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Article ; Online: Biomarkers in atopic dermatitis.

Bakker, Daphne / de Bruin-Weller, Marjolein / Drylewicz, Julia / van Wijk, Femke / Thijs, Judith

The Journal of allergy and clinical immunology

2023 Volume 151, Issue 5, Page(s) 1163–1168

Abstract: Atopic dermatitis (AD) is a complex and highly heterogeneous inflammatory skin disease. Given the highly heterogeneous character of AD, it is unlikely that every patient will respond equally to a particular treatment. The recent introduction of novel ... ...

Abstract	Atopic dermatitis (AD) is a complex and highly heterogeneous inflammatory skin disease. Given the highly heterogeneous character of AD, it is unlikely that every patient will respond equally to a particular treatment. The recent introduction of novel targeted therapies for AD has driven the need for patient stratification based on immunologic biomarkers. We have reviewed the use of different types of biomarkers as potential tools in the movement toward personalized medicine in AD, comprising different ways of endotyping patients with AD based on immunologic profiles and predictive biomarkers. The application of biomarkers will result in better characterization and stratification of patients and allow better comparison of current and new treatments. The ultimate goal will be to switch from the current generalized "one-drug-fits-all" management to more personalized "patient endotype-specific" management.
MeSH term(s)	Humans ; Dermatitis, Atopic/diagnosis ; Biomarkers ; Precision Medicine
Chemical Substances	Biomarkers
Language	English
Publishing date	2023-02-14
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	121011-7
ISSN	1097-6825 ; 1085-8725 ; 0091-6749
ISSN (online)	1097-6825 ; 1085-8725
ISSN	0091-6749
DOI	10.1016/j.jaci.2023.01.019
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Article ; Online: Limited excretion of dupilumab into breastmilk: A case report.

Dekkers, Coco / El Amrani, Mohsin / van Luin, Matthijs / Bakker, Daphne / Plusjé, Leon / van Wijk, Femke / de Bruin-Weller, Marjolein

Journal of the European Academy of Dermatology and Venereology : JEADV

2023 Volume 37, Issue 9, Page(s) e1154–e1155

MeSH term(s)	Humans ; Milk, Human ; Antibodies, Monoclonal, Humanized ; Antibodies, Monoclonal
Chemical Substances	dupilumab (420K487FSG) ; Antibodies, Monoclonal, Humanized ; Antibodies, Monoclonal
Language	English
Publishing date	2023-05-12
Publishing country	England
Document type	Case Reports ; Letter
ZDB-ID	1128828-0
ISSN	1468-3083 ; 0926-9959
ISSN (online)	1468-3083
ISSN	0926-9959
DOI	10.1111/jdv.19164
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Article ; Online: IgE levels in patients with atopic dermatitis steadily decrease during treatment with dupilumab regardless of dose interval.

Dekkers, Coco / van der Wal, M Marlot / van den Noort, Leonie / Bakker, Daphne S / de Bruin-Weller, Marjolein / van Wijk, Femke

Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology

2023 Volume 53, Issue 11, Page(s) 1222–1225

MeSH term(s)	Humans ; Dermatitis, Atopic/drug therapy ; Antibodies, Monoclonal, Humanized/therapeutic use ; Antibodies, Monoclonal/therapeutic use ; Immunoglobulin E
Chemical Substances	dupilumab (420K487FSG) ; Antibodies, Monoclonal, Humanized ; Antibodies, Monoclonal ; Immunoglobulin E (37341-29-0)
Language	English
Publishing date	2023-09-12
Publishing country	England
Document type	Letter
ZDB-ID	645204-8
ISSN	1365-2222 ; 0954-7894 ; 0960-2178
ISSN (online)	1365-2222
ISSN	0954-7894 ; 0960-2178
DOI	10.1111/cea.14384
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Article ; Online: Differential dynamics of TARC during JAK-inhibitor therapy compared to biological therapies targeting type 2 inflammation.

