Table 2.
IRs and RRs 30 days before and after the first exacerbation for the most common NRSAEs by SOC and prespecified adverse event category (N ≥ 5 in either category) (N = 3,512 for patients in the analysis)
| Before exacerbation | After exacerbation | Incidence RR (95% CI) | |||
|---|---|---|---|---|---|
| N | IRa | N | IRa | ||
| SOC | |||||
| Total | 58 | 20.2 | 181 | 65.2 | 3.22 (2.40–4.33) |
| Cardiac | 8 | 2.78 | 75 | 26.4 | 9.52 (4.59–19.7) |
| Respiratory system (other)b | 6 | 2.08 | 28 | 9.77 | 4.69 (1.94–11.3) |
| Gastrointestinal | 15 | 5.21 | 18 | 6.26 | 1.20 (0.61–2.39) |
| General and administration sitec | 5 | 1.73 | 14 | 4.86 | 2.80 (1.01–7.79) |
| Nervous system | 7 | 2.43 | 14 | 4.87 | 2.00 (0.81–4.96) |
| Infections and infestationsd | 2 | 0.69 | 13 | 4.52 | 6.51 (1.47–28.9) |
| Vascular | 0 | 0 | 12 | 4.17 | NE |
| Respiratory system (upper)b | 2 | 0.69 | 10 | 3.48 | 5.01 (1.10–22.9) |
| Neoplasms (not lung)d | 3 | 1.04 | 6 | 2.08 | 2.00 (0.50–8.00) |
| Psychiatric disorders | 3 | 1.04 | 6 | 2.08 | 2.00 (0.50–8.00) |
| Metabolism and nutrition | 3 | 1.04 | 6 | 2.08 | 2.00 (0.50–8.00) |
| Injury, poisoning, procedural | 2 | 0.69 | 5 | 1.73 | 2.50 (0.49–12.9) |
| Renal and urinary | 2 | 0.69 | 5 | 1.73 | 2.50 (0.49–2.9) |
| Prespecified adverse event category | |||||
| Cardiac failure | 2 | 0.69 | 28 | 9.77 | 14.08 (3.36–59.1) |
| Ischemic heart disease | 5 | 1.73 | 23 | 8.01 | 4.62 (1.76–12.2) |
| Atrial fibrillation/flutter | 1 | 0.35 | 17 | 5.92 | 17.06 (2.27–128) |
| MI | 1 | 0.35 | 13 | 4.52 | 13.04 (1.71–99.7) |
| Angina | 4 | 1.39 | 11 | 3.82 | 2.75 (0.88–8.65) |
| Stroke | 2 | 0.69 | 9 | 3.12 | 4.51 (0.97–20.86) |
| Upper respiratory tract infection | 1 | 0.35 | 7 | 2.43 | 7.01 (0.86–57.00) |
| Non-ventricular tachycardia, including SVT | 0 | 0 | 7 | 2.43 | NE |
| Body temperature increased | 2 | 0.69 | 6 | 2.08 | 3.00 (0.61–14.87) |
IR incidence rate, RR rate ratio (after/before), NRSAE nonlower respiratory serious adverse event, CI confidence interval, SOC system organ class, NE not estimable as pre-exacerbation IR = 0, MI myocardial infarction, SVT supraventricular tachycardia, MedDRA Medical Dictionary for Regulatory Activities
aIR per 100 patient-years
bAll primary SOCs are defined by MedDRA with the exception of “Respiratory, thoracic, and mediastinal disorders,” which has been divided into separate classes of respiratory system disorders: Lower, Upper, and Other
cSOC “General disorders and administration site conditions” includes the cardiac preferred terms chest discomfort, chest pain, edema peripheral, sudden death, edema due to cardiac disease, and cardiac death
dPreferred terms with a secondary relationship to MedDRA SOC respiratory, thoracic, and mediastinal disorders are not included