Severity Of Alopecia Tool Score Research Articles

Distribution of SALT Scores with Ritlecitinib Treatment up to 24 months from the ALLEGRO Phase 2b/3 and Long-Term Phase 3 Clinical Studies in Alopecia Areata

Background:• Alopecia areata (AA) is an autoimmune disease that has an underlying immuno-inflammatorypathogenesis and is characterized by non-scarring hair loss ranging from small patches to completescalp, face, and/or body hair loss1• Ritlecitinib, an oral JAK3/TEC family kinase inhibitor, demonstrated efficacy and safety up to 48 weeks inpatients aged ≥12 years with AA in the ALLEGRO phase 2b/3 study (NCT03732807; “ALLEGRO-2b/3”)2• The long-term efficacy of ritlecitinib in patients who rolled over from ALLEGRO-2b/3 to the ongoingphase 3, open-label ALLEGRO-LT study (NCT04006457) has been reported in terms of the proportions ofpatients with Severity of Alopecia Tool (SALT) scores of ≤20 and ≤10 (≤20% or ≤10% scalp without hair)at Month 243• However, the distribution of SALT scores in the overall population, including patients not reaching theSALT score ≤20 and ≤10 thresholds, has not yet been describedOBJECTIVE• This study describes changes in the distribution of SALT scores over 24 months of ritlecitinib treatmentin the overall population and in age and disease severity subgroups Methods: Study design and patients• Key inclusion criteria in ALLEGRO-2b/3:- Age ≥12 years- Diagnosis of AA with ≥50% scalp hair loss due to AA (including alopecia totalis [AT] and alopecia universalis [AU])- Maximum duration of current episode of hair loss ≤10 years• This analysis includes patients who received ritlecitinib 50 mg once daily (QD) without a loading dose inALLEGRO-2b/3 and who subsequently rolled over into ALLEGRO-LT where they continued to receiveritlecitinib 50 mg QD (Figure 1)- Continuation criteria for adolescents (aged 12-17 years) in ALLEGRO-LT: ≥50% improvement from baseline in SALT scoreby Month 3 for rollover patients from ALLEGRO-2b/3 and SALT score ≤20 by Month 6 in ALLEGRO-LTFigure 1. Study design and patient populationCombinedritlecitinib50 mg group(N=191)ALLEGRO phase 2b/3 ALLEGRO-LTLoading(4 weeks)Maintenance(20 weeks)Extension(24 weeks)Long-term study(60 months)Group A (n=131) 200 mg 50 mg 50 mg 50 mgGroup B (n=129) 200 mg 30 mg 30 mg 50 mgGroup C (n=130) 50 mg 50 mg 50 mg 50 mgGroup D (n=132) 30 mg 30 mg 30 mg 50 mgGroup E (n=61) 10 mg 10 mg 10 mg 50 mgGroup F (n=63) Placebo Placebo 200 mg 50 mg 50 mgGroup G* (n=61) Placebo Placebo 50 mg 50 mgDe novo group (n=447) 200 mg 50 mg*Data while on placebo were not included in this analysis; data from patients in Groub G were rebaselined from the start of treatment with ritlecitinib.Assessments and statistical analysis• The distribution of patients according to SALT score (as observed) was assessed through Month 24 forthe overall population and subgroups based on age (adults [≥18 years] vs adolescents [12-17 years]) anddisease severity (patients with AT/AU vs those without AT/AU)• The data cutoff date was December 9, 2022 Results: The analysis included 191 patients (27 adolescents and 164 adults) (Table 1)• At the time of data cutoff, 71 patients had discontinued; withdrawal bypatient (n=19), adverse events (n=18), and lack of efficacy (n=14) were themost common reasons for discontinuation• The distribution of participants by SALT score (as observed) at baseline, Month12, and Month 24 are presented for the overall population (Figure 2)(Interactive dynamic plot)• Per the inclusion criteria, all participants had a SALT score of ≥50 at baseline;136/191 patients (71.2%) had SALT >90• Among patients who had a nonmissing SALT score, 56/178 (31.5%), 37/164(22.6%), and 17/120 (14.2%) were in the SALT >90-100 category at Months 6,12, and 24, respectively• Reductions in the number of patients in the other SALT >50 categories wereobserved from baseline through Month 24• At Month 12, 56/164 (34.2%) and 18/164 (11.0%) patients were in the SALT0-10 and >10-20 categories, respectively, with 61/120 (50.8%) and 12/120(10.0%) patients in these categories at Month 24• Among the patients with AT/AU at baseline, 18/69 (26.1%) and 6/69 (8.7%)were in the SALT 0-10 and >10-20 categories, respectively, at Month 12; 25/47(53.2%) and 3/47 (6.4%) were in these categories, respectively, at Month 24(Figure 3) (Interactive dynamic plot)• For the adolescent participants, 10/22 (45.5%) and 4/22 (18.2%) were in theSALT 0-10 and >10-20 categories, respectively, at Month 12, and 11/14(78.6%) and 0/14 (0%) were in these categories at Month 24 (Figure 4) Conclusions:• Over 24 months, daily treatment with ritlecitinib 50 mg resulted in fewer patients inthe highest SALT score categories• These data provide a comprehensive overview of patient response to ritlecitinibtreatment and enable us to understand treatment response and time frames whileon treatment with ritlecitinib • This information can empower clinicians when counseling patients and managingtreatment expectations based on patient characteristics• This study also shows that response to treatment improves over time, whichsuggests that adequate time should be given when assessing treatment efficacy

