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IL-17 inhibition: is it the long-awaited savior for alopecia areata?

Authors:
Yuval Ramot at Hadassah Medical Center
Yuval Ramot
Barbara Marzani at Giuliani, Milan, Italy
Barbara Marzani
  • Giuliani, Milan, Italy
Daniela Pinto at Giuliani
Daniela Pinto
Elisabetta Sorbellini at Private Office , Milan, Italy
Elisabetta Sorbellini
  • Private Office , Milan, Italy
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Abstract and Figures

Interleukin-17 (IL-17) has been implicated in the pathogenesis of a large number of inflammatory and autoimmune conditions, including skin disorders such as psoriasis. Recently, much data have accumulated on the possible role of IL-17 in the pathogenesis of alopecia areata (AA). In this review, the available information on the connection between AA and IL-17 is described. While IL-17 levels are consistently reported to be elevated in the serum and lesional skin of AA patients, there is no clear connection between IL-17 levels and disease severity or duration. Some evidence has suggested an association between IL-17 and an early-onset disease, although this awaits further confirmation. While there is enough information to support clinical trials with IL-17-targeted treatments, it is possible that they will be effective only in a subset of AA patients. Further studies are warranted to better delineate the exact role of IL-17 in AA pathogenesis.
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Vol.:(0123456789)
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Archives of Dermatological Research (2018) 310:383–390
https://doi.org/10.1007/s00403-018-1823-y
REVIEW
IL-17 inhibition: isit thelong-awaited savior foralopecia areata?
YuvalRamot1· BarbaraMarzani2· DanielaPinto2· ElisabettaSorbellini3· FabioRinaldi3
Received: 11 July 2016 / Revised: 24 January 2018 / Accepted: 23 February 2018 / Published online: 1 March 2018
© Springer-Verlag GmbH Germany, part of Springer Nature 2018
Abstract
Interleukin-17 (IL-17) has been implicated in the pathogenesis of a large number of inflammatory and autoimmune condi-
tions, including skin disorders such as psoriasis. Recently, much data have accumulated on the possible role of IL-17 in the
pathogenesis of alopecia areata (AA). In this review, the available information on the connection between AA and IL-17 is
described. While IL-17 levels are consistently reported to be elevated in the serum and lesional skin of AA patients, there
is no clear connection between IL-17 levels and disease severity or duration. Some evidence has suggested an association
between IL-17 and an early-onset disease, although this awaits further confirmation. While there is enough information to
support clinical trials with IL-17-targeted treatments, it is possible that they will be effective only in a subset of AA patients.
Further studies are warranted to better delineate the exact role of IL-17 in AA pathogenesis.
Keywords Alopecia areata· IL-17· Autoimmunity· Hair· Secukinumab
Introduction
Interleukin-17 (IL-17) has gained much interest in recent
years, due to its main role in the pathogenesis of a large
number of inflammatory and autoimmune disorders. This
interest has been further fueled following the recent develop-
ment of specific inhibitors of this cytokine and its receptors,
which show very promising efficacy in several inflammatory
conditions, such as psoriasis and rheumatoid arthritis. The
dermatology field, which has been exposed to IL-17 mainly
due to the recent approval of IL-17 inhibitors for psoriasis,
has explored the potential benefit of these drugs in other
skin conditions, such as atopic dermatitis, hidradenitis sup-
purativa and cutaneous lupus [88]. Alopecia areata (AA)
is one of the skin conditions being explored as a potential
target for IL-17 inhibition, as data have accumulated on the
possible role of IL-17 and Th17 in its pathogenesis. Much
of these data have been published in the last 5years, and the
reported results depict a more or less clear picture on its role
in the pathological mechanism of the disease.
The aim of this manuscript is to provide a comprehensive
review on the role of IL-17 and Th17 in AA pathogenesis.
