Supplementary appendix

Transcription

1 Supplementary appendix This appendix formed part of the original submission and has been peer reviewed. We post it as supplied by the authors. Supplement to: Bryan P, Seabroke S, Wong J, et al. Safety of multicomponent meningococcal group B vaccine (4CMenB) in routine infant immunisation in the UK: a prospective surveillance study. Lancet Child Adolesc Health 2018; published online April 24.

2 Report Run Date: 06-Dec-2017 Data Lock Date: 15-Nov :00:05 Earliest Reaction Date: 27-Jan-2015 MedDRA Version: MedDRA 20.1 Bexsero PAP: Bexsero Product Analysis Print (PAP) of all cases received between 01/09/2017 and 31/05/2017 in patients aged under 18 months. Report Run Date: 06-Dec-2017, Page 1

3 Cardiac disorders Cardiac signs and symptoms NEC Cyanosis 9 0 Palpitations 2 0 Rate and rhythm disorders NEC Bradycardia 6 0 Bradycardia neonatal 3 0 Tachycardia 11 0 Supraventricular arrhythmias Supraventricular tachycardia 1 0 Ventricular arrhythmias and cardiac arrest Cardiac arrest 2 0 Cardio-respiratory arrest 1 0 Cardiac disorders SOC TOTAL 35 0 Report Run Date: 06-Dec-2017, Page 2

4 Ear disorders Tympanic membrane disorders (excl infections) Tympanic membrane hyperaemia 1 0 Ear disorders SOC TOTAL 1 0 Report Run Date: 06-Dec-2017, Page 3

5 Eye disorders Lacrimation disorders Lacrimation increased 1 0 Lid, lash and lacrimal infections, irritations and inflammations Eyelid oedema 1 0 Ocular disorders NEC Eye disorder 1 0 Eye swelling 1 0 Ocular infections, inflammations and associated manifestations Ocular hyperaemia 1 0 Ocular nerve and muscle disorders Eye movement disorder 5 0 Strabismus 2 0 Ocular sensation disorders Photophobia 1 0 Pupil disorders Mydriasis 1 0 Pupils unequal 1 0 Scleral structural change, deposit and degeneration Scleral discolouration 1 0 Visual disorders NEC Vision blurred 1 0 Eye disorders SOC TOTAL 17 0 Report Run Date: 06-Dec-2017, Page 4

6 Gastrointestinal disorders Abdominal findings abnormal Gastrointestinal sounds abnormal 1 0 Diarrhoea (excl infective) Diarrhoea 44 0 Faecal abnormalities NEC Abnormal faeces 2 0 Faeces discoloured 3 0 Faeces soft 1 0 Mucous stools 3 0 Flatulence, bloating and distension Abdominal distension 3 0 Flatulence 3 0 Gastritis (excl infective) Reflux gastritis 1 0 Gastrointestinal and abdominal pains (excl oral and throat) Abdominal pain 4 0 Abdominal pain upper 4 0 Gastrointestinal atonic and hypomotility disorders NEC Constipation 4 0 Gastrooesophageal reflux disease 1 0 Gastrointestinal dyskinetic disorders Change of bowel habit 1 0 Gastrointestinal signs and symptoms NEC Abdominal discomfort 7 0 Dysphagia 1 0 Gastrointestinal stenosis and obstruction NEC Intussusception 1 0 Nausea and vomiting symptoms Infantile vomiting 6 0 Retching 1 0 Vomiting 61 0 Vomiting projectile 5 0 Non-site specific gastrointestinal haemorrhages Haematochezia 1 0 Oral soft tissue pain and paraesthesia Oral pain 1 0 Oral soft tissue signs and symptoms Oral mucosal blistering 1 0 Oral soft tissue swelling and oedema Lip swelling 2 0 Stomatitis and ulceration Mouth ulceration 1 0 Tongue signs and symptoms Swollen tongue 3 0 Gastrointestinal disorders SOC TOTAL Report Run Date: 06-Dec-2017, Page 5

