most of which cannot be definitively tied to the vaccine, according to two large studies published simultaneously in Pediatrics.
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“The body of evidence on the safety of 9vHPV now includes prelicensure clinical trial data on 15,000 study subjects, reassuring results from postlicensure near real-time sequential monitoring by the Centers for Disease Control and Prevention’s Vaccine Safety Datalink, on approximately 839 000 doses administered, and our review of VAERS [Vaccine Adverse Event Reporting System] reports over a 3-year period, during which time approximately 28 million doses were distributed in the United States,” Tom T. Shimabukuro, MD, and colleagues reported in Pediatrics.
James G. Donahue, PhD, and colleagues, authors of the Vaccine Safety Datalink study published in the same issue, concluded much the same thing.
The new numbers bolster extant safety data on the vaccine, which was approved in 2015, wrote Dr. Donahue, an epidemiologist at the Marshfield (Wis.) Clinic Research Institute, and coauthors. “With this large observational study, we contribute reassuring postlicensure data that will help bolster the safety profile of 9vHPV. Although we detected several unexpected potential safety signals, none were confirmed after further evaluation.”
The Vaccine Safety Datalink study of 838,991 doses looked for safety signals in a prespecified group of potential events, including anaphylaxis, appendicitis, Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, pancreatitis, seizures, stroke, and venous thromboembolism.
Dr. Donahue and coauthors used real-time vaccination data and time-matched historical controls to evaluate any changes in expected disease rates, compared with those occurring in vaccine recipients.
Most doses in the study (76%) were given to children aged 9-17 years, with 48% going to girls. The remaining 24% of doses were given to persons aged 18-26 years, with 64% going to women.
The analysis found potential safety signals in allergic reactions (43 cases), appendicitis (30 cases), pancreatitis (8 cases), and syncope (67). None of these were confirmed after further investigation.
“The safety profile of 9vHPV is favorable and comparable to that of its predecessor, 4vHPV,” Dr. Donahue and associates concluded.
The VAERS analysis was similarly reassuring. It examined all reported adverse events, not predetermined events.
Among 28 million doses, there were 7,244 adverse event reports – a rate of about 1 event per 7 million doses. Of these, 97% were nonserious, wrote Dr. Shimabukuro, deputy director of the CDC’s Immunization Safety Office, and colleagues.
The vaccine manufacturer submitted 64% of these to VAERS; health care providers submitted 27%. Adverse events were reported from postvaccine day 0 to 2 years afterward. 9vHPV was the only vaccine given in 75% of reports. Coadministered vaccines included meningococcal conjugate (1,028); tetanus and diphtheria (Td) or Tdap (673); and hepatitis A (434).
There were nine reports of anaphylaxis (five males, four females); 9vHPV was the only vaccine administered in five cases. Three reports involved coadministration of meningococcal vaccine, two with hepatitis A, one with TDaP, and one with varicella.
There were eight reports of Guillain-Barré.
There were 17 reports of postural orthostatic tachycardia syndrome, most of which (71%) did not meet diagnostic criteria. Five cases, however, did.
One possible case of complex regional pain syndrome was reported in a 13-year-old girl with comorbid anxiety.
There were two reports of acute disseminated encephalomyelitis, both in boys. There were no reports of transverse myelitis or chronic inflammatory demyelinating polyneuropathy.
Seven vaccine recipients died after vaccination. Five of these reports did not contain medical information or any proof-of-death confirmation. The other two were verified by autopsy. A 14-year-old girl who received a flu vaccination with 9vHPV died of a thoracic aorta dissection 7 days postvaccination. The other death was a 16-year-old boy who received a concurrent hepatitis A vaccine. Four days later, he died of a cerebellar hemorrhage.
“We did not identify any unusual or unexpected safety concerns in our review of 9vHPV reports to the VAERS; most (97%) reports were nonserious, and adverse events were analogous to those observed in the prelicensure clinical trials,” Dr. Shimabukuro and associates concluded.
Neither Dr. Shimabukuro nor Dr. Donahue had financial disclosures. Dr. Donahue’s study was funded by the Centers for Disease Control and Prevention. One coauthor had ties to several pharmaceutical companies. Dr. Shimabukuro’s study had no external funding. One coauthor is employed by Merck, but was not at the time of the study.
SOURCES: Shimabukuro T et al. Pediatrics. 2019 Nov 1. doi: 10.1542/peds.2019-1791; Donahue J et al. Pediatrics. 2019 Nov 1. doi: 10.1542/peds.2019-1808.