IL‐17A is not a treatment target in progressive vitiligo

Speeckaert, Reinhart; Mylle, Sofie; Geel, Nanja van

doi:10.1111/pcmr.12789

Cited by 50 publications

(60 citation statements)

References 19 publications

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“…The authors of that study concluded that the blockade of IL‐17A receptors could be a therapeutic target in vitiligo. A recent pilot study, however, failed to show any benefit of secukinumab, an IL‐17 inhibitor, in 8 patients of progressive, non‐segmental vitiligo. The study proposed that the raised IL‐17 level in vitiligo was due to the increased percentage of Th17.1 cells instead.…”

Section: Discussionmentioning

confidence: 99%

Interleukin‐17 level in patients with vitiligo: A systematic review and meta‐analysis

Acharya

Mathur

2020

Aust J Dermatology

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Background/Objectives: The role of the pro-inflammatory cytokine, interleukin (IL)-17 is being continuously explored in various autoimmune disorders. Studies have assessed the levels of IL-17 in vitiligo patients. This study aims to evaluate the IL-17 levels in vitiligo patients in comparison with the healthy controls by performing a meta-analysis.Methods: A systematic review of the existing literature was performed in PubMed, Scopus and Cochrane databases by two authors independently. The data required to calculate the pooled effect size in the form of standardised mean difference (SMD) with the corresponding 95% confidence interval (CI) were extracted from the eligible studies. Separate analyses for active and stable vitiligo were also performed.Results: A total of 11 case-control studies with 626 vitiligo patients and 475 healthy controls were included. Random-effects meta-analysis found significantly higher serum IL-17 levels in vitiligo patients compared with the healthy controls (SMD = 1.67, 95% CI 1.11 to 2.22, P < 0.001). The IL-17 levels were higher in both active (SMD = 1.31, 95% CI 0.76 to 1.86) and stable (SMD = 1.47, 95% CI 0.59 to 2.35) vitiligo patients compared with the healthy controls. The skin IL-17 levels were also significantly higher in vitiligo patients (SMD = 1.28, 95% CI 0.82 to 1.74). Heterogeneity in the baseline characteristics of the included studies was the major limitation of this study.Conclusions: These results suggest that vitiligo patients have significantly elevated IL-17 levels. Further examination of this association could have implications for the treatment of vitiligo.

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Section: Discussionmentioning

confidence: 99%

Interleukin‐17 level in patients with vitiligo: A systematic review and meta‐analysis

Acharya

Mathur

2020

Aust J Dermatology

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“…The same result was observed in our trial using secukinumab in progressive vitiligo which showed that 7/8 patients developed new skin depigmentations leading to an early halt of further recruitment. In subsequent experiments, we showed that Th17.1 cells rather than Th17 cells are increased in active vitiligo (11). Th17.1 lymphocytes are a subgroup of Th17 cells gradually differentiating into non-classical Th1 cells.…”

Section: Disorders Based On Targeted Immune-based Cell Destruction: Amentioning

confidence: 84%

“…Several promising results have been obtained by the off-label use of biologics and by pilot trials (Table 1, Figure 1) although disappointing results can be equally important to clarify the underlying pathogenic pathways. Failure of both TNF-α inhibitors and IL-17A-blockers in alopecia areata and vitiligo limits the involvement of these cytokines in the immune-mediated destruction of skin cells (10, 11). However, the apparent efficacy of TNF-α inhibitors in toxic epidermal necrolysis and occasional cases of alopecia areata and vitiligo suggest that the role of TNF-α is more complex (4, 7, 91).…”

Section: Discussionmentioning

confidence: 99%

Learning From Success and Failure: Biologics for Non-approved Skin Diseases

2019

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The impressive potential of biologics has been demonstrated in psoriasis, hidradenitis suppurativa, and urticaria. Numerous biologicals are entering the field for a restricted number of skin disorders. Off-label use of biologics in other recalcitrant skin diseases has increased. Mounting data point to the potential of already existing biologics acting on the IL-17/IL-23 pathway in skin disorders with epidermal hyperkeratosis (e.g., pityriasis rubra pilaris), acneiform inflammation (e.g., hidradenitis suppurativa), and loss of mucosal integrity (e.g., aphthosis). TNF-α blockers are also effective in the latter conditions but seem of particular value in granulomatous (e.g., granuloma annulare) and neutrophilic disorders (e.g., pyoderma gangrenosum). Failure of IL-17 blockade in skin diseases resulting from immune-mediated cell destruction (e.g., alopecia areata and vitiligo) illustrates its limited involvement in Th1-dependent skin immunology. Overall, disappointing results of TNF-α blockers in alopecia areata and vitiligo point to the same conclusion although promising results in toxic epidermal necrolysis suggest TNF-α exerts at least some in vivo Th1-related activities. Acting on both the Th1 and Th17 pathway, ustekinumab has a rather broad potential with interesting results in lupus and alopecia areata. The efficacy of omalizumab in bullous pemphigoid has revealed an IgE-mediated recruitment of eosinophils leading to bullae formation. Reconsidering reimbursement criteria for less common but severe diseases seems appropriate if substantial evidence is available (e.g., pityriasis rubra pilaris). For other disorders, investigator-and industry-initiated randomized clinical trials should be stimulated. They are likely to improve patient outcome and advance our understanding of challenging skin disorders.

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“…Based on data supporting increased levels of Th17-related cytokines, such as IL-17 and IL-23, in the blood and skin of vitiligo patients, targeting the IL-23/IL-17 immune axis might represent another option for patients with vitiligo [ 55 , 66 ]. However, a recent clinical trial evaluating the efficacy and safety of secukinumab, a monoclonal antibody directed against IL-17, was prematuraly stopped due to the absence of clinical improvement, with worsening of the disease observed in some patients [ 67 ].…”

Section: Blocking the Initiation And Restraining The Progression Of Tmentioning

confidence: 99%

Vitiligo, From Physiopathology to Emerging Treatments: A Review

Migayron

Boniface

Sénéschal

2020

Dermatol Ther (Heidelb)

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Vitiligo is a chronic inflammatory skin disease leading to the loss of epidermal melanocytes. To date, treatment options for vitiligo patients are limited, lack sustained efficacy, and are mainly based on off-label use of immunosuppressive agents, such as systemic or topical steroids or topical calcineurin inhibitors, in association with the use of ultraviolet light. However, recent insights into the understanding of the immune pathogenesis of the disease have led to the identification of several therapeutic targets and the development of targeted therapies that are now being tested in clinical trials. In this review, based on the physiopathology of the disease, we summarize emerging targets that could be developed for the treatment of vitiligo and discuss recent and ongoing developments of drugs for the management of the disease.

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IL‐17A is not a treatment target in progressive vitiligo

Cited by 50 publications

References 19 publications

Interleukin‐17 level in patients with vitiligo: A systematic review and meta‐analysis

Interleukin‐17 level in patients with vitiligo: A systematic review and meta‐analysis

Learning From Success and Failure: Biologics for Non-approved Skin Diseases

Vitiligo, From Physiopathology to Emerging Treatments: A Review

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