Patient considerations when using ritlecitinib for alopecia areata in adolescents: Guidance for the clinicians

Background: Alopecia areata (AA) is an autoimmune disease characterized by non-scarring hair loss that can affect children, adolescents, and adults. Ritlecitinib, an orally administered Janus kinase (JAK) 3/tyrosine kinase expressed in hepatocellular carcinoma (TEC) kinase family inhibitor, is the first and currently the only treatment approved by the United States Food and Drug Administration for adolescents (aged 12-17 years) with severe AA. Summary: The ALLEGRO Phase 2b–3 trial demonstrated that 25% and 50% of adolescents with a Severity of Alopecia Tool (SALT) score ≥50 at baseline achieved a SALT score ≤20 at week 24 and week 48 after receiving 50mg ritlecitinib daily, respectively. The most common adverse events were headache, acne, and nasopharyngitis in adolescents. This review summarizes the mechanism of action, clinical trial evidence on efficacy and safety profile, factors associated with treatment response to JAK inhibitors for AA, and vaccination considerations for adolescents. Key Messages: This review aims to facilitate the risk-benefit assessment and shared decision-making between clinicians and patients and provide clinical considerations and management recommendations for ritlecitinib use in adolescents with AA.

Therapeutic potential of oral tofacitinib in alopecia areata: a retrospective study

Background: Alopecia areata (AA), a prevalent autoimmune disorder, poses challenges in management, particularly in severe cases. Recent advancements highlight janus kinase (JAK) inhibitors-tofacitinib demonstrating promise. However, the literature reports conflicting information on its safety profile, especially at higher doses, necessitating a comprehensive evaluation. Methods: This retrospective analysis investigates the long-term efficacy and safety of oral tofacitinib in AA patients from January 2017 to October 2022. The study included 69 patients diagnosed with patchy multifocal AA (mfAA), alopecia totalis (AT), alopecia universalis (AU) or alopecia sub-totalis (AS). Data analysis incorporated demographic details, treatment history, autoimmune comorbidities, tofacitinib dosages, prior investigations, recurrence rates, and adverse effects. Efficacy was assessed using severity of alopecia tool (SALT) scores, with a grading system for percentage of hair regrowth. Results: The study comprising of 58% males and 42% females, exhibited varied alopecia types. Treatment response analyzed through percent change in SALT score revealed 46.5% showed very good response to tofacitinib treatment, while 4.3% had excellent response (100% change in SALT score). 44.9% of patients showed no recurrence. Adverse effects were minimal, including acneiform eruptions and upper respiratory tract infections. Pearson correlations revealed age negatively correlated with hair regrowth percentage, suggesting older individuals exhibited lower regrowth responses. Conclusions: Our findings endorse tofacitinib as a promising therapeutic option for the management of AA, with no serious side effects observed even during longer treatment durations. It can be regarded as the primary choice of treatment modality for moderate to severe forms of AA.

Systematic review and indirect treatment comparisons of ritlecitinib against baricitinib in alopecia areata.

