Table 3.
EAIRs for AEs in the pediatric and adult population: Up to week 52 (safety set)
| Pediatric population: EAIR/100 patient-years (95% CI) | Adult population: EAIR/100 patient-years (95% CI) | |||||||
|---|---|---|---|---|---|---|---|---|
| Any SEC LD N = 98 |
Any SEC HD N = 100 |
Any SEC N = 198 |
ETN N = 41 |
Any SEC 150 mg N = 999 |
Any SEC 300 mg N = 990 |
Any SEC N = 1989 |
ETN N = 323 |
|
| Total AEs | 190.5 (149.3, 239.5) | 207.7 (163.1, 260.8) | 198.8 (167.9, 233.6) | 266.3 (184.4, 372.2) | 255.5 (238.1, 273.9) | 256.6 (239.2, 274.9) | 256.1 (243.7, 268.9) | 248.0 (218.5, 280.4) |
| SAEs | 7.8 (3.1, 16.1) | 6.7 (2.5, 14.6) | 7.3 (3.9, 12.4) | 14.5 (4.7, 33.9) | 7.5 (5.8, 9.6) | 7.5 (5.8, 9.6) | 7.5 (6.3, 9.0) | 6.9 (4.2, 10.7) |
| Discontinued study treatment due to any AE | 2.2 (0.3, 7.8) | 3.3 (0.7, 9.6) | 2.7 (0.9, 6.4) | 2.7 (0.1, 14.8) | 3.6 (2.4, 5.1) | 3.4 (2.3, 4.9) | 3.5 (2.7, 4.5) | 4.1 (2.1, 7.1) |
| Most frequent AEs (by SOC)a | ||||||||
| Infections and infestation | 107.2 (81.4, 138.5) | 110.6 (83.8, 143.3) | 108.8 (89.9, 130.6) | 125.8 (82.9, 183.0) | 98.1 (90.0, 106.8) | 104.5 (96.1, 113.5) | 101.3 (95.4, 107.5) | 92.0 (78.7, 106.8) |
| Skin and subcutaneous tissue disorders | 29.5 (18.7, 44.2) | 26.2 (16.2, 40.1) | 27.8 (20.2, 37.3) | 30.0 (14.4, 55.1) | 26.7 (23.2, 30.7) | 28.9 (25.2, 33.1) | 27.8 (25.2, 30.6) | 24.3 (18.6, 31.1) |
| Gastrointestinal disorders | 22.2 (13.2, 35.1) | 32.9 (21.3, 48.6) | 27.4 (19.8, 36.9) | 49.6 (27.1, 83.2) | 28.7 (25.0, 32.8) | 28.7 (25.0, 32.9) | 28.7 (26.1, 31.6) | 26.9 (20.9, 34.1) |
| General disorders and administration-site conditions | 15.5 (8.3, 26.6) | 18.7 (10.4, 30.8) | 17.1 (11.3, 24.7) | 25.1 (10.8, 49.4) | 15.4 (12.8, 18.4) | 16.5 (13.8, 19.6) | 16.0 (14.1, 18.0) | 33.0 (26.1, 41.1) |
| Respiratory, thoracic, and mediastinal disorders | 11.5 (5.5, 21.2) | 19.1 (10.9, 31.1) | 15.3 (10.0, 22.4) | 11.1 (3.0, 28.4) | 15.0 (12.5, 18.0) | 21.5 (18.4, 25.0) | 18.2 (16.2, 20.5) | 12.7 (8.9, 17.7) |
| Most frequent AEs (by PT)a | ||||||||
| Nasopharyngitis | 29.6 (18.8, 44.5) | 34.8 (22.8, 51.0) | 32.2 (23.8, 42.5) | 33.3 (16.6, 59.6) | 29.2 (25.4, 33.3) | 30.0 (26.2, 34.2) | 29.6 (26.9, 32.5) | 36.0 (28.8, 44.4) |
