American Journal of Clinical Dermatology

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Regeneron Pharmaceuticals

Dermatol Reports.

Allergol Immunopathol (Madr)

Ann Allergy Asthma Immunol

Expert Rev Clin Immunol

J Allergy Clin Immunol

PNAS USA

Nat Rev Drug Discov

Allergy

Lancet

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Br J Dermatol

J Cutan Med Surg

Dermatitis

Dermatol Ther (Heidelb).

Dermatol Ther (Heidelb)

Acta Derm Venereol

JAMA Dermatol

Atopic dermatitis (AD), a chronic systemic disease, can cause intense skin itching and negatively impact sleep, mood, and quality of life (QoL) for patients and families.
PEDISTAD is an ongoing, 10-year, observational registry describing disease characteristics, atopic comorbidities, and treatment patterns in pediatric patients (aged <12 years at enrollment) with moderate-to-severe AD. This 3-year interim analysis evaluates clinician-reported and caregiver-reported/patient-reported outcomes (Eczema Area and Severity Index [EASI], percent body surface area affected, worst itching/scratching, Children's Dermatology Life Quality Index, and Dermatitis Family Impact) in children treated with dupilumab, methotrexate, and/or cyclosporine. Outcomes were assessed as change from therapy start to last observation (either data cutoff date or treatment discontinuation).
Mean (±SE) EASI scores at the time of the last 3-year interim observation were consistent with mild disease in the dupilumab cohort and moderate disease in the methotrexate and cyclosporine cohorts. Improvements in pruritus were numerically greater in the dupilumab cohort relative to the methotrexate and cyclosporine cohorts, while improvements in QoL were similar in the dupilumab and methotrexate cohorts, with no significant change in the cyclosporine cohort. Rates of AD exacerbation were numerically lower with dupilumab treatment relative to methotrexate treatment which were numerically lower than cyclosporine treatment. Dupilumab discontinuation rates were numerically lower relative to methotrexate which were numerically lower than cyclosporine.
This PEDISTAD 3-year interim analysis of dupilumab, methotrexate, and cyclosporine treatment in children with AD demonstrates numerically greater improvements in AD signs, symptoms and QoL with dupilumab treatment relative to methotrexate and cyclosporine [Video abstract and graphical abstract available].
NCT03687359. Supplementary file1 (MP4 58163 KB).
Atopic dermatitis (AD) is a chronic inflammatory skin disease, often diagnosed before 5 years of age. AD causes intense itching and negatively impacts the sleep, mood, and quality of life of affected children and their families. Children may be treated with skin creams and ointments, which are often not enough to treat all AD signs (extent and severity of disease assessed by a clinician) and symptoms (burden of disease reported by a patient and/or caregiver). The drug dupilumab is approved for use in children as young as 6 months with moderate-to-severe AD and has shown improvements in signs and symptoms in clinical trials (sponsored by Regeneron Pharmaceuticals Inc., and Sanofi). We compared the use of dupilumab, methotrexate, and cyclosporine in routine clinical practice in children under the age of 12 years with moderate-to-severe AD using 3-year data from the PEDISTAD study. Compared with children treated with methotrexate and cyclosporine, children treated with dupilumab had greater improvements in the extent and severity of their AD, as assessed by their doctor. Children treated with dupilumab also showed greater improvements in how they described the severity of their symptoms, such as daytime/nighttime itching, and their quality of life. Fewer children using dupilumab stopped treatment and fewer reported side effects compared with those using methotrexate and cyclosporine. In summary, dupilumab-treated children had greater improvements in AD signs, AD symptoms, and quality of life, were more likely to continue treatment, and had fewer reported side effects than those given cyclosporine and methotrexate.

Systemic Treatments in Moderate-to-Severe Atopic Dermatitis in Pediatric Patients up to 12 Years of Age: Real-World Treatment Outcomes from the PEDISTAD Registry.

Systemic Treatments in Moderate-to-Severe Atopic Dermatitis in Pediatric Patients up to 12 Years of Age: Real-World Treatment Outcomes from the PEDISTAD Registry

JAMA Dermatology

<jats:p>This case series examines the effectiveness of dupilumab as a steroid-sparing therapy among patients with antibody-drug conjugate–related cutaneous toxicities.</jats:p>

A review of the clinical efficacy of FDA-approved antibody–drug conjugates in human cancers.

