Table 2.
Pooled safety outcomes across indications
| Pooled PsO IXE (N = 6892) | Pooled PsA IXE (N = 1401) | Pooled axSpA IXE (N = 932) | |||||||
|---|---|---|---|---|---|---|---|---|---|
| Total patient-years | 18025.7 | 2247.7 | 2097.7 | ||||||
| Maximum exposure (days) | 2236 | 1219 | 1241 | ||||||
| n (%) | IR | 95% CI of IR | n (%) | IR | 95% CI of IR | n (%) | IR | 95% CI of IR | |
| TEAEsa,b | 5857 (85.0) | 32.5 | 31.7, 33.3 | 1131 (80.7) | 50.3 | 47.5, 53.3 | 798 (85.6) | 38.0 | 35.5, 40.8 |
| Mild | 1799 (26.1) | 10.0 | 9.5, 10.5 | 461 (32.9) | 20.5 | 18.7, 22.5 | 276 (29.6) | 13.2 | 11.7, 14.8 |
| Moderate | 3025 (43.9) | 16.8 | 16.2, 17.4 | 556 (39.7) | 24.7 | 22.8, 26.9 | 419 (45.0) | 20.0 | 18.2, 22.0 |
| Severe | 1032 (15.0) | 5.7 | 5.4, 6.1 | 114 (8.1) | 5.1 | 4.2, 6.1 | 103 (11.1) | 4.9 | 4.0, 6.0 |
| Most Common TEAEsn | |||||||||
| Nasopharyngitis | 1592 (23.1) | 8.8 | 8.4, 9.3 | 202 (14.4) | 9.0 | 7.8, 10.3 | 176 (18.9) | 8.4 | 7.2, 9.7 |
| Upper respiratory tract infection | 1114 (16.2) | 6.2 | 5.8, 6.6 | 186 (13.3) | 8.3 | 7.2, 9.6 | 122 (13.1) | 5.8 | 4.9, 6.9 |
| Injection site reaction | 698 (10.1) | 3.9 | 3.6, 4.2 | 156 (11.1) | 6.9 | 5.9, 8.1 | 93 (10.0) | 4.4 | 3.6, 5.4 |
| Arthralgia | 642 (9.3) | 3.6 | 3.3, 3.8 | 34 (2.4) | 1.5 | 1.1, 2,1 | 66 (7.1) | 3.1 | 2.5, 4.0 |
| Headache | 541 (7.8) | 3.0 | 2.8, 3.3 | 56 (4.0) | 2.5 | 1.9, 3.2 | 41 (4.4) | 2.0 | 1.4, 2.7 |
| Back pain | 447 (6.5) | 2.5 | 2.3, 2.7 | 65 (4.6) | 2.9 | 2.3, 3.7 | 50 (5.4) | 2.4 | 1.8, 3.1 |
| Hypertension | 433 (6.3) | 2.4 | 2.2, 2.6 | 64 (4.6) | 2.8 | 2.2, 3.6 | 46 (4.9) | 2.2 | 1.6, 2.9 |
| Bronchitis | 410 (5.9) | 2.3 | 2.1, 2.5 | 91 (6.5) | 4.0 | 3.3, 5.0 | 72 (7.7) | 3.4 | 2.7, 4.3 |
| Diarrhoea | 387 (5.6) | 2.1 | 1.9, 2.4 | 61 (4.4) | 2.7 | 2.1, 3.5 | 60 (6.4) | 2.9 | 2.2, 3.7 |
| Sinusitis | 384 (5.6) 364 | 2.1 | 1.9, 2.4 | 77 (5.5) | 3.4 | 2.7, 4.3 | 39 (4.2) | 1.9 | 1.4, 2.5 |
| Urinary Tract Infection | (5.3) | 2.0 | 1.8, 2.2 | 69 (4.9) | 3.1 | 2.4, 3.9 | 45 (4.8) | 2.1 | 1.6, 2.9 |
| Pharyngitis | 307 (4.5) | 1.7 | 1.5, 1.9 | 54 (3.9) | 2.4 | 1.8, 3.1 | 61 (6.5) | 2.9 | 2.3, 3.7 |
| Injection site erythema | 203 (2.9) | 1.1 | 1.0, 1.3 | 60 (4.3) | 2.7 | 2.1, 3.4 | 33 (3.5) | 1.6 | 1.1, 2.2 |
| Cough | 334 (4.8) | 1.9 | 1.7, 2.1 | 48 (3.4) | 2.1 | 1.6, 2.8 | 17 (1.8) | 0.8 | 0.5, 1.3 |
| SAEso | 969 (14.1) | 5.4 | 5.0, 5.7 | 134 (9.6) | 6.0 | 5.0, 7.1 | 101 (10.8) | 4.8 | 4.0, 5.9 |
| Deaths | 36 (0.5) | 0.2 | 0.1, 0.3 | 6 (0.4) | 0.3 | 0.1, 0.6 | 3 (0.3) | 0.1 | 0.0, 0.4 |
| AE leading to discontinuation (including death) | 519 (7.5) | 2.9 | 2.6, 3.1 | 115 (8.2) | 5.1 | 4.3, 6.1 | 66 (7.1) | 3.1 | 2.5, 4.0 |
| Selected AEs of interest | |||||||||
| Infections | 4307 (62.5) | 23.9 | 23.2, 24.6 | 759 (54.2) | 33.8 | 31.4, 36.3 | 540 (57.9) | 25.7 | 23.7, 28.0 |
