Update on safety of pandemic influenza A (H1N1) vaccines

Transcription

1 Update on safety of pandemic influenza A (H1N1) vaccines Dr David Wood Department of Immunization Vaccines and Biologicals Quality, safety and standards SAGE 28 October 2009

2 Context of vaccine safety discussions Safety concerns expressed outside of scientific context and by media are repeatedly raised Vigorous anti-vaccine campaigns are occurring in several parts of the world Effective communication responses for both lay and scientific audiences are needed 2

3 Communication on H1N1 vaccines safety Anticipate the issues: Q&As. Information documents. Ensure consistency of messages within and across organizations. Acknowledge known risks and explain safety monitoring and investigation systems in place. Address irrational allegations with clear facts and simple messages. 3

4 What we know about the safety of seasonal influenza vaccines? Relatively few adverse events are reported after TIV and LAIV in children and adult population when compared with AEFI reporting rate for other vaccines. Reactogenicity profile differs by type of vaccine and age of vaccine recipient (local reactions "very common", systemic reaction common) Observed reactions are mostly mild and self-limited WHO Position paper GACVS reviews (neurological side effects, safety in pregnancy, review of Bells palsy and ORS signal and review of clusters of events) 4

5 Public concerns about the safety of pandemic H1N1 influenza vaccines Guillain Barré syndrome (GACVS 2009) - the underlying reasons for the association observed in 1976 are unknown - since then, either no association with GBS or, in a few studies, a very small risk (app. 1 case/ vaccinations) - importance of preparing for active surveillance for GBS syndrome and availability of background rates Adjuvanted influenza vaccines (GACVS 2009) - relatively small scale experience, especially in risk groups - potential for higher reactogenicity - autoimmune events following immunization Squalene (GACVS 2006) - fears of squalene in vaccine inducing pathological anti-squalene antibodies are unfounded - but experience of squalene-containing vaccines has been primarily in older age-groups Thiomersal (GACVS 2008) - no evidence of toxicity in infants, children or adults exposed to thiomersal in vaccines Risks in special groups (eg. pregnancy) -Risk-benefit of influenza vaccination during pregnancy, at all stages, - given the high risk to the mother - and thus to the fetus - of the disease itself, and (as far as is known) the small potential risk to mother and fetus of the seasonal inactivated influenza vaccine, SAGE made recommendations in July but current SAGE recommendations requires clarification 5

6 Adverse events of special interest 6

7 Adverse events of special interest Preterm Labor SAGE 7 28 Oct 2009 Disease/ Disease Category Acute infectious and post-infectious polyneuritis (includes GBS) Acute transverse myelitis Optic neuritis Bell s palsy Anaphylaxis Seizure Multiple Sclerosis (MS) Spontaneous Abortion Autoimmune thrombocytopenia (ITP) Sudden death, cause unknown < 24 hrs after onset of symptoms Any death ICD-9 code * * ICD-10 Code G61.0 G36.0, G37.0, G37.8, G37.9 H46. G51.0 T78.2 R56.0, R56.8 G35 O D69.4 R96.1 R95, R96.0, R96.1, R98 O60

8 Safety of pandemic H1N1 vaccines in clinical trials Most of the evidence generated on phase 2 trials with H1N1 vaccines, and by reference to H5N1 pandemic vaccines Profile most reactions mild in nature, of short duration, fewer reaction with second dose (inactivated vaccines=blue, LAIV=orange) Very common Common Uncommon Administration site conditions (induration, swelling, pain, redness), fever, chills, fatigue, headache, arthralgia, myalgia Rhinorrhoea, nasal congestion, irritability, malaise Sweating Lymphadenopathy, dizziness, influenza like illness, cough, rhinorrhoea, nasal congestion, malaise Cough, lethargy, headache, sore throat, myalgia Fever, chills, abdominal pain Pruritus, rash, urticaria, diarrhoea, vomiting, abdominal pain, nausea, insomnia, paraesthesia 8

9 Safety monitoring of pandemic H1N1 vaccines in large-scale usage Safety information becoming available from USA, Australia, Japan, China, Sweden, Norway # of doses administered not yet validated, therefore no rates of reporting TODAY Started in September Australia, China Started in mid- October Japan Sweden Started last week Belgium, Finland, France, Norway, United Kingdom Countries starting campaigns this week: Austria, Canada, Germany, Portugal, Republic of Korea 9