Mol Cancer

Dermatologic toxicities of antibody-drug conjugates.

Management of immune-related cutaneous adverse events with dupilumab.

J Immunother Cancer

Treatment-related skin reactions in enfortumab vedotin as a surrogate marker of survival and treatment response.

Int J Clin Oncol

Maytansine-bearing antibody-drug conjugates induce in vitro hallmarks of immunogenic cell death selectively in antigen-positive target cells.

Oncoimmunology

Types of necroinflammation, the effect of cell death modalities on sterile inflammation.

Cell Death Dis

This case series examines the effectiveness of dupilumab as a steroid-sparing therapy among patients with antibody-drug conjugate–related cutaneous toxicities.

Use of Dupilumab to Manage Antibody-Drug Conjugate-Induced Cutaneous Toxicities.

Use of Dupilumab to Manage Antibody-Drug Conjugate–Induced Cutaneous Toxicities

<jats:sec id="ab-doi250022-4"><jats:title>Importance</jats:title><jats:p>Patients with atopic dermatitis (AD) have been reported to develop psoriasis during dupilumab treatment. Whether this represents a true association or an incidental event remains unclear.</jats:p></jats:sec><jats:sec id="ab-doi250022-5"><jats:title>Objective</jats:title><jats:p>To compare psoriasis risk in patients with AD who are prescribed dupilumab vs other systemic agents.</jats:p></jats:sec><jats:sec id="ab-doi250022-6"><jats:title>Design, Setting, and Participants</jats:title><jats:p>This population-based retrospective cohort study with 3-year follow-up, with analyses completed on October 19, 2024, included 214 430 adult patients with AD  from the TriNetX Global Collaborative Network. Individuals newly prescribed dupilumab (dupilumab cohort) and those newly prescribed the other systemic agents without dupilumab exposure (control cohort) were included. Propensity score matching at a 1:1 ratio based on age, sex, race, comorbidities, laboratory measurements, and prior medications was conducted.</jats:p></jats:sec><jats:sec id="ab-doi250022-7"><jats:title>Exposures</jats:title><jats:p>Dupilumab vs the other systemic agents (corticosteroids, methotrexate, cyclosporine, azathioprine, or mycophenolate mofetil).</jats:p></jats:sec><jats:sec id="ab-doi250022-8"><jats:title>Main Outcomes and Measures</jats:title><jats:p>The primary outcome was incident psoriasis. Cumulative incidence was assessed using Kaplan-Meier plots and risks via Cox regression.</jats:p></jats:sec><jats:sec id="ab-doi250022-9"><jats:title>Results</jats:title><jats:p>After matching, each cohort comprised 9860 patients, with 10 891 female individuals (55.2%), a mean (SD) age of 44.8 (20.3) years, 3582 African American or Black individuals (18.2%), 2004 Asian individuals (10.2%), and 9901 White individuals (50.2%). The 3-year cumulative psoriasis incidence was higher in the dupilumab cohort than the control cohort (2.86% vs 1.79%; <jats:italic>P</jats:italic> &amp;amp;lt; .001). The number needed to harm for psoriasis was 94 for dupilumab vs the other systemic agents. The dupilumab cohort showed an increased risk for psoriasis (hazard ratio [HR], 1.58; 95% CI, 1.25-1.99), although the risk for psoriatic arthritis was not significant (HR, 1.97; 95% CI, 0.75-5.18). This increased risk was also observed in various AD subgroups, including those without atopic comorbidities (HR, 1.42; 95% CI, 1.06-1.89) or with pretreatment immunoglobulin E levels less than 0.048 mg/dL (to convert to mg/L, multiply by 10; HR, 1.59; 95% CI, 1.26-2.01). The association between dupilumab and psoriasis was further supported by validation in patients with asthma without AD (HR, 2.13; 95% CI, 1.38-3.31).</jats:p></jats:sec><jats:sec id="ab-doi250022-10"><jats:title>Conclusions and Relevance</jats:title><jats:p>The results of this cohort study suggest that patients with AD who were prescribed dupilumab exhibited a higher relative risk of developing psoriasis compared with those receiving other systemic agents. Given an estimated number needed to harm of 94, the absolute risk may have limited clinical relevance and should be weighed against dupilumab’s established efficacy in treating AD.</jats:p></jats:sec>

Two phase 3 trials of dupilumab versus placebo in atopic dermatitis.

