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.

Baricitinib Withdrawal and Retreatment in Patients With Severe Alopecia Areata: The BRAVE-AA1 Randomized Clinical Trial.

Importance: Baricitinib has demonstrated efficacy for treating severe alopecia areata in adults. There is currently limited information about the need for continuous therapy after achieving scalp hair regrowth. Objective: To report results from the randomized withdrawal period of the BRAVE-AA1 trial. Design, Setting, and Participants: BRAVE-AA1 was a randomized, placebo-controlled, phase 3 randomized clinical trial with a treatment withdrawal substudy that was conducted at 70 centers in 3 countries beginning in March 2019. It included 654 adults with severe alopecia areata (AA) (Severity of Alopecia Tool [SALT] score ≥50) who were randomized 3:2:2 to receive treatment with baricitinib, 4 mg; baricitinib, 2 mg; or placebo. Data were analyzed in August 2023. Intervention: At week 52, 154 patients who were responders (SALT score ≤20) were rerandomized 3:1 to continue to take their current dose of baricitinib or transition to placebo (randomized withdrawal). Responders randomized to placebo who experienced a loss of treatment benefit (>20-point worsening in SALT score) at any time after week 52 were retreated with their original baricitinib dose. Main Outcome and Measures: The proportion of patients who lost treatment benefit through week 152 and the proportion of patients who recaptured response after retreatment. The last observation carried forward was used to impute missing or censored data. Results: Of 654 patients who received treatment, the mean (SD) age was 37.1 (13.0) years, and there were 383 women (58.6%). At week 52, 10 of 39 responders taking baricitinib, 2 mg, and 30 of 115 responders taking baricitinib, 4 mg, were rerandomized to placebo. At 4 and 8 weeks of treatment withdrawal, 0% and 10% to 11% of patients, respectively, lost treatment benefit regardless of dose. At week 152, 80% of patients had lost benefit compared with 7% for those who continued baricitinib therapy for both dose groups. Within the follow-up observation periods, 5 of 8 patients taking 2 mg (63%) and 21 of 24 patients taking 4 mg (87.5%) recaptured a SALT score of 20 or less response after retreatment. Conclusions and Relevance: Severe AA is a chronic, relapsing condition, and this randomized clinical trial found that withdrawal of therapy for a patient population with severe AA who had achieved meaningful hair regrowth after 1 year of treatment with baricitinib resulted in loss of benefit for almost all patients, indicating that continued therapy is required to maintain hair regrowth. Trial Registration: ClinicalTrials.gov Identifier: NCT03570749.

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.

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.

Female genital mutilation: Overview and dermatologic relevance.

Female genital mutilation (FGM) is a common cultural practice, which involves the partial or complete removal of the external female genitalia. With increasing immigration from regions where the practice is endemic, there has been a growing prevalence of FGM in the United States and other developed nations. However, most medical professionals lack the baseline knowledge regarding FGM and its associated health complications. Given this increasing trend, dermatologists should anticipate an increasing number of patients with a history of FGM in their practice. While some of the obstetric, gynecologic, and psychologic consequences of FGM have been well-reported, the dermatologic findings are less characterized. Thus, this review article aims to provide dermatologists with a fundamental understanding of the prevalence, cultural significance, and health implications of FGM with a focus on the associated dermatological findings and provides recommendations on how dermatologists can address this sensitive matter.

Integrated Safety Analysis of Ritlecitinib, an Oral JAK3/TEC Family Kinase Inhibitor, for the Treatment of Alopecia Areata from the ALLEGRO Clinical Trial Program.

BACKGROUND: The ALLEGRO phase 2a and 2b/3 studies demonstrated that ritlecitinib, an oral JAK3/TEC family kinase inhibitor, is efficacious at doses of ≥ 30 mg in patients aged ≥ 12 years with alopecia areata (AA). OBJECTIVE: The objective of this study was to evaluate the safety of ritlecitinib in an integrated analysis of four studies in AA. METHODS: Two cohorts were analyzed: a placebo-controlled and an all-exposure cohort. Proportions and study size-adjusted incidence rates (IRs) of adverse events (AEs) of interest and laboratory abnormalities are reported. RESULTS: In the placebo-controlled cohort (n = 881; median exposure: 169 days), the proportion of ritlecitinib-treated patients with AEs was 70.2-75.4% across doses versus 69.5% in the placebo group; serious AEs occurred in 0-3.2% versus 1.9% for the placebo. A total of 19 patients permanently discontinued due to AEs (5 while receiving the placebo). In the all-exposure cohort (n = 1294), median ritlecitinib exposure was 624 days [2091.7 total patient-years (PY)]. AEs were reported in 1094 patients (84.5%) and serious AEs in 57 (4.4%); 78 (6.0%) permanently discontinued due to AEs. The most common AEs were headache (17.7%; 11.9/100 PY), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive test (15.5%; 9.8/100 PY), and nasopharyngitis (12.4%; 8.2/100 PY). There were two deaths (breast cancer and acute respiratory failure/cardiorespiratory arrest). Proportions (IRs) were < 0.1% (0.05/100 PY) for opportunistic infections, 1.5% (0.9/100 PY) for herpes zoster, 0.5% (0.3/100 PY) for malignancies (excluding nonmelanoma skin cancer), and 0.2% (0.1/100 PY) for major adverse cardiovascular events. CONCLUSIONS: Ritlecitinib is well tolerated with an acceptable safety profile up to 24 months in patients aged ≥ 12 years with AA (video abstract and graphical plain language summary available). TRIAL REGISTRIES: ClinicalTrials.gov: NCT02974868 (date of registration: 11/29/2016), NCT04517864 (08/18/2020), NCT03732807 (11/07/2018), and NCT04006457 (07/05/2019).

