Expert Review of Clinical Pharmacology

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Dupilumab for treatment of atopic dermatitis

Marlene Seegräber, Jerome Srour, Alexandra Walter, Macarena Knop &

Andreas Wollenberg

To cite this article: Marlene Seegräber, Jerome Srour, Alexandra Walter, Macarena Knop &
Andreas Wollenberg (2018): Dupilumab for treatment of atopic dermatitis, Expert Review of Clinical
Pharmacology, DOI: 10.1080/17512433.2018.1449642

To link to this article: https://doi.org/10.1080/17512433.2018.1449642

Published online: 20 Mar 2018.

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EXPERT REVIEW OF CLINICAL PHARMACOLOGY, 2018
https://doi.org/10.1080/17512433.2018.1449642

DRUG PROFILE

Dupilumab for treatment of atopic dermatitis

Marlene Seegräber, Jerome Srour, Alexandra Walter, Macarena Knop and Andreas Wollenberg
Derpartment of Dermatology and Allergy, Ludwig-Maximilian-University, Munich, Germany

ABSTRACT ARTICLE HISTORY

Introduction: Dupilumab is a new treatment option for patients with moderate-to-severe atopic Received 29 August 2017
dermatitis. It blocks IL-4/IL13-signaling and thereby inhibits receptor signaling downstream the JAK- Accepted 5 March 2018
STAT-pathway. Three of the main disease mechanisms of atopic dermatitis are affected by blocking this KEYWORDS
pathway; the decrease of skin barrier function, the class switch to IgE and the TH2-differentiation. Dupilumab; IL-4; IL-13;
Areas Covered: Dupilumab showed promising results in clinical trials of phase I-III. Clinical outcome atopic dermatitis treatment;
parameters such as SCORAD, EASI, IGA and BSA improved with dupilumab. A positive effect on patient- biologics; monoclonal
reported outcomes like DLQI or pruritus-rating-scales was also demonstrated. The safety profile of antibody
dupilumab is superior to conventional immunosuppressive drugs, such as cyclosporine or methotrex-
ate. Injection-site reactions and conjunctivitis were the most relevant side-effects. Skin infections were
less frequently observed compared to placebo. Data on the use of dupilumab during pregnancy or in
children are not published to date.
Expert Commentary: Dupilumab was approved by the FDA in April 2017 for the treatment of adult
patients with moderate-to-severe atopic dermatitis whose disease is not adequately controlled with
topical prescription therapies or when those therapies are not advisable.