7 General disorders Administration site reactions NEC Administration site erythema 1 0 Asthenic conditions Asthenia 3 0 Fatigue 4 0 Malaise 45 0 Body temperature altered Hypothermia 1 0 Death and sudden death Death 3 3 Sudden death 1 1 Sudden infant death syndrome 1 1 Febrile disorders Fever neonatal 1 0 Hyperpyrexia 3 0 Pyrexia Feelings and sensations NEC Chills 8 0 Feeling abnormal 8 0 Feeling cold 2 0 Feeling hot 6 0 Feeling jittery 1 0 Gait disturbances Gait disturbance 8 0 Gait inability 3 0 Loss of control of legs 1 0 General signs and symptoms NEC Condition aggravated 3 0 Crying 95 0 Developmental delay 1 0 General physical health deterioration 2 0 Glassy eyes 2 0 Induration 9 0 Irritability postvaccinal 4 0 Local reaction 7 0 Moaning 3 0 Peripheral swelling 24 0 Secretion discharge 1 0 Swelling 20 0 Inflammations Inflammation 6 0 Injection site reactions Injected limb mobility decreased 1 0 Injection site bruising 2 0 Injection site discolouration 1 0 Injection site discomfort 1 0 Injection site erythema 13 0 Injection site haemorrhage 1 0 Injection site induration 2 0 Injection site inflammation 2 0 Injection site joint erythema 1 0 Injection site joint inflammation 1 0 Injection site mass 43 0 Report Run Date: 06-Dec-2017, Page 6

8 General disorders General disorders cont'd Injection site nodule 1 0 Injection site oedema 1 0 Injection site pain 3 0 Injection site pruritus 1 0 Injection site rash 1 0 Injection site swelling 10 0 Injection site vesicles 3 0 Injection site warmth 3 0 Mass conditions NEC Mass 11 0 Pain and discomfort NEC Discomfort 3 0 Pain 21 0 Tenderness 1 0 Vaccination site reactions Extensive swelling of vaccinated limb 2 0 Vaccination site bruising 8 0 Vaccination site cyst 1 0 Vaccination site discharge 3 0 Vaccination site discolouration 9 0 Vaccination site discomfort 2 0 Vaccination site eczema 1 0 Vaccination site erythema 55 0 Vaccination site haematoma 2 0 Vaccination site induration 34 0 Vaccination site inflammation 7 0 Vaccination site irritation 1 0 Vaccination site joint movement impairment 1 0 Vaccination site mass 54 0 Vaccination site movement impairment 1 0 Vaccination site nodule 5 0 Vaccination site oedema 1 0 Vaccination site pain 17 0 Vaccination site pallor 1 0 Vaccination site rash 11 0 Vaccination site reaction 6 0 Vaccination site scar 6 0 Vaccination site swelling 56 0 Vaccination site warmth 10 0 General disorders SOC TOTAL Report Run Date: 06-Dec-2017, Page 7

9 Immune system disorders Allergic conditions NEC Hypersensitivity 8 0 Multiple allergies 2 0 Allergies to foods, food additives, drugs and other chemicals Allergy to vaccine 1 0 Anaphylactic and anaphylactoid responses Anaphylactic reaction 4 0 Immune system disorders SOC TOTAL 15 0 Report Run Date: 06-Dec-2017, Page 8