Ritlecitinib and baricitinib are recently approved systemic treatments for severe alopecia areata (AA). Both demonstrated superiority over placebo in hair regrowth measured by the Severity of Alopecia Tool (SALT), but they have not been directly compared in randomized controlled trials (RCTs). We conducted a systematic review of RCTs evaluating treatments in AA and estimated the efficacy and safety of ritlecitinib and baricitinib at Week 24 using Bayesian network meta-analysis. To adjust and explore effect modifiers, population-adjusted indirect comparison was performed via multilevel network meta-regression (ML-NMR) using ritlecitinib individual patient data (IPD). Co-primary endpoints were SALT ≤20 and SALT ≤10 at Week 24. Unanchored population adjusted ITCs were also computed to evaluate SALT ≤10 and SALT ≤20 endpoints at Week 48/52. Four RCTs (ALLEGRO 2a [NCT02974868], ALLEGRO 2b/3 [NCT03732807], BRAVE-AA1 [NCT03570749] and BRAVE-AA2 [NCT03899259]) were included. No evidence of a difference between ritlecitinib 50 mg and baricitinib 4 mg on SALT ≤10 (odds ratio, OR: 0.96, 95% credible interval, CrI: 0.18-7.21) and SALT ≤20 (OR: 2.16, 95% CrI: 0.48-16.46) at Week 24 was found. ML-NMR using ALLEGRO IPD adjusted for sex, SALT score at baseline, duration of current episode and disease duration found evidence of effect modification, although relative efficacy between ritlecitinib 50 mg and baricitinib 4 mg remained unchanged. Unanchored population-adjusted ITC at Week 48/52 was consistent with previous results. We found similar efficacy between ritlecitinib 50 mg and baricitinib 4 mg. These ITCs was informed by only four RCTs, uncertainty was considerable, and there was evidence of effect modification, highlighting the need for further quality research in AA.

Patient-Reported Hair Loss and Its Impacts as Measured by the Alopecia Areata Patient Priority Outcomes Instrument in Patients Treated with Ritlecitinib: The ALLEGRO Phase 2b/3 Randomized Clinical Trial.

The ALLEGRO phase 2b/3 study investigated the efficacy and safety of ritlecitinib in patients with alopecia areata (AA). To describe the impact of ritlecitinib on patient-reported hair loss using the Alopecia Areata Patient Priority Outcomes (AAPPO) instrument and evaluate the relationship between clinically meaningful hair regrowth and improvements in patient-reported impacts. In ALLEGRO-2b/3, patients aged ≥ 12 years with AA and ≥ 50% scalp hair loss received once-daily ritlecitinib 50 or 30 mg (± 4-week 200-mg daily loading dose), 10 mg, or placebo for 24 weeks andthen continued ritlecitinib or switched from placebo to ritlecitinib 200/50 or 50 mg for 24 weeks. The AAPPO instrument evaluated improvement in hair loss, emotional symptoms (ES), and activity limitations (AL) from weeks 4 to 48 (secondary endpoint). Mean changes in ES and AL domain scores and individual items at weeks 24 and 48 were calculated for Severity of Alopecia Tool (SALT) score ≤ 20 responders and nonresponders (exploratory endpoint). Overall, 718 patients were randomized. At week 24, 5-36% of patients receiving ritlecitinib 10-200/50 mg reported improvement in scalp hair loss versus 9% receiving placebo. The results for eyebrow, eyelash, and body hair loss were similar. Mean change from baseline in ES and AL scores at weeks 24 and 48 was small and similar between groups. Mean change was larger for individual hair loss and ES items at weeks 24 and 48 in SALT score ≤ 20 responders versus nonresponders. The AAPPO instrument demonstrated the beneficial impact of ritlecitinib on patient-reported hair growth, which was consistent with improvements in clinician-reported outcomes. NCT03732807. INFOGRAPHIC.

Efficacy and safety of the oral JAK3/TEC family kinase inhibitor ritlecitinib over 24 months: integrated analysis of the ALLEGRO phase 2b/3 and long-term phase 3 clinical studies in alopecia areata.

