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.).

Efficacy and safety of ritlecitinib in adults and adolescents with alopecia areata: a randomised, double-blind, multicentre, phase 2b-3 trial.

BACKGROUND: Alopecia areata is characterised by non-scarring loss of scalp, face, or body hair. We investigated the efficacy and safety of ritlecitinib, an oral, selective dual JAK3/TEC family kinase inhibitor, in patients with alopecia areata. METHODS: In this randomised, double-blind, multicentre, phase 2b-3 trial done at 118 sites in 18 countries, patients aged 12 years and older with alopecia areata and at least 50% scalp hair loss were randomly assigned to oral ritlecitinib or placebo once-daily for 24 weeks, with or without a 4-week loading dose (50 mg, 30 mg, 10 mg, 200 mg loading dose followed by 50 mg, or 200 mg loading dose followed by 30 mg), followed by a 24-week extension period during which ritlecitinib groups continued their assigned doses and patients initially assigned to placebo switched to ritlecitinib 50 mg or 200 mg loading dose followed by 50 mg. Randomisation was done by use of an interactive response system and was stratified by baseline disease severity and age. The sponsor, patients, and investigators were masked to treatment, and all patients received the same number of tablets to maintain masking. The primary endpoint was Severity of Alopecia Tool (SALT) score 20 or less at week 24. The primary endpoint was assessed in all assigned patients, regardless of whether they received treatment. This study was registered with ClinicalTrials.gov, NCT03732807. FINDINGS: Between Dec 3, 2018, and June 24, 2021, 1097 patients were screened and 718 were randomly assigned to receive ritlecitinib 200 mg + 50 mg (n=132), 200 mg + 30 mg (n=130), 50 mg (n=130), 30 mg (n=132), 10 mg (n=63), placebo to 50 mg (n=66), or placebo to 200 mg + 50 mg (n=65). 446 (62%) of 718 patients were female and 272 (38%) were male. 488 (68%) were White, 186 (26%) were Asian, and 27 (4%) were Black or African American. Of 718 patients randomly assigned, 104 patients discontinued treatment (34 withdrew, 19 adverse events [AEs], 12 physician decision, 12 lack of efficacy, 13 lost to follow up, five rolled over to long-term study transfer, four pregnancies, two protocol deviations, one declined to attend follow-up due to COVID-19, one attended last visit very late due to COVID-19, and one non-compliance). At week 24, 38 (31%) of 124 patients in the ritlecitinib 200 mg + 50 mg group, 27 (22%) of 121 patients in the 200 mg + 30 mg group, 29 (23%) of 124 patients in the 50 mg group, 17 (14%) of 119 patients in the 30 mg group, and two (2%) of 130 patients in the placebo group had a response based on SALT score 20 or less. The difference in response rate based on SALT score 20 or less between the placebo and the ritlecitinib 200 mg + 50 mg group was 29·1% (95% CI 21·2-37·9; p<0·0001), 20·8% (13·7-29·2; p<0·0001) for the 200 mg + 30 mg group, 21·9% (14·7-30·2; p<0·0001) for the 50 mg group, and 12·8% (6·7-20·4; p=0·0002) for the 30 mg group. Up to week 48 and including the follow-up period, AEs had been reported in 108 (82%) of 131 patients in the ritlecitinib 200 mg + 50 mg group, 105 (81%) of 129 patients in the 200 mg + 30 mg group, 110 (85%) of 130 patients in the 50 mg group, 106 (80%) of 132 patients in the 30 mg group, 47 (76%) of 62 patients in the 10 mg group, 54 (83%) of 65 patients placebo to ritlecitinib 200 mg + 50 mg in the extension period, and 57 (86%) of 66 patients in the placebo to 50 mg group. The incidence of each AE was similar between groups, and there were no deaths. INTERPRETATION: Ritlecitinib was effective and well tolerated in patients aged 12 years and older with alopecia areata. Ritlecitinib might be a suitable treatment option for alopecia areata in patients who are candidates for systemic therapy. FUNDING: Pfizer.

