Article summary
Strengths (S) and limitations (L) of this study
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(S) Integrates safety data from a large patient population pooled over 21 clinical trials across multiple indications complemented with large post-marketing surveillance safety data
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(S) Exposure-adjusted incidence rates for reporting safety data enhances the robustness of the results by adjusting for treatment duration
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(S) Provides valuable evidence on the comprehensive safety profile of secukinumab that should inform clinical decision-making
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(L) Conduct of clinical trials is protocol-specified and may not fully reflect real-world clinical experience and lack of a long-term placebo comparison, due to ethical considerations, limits comparisons
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(L) Inflammatory bowel disease events were not adjudicated and post-marketing safety surveillance results have not been separated by individual dose regimen or by indication
Background
Methods
Studies and patients
Safety assessments
Results
Pooled clinical trial safety results
Baseline characteristics
Characteristic | PsO studies | PsA studies | AS studies |
---|---|---|---|
Any secukinumab N = 5181 | Any secukinumab N = 1380 | Any secukinumab N = 794 | |
Age (years), mean (SD) | 45.7 (13.3) | 48.8 (12.0) | 42.4 (12.3) |
Female, n (%) | 1743 (33.6) | 742 (53.8) | 265 (33.4) |
Caucasian, n (%) | 4236 (81.8) | 1212 (87.8) | 612 (77.1) |
BMI, mean (SD) | 29.1 (6.6) | 29.8 (6.3) | 27.2 (5.5) |
Relevant medical history or current medical condition, n (%) | |||
Hypertension | 1089 (21.0) | 551 (39.9) | 176 (22.2) |
Hyperlipidemia | 667 (12.9) | 318 (23.0) | 65 (8.2) |
Diabetes mellitus | 341 (6.6) | 171 (12.4) | 22 (2.8) |
IBD | 0 (0) | 4 (0.3) | 17 (2.1) |
Crohn’s disease | 5 (0.1) | 2 (0.1) | 5 (0.6) |
Ulcerative colitis | 10 (0.2) | 2 (0.1) | 3 (0.4) |
Uveitis | 0 (0) | 8 (0.6) | 135 (17.0) |
Current smoker | 1585 (30.6) | 262 (19.0) | 234 (29.5) |
Anti-TNF inadequate responder | 784 (15.1) | 435 (31.5) | 227 (28.6) |
Safety summary
PsO studies | PsA studies | AS studies | |
---|---|---|---|
Any secukinumab N = 5181 | Any secukinumab N = 1380 | Any secukinumab N = 794 | |
Total exposure, pt-years | 10,416.9 | 3866.9 | 1943.1 |
Min–max exposure (days) | 1–1825 | 8–1827 | 1–1530 |
Death, n (%) | 9 (0.2) | 11 (0.8) | 5 (0.6) |
Discontinuations due to AEs, n (%) | 331 (6.4) | 104 (7.5) | 58 (7.3) |
AEs, EAIR per 100 pt-years (95% CI) | |||
Any AE | 204.4 (198.4, 210.5) | 147.0 (138.9, 155.5) | 140.1 (129.8, 151.0) |
