Two Phase 3 Trials of Baricitinib for Alopecia Areata.

BACKGROUND: Alopecia areata is an autoimmune condition characterized by rapid hair loss in the scalp, eyebrows, and eyelashes, for which treatments are limited. Baricitinib, an oral, selective, reversible inhibitor of Janus kinases 1 and 2, may interrupt cytokine signaling implicated in the pathogenesis of alopecia areata. METHODS: We conducted two randomized, placebo-controlled, phase 3 trials (BRAVE-AA1 and BRAVE-AA2) involving adults with severe alopecia areata with a Severity of Alopecia Tool (SALT) score of 50 or higher (range, 0 [no scalp hair loss] to 100 [complete scalp hair loss]). Patients were randomly assigned in a 3:2:2 ratio to receive once-daily baricitinib at a dose of 4 mg, baricitinib at a dose of 2 mg, or placebo. The primary outcome was a SALT score of 20 or less at week 36. RESULTS: We enrolled 654 patients in the BRAVE-AA1 trial and 546 in the BRAVE-AA2 trial. The estimated percentage of patients with a SALT score of 20 or less at week 36 was 38.8% with 4-mg baricitinib, 22.8% with 2-mg baricitinib, and 6.2% with placebo in BRAVE-AA1 and 35.9%, 19.4%, and 3.3%, respectively, in BRAVE-AA2. In BRAVE-AA1, the difference between 4-mg baricitinib and placebo was 32.6 percentage points (95% confidence interval [CI], 25.6 to 39.5), and the difference between 2-mg baricitinib and placebo was 16.6 percentage points (95% CI, 9.5 to 23.8) (P<0.001 for each dose vs. placebo). In BRAVE-AA2, the corresponding values were 32.6 percentage points (95% CI, 25.6 to 39.6) and 16.1 percentage points (95% CI, 9.1 to 23.2) (P<0.001 for each dose vs. placebo). Secondary outcomes for baricitinib at a dose of 4 mg but not at a dose of 2 mg generally favored baricitinib over placebo. Acne, elevated levels of creatine kinase, and increased levels of low- and high-density lipoprotein cholesterol were more common with baricitinib than with placebo. CONCLUSIONS: In two phase 3 trials involving patients with severe alopecia areata, oral baricitinib was superior to placebo with respect to hair regrowth at 36 weeks. Longer trials are required to assess the efficacy and safety of baricitinib for alopecia areata. (Funded by Eli Lilly under license from Incyte; BRAVE-AA1 and BRAVE-AA2 ClinicalTrials.gov numbers, NCT03570749 and NCT03899259.).

Platelet-Rich Plasma: Advances and Controversies in Hair Restoration and Skin Rejuvenation.

BACKGROUND: Platelet-rich plasma (PRP) and its combined therapeutic modalities have catalyzed new possibilities in dermatology; however, limitations in evidence and lack of consensus remain among clinicians regarding optimal composition, protocol, technique, and application. OBJECTIVE: To provide an update and analysis of the evidence for PRP in hair restoration and skin rejuvenation through review of recent available data, highlighting controversies and expert insights to guide future studies, and stimulate discourse and innovations benefitting patients. METHODS: A structured review and expert analysis of PubMed publications before October 2023, with a focus on recent literature from January 2020 through October 2023. RESULTS AND CONCLUSION: Growing literature supports the utility and benefits of PRP and related autologous products for applications for skin and hair, with strongest evidence for androgenetic alopecia and skin rejuvenation. However, this is limited by lack of consensus regarding best practices and protocols. Randomized, controlled trials with uniform metrics comparing outcomes of various compositions of autologous blood products, preparation methods, dosimetry, and frequency of treatments are still required. This will allow the medical discourse to grow beyond the realm of expert opinion into consensus, standardization, and more wide spread adoption of best practices that will benefit patients.

Safety and Efficacy of Minoxidil Treatment in Scarring Alopecia: A Scoping Review.

