Table 4.
Safety assessment
| Safety assessment | Current study (OLE) | CHRONOS (52 weeks) | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 300 mg qw/q2w (N = 2677) | Placebo + TCS (n = 315) | 300 mg qw + TCS (n = 315) | ||||||||||
| Event | Patients with ≥1 event, n (%) | nE/100 PY | nP/100 PY | Event | Patients with ≥1 event, n (%) | nE/100 PY | nP/100 PY | Event | Patients with ≥1 event, n (%) | nE/100 PY | nP/100 PY | |
| TEAE | 14,569 | 2273 (84.9) | 256.86 | 167.50 | 1520 | 268 (85.1) | 531.9 | 325.08 | 1500 | 263 (83.5) | 504.47 | 322.43 |
| Serious TEAE | 383 | 278 (10.4) | 6.75 | 5.20 | 24 | 16 (5.1) | 8.40 | 5.75 | 11 | 10 (3.2) | 3.70 | 3.40 |
| Severe TEAE | 383 | 263 (9.8) | 6.75 | 4.96 | 46 | 28 (8.9) | 16.10 | 10.31 | 24 | 17 (5.4) | 8.07 | 5.88 |
| TEAE leading to study drug discontinuation | 120 | 99 (3.7) | 2.12 | 1.76 | 29 | 25 (7.9) | 10.15 | 9.14 | 10 | 9 (2.9) | 3.36 | 3.06 |
| Serious TEAE related to treatment | 38 | 33 (1.2) | 0.67 | 0.58 | 3 | 3 (1.0) | 1.05 | 1.06 | 2 | 2 (0.6) | 0.67 | 0.68 |
| Deatha | 3 | 3 (0.1) | 0.05 | 0.05 | 0 | 0 | 0 | 0 | 1 | 1 (0.3) | 0.34 | 0.34 |
| Most common TEAEs by PT (≥5% of patients in the OLE) | ||||||||||||
| Nasopharyngitis | 1593 | 773 (28.9) | 28.09 | 17.95 | 90 | 62 (19.7) | 31.49 | 24.93 | 86 | 62 (19.7) | 28.92 | 24.16 |
| Atopic dermatitisb | 780 | 444 (16.6) | 13.75 | 8.95 | 243 | 147 (46.7) | 85.03 | 74.32 | 91 | 55 (17.5) | 30.60 | 20.71 |
| Upper respiratory tract infection | 561 | 362 (13.5) | 9.89 | 7.15 | 48 | 32 (10.2) | 16.80 | 12.03 | 65 | 43 (13.7) | 21.86 | 15.85 |
| Oral herpes | 446 | 199 (7.4) | 7.86 | 3.77 | 13 | 9 (2.9) | 4.55 | 3.20 | 29 | 15 (4.8) | 9.75 | 5.21 |
| Conjunctivitis | 415 | 276 (10.3) | 7.32 | 5.33 | 7 | 5 (1.6) | 2.45 | 1.77 | 11 | 8 (2.5) | 3.70 | 2.73 |
| Headache | 411 | 218 (8.1) | 7.25 | 4.14 | 31 | 19 (6.0) | 10.85 | 6.98 | 48 | 25 (7.9) | 16.14 | 8.97 |
| Injection-site reaction | 506 | 138 (5.2) | 8.92 | 2.54 | 105 | 25 (7.9) | 36.74 | 9.39 | 229 | 61 (19.4) | 77.015 | 24.46 |
| Injection-site reactions (HLT) | 857 | 263 (9.8) | 15.11 | 5.04 | 105 | 25 (7.9) | 36.74 | 9.39 | 232 | 63 (20.0) | 78.02 | 25.46 |
| Skin infectionsc | 316 | 248 (9.3) | 5.57 | 4.69 | 83 | 57 (18.1) | 29.04 | 20.21 | 29 | 26 (8.3) | 9.75 | 7.87 |
| Herpes viral infections (HLT) | 809 | 343 (12.8) | 14.26 | 6.78 | 32 | 25 (7.9) | 11.20 | 9.17 | 43 | 22 (7.0) | 14.46 | 7.72 |
| Eczema herpeticum (PT) | 15 | 13 (0.5) | 0.26 | 0.23 | 6 | 6 (1.9) | 2.10 | 2.13 | 0 | 0 | 0 | 0 |
| Most common serious TEAEs by PT (≥0.2% of patients in the OLE) | ||||||||||||
| Squamous cell carcinoma of skin | 14 | 8 (0.3) | 0.25 | 0.14 | 0 | 0 | 0 | 0 | 1 | 1 (0.3) | 0.34 | 0.34 |
| Osteoarthritis | 10 | 9 (0.3) | 0.18 | 0.16 | 0 | 0 | 0 | 0 | 1 | 1 (0.3) | 0.34 | 0.34 |
| Dermatitis atopic | 7 | 6 (0.2) | 0.12 | 0.11 | 1 | 1 (0.3) | 0.35 | 0.35 | 2 | 1 (0.3) | 0.67 | 0.34 |
| Syncope | 6 | 5 (0.2) | 0.11 | 0.09 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Inguinal hernia | 5 | 5 (0.2) | 0.09 | 0.09 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Appendicitis | 5 | 5 (0.2) | 0.09 | 0.09 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Ligament rupture | 5 | 5 (0.2) | 0.09 | 0.09 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Conjunctivitisd | ||||||||||||