1. Introduction 2. Overview of conventional therapies

Atopic dermatitis is the most common chronic inflammatory
skin disease, with a prevalence of 25–30% in children and up
to 10% in adults [1–5]. It is a highly pruritic, chronic disease
with frequent relapses [6]. The disease impacts the patient’s
quality of life as a result of sleep deprivation, anxiety and
stigmatizing skin lesions [7–9].
Atopic dermatitis is characterized by a damaged skin bar-
rier function, a reduction of long chain fatty acids in the lipid
bilayer and a lympho-histiocytic infiltration [10–13].
This leads to an increased transepidermal water loss and
inflammation of the skin [14]. Both, the inflammation and the
skin barrier defects are mainly Th2-cell-mediated. Th2 biomarkers
such as IL-4, IL-10, IL 13, and IL-31, as well as inflammatory
dendritic epidermal cells are increased in atopic skin, whereas
Th-1 cytokines like INF-gamma and IL-2 as well as cathelicidin
and plasmacytoidic dendritic cells are decreased [15–22]. IL-4
and IL-13 induce spongiosis of the epidermis and reduce filag-
grin gene expression in keratinocytes, which leads to a disruption
of the skin barrier [18,23]. IL-4 and IL-13 also induce the expres-
sion of IL-31. The higher expression of IL-31 by TH2 cells leads to
increased pruritus in atopic dermatitis patients [24].
This defective skin barrier combined with the lack of defen-
sive Th-1 cytokines explains the high susceptibility to bacterial
and viral pathogens in atopic patients [25]. IL-4 and IL-13 have
also been associated with B-cell differentiation and increased
IgE-production [1,26,27]. The fact that overexpression of Th-2
cytokines can cause atopic dermatitis has been demonstrated
in transgenic mouse models [28,29].
Topical therapy with corticosteroids or calcineurin-inhibitors is
sufficient to control most patients with mild-to-moderate dis-
ease and is, therefore, recommended in various guidelines
[6,30–33]. Proactive application of the substances is useful for
flare prevention, and may be a long-term alternative for mod-
erate-to-severe patients otherwise needing systemic therapy
[10,34–36]. Therapy escalation to systemic treatment options
may be needed in cases of moderate-to-severe atopic dermati-
tis or refractory disease, since topical treatment may be insuffi-
cient in these patients [37]. Some general measures, such as
assessment of compliance and potential trigger factors, should
be observed before systemic therapy is initiated [38]. Broad
systemic immunosuppressants can be given to manage those
cases (see Table 1). Cyclosporine, Azathioprine, Methotrexate
and Mycophenolate mofetil have shown positive effects in case
series and clinical trials and are mentioned in the European,
Japanese, and US-American guidelines [6,30,31,39–43].
However, none of them are long-term treatment options,
because of potential drug toxicity. Another disadvantage is
that most of these drugs are not licensed for the use in atopic
dermatitis patients in many European countries and the United
States.
Cyclosporine is licensed for the short-term treatment of
adults with atopic dermatitis in Europe; it is not licensed for
this indication in the US. Cyclosporine acts as calcineurin inhi-
bitor and blocks the IL-2 pathway, which limits the proliferation
of T-cells. A large meta-analysis including 602 patients showed
a decrease in disease severity of about 55% after 6–8 weeks of