N Engl J Med

Long-term management of moderate-to-severe atopic dermatitis with dupilumab and concomitant topical corticosteroids (LIBERTY AD CHRONOS): a 1-year, randomised, double-blinded, placebo-controlled, phase 3 trial.

Dupilumab with concomitant topical corticosteroid treatment in adults with atopic dermatitis with an inadequate response or intolerance to ciclosporin A or when this treatment is medically inadvisable: a placebo-controlled, randomized phase III clinical trial (LIBERTY AD CAFÉ).

Facial and neck erythema associated with dupilumab treatment: a systematic review.

Dupilumab therapy for atopic dermatitis is associated with increased risk of cutaneous T cell lymphoma: a retrospective cohort study.

Development of psoriasis during treatment with dupilumab: a systematic review.

Dupilumab-associated psoriasis and psoriasiform manifestations: a scoping review.

Dermatology

“De novo” psoriasis and relapse of psoriasis induced by dupilumab: three new cases and review of the literature.

J Clin Med

An asthmatic case of psoriasiform eruption caused by administration of dupilumab.

Allergol Int

Psoriasis onset under dupilumab treatment in two patients affected by atopic dermatitis and one patient affected by alopecia areata: clinical and dermoscopic patterns.

Dermatol Ther

Dupilumab-induced skin-associated side effects in patients with chronic rhinosinusitis with nasal polyposis.

J Dermatol

Development of inflammatory arthritis and enthesitis in patients on dupilumab: a case series.

Characterization of a musculoskeletal syndrome of enthesitis and arthritis in patients with atopic dermatitis treated with dupilumab, an interleukin–4/13 inhibitor.

Arthritis Rheumatol

Review of dupilumab-associated inflammatory arthritis: an approach to clinical analysis and management.

JAAD Case Rep

Contrasting pathogenesis of atopic dermatitis and psoriasis–part I: clinical and pathologic concepts.

Contrasting pathogenesis of atopic dermatitis and psoriasis–part II: immune cell subsets and therapeutic concepts.

Can atopic eczema and psoriasis coexist? a systematic review and meta-analysis.

Skin Health Dis

Concomitant atopic dermatitis and psoriasis - a retrospective review.

J Dermatolog Treat

Atopic dermatitis and psoriasis: two different immune diseases or one spectrum?

Curr Opin Immunol

IL-4 abrogates T(H)17 cell-mediated inflammation by selective silencing of IL-23 in antigen-presenting cells.

Proc Natl Acad Sci U S A

Regulation of entheseal IL-23 expression by IL-4 and IL-13 as an explanation for arthropathy development under dupilumab therapy.

Rheumatology (Oxford)

Unexpected connections of the IL-23/IL-17 and IL-4/IL-13 cytokine axes in inflammatory arthritis and enthesitis.

Semin Immunol

Evidence to support IL-13 as a risk locus for psoriatic arthritis but not psoriasis vulgaris.

Ann Rheum Dis

Genetically proxied interleukin-13 inhibition is associated with risk of psoriatic disease: a mendelian randomization study.

Reduced atopic march risk in pediatric atopic dermatitis patients prescribed dupilumab versus conventional immunomodulatory therapy: a population-based cohort study.

Association between biological immunotherapy for psoriasis and time to incident inflammatory arthritis: a retrospective cohort study.

Lancet Rheumatol

European guideline (EuroGuiDerm) on atopic eczema: part I—systemic therapy.

J Eur Acad Dermatol Venereol

New biological treatments for asthma and skin allergies.

Validity of diagnostic codes and prevalence of psoriasis and psoriatic arthritis in a managed care population, 1996-2009.

Pharmacoepidemiol Drug Saf

Validity of diagnostic codes and prevalence of physician-diagnosed psoriasis and psoriatic arthritis in southern Sweden—a population-based register study.

PLoS One

Validity of diagnostic codes for identification of psoriasis patients in Korea.

Ann Dermatol

Atopic dermatitis endotypes and implications for targeted therapeutics.

Diversity of atopic dermatitis and selection of immune targets.

Psoriasis.