The ALLEGRO phase 2a and 2b/3 studies demonstrated that ritlecitinib is efficacious and well tolerated in adult and adolescent patients with alopecia areata (AA) up to 48 weeks. The efficacy of ritlecitinib through Month 24 and safety through data cutoff were assessed in the ALLEGRO phase 2b/3 study and the ongoing long-term, open-label, phase 3 ALLEGRO-LT study. Patients aged ≥12 years with AA and ≥50% scalp hair loss from ALLEGRO-2b/3 who rolled over to ALLEGRO-LT after up to 48 weeks were included. Proportions of patients with responses based on clinician-reported Severity of Alopecia Tool (SALT) score of ≤20 and ≤10, eyebrow assessment (EBA) and eyelash assessment (ELA), patient global impression of change (PGI-C) and patient satisfaction with hair growth are reported through Month 24 for patients who received ritlecitinib 50 mg daily with or without a 200-mg 4-week daily loading dose. Observed and imputed data (last observation carried forward [LOCF]) were reported until December 9, 2022. Safety was assessed throughout. At Month 12, SALT score ≤20 was achieved by 45.1% and 45.9% (observed) and 40.3% and 41.8% (LOCF) of the 191 and 194 patients who received ritlecitinib 50 mg and ritlecitinib 200/50 mg, respectively. At Month 24, proportions increased to 60.8% and 63.1% (observed) and 46.1% and 50.8% (LOCF), respectively. Patients with abnormal EBA or ELA scores at baseline achieved responses at Month 24 (EBA observed: 57.6% [50 mg], 61.0% [200/50 mg]; EBA LOCF: 46.8% [50 mg], 50.9% [200/50 mg]; ELA observed: 51.2% [50 mg], 62.7% [200/50 mg]; ELA LOCF: 43.2% [50 mg], 51.7% [200/50 mg]). PGI-C response was achieved by patients at Month 24 (observed: 70.0% [50 mg], 76.4% [200/50 mg]; LOCF: 56.6% [50 mg], 65.5% [200/50 mg]). Safety profiles for both treatment groups were consistent with the known safety profile of ritlecitinib. Ritlecitinib has clinically meaningful and sustained efficacy beyond 1 year with a favourable safety and tolerability profile, supporting its long-term use in patients aged ≥12 years with AA. ClinicalTrials.gov: NCT03732807, NCT04006457.

Sustained hair regrowth with continued ritlecitinib treatment through Week 48 in patients with alopecia areata with or without early target responses: post hoc analysis of the ALLEGRO phase 2b/3 trial

Few treatments for alopecia areata (AA) have demonstrated sustained efficacy. Evaluate the efficacy and safety of continued ritlecitinib treatment to Week 48 in patients with AA with or without target efficacy responses at Week 24. Patients aged ≥12 years received daily ritlecitinib (± 4-week loading dose): 200/50 mg, 200/30 mg, 50 mg, or 30 mg. Patients with clinical response at Week 24, based on a Severity of Alopecia Tool (SALT) score ≤20 and ≤10 were evaluated for sustained response through Week 48. Nonresponders at Week 24 were assessed for response through Week 48. Among ritlecitinib-treated patients with SALT score ≤20 and ≤10 responses at Week 24, ≥85% and ≥68%, respectively, sustained these responses through Week 48. Of those with SALT score >20 at Week 24, 22%-34% achieved SALT score ≤20 at Week 48. Of those with a SALT score >10 at Week 24, 20%-26% achieved SALT score ≤10 at Week 48. Safety was similar across subgroups. Small sample size. Hair regrowth was sustained through Week 48 in patients with response at Week 24. Up to one-third of patients who did not meet target efficacy at Week 24 achieved response with continued ritlecitinib treatment.

Long-term outcomes of intravenous corticosteroid pulse therapy for rapidly progressive alopecia areata: A single-center retrospective analysis of 106 cases and usefulness evaluation of a scoring system originally designed for half-year efficacy prediction for extended periods.

Intravenous corticosteroid pulse therapy (IVPT) has been preferentially conducted for rapidly progressive alopecia areata (RP-AA); however, the evaluation of long-term outcomes has been insufficient. In this study, 106 IVPT-treated RP-AA patients (36 males and 70 females) who were followed up for more than 1 year and up to 6.8 years were retrospectively analyzed. The mean observation period was 1137.8 ± 587.9 days (range 380-2490). The mean severity of alopecia tool (SALT) score before IVPT was 21.3 ± 23.4 but whole-scalp hair loss was observed in all cases after the intervention, suggesting that IVPT was performed soon after the onset. With additional interventions represented by intralesional triamcinolone acetonide injection with or without topical potent corticosteroid for those who insufficiently responded at 6 months after IVPT, 64.2%, 14.2%, and 21.7% of the patients respectively achieved good response (GR; SALT score ≤25), moderate response (MR; 25 < SALT score <75), and poor response (PR; 75 ≤ SALT score) 1 year after IVPT. On the final evaluation, the proportions of patients with GR, MR, and PR were 79 (74.5%), 7 (6.6%), and 20 (18.9%). Sixteen patients achieved and maintained full hair regrowth with IVPT alone until the end of observation. A previously reported scoring system for the short-term outcome prediction was shown to be useful for distinguishing the final-point GR responders from PR responders (P = 0.003). Of note, 21 patients were found to have some symptoms suggestive of the existence of preceding infectious diseases and tended to relapse. The revised scoring system adding the absence of preceding infectious diseases as one factor successfully predicted the occurrence of the relapse in our cohort (P = 0.002). Taken together, previously unreported real-world efficacy of IVPT to RP-AA was elucidated with the invention of a tool putatively enabling optimal long-term management.

