Table 2.
Indirect comparison of the incidences of adverse events during the induction period (first 12–20 weeks) in phase 2/3 trials of interleukin (IL)-17–targeted biologic therapies; values are number of patients (%)
| Safety and tolerability over 12 weeks | |||
|---|---|---|---|
|
Secukinumaba | |||
| Phase 3 ERASURE study (26) | |||
| Secukinumab 300 mg (n = 245) | Secukinumab 150 mg (n = 245) | Placebo (n = 247) | |
| Any AE | 135 (55.1) | 148 (60.4) | 116 (47.0) |
| Any SAE | 6 (2.4) | 4 (1.6) | 4 (1.6) |
| Death | 0 | 0 | 0 |
| Treatment discontinuation due to AE | 3 (1.2) | 5 (2.0) | 4 (1.6) |
| Most common AEsb | |||
| Nasopharyngitis | 22 (9.0) | 23 (9.4) | 19 (7.7) |
| Headache | 12 (4.9) | 13 (5.3) | 7 (2.8) |
| Infection or infestation | 72 (29.4) | 66 (26.9) | 40 (16.2) |
| Other safety findings | No cases of grade 3 or 4 neutropenia reported for the 12-week induction period | ||
| Phase 3 FIXTURE study (26) | ||||
|---|---|---|---|---|
| Secukinumab 300 mg (n = 326) | Secukinumab 150 mg (n = 327) | Etanercept (n = 323) | Placebo (n = 327) | |
| Any AE | 181 (55.5) | 191 (58.4) | 186 (57.6) | 163 (49.8) |
| Any SAE | 4 (1.2) | 7 (2.1) | 3 (0.9) | 6 (1.8) |
| Death | 0 | 0 | 0 | 0 |
| Treatment discontinuation due to AE | 4 (1.2) | 2 (0.6) | 6 (1.9) | 3 (0.9) |
| Most common AEsb | ||||
| Nasopharyngitis | 35 (10.7) | 45 (13.8) | 36 (11.1) | 26 (8.0) |
| Headache | 30 (9.2) | 16 (4.9) | 23 (7.1) | 23 (7.0) |
| Diarrhea | 17 (5.2) | 12 (3.7) | 11 (3.4) | 6 (1.8) |
| Infection or infestation | 87 (26.7) | 101 (30.9) | 79 (24.5) | 63 (19.3) |
| Phase 3 FEATURE study (27) | |||
|---|---|---|---|
| Secukinumab 300 mg (n = 59) | Secukinumab 150 mg (n = 59) | Placebo (n = 59) | |
| Any AE | 30 (50.8) | 34 (57.6) | 28 (47.5) |
| Any SAE | 3 (5.1) | 0 | 1 (1.7) |
| Death | 0 | 0 | 0 |
| Treatment discontinuation due to AE | 1 (1.7) | 0 | 1 (1.7) |
| Most common AEsb | |||
| Diarrhea | 5 (8.5) | 2 (3.4) | 1 (1.7) |
| Nasopharyngitis | 3 (5.1) | 3 (5.1) | 5 (8.5) |
| Headache | 0 | 4 (6.8) | 3 (5.1) |
| Back pain | 3 (5.1) | 0 | 0 |
| Nausea | 3 (5.1) | 0 | 1 (1.7) |
| Infection or infestation | NR | NR | NR |
| Phase 3 JUNCTURE study (28) | |||
|---|---|---|---|
| Secukinumab 300 mg (n = 60) | Secukinumab 150 mg (n = 61) | Placebo (n = 61) | |
| Any AE | 42 (70.0) | 39 (63.9) | 33 (54.1) |
| Any SAE | 1 (1.7) | 3 (4.9) | 1 (1.6) |
| Death | 0 | 0 | 0 |
| Treatment discontinuation due to AE | 0 | 0 | 1 (1.6) |
| Most common AEsb | |||
| Nasopharyngitis | 19 (31.7) | 14 (23.0) | 10 (16.4) |
| Headache | 3 (5.0) | 5 (8.2) | 3 (4.9) |
| Pruritus | 5 (8.3) | 1 (1.6) | 2 (3.3) |
| Sinusitis | 3 (5.0) | 1 (1.6) | 0 |
| Cough | 3 (5.0) | 0 | 2 (3.3) |
| Infection or infestation | NR | NR | NR |
| Phase 2 study (30) | ||||
|---|---|---|---|---|
| Single dose Secukinumab 150 mg (n = 66) | Monthly dosing Secukinumab 150 mg (n = 138) | Early dosing Secukinumab 150 mg (n = 133) | Placebo (n = 67) | |
| Any AE | 41 (62.1) | 91 (65.9) | 89 (66.9) | 47 (70.1) |
| Any SAE | 3 (4.5) | 3 (2.2) | 6 (4.5) | 1 (1.5) |