| Serious Infections | 231 (3.4) | 1.3 | 1.1, 1.5 | 28 (2.0) | 1.2 | 0.9, 1.8 | 23 (2.5) | 1.1 | 0.7, 1.6 |
| Opportunistic Infections | 536 (7.8) | 3.0 | 2.7, 3.2 | 86 (6.1) | 3.8 | 3.1, 4.7 | 28 (3.0) | 1.3 | 0.9, 1.9 |
| Oral candidiasis | 144 (2.1)c | 0.8 | 0.7, 0.9 | 16 (1.1)d | 0.7 | 0.4, 1.2 | 5 (0.5)e | 0.2 | 0.1, 0.6 |
| Oral fungal infectionf | 11 (0.2) | 0.1 | 0.0, 0.1 | 6 (0.4) | 0.3 | 0.1, 0.6 | 3 (0.3) | 0.1 | 0.0, 0.4 |
| Esophageal candidiasis | 14 (0.2) | 0.1 | 0.0, 0.1 | 2 (0.1) | 0.1 | 0.0, 0.4 | 4 (0.4) | 0.2 | 0.1, 0.5 |
| Herpes zoster | 120 (1.7) | 0.7 | 0.6, 0.8 | 16 (1.1) | 0.7 | 0.4, 1.2 | 12 (1.3) | 0.6 | 0.3, 1.0 |
| Candida Infections | 337 (4.9) | 1.9 | 1.7, 2.1 | 45 (3.2) | 2.0 | 1.5, 2.7 | 26 (2.8) | 1.2 | 0.8, 1.8 |
| Oral Candidag | 160 (2.3) | 0.9 | 0.8, 1.0 | 22 (1.6) | 1.0 | 0.6, 1.5 | 8 (0.9) | 0.4 | 0.2, 0.8 |
| Vulvovaginal Candidah | 97 (4.4) | 1.7 | 1.4, 2.1 | 13 (1.8) | 1.1 | 0.7, 2.0 | 7 (2.5) | 1.2 | 0.6, 2.5 |
| Skin Candida | 52 (0.8) | 0.3 | 0.2, 0.4 | 5 (0.4) | 0.2 | 0.1, 0.5 | 2 (0.2) | 0.1 | 0.0, 0.4 |
| Esophageal candidiasis | 16 (0.2) | 0.1 | 0.1, 0.1 | 2 (0.1) | 0.1 | 0.0, 0.4 | 5 (0.5) | 0.2 | 0.1, 0.6 |
| Latent Tuberculosis | 106 (1.5) | 0.6 | 0.5, 0.7 | 35 (2.5) | 1.6 | 1.1, 2.2 | 2 (0.2) | 0.1 | 0.0, 0.4 |
| Inflammatory bowel diseasei | 26 (0.4) | 0.1 | 0.1, 0.2 | 3 (0.2) | 0.1 | 0.0, 0.4 | 17 (1.8) | 0.8 | 0.5, 1.3 |
| Crohn’s disease | 10 (0.1) | 0.1 | 0.0, 0.1 | 2 (0.1) | 0.1 | 0.0, 0.4 | 7 (0.8) | 0.3 | 0.2, 0.7 |
| Ulcerative colitis | 16 (0.2) | 0.1 | 0.1, 0.1 | 1 (0.1) | 0.0 | 0.0, 0.3 | 10 (1.1) | 0.5 | 0.3, 0.9 |
| Injection site reactionsP | 1056 (15.3) | 5.9 | 5.5, 6.2 | 260 (18.6) | 11.6 | 10.2, 13.1 | 156 (16.7) | 7.4 | 6.4, 8.7 |
| Allergic reactions/hypersensitivities | 1001 (14.5) | 5.6 | 5.2, 5.9 | 102 (7.3) | 4.5 | 3.7, 5.5 | 88 (9.4) | 4.2 | 3.4, 5.2 |
| Malignancies | 141 (2.0) | 0.8 | 0.7, 0.9 | 15 (1.1) | 0.7 | 0.4, 1.1 | 9 (1.0) | 0.4 | 0.2, 0.8 |
| NMSC | 55 (0.8) | 0.3 | 0.2, 0.4 | 9 (0.6) | 0.4 | 0.2, 0.8 | 0 (0.0) | 0.0 | 0.0, 0.4 |
| Malignancies excluding NMSC | 88 (1.3) | 0.5 | 0.4, 0 .6 | 7 (0.5) | 0.3 | 0.1, 0.7 | 9 (1.0) | 0.4 | 0.2, 0.8 |
| Asthma | 49 (0.7) | 0.3 | 0.2, 0.4 | 10 (0.7) | 0.4 | 0.2, 0.8 | 5 (0.5) | 0.2 | 0.1, 0.6 |
| Depression and suicide/self-injuryj | 215 (3.1) | 1.2 | 1.0, 1.4 | 37 (2.6) | 1.6 | 1.2, 2.3 | 19 (2.0) | 0.9 | 0.6, 1.4 |
| MACEk | 91 (1.3) | 0.5 | 0.4, 0.6 | 12 (0.9) | 0.5 | 0.3, 0.9 | 6 (0.6) | 0.3 | 0.1, 0.6 |
| Cytopenial | 171 (2.5) | 0.9 | 0.8, 1.1 | 56 (4.0) | 2.5 | 1.9, 3.2 | 28 (3.0) | 1.3 | 0.9, 1.9 |
| Iridocyclitism | 2 (0.0) | 0.0 | 0.0,0.0 | 0 (0) | 0 | 0.0, 0.0 | 58 (6.2) | 2.8 | 2.1, 3.6 |