| Headache | 11.4 (5.5, 21.0) | 11.6 (5.6, 21.4) | 11.5 (7.0, 17.8) | 11.2 (3.0, 28.6) | 10.3 (8.2, 12.7) | 12.6 (10.3, 15.3) | 11.5 (9.9, 13.2) | 15.0 (10.7, 20.4) |
| Pharyngitis | 9.0 (3.9, 17.7) | 8.1 (3.3, 16.7) | 8.6 (4.8, 14.1) | 8.2 (1.7, 24.0) | 2.8 (1.8, 4.2) | 2.9 (1.9, 4.3) | 2.8 (2.1, 3.8) | 2.0 (0.8, 4.5) |
| URTI | 6.7 (2.5, 14.6) | 5.6 (1.8, 13.1) | 6.2 (3.1, 11.0) | 8.4 (1.7, 24.7) | 9.9 (7.9, 12.3) | 8.3 (6.5, 10.5) | 9.1 (7.7, 10.7) | 6.3 (3.7, 9.9) |
| Acne | 9.1 (3.9, 17.9) | 3.3 (0.7, 9.7) | 6.2 (3.1, 11.0) | 0.0 (0.0, 9.7) | 0.5 (0.1, 1.2) | 1.1 (0.6, 2.1) | 0.8 (0.4, 1.3) | 1.0 (0.2, 3.0) |
| Diarrhea | 4.5 (1.2, 11.4) | 7.9 (3.2, 16.3) | 6.2 (3.1, 11.1) | 2.7 (0.1, 15.0) | 6.5 (4.9, 8.5) | 7.6 (5.8, 9.7) | 7.1 (5.8, 8.4) | 7.8 (4.9, 11.8) |
| AEs of special interesta | ||||||||
| Hypersensitivity (SMQ) (narrow) | 8.0 (3.2, 16.4) | 14.2 (7.3, 24.8) | 11.0 (6.6, 17.2) | 14.5 (4.7, 33.9) | 11.2 (9.0, 13.8) | 11.8 (9.6, 14.4) | 11.5 (9.9, 13.3) | 11.2 (7.6, 15.9) |
| Neutropenia (NMQ) (narrow) | 5.6 (1.8, 13.2) | 3.3 (0.7, 9.7) | 4.5 (1.9, 8.8) | 2.7 (0.1, 14.9) | 1.3 (0.6, 2.3) | 1.3 (0.6, 2.3) | 1.3 (0.8, 1.9) | 1.7 (0.6, 4.0) |
| Neutropenia (PT) | 4.5 (1.2, 11.4) | 2.2 (0.3, 7.9) | 3.3 (1.2, 7.2) | 2.7 (0.1, 14.9) | 0.7 (0.3, 1.5) | 0.7 (0.3, 1.5) | 0.7 (0.4, 1.2) | 1.4 (0.4, 3.5) |
| Candida infections (HLT) | 2.2 (0.3, 7.9) | 2.2 (0.3, 8.0) | 2.2 (0.6, 5.6) | 0.0 (0.0, 9.7) | 2.2 (1.3, 3.4) | 4.2 (2.9, 5.8) | 3.2 (2.4, 4.2) | 1.4 (0.4, 3.5) |
| Vulvovaginal candidiasis (PT) | 1.1 (0.0, 6.1) | 1.1 (0.0, 6.1) | 1.1 (0.1, 3.9) | 0.0 (0.0, 9.7) | 0.6 (0.2, 1.3) | 0.8 (0.3, 1.7) | 0.7 (0.4, 1.2) | 0.0 (0.0, 1.2) |
| Nail Candida (PT) | 0.0 (0.0, 4.0) | 1.1 (0.0, 6.1) | 0.5 (0.0, 3.0) | 0.0 (0.0, 9.7) | 0.0 (0.0, 0.4) | 0.0 (0.0, 0.4) | 0.0 (0.0, 0.2) | 0.0 (0.0, 1.2) |
| Skin Candida (PT) | 1.1 (0.0, 6.0) | 0.0 (0.0, 4.0) | 0.5 (0.0, 3.0) | 0.0 (0.0, 9.7) | 0.5 (0.1, 1.2) | 0.2 (0.0, 0.8) | 0.3 (0.1, 0.7) | 0.7 (0.1, 2.4) |
| Suicide/self-injury (SMQ) | 2.2 (0.3, 7.8) | 0.0 (0.0, 4.0) | 1.1 (0.1, 3.9) | 0.0 (0.0, 9.7) | 0.2 (0.0, 0.8) | 0.0 (0.0, 0.4) | 0.1 (0.0, 0.4) | 0.0 (0.0, 1.2) |
