Use of dupilumab in patients with moderate-to-severe atopic dermatitis led to a reduction in COVID-19 symptom burden suggesting a protective effect of the drug
Patients who have moderate-to-severe atopic eczema and are prescribed dupilumab experienced less severe COVD-19 symptoms according to the results of a prospective study by researchers from the Department of Dermatology, and Laboratory of Inflammatory Skin Diseases, Icahn School of Medicine at Mount Sinai, New York, US.
Atopic eczema is considered to be a chronic skin disease and characterised by T helper 2 (Th2)-driven inflammation due to an imbalance of the Th1/Th2 ratio. In addition, cytokines released by the Th2 cells including IL-4, IL-5 and IL-13 increase production of IgE, leading to skin inflammation, which aggravates the skin barrier defect seen in atopic eczema.
Work during the COVID-19 pandemic has revealed how infection with the virus also results in an increased production of a number of interleukins, including IL-13. Since dupilumab works by blocking the interleukins, IL-4 and IL-13, it might be possible that the drug could lessen the severity of symptoms in those with COVID-19.
For the present study, the US researchers examined a disease registry within their department of dermatology who had been prescribed treatment for moderate-to-severe atopic eczema. They enrolled patients 9 years of age and older either at the time of a clinic visit or invited them to participate over the telephone. Prescribed treatments included dupilumab, oral systemic agents and either limited or no current treatment. Individuals were asked about the presence and duration of COVID-19 symptoms and based on their responses, categorised using a 1 – 5 scale ranging from mild disease (1), severe (3) through to 5 (fatal). The primary outcome was the presence of moderate-to-severe COVID-19 symptoms.
Findings
In total, data for 1237 patients were included in the analysis, of which, 632 with a mean age of 41.2 years (47% male), were prescribed dupilumab, 107 systemic agents including oral JAK inhibitors, prednisolone, methotrexate and mycophenolate. The remaining 498 patients were on limited treatment or no treatment, with the majority (71%) prescribed only topical agents. In terms of COVID-19 severity, the majority (77%) of all individuals scored 0 on the 1 – 5 scale.
Among non-dupilumab treated patients, there was a nearly four-fold increased risk of experiencing moderate-to-severe COVID-19 symptoms (odds ratio, OR = 3.89, p = 0.01) compared to those prescribed dupilumab. Similarly, this risk was elevated for those with either limited or no treatment (OR = 1.95, p = 0.04).
In addition, when examining the relationship among those with a PCR confirmed COVID-19 diagnosis, non-dupilumab treated patients again had a significantly increased risk of moderate-to-severe COVID-19 symptoms compared to those prescribed dupilumab (OR = 13.79, p = 0.002), as did those with limited or no treatment (OR = 2.44, p = 0.05).
Commenting on their findings, the authors speculated that given the over-expression of Th2 cells in atopic eczema, patients were unable to mount a sufficient Th1 response to viral infections. With use of dupilumab, which attenuated the Th2 response, the Th1/Th2 imbalance could be redressed allowing individuals to mount a greater Th1 response against the virus.
They concluded by suggesting that future studies should seek to understand the implications of their findings for other specific viral infections.
Citation
Ungar B et al. COVID-19 Symptoms Are Attenuated in Moderate-to-Severe Atopic Dermatitis Patients Treated with Dupilumab. J Allergy Clin Immunol