COMPARATIVE EVALUATION OF EFFICACY AND SAFETY OF TOPICAL METHOTREXATE WITH TRETINOIN VERSUS BETAMETHASONE WITH TRETINOIN IN PATIENTS OF ALOPECIA AREATA: A PROSPECTIVE RANDOMIZED DOUBLE-BLIND STUDY

Objectives: Alopecia areata (AA) is a reiterative and non-scarring type of hair loss that can affect any hairy area of the body, particularly the scalp. The present study is aimed at comparing the safety and efficacy of methotrexate with tretinoin versus betamethasone with tretinoin in patients of AA. Methods: A prospective and comparative study was carried out in 80 cases of AA in Gajra Raja Medical College, Gwalior (M.P.) from December 2022 to November 2023. Subjects were randomly allocated to two groups, namely, MXT and BMT, 40 patients in each group. In group MXT, patients were asked to apply methotrexate 1% gel in the morning and tretinoin 0.025% cream in the evening, and in group BMT patients were asked to apply betamethasone 0.05% cream once daily in the morning and tretinoin 0.025% cream in the evening for 6 months. Mean severity of alopecia tool (SALT) score, mean regrowth scale (RGS) score, and adverse drug reactions due to treatments were recorded at 0, 3, and 6 months. Results: Mean SALT score decreased from 4.40 to 0.57 in MXT and from 3.34 to 0.63 in BMT group after 6 months and is significant (p&lt;0.05) from baseline values. MXT showed a better response, than BMT group but was not significant (p&gt;0.05). RGS Grade 3 was observed in 13% of patients and RGS Grade 4 was observed in 87% of patients in MXT group patients. RGS Grade 3 was observed in 19% of patients and RGS Grade 4 was observed in 81% of patients in BMT group. On intergroup comparison, a greater number of patients treated with methotrexate and tretinoin showed RGS Grade 4 as compared to patients treated with betamethasone and tretinoin treated group but was not significant (p&gt;0.05). Twenty-five patients in the MXT group and 17 patients in BMT group showed mild adverse drug reactions at the end of 1 month that included burning, itching, redness, stinging, folliculitis, and scaling and all were resolved with minor treatment. Conclusion: Topical methotrexate is more efficacious and equally safe as betamethasone, making it the first line of drug for the management of AA.

Efficacy and safety of ritlecitinib, an oral JAK3/TEC family kinase inhibitor, in adolescent and adult patients with alopecia totalis and alopecia universalis.

This post-hoc analysis of the ALLEGRO phase 2b/3 study (NCT03732807) evaluated the efficacy and safety of ritlecitinib, an oral Janus kinase 3/TEC family kinase inhibitor, in patients with alopecia totalis (AT) and alopecia universalis (AU). Patients aged ≥ 12 years with alopecia areata (AA) and ≥50% scalp hair loss received once-daily ritlecitinib 50 or 30 mg (± 4-week 200-mg loading dose) or placebo for 24 weeks. In a subsequent 24-week extension period, the ritlecitinib groups continued their doses and patients initially assigned to placebo switched to ritlecitinib (200/50 or 50 mg daily). In this analysis, clinician- and patient-reported hair regrowth outcomes were assessed at weeks 24 and 48 in four AA subgroups: AT/AU, AT, AU, and non-AT/AU. Safety was monitored throughout. Of the 718 randomized patients, 151 (21%) and 147 (20%) were defined as having AT or AU, respectively. At week 24, Severity of Alopecia Tool (SALT) score ≤20 (≤20% scalp hair loss) response rates were higher in the ritlecitinib-treated AT/AU, AT, and AU groups (7%-14%, 7%-21%, and 4%-10%, respectively) vs the placebo group (0% in the AT/AU, AT, and AU groups). The proportions of patients with a SALT score of ≤20 increased through week 48 (AT/AU, 13%-31%; AT, 11%-27%; AU, 6%-41%). Additionally, at week 24, 25%-43%, 32%-42%, and 12%-50% of patients with AT/AU, AT, and AU, respectively, who received ritlecitinib achieved a moderately or greatly improved response based on the Patient Global Impression of Change scale. Response rates generally increased through week 48 and were similar across AA subgroups. In patients with AT/AU, ritlecitinib was well tolerated with a safety profile consistent with that of the overall AA population. Ritlecitinib demonstrated clinical efficacy, patient-reported improvement, and an acceptable safety profile in patients with AT and AU through week 48. A plain language summary of this study is available at https://doi.org/10.25454/pfizer.figshare.26879161. Clinicaltrials.gov: NCT03732807.

