Ruxolitinib 1.5% Topical Cream for the Treatment of Pediatric Alopecia Areata.

Alopecia areata (AA) is a common autoimmune disorder. Although its pathogenesis is not fully understood, AA involves CD8 T cell-mediated destruction of the hair follicle. Several treatment options exist; however, there is minimal evidence in the pediatric population. Currently, there are no curative treatments for AA. The literature suggests that Janus kinase (JAK) inhibitors may be an effective treat-ment for AA, but evidence in pediatric patients is limited. Here, we report a case of severe pediatric AA treated with topical ruxolitinib, a JAK inhibitor. J Drugs Dermatol. 2024;23(5):378-379. doi:10.36849/JDD.7782.

Effect of minoxidil combined with triamcinolone acetonide on alopecia areata by microneedle injection.

OBJECTIVE: Alopecia areata (AA) is often characterized by sudden onset of patchy hair loss. Topical corticosteroid injection is the most common treatment. This study retrospectively observed the clinical efficacy of microneedle minoxidil combined with triamcinolone acetonide in the treatment of AA. METHODS: A total of 230 patients with AA were selected. The experimental group (n = 120) received physician training and home microneedle treatment with minoxidil combined with triamcinolone acetonide once a week. Topical minoxidil and triamcinolone acetonide were used twice daily at other times. The control group (n = 110) was treated with minoxidil combined with triamcinolone acetonide, twice a day. Cure rate, response rate, SALT, dermatological Quality of Life Index (DLQI), visual analogue (VAS), and cost were assessed at weeks 4 and 12. RESULTS: Treated group SALT score(Severity of Alopecia Tool) remarkable lower than control group after treated 4 and 12 weeks. After 12 weeks treatment, DLQI score of the treated group (1.8 ± 1.67) were significantly lower than those of the control group (2.45 ± 1.88) (p < 0.05). VAS score and adverse reaction between two group showed no significant different (p = 0.823, p = 0.484 respectively). The total cost was 53.93 ± 15.85 in the treatment group and 53.26 ± 11.51 in the control group. There was no significant difference between the two groups (p = 0.72). In the treated group, the complete response rate (CR: 78.33%) and total effective rate (CR+PR: 95%) were significantly higher than those in the control group (CR: 40.91% and CR+PR: 51.82%), with statistically significant differences (p < 0.001). CONCLUSION: Microneedle introduction of minoxidil and triamcinolone acetonide in the treatment of AA is a safe, effective, economical, and convenient method, with few adverse reactions, and has a good application prospect.

Alopecia areata: review of epidemiology, pathophysiology, current treatments and nanoparticulate delivery system.

Alopecia areata (AA) is a kind of alopecia that affects hair follicles and nails. It typically comes with round patches and is a type of nonscarring hair loss. Various therapies are accessible for the management and treatment of AA, including topical, systemic and injectable modalities. It is a very complex type of autoimmune disease and is identified as round patches of hair loss and may occur at any age. This review paper highlights the epidemiology, clinical features, pathogenesis and new treatment options for AA, with a specific emphasis on nanoparticulate drug-delivery systems. By exploring these innovative treatment approaches, researchers aim to enhance the effectiveness and targeted delivery of therapeutic agents, ultimately improving outcomes for individuals living with AA.

MiR-200c-3p as a novel genetic marker and therapeutic tool for alopecia areata.

BACKGROUND: MicroRNAs (miRNAs) are small RNA molecules that regulate gene expression in diverse biological processes. They hold promise as therapeutic candidates for targeting human disease pathways, although our understanding of their gene regulatory mechanism remains incomplete. Alopecia areata (AA) is a prevalent inflammatory ailment distinguished by the infiltration of T cells targeting the anagen-stage hair follicles. The scarcity of effective remedies for AA may stem from limited understanding regarding its precise cellular mechanism. AIM: To investigate and examine the importance and role of the miR-200c-3p as a genetic indicator for AA, and its possible impact on disease progression. SUBJECTS AND METHODS: Case-control study included 65 patients with AA and 65 matched healthy controls. A real-time PCR technique was used to measure the expression of miR-200c-3p for both groups. Bioinformatic tools were used for prediction with genes and gene-gene interaction, and protein-protein interaction. RESULTS: The expression levels of miR-200c-3p were significantly higher in AA patients than in healthy controls. We predicted that miR-200c-3p plays a markable role in the development of AA by its effect on the EGFR tyrosine kinase inhibitor resistance pathway. CONCLUSION: We were able to identify the influence of miR-200c-3p on both PLCG1 and RPS6KP1 genes which in turn regulate the EGFR tyrosine kinases resistance pathway that displayed the most substantial increase in activity. Our outcomes shed light on the era of the potential theranostic role of this innovative miRNA in AA.

