Alopecia areata profiling shows TH1, TH2, and IL-23 cytokine activation without parallel TH17/TH22 skewing

Suárez‐Fariñas, Mayte; Ungar, Benjamin; Noda, Shinichi; Shroff, Anjali; Mansouri, Yasaman; Fuentes‐Duculan, Judilyn; Czernik, Annette; Zheng, Xiuzhong; Estrada, Yeriel; Xu, Hui; Peng, Xiangyu; Shemer, Avner; Krueger, James G.; Lebwohl, Mark; Guttman‐Yassky, Emma

doi:10.1016/j.jaci.2015.06.032

Cited by 191 publications

(246 citation statements)

References 108 publications

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“…Suárez-Fariñas et al reported a highly increase of PDE4 in human AA lesions in their study [12]. In a furher study by Guttman-Yassky et al, levels of PDE4 were found to decrease after treatment with IL-12/IL-23 antagonist [92].…”

Section: Apremilastmentioning

confidence: 84%

“…Several studies support a shared genetic background between AA and AD, besides both diseases were shown to have upregulation of Th2 component and an IL-23 [12,134,135]. The history of atopy and autoimmune disease was also found to be associated with an increased risk of AA [2,16,136].…”

Section: Dupilumabmentioning

confidence: 91%

“…TNF-α was shown to be elevated in the serum of patients with AA [78] and in lesional AA skin than nonlesional skin [12]. Although this evidence suggests that blocking TNF activity may improve AA, a clinical trial of 17 individuals was performed to investigate the effect of etanercept in AA.…”

Section: Tumor Necrosis Factor (Tnf)-α Inhibitorsmentioning

confidence: 99%

“…Genes associated with T-cell migration/activation were found to be significantly induced in lesional vs. nonlesional AA tissues. IL-12/23p40 showed the highest increase in mRNA expression of all measured inflammatory markers in lesional scalp of AA compared with normal scalp from healthy subjects [12]. As increased Th1 serum cytokine levels have been associated with extensive AA, IL-12 inhibitors (ustekinumab) would be expected to treat or at least to prevent hair loss [11,91].…”

Section: Ustekinumabmentioning

confidence: 99%

“…Secukinumab is a recombinant, high-affinity, fully human IgG1κ monoclonal antibody that selectively inhibits IL-17A [12,96,97].…”

Section: Secukinumabmentioning

confidence: 99%

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New Modalities in the Treatment of Refractory Alopecia Areata

Kılıç¹

2017

Hair and Scalp Disorders

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Alopecia areata (AA) is a common and complex T-cell-mediated inflammatory disorder. It may be patchy (localized), involve the entire scalp (alopecia totalis) or entire body (alopecia universalis). Alopecia totalis and universalis are often difficult to treat. Although many therapeutic options currently exist in alopecia areata, none of them are curative or preventive. Besides, none of them are approved by Food and Drug Administration (FDA). The disease unfortunately has an unpredictable course. The factors indicating a poor prognosis are the extent of hair loss at the presentation, long duration of the disease, and ophiasis pattern of hair loss. There are only a few randomized controlled studies conducted on recalcitrant AA. Recent research on immunology of hair follicle and recent developments in immunopathogenesis, together with the shared pathways of the disease with other autoimmune disorders, led investigators to focus on novel therapies that target specific immunological pathways. Herein, we will review shortly the current treatment options in recalcitrant alopecia areata based on recently published studies and then will focus on the recently developed broad-spectrum and targeted therapeutics.

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Section: Apremilastmentioning

confidence: 84%

Section: Dupilumabmentioning

confidence: 91%

Section: Tumor Necrosis Factor (Tnf)-α Inhibitorsmentioning

confidence: 99%

Section: Ustekinumabmentioning

confidence: 99%

“…Secukinumab is a recombinant, high-affinity, fully human IgG1κ monoclonal antibody that selectively inhibits IL-17A [12,96,97].…”

Section: Secukinumabmentioning

confidence: 99%

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New Modalities in the Treatment of Refractory Alopecia Areata

