FDA approves new zoster vaccine

 The FDA just approved a second herpes zoster vaccine for adults aged >50. There is no formal FDA announcement, just one by the manufacturer (see https://www.gsk.com/en-gb/media/press-releases/shingrix-approved-in-the-us-for-prevention-of-shingles-in-adults-aged-50-and-over/ ).

Details:

--Shingrix (Zoster Vaccine Recombinant, Adjuvanted) was approved for the prevention of zoster in adults aged 50 or older

--the vaccine is a non-live vaccine, administered intramuscularly in 2 doses

--this vaccine was approved in Canada for people over 50yo in October 2017

Relevant recent studies: (both done by the same research group and drug-company supported)

1. Lal, H. N Engl J Med 2015; 372:2087

    --15,411 people from 18 countries were randomized to a subunit vaccine containing varicella-zoster virus glycoprotein E and the AS01_B adjuvant system (called HZ/su), vs placebo. 

    --During followup of 3.2 years, herpes zoster infection was confirmed in 6 of those in the vaccine group vs 210 in the controls (incidence rate of 0.3 vs 9.1 per 1000 person-yrs), a 97.2% efficacy, which was evident in all age groups involved (50-59, 60-69, >70). 

    --adverse events: within 7 days of vaccination, 84.4% had some reported adverse event vs 37.8% in controls​. 17% of vaccine vs 3.2% of controls had grade 3 adverse symptoms (severe enough to prevent normal daily activities): 9.5% with injection site pain, 11.4% with systemic reactions (myalgia, fatigue, headache, shivering, fever, GI sx)

2. Cunningham AL. N Engl J Med 2016; 375: 1019-31

    --same vaccine as above, for 13,900 people aged >70 (mean age 75.6) in the same countries as above and followed 3.7 years

    --herpes zoster occurred in 23 vaccine recipients and 223 placebo (0.9 vs 9.2/1000 person-yrs), with efficacy of 89.8%, similar in patients 70-79 (90% efficacy) and >80yo (89%). 

    --vaccine was also 89% effective against postherpetic neuralgia (defined as "a worst pain score for pain that persisted or developed more than 90 days after the onset of herpes zoster rash"). 

    --adverse events: within 7 days of vaccination, 79% having some reported adverse event vs 29.5% in controls. 11.9% of vaccine vs 2.0% of controls had grade 3 adverse symptoms (severe enough to prevent normal daily activities): 8.5% with injection site pain, 6.0% with systemic reactions (myalgia, fatigue, headache, shivering, fever, GI sx).​

Commentary:

--more than 90% of people have been previously infected with varicella-zoster

--the CDC estimates the zoster rate to be 4 cases/1000 in the US, but 10 cases/1000 in those >60yo (and 1-4% get hospitalized, 30% in those immunocompromised)

--the incidence of post-herpetic neuralgia increases with age (>30% in  those >80yo), which can be disabling and typically requires meds that are less-well tolerated in the elderly (tricyclics, gabapentenoids, etc)

--and a Mayo Clinic study found that of 1669 patients with documented zoster, 95 had 105 recurrences after a follow-up of 7.3 years.

--but there are a couple of lingering concerns about this new vaccine: 

    --is it durable? (we have clinical data from only <4 years after vaccination)

    ​--and it is always better to have more than one group study a new drug or vaccine, especially in a drug-company sponsored study where the allegiances may not be with public health over drug company profits (and a vaccine like this one will undoubtedly cost a lot and potentially be used lots in our increasingly aging population).

so,

--we are awaiting the CDC's Advisory Committee on Immunization Practices to convene soon to issue their recommendation on the use of this new vaccine

--but, the data from the above studies are pretty impressive (and many of us have been holding off on giving the old vaccine, given the impressive efficacy of this new one).  the only other vaccine (Zostavax) was much less effective: around 67% for preventing post-herpetic neuralgia, 51% against zoster (and varied by age: 64% in those 60-69, 18% in those >80yo; see Gabutti G. J Prev Med Hyg 2014; 55(4): 130-6; another study found 38% efficacy in those >70yo).  And Zostavax is a live, attenuated virus vaccine, with its attendant issues (eg including not using the vaccine in those immunologically compromised and is associated with occasional cases of clinical herpes zoster even in an immunocompetent person)

--so, i suspect that the new vaccine will be approved and embraced by the feds. And most likely will benefit many more people than the old vaccine.