CONTACT Andreas Wollenberg wollenberg@lrz.uni-muenchen.de Dept. of Dermatology and Allergy, Ludwig-Maximilian-University, Frauenlobstr. 9-11,
80337 Munich, Germany
© 2018 Informa UK Limited, trading as Taylor & Francis Group
2 M. SEEGRÄBER ET AL.
Table 1. Overview of systemic treatment options for patients with atopic dermatitis.
Dupilumab Cyclosporine
Mode of action IL4-R-alpha inhibitor Calcineurin inhibitor
Application Subcutaneous Oral
Common side effects Injection-site reactions Kidney failure
Conjunctivitis Arterial hypertension
Gastrointestinal symptoms
Increased risk of infection.
Use in pregnancy No data May be used off-label
treatment [41]. Side effects are kidney failure, arterial hyperten-
sion, gastrointestinal symptoms, and increased risk of infection.
Treatment of pregnant patients is possible according to clinical
experience and guideline information, even if the drug is not
officially licensed during pregnancy [31].
Azathioprine serves as a purine analog after its conversion
to 6-mercaptopurine. Positive effects were demonstrated in
smaller studies [40]. Common side effects include gastrointest-
inal symptoms and cytopenia with increased risk of infection.
Azathioprine is contraindicated during pregnancy.
Methotrexate is a folic acid antagonist and available world-
wide since many decades. The drug has not been tested in
randomized, controlled trials for patients with atopic dermati-
tis. Nonetheless, it is widely used around the world for treat-
ment of severe AD. A smaller study with 12 patients
demonstrated a decrease in disease activity of about 50%
[42]. Methotrexate may cause cytopenia, hepatotoxicity, sto-
matitis, lung fibrosis, and kidney failure. The risk of infection is
increased. Methotraxate is a well-known teratogenic sub-
stance, and must not be used during pregnancy [6].
Mycophenolate mofetil inhibits purine synthesis by block-
ing the inosine monophosphate dehydrogenase function.
Though it has lower efficacy than the other commonly used
immunosuppressants in atopic dermatitis patients, it also has
the lowest risk profile of the four. Adverse reactions include
lymphocytopenia, gastrointestinal symptoms, fatigue and
increased risk of infection. The drug must not be administered
during pregnancy. A retrospective analysis showed varying
degrees of improvement under mycophenolate mofetil [39].
In summary, there is lack of an effective drug with low risk
profile for patients with refractory, moderate-to-severe atopic
dermatitis.
3. Dupilumab: pharmacodynamics and
pharmacokinetics
Dupilumab is a human monoclonal antibody, which inhibits
the IL-4 and IL-13 signaling by binding to the IL-4R-alpha and
IL-13R-alpha-1 subunits of the receptor [44]. This results in a
down regulation of receptor signaling downstream the JAK-
STAT pathway. Binding of IL-4 or IL-13 to the unblocked
receptor activates tyrosine kinases 2 and Januskinase (JAK) 1/
2 [45]. These kinases activate transcription factors, STAT, which
regulate gene expression [46]. Many genes, which play an
essential part in the pathogenesis of atopic dermatitis, are
regulated through the JAK-STAT pathway [46].
Azathioprine Methrotrexate MMF
Purine analog Folic acid antagonist IMP dehydrogenase inhibitor
Oral Oral or subcutaneous Oral
Cytopenia Cytopenia Lymphopenia
Increased risk of infection Hepatotoxicity Gastrointestinal symptoms
Stomatitis Fatigue
Lung fibrosis Increased risk of infection.
Kidney failure
Increased risk of infection
Conflicting data Contraindicated Contraindicated
The activation of the JAK-STAT pathway can down regulate
skin-barrier proteins and interfere with the differentiation of
keratinocytes [47,48]. Additionally, IL-4 signaling induces TH2-
cell activation. This could be demonstrated in mouse models,
where TH2 cytokine production was down regulated, if the IL-
4 pathway was blocked, but was up regulated in IL-4 trans-
genic mice [49,50]. Lastly, IL4 signaling along the JAK-STAT
pathway promotes B-cell differentiation and an immunoglo-
bulin subclass switch of the B-cell, which results in IgE produc-
tion of the B-cell [26,27,51] (Figure 1).
By blocking the IL-4 and IL-13 pathway, Dupilumab blocks
three different, relevant disease mechanisms in atopic derma-
titis: The decrease of skin barrier function caused by down-
regulation of the filaggrin protein, the class switch to IgE
caused by Th2 cytokines, and the overall TH2-differentiation
of the inflammatory infiltrate.
Dupilumab is licensed in the United States for subcuta-
neous administration. The recommended dose is an initial
dose of 600 mg (two 300 mg injections in different injection
sites), followed by 300 mg given every other week [44].
Steady-state concentrations are reached after about
16 weeks of weekly administrations of 300 mg and an initial
loading dose of 600 mg [44]. Bioavailability was estimated to
be 60.7% and maximal target-mediated elimination rate was
estimated at 0.968 mg/L/d [52]. The metabolic pathway of
dupilumab is yet to be defined.
4. Efficacy of dupilumab in clinical trials
Dupilumab was tested first in patients with persistent asthma
and elevated eosinophils, where it improved lung function,
reduced exacerbations, and decreased Th-2 biomarkers [53].
Allergic asthma and atopic dermatitis are genetically linked
and share common mediators of atopic inflammation [6].
Clinical trials with dupilumab for the indication of atopic
dermatitis followed shortly after. As of August 2017, rando-
mized, controlled trials of phase II and phase III have been
conducted in atopic dermatitis (see Table 2 and Table 3).
4.1. Phase I trials
An international study group conducted four separate trials,
which analyzed safety, dosing, pharmacodynamics and clinical
efficacy in adults with moderate to severe atopic dermatitis
[54]. Two of them were carried out as phase I trials. In study
M4A, patients received dupilumab vs placebo at a 1:4 ratio.
The drug was given in dose-escalation cohorts of 75 mg,
 EXPERT REVIEW OF CLINICAL PHARMACOLOGY 3

Skin pruritus
Eosinophil activtion
IL-31 Eosinophil
growth and
IL-5 proliferation

IL-4
Il-13
Th0 cell Th2 cell
IL-4 Cytokine production
CCL8, CCL24, CCL26
IL-1, IL-19, IL-27
VEGF, ANG-1, MCP-1

IL-4
IL-5

B cell maturation
B cell /
Plasma cell
Isotope switch to IgE

Figure 1. Effects of Th2 cell activation by signalling the IL4/IL13 receptor.