Treatment Options for Alopecia Areata in Children and Adolescents.

Alopecia areata (AA) lifetime incidence is around 2%, with many patients first experiencing symptoms during childhood. However, ritlecitinib is the only FDA-approved treatment for pediatric patients 12 years and older. This review outlines reported topical, injectable, and oral treatment options for pediatric patients with AA. Clinical studies were obtained via a PubMed search using the following search terms: alopecia areata, areata, universalis, or totalis and medication, therapy, treatment, drug, or management. Only studies with pediatric patients were included in this review. Commonly used therapies, including corticosteroids, methotrexate, and minoxidil, newer promising medications, such as Janus kinase inhibitors, and less frequently used topical and systemic treatments are included. A summary of the drug development pipeline and ongoing interventional clinical trials with pediatric patients is provided. Treatments demonstrate variable efficacy, and many patients require combination therapy for maximal response. More robust clinical data is needed for many of the medications reviewed in order to provide better care for these patients.

Long-term efficacy and safety of baricitinib in patients with severe alopecia areata: 104-week results from BRAVE-AA1 and BRAVE-AA2.

BACKGROUND: Efficacy of the Janus kinase (JAK) inhibitor baricitinib for severe alopecia areata (AA) continuously increased over 52 weeks in two Phase 3 trials. There are limited long-term data on JAK inhibitors in AA. OBJECTIVES: To evaluate efficacy and safety of baricitinib for severe AA through 104 weeks of continuous therapy. METHODS: Integrated data from the BRAVE-AA1 and BRAVE-AA2 Phase 3 trials included adults with Severity of Alopecia Tool (SALT) scores ≥50 (≥50% scalp hair loss) randomized to and continuously treated with 2-mg or 4-mg baricitinib through Week 104. Patients who qualified to remain on continuous treatment included subjects who achieved SALT score ≤20 at Week 52 (Week-52 responders; 2-mg: N = 65; 4-mg: N = 129) and baricitinib 4-mg-treated patients who had SALT score >20 at Week 52 but achieved SALT score ≤20 at prior visit(s) and/or had significant improvement in eyebrow or eyelash hair growth relative to baseline by Week 52 (Week-52 mixed responders; N = 110). Week-104 outcomes included the proportion of patients achieving SALT score ≤20 (≤20% scalp hair loss). Data were censored after treatment discontinuation. RESULTS: Among baricitinib 4-mg-treated and baricitinib 2-mg-treated Week-52 responders, 90.7% and 89.2%, respectively, maintained SALT score ≤20 at Week 104. Among Week-52 mixed responders, 39.1% reached SALT score ≤20 by Week 104. Continued improvement in eyebrow and eyelash regrowth was observed across groups. The most frequent treatment-emergent adverse events were COVID-19, upper respiratory tract infection, headache, nasopharyngitis, acne, urinary tract infection and creatine phosphokinase increase. CONCLUSIONS: Baricitinib demonstrated a high level of maintenance of efficacy over 104 weeks in patients with severe AA. Efficacy increased in Week-52 mixed responders, illustrating that long-term treatment is necessary to observe maximum benefit in some patients. No new safety signals were observed.

Dupliumab therapy for alopecia areata: a case series and review of the literature.

BACKGROUND: A growing body of research supports the important role of the TH2 axis in alopecia areata (AA). Dupilumab is a humanized monoclonal antibody against IL-4Rα that downregulates TH2 response. Although efficacy has been shown in clinical trials, real-world data on the use of dupilumab in AA patients is limited. OBJECTIVES: To report on a case series of 10 patients with AA who were treated with dupilumab and provide real-world evidence regarding its efficacy in treating severe AA. METHODS: In this retrospective single-center study, all AA patients treated with dupilumab treatment were included between May 2022 and October 2023. Clinical outcome measures (Severity of Alopecia Tool, SALT) and adverse events (AEs) were analyzed. In addition, a literature review was conducted to summarize the efficacy of AA with dupilumab and the characteristics of patients previously reported in the literature. RESULTS: We identified 10 patients with AA who were or are being treated with dupilumab, with a median (range) treatment duration of 8 (3-15) months. Of these, four patients have high serum immunoglobulin E (IgE) levels (≥200IU/ml). The mean (IQR) pretreatment SALT score was 79% (52-100). Seven of 10 patients achieved at least 50% re-growth. Of those who improved, the mean (IQR) percentage change in SALT score at 3 months and the end of follow-up was 57% (29%-89%) and 95% (68-100), respectively. Notably, seven patients (70%) had white hair regrowth, with the white hair slowly decreasing over time and the proportion of pigmented black hair increasing. Dupilumab was well tolerated by all patients. No adverse events were reported. CONCLUSIONS: Overall, our research supports dupilumab as another candidate that possesses potential benefits for AA. High levels of IgE may be not prerequisites for dupilumab's successful treatment response.

