Discussion
This observational study included a large population of patients (1831
adult subjects) affected by moderate-to-severe AD and treated with
systemic therapies or phototherapy, and managed during the COVID-19
pandemic in Italy. The participating centers (n=35) were highly
representative of the different incidence distribution of SARS-CoV-2
infection nationwide, having 15, 10, and 10 centers located in Northern,
Central, and Southern Italy, respectively.8 During the
observation period, a total number of 240,578 SARS-CoV2 positive cases
was registered, with a cumulative number of 190,248 recovered cases and
34,767 deaths.8 In details, national incidence at
timepoint 1, 2, and 3 was 0.71% (95% CI: 0.4-1.2), 0.27% (95% CI:
0.1 - 0.64), and 0.11% (95% CI: 0.0 – 0.4), in line with the
infection rate observed in our AD population (timepoint 1: 0.71%;
timepoint 2: 0.16%; timepoint 3: 0%). In our study population, less
than 1% of patients (16/1831) resulted positive to SARS-CoV-2, with
only three patients who required hospitalization, though swab testing
was not massively performed throughout the study period. During this
critical sanitary emergency, clinical activity in dermatology clinics
was markedly limited, and teledermatology (web- and phone- counselling)
was extremely useful for reducing patient access to hospital. This
modality was well accepted by AD patients who continued to have access
to dermatologist consultation, guaranteeing support and treatment
continuation in the majority of cases. Indeed, a relatively low number
of patients were lost to follow-up (7.7%). As suggested by both
national and international scientific societies, most patients were
recommended to continue their current treatment during COVID-19
pandemic.2 About 86% of patients continued treatment,
including 8 patients who resulted positive to SARS-CoV-2 infection,
albeit common recommendations suggested to withdraw therapy. Notably,
85% of patients included in this study were treated with dupilumab,
mostly prescribed as monotherapy.
Considering disease severity assessment, patients undergoing dupilumab
monotherapy showed lower disease activity suggesting a better control of
AD compared to patients treated with systemic immunosuppressive
compounds or dupilumab combined with other systemic therapies. Albeit
dupilumab-treated patient cohort exhibited lower disease severity at
baseline and throughout the study period compared to the other
treatments, superiority of dupilumab during COVID pandemic cannot be
suggested based on this data referring to a limited timeframe and
heterogeneous baseline patients’ characteristics across different
treatment groups. The therapeutic regimen combining dupilumab with other
systemic agents occurred in a cohort of patients with significantly
higher prevalence of atopic disorders who may require this combined
approach as likely they represent a high-need patient population.
Nevertheless, no worsening of atopic comorbid conditions was reported.
Response to treatment in these patients resulted similar to patients
treated with dupilumab monotherapy or systemic immunosuppressive
compounds. This latter class of agents was supposed to have an
unfavorable safety profile compared to biologics but no warning signal
was detected in our study. Dupilumab, does not impair the immune
compartments implicated in host defense against viral infections, and
thus may be considered a safer therapeutic choice for
AD.9-12 In dupilumab clinical trials, rates of general
infections, upper respiratory tract infections, and nasopharyngitis
resulted similar to placebo, and, in particular, viral infections, were
not reported as meaningful adverse event.7,13 In terms
of effectiveness, dupilumab therapy obtained a satisfactory control of
the disease and consistently with the other systemic compounds,
treatment interruption did not cause a rapid and relevant worsening of
the disease, as highlighted by the decrease of both patient-assessed
severity scores and EASI score in patients discontinuing therapy. This
finding is in line with a recent study reporting maintenance of EASI-75
response in 30.4% of high-responding patients treated with dupilumab,
after rerandomization to placebo.14 However, the
reduction of disease severity in patients discontinuing therapy was not
associated with a positive patient perception of AD status: a higher
percentage of patients withdrawing therapy evaluated their AD status as
worsened. Likely, therapy continuation, compared to an intermittent or
discontinued therapeutic regimen, might positively impact on patient
perception of both disease control and severity.
Dupilumab was interrupted in a small percentage of patients, conversely
to cyclosporine and oral corticosteroids. In addition, phototherapy was
interrupted in most cases (about 74%) due to the lack of accessibility
to phototherapy services during phase I (lockdown). Dupilumab
interruption was mainly based on patient decision and the main cause of
interruption was represented by non-medical reasons (lack of drug
supply). Fear of having an increased risk of COVID -19 disease
determined treatment interruption in 25% of patients withdrawing
therapy, similarly to recent findings observed in psoriasis
patients.15 Another study confirmed that patients
affected by either psoriasis (233 patients) or AD (68 patients) who felt
unsafe about their immunomodulatory treatment, were more concerned about
having SARS-CoV-2 infection and more likely discontinued therapy during
pandemic (overall treatment interruption: 7.3%).16 In
particular, AD patients with asthma were more concerned about being at
risk of COVID-19 disease because of AD and its
treatment.16
The strength of our study is the large AD population treated with
systemic therapies who was observed longitudinally, during the national
lockdown period (phase I) and the following phase of partial and gradual
re-opening of health care services (phase II and III), that were planned
in order to face COVID-19 outbreak. In particular, this study provided
evidence that continuation of immunomodulant/immunosuppressive therapies
during COVID-19 pandemic can be considered safe and effective in
controlling AD. This finding strengthens the recommendations issued by
national and international scientific societies at the beginning of the
COVID-19 outbreak that are based on experts’
opinion.2-5 Notably, this study also suggested that
drug interruption did not cause AD flares, as treatment response was
maintained in the short-term.
However, some limitations related to the data collection, management and
disease severity evaluation via web- or phone-counselling should be
considered as most of the assessment tools used were patient-reported
and only a minor percentage of patients could be evaluated by regular
visits during phase 3. Detailed information about atopic comorbid
conditions, SARS-CoV-2 serology testing were not collected. In addition,
most patients were undergoing dupilumab therapy with a satisfactory
control of the disease, particularly with dupilumab monotherapy (mean T1
EASI score significantly lower than other treatment groups), and this
could represent a selection bias of the study population likely related
to the relatively higher number of dupilumab-treated patients managed in
a dedicated AD outpatient clinic.
Data collection related to AD patients treated with systemic compounds
and/or photherapy during COVID-19 pandemic is continuing by the
DA-COVID-19 registry, willing to delineate the infectious risk related
to the use of each immunomodulant/immunosuppressant agent in AD patient
population and to better characterize COVID-19 outcomes in patients with
AD, as internationally promoted by the SECURE-AD
registry.17