Efficacy and safety of deuruxolitinib, an oral selective Janus kinase inhibitor, in adults with alopecia areata: Results from the Phase 3 randomized, controlled trial (THRIVE-AA1).

BACKGROUND: Alopecia areata (AA) is a hair loss disorder that can seriously impact quality of life. Janus kinase (JAK) inhibitors, including deuruxolitinib, have previously demonstrated significant hair regrowth in AA. OBJECTIVE: The Phase 3 THRIVE-AA1 randomized, double-blinded, placebo-controlled trial (NCT04518995) evaluated the safety and efficacy of the oral JAK1/JAK2 inhibitor deuruxolitinib in adult patients with AA. METHODS: Patients aged 18-65 years with ≥50% hair loss were randomized to deuruxolitinib 8 mg twice daily, deuruxolitinib 12 mg twice daily, or placebo for 24 weeks. The primary end point was the percentage of patients achieving a Severity of Alopecia Tool score ≤20. A key secondary end point was the percentage of satisfaction of hair patient-reported outcome responders. RESULTS: Significantly higher proportions of patients taking deuruxolitinib met the primary end point (8 mg 29.6%; 12 mg 41.5% versus placebo 0.8%). Both deuruxolitinib doses achieved significant improvements in all secondary end points versus placebo, including satisfaction of hair patient-reported outcome (8 mg 42.1%; 12 mg 53.0% versus placebo 4.7%). Most treatment-emergent adverse events were mild or moderate, consistent with other oral JAK inhibitors. LIMITATIONS: Further studies are required to understand longer-term safety, efficacy, and impact of treatment cessation. CONCLUSION: Both doses of deuruxolitinib were effective for hair regrowth. Patient satisfaction aligned with hair growth.

Patient-Reported Satisfaction with Hair Regrowth in a Study of Ritlecitinib in Alopecia Areata: Results from ALLEGRO-2b/3.

INTRODUCTION: Patients with alopecia areata (AA) report high levels of dissatisfaction with commonly used treatments. Patient-reported outcomes are essential to understanding patients' experiences with AA treatments. The objective of this study was to evaluate patient-reported satisfaction with hair growth among patients with AA receiving ritlecitinib or placebo and the correlation between clinician-assessed efficacy and patient-reported satisfaction. METHODS: In the ALLEGRO-2b/3 (NCT03732807) trial, patients with AA and ≥50% scalp hair loss were randomized to daily ritlecitinib or placebo for 24 weeks, with a 24-week extension of continued ritlecitinib or switch from placebo to ritlecitinib. The Patient Satisfaction with Hair Growth (P-Sat) measure evaluated patients' satisfaction with hair growth in 3 domains: amount, quality, and overall satisfaction with hair growth. The prespecified analysis evaluated the proportion of patients who were slightly, moderately, or very satisfied with hair growth. Several post hoc analyses assessed the proportion of patients who were moderately/very satisfied and moderately/very dissatisfied and calculated polyserial correlations between change from baseline (CFB) in Severity of Alopecia Tool (SALT) and P-Sat scores at weeks 24 and 48. RESULTS: At week 24, the proportion of patients (N = 718) reporting satisfaction (slightly, moderately, or very satisfied) overall with their hair growth ranged from 36.4% in the ritlecitinib 10-mg group (evaluated for dose ranging only) to 67.5% in the 200/50-mg group versus 22.6% in the placebo groups. In patients randomized to ritlecitinib, the proportion who were satisfied increased or was maintained at week 48. A substantially greater proportion of placebo patients who switched to ritlecitinib reported satisfaction at week 48 than at week 24. Similar results were observed for patient satisfaction with the amount and quality of hair growth. In the post hoc analyses defining satisfaction as moderately/very satisfied and dissatisfaction as moderately/very dissatisfied, the benefit of ritlecitinib was also observed. All P-Sat domain scores strongly correlated with CFB-SALT scores at weeks 24 (range 0.73-0.76; p < 0.05) and 48 (0.74-0.77; p < 0.05). CONCLUSIONS: Patients receiving active ritlecitinib doses reported favorable results versus placebo in satisfaction with hair growth up to week 48. High concordance was observed between improvement in scalp hair growth evaluated by clinicians and patient-reported satisfaction.