Changes and significance of Th1/Th2 and Treg/Th17 cells and their cytokines in patients with alopecia areata

BackgroundAlopecia areata (AA) is a chronic autoimmune disease. Th1/Th2 and Treg/Th17 cells and their cytokines are implicated in AA, and we explored their clinical significance in AA. MethodsAA patients and healthy people (controls) were enrolled, with their Th1/Th2/Th17/Treg cell proportion changes and serum Th1 (INF-γ)/Th2 (IL-5, IL-6)/Th17 (IL-17, IL-22)/Treg (IL-35) cytokine levels assessed. AA patients were assigned into mild, moderate and severe alopecia according to Severity of Alopecia Tool (SALT). The relationship between alopecia severity and initial onset age, disease course, family/smoking/drinking history and sleep disorders was explored. Th1/Th2 and Treg/Th17 cells and their cytokine levels in AA patients with different severity levels were compared. The correlation between cytokine levels and SALT scores was analyzed using Spearman. Additionally, the changes of serum cytokine levels in inactive/active AA patients were compared. ResultsAA patients differed from controls in family history/smoking history/drinking history/sleep disorders. Peripheral blood Th1/Th2/Th17 cell proportions and INF-γ/IL-5/IL-6/IL-17/IL-22 levels increased, while Treg cell proportions and IL-35 level dropped. With higher alopecia severity, the proportions of Th1, Th2 and Th17 cells increased, and Treg cell proportion decreased. AA patients with mild/moderate alopecia had significant differences in IL-17 level. Serum INF-γ, IL-5, IL-17 and IL-22 levels were elevated, and IL-35 level dropped in severe AA patients versus moderate AA patients. ConclusionTh1/Th2/Th17 cell proportions and serum INF-γ/IL-5/IL-6/IL-17/IL-22 levels in AA patients were up-regulated, while Treg cell proportion and IL-35 level were repressed. SALT scores were positively-correlated with serum IL-5/IL-17 levels. SALT scores were negatively-correlated with serum IL-35.

Impact of Previous Alopecia Areata Treatment on Efficacy Responses up to Week 48 Following Ritlecitinib Treatment: A Post Hoc Analysis.

Patients with alopecia areata (AA) may have received several therapies for management of AA during their lives. In the ALLEGRO phase 2b/3 (NCT03732807) study, the oral JAK3/TEC family kinase inhibitor ritlecitinib demonstrated efficacy and an acceptable safety profile in patients aged ≥ 12years with AA and ≥ 50% scalp hair loss. This post hoc analysis investigated associations between prior use of AA therapies and Severity of Alopecia Tool (SALT) responses in patients receiving ritlecitinib for AA. Patients receiving ritlecitinib 30mg or 50mg once daily with or without an initial 4-week 200-mg daily loading dose were grouped by previous exposure to AA treatments, including topicals, intralesional corticosteroids (ILCS), topical immunotherapy, and systemic immunosuppressants or any prior AA treatment. Multivariable logistic regression analyses evaluated the association between response based on a SALT score of ≤ 20 and any prior treatment for AA at weeks 24 and 48. Of 522 patients, 360 (69.0%) had previous exposure to any AA treatment. At Week 24, SALT ≤ 20 response was positively associated with prior use of ILCS (odds ratio [OR], 2.12; 95% confidence interval [CI], 1.23-3.65; P < 0.05) and negatively associated with prior use of systemic immunosuppressants (OR 0.50; 95% CI 0.28-0.88; P < 0.05). Prior use of topicals or topical immunotherapy was not associated with SALT ≤ 20 response at Week 24. By Week 48, no association was identified between SALT ≤ 20 response and prior use of topicals, ILCS, topical immunosuppressants, or systemic immunosuppressants (all P > 0.05). Previous exposure to any AA therapy was not associated with SALT ≤ 20 response at weeks 24 or 48 (all P > 0.05). Prior AA treatment history had no effect on longer-term treatment response to ritlecitinib. NCT03732807.