Boesjes, Celeste M / Bakker, Daphne S / Knol, Edward F / de Graaf, Marlies / van Wijk, Femke / de Bruin-Weller, Marjolein S

Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology

2023 Volume 54, Issue 4, Page(s) 294–296

MeSH term(s)	Humans ; Chemokine CCL17 ; Inflammation ; Biological Therapy
Chemical Substances	Chemokine CCL17
Language	English
Publishing date	2023-12-30
Publishing country	England
Document type	Journal Article
ZDB-ID	645204-8
ISSN	1365-2222 ; 0954-7894 ; 0960-2178
ISSN (online)	1365-2222
ISSN	0954-7894 ; 0960-2178
DOI	10.1111/cea.14442
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Article ; Online: Dupilumab‐associated ocular surface disease in atopic dermatitis patients: Clinical characteristics, ophthalmic treatment response and conjunctival goblet cell analysis

Achten, Roselie / Thijs, Judith / van der Wal, Marlot / van Luijk, Chantal / de Graaf, Marlies / Bakker, Daphne / Boer, Joke de / van Wijk, Femke / de Bruin‐Weller, Marjolein

Allergy. 2023 Aug., v. 78, no. 8, p. 2266-2276

2023 , Page(s) 2266–2276

Abstract: BACKGROUND: Dupilumab‐associated ocular surface disease (DAOSD) is frequently reported as side effect in atopic dermatitis (AD) patients. Therefore, the aim of this study was to investigate the frequency and severity of DAOSD, ophthalmic treatment ... ...

Abstract	BACKGROUND: Dupilumab‐associated ocular surface disease (DAOSD) is frequently reported as side effect in atopic dermatitis (AD) patients. Therefore, the aim of this study was to investigate the frequency and severity of DAOSD, ophthalmic treatment response and to learn more about the effect of dupilumab on conjunctival goblet cells (GC). METHODS: This prospective study included dupilumab‐treated AD patients between February 2020 and June 2022 from the University Medical Centre Utrecht. Patients were examined by an ophthalmologist and a dermatologist before start (baseline), and after 4 and 28 weeks of dupilumab treatment. Ophthalmological examination was assessed by the Utrecht Ophthalmic Inflammatory and Allergic disease (UTOPIA) score. DAOSD was defined as an increase in UTOPIA score of ≥3 points from baseline. To quantify conjunctival GCs and to investigate the percentage of Cytokeratin 19 (CK19)‐CD45‐Mucin 5 AC (MUC5AC)+ cells, conjunctival impression cytology samples were analysed. RESULTS: Ocular surface disease (OSD) was present in 91.3% (n = 63/69) patients at baseline. DAOSD was observed in 28.9% (n = 20/69) patients, in whom GC numbers remained stable and the percentage of CK19‐CD45‐MUC5AC+ cells decreased at onset of DAOSD compared with baseline. After 28 weeks of dupilumab treatment, DAOSD was seen in 14.5% (n = 10/69) patients. Of the 85.5% (n = 59/69) patients without DAOSD or with controlled DAOSD at Week 28, 40.7% (n = 24/59) patients received anti‐inflammatory ophthalmic drugs. CONCLUSIONS: Ocular surface disease is common in moderate‐to‐severe AD patients before starting dupilumab. During treatment with dupilumab DAOSD severity improves with early ophthalmic treatment. The decrease in percentage of CK19‐CD45‐MUC5AC+ cells during dupilumab treatment suggests an impairment of the GC function due to dupilumab treatment.
Keywords	adverse effects ; atopic dermatitis ; cell biology ; medical facilities ; prospective studies ; Netherlands
Language	English
Dates of publication	2023-08
Size	p. 2266-2276
Publishing place	John Wiley & Sons, Ltd
Document type	Article ; Online
Note	JOURNAL ARTICLE
ZDB-ID	391933-x
ISSN	1398-9995 ; 0105-4538
ISSN (online)	1398-9995
ISSN	0105-4538
DOI	10.1111/all.15717
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Ocular surface disease in moderate-to-severe atopic dermatitis patients and the effect of biological therapy.