A plain language summary on ritlecitinib treatment for adults and adolescents with alopecia areata.

WHAT IS THIS SUMMARY ABOUT?: This is a summary of the results of the ALLEGRO phase 2b/3 clinical trial, originally published in The Lancet. ALLEGRO-2b/3 looked at how well and safely the study medicine, ritlecitinib, works in treating people with alopecia areata ('AA' for short). The immune system protects your body from outside invaders such as bacteria and viruses. AA is an autoimmune disease, meaning a disease in which one's immune system attacks healthy cells of the body by mistake. In AA, the immune system attacks hair follicles, causing hair to fall out. AA causes hair loss ranging from small bald patches to complete hair loss on the scalp, face, and/or body. Ritlecitinib is a medicine taken as a pill every day, by mouth, that is approved for the treatment of severe AA. It blocks processes that are known to play a role in causing hair loss in patients with AA. WHAT WERE THE RESULTS OF THE STUDY?: Adults and adolescents (12 years and older) took part in the ALLEGRO-2b/3 study. They either took ritlecitinib for 48 weeks or took a placebo (a pill with no medicine) for 24 weeks. Participants taking placebo later switched to taking ritlecitinib for 24 weeks. The study showed that participants taking ritlecitinib had more hair regrowth on their scalp after 24 weeks than those taking the placebo. Hair regrowth was also seen on the eyebrows and eyelashes in participants taking ritlecitinib. Hair regrowth continued to improve to week 48 with continued ritlecitinib treatment. In addition, more participants taking ritlecitinib reported that their AA had 'moderately' or 'greatly' improved after 24 weeks than those taking the placebo. Similar numbers of participants taking ritlecitinib or placebo had side effects after 24 weeks. Most side effects were mild or moderate. WHAT DO THE RESULTS OF THE STUDY MEAN?: Ritlecitinib was an effective and well-tolerated treatment over 48 weeks for people with AA. Clinical Trial Registration: NCT03732807 (phase 2b/3 ALLEGRO study).

Baricitinib as the first systemic treatment for severe alopecia areata.

INTRODUCTION: Alopecia areata is a heterogenous, immune-mediated hair loss disorder that can affect any hair-bearing site on the body. Despite being one of the most prevalent autoimmune skin diseases, treatments have historically been limited to off-label medications that have demonstrated limited efficacy, especially in more severe forms of disease. Thus, there has long been an unmet need for rigorously studied therapeutics in alopecia areata. AREAS COVERED: Janus kinase inhibitors have proven to be an effective class of drugs for treating several inflammatory disorders. One such drug, baricitinib, has recently demonstrated significant hair regrowth in phase 2 and 3 alopecia areata trials. It has since become the first systemic therapy approved for treating severe alopecia areata. This review examines the role of Janus kinase pathways in alopecia areata's pathogenesis and the safety and efficacy of baricitinib for treating severe alopecia areata. EXPERT OPINION: The approval of baricitinib for treating severe alopecia areata marks a major milestone in the disease's history. While baricitinib has proven to be efficacious for this indication and has demonstrated an overall good safety profile, patients' individual risk factors for serious adverse events should be assessed during shared decision-making with patients before initiating treatment.

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.

A systematic review on the lipid composition of human hair.

Hair lipid composition varies by ethnic hair type and by hair layer. Lipids in the cuticle, cortex, and medulla of the hair shaft provide a protective barrier to environmental and chemical damage, prevent hair breakage and desorption, and affect the elastic and tensile properties of hair. The aim of this systematic review is to provide an overview of the lipid composition and ethnic differences of human hair, effects of external damage on lipid content and properties, and changes in hair lipid composition associated with disease states. PubMed/MEDLINE was searched up to March 2021 according to PRISMA guidelines for articles discussing the lipid content of human hair and effects of physical, chemical, or environmental damage, and disease. Fifty-nine articles investigating the lipid content of hair were included for review. Lipids affect fluid permeability, hydration, strength, and texture of ethnic hair fibers. Lipid loss is accelerated by hair-damaging treatments such as bleach, dye, perm, straightening, and surfactant use, and sun and aging processes, leading to dehydrated, breakable, disordered, and dull hair. Diseases including acne, alopecia, and breast, gastric, prostate, lung, and rectal cancers display elevated hair lipid levels. Lipids are vital in protection against damage and maintenance of healthy hair. Further studies are needed to investigate the effects of lipids on the structural properties of ethnic hair, and changes in hair lipid composition with various dermatologic and systemic diseases.