Post-hoc analysis of injection-site reactions following vaccination with quadrivalent human papillomavirus vaccine in Japanese female clinical trial participants

Abstract

Aim The quadrivalent human papillomavirus (4vHPV) vaccine has demonstrated efficacy and immunogenicity and was generally well tolerated in clinical trials conducted in Japan. We report a detailed safety analysis of injection-site reactions in female Japanese 4vHPV clinical trial participants. Methods This post-hoc analysis included data from 2 double-blind, placebo-controlled phase II clinical trials of a 3-dose (Day 1, Month 2, Month 6) regimen of 4vHPV vaccine in Japanese young women aged 18–26 years (N = 1021; NCT00378560) and girls aged 9–17 years (N = 107; NCT00411749). Injection-site and systemic adverse events (AEs) were monitored using vaccination report cards for 15 days after each vaccine dose; serious AEs were reported throughout the trials. Post-hoc analyses of data from these trials were performed to examine details of injection-site AEs, including day of onset, time from onset to resolution, and maximum intensity. Results Injection-site AEs were reported by 85.6% of 4vHPV vaccine recipients and 72.4% of placebo recipients, most commonly erythema, pain, pruritus, and swelling (each >5% of 4vHPV vaccine recipients). The majority of injection-site AEs had an onset within 3 days of vaccination and were mild to moderate in intensity; few 4vHPV vaccine recipients reported severe injection-site AEs (2.0% overall). All injection-site AEs resolved, and most (4vHPV: 87.5%; placebo: 92.7%) resolved within 5 days of onset. Conclusions Most injection-site reactions are mild or moderate in intensity and of short duration. The 3-dose regimen of 4vHPV vaccine is well tolerated in Japanese female clinical trial participants based on this post-hoc analysis. These results will further support safety communication between healthcare providers and vaccine recipients regarding the HPV vaccine. Trial registration Clinicaltrials. gov: NCT00378560 and NCT00411749.

The comparative safety of human papillomavirus vaccines: A Bayesian network meta‐analysis

“…Among the 23 included RCTs, all claimed to have used the exact randomized controlled procedures, but eight studies had an unclear risk of bias due to inadequate reporting of the random sequence generation 8,24,29,30,39,40,42,43 and eight studies showed inadequate reporting of allocation concealment. 7,8,26,30,34,40,42,43 In addition, two studies did not explain how participants and personnel were blinded, 30,34 and 11 did not explain how the outcome assessment was blinded. 25,[27][28][29][30][31]33,38,[40][41][42] The outcome data of one study were incomplete, 28 and there was an unclear risk of bias on the selectivity reports of 11 studies.…”

“…The details of the study selection process are presented in Figure 1. After screening 1985 titles and abstracts and 198 full‐text articles, 23 trials that met our eligibility criteria were finally assessed 6–8,24–43 . All studies were two‐arm, RCTs.…”

“…After screening 1985 titles and abstracts and 198 full-text articles, 23 trials that met our eligibility criteria were finally assessed. [6][7][8][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43] All studies were two-arm, RCTs.…”

“…8,39,41 All studies were published between 2004 and 2020, involving a total of 52 129 healthy women, with an age range of 9-45 years. Ten of the 23 trials were conducted in a single country 27,29,[32][33][34][35]37,38,42,43 and the rest in multiple countries. [6][7][8][24][25][26]28,30,31,36,[39][40][41] All HPV vaccines or placebos used in the studies contained aluminum adjuvants, except for one study that used normal saline.…”

Vaccines

“…This suspension resulted in sharp declines in HPV vaccination (rate 14.3%) in Japan ( Nakagawa et al, 2020 ) [R]. While HPV has been shown effective and safe (minimal SAE and AE) ( Murata et al, 2020 ), Japan has not changed its official position ( Bodily et al, 2020 [r]; Ueda et al, 2020 [R]).…”