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 with moderate-to-severe atopic eczema prescribed the monoclonal antibody dupilumab experienced less severe COVID-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 a chronic skin disease and is characterised by T helper 2 (Th2)-driven inflammation due to a Th1/Th2 imbalance. Moreover, cytokines released by Th2 cells including IL-4, IL-5 and IL-13 elevate production of IgE and increased inflammation in the skin and aggravate the skin barrier defect seen in atopic eczema. Interestingly, research suggests that infection with COVID-19 leads to an increased level of various interleukins, including IL-13. Since the mode of action for dupilumab involves blockage of the two interleukins, IL-4 and IL-13, it might be possible that the drug impacts on the severity of symptoms in those with COVID-19.
For the present study, the US researchers examined a disease registry within the department of dermatology at their hospital which included medication prescribed for patients with 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. They included patients prescribed dupilumab, other 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 on 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.
A total of 1237 patients were included, of which 632 with a mean age of 41.2 years (47% male), were prescribed dupilumab, 107 other 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 the 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.
Ungar B et al. COVID-19 Symptoms Are Attenuated in Moderate-to-Severe Atopic Dermatitis Patients Treated with Dupilumab. J Allergy Clin Immunol Pract 2021