We start by providing information on the IL-17 pathway,
continue by exploring the reports which link IL-17 to AA,
and summarize by integrating the available information to
provide some leads to the possibility of treating AA with
IL-17-targeted therapies. This manuscript focuses on IL-17
and AA, and does not intend to provide a complete picture
of the different cytokine pathways that take part in AA
pathogenesis, as this is beyond the scope of this review, and
has been reviewed in detail in several recent papers [38, 96,
98]. However, some of the more important pathways that are
activated in AA will be reviewed briefly, to give the reader
a more comprehensive understanding on the complexity of
this condition.
The IL‑17 pathway
The IL-17 family of cytokines includes six members: IL-
17A, IL-17B, IL-17C, IL-17D, IL-17E/IL-25, and IL-17F.
IL-17 is produced by neutrophils, natural killer cells, CD8+
T cells and γδ T cells [23]. However, the major source for
IL-17 is the Th17 cells. These are a subset of CD4+ helper
T cells, which are induced to differentiate into Th17 cells by
transforming growth factor-β, IL-6, IL-1β, and tumor necro-
sis factor (TNF)-α, and their maintenance is supported by
* Yuval Ramot
yramot@gmail.com
1 Department ofDermatology, Hadassah–Hebrew University
Medical Center, PO Box12000, 9112001Jerusalem, Israel
2 Giuliani S.p.a., Milan, Italy
3 International Hair Research Foundation (IHRF), Milan, Italy
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
... Frontal fibrosing alopecia (FFA) is currently considered a clinical variant of LPP sharing some similar histopathologic findings [1][2][3][4]. A common cause of non-scarring alopecia is alopecia areata (AA), which estimated prevalence is about 0.1 to 0.2% in the general population [5]. ...
... IL-17 evokes cellular reactions in keratinocytes, fibroblasts, neutrophils and endothelial cells. It is characterized by a proinflammatory activity with the ability to induce the expression of other proinflammatory cytokines and chemokines [5,[27][28][29]. ...
... It has been indicated that AA is an autoimmune T-cell-mediated disease with the involvement of some proinflammatory cytokines such as IL-1β, IL-15, IFN-γ, and TNF-α. Histologically, alopecia areata is characterized by the presence of lymphocytic infiltrate surrounding the bulb of the hair follicles [5,42]. In the current study we investigated for the first time expression of S100A7 and S100A4 in AA lesional skin. ...
Increased expression of psoriasin (S100A7) and interleukin 17 (IL-17) in lesional skin in lichen planopilaris
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Introduction Lichen planopilaris (LPP) is an inflammatory, primary scarring alopecia, however its pathogenesis is not completely elucidated. S100A7 is a multifunctional, antimicrobial protein with proinflammatory properties. Interleukin-17 (IL-17) is implicated in the development of various autoimmune skin diseases. Aim To determine the tissue expression of S100A7, S100A4 and IL-17 in LPP. Material and methods The immunohistochemical analysis was performed on biopsy specimens obtained from individuals with histologically confirmed lichen planopilaris (n = 23), alopecia areata (AA) (n = 11), and healthy controls (n = 14). The expression was evaluated using Zeiss Axio Imager A2 light microscope. Results The number of cells showing S100A7 expression was significantly higher in LPP lesional skin compared to AA lesional skin (p = 0.0002) and normal skin of healthy controls (p < 0.0001). The number of cells showing IL-17 expression was significantly higher in LPP lesional skin compared to normal skin of healthy controls (p < 0.0001) and the number of cells showing IL-17 expression was significantly higher in AA lesional skin compared to normal skin of healthy controls (p < 0.0001). The number of cells showing IL-17 expression was not significantly different in LPP lesional skin and in AA lesional skin (p > 0.05). The number of cells showing S100A4 expression was not significantly different in LPP lesional skin, AA lesional skin and in normal skin of healthy controls. Conclusions The results of our study suggest the possible role of S100A7 and IL-17 in the pathogenesis of LPP.
