccine (Shingrix) is preferred over Zoster Vaccine Live (Zostavax) for the prevention of herpes zoster and related complications.” [It is most unusual for ACIP to recommend one vaccine over another and this vote was split 8 yes, 7 nay]
Please notice they only recommend the vaccine for immunocompetent patients over 50. That would exclude everyone with CLL. Canada makes no such recommendations.
Let’s dig into this a little more and look at the science and the data as it pertain to chronic lymphocytic leukemia, including why we were excluded from the American recommendations.
The Scope of the Problem:
About 99% of those older than 50 years are infected with varicella zoster virus (VZV) because nearly all of us had chickenpox as a kid. 1 in 3 will develop shingles in their lifetime. The risk increases to 1 in 2 for adults aged 85 years and older. The chickenpox virus, like all herpes viral infections, never goes away, but does become dormant or latent in our body, specifically in the sensory neurons of dorsal root and cranial nerve ganglia. It can wake up when our immunity is suppressed. Kicks us when we are down. It can then cause a severely painful cluster of small blisters called shingles, usually following a nerve root. If it breaks out on certain areas of the face, it can damage the cornea and lead to vision problem. Some never get the rash, only the pain.
But what is worse is its sequela. Zoster can lead to a terrible chronically painful condition called post-herpetic neuralgia (PHN) that nobody wants. That nerve pain, is felt in areas where the shingles rash occurred and can last for years. In the worse cases, the pain can be so severe that it has driven patients to consider suicide.
According to CDC, in the USA, there are 1 million cases of shingles every year. About half of all cases occur in people 60 and older. Between 10% and 20% of those with shingles will develop PHN.
The Good News:
Just how effective is the new vaccine? Here’s what the studies show.
- Shingrixis 97% effective against shingles for those 50 to 59 years
- Forthose in their 60s, the new vaccine is 97% effective, compared to 64% for Zostavax.
- Forthose in their 70s, Shingrix is 91% effective, compared to 41% for
- For those in their 80s, who are at the highest risk for HZ:91% versus 18%.
- Shingrixis also 91% effective in preventing PHN, the most common complication of shingles in those 50 and
- Vaccine efficacy in preventing HZ is durable too. In subjects aged 50 years and older, efficacy was still 93.1% in the fourth year post-vaccination. Zostavax loses most of its potency within 3-5 years.
The most common side effects were pretty mild and were what would be expected from an effective vaccine, mostly a reaction at the injection site, including redness or swelling, but also muscle pain, fever and headache. The side effects can last up to three days.
GlaxoSmithKline has set the price of Shingrix at $280 for the required two shots compared to Merck’s one-shot Zostavax that costs $223. Most insurance plans will likely cover the shingles vaccine, but Medicare might be an issue.
The Not So Good News:
From the Canadian product monogram:
Immunocompromised (IC) individuals (≥50 years of age): There are limited data available on the use of SHINGRIX in immunocompromised adults 50 years of age or older.
Here is what little data there are:
Immunocompromised (IC) subjects
In the 164 IC subjects studied who either had a history of an Autologous Haematopoietic Cell Transplant (HCT) and HIV infection, no safety concerns were identified as evaluated one year post-vaccination.
So how do the experts feel about this?
The Washington Post interviewed Dr. Edward Belongia, who chaired the shingles vaccine work group of the ACIP that just approved the vaccine.
Here is the part of that interview that is critical for the CLL community
Q: Can people with compromised immune systems get Shingrix?
A: At this point, the license is for prevention in people ages 50 and older, with normal immune systems. But there are studies underway, and over the next year we expect to be looking at results that have the potential to be helpful for this population.
Actually the PI in the USA and the monogram in Canada are both mute on giving the vaccine to those with depressed immunity. Even if they did say something, doctors could always give drugs off label. But doctors tend to stick with recommendations around vaccines, and insurance may not pay for a non-recommended treatment.
In fact, we have no data that it is effective. We know we don’t respond well to other vaccines.
Antivirals such as acyclovir taken daily as prophylaxis can help many avoid shingles and they are safe and inexpensive and been around for decades
My Bottom Line:
First, I would strongly recommend Shingrix for the appropriate family members of those of us with CLL, not that we could catch shingles from a loved one. We can’t. Rather we want them to be protected and it is a great vaccine. And we don’t want them to potentially endanger us in the process by getting a live vaccine.
My bet is that the vaccine will soon be recommended for the immune-compromised, including chronic lymphocytic leukemia.
There isn’t much downside to getting the two shots now, but I wouldn’t rush. I want to wait to see if there are any surprises in the real world data.
Brian Koffman, MD 11/7/17