June 15, 2007 • www.internalmedicinenews.com Infectious Diseases 35 New Smallpox Vaccine Backed for High-Risk Needs

BY ELIZABETH MECHCATIE that magnitude associated with other vac- which was developed under a contract In a second study of people aged 31-84 Senior Writer cines, emphasized Dr. Jack Stapleton, pro- with the Centers for Disease Control and years who had been vaccinated against fessor and director of infectious diseases at Prevention for stockpiling purposes. In smallpox, however, the take rate was 84% G AITHERSBURG, MD . — A more the University of Iowa, Iowa City. fact, Acambis has already supplied 192.5 among those who received ACAM2000, modern version of the smallpox vaccine If this were a vaccine being considered for million doses to the U.S. Strategic Na- compared with 98% of those who re- appears to be safe and effective enough to routine use in the general population, the tional Stockpile, according to the compa- ceived Dryvax. use “where it is determined that there is a risk of myocarditis ny. There is a limited The majority of side effects were inoc- high risk of exposure to smallpox virus,” seen in clinical trials The new vaccine is derived supply of Dryvax re- ulation site reactions and systemic symp- according to a Food and Drug Adminis- would be unaccept- maining, which is it- toms, including vaccine site pain, lymph tration advisory panel. able, added Dr. Mon- from the currently licensed self reserved for the node pain, headache, fatigue, and myalgia. At a meeting, members of the FDA’s ica Farley, professor of Dryvax using modern cell military and labora- In both studies, participants were close- Vaccines and Related Biological Products medicine at Emory tory workers. ly monitored for myocarditis, which was Advisory Committee agreed that the University, Atlanta. culture techniques without The derivation of diagnosed in 10 naive recipients (7 of ACAM2000 vaccine should be submitted Some other well- animal serum, and is grown ACAM2000 from whom were in the ACAM2000 treatment to postmarketing studies that follow peo- documented compli- Dryvax uses modern group). The myocarditis cases occurred at ple who developed vaccine-associated my- cations of smallpox in a continuous cell line. cell culture tech- a mean of 11 days after receiving the vac- ocarditis and determine risk factors for vaccination that date niques without ani- cine and resolved in all but one case, ac- myocarditis. back to the era of routine smallpox vacci- mal serum. The vaccine is grown in a con- cording to Acambis. The vaccine, which is derived from Dry- nation include generalized vaccinia, tinuous cell line, which provides a In the study of people without prior vax, the currently licensed smallpox vac- eczema vaccinatum, postvaccinial en- predictable, standardized manufacturing vaccination, the rate of myocarditis was cine, is not being considered for use in the cephalitis, inadvertent inoculation, fetal process, according to Acambis. about one case per 145 vaccinations, which general population. Panelists emphasized vaccinia, and death. Dryvax was compared with ACAM2000 is higher than anticipated, according to the the nature of the situations in which the The panel was not asked to vote specif- in two multicenter, double-blind random- FDA. That study’s myocarditis rate was risk-benefit profile of ACAM2000 would ically on whether to approve the vaccine. ized studies of about 2,800 previously greater than the military’s rate, which a be considered favorable. The FDA typically follows the advice of its healthy adults. Those studies were de- Department of Defense official at the “This and Dryvax are the least-safe vac- advisory panels, although that advice is not signed to show that ACAM2000 was not meeting said has been about one case per cines that we will have licensed in this binding. inferior to Dryvax. 6,000 primary vaccinations. country, and we have to weigh that against If approved by the FDA, the vaccine In one study of people aged 18-30 years If the vaccine is approved, Acambis the risk of smallpox,” said the panel chair, would not be made available commer- who had never been vaccinated against would launch a Risk Minimization Action Dr. Ruth A. Karron, professor in the de- cially. Instead, it would be used for the na- smallpox, the “take rate” of a cutaneous Plan (RiskMAP). That would include edu- partment of international health at Johns tional vaccine stockpile and for military response—a generally accepted surrogate cation of vaccinees and health care Hopkins University, Baltimore. personnel deployed to areas of the world of protection—was 96% among those providers, expedited reporting of serious The rate of myocarditis—one in about where the threat of exposure to smallpox who received ACAM2000 and 99% among adverse events, and phase IV studies to as- every 150 vaccine recipients—was “far as a biologic weapon is considered high. those who received Dryvax, a difference sess the vaccine’s safety profile, long-term and above” any serious adverse event of Acambis Inc. manufactures the vaccine, indicating noninferiority. outcomes, and myocarditis risk factors. ■ Role of Flu Vaccination in Reducing Some Patients’ Memory Can Health Care Utilization