Achten, Roselie / Thijs, Judith / van der Wal, Marlot / van Luijk, Chantal / Bakker, Daphne / Knol, Edward / van Luin, Matthijs / El Amrani, Mohsin / Delemarre, Eveline / Elfiky, Ahmed M I / de Boer, Joke / van Wijk, Femke / de Graaf, Marlies / de Bruin-Weller, Marjolein

Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology

2024 Volume 54, Issue 4, Page(s) 241–252

Abstract: Atopic dermatitis (AD) is a chronic inflammatory skin disease for which new targeted therapies are currently available. Due to the increased rates of ocular surface disease (OSD) reported during treatment with these new targeted treatments, more insight ... ...

Abstract	Atopic dermatitis (AD) is a chronic inflammatory skin disease for which new targeted therapies are currently available. Due to the increased rates of ocular surface disease (OSD) reported during treatment with these new targeted treatments, more insight into the occurrence and pathomechanism of OSD in moderate-to-severe AD patients is needed. Therefore, this review's first part highlights that most patients with moderate-to-severe AD already have characteristics of OSD before starting targeted treatment. Remarkably, not all AD patients with OSD report ocular symptoms. OSD in AD is associated with less conjunctival goblet cells (GC) compared to healthy controls. In addition, OSD severity in AD patients is associated with high AD activity, the presence of eyelid and/or facial eczema, and high levels of AD-related severity biomarkers in tear fluid. The second part of this review highlights that pre-existing ocular pathology (e.g. in combination with the use of ophthalmic medication or eyelid eczema) may be associated with the development of dupilumab-associated ocular surface disease (DAOSD). During dupilumab treatment, DAOSD (which can be new-onset OSD or worsening of pre-existing OSD) is observed in approximately one-third of the dupilumab-treated AD patients. Anti-inflammatory ophthalmic treatment improves DAOSD, and dose reduction of dupilumab may also be an effective treatment option. The pathomechanism of DAOSD is still not fully elucidated. In a prospective study low, but stable conjunctival GC numbers were observed in moderate-to-severe AD patients, before and during dupilumab treatment. However, the Mucin 5 AC (MUC5AC) expression of GCs decreased during dupilumab treatment, suggesting an impairment of the GC function by dupilumab treatment. In addition, higher dupilumab tear fluid levels were found in dupilumab-treated AD patients with moderate-to-severe OSD compared to patients with no or mild OSD, whereas the dupilumab serum levels are similar. Clinicians should be aware of the frequent occurrence of OSD in moderate-to-severe AD patients, and a low-threshold referral to an ophthalmologist is recommended.
MeSH term(s)	Humans ; Dermatitis, Atopic ; Antibodies, Monoclonal/therapeutic use ; Prospective Studies ; Eczema ; Treatment Outcome ; Biological Therapy ; Severity of Illness Index
Chemical Substances	Antibodies, Monoclonal
Language	English
Publishing date	2024-02-08
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	645204-8
ISSN	1365-2222 ; 0954-7894 ; 0960-2178
ISSN (online)	1365-2222
ISSN	0954-7894 ; 0960-2178
DOI	10.1111/cea.14461
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Article ; Online: Dupilumab-Associated Lymphoid Reactions in Patients With Atopic Dermatitis.

Boesjes, Celeste M / van der Gang, Lian F / Bakker, Daphne S / Ten Cate, Tess A / Spekhorst, Lotte S / de Graaf, Marlies / van Dijk, Marijke R / de Bruin-Weller, Marjolein S

JAMA dermatology

2023 Volume 159, Issue 11, Page(s) 1240–1247

Abstract: Importance: Since the increased use of dupilumab for atopic dermatitis (AD) in daily practice, several cases have been reported on the development of cutaneous T-cell lymphomas (CTCL) and lymphoid infiltrates.: Objective: To provide insight in the ... ...