Psychometric Properties of the EQ-5D-5L in Patients with Alopecia Areata.

For many decision makers in Health Technology Assessment the EQ-5D-5L is the standard measure of health-related quality of life (HRQL). However, evidence has shown the limitations of the measure in certain disease areas, including dermatology. Alopecia areata (AA) is associated with a significant HRQL impact, partly due to the emotional impact of hair loss. This study explores the psychometric properties of the EQ-5D-5L in people with AA in reference to the short-form 36 version 2 (SF-36v2), the Alopecia Areata Patient Priority Outcomes (AAPPO), the Severity of Alopecia Tool (SALT) and the Patient Global Impressions of Change (PGI-C). Data from participants with AA enrolled in the ALLEGRO-2b/3 trial (NCT03732807) of ritlecitinib were analysed. Participants completed the AAPPO measure (an AA-specific measure assessing emotional symptoms and activity limitations), PGI-C, EQ-5D-5L and SF-36v2 across 48-weeks of follow up. Extent of scalp hair loss was assessed using the SALT. Ceiling effects, known groups validity, convergent validity and responsiveness were examined. Known groups were defined by SALT score and a PGI-C defined response from baseline. Exploratory factor analysis was also performed. Data were available from 612 adult participants. Ceiling effects were observed for the EQ-5D-5L (55.3-61.2%) and analyses suggested that the EQ-5D did not capture important differences between patients that the SF-36v2 did. The EQ-5D-5L very weakly correlated with SALT score, whereas the AAPPO correlated more strongly with the extent of hair loss. Compared with the EQ-5D-5L, the AAPPO was better able to discriminate between known groups defined by SALT and PGI-C. An exploratory factor analysis suggested that the EQ-5D-5L had limitations in content validity compared with the AAPPO. The EQ-5D-5L may not adequately measure the burden of AA on patients' HRQL. Insensitivity to the burden of AA suggests that the EQ-5D-5L may not measure treatment-related benefit with hair regrowth. Data from other measures could be considered if they are shown to be more relevant.

Comparative study between intralesional injection of prostaglandin F2α alone or combined with corticosteroids in the treatment of alopecia areata

Background Alopecia areata (AA) is an autoimmune disorder causing hair loss, yet its treatment remains challenging due to limited Food and Drug Administration approved therapies. Prostaglandin F2α (PGF2α) has emerged as a potential therapy. Objective To assess the efficacy of PGF2α intralesional injection in AA treatment. Patients and methods This case comparative work was performed on 75 localized AA patients who were split into three groups receiving different intralesional injections: group A received triamcinolone acetonide (TRA), group B received a combination of TRA and latanoprost (a PGF2α analog), and group C received latanoprost alone. Treatment response was assessed using the Severity of Alopecia Tool score, Severity of Alopecia Tool II, and Alopecia Areata Severity Index. Results High treatment response was observed in 76% of group B, compared to 64% in group A and 40% in group C. Group B showed the most significant reduction in severity score (median=0), followed by group A (median=1), and group C (median=3). Multivariate analysis identified group B as a significant predictor of a high treatment response (odds ratio=10.292, 95% confidence interval=1.904–55.632, P=0.007). Conclusion Intralesional injection of TRA and latanoprost (PGF2α analog) demonstrated superior efficacy in treating localized AA compared to other treatment modalities.

Topical immunotherapy with diphenylcyclopropenone in paediatric patients with alopecia areata-A retrospective study of 97 patients.

