Tag Archives: Sanofi

Should You Choose The High-Dose Flu Vaccine?

Between patients last week the skeptical cardiologist skipped over to the employee health office at St. Luke’s and requested he be given a flu shot.

To my surprise, I was given a choice between a “high dose” flu shot which was “recommended for individuals 65 and older” and the regular quadrivalent flu vaccine.

I hadn’t been aware of this “high dose” flu shot previously thus had not had a chance to research it.  My time was limited and I decided to go with the high dose flu vaccine hoping that high dose did not also mean more chance for side effects.

Fortunately, I had no side effects and thus far have not contracted the flu.

Influenza More Deadly In Elderly But Vaccine Less Effective

Influenza, of course, is a huge killer which causes around 36,000 deaths per year in the United States. We adults 65 and older particularly vulnerable to complications of influenza and we are the ones that account for most of the more than 200,000 hospitalizations per year from the disease.

Hospital cardiology consultations typically spike during flu season as a bad case can worsen heart failure or trigger heart attacks and arrhythmias.

Although vaccination is the most effective intervention against influenza and associated complications, older individuals mount a lower antibody response to the vaccine compared to younger individuals.

Fluzone HD: High Dose Antigen Which Increases Antibody Reponse

To improve protect strategies to improve antibody responses to influenza vaccine in the older population, such as increasing the amount of antigen in the vaccine have been developed.

The vaccine I received is called Fluzone HD and is manufactured by the French pharmaceutical company Sanofi. It is a high-dose, trivalent, inactivated influenza vaccine (IIV3-HD) and contains four times as much hemagglutinin (HA) as is contained in standard-dose vaccines.

AFter studies demonstrating an acceptable safety profile and superior immunogenicity as compared with a standard-dose vaccine, IIV3-HD was licensed for use in the United States in December 2009,

Studies Show Improved Relative Efficacy Of Fluzone Compared to Standard Dose Flu Vaccine

A study published NEJM in 2014 proved the clinical superiority of Fluzone. It has a relative efficacy compared to standard vaccines of around 24%.

The CDC summarizes it as follows

Fluzone High-Dose (HD-IIV3) met prespecified criteria for superior efficacy against laboratory-confirmed influenza to that of SD-IIV3 in a randomized trial conducted over two seasons among 31,989 persons aged ≥65 years, and might provide better protection than SD-IIV3 for this age group . For the primary outcome (prevention of laboratory-confirmed influenza caused by any viral type or subtype and associated with protocol-defined ILI), relative efficacy of HD-IIV3 compared with SD-IIV3 was 24.2% (95% CI = 9.7–36.5%).

Subsequent studies have provided further support for the improved efficacy of Fluzone according to the CDC:

These findings are further supported by results from retrospective studies of Centers for Medicare and Medicaid Services (CMS) and Veterans Administration data, as well as a cluster-randomized trial of HD-IIV3 versus SD-IIV among older adults in nursing homes  A meta-analysis reported that HD-IIV3 provided better protection than SD-IIV3 against ILI (relative VE = 19.5%; 95% CI = 8.6–29.0%); all-cause hospitalizations (relative VE = 9.1%; 95% CI = 2.4–15.3); and hospitalizations due to influenza (relative VE = 17.8%; 95% CI = 8.1–26.5), pneumonia (relative VE = 24.3%; 95% CI = 13.9–33.4), and cardiorespiratory events (relative VE = 18.2%; 95% CI = 6.8–28.1)

Should You Choose Fluzone?

Most likely, now that I have had a chance to look in detail at the studies supporting Fluzone HD for the elderly and review the CDC recommendations, I would choose it for myself for  vaccination this year.

This is not a slam dunk decision and the CDC is actually quite wishy washy in its recommendations basically saying any formulation of vaccine is OK with them

For persons aged ≥65 years, any age-appropriate IIV formulation (standard-dose or high-dose, trivalent or quadrivalent, unadjuvanted or adjuvanted) or RIV4 are acceptable options.

As the CDC points out, we need more studies comparing these different flu vaccines to help guide decision-making.

Skeptically Yours,

-ACP

Addendum. Dr. Chelsea Pearson, the prominent St. Louis internist,tells me she recommends Fluzone or Flublok to her patients 65 or older.

Flublok is a quadrivalent recombinant vaccine of standard dosage.

A head to head comparison of these two vaccines would be nice to help patients and physicians decide which to take.

Cost was not an issue in my decision but a year ago Canadian health officials felt the five-fold greater cost of flu zone HD was not warranted (see here.)

N.B. Be aware there is a quadrivalent flu vaccine from Sanofi also called fluzone.  From the FDA:

Tradename: Fluzone, Fluzone High-Dose and Fluzone Intradermal
Manufacturer: Sanofi Pasteur, Inc (for Fluzone High-Dose and Fluzone Intradermal only)
Indication:

  • Fluzone is indicated for active immunization of persons 6 months of age and older against influenza disease caused by influenza virus subtypes A and type B contained in the vaccine.
  • Fluzone High-Dose is indicated for active immunization of persons 65 years of age and older against influenza disease caused by influenza virus subtypes A and type B contained in the vaccine.
  • Fluzone Intradermal indicated for active immunization for use in adults 18 through 64 years of age against influenza disease caused by influenza virus subtypes A and type B contained in the vaccine.

 

Dupixen Has Miraculously Cured My Eczema

Although this post is most unskeptical and decidedly noncardiac, the skeptical cardiologist feels compelled to share this information with readers who have or know friends or family with eczema or atopic determatitis, a chronic skin condition that results in itchy, scaly, dry and red skin.