BACKGROUND: Topical minoxidil (TM) has been a cornerstone in treating various hair loss disorders, while low-dose oral minoxidil (LDOM) is emerging as an effective alternative. Despite their widespread use, there is a notable gap in the literature regarding their use in treating scarring alopecia. OBJECTIVE: This study evaluates the efficacy and safety of TM and LDOM in managing scarring alopecia. METHODS: A systematic literature search identified relevant studies on TM and LDOM use in central centrifugal cicatricial alopecia, frontal fibrosing alopecia, lichen planopilaris, and traction alopecia. Key metrics included disease stabilization, hair thickness improvement, hair regrowth, and side effect profiles. RESULTS: Analysis of the selected studies revealed mixed outcomes. Most participants experienced benefits in terms of disease stabilization and hair regrowth with TM and LDOM. The majority of cases reported good tolerability of the treatment, although some side effects were noted. CONCLUSION: TM and LDOM show promise in scarring alopecia treatment, demonstrating benefits in disease stabilization and hair regrowth. Despite these positive indications, the variability in results and reported side effects underline the need for further research to establish their consistent efficacy and safety profiles in scarring alopecia treatment. J Drugs Dermatol. 2024;23(3):     doi:10.36849/JDD.7743.

Beyond health-related quality of life: initial psychometric validation of a new scale for addressing the gap in assessing the full range of alopecia areata psychosocial burden.

BACKGROUND: Patients with alopecia areata (AA) report a broad range of psychosocial outcomes beyond those assessed in existing health-related quality of life measures. Yet, to date, no psychometrically validated scale based on patient-reported outcomes (PROs) appears to exist to comprehensively measure these AA-specific psychosocial outcomes. OBJECTIVES: The objective of this study was to develop such a scale, the Scale of Alopecia Areata Distress (SAAD), and to provide its initial validation evidence. METHODS: Using existing qualitative research on PROs for patients with AA, a pool of 144 items was generated and subsequently reviewed for relevance, redundancy, clarity and comprehensiveness by subject matter experts in AA psychosocial impacts and the research team. This review resulted in a reduced pool of 122 items, which was then administered to adult patients with AA residing in the USA. Exploratory Factor Analysis using Principal Axis Factoring extraction with oblique rotation identified the SAAD's underlying factor structure. To reduce the SAAD item length, additional item-reduction strategies were used. RESULTS: There were 392 participants who responded to the 122 items, each with four or fewer missing item responses. Three iterations of the data analysis plan resulted in a 41-item SAAD with seven underlying factors of psychosocial impact: Emotional and Cognitive Functioning, Romantic Relationships, Family Relationships, Primary Life Responsibilities, Non-Primary Life Responsibility Activities, Stigma, and Self-Perception Change. Each factor demonstrated acceptable to high levels of internal consistency reliability. CONCLUSIONS: Initial validation evidence of the SAAD-41 scale supports its potential as a comprehensive measure of AA-related psychosocial distress for US-based adults. Further scale validation is needed.

Medical and procedural treatment of androgenetic alopecia - Where are we?

Novel medical and procedural options for androgenetic alopecia have arrived. Low-dose oral minoxidil has made its clinical debut, while data on spironolactone, finasteride, and nutritional supplements have advanced. Minimally invasive technological advancements include photobiomodulation and platelet-rich plasma. Within hair transplantation, follicular unit extraction and robotics are now at the clinicians' fingertips.

Photobiomodulation and alopecia: a crowdsourced survey study on patient preferences.

Photobiomodulation is a treatment option for hair loss and is currently FDA cleared for androgenetic alopecia. There are a variety of photobiomodulation devices intended for at-home patient use. However, data examining user preferences is lacking. A social media-based, online survey study was completed to understand patient preferences when selecting a photobiomodulation device. Secondary outcomes examined patient experience with the device. Sixty participants responded to the 21-question survey. The majority of participants had never used a photobiomodulation device (n = 50; 86.2%). Most respondents (n = 40; 67.8%) felt the efficacy of the device was the most important aspect to consider when selecting a photobiomodulation device. Additionally, a majority of participants thought 15 (n = 22; 37.3%) or 20 minutes (n = 17; 28.8%) would be a reasonable treatment duration and would prefer a hand-free device (n = 51; 86.4%). Of the eight participants who had used a photobiomodulation device, only one was dissatisfied with the device and discontinued treatment.

Psychosocial impact of pediatric alopecia areata: A survey study.