10 Safety of pandemic H1N1 vaccines in large-scale usage - examples of current reports Country X snapshot of first 300 reports received mostly mild, allergic reactions (hives, rash) one report of AEFI found to be coincidental H1N1 infection in temporal association with immunization Country Y snapshot of first 300 reports received include 4 anaphylaxis and 2 deaths (confirmed H1N1 infection, coincidental cardiovascular event) Country W snapshot of first 30 reports received (more than one event associated with a single report) types of reactions: allergic reactions (3, one severe), gastrointestinal symptomatology (1), pain at injection site (14), fever (14), headache (7) Country Z phase IV trial, app doses 7 reports of serious AEFI, all recovered, 1 case of anaphylaxis 10

11 Preliminary conclusions Safety of pandemic H1N1 vaccines in large-scale usage Relatively low number of local and systemic reactions reported so far (possibly lower rate than expected?) Number of severe events small, mainly allergic reactions Small number of deaths reported around the time of vaccination; so far follow-up indicates unrelated causes Some difficulties with reports not clearly indicating association with pandemic or seasonal vaccine. Quick validation and follow-up of severe cases essential. 11

12 Safety monitoring of pandemic H1N1 vaccines in large-scale usage; two groups of countries Countries with well performing vaccine pharmacovigilance systems: Tend to have established their own procurement contracts. Focus on a limited range of vaccine products. Countries with limited or no vaccine pharmacovigilance systems: Broad range of products to consider. Many expecting U.N.-supported vaccine procurement. Other products for local distribution with limited information. 12

13 Vaccine effectiveness studies: effect of prior seasonal TIV immunization Several studies show that VE of prior seasonal TIV is not different from zero (Australia; plus unpublished US and UK studies) Some minor positive VE claimed (Mexico BMJ paper) Some minor negative VE claimed (unpublished Canadian studies) WHO considers that seasonal influenza vaccination does not increase risk of H1N1 infection 13

14 Safety in pregnancy (1) GACVS seasonal influenza vaccine recommendation Such advice (immunization in all three trimesters) would not apply to situations where the risk of influenza is low or to live attenuated vaccines, which in any event would not be indicated in pregnancy ( GACVS pandemic influenza vaccine recommendation There are currently no data on the safety profile of candidate pandemic influenza vaccines when administered during pregnancy. Where appropriate (e.g. with use of novel adjuvants), reproductive toxicity studies using animal models should be conducted. SAGE recommendation (Jul 09) Inactivated nonadjuvanted vaccines similar to most seasonal influenza vaccines are considered the preferred option given the extensive safety data on their use in pregnant women. However, if such a product is not available, pregnant women should be vaccinated with another pandemic influenza vaccine available at that time, for example, an adjuvanted inactivated influenza vaccine or a live attenuated influenza vaccine. 14

15 Safety in pregnancy (2) Reproductive toxicity studies do not indicate direct or indirect harmful effects with respect to fertility, pregnancy, embryonic/fetal development, parturition or post-natal development (relevant for adjuvanted and non-adjuvanted vaccines licensed by EMEA) There are currently no data available on the use of ph1n1 vaccines in pregnancy. Clinical studies underway however final results make take long time as pregnancies and offspring need to be followed up. Regulatory standpoint: EMEA - The use of XX product (NB. refers to adjuvanted and unadjuvanted products) may be considered during pregnancy if this is thought to be necessary, taking into account official recommendations. US FDA - Influenza A (H1N1) 2009 monovalent Vaccine (inactivated or LAIV) should be given to a pregnant woman only if clearly needed. 15

16 Discussion points Revisions of current SAGE recommendation concerning immunization with H1N1 vaccines in pregnancy Potential key messages concerning the safety of H1N1 vaccines: - so far, the adverse events following immunization that have been notified are well within the known safety profile of influenza vaccines. - there is no indication at this stage that unusual adverse reactions are being observed. - continued vigilance and regular evaluation by health authorities is needed and is ongoing 16