Dupilumab: A review of its use in the treatment of atopic dermatitis

Gooderham, Melinda; Hong, Hwanhee; Eshtiaghi, Panteha; Papp, Kim

doi:10.1016/j.jaad.2017.12.022

Cited by 252 publications

(234 citation statements)

References 16 publications

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“…In the skin, molecular profiling reveals dysregulation in cytokines associated with type 1 and type 2 inflammation, while also indicating altered expression of IL‐23 . These data and those based on other skin inflammatory diseases indicate the central role of cytokines in driving skin pathology . Furthermore, evidence from a range of autoimmune diseases indicates that inflammatory cytokines are implicated in wider comorbidities, impacting vascular, metabolic and psychological pathways …”

mentioning

confidence: 67%

“…Depression and anxiety experienced by patients with AA were measured using the Hospital Anxiety and Depression Scale (HADS) questionnaire. 37 HADS scores were interpreted as no depression/anxiety (0-7), mild depression/anxiety (8-10), moderate depression/anxiety (11)(12)(13)(14) and severe depression/ anxiety (15)(16)(17)(18)(19)(20). Severity of Alopecia Tool (SALT) 38 scores were calculated to assess severity of hair loss, and patients were stratified accordingly: inactive disease (S0), patchy hair loss (S3 ≥ S4a), severe hair loss (S4b ≥ S5, alopecia universalis and totalis).…”

Section: Clinical Datamentioning

confidence: 99%

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Alopecia areata is characterized by dysregulation in systemic type 17 and type 2 cytokines, which may contribute to disease‐associated psychological morbidity

et al. 2019

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Summary Background Alopecia areata (AA) is a common autoimmune disease, causing patchy hair loss that can progress to involve the entire scalp (totalis) or body (universalis). CD8+NKG2D+ T cells dominate hair follicle pathogenesis, but the specific mechanisms driving hair loss are not fully understood. Objectives To provide a detailed insight into the systemic cytokine signature associated with AA, and to assess the association between cytokines and depression. Methods We conducted multiplex analysis of plasma cytokines from patients with AA, patients with psoriatic arthritis (PsA) and healthy controls. We used the Hospital Anxiety and Depression Scale (HADS) to assess the occurrence of depression and anxiety in our cohort. Results Our analysis identified a systemic inflammatory signature associated with AA, characterized by elevated levels of interleukin (IL)‐17A, IL‐17F, IL‐21 and IL‐23 indicative of a type 17 immune response. Circulating levels of the type 2 cytokines IL‐33, IL‐31 and IL‐17E (IL‐25) were also significantly increased in AA. In comparison with PsA, AA was associated with higher levels of IL‐17F, IL‐17E and IL‐23. We hypothesized that circulating inflammatory cytokines may contribute to wider comorbidities associated with AA. Our assessment of psychiatric comorbidity in AA using HADS scores showed that 18% and 51% of people with AA experienced symptoms of depression and anxiety, respectively. Using linear regression modelling, we identified that levels of IL‐22 and IL‐17E are positively and significantly associated with depression. Conclusions Our data highlight changes in both type 17 and type 2 cytokines among people with AA, suggesting that complex systemic cytokine profiles may contribute both to the pathogenesis of AA and to the associated depression. What's already known about this topic? NKG2D+CD8+ T cells cause hair loss in alopecia areata (AA) but the immunological mechanisms underlying the disease are not fully understood. AA is associated with changes in levels of interleukin (IL)‐6, tumour necrosis factor‐α, IL‐1β and type 17 cytokines. Psychiatric comorbidity is common among people with AA. What does this study add? People with AA have increased plasma levels of the type 2 cytokines IL‐33, IL‐31 and IL‐17E (IL‐25), in addition to the type 17 cytokines IL‐17A, IL‐21, IL‐23 and IL‐17F. Levels of IL‐17E and IL‐22 positively predict depression score. What is the translational message? AA is associated with increased levels of multiple inflammatory cytokines, implicating both type 17‐ and type 2 immune pathways. Our data indicate that therapeutic strategies for treating AA may need to address the underlying type 17‐ and type 2 immune dysregulation, rather than focusing narrowly on the CD8+ T‐cell response. An immunological mechanism might contribute directly to the depression observed in people with AA.

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confidence: 67%

Section: Clinical Datamentioning

confidence: 99%

Alopecia areata is characterized by dysregulation in systemic type 17 and type 2 cytokines, which may contribute to disease‐associated psychological morbidity

et al. 2019

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“…Dupilumab is a monoclonal antibody inhibiting interleukin (IL)‐4 and IL‐13 signaling . Having shown its efficacy and safety in several large trials, this biologic has now become widely available for the treatment of atopic dermatitis (AD). So far, only three case studies have been published on the effect of dupilumab on (isolated) hand eczema .…”

Section: Introductionmentioning

confidence: 99%

Effect of dupilumab on hand eczema in patients with atopic dermatitis: An observational study

Oosterhaven

Voorberg

Romeijn

et al. 2019

The Journal of Dermatology

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Systemic treatment options for chronic hand eczema are limited. Dupilumab is used in atopic dermatitis (AD) but is not licensed for (isolated) hand eczema. In this observational prospective study we aimed to determine the response of hand eczema to dupilumab in patients with AD. Adult patients with hand eczema and AD received dupilumab s.c. at a 600 mg loading dose, followed by 300 mg every 2 weeks. Primary outcome was a minimum improvement of 75% on the Hand Eczema Severity Index after 16 weeks (HECSI‐75). Secondary outcomes were severity, measured using the Photographic guide; quality of life improvement as patient‐reported outcome, measured using the Dermatology Life Quality Index (DLQI); and AD severity, measured using the Eczema Area and Severity Index (EASI). Forty‐seven patients were included (32 males; mean age, 45 years). HECSI‐75 was achieved by 28 (60%). Mean HECSI score reduction was 49.2 points (range, 0–164; 95% within‐subject confidence interval, 46.4–52.0), which was already significantly decreased after 4 weeks (P < 0.001). DLQI score mean improvement was 8.8 points (standard deviation [SD], 6.0) or 70.0% decrease (SD, 26.4) (P < 0.001). Eighteen patients (38%) were classified as responders on the Photographic guide. There was no difference in response between chronic fissured and recurrent vesicular clinical subtypes. Similar percentages of patients achieving EASI‐75 and HECSI‐75 were seen after 16 weeks. In conclusion, this study shows a favorable response of hand eczema to dupilumab in patients with AD. This raises the question whether a response will also be seen in isolated hand eczema.

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“…Another important aspect when assessing the clinical efficacy of treatment is the placebo effect, which is notoriously high in AD, and which should therefore always be compared to the drug effect. For example, EASI 50 for the placebo arm was 35% compared to 85% for dupilumab in an early‐phase 12‐week study .…”

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confidence: 99%

Personalized medicine—concepts, technologies, and applications in inflammatory skin diseases

Litman

2019

APMIS

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Dupilumab: A review of its use in the treatment of atopic dermatitis

Cited by 252 publications

References 16 publications

Alopecia areata is characterized by dysregulation in systemic type 17 and type 2 cytokines, which may contribute to disease‐associated psychological morbidity

Alopecia areata is characterized by dysregulation in systemic type 17 and type 2 cytokines, which may contribute to disease‐associated psychological morbidity

Effect of dupilumab on hand eczema in patients with atopic dermatitis: An observational study

Personalized medicine—concepts, technologies, and applications in inflammatory skin diseases

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