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ImportanceCurrent measures of alopecia areata (AA) severity, such as the Severity of Alopecia Tool score, do not adequately capture overall disease impact.ObjectiveTo explore factors associated with AA severity beyond scalp hair loss, and to support the development of the Alopecia Areata Severity and Morbidity Index (ASAMI).Evidence reviewA total of 74 hair and scalp disorder specialists from multiple continents were invited to participate in an eDelphi project consisting of 3 survey rounds. The first 2 sessions took place via a text-based web application following the Delphi study design. The final round took place virtually among participants via video conferencing software on April 30, 2022.FindingsOf all invited experts, 64 completed the first survey round (global representation: Africa [4.7%], Asia [9.4%], Australia [14.1%], Europe [43.8%], North America [23.4%], and South America [4.7%]; health care setting: public [20.3%], private [28.1%], and both [51.6%]). A total of 58 specialists completed the second round, and 42 participated in the final video conference meeting. Overall, consensus was achieved in 96 of 107 questions. Several factors, independent of the Severity of Alopecia Tool score, were identified as potentially worsening AA severity outcomes. These factors included a disease duration of 12 months or more, 3 or more relapses, inadequate response to topical or systemic treatments, rapid disease progression, difficulty in cosmetically concealing hair loss, facial hair involvement (eyebrows, eyelashes, and/or beard), nail involvement, impaired quality of life, and a history of anxiety, depression, or suicidal ideation due to or exacerbated by AA. Consensus was reached that the Alopecia Areata Investigator Global Assessment scale adequately classified the severity of scalp hair loss.Conclusions and relevanceThis eDelphi survey study, with consensus among global experts, identified various determinants of AA severity, encompassing not only scalp hair loss but also other outcomes. These findings are expected to facilitate the development of a multicomponent severity tool that endeavors to competently measure disease impact. The findings are also anticipated to aid in identifying candidates for current and emerging systemic treatments. Future research must incorporate the perspectives of patients and the public to assign weight to the domains recognized in this project as associated with AA severity.

Background: The Severity of Alopecia Tool (SALT) is a standardized method for quantifying scalp hair loss in alopecia areata (AA). SALT scores can be used to guide treatment decisions and are widely used as eligibility criteria and endpoints for clinical trials in AA. However, clinicians may be unfamiliar with assessing and envisioning SALT scores in practice. Objectives: To aid clinicians in the determination and application of SALT scores in a clinical setting, this manuscript seeks to contextualize SALT scores using patient images from a clinical trial of adults with severe AA. Methods: Images from 722 patients enrolled in BRAVE-AA1, a phase 2/3 study of baricitinib in adults with severe AA (SALT score ≥50; ≥50% scalp hair loss), were obtained at baseline and Weeks 12, 36, and 52 and compiled into a repository. Photographs were selected to represent SALT scores across the full range of disease (SALT scores 0–100) and to demonstrate the progression of SALT scores during the course of treatment. Results: Images of six patients depict the range of SALT scores (0–100). Photographs are of male and female patients of different ages (21–69) and races (Asian, Black, White) with varying extent, density, and patterns of hair loss. Images of two additional patients demonstrate the use of SALT to monitor treatment progress, showing distinct patterns and timing of clinical response over 52 weeks of therapy. Conclusions: The SALT is widely used in clinical trials for AA, but clinicians may lack familiarity. Presented patient images show SALT scores commonly used as eligibility criteria and endpoints in clinical trials, which may be useful in identifying patients eligible for systemic treatment and in visualizing therapeutic response.

BackgroundThe 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).ObjectiveThe objective of this study was to evaluate the safety of ritlecitinib in an integrated analysis of four studies in AA.MethodsTwo 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.ResultsIn 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.ConclusionsRitlecitinib 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 registriesClinicalTrials.gov: NCT02974868 (date of registration: 11/29/2016), NCT04517864 (08/18/2020), NCT03732807 (11/07/2018), and NCT04006457 (07/05/2019).

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).

BackgroundAlopecia 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.MethodsIn 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.FindingsBetween 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

PurposeTraditionally, 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).MethodsA 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.ResultsBoth 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.ConclusionThis 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.