10 Infections Abdominal and gastrointestinal infections Gastroenteritis 1 0 Bacterial infections NEC Arthritis bacterial 2 0 Bacterial infection 1 0 Cellulitis 9 0 Meningitis bacterial 1 0 Skin bacterial infection 1 0 Vaccination site cellulitis 7 0 Bone and joint infections Osteomyelitis 1 0 Central nervous system and spinal infections Encephalitis 1 0 Meningitis 2 0 Meningitis aseptic 3 0 Ear infections Ear infection 1 0 Otitis externa 1 0 Eye and eyelid infections Conjunctivitis 1 0 Infections NEC Abscess 3 0 Infection 1 0 Lymph gland infection 1 0 Vaccination site abscess 1 0 Vaccination site infection 3 0 Lower respiratory tract and lung infections Lower respiratory tract infection 2 0 Lung infection 1 0 Sepsis, bacteraemia, viraemia and fungaemia NEC Sepsis 10 0 Sepsis neonatal 1 0 Skin structures and soft tissue infections Skin infection 1 0 Subcutaneous abscess 1 0 Staphylococcal infections Furuncle 1 0 Streptococcal infections Scarlet fever 1 0 Tuberculous infections Erythema induratum 1 0 Upper respiratory tract infections Croup infectious 2 0 Nasopharyngitis 3 0 Tonsillitis 1 0 Viral infections NEC Bronchiolitis 2 0 Gastroenteritis viral 2 0 Viral infection 1 0 Viral rash 1 0 Viral upper respiratory tract infection 1 0 Infections SOC TOTAL 73 0 Report Run Date: 06-Dec-2017, Page 9

11 Injuries Medication errors, product use errors and issues NEC Inadequate aseptic technique in use of product 1 0 Non-site specific procedural complications Post procedural swelling 1 0 Product administration errors and issues Drug administered at inappropriate site 1 0 Drug administered to patient of inappropriate age 1 0 Drug administration error 1 0 Inappropriate schedule of drug administration 1 0 Incorrect route of drug administration 1 0 Skin injuries NEC Contusion 7 0 Laceration 1 0 Injuries SOC TOTAL 15 0 Report Run Date: 06-Dec-2017, Page 10

12 Investigations Blood gas and acid base analyses Oxygen saturation decreased 6 0 Cerebrospinal fluid tests (excl microbiology) CSF white blood cell count increased 1 0 Chemistry analyses NEC Inflammatory marker increased 2 0 Heart rate and pulse investigations Heart rate abnormal 1 0 Heart rate increased 7 0 Physical examination procedures and organ system status Body temperature abnormal 5 0 Body temperature decreased 3 0 Body temperature fluctuation 1 0 Body temperature increased 30 0 Respiratory rate increased 8 0 Protein analyses NEC C-reactive protein increased 10 0 Respiratory tract and thoracic imaging procedures Chest X-ray abnormal 1 0 Vascular tests NEC (incl blood pressure) Capillary nail refill test abnormal 1 0 White blood cell analyses White blood cell count increased 4 0 Investigations SOC TOTAL 80 0 Report Run Date: 06-Dec-2017, Page 11

13 Metabolic disorders Appetite disorders Decreased appetite 18 0 Hypophagia 4 0 General nutritional disorders NEC Food aversion 1 0 Poor feeding infant 41 0 Hypoglycaemic conditions NEC Hypoglycaemia 1 0 Metabolic acidoses (excl diabetic acidoses) Metabolic acidosis 1 0 Potassium imbalance Hyperkalaemia 1 0 Sodium imbalance Hyponatraemia 1 0 Total fluid volume decreased Dehydration 2 0 Metabolic disorders SOC TOTAL 70 0 Report Run Date: 06-Dec-2017, Page 12

14 Muscle & tissue disorders Joint related signs and symptoms Arthralgia 2 0 Muscle pains Myalgia 2 0 Muscle related signs and symptoms NEC Muscle spasms 1 0 Muscle twitching 5 0 Muscle tone abnormalities Floppy infant 15 0 Muscle rigidity 3 0 Muscle weakness conditions Muscular weakness 2 0 Musculoskeletal and connective tissue pain and discomfort Limb discomfort 1 0 Musculoskeletal discomfort 1 0 Pain in extremity 9 0 Musculoskeletal and connective tissue signs and symptoms NEC Limb mass 3 0 Musculoskeletal stiffness 6 0 Posture abnormal 1 0 Weight bearing difficulty 5 0 Muscle & tissue disorders SOC TOTAL 56 0 Report Run Date: 06-Dec-2017, Page 13