Any serious AE | 6.9 (6.3, 7.4) | 7.9 (7.0, 8.9) | 6.3 (5.2, 7.6) |
Most common AEs1 | |||
Viral URTI2 | 21.0 (19.9, 22.0) | 12.1 (10.9, 13.4) | 9.8 (8.4, 11.5) |
Headache | 6.2 (5.8, 6.8) | 3.8 (3.2, 4.5) | 5.3 (4.3, 6.5) |
Diarrhea | 3.8 (3.4, 4.2) | 3.7 (3.1, 4.4) | 5.2 (4.2, 6.4) |
URTI | 5.4 (4.9, 5.9) | 9.1 (8.1, 10.2) | 5.2 (4.2, 6.4) |
Variable | PsO studies | PsA studies | AS studies |
---|---|---|---|
Any secukinumab N = 5181 | Any secukinumab N = 1380 | Any secukinumab N = 794 | |
EAIR per 100 patient-years (95% CI) | |||
Serious infections1 | 1.4 (1.2, 1.6) | 1.9 (1.5, 2.4) | 1.2 (0.8, 1.8) |
Candida infections2 | 2.2 (1.9, 2.5) | 1.5 (1.1, 2.0) | 0.7 (0.4, 1.2) |
IBD3 | 0.01 (0.00, 0.05) | 0.05 (0.01, 0.2) | 0.1 (0.0, 0.3) |
Crohn’s disease3 | 0.05 (0.02, 0.1) | 0.08 (0.02, 0.2) | 0.4 (0.2, 0.8) |
Ulcerative colitis3 | 0.1 (0.07, 0.2) | 0.08 (0.02, 0.2) | 0.2 (0.1, 0.5) |
MACE4 | 0.3 (0.2, 0.5) | 0.4 (0.3, 0.7) | 0.6 (0.3, 1.1) |
Neutropenia3 | 0.3 (0.2, 0.4) | 0.2 (0.1, 0.4) | 0.5 (0.3, 1.0) |
Uveitis3 | 0.02 (0.0, 0.07) | 0.1 (0.0, 0.2) | 1.4 (0.9, 2.0) |
Malignancy5 | 0.8 (0.6, 1.0) | 1.1 (0.8, 1.5) | 0.5 (0.2, 0.9) |
Infections
Candida infection
Neutropenia
Inflammatory bowel disease
Major adverse cardiovascular events
Uveitis
Malignancy
Suicidality
Immunogenicity
Injection site reactions
Incidence of AEs by secukinumab dose
Incidence of AEs year-by-year
Post-marketing safety surveillance results
Reporting period | 26 Dec 2014–25 June 2015 | 26 June 2015–25 Dec 2015 | 26 Dec 2015–25 June 2016 | 26 June 2016–25 Dec 2016 | 26 Dec 2016–25 June 2017 | Cumulative rate |
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Exposure | 1838 | 7450 | 16,871 | 28,549 | 41,346 | 96,054 |
Infections and infestations/serious infections and infestations | ||||||
Cases (n) | 178/89 | 495/149 | 712/232 | 1136/475 | 1730/573 | 4483/1688 |
EARR (per 100 PY) | 9.7/4.8 | 6.6/2.0 | 4.2/1.4 | 4.0/1.7 | 4.2/1.4 | 4.7/1.8 |
Neutropenia | ||||||
Cases (n) | 0 | 11 | 12 | 22 | 24 | 66 |
EARR (per 100 PY) | 0 | 0.2 | 0.07 | 0.08 | 0.06 | 0.07 |
Hypersensitivity | ||||||
Cases (n) | 82 | 293 | 425 | 573 | 752 | 2293 |
EARR (per 100 PY) | 4.5 | 3.9 | 2.5 | 2.0 | 1.8 | 2.4 |
Malignant or unspecified tumors | ||||||
Cases (n) | 2 | 15 | 21 | 50 | 76 | 173 |
EARR (per 100 PY) | 0.1 | 0.2 | 0.1 | 0.2 | 0.2 | 0.2 |
Total IBD | ||||||
Cases (n) | 4 | 12 | 37 | 46 | 93 | 195 |
EARR (per 100 PY) | 0.2 | 0.2 | 0.2 | 0.2 | 0.2 | 0.2 |
MACE | ||||||
Cases (n) | 6 | 15 | 16 | 39 | 58 | 148 |
EARR (per 100 PY) | 0.3 | 0.2 | 0.09 | 0.1 | 0.1 | 0.2 |
SIB | ||||||
Cases (n) | 1 | 3 | 6 | 8 | 12 | 35 |
EARR (per 100 PY) | 0.05 | 0.04 | 0.04 | 0.03 | 0.03 | 0.04 |