| Conjunctivitis | 888 | 536 (20.0) | 15.66 | 11.37 | 29 | 25 (7.9) | 10.15 | 9.24 | 91 | 61 (19.4) | 30.60 | 23.37 |
| Serious conjunctivitis | 1e | 1 (<0.1) | 0.02 | 0.02 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Conjunctivitis related to study drug | 369 | 258 (9.6) | 6.51 | 4.94 | 7 | 5 (1.6) | 2.45 | 1.77 | 23 | 15 (4.8) | 7.74 | 5.21 |
| Conjunctivitis that recovered/resolved during the treatment period | 775 | 463 (17.3) | 13.66 | 9.64 | 27 | 23 (7.3) | 9.45 | 8.47 | 81 | 55 (17.5) | 27.24 | 20.80 |
| Conjunctivitis by severity |
11.1 9.96 0.68 |
|||||||||||
| Mild | 451 | 248 (9.3) | 7.95 | 4.71 | 17 | 15 (4.8) | 5.95 | 5.41 | 49 | 31 (9.8) | 16.48 | |
| Moderate | 408 | 262 (9.8) | 7.19 | 5.05 | 11 | 9 (2.9) | 3.85 | 3.22 | 39 | 28 (8.9) | 13.12 | |
| Severe | 29 | 26 (1.0) | 0.51 | 0.46 | 1 | 1 (0.3) | 0.35 | 0.35 | 3 | 2 (0.6) | 1.01 | |
| Conjunctivitis leading to discontinuation | 14 | 14 (0.5) | 0.25 | 0.25 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Conjunctivitis by range of study drug exposure, weeks | ||||||||||||
| < 26 | 354 | 282/2677 (10.5) | 27.07 | 23.04 | 18 | 17/315 (5.4) | 12.16 | 11.87 | 50 | 41/315 (13.0) | 33.29 | 29.25 |
| 26 to <51 | 192 | 164/2578 (6.4) | 16.15 | 14.31 | 11 | 10/283 (3.5) | 8.41 | 7.83 | 39 | 33/297 (11.1) | 27.89 | 25.28 |
| 51 to <76 | 141 | 119/2316 (5.1) | 13.52 | 11.76 | 0 | 0/265 (0.0) | 0 | 0 | 2 | 2/286 (0.7) | 27.36 | 27.43 |
| 76 to <101 | 71 | 66/2025 (3.3) | 9.15 | 8.66 | – | – | – | – | – | – | – | – |
| 101 to <126 | 44 | 37/1316 (2.8) | 8.97 | 7.66 | – | – | – | – | – | – | – | – |
| 126 to <151 | 34 | 25/803 (3.1) | 10.73 | 8.06 | – | – | – | – | – | – | – | – |
| 151 to <176 | 24 | 23/567 (4.1) | 11.30 | 11.15 | – | – | – | – | – | – | – | – |
| 176 to <201 | 13 | 9/355 (2.5) | 9.10 | 6.40 | – | – | – | – | – | – | – | – |
| 201 to <226 | 10 | 10/248 (4.0) | 8.57 | 8.73 | – | – | – | – | – | – | – | – |
| 226 to <251 | 4 | 3/238 (1.3) | 4.39 | 3.33 | – | – | – | – | – | – | – | – |
| 251 to <276 | 1 | 1/132 (0.8) | 2.56 | 2.57 | – | – | – | – | – | – | – | – |
| 276 to <301 | 0 | 0/30 (0.0) | 0 | 0 | – | – | – | – | – | – | – | – |
| 301 to <326 | 0 | 0/5 (0.0) | 0 | 0 | – | – | – | – | – | – | – | – |
HLT MedDRA high-level term, MedDRA Medical Dictionary for Regulatory Activities, nE number of events, nP number of patients, OLE open-label extension, PT MedDRA preferred term, PY patient-year, q2w every 2 weeks, qw weekly, SOC MedDRA system organ class, TCS topical corticosteroid, TEAE treatment-emergent adverse event
aAll three deaths in the OLE were unrelated to dupilumab treatment: one death in the OLE was because of natural causes in an 88-year-old woman, one was because of unknown causes in a 60-year-old woman approximately 5 months after the final dose of study drug, one was because of unknown causes in a 42-year-old man; death in CHRONOS previously reported
bWorsening of atopic dermatitis
cAdjudicated PTs reported under the SOC “infections and infestations”
dConjunctivitis reported as TEAEs and includes the following PTs: conjunctivitis, conjunctivitis allergic, conjunctivitis bacterial, conjunctivitis viral, and atopic keratoconjunctivitis
ePatient with atopic keratoconjunctivitis was hospitalized for excision of corneal pannus; not related to study drug