Activation of Th2 cells induces different effects and signals, which include pruritus, eosinophil activation, B cell maturation and cytokine production.

Table 2. Summary of Phase I and IIa trials with dupilumab.

M4A M4B M12 C4
Phase I I IIa IIa
Region USA USA Europe Europe
Groups ● Placebo ● Placebo ● Placebo ● Placebo
● 75 mg Dupilumab ● 150 mg Dupilumab ● Dupilumab 300 mg ● Dupilumab 300 mg
● 150 mg Dupilumab ● 300 mg Dupilumab
● 300 mg Dupilumab
Application Mode Subcutaneous Subcutaneous Subcutaneous Subcutaneous (+topical corticosteroids
Inclusion Criteria
Age ≥ 18 years ≥ 18 years ≥ 18 years ≥ 18 years
IGA ≥3 ≥3 ≥3 ≥3
EASI ≥ 12 ≥ 12 ≥ 16 -
SCORAD - - - ≥ 20
BSA ≥ 15% ≥ 10% ≥ 10% ≥ 10%
Duration 4 weeks 4 weeks 12 weeks 4 weeks

Table 3. Summary of phase IIb and III trials with dupilumab.

NCT01859988 SOLO1 SOLO2
Phase IIb III III
Region Asia, Europe, North America Asia, Europe, North America Asia, Europe, North America
Groups ● Placebo ● Placebo ● Placebo
● Dupilumab: 300 mg weekly, every 2 weeks, every 4 weeks; ● Dupilumab: 300 mg weekly, ● Dupilumab: 300 mg weekly,
200 mg every 2 weeks; 100 mg every 4 weeks 300 mg every 2 weeks 300 mg every 2 weeks
Application Mode Subcutaneous Subcutaneous Subcutaneous
Inclusion Criteria
Age ≥ 18 years ≥ 18 years ≥ 18 years
IGA ≥3 ≥3 ≥3
EASI ≥ 12 ≥ 16 ≥ 16
SCORAD - - -
BSA ≥ 10% ≥ 10% ≥ 10%
Duration 16 weeks 16 weeks 16 weeks
4 M. SEEGRÄBER ET AL.
150 mg and 300 mg. Each escalation cohort consisted of eight
patients, six patients received placebo. The patients in study
M4B were randomized at a 1:3 ratio and doses were 150 mg
and 300 mg. In this trial, 10 patients received placebo, 14
patients received 150 mg and 13 patients received 300 mg.
The drug was administered subcutaneously for four weeks
(Tbl. 1). A dose-dependent improvement of EASI and pruritus
was demonstrated in both studies. TARC levels, which were
used to measure the pharmacodynamic response, decreased
in both studies. Significant changes were observed in the
transcriptome of lesional skin [55]. The drug was safe in both
M4A and M4B trials. This was reflected by an equal numbers of
adverse events, serious adverse events and skin infections in
the placebo groups and the treatment groups.
4.2. Phase IIa trials
The same study group carried out two randomized, controlled
phase IIa trials, the M12 and C4 studies [54]. M12 included 109
European patients with moderate-to-severe atopic dermatitis.
The primary objective was to measure clinical efficacy using
established scoring systems like IGA and EASI. Pruritus was
assessed with a subjective, numerical rating scale. Half of the
patients received 300 mg dupilumab weekly for a total of
12 weeks, the other half received placebo (Tbl. 1).
Dupilumab decreased the IGA-Scores, EASI-Scores and pruri-
tus-ratings effectively. Th2-biomarkers were reduced and the
TARC-level reduction was correlated with the change in prur-
itus-ratings. Dupilumab was safe; the amount of serious
adverse events was higher in the placebo group. This most
likely resulted from a higher number of eczema exacerbations
and skin infections in that group. However, injection site
reactions appeared more often in the dupilumab group.
The C4 trial was conducted in Europe for four weeks.
Patients were randomized at a 2:1 ratio to the 300 mg dupi-
lumab group or the placebo group. All patients used topical
corticosteroids additionally. (Tbl. 1) The assessment of clinical
efficacy included the previously mentioned scores, as well as
SCORing of Atopic Dermatitis (SCORAD) and the individual
scoring of a single active lesion [56]. Patients who used the
combination therapy of dupilumab and topical corticosteroids
showed better and more rapid improvement of clinical
eczema scores and pruritus ratings.