Abbreviations: axSpA Axial spondyloarthritis, CI Confidence interval, IR Incidence rate, IXE Ixekizumab, MACE Major adverse cerebro-cardiovascular event, MedDRA Medical Dictionary for Regulatory Activities, N Number of patients in the analysis population; n, number of patients in each category, NMSC Non-melanoma skin cancer, PsA Psoriatic arthritis, PsO Psoriasis, SAE Serious adverse event, SMQ Standardized MedDRA Queries TEAE treatment-emergent adverse event
aPatients with multiple occurrences of the same event are counted under the highest severity
b1 missing case of severity in the PsO cohort
cThe data include 3 cases considered severe, 65 cases considered moderate, and 76 cases considered mild
dData included 3 cases considered moderate and 13 cases considered mild
eData included 2 cases considered moderate and 3 cases considered mild
fAs reported by investigator
gOral Candida infection includes oral candidiasis, oral fungal infection and oropharyngeal candidiasis
hPsO Cohort: Denominator adjusted because gender-specific event for females; N = 2196, PY = 5580.5. PsA Cohort: Denominator adjusted due to gender-specific event for females; N = 722, PY = 1142.2 (pooled IXE). axSpA Cohort: Denominator adjusted because gender-specific event for females; N = 282, PY = 592.8 (pooled IXE)
iData represent adjudicated cases. For the PsO cohort, the data represents cases classified as “definite” and “probable” per external adjudication. IR was calculated as the total of “definite” and “probable” cases /total patient-years, then multiplied by 100. There were 5 cases of adjudicated IBD that were not considered TEAEs. Total adjudicated IBD n = 31 (0.4%, IR of 0.2 per 100 PY). 5 additional cases confirmed by adjudication occurred either on the safety follow-up period (n = 3) or on the placebo maintenance period after IXE treatment (n = 2). 3 patients with PsO had a history of IBD. For the axSpA cohort, 12 cases de novo, 5 patients had a history of IBD and experienced a flare during the study period. 1 additional case of IBD was reported in the safety follow-up
jBroad, according to Standardized MedDRA Queries (SMQ) or sub-SMQ classification
kadjudicated cases
lSMQ classification
m4 cases of uveitis were reported among patients in the PsO cohort (0.1%, IR 0.0 per 100 PY), 8 cases of uveitis were reported among patients in the axSpA cohort (0.9%, IR 0.4 per 100 PY). All studies were conducted using the original, citrate-containing formulation of IXE. AE terms were derived from MedDRA version 24.1 for PsO and axSpA-related studies, version 23.1 for PsA-related studies
nMost common TEAEs are defined as those with an IR > 2.0
oData collection for the clinical trial database does not specify when events became serious and therefore the numbers shown may represent more serious events than what actually occurred during the treatment period
PPreferred MedDRA term. All studies included in these analyses used the original, citrate-containing IXE formulation. axSpA cohort includes patients with AS and nr-axSpA