Should biologics for psoriasis be interrupted in the era of COVID-19?

Published:March 18, 2020DOI:https://doi.org/10.1016/j.jaad.2020.03.031
      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 IRate of infections in available biologic agents for psoriasis, n (%)
      ClassBiologicsInfections, overall: biologics/placeboURTI: biologics/placeboNasopharyngitis: biologics/placebo
      TNFEtanerceptNR51 (13)/25 (13)
      Combined doses are reported as the mean.
      NR
      Adalimumab235 (29)/89 (22)59 (7)/14 (4)73 (8)/37 (8)
      Data were collected from 2 pivotal phase 3 trials and are reported as the mean.
      Infliximab125 (42)/30 (40)135 (15)/41 (14)
      Data were collected from 2 pivotal phase 3 trials and are reported as the mean.
      ,
      Combined doses are reported as the mean.
      50 (5)/13 (5)
      Data were collected from 2 pivotal phase 3 trials and are reported as the mean.
      ,
      Combined doses are reported as the mean.
      Certolizumab129 (36)/31 (31)
      Data were collected from 2 pivotal phase 3 trials and are reported as the mean.
      ,
      Combined doses are reported as the mean.
      24 (7)/5 (5)
      Data were collected from 2 pivotal phase 3 trials and are reported as the mean.
      ,
      Combined doses are reported as the mean.
      50 (14)/12 (12)
      Data were collected from 2 pivotal phase 3 trials and are reported as the mean.
      ,
      Combined doses are reported as the mean.
      IL-12/IL-23Ustekinumab326 (25)/150 (23)
      Data were collected from 2 pivotal phase 3 trials and are reported as the mean.
      ,
      Combined doses are reported as the mean.
      64 (5)/30 (5)
      Data were collected from 2 pivotal phase 3 trials and are reported as the mean.
      ,
      Combined doses are reported as the mean.
      105 (8)/29 (8)
      Data were collected from 2 pivotal phase 3 trials and are reported as the mean.
      ,
      Combined doses are reported as the mean.
      IL-23Guselkumab191 (23)/90 (21)
      Data were collected from 2 pivotal phase 3 trials and are reported as the mean.
      41 (5)/19 (5)
      Data were collected from 2 pivotal phase 3 trials and are reported as the mean.
      65 (8)/33 (8)
      Data were collected from 2 pivotal phase 3 trials and are reported as the mean.
      TildrakizumabNR25 (2)/9 (3)
      Data were collected from 2 pivotal phase 3 trials and are reported as the mean.
      ,
      Combined doses are reported as the mean.
      120 (10)/20 (6)
      Data were collected from 2 pivotal phase 3 trials and are reported as the mean.
      ,
      Combined doses are reported as the mean.
      Risankizumab131 (22)/26 (13)
      Data were collected from 2 pivotal phase 3 trials and are reported as the mean.
      28 (5)/4 (2)
      Data were collected from 2 pivotal phase 3 trials and are reported as the mean.
      NR
      IL-17Secukinumab326 (29)/103 (18)
      Data were collected from 2 pivotal phase 3 trials and are reported as the mean.
      ,
      Combined doses are reported as the mean.
      36 (3)/3 (1)
      Data were collected from 2 pivotal phase 3 trials and are reported as the mean.
      ,
      Combined doses are reported as the mean.
      125 (11)/45 (8)
      Data were collected from 2 pivotal phase 3 trials and are reported as the mean.
      ,
      Combined doses are reported as the mean.
      Ixekizumab381 (26)/74 (21)
      Data were collected from 2 pivotal phase 3 trials and are reported as the mean.
      ,
      Combined doses are reported as the mean.
      51 (3)/12 (3)
      Data were collected from 2 pivotal phase 3 trials and are reported as the mean.
      ,
      Combined doses are reported as the mean.
      119 (8)/28 (8)
      Data were collected from 2 pivotal phase 3 trials and are reported as the mean.
      ,
      Combined doses are reported as the mean.
      BrodalumabNR112 (5)/40 (6)
      Data were collected from 2 pivotal phase 3 trials and are reported as the mean.
      ,
      Combined doses are reported as the mean.
      157 (6)/36 (6)
      Data were collected from 2 pivotal phase 3 trials and are reported as the mean.
      ,
      Combined doses are reported as the mean.
      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.
      • Gee K.
      • Guzzo C.
      • Che Mat N.F.
      • Ma W.
      • Kumar A.
      The IL-12 family of cytokines in infection, inflammation and autoimmune disorders.
      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.
      • Reich K.
      • Ortonne J.P.
      • Gottlieb A.B.
      • et al.
      Successful treatment of moderate to severe plaque psoriasis with the PEGylated Fab' certolizumab pegol: results of a phase II randomized, placebo-controlled trial with a re-treatment extension.
      • Ortonne J.P.
      • Taïeb A.
      • Ormerod A.D.
      • et al.
      Patients with moderate-to-severe psoriasis recapture clinical response during re-treatment with etanercept.
      • Blauvelt A.
      • Papp K.A.
      • Sofen H.
      • et al.
      Continuous dosing versus interrupted therapy with ixekizumab: an integrated analysis of two phase 3 trials in psoriasis [published correction appears in J Eur Acad Dermatol Venereol. 2017;31(10):1764].
      All of these factors must be considered when advising patients about continuing or discontinuing biologic therapies.

