Phase 2 randomized, dose-ranging trial of CTP-543, a selective Janus Kinase inhibitor, in moderate-to-severe alopecia areata

King, Brett; Mesinkovska, Natasha Atanaskova; Mirmirani, Paradi; Bruce, Suzanne; Kempers, Steve; Guttman‐Yassky, Emma; Roberts, Janet L.; McMichael, Amy J.; Colavincenzo, Maria; Hamilton, Colleen; Braman, Virginia; Cassella, James V.

doi:10.1016/j.jaad.2022.03.045

Cited by 45 publications

(73 citation statements)

References 11 publications

(12 reference statements)

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“…Primary outcomes: 30%, 50%, 75%, 90% and 100% improvement in SALT score. Five randomized studies provided data on improvement in SALT score and were included in the meta-analysis (22,26,27,19,20). Alopecia areata defined as ≥ 50% scalp hair loss.…”

Section: Meta-analysismentioning

confidence: 99%

Comparative Efficacy and Safety of Janus Kinase Inhibitors Used in Alopecia Areata: A Systematic Review and Meta-analysis

et al. 2023

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The aim of this study was to compare the efficacy and safety of treatment with Janus kinase inhibitors for alopecia areata, measured by change in Severity of Alopecia Tool (SALT) score. A systematic review following Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines was performed using Medline, EMBASE and Cochrane library. All studies investigating the efficacy of treatments for alopecia areata were included. Primary outcomes were the proportion of patients with alopecia areata achieving 30%, 50%, 75%, 90% and 100% improvement in SALT score after treatment with a Janus kinase inhibitor. A meta-analysis was performed including all randomized controlled trials investigating Janus kinase inhibitors. A total of 37 studies matched the inclusion criteria and were included. Meta-analysis was performed based on 5 randomized studies. Regarding patients with alopecia areata defined as ≥ 50% scalp hair loss, baricitinib 4 mg once daily demonstrated the highest efficacy. However, among patients with alopecia areata defined as a SALT score ≥ 50, oral deuruxolitinib 12 mg twice daily demonstrated the highest efficacy. Deuruxolitinib and baricitinib appear to be promising drugs for the treatment of alopecia areata. However, the response depends on the dosage of the drug. More randomized trials, with identical inclusion criteria and dose and duration of treatment, are required to confirm these findings.

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Section: Meta-analysismentioning

confidence: 99%

Comparative Efficacy and Safety of Janus Kinase Inhibitors Used in Alopecia Areata: A Systematic Review and Meta-analysis

et al. 2023

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“…Additionally, serum levels of Cxcl10, an IFN-inducible chemokine, were noticeably lower after 4 weeks of tofacitinib treatment. However, upon ceasing treatment, the patient presented with near complete loss of hair at the 16-week timepoint ( 77 ). A more recent entry in the literature reported the efficacy of treating a patient that presented with AU, atopic dermatitis, and ulcerative colitis simultaneously.…”

Section: First Generation Jak Inhibitorsmentioning

confidence: 99%

An overview of JAK/STAT pathways and JAK inhibition in alopecia areata

Lensing

Jabbari

2022

Front. Immunol.

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Alopecia Areata (AA) is a common autoimmune disease characterized by non-scarring hair loss ranging from patches on the scalp to complete hair loss involving the entire body. Disease onset is hypothesized to follow the collapse of immune privilege of the hair follicle, which results in an increase in self-peptide/MHC expression along the follicular epithelium. Hair loss is associated with infiltration of the hair follicle with putatively self-reactive T cells. This process is thought to skew the hair follicle microenvironment away from a typically homeostatic immune state towards one of active inflammation. This imbalance is mediated in part by the dominating presence of specific cytokines. While interferon-γ (IFNγ) has been identified as the key player in AA pathogenesis, many other cytokines have also been shown to play pivotal roles. Mechanistic studies in animal models have highlighted the contribution of common gamma chain (γc) cytokines such as IL-2, IL-7, and IL-15 in augmenting disease. IFNγ and γc cytokines signal through pathways involving receptor activation of Janus kinases (JAKs) and signal transducers and activators of transcription (STATs). Based on these findings, JAK/STAT pathways have been targeted for the purposes of therapeutic intervention in the clinical setting. Case reports and series have described use of small molecule JAK inhibitors leading to hair regrowth among AA patients. Furthermore, emerging clinical trial results show great promise and position JAK inhibitors as a treatment strategy for patients with severe or recalcitrant disease. Demonstrated efficacy from large-scale clinical trials of the JAK inhibitor baricitinib led to the first-in-disease FDA-approved treatment for AA in June of 2022. This review aims to highlight the JAK/STAT signaling pathways of various cytokines involved in AA and how targeting those pathways may impact disease outcomes in both laboratory and clinical settings.

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“…This led to dose interruption, but was resolved after 11 days and the patient completed the study. Other adverse events leading to treatment cessation include anaemia and asthma seen in the 8 mg twice daily group 23 …”

Section: Resultsmentioning

confidence: 99%

“…Other adverse events leading to treatment cessation include anaemia and asthma seen in the 8 mg twice daily group. 23…”

Section: Adverse Eventsmentioning

confidence: 99%

Systematic review of newer agents for the management of alopecia areata in adults: Janus kinase inhibitors, biologics and phosphodiesterase‐4 inhibitors

Gupta

Wang

Ravi

et al. 2022

Acad Dermatol Venereol

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Management options for moderate‐to‐severe alopecia areata (AA) are limited owing to a lack of safe and effective treatments suitable for long‐term use. However, newer agents have the potential to induce and maintain hair regrowth in patients with a better side‐effects profile compared to systemic steroids or conventional systemic agents. In this article, we conducted a systematic review of newer agents, including Janus kinase (JAK) inhibitors, biologics and phosphodiesterase‐4 (PDE‐4) inhibitors, for the treatment of AA in adult patients evaluated in randomized controlled trials (RCTs) using the Severity of Alopecia Tool score. A literature search was performed on PubMed and ClinicalTrials.gov, which identified 106 items with 12 RCTs eligible for review. Information regarding the treatment regimen, duration, endpoints, efficacy and adverse events were extracted; product monograph information was also summarized for approved agents with or without indications for AA. Overall, current data suggest the oral JAK inhibitors (baricitinib, ritlecitinib, deuruxolitinib, brepocitinib) as a promising new class of agents that can induce significant hair regrowth, with mild to moderate adverse effects. Baricitinib recently received US FDA approval for the treatment of severe AA, while ritlecitinib and deuruxolitinib have received the breakthrough therapy designation for AA. In contrast, PDE‐4 inhibitors (apremilast) and the biologics (dupilumab, secukinumab and aldesleukin) appear to have limited efficacy thus far. Results from ongoing and future long‐term studies could shed light on the utility of the newer agents in altering the progression of AA.

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Phase 2 randomized, dose-ranging trial of CTP-543, a selective Janus Kinase inhibitor, in moderate-to-severe alopecia areata

Cited by 45 publications

References 11 publications

Comparative Efficacy and Safety of Janus Kinase Inhibitors Used in Alopecia Areata: A Systematic Review and Meta-analysis

Comparative Efficacy and Safety of Janus Kinase Inhibitors Used in Alopecia Areata: A Systematic Review and Meta-analysis

An overview of JAK/STAT pathways and JAK inhibition in alopecia areata

Systematic review of newer agents for the management of alopecia areata in adults: Janus kinase inhibitors, biologics and phosphodiesterase‐4 inhibitors

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