Abstract	Importance: Since the increased use of dupilumab for atopic dermatitis (AD) in daily practice, several cases have been reported on the development of cutaneous T-cell lymphomas (CTCL) and lymphoid infiltrates. Objective: To provide insight in the clinical and histopathologic features of patients with AD clinically suspected for CTCL during dupilumab treatment. Design, setting, and participants: This retrospective observational case series included adult (≥18 years) patients with AD treated with dupilumab between October 2017 and July 2022 at the University Medical Center Utrecht in the Netherlands. Main outcomes and measures: Relevant patient, disease, and treatment characteristics were evaluated. Skin biopsies before, during, and after treatment were collected and reassessed. Results: Fourteen patients (54.5% male) with a median (IQR) age of 56 (36-66) years suspected for CTCL with deterioration of symptoms during dupilumab treatment were included. Of 14 patients, 3 were retrospectively diagnosed with preexistent mycosis fungoides (MF). Eleven patients with AD were eventually diagnosed with a lymphoid reaction (LR). These patients showed MF-like symptoms; however, histopathologic findings were different, and included sprinkled distribution of small hyperchromatic lymphocytes in the upper epidermal section, a dysregulated CD4:CD8 ratio, and CD30 overexpression, without loss of CD2/CD3/CD5. The median time to clinical worsening was 4.0 months (IQR, 1.4-10.0). Posttreatment biopsies showed complete clearance of the LR in all patients. Conclusions and relevance: This study found that dupilumab treatment can cause a reversible and benign LR, which mimics a CTCL, though has distinctive histopathologic features.
MeSH term(s)	Adult ; Humans ; Male ; Middle Aged ; Aged ; Female ; Dermatitis, Atopic/diagnosis ; Dermatitis, Atopic/drug therapy ; Retrospective Studies ; Skin Neoplasms/pathology ; Mycosis Fungoides/diagnosis ; Mycosis Fungoides/drug therapy ; Mycosis Fungoides/pathology ; Lymphoma, T-Cell, Cutaneous/pathology
Chemical Substances	dupilumab (420K487FSG)
Language	English
Publishing date	2023-10-18
Publishing country	United States
Document type	Journal Article
ZDB-ID	2701761-8
ISSN	2168-6084 ; 2168-6068
ISSN (online)	2168-6084
ISSN	2168-6068
DOI	10.1001/jamadermatol.2023.3849
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Article ; Online: Effectiveness of Upadacitinib in Patients with Atopic Dermatitis including those with Inadequate Response to Dupilumab and/or Baricitinib: Results from the BioDay Registry.

Boesjes, Celeste M / Van der Gang, Liana F / Zuithoff, Nicolaas P A / Bakker, Daphne S / Spekhorst, Lotte S / Haeck, Inge / Kamsteeg, Marijke / De Graaf, Marlies / De Bruin-Weller, Marjolein S

Acta dermato-venereologica

2023 Volume 103, Page(s) adv00872

Abstract: Clinical trials showed that upadacitinib, a selective Janus kinase-1 inhibitor, is effective for treatment of moderate-to-severe atopic dermatitis. However, daily practice studies are limited. This multicentre prospective study evaluated the ... ...