All phase IIa trials were published together in the same
publication [54].
4.3. Phase IIb trials
An international study group consisting of centers in the
United States, Japan, Europe, and Canada conducted a rando-
mized, placebo-controlled, double-blind dose finding trial for
adults with moderate-to-severe atopic dermatitis [57,58]. A
total of 380 patients were randomized into one of the five
different dupilumab dosing groups (300 mg weekly, 300 mg
every 2 weeks, 300 mg every 4 weeks, 200 mg every 2 weeks,
and 100 mg every 4 weeks) or a placebo group. Improvement
of the EASI was significantly higher in the dupilumab groups
compared to the placebo group. Patients who had received
300 mg of dupilumab weekly showed the best results with a
73.7% change of the EASI-score from baseline and an improve-
ment of 59% in DLQI from baseline.
4.4. Phase III trials
Two larger phase III studies with identical design were con-
ducted in patients with moderate-to-severe atopic dermatitis
inadequately controlled by topical treatment [59]. Inclusion
criteria included a history of atopic dermatitis of at least
three years prior to screening and an IGA score of ≥ 3.
Patients were randomized into three groups at a 1:1:1
ratio: Group 1 received placebo, group 2 received 300 mg
dupilumab weekly and group 3 received dupilumab every
other week. A total of 671 patients were enrolled in the
SOLO1 and 708 patients in the SOLO2 trial. Significantly
more patients receiving dupilumab showed an improvement
of at least 75% in the EASI score compared to the placebo
groups. The percentage of patients reaching EASI-50 and
EASI-90, as well as the improvement in SCORAD and the
decrease of body surface area affected were significantly
higher in the dupilumab groups than in the placebo groups.
Dupilumab also improved some patient reported outcomes
such as pruritus VAS, psychological symptoms and quality of
life. Worsening of atopic dermatitis and skin infections were
more frequent in the placebo groups. Injection-site reactions
and conjunctivitis occurred more often in the dupilumab
groups.
A further phase III trial, CHRONOS, aimed to analyze the
long-term management of moderate-to-severe atopic derma-
titis with dupilumab and concomitant topical corticosteroids
[60]. The study took place in 14 countries in Europe, Asia and
North America over the course of one year; 740 patients were
enrolled. 106 patients received dupilumab and topical corti-
costeroids, the other 315 patients received placebo and topi-
cal corticosteroids. Skin scores, such as IGA or EASI improved
significantly better in patients, who received dupilumab in
addition to topical corticosteroids. Injection-site reactions
and conjunctivitis occurred more often in patients who had
received dupilumab.
The CAFÉ trial was a phase III trial, which screened 390
patients out of which 325 were randomized [61]. The patients
were randomized at a 1:1:1 ratio to subcutaneous dupilumab
300 mg weekly, every other week or placebo; all in combina-
tion with topical corticosteroids. The aim of the study was to
evaluate dupilumab with concomitant topical corticosteroids
as treatment option in patients with atopic dermatitis, who
were not adequately controlled with or intolerant to ciclos-
porin A. Dupilumab in combination with topical corticoster-
oids led to significant improvement of objective skin scores as
well as improved quality of life of the patients. Conjunctivits
ocurred more often in the dupilumab group.
5. Safety and tolerability of dupilumab
The drug is administered subcutaneously. Dosing trials
demonstrated highest efficacy for weekly injections with
300 mg. Data on the use of dupilumab in children have not
been published to date, but trials are currently running [62].