This study, which aimed to identify distress by sites of hair loss and psychosocial stressors for a pediatric alopecia areata population, enrolled 50 patients (32 females, 18 males, ages 7-17 years) from pediatric dermatology clinics, including a monthly hair disease clinic. Patients completed a 47-question survey. Scalp hair loss was rated as often or always bothersome in 34.7%; eyebrow loss in 24.3%; and eyelash loss in 21.6%, and 6 patients (12%) discontinued a social activity due to hair loss. Referral to behavioral/mental health specialists should be considered to improve psychosocial outcomes.

Efficacy and safety of ritlecitinib in adolescents with alopecia areata: Results from the ALLEGRO phase 2b/3 randomized, double-blind, placebo-controlled trial.

BACKGROUND/OBJECTIVES: This subgroup analysis of the ALLEGRO phase 2b/3 trial (NCT03732807) evaluated the efficacy and safety of ritlecitinib, an oral, selective dual JAK3/TEC family kinase inhibitor, for the treatment of alopecia areata (AA) in patients aged 12-17 years. METHODS: In ALLEGRO-2b/3, patients aged ≥12 years with AA and ≥50% scalp hair loss received once-daily ritlecitinib 50 or 30 mg (±4-week 200-mg loading dose) or 10 mg or placebo for 24 weeks. In a subsequent 24-week extension period, ritlecitinib groups continued their doses, and patients initially assigned to placebo switched to 200/50 or 50 mg daily. Clinician- and patient-reported hair regrowth outcomes and safety were assessed. RESULTS: In total, 105 adolescents were randomized. At Week 24, 17%-28% of adolescents achieved a Severity of Alopecia Tool (SALT) score ≤20 (≤20% scalp without hair) in the ritlecitinib 30 mg and higher treatment groups versus 0% for placebo. At Week 48, 25%-50% of patients had a SALT score ≤20 across ritlecitinib treatment groups (30 mg and higher). Adolescents reporting that their AA "moderately" or "greatly" improved were 45%-61% in the ritlecitinib groups (30 mg and higher) (vs. 10%-22% for placebo) at Week 24 and 44%-80% at Week 48. The most common adverse events in adolescents were headache, acne, and nasopharyngitis. No deaths, major adverse cardiovascular events, malignancies, pulmonary embolisms, opportunistic infections, or herpes zoster infections were reported. CONCLUSION: Ritlecitinib treatment demonstrated clinician-reported efficacy, patient-reported improvement, and an acceptable safety profile through Week 48 in adolescents with AA with ≥50% scalp hair loss.

Development of the alopecia areata scale for clinical use: Results of an academic-industry collaborative effort.

BACKGROUND: The current classification for alopecia areata (AA) does not provide a consistent assessment of disease severity. OBJECTIVE: To develop an AA severity scale based on expert experience. METHODS: A modified Delphi process was utilized. An advisory group of 22 AA clinical experts from the United States was formed to develop this AA scale. Representatives from the pharmaceutical industry provided feedback during its development. RESULTS: Survey responses were used to draft severity criteria, aspiring to develop a simple scale that may be easily applied in clinical practice. A consensus vote was held to determine the final AA severity statement, with all AA experts agreeing to adopt the proposed scale. LIMITATIONS: The scale is a static assessment intended to be used in clinical practice and not clinical trials. CONCLUSION: The final AA disease severity scale, anchored in the extent of hair loss, captures key features commonly used by AA experts in clinical practice. This scale will better aid clinicians in appropriately assessing severity in patients with this common disease.

Topical bimatoprost in the treatment of eyelash loss in alopecia totalis and universalis: A prospective, open-label study.

Bimatoprost is a synthetic prostaglandin structural analogue used among other indications to increase eyelash growth. The aim of this prospective, open-label study was to evaluate the safety and efficacy of topical bimatoprost in the treatment of eyelash loss in alopecia areata totalis (AT) and universalis (AU). Study subjects applied ophthalmic bimatoprost (0.3 mg/ml) solution to the eyelid margins once nightly for at least 12 weeks (mean treatment period was 30.6 weeks). A total of 16 out of 17 subjects completed the study. Only the subjects with eyelashes present at baseline experienced an increase in eyelash length and thickness. No new eyelash regrowth was induced. In patients with AT and AU topical bimatoprost affected existing eyelashes, but failed to induce regrowth of new eyelashes.

