Investigating Reports of Complex Regional Pain Syndrome: An Analysis of HPV-16/18-Adjuvanted Vaccine Post-Licensure Data.
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.
Center for Pain Medicine, Erasmus MC, University Hospital, Rotterdam 3000CA, The Netherlands.
Frank
F
Huygen
Safety Evaluation and Risk Management, GSK Vaccines, 20 Avenue Fleming, B-1300 Wavre, Belgium.
Kristin
K
Verschueren
Bath Centre for Pain Services, Royal National Hospital for Rheumatic Diseases, Bath, BA1 1RL, United Kingdom ; University of the West of England, Bristol, BS16 1DD, United Kingdom.
Candida
C
McCabe
Vaccines Clinical Safety and Pharmacovigilance, GSK Vaccines, 20 Avenue Fleming, B-1300 Wavre, Belgium.
Jens-Ulrich
JU
Stegmann
Safety Evaluation and Risk Management, GSK Vaccines, 20 Avenue Fleming, B-1300 Wavre, Belgium.
Julia
J
Zima
Vaccines Safety and Research Group, GSK Vaccines, 20 Avenue Fleming, B-1300 Wavre, Belgium.
Olivia
O
Mahaux
Vaccines Safety and Research Group, GSK Vaccines, 20 Avenue Fleming, B-1300 Wavre, Belgium.
Lionel
L
Van Holle
Safety Evaluation and Risk Management, GSK Vaccines, 20 Avenue Fleming, B-1300 Wavre, Belgium.
Maria-Genalin
MG
Angelo
D000276:Adjuvants, Immunologic / Q000009:adverse effects*; D059350:Chronic Pain / Q000139:chemically induced; D002986:Clinical Trials as Topic; D020918:Complex Regional Pain Syndromes / Q000139:chemically induced* / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D052162:Human papillomavirus 16 / Q000276:immunology*; D052161:Human papillomavirus 18 / Q000276:immunology*; D006801:Humans; D008004:Licensure; D053918:Papillomavirus Vaccines / Q000009:adverse effects*; D014611:Vaccination / Q000009:adverse effects
D000276:Adjuvants, Immunologic; D053918:Papillomavirus Vaccines; C510352:human papillomavirus vaccine, L1 type 16, 18
Chronic pain; Complex regional pain syndrome; Human papillomavirus vaccine; Safety