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... Primarily, two subtypes of CD4+ T cells contribute to autoimmunity in AA, i.e., T helper 17 (Th17) cells and regulatory T (Treg) cells [107,108]. Th17 cells, characterized by the production of IL-17, IL-22, and IL-23, infiltrate the dermal area in the proximal vicinity of HFs in AA patients, taking the helper role together with Th1 to induce inflammation and contributing to cell-mediated autoimmunity [108,109]. Additionally, Th17 cells are implicated in autoimmunity processes in psoriasis and vitiligo, two autoimmune diseases often comorbid with AA [108,110]. CD4+ T cells mainly infiltrate the peribulbar area in the dermis [91]. ...
... The level of IL-17 is particularly elevated in the immediate environment of HF [108]. IL-17 showed a positive correlation with early onset and severity of AA, while its concentration significantly decreases after AA therapy, such as phototherapy, diphenylcyclopropenone, or JAK inhibitors [109]. Serum level of IL-22 has been positively correlated with AA duration and depression [112]. ...
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Alopecia areata (AA) is an autoimmune-mediated disorder in which the proximal hair follicle (HF) attack results in non-scarring partial to total scalp or body hair loss. Despite the growing knowledge about AA, its exact cause still needs to be understood. However, immunity and genetic factors are affirmed to be critical in AA development. While the genome-wide association studies proved the innate and acquired immunity involvement, AA mouse models implicated the IFN-γ- and cytotoxic CD8+ T-cell-mediated immune response as the main drivers of disease pathogenesis. The AA hair loss is caused by T-cell-mediated inflammation in the HF area, disturbing its function and disrupting the hair growth cycle without destroying the follicle. Thus, the loss of HF immune privilege, autoimmune HF destruction mediated by cytotoxic mechanisms, and the upregulation of inflammatory pathways play a crucial role. AA is associated with concurrent systemic and autoimmune disorders such as atopic dermatitis, vitiligo, psoriasis, and thyroiditis. Likewise, the patient’s quality of life (QoL) is significantly impaired by morphologic disfigurement caused by the illness. The patients experience a negative impact on psychological well-being and self-esteem and may be more likely to suffer from psychiatric comorbidities. This manuscript aims to present the latest knowledge on the pathogenesis of AA, which involves genetic, epigenetic, immunological, and environmental factors, with a particular emphasis on immunopathogenesis.
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... Secukinumab works by inhibiting the pro-inflammatory effects of interleukin-17A, a cytokine involved in the pathogenesis of these conditions. It is hypothesized to be a potential treatment choice for AA, although results thus far have shown no benefit [3,4]. In addition, our presented case, together with four other reports, has described the new onset of AA in IL-17 therapy ( Table 1). ...
... In addition, our presented case, together with four other reports, has described the new onset of AA in IL-17 therapy ( Table 1). In all previously published cases, patients received IL-17 therapy for the treatment of psoriasis [4][5][6]. There were two cases of patchy AA and two cases of diffuse AA. ...
Ophiasis Alopecia Areata in a Patient With Spondyloarthritis on Secukinumab: A Case Report and Review of the Literature
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Secukinumab (Cosentyx), an interleukin-17A-targeting biological agent, is commonly prescribed for psoriasis, psoriatic arthritis, and spondyloarthritis (SpA). Alopecia areata (AA), an IL-17-mediated autoimmune disorder characterized by nonscarring hair loss, particularly in an ophiasis pattern, represents a rare adverse effect associated with secukinumab therapy. We present a case of a 46-year-old female with SpA undergoing secukinumab treatment, who developed an ophiasis pattern of AA, subsequently experiencing regrowth upon medication discontinuation. The patient's clinical course and treatment response are detailed, alongside a discussion on the potential pathophysiological mechanisms underlying secukinumab-induced AA. Additionally, we provide a review of existing literature, discussing similar cases and proposing hypotheses on the immunological basis of this adverse event. This report underscores the importance of recognizing and managing secukinumab-induced AA, highlighting the need for further investigation and tailored therapeutic approaches in affected patients.
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... The IL-17A cytokine is associated with inflammation, which is believed to have a key role in both psoriasis and AA [4,7]. Interleukin 17 inhibitors were hoped to be a potential option for treating alopecia [7]. ...
