Luigi Naldi, MD
Centro Studi GISED
PUBLICATIONThe 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.
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.