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  • Assessments of CRPS and HPV adjuvanted vaccine have

    2018-11-13

    Assessments of CRPS and HPV-16/18-adjuvanted vaccine have been conducted independently by regulatory agencies. In December 2012 the UK Medicines and Healthcare products Regulatory Agency (MHRA) published an observed-versus-expected analysis and a safety assessment report after 4years of HPV-16/18-adjuvanted vaccine use in the UK (Medicines and Healthcare products Regulatory Agency (MHRA), 2012). The report concluded that “Reported cases of CRPS are consistent with chance and there is insufficient evidence of a causal association with Cervarix” (Medicines and Healthcare products Regulatory Agency (MHRA), 2012). The World Health Organization\'s Global Advisory Committee on Vaccine Safety could not ascertain a causal relationship of CRPS to HPV buy SB525334 given lack of sufficient case information and inability to reach a definitive diagnosis in many cases (Global Advisory Committee on Vaccine Safety, 2013). Finally, in April 2014 after review of cumulative data, quantitative analyses and database searches provided by GSK, the European Medicines Agency concluded that the available data do not support a causal relationship between the use of HPV-16/18-adjuvanted vaccine and CRPS onset at this stage (EMA European Medicines Agency, 2014). CRPS remains under close surveillance. We identified two case-series of CRPS after HPV vaccination in the literature. One article described peripheral sympathetic nerve dysfunction in 40 adolescent Japanese girls following immunisation with HPV vaccine (Kinoshita et al., 2014). According to the authors, four girls fulfilled the Japanese clinical diagnostic criteria of CRPS-1 (CRPS without known major nerve injury), and 14 fulfilled the Budapest diagnostic criteria (Harden et al., 2007). The paper describes five representative case reports. However, based on the case descriptions, none fulfil either of the CRPS diagnostic criteria (Japanese or Budapest); which raises the question of how the diagnostic criteria were applied. The authors also describe a postural orthostatic tachycardia syndrome (POTS), orthostatic hypotension (OH) and low plasma levels of noradrenaline in some patients. Whereas low levels of noradrenaline are described in CRPS, POTS and OH are not general findings in CRPS. Moreover, the sympathetic dysfunction is typically local and distal in buy SB525334 one of the extremities and in no way general (Wasner, 2010), as seems to be the case with the girls described in the article. The second article described five CRPS cases that the authors state fulfilled Budapest diagnostic criteria (Harden et al., 2007): four cases followed HPV vaccination (HPV-16/18-adjuvanted vaccine or HPV-6/11/16/18 vaccine ) and one followed diphtheria–tetanus–pertussis vaccine (Richards et al., 2012). In view of the different antigens administered, the authors proposed that the intramuscular injection was the event trigger, rather than the vaccine antigens themselves. Altogether, based on the outcomes of this valuation, 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 vaccination in adolescent girls and adult women (Angelo et al., 2014a).
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    Declaration of Interests All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: GA, OM, J-US, LVH, KV and JZ are employees of the GSK group of companies; GA, LVH and JZ additionally hold restricted shares in the GSK group of companies as part of their employee remuneration. FH declares receipt of financial compensation from GSK for consultancy previous to the study in question. CM declares the following remunerations made to her employer the University of the West of England, Bristol, UK: by GSK as a consultancy fee for reviewing and reporting on the data in this study; and outside the submitted work by Pfizer for delivery of a lecture series.