There is no information on the effects of dupilumab in preg-
nancy. Pregnancy was an exclusion criterion in all of the
mentioned trials, and eligible female patients had to undergo
frequent pregnancy testing once enrolled.
The most common side effect of dupilumab is injection-site
reactions, which mainly consist of transient erythema or
edema. Conjunctivitis seems the only specific side effect [63].
The reason why dupilumab causes conjunctivitis is not fully
understood and is currently being evaluated in ophthalmolo-
gical sub-trials. Effects on vital functions were not observed.
Dupilumab needs to be stored at 2–8°C, which may pose a
disadvantage to some patients [44]. The product is stable at
room temperature for up to 2 weeks, after taking it out of the
refrigerator. The administration of live vaccines under treat-
ment with dupilumab is currently not recommended accord-
ing to the current label. This might be another disadvantage in
case of intended travel or need of required booster shots.
According to clinical trials, dupilumab is a highly effective,
systemic treatment option for moderate-to-severe atopic der-
matitis. Most of the immunosuppressants representing a cur-
rent treatment alternative have not shown a comparable
safety/efficacy profile in studies or have not even been tested
in larger, randomized, placebo-controlled trials. Compared to
conventional immunosuppressants, dupilumab also represents
the safer option (Tbl. 3). Severe side effects such as kidney-
failure, pancytopenia or hepatotoxicity may appear under the
use of some conventional immunosuppressants, but have not
been reported under dupilumab. Most importantly, conven-
tional immunosuppressants increase the risk of infections; this
was not described for dupilumab. Dupilumab actually appears
to reduce the risk of skin infections in patients with atopic
dermatitis.
6. Drug regulations and approval for atopic
dermatitis
The FDA has approved dupilumab in the United States in
March 2017 for the treatment of adults with moderate-to-
severe atopic dermatitis, in whom topical treatment was insuf-
ficient or contraindicated [64]. The approved therapeutic
scheme includes an initial double dose of 600 mg followed
by single doses of 300 mg every second week [44]. In Europe,
the EMA recently accepted dupilumab for review [65], and a
market authorization for the EU is expected by the end of
2017. Patients in Britain will be granted the chance to receive
dupilumab early through the Early Access To Medicines Scheme.
The program will offers patients with severe atopic dermatitis
access to the drug before market authorization if other treat-
ment options failed [66].
7. Conclusion
Dupilumab blocks IL-4/IL-13 signaling and thereby inhibits the
JAK-STAT pathway. It is a safe, effective treatment option for
patients with moderate-to-severe atopic dermatitis, in whom
topical treatment options were ineffective. It improves clinical
outcome measures as well as patient reported outcomes.
EXPERT REVIEW OF CLINICAL PHARMACOLOGY 5
8. Expert commentary
Dupilumab is the first biologic approved for the treatment
of atopic dermatitis. It is a long-term disease modifying
drug, which is neither intended nor suitable for acute inter-
vention of severe flares, because it takes several weeks
before the full effect is observed. All randomized, placebo
controlled clinical trials with dupilumab showed promising
results, making this new drug a valuable addition to the
therapeutic options for atopic dermatitis. It is likely that
many physicians will convert to prescribing the drug to
their severely affected patients. The side effect profile
demonstrated in clinical trials is low compared to the exist-
ing alternatives for systemic therapy. The most commonly
observed side effect, injection-site reactions, seems tolerable
and should not become an obstacle. The conjunctivitis,
however, needs to be evaluated further. All patients report-
ing ocular symptoms should be diagnosed and treated ade-