In Vivo Imaging Techniques for the Human Scalp: A Systematic Review of the Literature.

OBJECTIVE: Scalp inflammation and alopecia are distressing conditions for which patients regularly present to dermatology. Although some diagnoses can be made clinically, others require biopsy, which carries the risk of pain, infection, bleeding, and scarring. This review examines the existing literature regarding noninvasive in vivo imaging techniques and their evidence and utility in evaluating scalp pathology, with a focus on the diagnostics of hair conditions. METHODS: A systematic literature search was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines without timeframe restrictions. The PubMed and Clarivate (Web of Science) databases were searched using the terms ("imaging" OR "in-vivo imaging" OR "non-invasive imaging" OR "non-invasive in vivo imaging" "imaging," "in-vivo imaging) AND ("human scalp disorders" OR "scalp" OR "hair loss" OR "alopecia"). Peer-reviewed randomized control trials (RCTs), prospective studies, retrospective studies, and case series or reports discussing in vivo imaging of the scalp published before 2022 were selected. RESULTS: Forty-two studies were included and discussed; modalities included laser devices (n = 27), ultrasound (US) (n = 13), infrared thermography (n = 1), skin capacitance imaging (SCI), and ultraviolet light-enhanced visualization (ULEV) (n = 1). The most common laser devices used were reflectance confocal microscopy (RCM), multiphoton microscopy (MPM), and optical coherence tomography (OCT). US techniques included high-frequency US (HFUS) and US biomicroscopy (UBM). CONCLUSION: Quality imaging of the scalp in the setting of alopecic, neoplastic, and inflammatory diseases is highly sought after. Many of these noninvasive imaging techniques show promise, each with individual advantages and disadvantages in imaging-specific conditions. Ultimately, noninvasive imaging techniques may be used to optimize patient management and minimize morbidity associated with scalp biopsies.

The Burden of Melasma: Race, Ethnicity, and Comorbidities.

INTRODUCTION: In an effort to define the characteristics of populations affected by melasma, we utilized a large global health research network database from 108 health care organizations (TriNetx) to quantify the associations between race, ethnicity, and comorbidities. METHODS: We identified the cohort of all patients with melasma from the TriNetx database, and subsequently generated a control cohort. ICD-10 codes were used to identify the prevalence of various comorbidities associated with melasma. RESULTS: A total of 41,283 patients with melasma (93% female, mean [SD] age 48.8 [12.6] year) were identified. The most frequently associated risk factors included hypertension (25% of the melasma cohort) and hormonal contraception (24%). Rosacea (OR=5.1), atopic dermatitis (OR=3.3), lupus (OR=2.5), history of skin cancer (OR=2.5), history of internal malignancy (OR=2.1), and hormonal contraception use (OR=2.1) possessed the highest odds ratios for development of melasma (all P< 0.01). A statistically significant association was identified for melasma in Asian or Other/Unknown races (OR=2.0 and OR=1.7, P< 0.01), as well as Hispanic ethnicity (OR=1.3, P< 0.01). White, Black/African American, and Not Hispanic groups all revealed slightly lower odds (all 0.8, P< 0.01). CONCLUSION: This latest global update on the etiopathology of melasma further supports findings from prior epidemiologic study reporting preference in melanized phenotypes (Fitzpatrick skin type III-V), but less so in extreme skin types (I, II, VI). Increased associations with rosacea, atopic dermatitis, and history of cancer may emphasize the importance of treating concurrent inflammatory environments and the consideration of more frequent malignancy surveillance. J Drugs Dermatol. 2024;23(8):691-693.  doi:10.36849/JDD.8233.

Evaluation of Pericardial Effusions in Alopecia Patients on Low-Dose Oral Minoxidil Therapy.

