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The Pfizer COVID-19 vaccine was shown to be highly effective in a large trial, but clinicians will be waiting and watching for reactions and adverse events in their vaccinated patients.
A two-dose regimen of the BNT162b2 mRNA COVID-19 vaccine was found to be safe and 95% effective in preventing SARS-CoV-2 infection in persons aged 16 years and older, according to an ongoing phase 2/3 trial. Pfizer and BioNTech published safety and efficacy results from the landmark global phase 1/2/3 trial of their COVID-19 vaccine candidate in the New England Journal of Medicine.
"We previously reported phase 1 safety and immunogenicity results from clinical trials of the vaccine candidate BNT162b2," lead author Fernando P. Polack, MD, of Vanderbilt University, Nashville, Tenn., and colleagues wrote. "This data set and [present] trial results are the basis for an application for emergency-use authorization," they explained.
The BNT162b2 Vaccine Trial
Among 43,448 individuals aged 16 years and older, the efficacy, safety, and immunogenicity of the BNT162b2 vaccine candidate was evaluated in a continuous phase 1/2/3 study. Participants were randomly assigned (1:1) to receive two injections of either 30 mcg of BNT162b2 (n = 21,720) or saline placebo (n = 21,728) administered intramuscularly 21 days apart. The safety evaluation, where subjects were monitored 30 minutes post vaccination for acute reactions, was observer blinded.
Eligibility criteria included healthy individuals or those with stable chronic medical conditions, including viral hepatitis B and C, as well as human immunodeficiency virus. Persons with a diagnosis of an immunocompromising condition, those receiving immunosuppressive therapy, and individuals with a medical history of COVID-19 were excluded.
The first primary endpoint was efficacy of BNT162b2 against laboratory-confirmed COVID-19 with onset at least 7 days following the second dose. The primary safety endpoint was local and systemic reactions occurring within 7 days post injection of BNT162b2 or placebo.
"At the data cutoff date of Oct. 9, a total of 37,706 participants had a median of at least 2 months of safety data available after the second dose and contributed to the main safety data set," the authors wrote.
Among these participants, 83% were White, 28% were Hispanic or Latinx, and 9% were Black or African American; 49% of subjects were female and the median age was 52 years, with 42% over aged 55 years.
Overall, BNT162b2 had a favorable safety profile. Mild to moderate pain at the injection site within 7 days after the injection was the most frequently reported local reaction (<1% across all age groups reported severe pain). Most local reactions resolved within 1-2 days and no grade 4 reactions were reported.
The investigators reported: "Fever (temperature, ≥38° C) was reported after the second dose by 16% of younger vaccine recipients and by 11% of older recipients. Only 0.2% of vaccine recipients and 0.1% of placebo recipients reported fever (temperature, 38.9-40° C) after the first dose, as compared with 0.8% and 0.1%, respectively, after the second dose."
BNT162b2 recipients had more injection-site pain than those receiving the placebo. After the first and second doses, younger recipients (under 55 years) had more pain at the injection site (83 vs. 14 and 78 vs. 12 events, respectively), redness (5 vs. 1 and 6 vs. 1), and swelling (6 vs. 0 and 6 vs. 0), compared with placebo recipients.
The same trend was observed for patients aged over 55 years, with vaccine recipients reporting more pain at the injection site (71 vs. 9 and 66 vs. 8 events, respectively), redness (5 vs. 1 and 7 vs. 1), and swelling (7 vs. 1 and 7 vs. 1) than placebo recipients.
Pain was less common overall among vaccine recipients aged over 55 years (71% reported pain after the first dose; 66% post second dose) than among younger vaccine recipients (83% post first dose; 78% post second dose).
The most common systemic events following the second dose were fatigue and headache, which occurred in 59% and 52% of younger vaccine recipients and 51% and 39% of older vaccine recipients, respectively. But fatigue and headache were also reported by participants in the placebo group (23% and 24%, respectively, post second dose, among younger vaccine recipients; 17% and 14% among older recipients).
The incidence of serious adverse events was low and similar in the vaccine (0.6%) and placebo (0.5%) arms. Severe systemic events occurred in 2% or less of vaccine recipients following either dose, except for fatigue (3.8%) and headache (2.0%) post second dose. No deaths were considered to be vaccine or placebo related.
"The safety appears comparable to other vaccines, but the relatively short period of observation, 2 months, and the relatively small number of subjects who have received the vaccine (less than 30,000), compared to the hundreds of millions likely to ultimately receive the vaccine, precludes conclusions regarding the potential for rare long term adverse effects," David L. Bowton, MD, FCCP, a pulmonologist and professor emeritus of critical care anesthesiology at Wake Forest University, Winston-Salem, N.C., said in an interview. "Clinicians should be aware of the risk of anaphylactic reactions and discuss it with their patients [who have] a history of these reactions."
Among 36,523 subjects without evidence of existing or prior COVID-19 infection, 8 cases of COVID-19 with onset at least 7 days after the second dose were seen among vaccine recipients and 162 among placebo recipients, corresponding to 95.0% vaccine efficacy (95% credible interval, 90.3%-97.6%).
"Supplemental analyses indicated that vaccine efficacy among subgroups defined by age, sex, race, ethnicity, obesity, and presence of a coexisting condition was generally consistent with that observed in the overall population," the authors wrote.
Between the first and second doses, 39 cases of COVID-19 were observed among BNT162b2 recipients and 82 cases among placebo recipients, corresponding to 52% vaccine efficacy during the 21-day interval (95% CI, 29.5%-68.4%) suggesting early protection may begin as soon as 12 days after the first injection.
"This is an incredible achievement given that an effective vaccine has never been developed and approved for use in such a short timeframe," Bowton explained. "That the vaccine is highly effective in reducing the incidence of symptomatic COVID-19 seems incontrovertible."
"This vaccine has shockingly amazing efficacy and is well tolerated, and the results are beyond even optimistic projections," Douglas S. Paauw, MD, of the University of Washington, Seattle, said in an interview.
"It is not yet known if the vaccine prevents asymptomatic infections, with their attendant risk of contagion, as rates of seroconversion of trial participants against betacoronavirus nucleoproteins not included in the vaccine has not been reported," Bowton commented.
"Common questions our patients will ask us remain unanswered for now, [including] how long will the protection last, is it safe in pregnant women, and does it prevent asymptomatic infection," Paauw explained. "We do not know everything about longer term side effects, but the benefits of this vaccine appear to outweigh the risks of the vaccine."
The researchers noted these and other limitations in their report, acknowledging that longer follow-up is needed to evaluate long-term safety of the vaccine.
This study was supported by BioNTech and Pfizer. Several authors disclosed financial relationships with Pfizer and other pharmaceutical companies outside the submitted work. Bowton and Paauw had no conflicts to disclose.
SOURCE: Polack FP et al. N Engl J Med. 2020 Dec 10. doi: 10.1056/NEJMoa2034577
This article originally appeared on MDedge.com, part of the Medscape Professional Network.
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Cite this: COVID-19 Vaccine Found Effective but Doctors Watching for Reactions, Adverse Events - Medscape - Dec 22, 2020.