Comparative safety of systemic immunomodulatory medications in adults with atopic dermatitis

Schneeweiss, Maria C.; Pérez-Chada, Lourdes M.; Merola, Joseph F.

doi:10.1016/j.jaad.2019.05.073

Cited by 23 publications

(28 citation statements)

References 52 publications

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“…In a head‐to‐head comparison of methotrexate (n = 50) vs cyclosporine (n = 47) in moderate‐to‐severe AD adults, infections rates were 32% and 24%, respectively 11 . While methotrexate and cyclosporine are associated with decreased infection rates and favored over treatment with systemic corticosteroids, 12 their impact on susceptibility to/severity of COVID‐19 is unknown and, if essential, precautions should be taken to avoid infection. Of interest, cyclosporine has anticoronavirus activity in vitro , but the effect in humans is unknown 13 …”

Section: Nonbiologic Systemic Therapiesmentioning

confidence: 99%

“…In a double‐blind, placebo‐controlled, crossover study of 37 AD adults treated with azathioprine, there were five cases of upper respiratory infections (URIs) (14%), two cases folliculitis (5%), and one report each impetigo (3%) and sore throat (3%) 18 . In a retrospective analysis of 232 611 systemically treated adults with AD (6 months), there were increased risks of serious and opportunistic infections with azathioprine (relative risk (RR) = 1.89) and prednisone (RR = 1.78) compared with methotrexate, with a reduced risk with cyclosporine (RR = 0.87) 12 . Therefore, azathioprine may increase susceptibility to infections, and if essential, exposure to COVID‐19 should be minimized.…”

Section: Nonbiologic Systemic Therapiesmentioning

confidence: 99%

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Considerations for safety in the use of systemic medications for psoriasis and atopic dermatitis during theCOVID‐19 pandemic

Ricardo

Lipner

2020

Dermatologic Therapy

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Coronavirus disease 2019 (COVID-19) is responsible for at least 2 546 527 cases and 175 812 deaths as of April 21, 2020. Psoriasis and atopic dermatitis (AD) are common, chronic, inflammatory skin conditions, with immune dysregulation as a shared mechanism; therefore, mainstays of treatment include systemic immunomodulating therapies. It is unknown whether these therapies are associated with increased COVID-19 susceptibility or worse outcomes in infected patients. In this review, we discuss overall infection risks of nonbiologic and biologic systemic medications for psoriasis and AD and provide therapeutic recommendations. In summary, in patients with active infection, systemic conventional medications, the Janus kinase inhibitor tofacitinib, and biologics for psoriasis should be temporarily held until there is more data; in uninfected patients switching to safer alternatives should be considered. Interleukin (IL)-17, IL-12/23, and IL-23 inhibitors are associated with low infection risk, with IL-17 and IL-23 favored over IL-12/23 inhibitors. Pivotal trials and postmarketing data also suggest that IL-17 and IL-23 blockers are safer than tumor necrosis factor alpha blockers. Apremilast, acitretin, and dupilumab have favorable safety data and may be safely initiated and continued in uninfected patients. Without definitive COVID-19 data, these recommendations may be useful in guiding treatment of psoriasis and AD patients during the COVID-19 pandemic.

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Section: Nonbiologic Systemic Therapiesmentioning

confidence: 99%

Section: Nonbiologic Systemic Therapiesmentioning

confidence: 99%

Considerations for safety in the use of systemic medications for psoriasis and atopic dermatitis during theCOVID‐19 pandemic

Ricardo

Lipner

2020

Dermatologic Therapy

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“…First data from Italy on dupilumab-treated non-infected in high epidemic areas, and current evidence from dupilumab trials, suggest no negative effect of dupilumab regarding viral infections 151 with reports on a reduced number of herpes simplex superinfections and less bacterial superinfections. [152][153][154] Should dupilumab treatment for atopic dermatitis patients be suspended or modified during the COVID-19 pandemic?…”