CXCL12 Neutralizing Antibody Promotes Hair Growth in Androgenic Alopecia and Alopecia Areata.

We had previously investigated the expression and functional role of C-X-C Motif Chemokine Ligand 12 (CXCL12) during the hair cycle progression. CXCL12 was highly expressed in stromal cells such as dermal fibroblasts (DFs) and inhibition of CXCL12 increased hair growth. Therefore, we further investigated whether a CXCL12 neutralizing antibody (αCXCL12) is effective for androgenic alopecia (AGA) and alopecia areata (AA) and studied the underlying molecular mechanism for treating these diseases. In the AGA model, CXCL12 is highly expressed in DFs. Subcutaneous (s.c.) injection of αCXCL12 significantly induced hair growth in AGA mice, and treatment with αCXCL12 attenuated the androgen-induced hair damage in hair organ culture. Androgens increased the secretion of CXCL12 from DFs through the androgen receptor (AR). Secreted CXCL12 from DFs increased the expression of the AR and C-X-C Motif Chemokine Receptor 4 (CXCR4) in dermal papilla cells (DPCs), which induced hair loss in AGA. Likewise, CXCL12 expression is increased in AA mice, while s.c. injection of αCXCL12 significantly inhibited hair loss in AA mice and reduced the number of CD8+, MHC-I+, and MHC-II+ cells in the skin. In addition, injection of αCXCL12 also prevented the onset of AA and reduced the number of CD8+ cells. Interferon-γ (IFNγ) treatment increased the secretion of CXCL12 from DFs through the signal transducer and activator of transcription 3 (STAT3) pathway, and αCXCL12 treatment protected the hair follicle from IFNγ in hair organ culture. Collectively, these results indicate that CXCL12 is involved in the progression of AGA and AA and antibody therapy for CXCL12 is promising for hair loss treatment.

The role of laser and energy-assisted drug delivery in the treatment of alopecia.

It has been recently established that laser treatment can be combined with topical or intralesional medications to enhance the delivery of drugs and improve overall results in a variety of different dermatological disorders. The aim of this review is to evaluate the use of laser and energy-assisted drug delivery (LEADD) for the treatment of alopecia with a specific focus on ablative fractional lasers (AFL), non-ablative fractional lasers (NAFL), and radiofrequency microneedling (RFMN). A comprehensive PubMed search was performed in December 2022 for "laser-assisted drug delivery" as well as "laser" and "alopecia." The evidence regarding LEADD for alopecia treatment is limited to two specific alopecia subtypes: alopecia areata (AA) and androgenetic alopecia (AGA)/pattern hair loss (PHL). LEADD with minoxidil and platelet-rich plasma (PRP) were evaluated for efficacy in both treatments of AA and AGA. LEADD with topical corticosteroids and intralesional methotrexate were studied for the treatment of AA, while LEADD with growth factors and stem cells were studied for the treatment of AGA. Multiple RCTs evaluated LEADD for topical corticosteroids with ablative fractional lasers for the treatment of AA. There is evidence in the literature that supports the use of topical minoxidil in combination with all devices for the treatment of AGA/PHL. All the reviewed studies show a positive treatment effect with LADD; however, some trials did not find LEADD to be superior to monotherapy or microneedling-assisted drug delivery. LEADD is a rapidly emerging treatment modality for the treatment of AGA and AA.

The role of fractional laser-assisted drug delivery in enhancing the efficacy of topical bimatoprost solution in the treatment of alopecia areata: An intra-patient comparative randomized clinical trial.