... The IL-17A cytokine is associated with inflammation, which is believed to have a key role in both psoriasis and AA [4,7]. Interleukin 17 inhibitors were hoped to be a potential option for treating alopecia [7]. However, a recent double-blinded, randomized clinical trial showed no significant benefit for treating AA with secukinumab [8]. ...
Alopecia Areata After Initiation of Secukinumab Therapy for Plaque Psoriasis
Article
Full-text available
  • May 2023
The development of psoriasis and alopecia areata (AA) is multifactorial. The interleukin-17 (IL-17) cytokine is believed to be associated with the pathophysiology of both diseases. This case report demonstrates a 64-year-old female patient who experienced a new onset of AA after the initiation of IL-17A inhibitor, secukinumab, for the treatment of her psoriasis. To our knowledge, there are only three case reports specifically discussing IL-17A inhibitors and AA. This case report highlights a potential rare but significant side effect of IL-17A inhibitors.
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... Monoclonal antibody targeting interleukin-17A (IL-17A), primarily expressed in Th17 cells. By binding to IL-17A, Secukinumab may reduce production of chemokines involved in AA pathogenesis, slowing or halting disease progression [163] In a double-blind, randomized pilot study involving 11 AA patients with 60% scalp involvement, no patient reached the primary endpoint of SALT50 post-treatment with secukinumab [164]. In a 2021 study on secukinumab treatment for psoriasis, a mild therapeutic response to AA was observed [165] Dupilumab ...
Innovative strategies for the discovery of new drugs against alopecia areata: taking aim at the immune system
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Introduction: The autoimmune hair loss condition alopecia areata (AA) exacts a substantial psychological and socioeconomic toll on patients. Biotechnology companies, dermatology clinics, and research institutions are dedicated to understanding AA pathogenesis and developing new therapeutic approaches. Despite recent efforts, many knowledge gaps persist, and multiple treatment development avenues remain unexplored. Areas covered: This review summarizes key AA disease mechanisms, current therapeutic methods, and emerging treatments, including Janus Kinase (JAK) inhibitors. The authors determine that innovative drug discovery strategies for AA are still needed due to continued unmet medical needs and the limited efficacy of current and emerging therapeutics. For prospective AA treatment developers, the authors identify the pre-clinical disease models available, their advantages, and limitations. Further, they outline treatment development opportunities that remain largely unmapped. Expert opinion: While recent advancements in AA therapeutics are promising, challenges remain, including the lack of consistent treatment efficacy, long-term use and safety issues, drug costs, and patient compliance. Future drug development research should focus on patient stratification utilizing robust biomarkers of AA disease activity and improved quantification of treatment response. Investigating superior modes of drug application and developing combination therapies may further improve outcomes. Spirited innovation will be needed to advance more effective treatments for AA.
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... Elevated levels of IL-17 have been observed in both intralesional and serum samples of AA patients, suggesting its potential involvement in the disease progression. 8 This finding has led to the exploration of IL-17 inhibitors as potential treatments for AA. Paradoxically, there have been reported cases of AA developing during treatment with IL-17 inhibitors. ...
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  • Oct 2023
Secukinumab, a monoclonal antibody targeting interleukin-17 (IL-17), has exhibited encouraging results in the therapeutic management of palmoplantar pustulosis (PPP). The development of alopecia areata (AA) is closely related to IL-17, and IL-17A inhibitors were considered as a potential treatment modality. Therefore, the development of AA during secukinumab treatment for PPP is a rare adverse event that has been rarely reported worldwide. Here we report a 35-year-old female patient with PPP who developed AA after completing the induction period of secukinumab treatment. Discontinuing secukinumab and initiating treatment with tofacitinib resulted in a significant improvement in both PPP and AA. The emergence of AA in this patient can be attributed to paradoxical skin reactions associated with IL-17 inhibitors. Tofacitinib appears to alleviate biologic-induced AA during PPP syndrome treatment.