quately, or referred to an ophthalmologist for further
assessment and co-treatment.
Other biologics beside dupilumab will enter the market
for atopic dermatitis in the future. The IL-13 neutralizing
antibody tralokinumab inhibits the interaction of IL-13
with the IL-13R-alpha receptor subunits [67]. Studies with
tralokinumab are currently performed and may somehow
resemble the results of the published dupilumab trials.
Nemolizumab, a human antibody blocking the Interleukin-
31 receptor is another biologic with high likelihood of
future approval for atopic dermatitis. The cytokine IL-31
seems to be the main cause of pruritus in patients with
atopic dermatitis [68]. Nemolizumab led to significant
improvement of pruritus in a randomized, placebo-con-
trolled, double-blind study on 265 patients with moderate-
to-severe atopic dermatitis [69].
9. Five-year view
It is very likely that dupilumab will become a well-estab-
lished treatment option for patients with atopic dermatitis
over the next five years. The efficacy and safety of the
upcoming new systemic drugs for atopic dermatitis will be
judged against this benchmark reference. Atopic dermatitis
affects the life quality of patients tremendously, especially
in more severe cases [8,9]. Proactive therapy with topical
calcineurin inhibitors or topical corticosteroids will probably
continue as a standard regimen for moderate to severe
atopic dermatitis patients for both medical and economic
reasons [10]. The need for an effective drug in more severe
patients is apparent and most patients would gladly admin-
ister every second week subcutaneous injections, if this will
result in an overall improvement of quality of life.
Dupilumab will probably decrease the number of hospitali-
zations for severe atopic dermatitis by reducing the number
and severity of disease exacerbations. Currently, hospitaliza-
tion is recommended for patients with serious exacerbations
[6]. It will be interesting to see how dupilumab works in
children. The prevalence of atopic dermatitis is higher in
children than in adults, making them a more relevant target
group. Tralokinumab and nemolizumab might obtain
6 M. SEEGRÄBER ET AL.
approval for atopic dermatitis over the course of the next
few years, and new oral drugs such as JAK inhibitors might
enter the market. Dupilumab might be approved for other
indications. Positive effects in patients with asthma and
elevated eosinophils have already been demonstrated [53].
So far, dupilumab is a safe treatment option for atopic
dermatitis. Follow-up studies looking specifically for yet
unnoticed, possible long-term side effects of dupilumab
will have to confirm the current favorable safety statement
in the long term.
Key issues
Dupilumab
– Indication: refractory, moderate-to-severe atopic derma-
titis in adults
– Function: inhibits IL-4/IL-13 signaling by blocking the IL-
4R-alpha subunit of the receptor
– Bioavailability: 60,7%
– Elimination rate: 0.968 mg/L/d
– Approval: FDA approved, EMA approved
– Dose: 300 mg weekly (600 mg loading dose)
– Side effects: injection-site reactions, conjunctivitis
Trials with Dupilumab (Tbl. 1, Tbl. 2)
– Phase I: M4A, M4B
– Phase IIa: M12, C4
– Phase IIb: NCT01859988
– Phase III: SOLO1, SOLO2, LIBERTY AD CHRONOS, LIBERTY
AD CAFE
Funding
This paper was not funded.
Declaration of Interest
A Wollenberg has been an advisor, speaker, or investigator for ALK Abello,
Almirall, Anacor, Astellas, Beiersdorf AG, Bencard, Bioderma, Chugai,
Galderma, Glaxo SmithKline, Hans Karrer, Leo, L’Oreal, Maruho,
MedImmune, Novartis, Pfizer, Pierre Fabre, Regeneron, and Sanofi. The
authors have no other relevant affiliations or financial involvement with
any organization or entity with a financial interest in or financial conflict
with the subject matter or materials discussed in the manuscript apart from
those disclosed. A reviewer on this manuscript has disclosed they have had a
lot of corporate support including consulting for Sanofi/Regeneron.
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