BACKGROUND: Transepidermal drug delivery is a novel therapeutic technique to boost efficacy of topical drugs. AIM: In this clinical trial we evaluate the efficacy of the combination of fractional carbon dioxide (FCO2) laser and bimatoprost solution compared to bimatoprost alone in the treatment of alopecia areata. METHODS: This is a prospective intra-patient comparative randomized clinical trial on 20 patients with alopecia areata. In each participant two patches were chosen to randomly receive either topical 0.03% bimatoprost solution (twice a day for 12 weeks) alone or in combination with FCO2 laser (every 2 weeks for 12 weeks). Then response to treatment was evaluated by the measurement of the severity of alopecia tool score system (SALT) score, percentage of hair regrowth, physician assessment and patients' satisfaction. RESULTS: SALT score was reduced significantly during treatment sessions and after a 3-month follow-up in both treatment groups (p = 0.000). The mean percentage of improvement in SALT score in the combination therapy and monotherapy groups were 46.43 ± 4.35% and 21.16 ± 4.06% at the end of the study and 46.42 ± 5.75% and16.11 ± 3.10% at the end of the follow-up period, respectively (p = 0.000). A general linear model of two-way analysis demonstrated a significantly superior outcome in the combination therapy group compared to the monotherapy group during time (F1.6, 13.2 = 43.8. p = 0.000). CONCLUSION: Fractional ablative laser can be considered as an assistant method for enhancing of efficacy of topical drugs especially in refractory cases of patchy alopecia areata.

[Dermatology. New uses for JAK inhibitors in dermatology: a panacea, but at what price?] / Dermatologie. Nouvelles utilisations des inhibiteurs de JAK en dermatologie : panacée mais à quel prix ?

Janus kinase inhibitors (JAKi) are small molecules which prevent the phosphorylation of JAKs, thereby blocking the intracellular phosphorylation cascade required for the transcription of several cytokines. In addition to approved indications that have been extensively studied, including atopic dermatitis, alopecia areata, vitiligo and psoriasis, JAKi are also proposed off-label, included topically, in several dermatological conditions where standard treatments are often disappointing, such as hidradenitis suppurativa (HS), extensive morphea, cutaneous sarcoidosis and lichen planus. On the other hand, the wide mechanism of action on cytokine blockade implies a safety profile that requires a case-by-case assessment of the risk/benefit ratio before their introduction.

Les inhibiteurs de Janus kinases (JAKi) sont de petites molécules empêchant la phosphorylation des JAK et bloquant ainsi la cascade de phosphorylation intracellulaire nécessaire à la transcription de plusieurs cytokines. Au-delà des indications approuvées ayant fait sujets de larges études, dont la dermatite atopique, la pelade, le vitiligo et le psoriasis, les JAKi sont aussi proposés off-label y compris en formulation topique dans plusieurs pathologies dermatologiques où les traitements habituellement utilisés sont souvent décevants : maladie de Verneuil, morphées étendues, sarcoïdose cutanée, lichen plan. En revanche, le mécanisme d'action assez large sur le blocage cytokinique implique un profil de sécurité nécessitant une évaluation cas pour cas du ratio risques/bénéfices avant leur introduction.

A cross-sectional analysis of medications used by patients reporting alopecia areata on the FDA adverse events reporting system.

BACKGROUND: Alopecia areata (AA) is an autoimmune condition that leads to patchy, nonscarring hair loss. Its etiology remains unknown; the condition can be debilitating for patients, impacting their psychosocial wellbeing. Various triggers have been reported, ranging from genetic predisposition and infections to environmental factors. Medications have also been thought to be an inciting factor in AA. METHODS: Using the Food and Drug Administration (FDA) Adverse Events Reporting System (FAERS), all cases reporting AA as an adverse event were used to capture associated medications and patient characteristics. RESULTS: There were 1,331 AA cases reported as an adverse event with medication use. Monoclonal antibodies accounted for 6 out of the top 10 drugs associated with the highest number of AA cases. Males were more likely to report AA when taking adalimumab (OR: 1.79, P = 0.04) and dupilumab (OR: 2.56, P = 0.03) compared to females. Individuals between 42 and 64 years old accounted for 46.7% of AA cases. Lastly, females in older age groups showed greater odds of developing AA compared to males (OR: 1.03, P < 0.01). CONCLUSIONS: Based on the FAERS, there has been a steady rise in AA cases, and monoclonal antibodies were the most frequently cited medication class tied to AA. With a dearth of literature on triggers and patient demographics, we sought to describe features of AA cases that could increase awareness and be used to improve future clinical outcomes in patients.