| Intentional self-injury (PT) | 1.1 (0.0, 6.0) | 0.0 (0.0, 4.0) | 0.5 (0.0, 3.0) | 0.0 (0.0, 9.7) | 0.0 (0.0, 0.4) | 0.0 (0.0, 0.4) | 0.0 (0.0, 0.2) | 0.0 (0.0, 1.2) |
| Suicidal ideation (PT) | 1.1 (0.0, 6.0) | 0.0 (0.0, 4.0) | 0.5 (0.0, 3.0) | 0.0 (0.0, 9.7) | 0.0 (0.0, 0.4) | 0.0 (0.0, 0.4) | 0.0 (0.0, 0.2) | 0.0 (0.0, 1.2) |
| Suicide attempt (PT) | 0.0 (0.0, 4.0) | 0.0 (0.0, 4.0) | 0.0 (0.0, 2.0) | 0.0 (0.0, 9.7) | 0.1 (0.0, 0.6) | 0.0 (0.0, 0.4) | 0.1 (0.0, 0.3) | 0.0 (0.0, 1.2) |
| IBDb (NMQ) (narrow) | 0.0 (0.0, 4.0) | 1.1 (0.0, 6.1) | 0.5 (0.0, 3.0) | 0.0 (0.0, 9.7) | 0.3 (0.1, 1.0) | 0.5 (0.1, 1.2) | 0.4 (0.2, 0.8) | 0.3 (0.0, 1.9) |
| MACE (MI, Stroke, CV death) (NMQ) | 0.0 (0.0, 4.0) | 0.0 (0.0, 4.0) | 0.0 (0.0, 2.0) | 0.0 (0.0, 9.7) | 0.7 (0.3, 1.5) | 0.5 (0.1, 1.2) | 0.6 (0.3, 1.1) | 0.3 (0.0, 1.9) |
| Malignant or unspecified tumors (SMQ) | 0.0 (0.0, 4.0) | 0.0 (0.0, 4.0) | (0.0 (0.0, 2.0) | 0.0 (0.0, 9.7) | 1.1 (0.6, 2.1) | 0.8 (0.3, 1.7) | 1.0 (0.6, 1.6) | 0.7 (0.1, 2.4) |
| ISRsc | 4.5 (1.2, 11.5) | 4.4 (1.2, 11.4) | 4.5 (1.9, 8.8) | 11.5 (3.1, 29.4) | 1.6 (0.9, 2.7) | 1.8 (1.1, 3.0) | 1.7 (1.2, 2.5) | 13.0 (9.1, 18.1) |
“Any SEC” for both the treatment groups (LD and HD) includes all patients treated with SEC from the start of the study and those who switched from PBO to SEC at week 12
AE adverse event, CI confidence interval, CV cardiovascular, EAIR exposure-adjusted incidence rate (per 100 patient-years), ETN etanercept, HD high dose, HLT High-Level Term, IBD inflammatory bowel disease, ISR injection-site reaction, LD low dose, MACE major adverse cardiovascular event, MedDRA Medical Dictionary for Regulatory Activities, MI myocardial infarction, N total number of patients, NMQ Novartis customized MedDRA Query, PBO placebo, PT preferred term, SAE serious AE, SEC secukinumab, SMQ Standardized MedDRA Query, SOC system organ class, URTI upper respiratory tract infection
aAEs ordered according to the incidence in “Any SEC” group in pediatric population
bOne patient reported a mild AE of hemorrhagic diarrhea, which was resolved and confirmed not to be IBD
cISRs corresponding to event coded with HLT “Injection-site reaction” and some with HLT “Administration-site reaction” or “Application- and instillation-site reactions”