Investigating reports of complex regional pain syndrome: An analysis of HPV-16/18-adjuvanted vaccine post-licensure data

Huygen, Frank; Verschueren, Kristin; McCabe, Candida; Stegmann, Jens Ulrich; Zima, Julia; Mahaux, Olivia; Van Holle, Lionel; Angelo, Maria-Genalin

doi:10.1016/j.ebiom.2015.07.003

Investigating reports of complex regional pain syndrome: An analysis of HPV-16/18-adjuvanted vaccine post-licensure data

Huygen, Frank; Verschueren, Kristin; McCabe, Candida; Stegmann, Jens Ulrich; Zima, Julia; Mahaux, Olivia; Van Holle, Lionel; Angelo, Maria-Genalin

Authors

Frank Huygen

Kristin Verschueren

Candy McCabe Candy.Mccabe@uwe.ac.uk
Professor of Clinical Research and Practice

Jens Ulrich Stegmann

Julia Zima

Olivia Mahaux

Lionel Van Holle

Maria-Genalin Angelo

Abstract

© 2015. Complex regional pain syndrome (CRPS) is a chronic pain disorder that typically follows trauma or surgery. Suspected CRPS reported after vaccination with human papillomavirus (HPV) vaccines led to temporary suspension of proactive recommendation of HPV vaccination in Japan. We investigated the potential CRPS signal in relation to HPV-16/18-adjuvanted vaccine (Cervarix®) by database review of CRPS cases with independent expert confirmation; a disproportionality analysis and analyses of temporality; an observed versus expected analysis using published background incidence rates; systematic reviews of aggregate safety data, and a literature review.The analysis included 17 case reports of CRPS: 10 from Japan (0.14/100,000 doses distributed) and seven from the United Kingdom (0.08/100,000). Five cases were considered by independent experts to be confirmed CRPS. Quantitative analyses did not suggest an association between CRPS and HPV-16/18-adjuvanted vaccine. Observed CRPS incidence after HPV-16/18 vaccination was statistically significantly below expected rates. Systematic database reviews using search terms varying in specificity and sensitivity did not identify new cases. No CRPS was reported during clinical development and no unexpected results found in the literature.There is not sufficient evidence to suggest an increased risk of developing CRPS following vaccination with HPV-16/18-adjuvanted vaccine. Post-licensure safety surveillance confirms the acceptable benefit-risk of HPV-16/18 vaccination.

Journal Article Type	Article
Acceptance Date	Jul 1, 2015
Online Publication Date	Jul 28, 2015
Publication Date	Sep 1, 2015
Deposit Date	Jul 31, 2015
Publicly Available Date	Feb 20, 2016
Journal	EBioMedicine
Electronic ISSN	2352-3964
Publisher	Elsevier
Peer Reviewed	Peer Reviewed
Volume	2
Issue	9
Pages	1114-1121
DOI	https://doi.org/10.1016/j.ebiom.2015.07.003
Keywords	complex regional pain syndrome, human papillomavirus vaccine, safety, chronic pain
Public URL	https://uwe-repository.worktribe.com/output/829115
Publisher URL	http://dx.doi.org/10.1016/j.ebiom.2015.07.003
Contract Date	Feb 20, 2016