Tofacitinib as a pragmatic treatment choice for alopecia areata: A retrospective review.

Alopecia areata (AA) is an immune-mediated hair loss disease for which targeted immune treatments including Janus kinase (JAK) inhibitors, for example, tofacitinib, are emerging. More literature is needed on the safety and efficacy of JAK inhibitors, and treatment has the potential to be cost prohibitive. This study was conducted to measure safety and efficacy outcomes of off-label use of tofacitinib in AA. A secondary outcome was analysis of payment methods. We reviewed 35 AA patients treated with tofacitinib in a specialty hair disease clinic between January 2013 and July 2019 for outcomes, adverse events, and feasibility of treatment. No serious adverse events were experienced. 83.9% of patients experienced clinically significant scalp regrowth, and 32.3% experienced near total/total regrowth. Though this study was confined to retrospective analysis, the results showed that tofacitinib was safe, effective, and practical for this cohort of 35 AA patients.

Fibrosing alopecia in a pattern distribution.

BACKGROUND/OBJECTIVES: Fibrosing alopecia in a pattern distribution (FAPD) is a newly recognized form of scarring alopecia sharing characteristics of both androgenetic alopecia (AGA) and lichen planopilaris. The existing literature on FAPD and current understanding of the epidemiology, pathogenesis, clinical features, diagnosis, and treatment of this disease are reviewed. METHODS: PubMed searches were performed to identify all articles discussing FAPD. The references of articles were used to identify additional articles. RESULTS: A total of 15 articles were found describing FAPD in a total of 188 patients (164 women and 24 men; average age, 53.8). CONCLUSIONS: FAPD affects the androgen-dependent scalp and is typically associated with hair follicle miniaturization. The scalp affected by FAPD shows features of both lichen planopilaris and AGA, and FAPD may possibly represent an exaggerated inflammatory response to damaged hair follicles, triggered by AGA. Physical examination and trichoscopic evidence of follicular inflammation and, occasionally, fibrosis are important to identify the condition, and a dermoscopy-guided biopsy can confirm the diagnosis. Unless recognized, clinicians may misdiagnose FAPD as AGA associated with seborrheic dermatitis. Data on treatment modalities are limited; however, based on pathogenesis, combined therapy with anti-inflammatory and hair growth-promoting agents is warranted.

The Alopecia Areata Consensus of Experts (ACE) study part II: Results of an international expert opinion on diagnosis and laboratory evaluation for alopecia areata.

BACKGROUND: We previously reported the Alopecia Areata Consensus of Experts study, which presented results of an international expert opinion on treatments for alopecia areata. OBJECTIVE: To report the results of the Alopecia Areata Consensus of Experts international expert opinion on diagnosis and laboratory evaluation for alopecia areata. METHODS: Fifty hair experts from 5 continents were invited to participate in a 3-round Delphi process. Consensus threshold was set at greater than or equal to 66%. RESULTS: Of 148 questions, expert consensus was achieved in 82 (55%). Round 1 consensus was achieved in 10 of 148 questions (7%). Round 2 achieved consensus in 47 of 77 questions (61%). The final face-to-face achieved consensus in 25 of 32 questions (78%). Consensus was greatest for laboratory evaluation (12 of 14 questions [86%]), followed by diagnosis (11 of 14 questions [79%]) of alopecia areata. Overall, etiopathogenesis achieved the least category consensus (31 of 68 questions [46%]). LIMITATIONS: The study had low representation from Africa, South America, and Asia. CONCLUSION: There is expert consensus on aspects of epidemiology, etiopathogenesis, clinical features, diagnosis, laboratory evaluation, and prognostic indicators of alopecia areata. The study also highlights areas where future clinical research could be directed to address unresolved hypotheses in alopecia areata patient care.

Heterogeneity in amount of growth factors secreted by platelets in platelet-rich plasma samples from alopecia patients.