BACKGROUND: Minoxidil is an anti-hypertensive vasodilator increasingly used off-label for the treatment of alopecia. It is associated with an increased risk of pericardial effusions, with recent reports even in patients on low-dose oral minoxidil (LDOM) therapy. OBJECTIVE: To evaluate whether LDOM is associated with increased prevalence of pericardial effusions in patients with alopecia. METHODS: In this cross-sectional study, point-of-care ultrasound was used to screen alopecia patients at dermatology appointments. Scans were evaluated by two independent cardiologists for the presence and size of effusions. The prevalence of effusions was compared between patients on LDOM therapy and patients not on minoxidil therapy. RESULTS: A total of 100 patients were evaluated for pericardial effusion: 51 LDOM patients and 49 control patients. The two groups were similar in terms of age (53.7 vs 54.1; P=0.91), sex (86% vs 73% female; P=0.14), and race. Small pericardial effusions (<1 cm) were identified in 5.8% of LDOM patients and 6% of control patients (P=1), none of which were symptomatic. LIMITATIONS: This is a small, cross-sectional study with limitations on speculation of causality in confirmed cases. CONCLUSION: We did not find evidence of increased prevalence of pericardial effusions in a small group of alopecia patients on LDOM. J Drugs Dermatol. 2024;23(9):725-728. doi:10.36849/JDD.8029.

Using qualitative methods to establish the clinically meaningful threshold for treatment success in alopecia areata.

PURPOSE: Traditionally, appropriate anchors are used to investigate the amount of change on a clinician-reported outcome assessment that is meaningful to individual patients. However, novel qualitative methods involving input from disease state experts together with patients may better inform the individual improvement threshold for demonstrating the clinical benefit of new treatments. This study aimed to establish a clinically meaningful threshold for treatment success for the clinician-reported Severity of Alopecia Tool (SALT) score for patients with alopecia areata (AA). METHODS: A purposive sample of 10 dermatologists expert in AA and 30 adult and adolescent patients with AA and a history of ≥ 50% scalp hair loss were recruited. Semi-structured interview questions explored the outcome that represented treatment success to clinicians and patients. Findings were analyzed using thematic methods to identify treatment success thresholds. RESULTS: Both informant groups confirmed scalp hair amount as the outcome of priority. Most expert clinicians considered a static threshold of 80% (n = 5) or 75% (n = 3) of the scalp hair as a treatment success. Most patient responses ranged from 70 to 90% (median: 80% of the scalp hair). Subsequently, queried patients confirmed that achieving SALT score ≤ 20 with treatment would be a success, as reflected in the Alopecia Areata Investigator Global Assessment (AA-IGA™). The novel qualitative processes used to inform this meaningful threshold reflects a clinician-then-patient process for: (a) confirmation of the patient outcome of priority; and (b) clinician input on a preliminary treatment success level for independent understanding among patients. CONCLUSION: This qualitative investigation of expert clinicians-then-patients with AA confirmed that achieving an amount of 80% or more scalp hair (SALT score ≤ 20) was an appropriate individual treatment success threshold indicating clinically meaningful improvement for patients with ≥ 50% scalp hair loss. A qualitative investigation of a quantifiable treatment success threshold is possible through a well-designed interview process with expert clinicians and the appropriate patient population.

Melatonin and the Human Hair Follicle.

