Health-related quality of life of adult and adolescent patients living with alopecia areata in Australia.

INTRODUCTION: To understand the experiences of adolescent and adult patients living with alopecia areata (AA) in Australia regarding symptom severity and the impact on psychosocial well-being and work/classroom productivity. MATERIALS AND METHODS: A cross-sectional online patient survey among adolescent and adult patients diagnosed with AA was recruited via the Australia Alopecia Areata Foundation. Patient-reported outcomes were also assessed. RESULTS: A total of 337 patients (49 adolescents; 288 adults), with a mean ± standard deviation age of 14.7 ± 1.55 and 38.9 ± 13.31 years for adolescents and adults, respectively, were included. In the group with extensive hair loss (Scalp Hair Assessment Patient-Reported Outcome, categories 3 + 4, n = 172), we observed higher emotional symptom and activity limitation scores (Alopecia Areata Patient Priority Outcomes, emotional symptoms: adults 2.5 ± 1.03, adolescents 2.2 ± 1.15; activity limitations: adults 1.4 ± 1.15, adolescents 1.2 ± 0.99). Additionally, in adults, the Alopecia Areata Symptom Impact Scale global score was 4.0 ± 2.10 (symptoms subscale score 4.1 ± 1.91; interference subscale scores 3.8 ± 2.73). Hospital Anxiety and Depression Scale scores were high across participants, irrespective of hair loss extent (adults: anxiety 9.2 ± 3.85, depression 6.6 ± 3.95; adolescents: anxiety 9.7 ± 4.65, depression 5.2 ± 3.59). Work and classroom productivity were substantially impaired due to AA, with 70.5% of adults and 57.1% of adolescents reporting activity impairment, and overall work/classroom impairment reported at 39.2% and 44.9%, respectively. CONCLUSIONS: AA impacts the physical, emotional and psychosocial well-being of both adult and adolescent patients. More extensive hair loss more profoundly impacts those living with AA. Patients may benefit from patient-centred care approaches addressing the impact of hair loss on mental and emotional well-being, daily activities and work productivity.

Novel investigational drugs for alopecia areata and future perspectives.

INTRODUCTION: Alopecia areata (AA) is an immune-mediated disease that causes non-scarring hair loss. While acute, solitary patches often spontaneously remit, developing secondary patches or failure of the disease to resolve within 6-12 months predicts a poor prognosis, with an increased risk of alopecia totalis or universalis. Chronic AA increases the risk of depression and suicidality and reduces quality of life. Treatment options for chronic or acute diffuse AA were previously limited to corticosteroids and traditional immunomodulators. Two Janus Kinase (JAK) inhibitors are now approved for the treatment of chronic AA. AREAS COVERED: The results of landmark phase 3 trials for three JAK inhibitors, baricitinib, ritlecitinib, and deuruxolitinib are discussed. Evidence for other JAK inhibitors, biologics, and phosphodiesterase-4 inhibitors are also presented. Therapies currently undergoing clinical trials are listed. EXPERT OPINION: JAK inhibitors are a safe and efficacious treatment of moderate-to-severe AA. Early intervention, regardless of severity, allows for improved treatment efficacy. It is uncertain how long patients should remain on JAK inhibitors; discontinuation often leads to relapse. A black-box warning for JAK inhibitors was extrapolated from safety data in a rheumatoid arthritis cohort; recent meta-analyses of JAK inhibitors used in dermatology cohorts do not demonstrate the same risk profile.

The Alopecia Areata Severity and Morbidity Index (ASAMI) Study: Results From a Global Expert Consensus Exercise on Determinants of Alopecia Areata Severity.

Importance: Current measures of alopecia areata (AA) severity, such as the Severity of Alopecia Tool score, do not adequately capture overall disease impact. Objective: To 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 Review: A 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. Findings: Of 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 Relevance: This 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.

Treatment of moderate-to-severe alopecia areata in patients over the age of 65 with baricitinib.