Section: Does Dupilumab Treatment Increase Sars-cov-2 Infection Suscementioning

confidence: 99%

A compendium answering over 140 questions on COVID-19 and SARS-CoV-2

Riggioni

Comberiati

Giovannini

et al. 2020

Preprint

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In December 2019, China reported the first cases of the coronavirus disease 2019 (COVID-19). This disease, caused by the severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2), has developed into a pandemic. To date it has resulted in~5.6 million confirmed cases and caused 353,334 related deaths worldwide. Unequivocally, the COVID-19 pandemic is the gravest health and socioeconomic crisis of our time. In this context, numerous questions have emerged in demand of basic scientific information and evidence-based medical advice on SARS-CoV-2 and COVID-19. Although the majority of the patients show a very mild, self-limiting viral respiratory disease, many clinical manifestations in severe patients are unique to COVID-19, such as severe lymphopenia and eosinopenia, extensive pneumonia, a "cytokine storm" leading to acute respiratory distress syndrome, endothelitis, thrombo-embolic complications and multiorgan failure. The epidemiologic features of COVID-19 are distinctive and have changed throughout the pandemic. Vaccine and drug development studies and clinical trials are rapidly growing at an unprecedented speed. However, basic and clinical research on COVID-19-related topics should be based on more coordinated high-quality studies. This paper answers pressing questions, formulated by young clinicians and scientists, on SARS-CoV-2, COVID-19 and allergy, focusing on the following topics: virology, immunology, diagnosis, management of patients with allergic disease and asthma, treatment, clinical trials, drug discovery, vaccine development and epidemiology. Over 140 questions were answered by experts in the field providing a comprehensive and practical overview of COVID-19 and allergic disease.

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“…On the other hand, should treatment need to be paused in the pandemic, the longer half‐life and particular pharmacokinetics of biological therapies will limit the speed of their systemic clearance. Although real‐world observational data suggest an increased risk of serious infections with some agents, their relative safety in relation to COVID‐19 is unknown . Conversely, there is a theoretical protective role of immunomodulators in attenuating a severe systemic inflammatory response to infection.…”

mentioning

confidence: 99%

Global reporting of cases of COVID‐19 in psoriasis and atopic dermatitis: an opportunity to inform care during a pandemic

et al. 2020

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Gambichler and colleagues 1 about a decline of programmed death (PD)-1 + circulating T regulatory cells (Tregs) predicting clinical outcome in anti-PD-1 therapy. The study highlights the potential and importance of immune monitoring in anti-PD-1 checkpoint therapy in malignant melanoma. However, their conclusion about anti-PD-1 antibody treatment effecting a decline of PD-1 + Tregs is misleading. A decline of a cell population infers 'disappearance', which normally is not the effect of therapeutic blocking antibodies. Their IgG4 backbones save target cells from antibody and/or complement-dependent cell-mediated cytotoxicity and depletion from circulation. The reported 'decrease' of CD4 + CD25 ++ CD127-PD-1 + T cells thus lacks acknowledging that cell-bound therapeutic anti-PD-1 antibodies may simply interfere with detection by anti-PD1 detection antibodies due to 'steric hindrance'. In fact, it is well established that therapeutic and several clones of detection anti-PD1 antibodies compete for the same epitope. 2,3 Differentiating a 'decrease' from 'not detectable' is important because blocking effects are reversible as soon as trough plasma levels of therapeutic antibodies subside. This implicates possible disease reactivation following treatment discontinuation but also the opportunity to accelerate a washout of the therapeutic antibody if needed. We learned this from natalizumab, an alpha-4 integrin blocking antibody used for the treatment of multiple sclerosis, where discontinuation turned out to be a major problem associated with alpha-4 re-expression dynamics. In contrast, in the case of a rare but fatal treatment complication due to John Cunningham virus reactivation, an accelerated natalizumab washout by plasma exchange allowed a hurrying up of reexpression of alpha-4 for re-establishing immune competence. 4 The question remains as to whether the extent of PD-1 expression is not detectable because of bound therapeutic antibody or because of a true decrease in the form of shedding or internalization of receptor-antibody complexes. Of note, Zelba and colleagues already approached this question and developed a flow cytometry method for quantifying PD-1-expressing T cells including the detection of cell-bound therapeutic antibodies with antihuman IgG4 detection antibodies. 3 Our second point concerns the patient highlighted in Figure 1 in the article by Gambichler et al., 1 showing a paradoxical increase of PD-1 + Treg frequencies under anti-PD-1 therapy. This astonishing observation raises the question of an increased drug-antibody turnover, possibly due to the presence of anti-PD-1 neutralizing antibodies. According to the European Medicines Agency/European Public Assessment Report product information for Opdivo and Keytruda, 5,6 antidrug antibodies occurred in 11% of 2022 nivolumab-treated patients, with neutralizing antidrug antibodies in 0Á7% patients, and in 2% of 2034 pembrolizumab-treated patients with neutralizing antidrug antibodies in 0Á4%. Although rare, anti-PD-1 neutralizing antibodies occur and...

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Comparative safety of systemic immunomodulatory medications in adults with atopic dermatitis

Cited by 23 publications

References 52 publications

Considerations for safety in the use of systemic medications for psoriasis and atopic dermatitis during theCOVID‐19 pandemic

Considerations for safety in the use of systemic medications for psoriasis and atopic dermatitis during theCOVID‐19 pandemic

A compendium answering over 140 questions on COVID-19 and SARS-CoV-2

Global reporting of cases of COVID‐19 in psoriasis and atopic dermatitis: an opportunity to inform care during a pandemic

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