| Death | 0 | 0 | 0 | 0 |
| Treatment discontinuation due to AE | 1 (1.5) | 0 | 3 (2.3) | 1 (1.5) |
| Most common AEsb | ||||
| Nasopharyngitis | 8 (12.1) | 31 (22.5) | 30 (22.6) | 12 (17.9) |
| Headache | 6 (9.1) | 8 (5.8) | 11 (8.3) | 3 (4.5) |
| Psoriasisc | 6 (9.1) | 8 (5.8) | 4 (3.0) | 7 (10.4) |
| Infection or infestation | 14 (21.2) | 56 (40.6) | 45 (33.8) | 26 (38.8) |
| Other safety findings | No injection-site reactions or antibodies to secukinumab detected | |||
| No cases of grade 3 or 4 neutropenia | ||||
|
Brodalumab | |||||
|---|---|---|---|---|---|
| Phase 2 study (32) | |||||
| Brodalumab 70 mg (n = 38) | Brodalumab 140 mg (n = 39) | Brodalumab 210 mg (n = 40) | Brodalumab 280 mg (n = 41) | Placebo (n = 37) | |
| Any AE | 26 (68) | 27 (69) | 33 (82) | 30 (73) | 23 (62) |
| Any SAE | 1 (3) | 0 | 1 (2) | 0 | 1 (3) |
| Death | 0 | 0 | 0 | 0 | 0 |
| Treatment discontinuation due to AE | 0 | 0 | 2 (5) | 1 (2) | 1 (3) |
| Most common AEsb | |||||
| Nasopharyngitis | 6 (16) | 1 (3) | 4 (10) | 2 (5) | 3 (8) |
| Upper respiratory tract infection | 3 (8) | 3 (8) | 2 (5) | 5 (12) | 2 (5) |
| Arthralgia | 1 (3) | 2 (5) | 0 | 4 (10) | 1 (3) |
| Injection site erythema | 1 (3) | 1 (3) | 3 (8) | 4 (10) | 1 (3) |
| Pain in extremity | 1 (3) | 0 | 3 (8) | 4 (10) | 0 |
| Nausea | 4 (11) | 1 (3) | 1 (2) | 0 | 1 (3) |
| Infection or infestation | NR | NR | NR | NR | NR |
| Other safety findings | Approximately 6% of patients had injection-site erythema 5% to 10% of patients developed antibodies to brodalumab (none neutralizing) 2 Cases of grade 3 neutropenia (210-mg group) | ||||
| Safety and tolerability over 20 weeks | |||||
|---|---|---|---|---|---|
|
Ixekizumab | |||||
| Phase 2 study (31) | |||||
| Ixekizumab 10 mg (n = 28) | Ixekizumab 25 mg (n = 30) | Ixekizumab 75 mg (n = 29) | Ixekizumab 150 mg (n = 28) | Placebo (n = 27) | |
| Any AE | 21 (75) | 21 (70) | 17 (59) | 13 (46) | 17 (63) |
| Any SAE | 0 | 0 | 0 | 0 | 0 |
| Death | 0 | 0 | 0 | 0 | 0 |
| Treatment discontinuation due to AE | NR | NR | NR | NR | NR |
| Most common AEsb | |||||
| Nasopharyngitis | 3 (11) | 3 (10) | 3 (10) | 4 (14) | 5 (19) |
| Upper respiratory tract infection | 1 (4) | 3 (10) | 1 (3) | 1 (4) | 1 (4) |
| Injection-site reaction | 0 | 3 (10) | 1 (3) | 2 (7) | 0 |
| Headache | 4 (14) | 4 (13) | 1 (3) | 1 (4) | 1 (4) |
| Allergy or hypersensitivity | 1 (4) | 1 (3) | 2 (7) | 1 (4) | 2 (7) |
| Infection or infestation | 12 (43) | 9 (30) | 9 (31) | 8 (29) | 7 (26) |
| Other safety findings | 0% to 10% of patients had injection-site reactions Incidence of antibodies to ixekizumab not reported No cases of grade 3 or 4 neutropenia | ||||
a
The phase 3 SCULPTURE study of secukinumab has not been included because results at week 12 have not yet been reported.
b
Reported in more than 5% of patients in any active treatment group.
c
Indicates worsening of psoriasis; the protocol suggested that psoriasis, being the studied indication, was not to be reported as an AE by the investigators.
AE: adverse event; NR: not reported; SAE: serious adverse event.