      References

        • Gee K.
        • Guzzo C.
        • Che Mat N.F.
        • Ma W.
        • Kumar A.
        The IL-12 family of cytokines in infection, inflammation and autoimmune disorders.
        Inflamm Allergy Drug Targets. 2009; 8: 40-52
        • Reich K.
        • Ortonne J.P.
        • Gottlieb A.B.
        • et al.
        Successful treatment of moderate to severe plaque psoriasis with the PEGylated Fab' certolizumab pegol: results of a phase II randomized, placebo-controlled trial with a re-treatment extension.
        Br J Dermatol. 2012; 167: 180-190
        • Ortonne J.P.
        • Taïeb A.
        • Ormerod A.D.
        • et al.
        Patients with moderate-to-severe psoriasis recapture clinical response during re-treatment with etanercept.
        Br J Dermatol. 2009; 161: 1190-1195
        • Blauvelt A.
        • Papp K.A.
        • Sofen H.
        • et al.
        Continuous dosing versus interrupted therapy with ixekizumab: an integrated analysis of two phase 3 trials in psoriasis [published correction appears in J Eur Acad Dermatol Venereol. 2017;31(10):1764].
        J Eur Acad Dermatol Venereol. 2017; 31: 1004-1013

      Linked Article

      • COVID-19, syphilis, and biologic therapies for psoriasis and psoriatic arthritis: A word of caution
        Journal of the American Academy of DermatologyVol. 82Issue 6
        • In Brief
          To the Editor: I read the timely and thought-provoking article about the coronavirus disease 2019 (COVID-19) pandemic and biologic therapy for psoriasis by Lebwohl et al.1 The authors compiled research data about almost all the most commonly used biologics in dermatology and their rates of infection, upper respiratory infections, and nasopharyngitis based on current published studies.
        • Full-Text
        • PDF
      • COVID-19 and immunomodulator/immunosuppressant use in dermatology
        Journal of the American Academy of DermatologyVol. 82Issue 5
        • In Brief
          To the Editor: We read with great interest the Commentary by Lebwohl et al1 recently published in the Journal of the American Academy of Dermatology. The authors provided a pertinent overview of infection risk associated with commonly used biologics to treat psoriasis in light of the current coronavirus disease 2019 (COVID-19) outbreak. We agree that this time has been particularly concerning for patients taking immunomodulators/immunosuppressants who are unsure of their risk for severe disease.
        • Full-Text
        • PDF
      • Adalimumab for treatment of hidradenitis suppurativa during the COVID-19 pandemic: Safety considerations
        Journal of the American Academy of DermatologyVol. 83Issue 1
        • In Brief
          To the Editor: With the peak of coronavirus disease 2019 (COVID-19) expected to occur in many regions of the United States in the coming weeks to months, physicians and patients alike are concerned about the use of immunosuppressive, biologic agents given the increased infection risk. A recent Letter to the Editor highlighted the risk of total infections, upper respiratory tract infections, and nasopharyngitis in patients with psoriasis on immunomodulating biologic therapy.1
        • Full-Text
        • PDF
      • Reply: “Biologics for psoriasis during COVID-19 outbreak”
        Journal of the American Academy of DermatologyVol. 82Issue 6
        • In Brief
          To the Editor: We read with interest the letter by Lebwohl et al,1 “Should biologics for psoriasis be interrupted in the era of COVID-19?” We share the concern that has been expressed about the possible impact of biologic therapies on the patient's susceptibility to COVID-19 infection. In addition to the infectious complications for biologic therapies reported during pivotal trials for psoriasis, we would like to draw attention to other aspects that might guide the decision whether to continue biologic therapy during the COVID-19 pandemic.
        • Full-Text
        • PDF