BackgroundThe validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD™) is a standardized severity assessment for use in clinical trials and registries for atopic dermatitis (AD).ObjectivesTo investigate the reliability, validity, responsiveness and within-patient meaningful change of the vIGA-AD.MethodsData were analysed from adult patients with moderate-to-severe AD in the BREEZE-AD1 (N = 624 patients; NCT03334396), BREEZE-AD2 (N = 615; NCT03334422) and BREEZE-AD5 (N = 440; NCT03435081) phase III baricitinib clinical studies.ResultsAcross studies, test-retest reliability for stable patients showed moderate-to-good agreement [range of Kappa values for Patient Global Impression of Severity-Atopic Dermatitis (PGI-S-AD), 0·516-0·639; for Eczema Area and Severity Index (EASI), 0·658-0·778]. Moderate-to-large correlations between vIGA-AD and EASI or body surface area (range at baseline, 0·497-0·736; Week 16, 0·716-0·893) supported convergent validity. Known-groups validity was demonstrated vs. EASI and PGI-S-AD (vIGA-AD for severe vs. moderate EASI categories at baseline, P

BackgroundThe 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.ObjectivesTo explore the content validity of the suite of AA PRO measures and accompanying photoguides in an adolescent sample.MethodsSemi-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.ResultsEleven 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).ConclusionsThe 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.

Alopecia areata (AA) is an autoimmune disease characterized by nonscarring hair loss. As a clinically heterogeneous disease, various classification systems have evolved for defining its severity. In this high-level review of the literature, we discuss the traditional classification systems for AA severity and their strengths and weaknesses. Most recent classifications have focused on the extent of scalp hair loss as a defining feature, but additional clinical aspects of the disease, including location, pattern, and duration of hair loss as well as impact on the patient's quality of life, are also relevant. These various components have typically been used unidimensionally to classify patients. We propose a multidimensional framework to define AA severity that incorporates multiple patient- and illness-related domains. Using such a framework, dermatologists may better assess the severity of the disease for the individual patient beyond the extent of hair loss.

IntroductionWhile autoimmune comorbidities are common in alopecia areata, little is known about comorbid cardiovascular disease. The purpose of this study was to evaluate the incidence of bradyarrhythmia in patients with alopecia areata.MethodsRetrospective review of electrocardiograms of 124 patients with [Formula: see text] 50% scalp hair loss (severe alopecia areata) was conducted and compared to National Health and Nutrition Examination Survey (NHANES) data.ResultsThe prevalence of bradycardia in females with alopecia areata was 24.3% (95% CI, 14.5-34.1%) and in those age 40 years or older was 40.8% (95% CI, 22.2-53.5%) compared to 19.5% in the NHANES III population. The prevalence of bradycardia in males with alopecia areata was 36.0% (95% CI, 22.7-49.3%) and in those age 40 years or older was 50.0% (95% CI, 21.7-78.3%) compared to 26.9% in the NHANES III population.ConclusionThe potential association between bradycardia and alopecia areata merits further investigation.

BackgroundAlopecia areata (AA) is characterized by hair loss that can affect the scalp and body. This study describes the psychosocial burden of AA.MethodsParticipants diagnosed with AA who had experienced ≥50% scalp hair loss according to the Severity of Alopecia Tool (SALT) were identified by clinicians. A semi-structured interview guide, developed with expert clinician input, included open-ended questions to explore patients' experiences of living with AA. Data were thematically analyzed to identify concepts and relationships.ResultsParticipants (n = 45, 58% female, mean age 33.3 years [range 15-72], mean SALT 67.2 [range 0-100]) described the AA diagnosis as "devastating". Both males and females reported emotional and psychological impacts of AA including feeling sad/depressed (n = 21), embarrassed/ashamed (n = 10) and angry/frustrated (n = 3). Patients felt helpless (n = 5) due to the unpredictability of disease recurrence, and anxious (n = 19) about judgement from others. Many patients avoided social situations (n = 18), which impaired relationships and increased isolation. Coping strategies included concealment of hair loss through wigs or make-up, although fear of the displacement of these coverings also caused anxiety and the avoidance of activities that could result in scalp exposure (n = 22). Some patients became more accepting of AA over time, which lessened the emotional impact, though efficacious treatment was still desired. A conceptual framework was developed, and a conceptual model was created to depict the relationship between the physical signs/symptoms and the associated psychosocial effects of AA.ConclusionAA impairs patients' emotional and psychological wellbeing, relationships and lifestyles. Greater disease awareness and effective treatments are needed.

BackgroundEyebrow and eyelash hair loss and nail damage-in addition to scalp hair loss-are important signs/symptoms of alopecia areata (AA) to patients and deserve assessment in AA clinical trials.ObjectivesOur objective was to develop clinician-reported outcome (ClinRO) and patient-reported outcome (PRO) measures and accompanying photoguides to aid in the assessment of AA-related eyebrow, eyelash and nail signs/symptoms.MethodsIterative rounds of qualitative, semi-structured interviews were conducted with US expert dermatologists and North American patients with AA. Patients with eyebrow, eyelash and nail involvement were purposefully sampled. Interview transcripts were qualitatively analyzed.ResultsDermatologists (n = 10) described eyebrow and eyelash loss as concerning for affected patients and, along with nail appearance, as deserving assessment. Dermatologist data informed the development of single item, 4-point Likert-type ClinRO and PRO measures of current eyebrow loss, eyelash loss and nail appearance and a PRO measure of eye irritation. Patients (n = 45, age 15-72 years) confirmed the importance and relevance of these signs/symptoms. Interim revision resulted in measures that were understood by and relevant to patients. Dermatologists (n = 5) and patients (n = 10, age 21-54 years) participated in the development of the eyebrow, eyelash and nail photoguides and confirmed that they included photos that appropriately represented different severity levels and were helpful to derive and standardize ratings across raters.ConclusionsThe ClinRO and PRO measures for eyebrow, eyelash and nail appearance, with their accompanying photoguides and the PRO Measure for Eye Irritation provide clear and meaningful assessments of outcomes important to patients with AA.

