Pharyngitis Upper respiratory tract injection 139 112 150 146

Pharyngitis

Upper respiratory tract injection

139 112

150 146

1 74 1 57

1 15

126

120

127

1 75

252 245

241 247

316 .293

Rash * includes events obtained through spontaneous repons following each dose and events reported 1 month after doses 1 a 2 (when all subjects were queried regarding the occurrence of any adverse event since the previous vaccination) a p-value <0 06 b p-value <0 01 c p-value <0 001 The most frequently reported (01%) unsolicited adverse events occurring more than 30 days (late) after vaccination for all subjects (n* 10.936) were similar in nature to those listed in Table 1. and most occurred at a frequency of <5%. m both the vaccine or placebo groups The only late adverse events occurring 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 ("30 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 pfacebo recipients to experience early events of arthralgia or myalgia after each dose (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(1 18. 2 16)| 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 % in the vaccine group and were noted to occur with a similar frequency in placebo recipients included carpal tunnel syndrome, migraine, paralysis, tremor, coma, dysphonia. 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 tfudy had a prior history of some musculoskeletal condition (19% vaccinees, 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 events (defined as arthritis, arthropathy, arthrosis, synovitis, tendinitis, polymyalgia rheumatica. bursitis or rheumatoid arthritis and lasting more than 30 days) m those with a prior history of musculoskeletal conditions However, both vaccine and placebo recipients with a prior history of musculoskeletal conditions were more likely to experience musculoskeletal events than subjects without such prior history Solicited Adverse Events The frequency of solicited local and systemic adverse events was evaluated m a subset of subjects (n=938) who comprised the total enrollment at one study center in the efficacy trial Of these 938 subjects. 800 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 the solicited events were mild to moderate m seventy and limited m duration