The new shingles vaccine about to be released in the US by Merck-the single-dose drug that is supposed to halve cases of shingles in the over-60s-not only doesn't work very well in anyone over 70, but may also increase the risk of serious heart conditions.
The study on which the US Food and Drug Administration (FDA) based its unanimous approval in May this year showed a small rise in congestive heart failure and heart attack.
Other rare, but serious, side-effects include worsening of asthma, polymyalgia rheumatica (stiffness and pain in the shoulder, neck and trunk muscles), an anaphylactic response including swelling, wheezing or diffi-culty breathing) and a rash that suspiciously resembles shingles.
Zostavax is targeted at those aged 60 and older to prevent shingles, which is caused by the same virus that causes chickenpox. The herpes zoster virus lies dormant in the nervous sys-tem in anyone who has had chicken-pox. At times of stress, it can re-activate to cause pain before, during and after a rash. On rare occasions, herpes zoster can cause pneumonia, encephalitis, visual impairment, loss of hearing and even death.
In the Shingles Prevention Study, the single large-scale study on which the FDA based its approval, nearly 40,000 volunteers, aged 60 or older, were given either a single dose of the vaccine or a placebo, then followed for an average of three years to see who developed shingles. The study excluded those who had compromis-ed immunity, were using steroids or had a history of herpes zoster, as well as those who experienced side-effects that might have confounded evalua-tion of the drug's effects.
The study found that the vaccine was, overall, only 51-per-cent effective in preventing shingles-and mostly only in those aged 60-69 years (N Engl J Med, 2005; 352: 2271-84). Its efficacy plummeted in those aged 70 and over, with only 41-per-cent effective-ness in the 70-79 age group and only 18-per-cent efficacy in those aged over 80.
Although the vaccine roughly halved the cases of shingles among the entire study population, nearly 2 per cent, or 315, went on to develop shingles despite being vaccinated. Also, of those who developed shingles, the vaccine did nothing to prevent its usual painful effects. Indeed, virtually the same percentage reported neural-gia (pain) that lasted for virtually the same length of time as in those in the placebo group who'd developed the condition.
In addition, similar percentages in both groups reported ophthalmic zoster, peripheral nerve palsies, scarring, extreme pain and sensitivity to touch or brushing, and spreading. Only impaired vision was significantly improved in the placebo group.
What's more, within the 42-day post-vaccination period, 53 of those vaccinated reported a zoster-like rash, compared with 36 of those taking the placebo. The Merck strain was found in two of those who had the rash.
A similar number of people reported serious side-effects in each study group. However, a subgroup study involving some 7000 volunteers found that the vaccine caused a third more side-effects. In fact, within this subgroup, more serious cardiovasc-ular events occurred more frequently in those given Zostavax than in those given the placebo.
Indeed, 51 of the approximately 3500 (1.5 per cent) individuals who received the Zostavax jab developed either congestive heart failure or pulmonary oedema, compared with 30 (1.2 per cent) of those given a placebo. In addition, of the more than 21,000 individuals given the vaccine, 58 (0.3 per cent) developed conges-tive heart failure or pulmonary edema, compared with 46 (0.2 per cent) of those receiving the placebo.
Besides cardiac events, the vaccine was definitely linked to worsening of asthma and polymyalgia rheumatica and, in rare instances, to pneumonitis and meningoencephalitis. There were also reported cases of arthralgia and myalgia. The number of deaths was similar in both study groups.
On top of all this bad news, certain questions still remain concerning the statistical methods used in the trial. For example, why were 45 subjects excluded from the final analysis-including 24 who had developed herpes zoster within 30 days of being vaccinated? Also, why did the follow-up time vary so widely from 31 days
to nearly five years?
For all the potential side-effects, Merck freely admits that Zostavax may not fully protect everyone who has it. It is also contraindicated in those who are allergic to any of its ingredients, including the antibiotic neomycin, as well as in those with weakened immune systems, those taking high doses of steroids and in women who are pregnant or planning to become so.
Zostavax is not yet available in the UK; as for its potential to cause cancer, it's a question that Merck has yet to answer.
Other minor side-effects
- Injection-site reactions, including pain, redness, swelling, itching or bruising
- Increased respiratory infections such as the common cold, fever and flu-like symptoms
- Stuffy or runny nose.
Vol. 20 05 August 2009