To the Editor: With daily media warnings of a looming pandemic, physicians are understandably concerned about immunosuppressive or immunomodulating effects that might render patients receiving biologic therapies more susceptible to COVID-19 infection. At this early stage, we do not have specific data about susceptibility to the virus, but we have data on infectious complications for biologic therapies from their pivotal trials for psoriasis.
In Table I , we compare overall infection rates as well as rates of upper respiratory infections and nasopharyngitis for each drug versus its placebo control based on published data from pivotal trials.
Table I.
Rate of infections in available biologic agents for psoriasis, n (%)
| Class | Biologics | Infections, overall: biologics/placebo | URTI: biologics/placebo | Nasopharyngitis: biologics/placebo |
|---|---|---|---|---|
| TNF | Etanercept | NR | 51 (13)/25 (13)† | NR |
| Adalimumab | 235 (29)/89 (22) | 59 (7)/14 (4) | 73 (8)/37 (8)∗ | |
| Infliximab | 125 (42)/30 (40) | 135 (15)/41 (14)∗,† | 50 (5)/13 (5)∗,† | |
| Certolizumab | 129 (36)/31 (31)∗,† | 24 (7)/5 (5)∗,† | 50 (14)/12 (12)∗,† | |
| IL-12/IL-23 | Ustekinumab | 326 (25)/150 (23)∗,† | 64 (5)/30 (5)∗,† | 105 (8)/29 (8)∗,† |
| IL-23 | Guselkumab | 191 (23)/90 (21)∗ | 41 (5)/19 (5)∗ | 65 (8)/33 (8)∗ |
| Tildrakizumab | NR | 25 (2)/9 (3)∗,† | 120 (10)/20 (6)∗,† | |
| Risankizumab | 131 (22)/26 (13)∗ | 28 (5)/4 (2)∗ | NR | |
| IL-17 | Secukinumab | 326 (29)/103 (18)∗,† | 36 (3)/3 (1)∗,† | 125 (11)/45 (8)∗,† |
| Ixekizumab | 381 (26)/74 (21)∗,† | 51 (3)/12 (3)∗,† | 119 (8)/28 (8)∗,† | |
| Brodalumab | NR | 112 (5)/40 (6)∗,† | 157 (6)/36 (6)∗,† |
IL, Interleukin; NR, not reported; TNF, tumor necrosis factor; URTI, upper respiratory tract infection.
Data were collected from 2 pivotal phase 3 trials and are reported as the mean.
Combined doses are reported as the mean.
For tumor necrosis factor blockers, during the placebo-controlled periods, overall infections and upper respiratory infections were increased by up to 7% compared with placebo, except for etanercept, which showed no increase. Tumor necrosis factor blockers carry a black box warning concerning infection. Ustekinumab showed a small increase in overall infections but not in respiratory tract infections. Ustekinumab blocks interleukin (IL) 12 and IL-23; IL-12 plays an important role in fighting viral infections.1 IL-23 blockers showed increases in overall infections of up to 9%, but upper respiratory infections were increased slightly in some trials but not in others. IL-17 blockers showed increases in overall infections of up to 11%, but much of that increase could be accounted for by increases in monilial infections. Upper respiratory infections were increased slightly for secukinumab, but not for ixekizumab or brodalumab.
It is difficult to extrapolate from these data to determine susceptibility to coronavirus infection, and this analysis is further flawed by small numbers of infections and short placebo-controlled periods. Moreover, minor respiratory infections may be underreported, and some infections may be reported doubly as upper respiratory infections and as nasopharyngitis.
Nonetheless, these data may be used to decide whether to continue biologic therapy during pandemics. We do not know if biologic therapies render patients more susceptible to coronavirus, but we know that in the pre-coronavirus era, respiratory infection rates were comparable to those with placebo. Conversely, discontinuation of some biologics can result in loss of response when treatments are reintroduced or even result in the formation of antibodies to the discontinued biologic.2, 3, 4 All of these factors must be considered when advising patients about continuing or discontinuing biologic therapies.
Footnotes
Funding sources: None.
Disclosure: Dr Lebwohl is an employee of Mount Sinai; receives research funds from AbbVie, Amgen, Eli Lilly, Janssen Research and Development, LLC, Novartis, Ortho Dermatologics, Sanofi-Regeneron, and UCB, Inc; and has been the principal investigator for numerous clinical trials but has no personal financial gain. Dr Murrell is an employee of St George Hospital; has been an investigator/advisor for Novartis, Sun Pharma, Janssen, and AbbVie; and is the director of a clinical trial center for dermatologic diseases. Dr Rivera-Oyola has no conflicts of interest to declare.
IRB approval status: Not applicable.
Accepted for publication March 11, 2020.
Reprints not available from the authors.
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