T helper 2 IL-4/IL-13 dual blockade with dupilumab is linked to some emergent T helper 17–type diseases, including seronegative arthritis and enthesitis/enthesopathy, but not to humoral autoimmune diseases.

J Invest Dermatol

De novo psoriasis in atopic dermatitis patients treated with dupilumab: a retrospective cohort.

Efficacy and safety of dupilumab in clinical practice: one year of experience on 165 adult patients from a tertiary referral centre.

Paradoxical eruptions to targeted therapies in dermatology: a systematic review and analysis.

Interleukin-4 therapy of psoriasis induces Th2 responses and improves human autoimmune disease.

Nat Med

Increased expression of interleukin-23A in lesional skin of patients with atopic dermatitis with psoriasiform reaction during dupilumab treatment.

Dupilumab-induced phenotype switch from atopic dermatitis to psoriasis is characterized by de novo interleukin-17A expression: a case report.

Comment on: development of psoriasis during treatment with dupilumab: a systematic review.

Cost-effectiveness analysis of abrocitinib compared with other systemic treatments for severe atopic dermatitis in Spain.

Pharmacoecon Open

Dupilumab-associated arthritis: a dermatology-rheumatology perspective.

Am J Clin Dermatol

Age-specific changes in the molecular phenotype of patients with moderate-to-severe atopic dermatitis.

The Asian atopic dermatitis phenotype combines features of atopic dermatitis and psoriasis with increased TH17 polarization.

Atopic dermatitis in Chinese patients shows TH2/TH17 skewing with psoriasiform features.

Extrinsic and intrinsic types of atopic dermatitis.

J Dermatol Sci

Intrinsic atopic dermatitis shows similar TH2 and higher TH17 immune activation compared with extrinsic atopic dermatitis.

The role of Janus kinase signaling in the pathology of atopic dermatitis.

Patients with atopic dermatitis (AD) have been reported to develop psoriasis during dupilumab treatment. Whether this represents a true association or an incidental event remains unclear.
To compare psoriasis risk in patients with AD who are prescribed dupilumab vs other systemic agents.
This population-based retrospective cohort study with 3-year follow-up, with analyses completed on October 19, 2024, included 214 430 adult patients with AD from the TriNetX Global Collaborative Network. Individuals newly prescribed dupilumab (dupilumab cohort) and those newly prescribed the other systemic agents without dupilumab exposure (control cohort) were included. Propensity score matching at a 1:1 ratio based on age, sex, race, comorbidities, laboratory measurements, and prior medications was conducted.
Dupilumab vs the other systemic agents (corticosteroids, methotrexate, cyclosporine, azathioprine, or mycophenolate mofetil).
The primary outcome was incident psoriasis. Cumulative incidence was assessed using Kaplan-Meier plots and risks via Cox regression.
After matching, each cohort comprised 9860 patients, with 10 891 female individuals (55.2%), a mean (SD) age of 44.8 (20.3) years, 3582 African American or Black individuals (18.2%), 2004 Asian individuals (10.2%), and 9901 White individuals (50.2%). The 3-year cumulative psoriasis incidence was higher in the dupilumab cohort than the control cohort (2.86% vs 1.79%; P < .001). The number needed to harm for psoriasis was 94 for dupilumab vs the other systemic agents. The dupilumab cohort showed an increased risk for psoriasis (hazard ratio [HR], 1.58; 95% CI, 1.25-1.99), although the risk for psoriatic arthritis was not significant (HR, 1.97; 95% CI, 0.75-5.18). This increased risk was also observed in various AD subgroups, including those without atopic comorbidities (HR, 1.42; 95% CI, 1.06-1.89) or with pretreatment immunoglobulin E levels less than 0.048 mg/dL (to convert to mg/L, multiply by 10; HR, 1.59; 95% CI, 1.26-2.01). The association between dupilumab and psoriasis was further supported by validation in patients with asthma without AD (HR, 2.13; 95% CI, 1.38-3.31).
The results of this cohort study suggest that patients with AD who were prescribed dupilumab exhibited a higher relative risk of developing psoriasis compared with those receiving other systemic agents. Given an estimated number needed to harm of 94, the absolute risk may have limited clinical relevance and should be weighed against dupilumab's established efficacy in treating AD.