15 Nervous system disorders Abnormal reflexes Kernig's sign 1 0 Absence seizures Petit mal epilepsy 2 0 Coordination and balance disturbances Balance disorder 2 0 Dysstasia 2 0 Disturbances in consciousness NEC Depressed level of consciousness 2 0 Lethargy 19 0 Loss of consciousness 3 0 Somnolence 23 0 Syncope 1 0 Dyskinesias and movement disorders NEC Dyskinesia 6 0 Hypokinesia 1 0 Movement disorder 1 0 Generalised tonic-clonic seizures Generalised tonic-clonic seizure 9 0 Headaches NEC Headache 2 0 Mental impairment (excl dementia and memory loss) Disturbance in attention 1 0 Muscle tone abnormal Hypertonia 2 0 Hypotonia 21 0 Narcolepsy and hypersomnia Hypersomnia 3 0 Neurological signs and symptoms NEC Decerebrate posture 1 0 Drooling 1 0 Exaggerated startle response 1 0 Fontanelle bulging 3 0 Hyporesponsive to stimuli 2 0 Meningism 2 0 Presyncope 3 0 Unresponsive to stimuli 24 0 Neuromuscular disorders NEC Hypotonic-hyporesponsive episode 2 0 Paraesthesias and dysaesthesias Hyperaesthesia 1 0 Seizures and seizure disorders NEC Epilepsy 1 0 Febrile convulsion 26 0 Partial seizures 3 0 Seizure 17 0 Seizure anoxic 1 0 Seizure like phenomena 1 0 Status epilepticus 1 0 Tonic clonic movements 1 0 Sleep disturbances NEC Poor quality sleep 1 0 Speech and language abnormalities Report Run Date: 06-Dec-2017, Page 14

16 Nervous system disorders Nervous system disorders cont'd Speech disorder developmental 1 0 Tremor (excl congenital) Tremor 9 0 Nervous system disorders SOC TOTAL Report Run Date: 06-Dec-2017, Page 15

17 Pregnancy conditions Neonatal metabolic and endocrine disorders Hypothermia neonatal 1 0 Pregnancy conditions SOC TOTAL 1 0 Report Run Date: 06-Dec-2017, Page 16

18 Psychiatric disorders Abnormal behaviour NEC Abnormal behaviour 8 0 Breath holding 2 0 Staring 3 0 Anxiety disorders NEC Separation anxiety disorder 1 0 Anxiety symptoms Agitation 8 0 Agitation neonatal 1 0 Anxiety 1 0 Stress 1 0 Behaviour and socialisation disturbances Personality change 1 0 Social avoidant behaviour 2 0 Decreased physical activity levels Catatonia 1 0 Disturbances in initiating and maintaining sleep Insomnia 8 0 Emotional and mood disturbances NEC Emotional distress 11 0 Irritability 80 0 Mood altered 2 0 Increased physical activity levels Restlessness 20 0 Mood alterations with depressive symptoms Decreased interest 1 0 Depressed mood 1 0 Mood disorders NEC Listless 5 0 Parasomnias Sleep terror 3 0 Sleep disorders NEC Sleep disorder 7 0 Somatic symptom disorders Conversion disorder 1 0 Speech articulation and rhythm disturbances Screaming 28 0 Psychiatric disorders SOC TOTAL Report Run Date: 06-Dec-2017, Page 17

19 Renal & urinary disorders Bladder and urethral symptoms Dysuria 1 0 Renal structural abnormalities and trauma Kidney enlargement 1 0 Renal & urinary disorders SOC TOTAL 2 0 Report Run Date: 06-Dec-2017, Page 18