Is Elusive Be Trusted on Tetanus Shots B ALTIMORE — In settings clinic of a large health care BY MIRIAM E. TUCKER Another study confounder is the outside of the flu season suggests with good access to care and organization were asked Senior Writer fact that the vaccine works better that “people who get the vaccine high immunization rates, ask- whether they had a Td boost- in some years than in others, a are high utilizers” year-round, Dr. ing patients whether they’ve er in the last 10 years. Of B ALTIMORE — Influenza vacci- phenomenon believed to be Baxter said. received a tetanus booster in those, 65.6% were able to an- nation is associated with lower caused at least in part by how good He and his associates compared the last 10 years is a fairly ac- swer either “yes” or “no.” rates of hospitalization and out- a “match” there is between the the data during each year’s in- curate way to determine if Comparison of their re- patient visits for flulike illness, but vaccine and the season’s circulating fluenza season with the off-sea- they need one, Dr. M. Hassan sponses with their charts only after statistical adjustment for strains. son control period of June 1-Aug. Murad and his associates said yielded high sensitivity the fact that people who get vac- Unadjusted, the rates of hospi- 31. This level of analysis revealed in a poster presentation at a (92.4%) and low specificity cinated are less healthy than are talization per 1,000 person-years that the difference in utilization conference on vaccine re- (26.5%). Accuracy of recall those who don’t, Dr. Roger P. Bax- during the influenza season ranged between vaccinated and unvacci- search sponsored by the Na- did not differ by age or gender, ter said at a vaccine research con- from 169/1,000 vaccinated vs. nated patients was even greater tional Foundation for Infec- Dr. Murad and his associates ference that was sponsored by the 159/1,000 unvaccinated in 2003- during the off-season than during tious Diseases. reported. National Foundation for Infectious 2004 (risk ratio 1.06 in favor of no influenza season, with a risk ratio Patients who answer “yes” The results from this study Diseases. vaccination), to 182/1,000 vs. of about 1.25 for each of the four are probably right and do not patient population are likely Raw data from Kaiser Perma- 150/1,000 in 2002-2003 (1.22 in fa- seasons. need readministration of the generalizable to those of oth- nente’s medical records of approx- vor of no vaccination). Dr. Baxter and his associates are vaccine. But those who say ei- er working-age adults of sim- imately 500,000 adults aged 65 and Even after adjustment for age, further analyzing the Kaiser data ther “no” or “I don’t know” ilar education level. “Since older during each of four consecu- gender, and three underlying di- to examine vaccine effectiveness in should receive a tetanus-diph- the results rely in significant tive influenza seasons showed that agnoses (diabetes, coronary artery younger, healthier people, as well theria (Td) booster as long as part on human memory of a hospitalization and outpatient visit disease, and heart failure), all of as adding mortality to the out- there are no contraindications, rare event—a once-every-10- rates were actually higher for those the values for the vaccine’s effec- comes and looking more closely at said Dr. Murad of the preven- years shot—they probably re- who received the influenza vaccine tiveness were negative, giving the the relationship between “good” tive medicine division of the flect useful information. ... than for those who didn’t, primari- counterintuitive impression that vs. “bad” vaccine matches in the Mayo Clinic, Rochester, Minn. The general characteristics of ly because the population is sicker. the vaccine actually causes disease. face of more or less virulent cir- Although previous studies our population are they were “People who get the flu vaccine The values were –8.4% for pre- culating influenza strains. Con- have demonstrated poor ac- mostly working age, educa- are less healthy and utilize the med- venting all hospital stays, –25.5% ducting such studies is “not easy,” curacy of patients’ recall of tion generally high school ical system much more than those for all pneumonia and influenza he noted. their last Td booster, this has graduate or greater, and near- who don’t get the vaccine. ... It’s a outpatient visits, –21.4% for other The Kaiser Permanente Vaccine not been evaluated previous- ly all have good access to rou- real confounder in all these stud- respiratory outpatient visits, and Study Center receives research ly in settings where immu- tine office care. That is prob- ies,” said Dr. Baxter, associate di- –23.3% for all respiratory visits, all grants from the influenza vaccine nization rates are high and ably similar to many [U.S.] rector of the Vaccine Study Center significant values. manufacturers Sanofi-Pasteur, good documentation is avail- office practices,” Dr. Murad at Kaiser Permanente, Oakland, But a second analysis that fo- GlaxoSmithKline, Novartis, and able. In this study, 572 pa- said in a follow-up interview. Calif. cused on health care utilization MedImmune. ■ tients of an employee health —Miriam E. Tucker