Table 2.
Rate of respiratory infections for biologics and small‐molecule agents at primary endpoint analysis during pivotal phase III dermatology trials
| Class and main indication in dermatology | Agent | URTI rate (treatment:placebo) | Nasopharyngitis rate (treatment:placebo) | Serious infection rate (treatment:placebo) |
|---|---|---|---|---|
| TNF‐alpha inhibitors (psoriasis) |
Adalimumab 34 (n = 1212) |
7.2% vs. 3.5% | 5.3% vs. 6.5% | 1.8% vs. 1.8% |
|
Infliximab 35 (n = 378) |
15% vs. 16% | NA | NA (treated infection rate 15% vs. 15%) | |
|
Etanercept 36 (n = 611) |
13% (high dose) vs. 13% (low dose) vs. 13% | NA | 1 case in placebo only | |
|
IL‐12/23 inhibitor (psoriasis) |
Ustekinumab 37 (n = 766) |
7.1% (high dose) vs. 6.3% (low dose) vs. 6.3% | 10.2% (high dose) vs. 8.2% (low dose) vs. 8.6 % | 0% (high dose) vs. 0.8% (low dose) vs. 0.4% |
|
IL‐17 inhibitors (psoriasis) |
Secukinumab 38 (n = 738; 2 trials) |
2.1% (high dose) vs. 3.1% (low dose) vs. 2.2% | 10.7% (high dose) vs. 13.8% (low dose) vs. 11.1% | 1% (high dose) vs. 0.7% (low dose) vs. 1.5% |
|
Ixekizumab 39 (n = 1296; 2 trials) |
4.4% (high dose) vs. 3.9% (low dose) vs. 3.5% | 9.5% (high dose) vs. 9% (low dose) vs. 8.7% | 0.4% (high dose) vs. 0.7% (low dose) vs. 0.4% | |
|
Brodalumab 40 (n = 1776; 2 trials) |
5.4% (high dose) vs. 4.9% (low dose) vs. 7.4% | 7.4% (high dose) vs. 7.4% (low dose) vs. 4.7% |
1% (high dose) vs. 2.1% (low dose) vs. 2.6% |
|
|
IL‐23 inhibitors (psoriasis) |
Guselkumab 41 (n = 992) |
5.1% vs. 2.8% | 7.1% vs. 6.5% | 0.2% vs. 0.4% |
|
Risankizumab 42 (n = 997; 2 trials) |
5% vs. 4% | NA | 2.2% vs. 2% | |
|
Tildrakizumab 43 (n = 1862; 2 trials) |
2.4% (high dose) vs. 1.6% (low dose) vs. 2.9% | 8.8% (high dose) vs. 10.6% (low dose) vs. 6.5% | 0.3% (high dose) vs. 0.2% (low dose) vs. 0.2% | |
|
IL‐4 and IL‐13 inhibitors (atopic dermatitis) |
Dupilumab 44 (n = 1379; 2 trials) |
5% (high dose) vs. 2.6% (low dose) vs. 2.3% | 11.5% (high dose) vs. 9.6% (low dose) vs. 7.7% | 0.9% (high dose) vs. 1.1% (low dose) vs. 2.9% |
|
IgE inhibitor (chronic spontaneous urticaria) |
Omalizumab 45 (n = 323) |
1.3% (high dose) vs. 1.3% (low dose) vs. 1.3% | 12.7% (high dose) vs. 17.1% (low dose) vs. 16.5% | 0% (high dose) vs. 1.3% (low dose) vs. 2.5% |
|
Janus kinase inhibitors (atopic dermatitis) |
Baricitinib 46 (n = 1239; 2 trials) |
3.2% (high dose) vs. 2.8% (low dose) vs. 2.2% | 8.9% (high dose) vs. 13.9% (low dose) vs. 11.4% | 1.2% (high dose) vs. 4.0% (low dose) vs. 3.0% |
| PDE‐4 inhibitors (psoriasis) |
Apremilast 47 (n = 844) |
10.2% vs. 7.4% | 7.3% vs. 8.2% | Nil in placebo‐controlled period |
| Anti B‐cell (anti‐CD20) † |
Rituximab 48 (n = 520; rheumatoid arthritis trial) |
7.8% vs. 6.7% | 7.5% vs. 5.7% | 2.3% vs. 1.4% |
Imbalances of greater than twofold between treatment and placebo have been bolded.
NA, not available. URTI, upper respiratory tract infection.
Rates of serious infection in patients with rheumatoid arthritis treated with rituximab appear to be dose related; serious infections that have been reported include HBV reactivation, Pneumocystis carinii and JC virus.