Platelet α-granules release growth factors (GFs) that promote healing and tissue regeneration. Platelet-rich plasma (PRP) is shown to be beneficial in treating alopecia, and however, clinical response can be inconsistent. Due to several fold enrichment of platelets secreting large quantities of GFs following PRP injections, heterogeneity in amounts of GFs secreted by platelets may contribute to inconsistent clinical responses. Herein, we evaluated factors that could potentially contribute to heterogeneous secretion of GFs by platelets. We measured platelet secretion of transforming growth factor beta1 (TGFß1), platelet-derived growth factor (PDGF-BB), epidermal growth factor (EGF), vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF2) in aliquots of de-identified PRP samples from female patients undergoing therapy in the hair disease clinic. Although secretion of GFs by platelets was comparable in PRP samples of patients with non-cicatricial and cicatricial alopecia, a Shapiro-Wilk test for normal distribution indicated significant variability across all patient samples. The amount of GF secreted by platelets was comparable when PRP prepared from two FDA-cleared devices with distinct techniques were compared. We provide evidence of platelets secreting heterogeneous amounts of GFs within each sample as high and low secretion of random factors could be simultaneously detected. These results suggest inherent heterogeneity in secretion of GFs by platelets in patient samples that are not influenced by the device used to prepare PRP. Since some GFs could have antagonistic effects on hair growth, a balance between amounts of growth promoting and inhibiting factors may be crucial in determining clinical response to PRP therapy.

"Normal-appearing" scalp areas are also affected in lichen planopilaris and frontal fibrosing alopecia: An observational histopathologic study of 40 patients.

Lichen planopilaris (LPP) and frontal fibrosing alopecia (FFA) are lymphocyte-mediated scarring alopecias which clinically affect primarily the anterior and mid-scalp. However, unaffected scalp areas have not yet been investigated in a systemic manner. In this study, we assessed histopathologic changes in affected and unaffected scalp in both diseases and healthy control subjects and compared these findings with clinical signs and scalp symptoms. We have demonstrated that "normal-appearing" scalp that is devoid of clinical lesions of LPP and FFA showed lymphocytic perifollicular inflammation around the isthmus/infundibulum areas in 65% of biopsy specimens, perifollicular fibrosis in 15% and mucin deposits in 7.5% of the cases. None of these findings were found in control samples. No direct correlation was found between the degree of histopathological inflammation, scalp symptoms and clinical lesions in the corresponding affected scalp areas. This preliminary study suggests that both diseases may be more generalized processes which affect the scalp and therefore need systemic or total scalp therapy.

Evidence for neurogenic inflammation in lichen planopilaris and frontal fibrosing alopecia pathogenic mechanism.

Lichen planopilaris (LPP) and frontal fibrosing alopecia (FFA) are lymphocytic scarring alopecias affecting primarily the scalp. Although both diseases may share some clinical and histopathological features, in the last decade, FFA has become an "epidemic" particularly in Europe, North and South America with unique clinical manifestations compared to LPP, thus, raising the idea that this disease may have a different pathogenesis. Symptoms such as scalp burning, pruritus or pain are usually present in both diseases, suggesting a possible role for nerves and neuropeptides in the pathogenesis of both diseases. Based on some previous studies, neuropeptides, such as substance P (SP) and calcitonin gene-related peptide (CGRP), have been associated with lipid metabolism and many chronic inflammatory disorders. In this study, we asked if these neuropeptides are associated with LPP and FFA scalp lesions. Alteration in the expression of SP and CGRP in affected and unaffected scalp skin from patients with both diseases was found with examination of sections using immunohistochemical techniques and confocal microscopy. We then quantitatively assessed and compared SP and CGRP expression from control, LPP and FFA scalp biopsies. Although LPP and FFA share similar histopathologic findings, opposite results were found in affected and unaffected scalp in the ELISA tests, suggesting that these diseases may have different pathogenic mechanisms. We also found presence of histopathological inflammation irrespective of evident clinical lesions, which raises the possibility that both diseases may be more generalized processes affecting the scalp.

Current Treatment of Alopecia Areata.

The number of alopecia areata (AA) clinical trials with Jak inhibitors of cytoplasmic tyrosine kinases, including Jak1, Jak2, Jak3, and tyrosine-protein kinase has increased significantly since the last Research Summit. This fact means that the conversation about current treatments for AA now also needs to include a discussion of traditionally used off-label therapies as well as evolving therapies as with Jak inhibitors.