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The clinical and immunological features of alopecia areata following SARS-CoV-2 infection or COVID-19 vaccines
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Inheritance-Specific Dysregulation of Th1- and Th17-Associated Cytokines in Alopecia Areata
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Efficacy of topical tofacitinib in promoting hair growth in non-scarring alopecia: possible mechanism via VEGF induction
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Tofacitinib is a Janus kinase 3 (JAK3) inhibitor that promotes hair growth; however, the efficacy and mechanism of this effect are not yet understood. This study aimed to evaluate the efficacy and mechanism of topical tofacitinib on hair growth in mice. Eight-week-old male C57BL/6 mice were divided equally into four groups and treated topically with tofacitinib, minoxidil, or vehicle once daily for 21 days. Weekly photographs were taken to determine the area and rate of hair growth, and tissue samples were collected for histopathological evaluation. mRNA and protein expression of anagen-maintaining growth factors, including vascular endothelial growth factor (VEGF) and insulin-like growth factor-1 (IGF-1), were determined via RT-PCR and ELISA, respectively. Tofacitinib-treated mice exhibited more hair regrowth than either minoxidil-treated or control mice did between day 7 and 21 (P < 0.05). Topical tofacitinib also promoted more rapid hair growth rate than topical minoxidil or control did (P < 0.001). Histopathology showed a distinct increase in the number of hair follicles, mostly in the anagen phase, in the tofacitinib-treated group. Hair follicles in the minoxidil- and vehicle-treated groups were more often classified as catagen and anagen. VEGF mRNA and protein expression in the tofacitinib-treated group was significantly greater than those in the other groups (P < 0.05). IGF-1 mRNA expression was not upregulated in tofacitinib-treated mice. Topical tofacitinib is effective in promoting hair growth, and the possible mechanism involves increased VEGF levels and lowered inflammation. This study will help develop a new therapeutic option for non-scarring alopecia.
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Alopecia Areata: a Comprehensive Review of Pathogenesis and Management
Article
Full-text available
Alopecia areata is a common hair loss condition that is characterized by acute onset of non-scarring hair loss in usually sharply defined areas ranging from small patches to extensive or less frequently diffuse involvement. Depending on its acuity and extent, hair loss is an important cause of anxiety and disability. The current understanding is that the condition represents an organ-specific autoimmune disease of the hair follicle with a genetic background. Genome-wide association studies provide evidence for the involvement of both innate and acquired immunity in the pathogenesis, and mechanistic studies in mouse models of alopecia areata have specifically implicated an IFN-γ-driven immune response, including IFNγ, IFNγ-induced chemokines and cytotoxic CD8 T cells as the main drivers of disease pathogenesis. A meta-analysis of published trials on treatment of alopecia areata states that only few treatments have been well evaluated in randomized trials. Nevertheless, depending on patient age, affected surface area and disease duration, an empiric treatment algorithm can be designed with corticosteroids and topical immunotherapy remaining the mainstay of therapy. The obviously limited success of evidence-based therapies points to a more important complexity of hair loss. At the same time, the complexity of pathogenesis offers opportunities for the development of novel targeted therapies. New treatment opportunities based on the results of genome-wide association studies that implicate T cell and natural killer cell activation pathways are paving the way to new approaches in future clinical trials. Currently, there are ongoing studies with the CTLA4-Ig fusion protein abatacept, anti-IL15Rβ monoclonal antibodies and the Janus kinase inhibitors tofacitinib, ruxolitinib and baricitinib. Ultimately, the options available for adapting to the disease rather than treating it in an effort to cure may also be taken into consideration in selected cases of long-standing or recurrent small spot disease.