Baricitinib is a Janus kinase inhibitor which is now FDA approved for the treatment of severe alopecia areata (AA) in adults. However, the clinical trials which demonstrated the efficacy of baricitinib in the treatment of severe AA did not include men aged >60 years and women aged >70 years. We retrospectively assessed the efficacy and safety of baricitinib in 14 patients aged ≥65 years with moderate-to-severe AA. After a mean (SD) duration of 18.5 (11.9) months, a 72.0% reduction in the mean SALT score from baseline was observed. Partial or complete eyebrow and eyelash hair was observed in 57.1% and 42.9% of patients respectively. Adverse effects of baricitinib were mild. No cases of venous thromboembolism (VTE), major adverse cardiovascular events (MACE) or malignancy were reported.

Efficacy and safety of switching from dupilumab to upadacitinib versus continuous upadacitinib in moderate-to-severe atopic dermatitis: Results from an open-label extension of the phase 3, randomized, controlled trial (Heads Up).

BACKGROUND: Characterization of upadacitinib use and switching from dupilumab to upadacitinib among patients with moderate-to-severe atopic dermatitis (AD) is needed. OBJECTIVE: To evaluate the long-term safety and efficacy of continuous upadacitinib 30 mg and switching to upadacitinib after 24 weeks of dupilumab. METHODS: Adults who completed the phase 3b clinical trial of oral upadacitinib 30 mg vs injectable dupilumab 300 mg (Heads Up) and entered a 52-week open-label extension (OLE) (NCT04195698) were included. All patients received 30-mg upadacitinib during the open-label period. We report results of a prespecified interim OLE 16-week analysis. RESULTS: Patients (n = 239) continuing upadacitinib maintained high levels of skin and itch response. Patients (n = 245) switching from dupilumab experienced additional incremental improvements in clinical responses within 4 weeks of starting upadacitinib. Most patients who did not achieve adequate clinical responses with dupilumab did so with upadacitinib. The safety profile of upadacitinib up to 40 weeks (week 16 of OLE) was consistent with previous phase 3 AD studies, with no new safety risks observed. LIMITATIONS: Open-label study design. CONCLUSIONS: Clinical responses are maintained with continuous upadacitinib through 40 weeks and patients regardless of prior dupilumab response experienced improved outcomes when switched to upadacitinib. No new safety risks were observed.

Upadacitinib treatment in patients with moderate to severe atopic dermatitis: A retrospective single-centre Australian review of 14 patients post phase 3 clinical trial.

Recent phase 2b and phase 3 clinical trials support the safety and efficacy of the selective Janus kinase (JAK)-1 inhibitor upadacitinib (UPA) in the treatment of moderate to severe atopic dermatitis (AD). However, to date, there is little experience with UPA therapy for AD in Australia. We report findings from a retrospective study to better understand the therapeutic response and side effects noted in a single-centre Australian cohort.

Early Biomarkers in the Prediction of Later Functional Impairment in Term Children with Cerebral Palsy.

AIM: To identify possible early biomarkers that could predict later functional capabilities in children at risk for cerebral palsy (CP). METHODS: Data from 869 term children with CP were extracted from the Canadian Cerebral Palsy Registry. Univariate analyses were conducted to measure the association between readily available objective early biomarkers (neonatal encephalopathy [NE], cord or first hour of life pH, magnetic resonance imaging [MRI]) and functional outcomes such as mobility and feeding status. Multivariable regressions were then modeled to study whether adding predictors would affect the strength of the observed association. RESULTS: Patients with NE have higher odds of having an assigned Gross Motor Function Classification Score level of IV to V (prevalence ratio [PR], 2.87; 95% confidence interval [CI], 2.07 to 3.97) and are more likely to require dependent tube feeding (PR, 2.09; 95% CI, 1.12 to 3.88); this was similarly seen in patients with MRI findings of deep gray matter injury, watershed injury, near-total brain injury, and/or cortical malformation (mobility status [PR, 5.13; 95% CI, 3.73 to 7.11] and feeding status [PR, 4.87; 95% CI, 2.57 to 9.75]). Patients with cord or first hour of life pH <7 were also more likely to predict dependent mobility status (PR, 2.86; 95% CI, 1.76 to 4.69), however, not significantly more likely to predict eventual dependent feeding status (PR, 1.47; 95% CI, 0.58 to 3.32). CONCLUSIONS: This retrospective cohort study demonstrates that NE, MRI findings and cord or first hour of life pH can reliably predict later CP related functioning. These associations can be used to inform and clarify early prognosis discussions between caregivers and health professionals.