BACKGROUND: Melatonin, a pleiotropic hormone, affects the physiological processes including that of the hair follicle. We seek to identify the scientific evidence to support the potential benefits of melatonin in human hair growth. OBJECTIVE: To summarize the evidence on the association between melatonin and hair health, denoted by hair growth. METHODS: A literature review using 3 databases (PubMed, Google Scholar, and Cochrane) identified studies investigating the relationship between melatonin and hair loss (2022). The following search terms were used: (hair OR hair loss OR alopecia OR hair growth OR effluvium OR scalp) and (melatonin). Two independent reviewers screened studies for inclusion criteria, and data collection included demographics, melatonin intervention, study type, and effects on hair. RESULTS: A total of 11 human studies were identified with evidence of melatonin use in subjects with diagnosed alopecia (2,267 patients; 1,140M). Eight of the studies reviewed observed positive outcomes after topical melatonin use in subjects with androgenetic alopecia (AGA). Most studies report improved scalp hair growth (n=8), density (n=4), and hair shaft thickness (n=2) among melatonin users compared with controls. Effective topical melatonin dosage appears to be 0.0033% or 0.1% solution applied once-daily for 90 to 180 days vs 1.5 mg twice-daily oral melatonin supplementation for 180 days. CONCLUSION: There is evidence to support melatonin use to facilitate scalp hair growth, particularly in men with AGA. Further studies should include more patients and investigate the mechanism of action. J Drugs Dermatol. 2023;22(3): doi:10.36849/JDD.6921.

A Systematic Review: Landscape of Private Equity in Dermatology From Past to Present.

The primary objective of this abstract is to define the growing trend of private equity (PE) backed consolidation of dermatology practices and explore its impact on patient care. The secondary objective is to better inform dermatologists of the acquisition process as well as how practices are valued in the event of a leveraged buyout. A systematic review was conducted using PRISMA guidelines using PubMed/MEDLINE and Web of Science in July 2021. Studies included were graded using the Oxford Center for Evidence-Based Medicine 2011 Levels of Evidence.1 A total of 18 articles met the inclusion/exclusion criteria. With the current environment of low interest rates combined with increasing cost of medical operations and non-clinical administrative burdens, PE is positioned to expand exponentially in total value through leveraged buyouts of solo and small dermatology groups.2 Selling dermatologists receive payment in form of upfront cash, and equity in escrow incentivizes them to continue the growth of their clinic so that it can be consolidated into a larger portfolio of practices to be sold to another buyer in 3-7 years at a far higher valuation. Within the fragmented $8.4 billion-dollar dermatology space, PE-backed practices represent approximately 10-15% of all private practices.3-5 Dermatologists should be aware of both the risks and the rewards of acquisition by PE given the fiduciary responsibility to shareholders and their patients. J Drugs Dermatol. 2023;22(4): doi:10.36849/JDD.6892 Citation: Sung CT, Salem S, Oulee A, et al. A systematic review: Landscape of private equity in dermatology from past to present. J Drugs Dermatol. 2023;22(4):404-408. doi:10.36849/JDD.6892.

Perceived Barriers to Career Advancement: Medical Students and Resident Physicians.

BACKGROUND: The path to becoming a physician is challenging, with various barriers influencing medical student and resident physician residency and fellowship training career decisions. Studies comparing perceived obstacles at disparate training levels are limited and given these obstacles are dynamic, studies are frequently needed to evaluate perceived barriers to pursuing residency specialty or fellowship of interest for physician trainees. OBJECTIVE: To evaluate and compare perceived barriers to obtaining residency specialty or fellowship of choice for medical students and resident physicians, respectively. METHODS: A Likert scale survey assessing perceived barriers was administered via the listservs of medical schools and organizations in 2021. Differences in the Likert scale score mean between medical students and resident physicians were measured with student t-tests (2-sided). RESULTS: A total of 404 medical trainees participated (301 medical students and 103 resident physicians). Medical students indicated lack of opportunity to obtain alpha omega alpha membership as the most crucial perceived barrier (mean Likert scale score ± standard deviation, 4.01±1.97), followed by USMLE Step 1 score (3.92±1.89) and lack of home program in specialty/fellowship of interest (3.62±1.85). Similarly, resident physicians implicated the lack of a home program in a specialty/fellowship of interest as the most prominent barrier (3.48±1.78), followed by lack of connections/networking (3.17±1.50) and probability of matching (3.14±1.44). CONCLUSIONS: The lack of a home program was an important barrier to pursuing a specialty or fellowship of choice for both medical students and resident physicians, respectively, and may have been heightened during the COVID-19 pandemic. J Drugs Dermatol. 2023;22(11):e17-e20    doi:10.36849/JDD.7005e.