For most of my life I have dealt with periodic flare-ups of eczema along with continuously itchy skin . Control of flare-ups was by meticulous attention to keeping my skin clean and moisturized along with frequent applications of topical corticosteroids.

Things worsened a few years ago and I began to think I might have Red Skin Syndrome, which some dermatologist believe is due to withdrawal from topical corticosteroids.

Two months ago, however, my spirits brightened when I heard that the FDA had approved a new biologic injectable called Dupixent (dupilumab), to treat adults with moderate-to-severe eczema (atopic dermatitis), whose eczema is not controlled adequately by topical steroids.

My fantastic dermatologist, Dr. Amy Ney, agreed this was appropriate therapy for me, and within a week I received a refrigerated package containing the initial dosage: two syringes filled with the drug.

The pre-loaded syringe filled with Dupixent. The syringes come with very detailed instructions to guide you through the process of injecting the liquid into either the abdominal region or the thighs.

 

Within a week of injecting the contents of the syringes into my abdomen, my itching ceased and I had no more eczematous rashes. For me this was a minor miracle.

Since then I’ve injected one 300 mg syringe every two weeks and I continue to be free of my life-long signs and symptoms of eczema.

Atopic Dermatitis and Dupixent

The cause of atopic dermatitis is a combination of genetic, immune and environmental factors. In atopic dermatitis, the skin develops red, scaly and crusted bumps, which are extremely itchy. Scratching leads to swelling, cracking, “weeping” clear fluid, and finally, coarsening and thickening of the skin.

Dupixent’s active ingredient is an antibody (dupilumab) that binds to a protein [interleukin-4 (IL-4) receptor alpha subunit (IL-4Ra)], that causes inflammation. By binding to this protein, Dupixent is able to inhibit the inflammatory response that plays a role in the development of atopic dermatitis.

Dupixent acts by inhibiting two cytokines that are responsible for the hyperimmune response in skin. They are called IL-4 and IL-13. IL is an abbreviation for interleukins, proteins that are produced by leukocytes (3) and play a part in regulation of the immune system. Steroids, such as prednisone, also suppress the immune system, but taking them for an extended period of time will get you into trouble. (See: Prednisone: Satan’s Little Helper) Unlike prednisone, Dupixent inhibits specific targets. It works more like a scalpel than a bomb.

More Stories of Miraculous Relief

I am not alone in experiencing miraculous relief from this new drug. I first heard of it from a  New York Times article in 2016 which details the dramatic responses of several patients who were involved in the clinical trials that proved the drug’s efficacy:

One participant in the trial, Lisa Tannebaum, a 53-year-old harpist in Stamford, Conn., was so thrilled that she wrote a letter to Regeneron suggesting they use her before and after photographs in advertisements. She developed a severe form of the disease 14 years ago and tried everything imaginable in conventional and alternative medicine without relief — specialized diets, immunosuppressive drugs, special clothing, bleach baths. She even had the gold fillings removed from her teeth on the theory that they may be causing an allergic response, but to no avail.

“It was like every day I had poison ivy and fire ants on myself,” she said. “You don’t sleep at all. You can’t go out, you have staph infections all the time,” because the skin’s protective barrier is broken by the rash. “I couldn’t drive my kids to school because the itching was so bad I couldn’t put my hands on the steering wheel.”

Now, she is performing again and will be playing her harp at Carnegie Hall on Oct. 30.

Randomized Controlled Trials Proving Efficacy

Of course we can’t rely on anecdotes to prove the safety and efficacy of drugs: we need randomized, controlled, double-blind studies.

Dupixent has three such clinical trials with a total of 2,119 adult participants, and the results were remarkable. (for details see here). Overall, participants who received Dupixent achieved greater response, defined as clear or almost clear skin, and experienced a reduction in itch after 16 weeks of treatment.

Panel A shows the proportions of patients with the primary end point (both a score of 0 or 1 [clear or almost clear] on the Investigator’s Global Assessment [IGA; scores range from 0 to 4, with higher scores indicating more severe disease] and a reduction from baseline of 2 points or more on the IGA at week 16) among patients who received dupilumab every week, dupilumab every other week, or placebo in SOLO 1 and SOLO 2. Panel B shows the proportions of patients with the key secondary end point (which was considered to be a coprimary end point by regulators in the European Union and Japan) of an improvement from baseline of at least 75% on the Eczema Area and Severity Index (EASI-75) at week 16 in the two trials. P<0.001 for all comparisons between dupilumab and placebo. For binary end points, patients who received rescue medications or withdrew from the study were categorized as having had no response, as were those with all other missing values.
The only side effect which was more common with Dupixent than placebo was conjunctivitis, an inflammation of the eye.

Cost of Dupixent

When I first read of this drug I assumed it would be horribly expensive. In cardiology we have two injectable biologics (Repatha and Praluent, PCSK9 inhibitors) for lowering cholesterol, which typically have been costing my patients with insurance coverage over 1000$ per month.

Fortunately Sanofi/Regeneron have learned from prior experience and priced the drug at $37,000, a number that insurance companies have apparently warmly welcomed. This article suggests that the drug is priced significantly lower than newer biologics now available for psoriasis and rheumatoid arthritis.

With my  insurance (United Health Care) coverage I was asked to pay 150$ for 2 injections per month.

I then discovered that Sanofi has a co-pay card that covers that 150$ so that for now I am paying zero dollars out of the 37,000$.

I’m paying nothing for a brand new biologic injectable that has cured my eczema. Now that is miraculous!

Unskeptically Yours,

-ACP

N.B. Featured Image before and after hand is from National Eczema organization and is not of my hand.