Acquired causes of eyebrow and eyelash loss: A review and approach to diagnosis and treatment.

Eyebrows and eyelashes serve important anatomical and social functions, and hair loss at these sites can impact patients significantly. Acquired eyebrow and eyelash loss (madarosis) may be due to a variety of underlying local or systemic disease processes; in other cases it may be idiopathic. There is a dearth of literature relating to eyebrow and eyelash loss, and there is limited guidance to help clinicians treat these clinical presentations in comparison with scalp alopecia. Here, we discuss the acquired causes of eyebrow and eyelash alopecia, our clinical approach to diagnosis and review treatment options for clinicians.

Abrocitinib induction, randomized withdrawal, and retreatment in patients with moderate-to-severe atopic dermatitis: Results from the JAK1 Atopic Dermatitis Efficacy and Safety (JADE) REGIMEN phase 3 trial.

BACKGROUND: The heterogeneous course of moderate-to-severe atopic dermatitis necessitates treatment flexibility. OBJECTIVE: We evaluated the maintenance of abrocitinib-induced response with continuous abrocitinib treatment, dose reduction or withdrawal, and response to treatment reintroduction following flare (JAK1 Atopic Dermatitis Efficacy and Safety [JADE] REGIMEN: National Clinical Trial 03627767). METHODS: Patients with moderate-to-severe atopic dermatitis responding to open-label abrocitinib 200 mg monotherapy for 12 weeks were randomly assigned in a 1:1:1 ratio to blinded abrocitinib (200 or 100 mg) or placebo for 40 weeks. Patients experiencing flare received rescue treatment (abrocitinib 200 mg plus topical therapy). RESULTS: Of 1233 patients, 798 responders to induction (64.7%) were randomly assigned. The flare probability during maintenance was 18.9%, 42.6%, and 80.9% with abrocitinib 200 mg, abrocitinib 100 mg, and placebo, respectively. Among patients with flare in the abrocitinib 200 mg, abrocitinib 100 mg, and placebo groups, 36.6%, 58.8%, and 81.6% regained investigator global assessment 0/1 response, respectively, and 55.0%, 74.5%, and 91.8% regained eczema area and severity index response, respectively, with rescue treatment. During maintenance, 63.2% and 54.0% of patients receiving abrocitinib 200 and 100 mg, respectively, experienced adverse events. LIMITATIONS: The definition of protocol-defined flare was not established, limiting the generalizability of findings. CONCLUSION: Induction treatment with abrocitinib was effective; most responders continuing abrocitinib did not flare. Rescue treatment with abrocitinib plus topical therapy effectively recaptured response.

Ritlecitinib: an investigational drug for the treatment of moderate to severe alopecia areata.

INTRODUCTION: Alopecia areata (AA) is an inflammatory and autoimmune form of hair loss, which can present with one patch of hair loss, but in more extreme cases can lead to total body hair loss. There are limited therapeutic options and no cure, but medication can sometimes induce sustained remission. Disease control cannot be guaranteed; even those who regrow all hair on treatment can experience relapse. There are no FDA approved systemic treatments; therefore, an unmet need for safe, and effective treatments exists. Few treatments have been evaluated by randomized controlled trials. Case reports and series indicate oral Janus Kinase (JAK) inhibitors as a potential therapy. Ritlecitinib is a novel oral JAK3-selective inhibitor being investigated as an AA treatment. AREAS COVERED: This article introduces ritlecitinib as treatment for AA and considers the mechanism of action, pharmacodynamics, pharmacokinetics, clinical efficacy, and safety [reporting data from a 24-week, phase 2a double-blinded placebo-controlled trial of ritlecitinib in patients with AA who have more than 50% scalp hair loss]. EXPERT OPINION: Ritlecitinib offers a novel mode of action, rapid onset, and the capacity for a superior safety profile over other JAK inhibitors. If approved, ritlecitinib will be widely prescribed by physicians overseeing the more severe AA patients for the foreseeable future. As JAK inhibitors regulate the hair growth cycle and have anti-inflammatory effects, the implementation of ritlecitinib in hair loss disorders other than AA, may prove beneficial.