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The Changing Landscape of Alopecia Areata: The Therapeutic Paradigm
Article
Full-text available
  • Jun 2017
  • ADV THER
Alopecia areata (AA), a prevalent inflammatory cause of hair loss, lacks FDA-approved therapeutics for extensive cases, which are associated with very poor rates of spontaneous hair regrowth and major psychological distress. Current treatments for severe cases include broad immune-suppressants, which are associated with significant adverse effects, precluding long-term use, with rapid hair loss following treatment termination. As a result of the extent of the disease in severe cases, topical contact sensitizers and intralesional treatments are of limited use. The pathogenesis of AA is not yet fully understood, but recent investigations of the immune activation in AA skin reveal Th1/IFN-γ, as well as Th2, PDE4, IL-23, and IL-9 upregulations. Tissue analyses of both animal models and human lesions following broad-acting and cytokine-specific therapeutics (such as JAK inhibitors and ustekinumab, respectively) provide another opportunity for important insights into the pathogenesis of AA. As reviewed in this paper, numerous novel therapeutics are undergoing clinical trials for AA, emphasizing the potential transformation of the clinical practice of AA, which is currently lacking. Dermatologists are already familiar with the revolution in disease management of psoriasis, stemming from better understanding of immune dysregulations, and atopic dermatitis will soon follow a similar path. In light of these recent developments, the therapeutic arena of AA treatments is finally getting more exciting. AA will join the lengthening list of dermatologic diseases with mechanism-targeted drugs, thus changing the face of AA.
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The Changing Landscape of Alopecia Areata: The Translational Landscape
Article
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  • Jun 2017
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Recent genetic and preclinical studies have increased our understanding of the immunopathogenesis of alopecia areata (AA). This has allowed expedited development of targeted therapies for the treatment of AA, and a paradigm shift in our approach and understanding of autoimmunity and the hair follicle. The synergy between preclinical studies, animal models, and translational studies has led to unprecedented advances in the treatment options for AA, ultimately benefiting patients who have had little recourse. In this review, we summarize the scientific field of contemporary AA research, and look forward to potential new technologies and developments.
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Effect of sinapic acid on hair growth promoting in human hair follicle dermal papilla cells via Akt activation
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  • Jul 2017
  • ARCH DERMATOL RES
Hair loss known as alopecia is caused by abnormal hair follicle cycling including shortening of the anagen (growth) phase and changing of hair follicle morphology with miniaturization. In accordance with the life extension, the quality of life is considered to be a most important thing. The yearning for healthy and beautiful hair and low self esteem due to hair loss had negative influence on the quality of life with psychosocial maladjustment. The objective of this research was to identify new compound that can be used as a drug to promote hair growth. We investigated whether the function of sinapic acid (SA) is able to promote hair growth in human hair follicle dermal papilla cells (hHFDPC). We showed that treatment of SA in hHFDPC could induce proliferation and the activation of Akt signaling in HFDPC. In addition, SA could stimulate the expressions of the several growth factors, insulin-like growth factor 1, and vascular endothelial growth factor for hair growth. We showed that SA led to an increased level of phospho-GSK-3β and β-catenin accumulation in HFDPC. Finally, the promoting effect of SA in hHFDPC cell growth occurred by the induction of cell cycle progression. These results suggest that SA could be one of the potential candidate compounds for the treatment of alopecia by inducing hair growth through triggering the expressions of growth factors via activation of Akt and subsequent inactivation of GSK-3β /β-catenin pathway.
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Reflectance confocal microscopy for scarring and non-scarring alopecia real-time assessment
Article
Full-text available
  • Jul 2016
  • ARCH DERMATOL RES
Clinical management of alopecia represents one of the major issues in dermatology. Scalp biopsies are not easily accepted because of the high bleeding and sensitive anatomical area. Trichoscopy is routinely used for diagnosis of alopecia, but in several cases lack to provide sufficient information on the status of the disease. Recently, reflectance confocal microscopy demonstrated its usefulness for the evaluation of several inflammatory skin condition and preliminary reports about alopecia have been proposed in the literature. The aim was to identify the confocal features characterizing scarring and non-scarring alopecia. Reflectance confocal microscopy from 86 patients affected by scarring (28 lichen planopilaris and 9 lupus erythematosus) and non-scarring alopecia (30 androgenic alopecia and 19 alopecia areata), were retrospectively, blinded evaluated. Good concordance between different readers on the confocal criteria has been assessed. Statistical significant features, specific for scarring alopecia and non-scarring alopecia have been identified. In this study, data on reflectance confocal microscopy features useful for the differential diagnosis between scarring and non-scarring alopecia have been identified. Further studies focusing on the use of this non-invasive technique in the therapeutic follow-up and distinction of sub-entities of alopecia are still required.