20 Respiratory disorders Breathing abnormalities Apnoea 14 0 Apnoeic attack 2 0 Dyspnoea 15 0 Grunting 3 0 Hypopnoea 7 0 Hypoventilation 1 0 Irregular breathing 1 0 Respiratory arrest 8 0 Respiratory depression 1 0 Respiratory distress 1 0 Tachypnoea 6 0 Bronchospasm and obstruction Wheezing 3 0 Conditions associated with abnormal gas exchange Respiratory acidosis 1 0 Coughing and associated symptoms Cough 6 0 Laryngeal spasm, oedema and obstruction Stridor 1 0 Lower respiratory tract signs and symptoms Rales 1 0 Nasal congestion and inflammations Nasal congestion 1 0 Neonatal hypoxic conditions Infantile apnoea 4 0 Neonatal hypoxia 4 0 Pharyngeal disorders (excl infections and neoplasms) Pharyngeal erythema 1 0 Respiratory failures (excl neonatal) Acute respiratory failure 1 0 Respiratory tract disorders NEC Respiratory disorder 4 0 Upper respiratory tract signs and symptoms Choking 2 0 Increased viscosity of upper respiratory secretion 1 0 Nasal obstruction 1 0 Oropharyngeal blistering 1 0 Oropharyngeal pain 1 0 Rhinorrhoea 7 0 Respiratory disorders SOC TOTAL 99 0 Report Run Date: 06-Dec-2017, Page 19

21 Skin disorders Angioedemas Angioedema 1 0 Swelling face 3 0 Apocrine and eccrine gland disorders Cold sweat 6 0 Hyperhidrosis 1 0 Bullous conditions Blister 4 0 Erythema multiforme 1 0 Dermal and epidermal conditions NEC Dry skin 1 0 Pain of skin 2 0 Papule 2 0 Skin burning sensation 1 0 Skin discolouration 24 0 Skin induration 3 0 Skin lesion 1 0 Skin reaction 6 0 Skin tightness 1 0 Skin warm 14 0 Dermatitis and eczema Dermatitis allergic 2 0 Dermatitis atopic 1 0 Dermatitis diaper 1 0 Eczema 2 0 Erythemas Erythema 58 0 Generalised erythema 1 0 Exfoliative conditions Skin exfoliation 1 0 Pruritus NEC Pruritus 5 0 Purpura and related conditions Henoch-Schonlein purpura 2 0 Petechiae 14 0 Purpura 4 0 Rashes, eruptions and exanthems NEC Rash 54 0 Rash erythematous 6 0 Rash generalised 11 0 Rash macular 18 0 Rash maculo-papular 3 0 Rash papular 6 0 Rash vesicular 1 0 Skin and subcutaneous conditions NEC Skin mass 3 0 Skin cysts and polyps Dermal cyst 1 0 Skin dystrophies Skin wrinkling 4 0 Skin vasomotor conditions Livedo reticularis 9 0 Urticarias Report Run Date: 06-Dec-2017, Page 20

22 Skin disorders Skin disorders cont'd Urticaria 19 0 Skin disorders SOC TOTAL Report Run Date: 06-Dec-2017, Page 21

23 Social circumstances Disability issues Immobile 1 0 Social circumstances SOC TOTAL 1 0 Report Run Date: 06-Dec-2017, Page 22

24 Vascular disorders Arterial inflammations Kawasaki's disease 3 0 Circulatory collapse and shock Circulatory collapse 4 0 Peripheral circulatory failure 1 0 Shock 3 0 Haemorrhages NEC Haematoma 1 0 Lymphoedemas Lymphoedema 1 0 Peripheral vascular disorders NEC Flushing 3 0 Peripheral vasoconstriction, necrosis and vascular insufficiency Peripheral coldness 6 0 Site specific vascular disorders NEC Pallor 53 0 Vascular disorders SOC TOTAL 75 0 TOTAL REACTIONS FOR DRUG TOTAL REPORTS 902 TOTAL FATAL OUTCOME REPORTS 5 Report Run Date: 06-Dec-2017, Page 23

25 Four component meningococcal group B vaccine (Bexsero, 4CMenB) Figure A.

26 Figure B. Figure C.

27 13-valent Pneumococcal Conjugate Vaccine (PCV13) Figure D.

28 Figure E.

29 Figure F. Rotavirus Vaccine

30 Figure G.

31 Figure H.