Ruxolitinib cream for the treatment of patients with alopecia areata: A 2-part, double-blind, randomized, vehicle-controlled phase 2 study.

BACKGROUND: There are currently no treatments for alopecia areata (AA) that are universally effective or approved by the US Food and Drug Administration. Oral ruxolitinib has shown efficacy in extensive AA. Ruxolitinib cream would potentially avoid systemic adverse effects. OBJECTIVE: To assess the efficacy and safety of 1.5% ruxolitinib cream in patients with AA who had at least 25% hair loss by Severity of Alopecia Tool score. METHODS: This was a 2-part study. Part A was an open-label, 24-week study of 1.5% ruxolitinib cream in patients with 25% to 99% hair loss followed by a 24-week extension period. Part B was a double-blind, vehicle-controlled, 24-week study of 1.5% ruxolitinib cream in patients with 25% to 100% hair loss, followed by a crossover to ruxolitinib cream in the vehicle group for 24 weeks and additional treatment time for the ruxolitinib cream group. RESULTS: Although Part A results suggested potential efficacy of 1.5% ruxolitinib cream, there was no significant difference in hair regrowth based on 50% improvement in Severity of Alopecia Tool scores between patients receiving 1.5% ruxolitinib cream and vehicle in part B. There were no significant safety issues with 1.5% ruxolitinib cream. LIMITATIONS: Single strength of ruxolitinib cream. CONCLUSIONS: The 1.5% ruxolitinib cream did not have a significant effect in patients with AA.

Increased risk of second primary hematologic and solid malignancies in patients with mycosis fungoides: A Surveillance, Epidemiology, and End Results analysis.

BACKGROUND: Mycosis fungoides (MF) is associated with increased risk of second primary hematologic malignancies, but its association with second primary solid tumors is less well characterized. OBJECTIVE: This retrospective analysis seeks to assess the risk of being diagnosed with a second primary hematologic or solid malignancy in patients with MF. DESIGN: We performed an analysis of patients diagnosed with MF from 2000 through 2015 in the United States cancer registries of SEER-18 (N = 6742). RESULTS: Relative risks were estimated by using standardized incidence ratios (SIRs). Among 6742 patients, there were 511 (7.5%) second cancer events (SIR, 10.15; 95% confidence interval [CI], 9.29-11.07). These included 184 (36.0%) hematologic malignancies (SIR, 39.71; 95% CI, 34.05-46.05) and 327 (64.0%) solid tumor malignancies (SIR, 7.33; 95% CI, 6.56-8.17). Patients with MF were at increased risk for non-Hodgkin lymphoma; Hodgkin lymphoma; melanoma; and lung, female breast, prostate, colon, and renal cancers. Females were at higher risk than males (P < .05). All ethnic groups showed a statistically significant elevation in SIRs. Elevation of SIRs was observed across all stages of MF. CONCLUSIONS AND RELEVANCE: Patients with MF are at increased risk for diagnosis of second primary malignancies and should be carefully screened for discernable signs and symptoms of second malignancies.

The Alopecia Areata Consensus of Experts (ACE) study: Results of an international expert opinion on treatments for alopecia areata.

BACKGROUND: A systematic review failed to identify any systemic therapy used in alopecia areata (AA) where use is supported by robust evidence from high-quality randomized controlled trials. OBJECTIVE: To produce an international consensus statement on the use and utility of various treatments for AA. METHODS: Fifty hair experts from 5 continents were invited to participate in a 3-round Delphi process. Agreement of 66% or greater was considered consensus. RESULTS: In the first round, consensus was achieved in 22 of 423 (5%) questions. After a face-to-face meeting in round 3, overall, consensus was achieved for only 130 (33%) treatment-specific questions. There was greater consensus for intralesional treatment of AA (19 [68%]) followed by topical treatment (25 [43%]). Consensus was achieved in 45 (36%) questions pertaining to systemic therapies in AA. The categories with the least consensus were phototherapy and nonprescription therapies. LIMITATIONS: The study included a comprehensive list of systemic treatments for AA but not all treatments used. CONCLUSION: Despite divergent opinions among experts, consensus was achieved on a number of pertinent questions. The concluding statement also highlights areas where expert consensus is lacking and where an international patient registry could enable further research.