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Alopecia areata
Article
  • Mar 2017
Alopecia areata is an autoimmune disorder characterized by transient, non-scarring hair loss and preservation of the hair follicle. Hair loss can take many forms ranging from loss in well-defined patches to diffuse or total hair loss, which can affect all hair-bearing sites. Patchy alopecia areata affecting the scalp is the most common type. Alopecia areata affects nearly 2% of the general population at some point during their lifetime. Skin biopsies of affected skin show a lymphocytic infiltrate in and around the bulb or the lower part of the hair follicle in the anagen (hair growth) phase. A breakdown of immune privilege of the hair follicle is thought to be an important driver of alopecia areata. Genetic studies in patients and mouse models have shown that alopecia areata is a complex, polygenic disease. Several genetic susceptibility loci were identified to be associated with signalling pathways that are important to hair follicle cycling and development. Alopecia areata is usually diagnosed based on clinical manifestations, but dermoscopy and histopathology can be helpful. Alopecia areata is difficult to manage medically, but recent advances in understanding the molecular mechanisms have revealed new treatments and the possibility of remission in the near future.
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Janus kinase inhibitors in dermatology: A systematic review
Article
  • Feb 2017
  • J AM ACAD DERMATOL
Background: Janus kinase (JAK) inhibitors are emerging as a promising new treatment modality for many inflammatory conditions. Objective: Our aim was to systematically review the available data on the use of JAK inhibitors in cutaneous diseases. Methods: This is a systematic review of PubMed and ClinicalTrials.gov. Results: One hundred thirty-four articles matched our search terms, of which 78 were original articles and 12 reports on adverse events. Eighteen clinical trials were found. JAK inhibitors have been extensively studied for psoriasis, showing beneficial results that were comparable to the effects achieved by etanercept. Favorable results were also observed for alopecia areata. Promising preliminary results were reported for vitiligo, dermatitis, graft versus host disease, cutaneous T cell lymphoma, and lupus erythematosus. The most common adverse events reported were infections, mostly nasopharyngitis and upper respiratory tract infections. Limitations: It was not possible to perform a meta-analysis of the results. Conclusions: This systematic review shows that while JAK inhibitors hold promise for many skin disorders, there are still gaps regarding the correct dosing and safety profile of these medications for dermatologic indications. Additional trials are necessary to address these gaps.
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Efficacy of tofacitinib in treatment of alopecia universalis in two patients
Article
  • Apr 2016
  • J EUR ACAD DERMATOL
Background: Autoimmune-triggered non-scarring hair loss is a feature of alopecia areata (AA). Initially patchy and often self-limited, severe hair loss forms include the complete loss of scalp hair or alopecia totalis (AT) and complete loss of all hair or alopecia universalis (AU). For AT and AU a reliable treatment has remained elusive. The targeted kinase inhibitor tofacitinib, in current use for treatment of other immune diseases, has been hypothesized as a viable option for AA, AT and AU therapy and a few case reports support this. Objective: Our study aims to provide evidence for the effectiveness of tofacitinib in the treatment of AU. Methods: Two patients diagnosed with long-term AU were prescribed tofacitinib citrate at a dosage of 5 mg twice daily and observed for eight months. Results: In the first patient, beard growth was significant by 3 months of treatment. By 6 months of treatment, hair growth was apparent throughout the entire body. By 8 months of treatment, scalp hair continued to grow longer and thicker. In addition, eyelashes and eyebrows were established. In the second patient, a noticeable increase in scalp hair was present just 1 month into treatment. By 4 months into treatment, significant scalp regrowth was observed as well as eyelash, eyebrow and beard regrowth. Axillary hair regrowth and isolated leg hair was noted by 8 months. Conclusion: In our patients, tofacitinib successfully alleviated AU in the absence of significant adverse side-effects. We recommend that further study be required to establish safety and confirm efficacy.
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