Kılıç¹

2017

Hair and Scalp Disorders

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Hair Regrowth in a Patient With Long-standing Alopecia Totalis and Atopic Dermatitis Treated With Dupilumab

et al. 2018

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Efficacy and Safety of Lebrikizumab, a High-Affinity Interleukin 13 Inhibitor, in Adults With Moderate to Severe Atopic Dermatitis

et al. 2020

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IMPORTANCE Interleukin 13 (IL-13) is a central pathogenic mediator driving multiple features of atopic dermatitis (AD) pathophysiology.OBJECTIVE To evaluate the efficacy and safety of lebrikizumab, a novel, high-affinity, monoclonal antibody targeting IL-13 that selectively prevents formation of the IL-13Rα1/IL-4Rα heterodimer receptor signaling complex, in adults with moderate to severe AD. DESIGN, SETTING, AND PARTICIPANTSA phase 2b, double-blind, placebo-controlled, dose-ranging randomized clinical trial of lebrikizumab injections every 4 weeks or every 2 weeks was conducted from January 23, 2018, to May 23, 2019, at 57 US centers. Participants were adults 18 years or older with moderate to severe AD.INTERVENTIONS Patients were randomized 2:3:3:3 to placebo every 2 weeks or to subcutaneous injections of lebrikizumab at the following doses: 125 mg every 4 weeks (250-mg loading dose [LD]), 250 mg every 4 weeks (500-mg LD), or 250 mg every 2 weeks (500-mg LD at baseline and week 2). MAIN OUTCOMES AND MEASURESThe primary end point was percentage change in the Eczema Area and Severity Index (EASI) (baseline to week 16). Secondary end points for week 16 included proportion of patients achieving Investigator's Global Assessment score of 0 or 1 (IGA 0/1); EASI improvement of at least 50%, 75%, or 90% from baseline; percentage change in the pruritus numeric rating scale (NRS) score; and pruritus NRS score improvement of at least 4 points. Safety assessments included treatment-emergent adverse events.RESULTS A total of 280 patients (mean [SD] age, 39.3 [17.5] years; 166 [59.3%] female) were randomized to placebo (n = 52) or to lebrikizumab at doses of 125 mg every 4 weeks (n = 73), 250 mg every 4 weeks (n = 80), or 250 mg every 2 weeks (n = 75). Compared with placebo (EASI least squares mean [SD] percentage change, −41.1% [56.5%]), lebrikizumab groups showed dose-dependent, statistically significant improvement in the primary end point vs placebo at week 16: 125 mg every 4 weeks (−62.3% [37.3%], P = .02), 250 mg every 4 weeks (−69.2% [38.3%], P = .002), and 250 mg every 2 weeks (−72.1% [37.2%], P < .001). Differences vs placebo-treated patients (2 of 44 [4.5%]) in pruritus NRS improvement of at least 4 points were seen as early as day 2 in the high-dose lebrikizumab group (9 of 59 [15.3%]). Treatment-emergent adverse events were reported in 24 of 52 placebo patients (46.2%) and in lebrikizumab patients as follows: 42 of 73 (57.5%) for 125 mg every 4 weeks, 39 of 80 (48.8%) for 250 mg every 4 weeks, and 46 of 75 (61.3%) for 250 mg every 2 weeks; most were mild to moderate and did not lead to discontinuation. Low rates of injection-site reactions (1 of 52 [1.9%] in the placebo group vs 13 of 228 [5.7%] in all lebrikizumab groups), herpesvirus infections (2 [3.8%] vs 8 [3.5%]), and conjunctivitis (0% vs 6 [2.6%]) were reported.CONCLUSIONS AND RELEVANCE During 16 weeks of treatment, lebrikizumab provided rapid, dose-dependent efficacy across a broad range of clinical manifestations in adult patients with moderate to severe ...

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Alopecia areata profiling shows TH1, TH2, and IL-23 cytokine activation without parallel TH17/TH22 skewing

Cited by 191 publications

References 108 publications

New Modalities in the Treatment of Refractory Alopecia Areata

New Modalities in the Treatment of Refractory Alopecia Areata

Hair Regrowth in a Patient With Long-standing Alopecia Totalis and Atopic Dermatitis Treated With Dupilumab

Efficacy and Safety of Lebrikizumab, a High-Affinity Interleukin 13 Inhibitor, in Adults With Moderate to Severe Atopic Dermatitis

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