International Psoriasis Council

Advancing Knowledge. Enhancing Care.

Advancing Knowledge. Enhancing Care.

Commentary: The risk of respiratory tract infections and symptoms in psoriasis patients treated with IL-17-pathway inhibiting biologics

Luigi Naldi, MD
Centro Studi GISED
Bergamo, Italy

PUBLICATION

The risk of respiratory tract infections and symptoms in psoriasis patients treated with IL-17-pathway inhibiting biologics: A meta-estimate of pivotal trials relevant to decision-making during the COVID-19 pandemic. Wan MT, Shin DB, Winthrop KL, Gelfand JM. Journal of the American Academy of Dermatology (2020), doi: https://doi.org/10.1016/j.jaad.2020.05.035.

COMMENTARY

Searching for signals of increased risk of infection in specific subgroups is vitally important, especially when confronted with a severe threat to health, like the worldwide spread of the SARS-CoV-2 virus. There are two complementary needs: 1. The need to interrupt or reduce the speed of viral dissemination within the community; 2. The need to mitigate the consequences of the infection and to inform timely clinical decisions, both at the population and at the clinical level – the cure should not be worse than the disease – and decisions should be informed by adequate evidence, balancing benefits and risks.

Whether biologic agents for psoriasis may place patients at a higher risk for COVID-19 or influence a more severe disease course, is an important question. In their paper, Marilyn T. Wan and colleagues, have tried to address the question for the IL-17 inhibitors. No data exist on exposure to IL-17 antagonists and COVID-19 incidence or outcome, and the authors’ approach to address the question was an indirect one, using surrogate measures.

Wan, et al., pooled in a meta-analysis, data on the rates of respiratory tract infection (RTI) obtained in placebo-controlled phase 3 studies of IL-17 antagonists. The meta-analysis documented a 56% increased risk of RTI in the IL-17 antagonist arm, compared with the placebo arm. The authors concluded there was a signal of a potential danger. I contend that the evidence presented by the authors may help inform clinical decisions when confronted with SARS-CoV-2 infection.

The questions raised by the paper are threefold: 1. Are all RTIs created equal?; 2. Can an increased risk for one agent be translated into an increased risk for any other agent causing RTI?; and 3. Is the severity and outcome of RTI influenced by the treatment?

The IL-17 cytokine family is a pleiotropic group of molecules that function in a wide variety of beneficial and pathological processes, mainly at the mucosal interface. The IL-17/IL-22 axis is important in both responding to, and recovering from, pathogens. However, aberrant expression or overexpression of IL-17 contributes to a number of pathological outcomes, including pneumonitis, and development of pulmonary fibrosis. As indicated by Dr. Wan and colleagues, severe COVID-19 illness is characterized by a dysregulated immune response, the so-called cytokine storm, with increased levels of plasma pro-inflammatory cytokines mainly derived from Th1-Th17 cells. Trials evaluating IL17 antagonists are ongoing in COVID-19 management.

Direct evidence is required to inform clinical decisions. We need to know if people with psoriasis exposed to IL-17 antagonists  are at an increased risk of SARS-CoV-2 infection as compared with people exposed to other treatments, if they develop a more severe disease, and if once infected, they may spread the virus more easily. In the lack of evidence, only a randomized withdrawal trial in people with COVID-19 and psoriasis exposed to IL-17 antagonists, may provide the definite answer.

Categories

Recent Posts

Getting to Know IPC’s Board Member Claudia de la Cruz: What Inspired Me to Specialize in Psoriasis

Introducing Our Latest IPC Councilors: Experts in Psoriasis Treatment and Research

Shining a Spotlight: Catching up with 2018 IPC Fellow, Jia Qi Chen, PhD

Also Read

Psoriasis

Psoriasis and the Pandemic: Lessons Learned from PsoProtect

The spread of COVID-19 in early 2020 brought many concerns and questions about COVID-19 and psoriasis. To help address these concerns dermatologists and researchers created PsoProtect and PsoProtectMe — two global registries aimed at understanding the impact of the pandemic on people with psoriasis. Co-directors of PsoProtect and PsoProtectMe, Catherine Smith and Satveer Mahil, speak about the data collection process and findings from these global registries.

Read More

Subscribe to the IPC Newsletter

Stay up-to-date on the latest research, news, and upcoming events right in your inbox.