Reversible axonal swelling and brainstem auditory evoked potential (BAEP) changes were observed in standard chronic (9‐month) toxicology studies in dogs treated with ritlecitinib, an oral Janus kinase 3/tyrosine kinase expressed in hepatocellular carcinoma family kinase inhibitor, at exposures higher than the approved 50‐mg human dose. To evaluate the clinical relevance of the dog toxicity finding, this phase 2a, double‐blind study assessed BAEP changes and intraepidermal nerve fiber (IENF) histology in adults with alopecia areata treated with ritlecitinib. Patients were randomized to receive oral ritlecitinib 50 mg once daily (QD) with a 4‐week loading dose of 200 mg QD or placebo for 9 months (placebo‐controlled phase); they then entered the active‐therapy extension and received ritlecitinib 50 mg QD (with a 4‐week loading dose of 200 mg in patients switching from placebo). Among the 71 patients, no notable mean differences in change from baseline (CFB) in Waves I–V interwave latency (primary outcome) or Wave V amplitude on BAEP at a stimulus intensity of 80 dB nHL were observed in the ritlecitinib or placebo group at Month 9, with no notable differences in interwave latency or Wave V amplitude between groups. The CFB in mean or median IENF density and in percentage of IENFs with axonal swellings was minimal and similar between groups at Month 9. Ritlecitinib treatment was also not associated with an imbalanced incidence of neurological and audiological adverse events. These results provide evidence that the BAEP and axonal swelling finding in dogs are not clinically relevant in humans. [ABSTRACT FROM AUTHOR]

Purpose: To develop criteria to predict visual hemifields with deep perimetric defects based on retinal nerve fibre layer (RNFL) reflectance, in a transparent process whose components can be assessed by independent laboratories analysing data from their own small groups. Methods: The analysis was carried out in four stages, using three independent groups of patients—30, 33 and 62 participants—with glaucoma and age‐similar controls. The first stage used Group 1 to develop a criterion for RNFL reflectance images at 24, 36 or 48 μm below the inner limiting membrane (ILM). The second stage evaluated the criterion using Group 2. The third stage developed a second criterion to improve performance for Groups 1 and 2 combined. The fourth stage evaluated the second criterion with Group 3. Confidence intervals for sensitivity and specificity were then computed by combining results from all three groups. Results: The first criterion identified all hemifields with deep defects and no hemifields from controls, using a within‐eye reference for healthy RNFL. For Group 2, specificity remained high but sensitivity was reduced. The second criterion improved sensitivity by using location‐specific reference values. For Group 3, sensitivity remained high but reduced specificity was found. Confidence intervals showed substantial overlap for the two criteria. Conclusions: We developed two criteria to identify patients with deep perimetric defects with high specificity and sensitivity. Several improvements are warranted: automated identification of the fovea‐disc angle and optic disc locations, evaluation of normal variation in patterns of RNFL thickness, improved segmentation of ILM and major vasculature, reduction of within‐eye variability in RNFL reflectance of healthy eyes, assessment of effects of image quality, assessment of effects of comorbidity and effectiveness of other devices. [ABSTRACT FROM AUTHOR]

Melanoma claims approximately 9,000 lives in the United States annually [1].  Patients who present with satellite, in-transit, or distant cutaneous metastases have limited treatment options and the prognosis for patients with metastatic disease remains poor. Surgical excision remains the most common treatment modality for cutaneous metastases, but may not address concurrent subclinical in-transit metastases. Other palliative treatment options include Bacillus Calmette–Guérin (BCG) and isolated limb perfusion (ILP).  Although intravenous IL-2 has been used for treatment of metastatic melanoma since 1998, intralesional IL-2 has only now been included in the most recent National Comprehensive Cancer Network (NCCN) guidelines after case series and phase I/II clinical trials have shown promising results against Stage IIIc and IV M1a melanoma. Intralesional IL-2 protocols have varied markedly from study to study and there are no consensus guidelines available to help direct treatment.  Herein, we present a detailed protocol for the administration of intralesional IL-2 that has been successfully used at two different institutions for treatment of cutaneous melanoma metastases.