Abstract	Clinical trials showed that upadacitinib, a selective Janus kinase-1 inhibitor, is effective for treatment of moderate-to-severe atopic dermatitis. However, daily practice studies are limited. This multicentre prospective study evaluated the effectiveness of 16 weeks of upadacitinib treatment for moderate-to-severe atopic dermatitis in adult patients, including those with previous inadequate response to dupilumab and/or baricitinib, in daily practice. A total of 47 patients from the Dutch BioDay registry treated with upadacitinib were included. Patients were evaluated at baseline, and after 4, 8 and 16 weeks of treatment. Effectiveness was assessed by clinician- and patient-reported outcome measurements. Safety was assessed by adverse events and laboratory assessments. Overall, the probabilities (95% confidence intervals) of achieving Eczema Area and Severity Index ≤ 7 and Numerical Rating Scale - pruritus ≤ 4 were 73.0% (53.7-86.3) and 69.4% (48.7-84.4), respectively. The effectiveness of upadacitinib was comparable in patients with inadequate response to dupilumab and/or baricitinib and in patients who were naïve for these treatments or who had stopped such treatments due to adverse events. Fourteen (29.8%) patients discontinued upadacitinib due to ineffectiveness, adverse events or both (8.5%, 14.9% and 6.4%, respectively). Most frequently reported adverse events were acneiform eruptions (n = 10, 21.3%), herpes simplex (n = 6, 12.8%), nausea and airway infections (both n = 4, 8.5%). In conclusion, upadacitinib is an effective treatment for patients with moderate-to-severe atopic dermatitis, including those with previous inadequate response to dupilumab and/or baricitinib treatment.
MeSH term(s)	Adult ; Humans ; Dermatitis, Atopic/diagnosis ; Dermatitis, Atopic/drug therapy ; Prospective Studies ; Double-Blind Method ; Treatment Outcome ; Severity of Illness Index
Chemical Substances	dupilumab (420K487FSG) ; baricitinib (ISP4442I3Y) ; upadacitinib (4RA0KN46E0)
Language	English
Publishing date	2023-02-16
Publishing country	Sweden
Document type	Multicenter Study ; Journal Article
ZDB-ID	80007-7
ISSN	1651-2057 ; 0001-5555
ISSN (online)	1651-2057
ISSN	0001-5555
DOI	10.2340/actadv.v103.5243
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Article ; Online: Biological Tipping Point in Patients with Atopic Dermatitis Treated with Different Dosing Intervals of Dupilumab.

Dekkers, Coco / der Wal, M Marlot van / El Amrani, Mohsin / Luin, Matthijs van / Bakker, Daphne S / Bruin-Weller, Marjolein de / van Wijk, Femke

The Journal of investigative dermatology

2023 Volume 143, Issue 9, Page(s) 1822–1825.e3

MeSH term(s)	Humans ; Dermatitis, Atopic/drug therapy ; Dermatitis, Atopic/chemically induced ; Antibodies, Monoclonal, Humanized/therapeutic use ; Antibodies, Monoclonal ; Treatment Outcome ; Severity of Illness Index
Chemical Substances	dupilumab (420K487FSG) ; Antibodies, Monoclonal, Humanized ; Antibodies, Monoclonal
Language	English
Publishing date	2023-03-28
Publishing country	United States
Document type	Letter
ZDB-ID	80136-7
ISSN	1523-1747 ; 0022-202X
ISSN (online)	1523-1747
ISSN	0022-202X
DOI	10.1016/j.jid.2023.03.1659
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Article ; Online: Muscle and joint pain during dupilumab treatment for atopic dermatitis: Lack of association with antinuclear antibodies.

Boesjes, Celeste M / van Emst, Madelon / Bakker, Daphne S / Spekhorst, Lotte S / van Wijk, Femke / de Graaf, Marlies / de Bruin-Weller, Marjolein S

Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology

2023 Volume 53, Issue 5, Page(s) 582–585

MeSH term(s)	Humans ; Dermatitis, Atopic/drug therapy ; Antibodies, Antinuclear/therapeutic use ; Muscles ; Arthralgia ; Treatment Outcome ; Severity of Illness Index
Chemical Substances	dupilumab (420K487FSG) ; Antibodies, Antinuclear
Language	English
Publishing date	2023-02-13
Publishing country	England
Document type	Letter ; Research Support, Non-U.S. Gov't
ZDB-ID	645204-8
ISSN	1365-2222 ; 0954-7894 ; 0960-2178
ISSN (online)	1365-2222
ISSN	0954-7894 ; 0960-2178
DOI	10.1111/cea.14296
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