Psoriasis Risk in Patients With Atopic Dermatitis Treated With Dupilumab.

Psoriasis Risk in Patients With Atopic Dermatitis Treated With Dupilumab

<jats:sec id="ab-doi230050-4"><jats:title>Importance</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec id="ab-doi230050-5"><jats:title>Objective</jats:title><jats:p>To provide insight in the clinical and histopathologic features of patients with AD clinically suspected for CTCL during dupilumab treatment.</jats:p></jats:sec><jats:sec id="ab-doi230050-6"><jats:title>Design, Setting, and Participants</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec id="ab-doi230050-7"><jats:title>Main outcomes and measures</jats:title><jats:p>Relevant patient, disease, and treatment characteristics were evaluated. Skin biopsies before, during, and after treatment were collected and reassessed.</jats:p></jats:sec><jats:sec id="ab-doi230050-8"><jats:title>Results</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec id="ab-doi230050-9"><jats:title>Conclusions and relevance</jats:title><jats:p>This study found that dupilumab treatment can cause a reversible and benign LR, which mimics a CTCL, though has distinctive histopathologic features.</jats:p></jats:sec>

Atopic dermatitis.

Dupilumab shows long-term effectiveness in a large cohort of treatment-refractory atopic dermatitis patients in daily practice: 52-Week results from the Dutch BioDay registry.

Progression of cutaneous T-cell lymphoma after dupilumab: Case review of 7 patients.

Evolution of dupilumab-associated cutaneous atypical lymphoid infiltrates.

Am J Dermatopathol

Development of nodular lesions after dupilumab therapy in erythrodermic mycosis fungoides with interleukin-13 receptor alpha2 expression.

Clinical and epidemiological profile of patients with early stage mycosis fungoides.

An Bras Dermatol

Early-stage Mycosis Fungoides: Epidemiology and Prognosis.

Safety and Danger Considerations of Novel Treatments for Atopic Dermatitis in Context of Primary Cutaneous Lymphomas.

Int J Mol Sci

Risk of lymphoma in patients with atopic dermatitis and the role of topical treatment: A systematic review and meta-analysis.

Association Between Atopic Eczema and Cancer in England and Denmark.

Interleukin-13 is overexpressed in cutaneous T-cell lymphoma cells and regulates their proliferation.

Blood

Sézary Syndrome and Atopic Dermatitis: Comparison of Immunological Aspects and Targets.

Biomed Res Int

The 2018 update of the WHO-EORTC classification for primary cutaneous lymphomas.

Cutaneous CD30 lymphoproliferative disorders and similar conditions: a clinical and pathologic prospective on a complex issue.

Semin Diagn Pathol

A new era for cutaneous CD30-positive T-cell lymphoproliferative disorders.

Long-standing dermatitis treated with dupilumab with subsequent progression to cutaneous T-cell lymphoma.

Cutis

Dupilumab unmasking cutaneous T-cell lymphoma: report of a fatal case.

Clin Exp Dermatol

From inflammation to neoplasia: mycosis fungoides evolves from reactive inflammatory conditions (lymphoid infiltrates) transforming into neoplastic plaques and tumors.

Arch Dermatol

Large CD30-positive cells in benign, atypical lymphoid infiltrates of the skin.

J Cutan Pathol

CD30+ lymphoproliferative disorders: histopathology, differential diagnosis, new variants, and simulators.

Drug-induced cutaneous pseudolymphoma: A systematic review of the literature.

Australas J Dermatol

Drug induced pseudolymphoma.

Expert consensus on the systemic treatment of atopic dermatitis in special populations.

Adult-Onset Atopic Dermatitis: Characteristics and Management.

Defining early mycosis fungoides.

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.
To provide insight in the clinical and histopathologic features of patients with AD clinically suspected for CTCL during dupilumab treatment.
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.
Relevant patient, disease, and treatment characteristics were evaluated. Skin biopsies before, during, and after treatment were collected and reassessed.
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.
This study found that dupilumab treatment can cause a reversible and benign LR, which mimics a CTCL, though has distinctive histopathologic features.

Dupilumab-Associated Lymphoid Reactions in Patients With Atopic Dermatitis.

Dupilumab-Associated Lymphoid Reactions in Patients With Atopic Dermatitis

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