Underrepresented Groups and Perceived Educational Barriers for Residency and Fellowship Success.

BACKGROUND: The study aimed to compare barriers perceived by medical students and resident physicians identifying as of underrepresented groups in medicine (UIM) and/or as sexual and gender minorities (SGM) to individuals not identifying with these groups, especially for trainees with an interest in dermatology. METHODS: Cross-sectional survey of medical students and resident physicians based in the United States from February 2021 to July 2021, with subgroup analysis of trainees with interest in dermatology. FINDINGS: Among trainees interested in dermatology, the most notable barriers for the UIM group were 1) lack of home program in specialty/fellowship of interest (4.71±1.73); 2) lack of connections/networking opportunities (4.14±1.29); 3) lack of opportunity to obtain AOA membership (4.00±1.96); 4) obtaining mentorship (4.00±1.47); and lack of diversity in specialty/fellowship of interest (3.93±1.14). CONCLUSIONS AND RELEVANCE: Increasing focused mentorship programs and fostering environments that embrace diversity are key to reducing perceived barriers for minority candidates. J Drugs Dermatol. 2023;22(12):1210-1215. doi:10.36849/JDD.7528R1.

A qualitative interview study to explore adolescents' experience of alopecia areata and the content validity of sign/symptom patient-reported outcome measures.

BACKGROUND: The content validity (appropriateness and acceptability) of patient-reported outcome (PRO) measures for scalp hair loss, eyebrow loss, eyelash loss, nail damage and eye irritation has been demonstrated in adults with alopecia areata (AA) but not adolescents. OBJECTIVES: To explore the content validity of the suite of AA PRO measures and accompanying photoguides in an adolescent sample. METHODS: Semi-structured, 90-min, combined concept elicitation and cognitive interviews were conducted face-to-face with adolescents who experienced ≥ 50% AA-related scalp hair loss. Transcripts underwent thematic and framework analysis. RESULTS: Eleven adolescents (aged 12-17 years, 55% female, 45% nonwhite) diagnosed with AA for 5·9 years (mean) participated. Participants had 69·6% scalp hair (mean) and current eyebrow (82%) and/or eyelash loss (82%) and/or nail involvement (36%). Adolescents reported scalp, eyebrow and eyelash hair loss as their top three most bothersome signs/symptoms. Despite mostly accepting their AA, impacts related to visible areas of hair loss were prominent. Participants demonstrated good understanding and appropriate use of the PRO measures, and advocated including hair loss percentages alongside descriptive categories in the Scalp Hair Assessment PRO™. Results confirmed treatment success thresholds established with adults: achievement of ≤ 20% scalp hair loss, no/minimal eyebrow and eyelash loss, no/a little nail damage and eye irritation (PRO measure categories 0 or 1). CONCLUSIONS: The Scalp Hair Assessment PRO™, PRO Measure for Eyebrows™, PRO Measure for Eyelashes™, PRO Measure for Nail Appearance™ and PRO Measure for Eye Irritation™ and accompanying photoguides are fit-for-purpose self-reported measures of AA signs/symptoms that are impactful to adolescents with AA.

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

BACKGROUND: Janus kinase (JAK) activation is suggested to have a pathological role in alopecia areata (AA). CTP-543, a deuterated compound that selectively inhibits JAK1 and JAK2, is being developed as an oral treatment for AA. OBJECTIVE: To assess the safety and efficacy of a 24-week regimen of CTP-543 in patients with chronic, moderate-to-severe AA. METHODS: In this phase 2, randomized, double-blind, placebo-controlled, sequential-design trial, patients were randomized to receive CTP-543 (4 mg, 8 mg, or 12 mg) or placebo every 12 hours for 24 weeks. RESULTS: A dose-related increase was observed in the percentage of patients with ≥50% relative reduction in Severity of Alopecia Tool scores from baseline at week 24 (9% placebo, 21% 4 mg twice daily, 47% 8 mg twice daily, and 58% 12 mg twice daily), with statistical significance versus placebo (P < .001) observed for the 8-mg twice daily and 12-mg twice daily groups, with differences from placebo noted as early as 12 weeks after the initiation of treatment. Safety results were consistent with the known safety profiles of JAK inhibitors. LIMITATIONS: These initial findings are from a relatively small controlled trial, and additional studies are needed to fully characterize the safety and efficacy of CTP-543 in adult patients with AA. CONCLUSIONS: Patients treated with CTP-543 (8 or 12 mg, twice daily) had a significant reduction in the severity of AA.

