Ptiaiynflitis Sinusitis Upp* respiiatofy tract interior 139 112 150

Ptiaiynflitis

Sinusitis Upp* respiiatofy tract interior

139 112

150 146

1 74 1 57

115 120

126 127

165 1 75

252

2 41

316

245

247

293

Rasft * Includes events obtained through spontaneous reports following each dose and events reported i month after doses i and 2 (when all subjects were queried regarding the occurrence of any adverse event since the previous vaccination) a Rvalue <005 b rvalue <001 c p-vaiue <0 001 The most frequently reported (£1%) unsolicited adverse events occurring more than 30 days (late) after vaccination for all subjects (n« 10.936) were similar m nature to those listed m Table 1. and most occurred at a frequency of <5%. in both the vaccine or placebo groups The only late adverse events occurnna with an incidence of >5% in vaccine or placebo recipients were arthralgia (13 64% vs 13 55%. respectively) and headache (5 06% vs 4 72%. respectively) No significant differences in late adverse events were noted between treatment groups after any dose and overall Separate post hoc analyses were conducted to assess two subsets of musculoskeletal events which occurred either early (S30 days) or late (>30 days) post-vaccination There were no significant differences, either early or late, between the vaccine and placebo recipients with regard to experiencing arthritis, aggravated arthritis, arthropathy or arthrosis

However, vaccine recipients were significantly more likely than placebo recipients to experience early events of arthralgia or myalgia after each close (for dose 1 odds ratio (OR). (95% Cl) » 1 35(1 13, 1 61). dose 2 OR = 1 28 (1 05. 1 56), dose 3 OR = 1 59(118. 2 16)1 With regard to late events of arthralgia or myalgia, there were no significant differences between vaccine and placebo recipients There was no significant difference in the rates of cardiac adverse events between vaccine and placebo recipients Neurologic adverse events which occurred at a rate < 1 % m the vaccine group and were noted to occur with a similar frequency in placebo recipients included carpal tunnel syndrome, migraine, paralysis, tremor, coma, dysphorwa. ataxia, multiple sclerosis. myasthenia gravis, meningitis, trigeminal neuralgia, nystagmus, neuritis, neuralgia, nerve root lesion, neuropathy, hyperesthesia, hyperkinesia, and intracranial hypertension Overall, approximately 18% of subjects enrolled in the study had a prior history of some musculoskeletal condition (19% vacctnees. 18% placebo recipients) In a post hoc subgroup analysis, there was no significant difference between vaccine and placebo recipients with regard to development of musculoskeletal eyents (defined as arthritis, arthropathy, arthrosis. synovitis, tendinitis, polymyalgia rheumatica. bursitis or rheumatoid arthritis and lasting more than 30 days) in those with a prior history of musculoskeletal conditions However, both vaccine and placebo recipients with a prior history of musculoskeletal condrtions were more likely to experience musculoskeletal events than subjects without such poor history Solicited Adverse Events The frequency of solicited local and systemic adverse events was evaluated in a subset of subjects (n=938) who comprised the total enrollment at one study center in the efficacy trial Of these 938 subjects. 000 completed a 4-day diary card following each of three doses, and were evaluable according to protocol Table 2 shows the percentage of subjects reporting a solicited symptom following any one of the three doses and overall The majority of tne solicited events were mild to moderate in severity and limited m duration