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.

Emerging Intralesional Treatments for Plantar Warts: A Systematic Review.

BACKGROUND: Therapies for plantar warts remain subjective and unclear, which has led to continual pursuit of an optimal treatment. As a consequence, many intralesional therapies have emerged over the last decade. This warrants a systematic review from a clinical lens which provides updates on intralesional treatment options for plantar warts from the last decade. METHODS: A PubMed/MEDLINE literature search was performed, in accordance with PRISMA reporting guidelines for systematic reviews. Original peer-reviewed articles on safety/efficacy of intralesional plantar wart treatments, published from January 2012 to January 2021, were considered for inclusion. RESULTS: Twenty-6 studies were included and the following intralesional modalities were identified (median cure rates): vitamin D3 (80%), bleomycin (74%), 5-fluorouracil (59%), Candida antigen (66%), zinc sulfate (70%), and purified protein derivative (67%). CONCLUSION: Intralesional vitamin D3, in particular, demonstrated promising results as a potential second- or even first-line agent although not accessible in the United States. Candida antigen and bleomycin are less effective than intralesional vitamin D3, but given their greater accessibility and superiority to cryotherapy, should continue to be considered for treating recalcitrant plantar warts. Moreover, the quadrivalent human papillomavirus (HPV) vaccine, showing success in case reports, warrants further attention for both the treatment and prevention of plantar warts. J Drugs Dermatol. 2022;21(12):1322-1329. doi:10.36849/JDD.6735.

Systemic Medications Associated With Hair Texture Changes.

BACKGROUND: In addition to hair loss, alterations in hair texture can be a worrisome side effect of certain medications yet are seldom reported and poorly characterized. OBJECTIVE: To systematically analyze the scientific literature to characterize medication-associated hair texture changes. METHODS: Relevant primary literature within PubMed and Cochrane was reviewed from 1985-2021 including 31 articles (1 randomized controlled trial with texture changes incidentally noted, 6 cohort, 1 cross-sectional, 23 case studies), comprising 2594 patients. RESULTS: Texture changes were associated primarily with antineoplastic agents (n = 97), antiepileptics (n = 56), retinoids (n = 15), immunomodulators (n = 3), and antiretroviral therapy (n = 1). Average age was 48.4 years old (41.2% female). De novo or exaggerated curling patterns were most commonly reported. Average time to texture change varied from 4.5 months (immunomodulators) to 17 months (antiretrovirals). Prognosis was seldom discussed with reversibility noted across all medication classes (n = 17/21; 3 weeks to 5 years post therapy). Irreversible changes were linked with antiretrovirals, retinoids, and antineoplastics. LIMITATIONS: Inability to define true incidence rates, ethnicity, and severity of texture changes due to the nature of available literature. CONCLUSIONS: Hair texture changes are potential side effects of antineoplastics, antiepileptics, retinoids, immunomodulators, and antiretroviral therapy. As these can have associated psychosocial impact, awareness among prescribing physicians is important.J Drugs Dermatol. 2022;21(9):989-996 doi:10.36849/JDD.6852.

A Systematic Review: Application of Rice Products for Hair Growth.

BACKGROUND: Rice bran extracts (RB) derived from Oryza sativa are part of cultural skin and hair care practices in Asia. Given the knowledge gap regarding clinical efficacy, marketplace availability, and safety, the growing popularity of nutraceuticals calls for better clinician awareness and scientific understanding of their applications and limitations. OBJECTIVE: To review available scientific evidence regarding therapeutic efficacy, safety, and consumer availability of RB on hair health. MATERIALS AND METHODS: A primary literature search was conducted using PubMed to identify articles on RB and hair growth in May 2021. A limited market analysis of rice-derivative-containing hair products was also conducted on Amazon.com. RESULTS: 10 studies were analyzed: six regarding the efficacy of RB for hair growth, and four analyzing the safety profile of RB. Topically applied RB increases expression of growth factors and molecular signals which promote cell proliferation in the anagen phase including β-catenin, while inhibiting enzymes responsible for propagating anagen to catagen/telogen transition including TGFβ and Type I 5α-reductase. RB is non-genotoxic, non-cytotoxic, and appropriate for human use in cosmetics. The Amazon.com search yielded 119 rice-containing hair products, reflecting their over-the-counter popularity. CONCLUSIONS: Current literature is promising for RB promoting hair growth given its ability to increase expression of growth factors and molecular signals associated with maintaining anagen phase, decreasing inflammation, inhibiting 5α-reductase, and promoting melanogenesis. J Drugs Dermatol. 2022;21(2):177-185. doi:10.36849/JDD.6345.

Coconut, Castor, and Argan Oil for Hair in Skin of Color Patients: A Systematic Review.

Coconut, castor, and argan oils are popular commercial hair oils culturally rooted in current and historical Indian and African heritages. Dermatologists treating hair and scalp conditions often face challenging patient questions of whether over-the-counter hair oils should be used. This is particularly challenging given the deeply rooted cultural practices of some skin of color patients. As a result, many dermatologists recommend patients to continue using hair oils not based on clinical efficacy but rather lack of foreseeable side effects. We analyzed the literature to investigate claims to substantiate whether these hair oils can improve hair growth, hair quality, and treat infestation clinically. Based on 22 articles that met inclusion criteria, coconut oil has been shown to treat both brittle hair and hair infestation clinically, with limited evidence regarding its impact on hair growth. There is weaker evidence for castor oil improving hair quality by increasing hair luster, and no strong evidence supporting its use for hair growth or treatment of infestation. Argan oil does not have any significant evidence supporting its use to improve hair growth, quality, or treatment of infestation. J Drugs Dermatol. 2022;21(7):751-757. doi:10.36849/JDD.6972.

The Role of Antihistamines and Dupilumab in the Management of Alopecia Areata: A Systematic Review.

BACKGROUND: Approximately 30% to 40% of alopecia areata (AA) patients have atopic dermatitis. Studies suggest that antihistamines and dupilumab may be effective treatments; however, the potential benefit of these therapies as either adjunct or monotherapy has yet to be elucidated. OBJECTIVE: To evaluate the use of antihistamines and dupilumab in the treatment of AA. METHODS: A literature search was conducted in August 2021 according to PRISMA guidelines. Inclusion criteria were articles describing the use of antihistamines or dupilumab for AA or those discussing AA development as an adverse event of these therapies. RESULTS: Forty-two articles with 395 patients describe the use of antihistamines or dupilumab in AA. The most common antihistamine regimens were oxatomide 30 mg twice a day, fexofenadine 60 or 120 mg/day, and ebastine 10 mg/day; and the majority of cases reported significant hair regrowth, decreased pruritus, and erythema. Studies on the use of dupilumab for AA demonstrated remarkable hair growth in some patients (n=23), no change in others (n=3), and no new hair loss in a patient with resolved alopecia universalis (AU) (n=1). In contrast, dupilumab therapy for AD has been implicated as a cause of AA (n=21), drug-induced alopecia (n=2), and AA-like psoriasis (n=1). CONCLUSION: Current literature is promising for the use of antihistamines as adjunct treatments for AA, while monotherapy needs to be further explored. The role of dupilumab in AA treatment and/or development also requires further research.J Drugs Dermatol. 2022;21(10):1070-1083. doi:10.36849/JDD.6553.