Alopecia areata (AA) is an autoimmune disease causing chronic non-scarring hair loss. Different therapeutic regimens have been suggested for AA, which depend on patients' age, scalp involvement extent and duration. Topical immunotherapy with diphenylcyclopropenone (DPCP) is one of the treatment options for these patients. We aimed to investigate the response to DPCP in paediatric AA patients. This retrospective study included 97 paediatric AA patients followed in the DPCP clinic from March 2016 to March 2021 at a referral dermatology hospital. In a cohort of 97 paediatric patients with AA under treatment with DPCP, with a mean age of 11.10±0.9, 53.6% of the patients were male. Patchy alopecia was the most prevalent type (45.4%). After 6months of DPCP treatment, 51.5% showed no response, while 3.1% achieved complete response. At the 12-month evaluation, among the 68 patients who continued treatment, complete response was observed in 8.8%. A significant positive correlation was found between alopecia type, specifically patchy, and treatment response (p=0.031). Additionally, treatment duration emerged as a significant predictor of positive response at both six (OR 1.450, p=0.026) and 12months (OR 1.310, p=0.043). A higher initial Severity of Alopecia Tool score was inversely correlated with treatment response (Spearman's rho -0.14, p=0.002), indicating that initial disease severity may predict treatment efficacy. One year after the onset of DPCP in paediatric AA patients, the complete response and any hair regrowth rates were 8.8% and 61.8%, respectively. The milder initial disease severity and longer duration of treatment resulted in a better response.

The value of immunohistochemical expression of SOX9 and CD34 in alopecia areata

ABSTRACT Background Alopecia areata (AA), an immune-mediated disorder, is marked by temporary, nonscarring hair loss. The bulge area is protected from immune attacks by immune privilege; however, recent studies demonstrated immune cells infiltrating the bulge area. Objective This study aims to investigate the immunohistochemical expression of the sex-determining region Y-box 9 (SOX9) and cluster of differentiation 34 (CD34) in AA patients as markers of hair follicle stem cells (HFSCs) and progenitor cells, respectively. Methods Immunohistochemical staining of SOX9 and CD34 was applied on skin samples of 20 AA patients and 20 healthy controls. Results SOX9 and CD34 were significantly lower in lesional samples of cases compared to perilesional and control skin biopsies. Furthermore, SOX9 level was negatively correlated with the severity of alopecia tool score (SALT score) among the studied AA patients. Moreover, lowered SOX9 expression was present in patients with recurrent attacks. Conclusions The significant reduction of stem cell markers (SOX9 and CD34) in our studied AA cases signifies the pathological affection of HFSCs and their progeny in AA. This is thought to cause a loss of competence in generating new hair in some AA cases, which needs to be validated in further research. Limitations of the study This study has a small sample size.

Prevalence of Thyrotropin Receptor Antibodies and Clinical Profile of Patients with Alopecia Areata: A Cross-Sectional Study

Introduction: Alopecia areata (AA) is associated with thyroid dysfunction and abnormal levels of thyroglobulin and thyroid peroxidase autoantibodies. One study detected high prevalence of thyrotropin receptor antibodies (TRAbs) in AA patients. Our aim was to investigate the prevalence of TRAb levels in AA patients and to assess their association with thyroid hormones, other thyroid antibodies, AA severity, and other epidemiological variables. Methods: In this observational study, 139 patients (97 females, 42 males), aged 12 and above, with newly presenting, relapsing, or treatment-resistant AA were included. Medical histories were reviewed, alopecia severity was assessed using the Severity of Alopecia Tool (SALT), and blood tests measured thyroid hormones and autoantibodies. Results: The prevalence of TRAb was significantly higher in AA patients (23.6%) compared to the general population (1–2%) (p < 0.001). Elevated TRAb titers did not correlate with diagnosed thyroid dysfunction or treatment, abnormal thyroid function tests and autoantibodies, AA severity, duration, and onset. Male patients exhibited a significantly higher prevalence of abnormal TRAb titers compared to females (75.0% vs. 21.3%, p = 0.002). Conclusion: A significant proportion of AA patients presented with elevated TRAb levels, independent of thyroid hormone titers, other thyroid autoantibodies, or SALT score. Prevalence of abnormal TRAb levels was higher in males.

Dupilumab induces hair regrowth in pediatric alopecia areata: a real-world, single-center observational study

Alopecia areata (AA) is nonscarring hair loss characterized by Th1 and concomitant Th2 skewing, particularly in atopic patients. Despite novel developments for adult AA, safe and effective treatments for pediatric patients remain limited. Dupilumab, with a well-studied safety profile, may have therapeutic potential for atopic pediatric AA. To evaluate the ability of dupilumab to regrow hair in pediatric AA patients. We conducted a single-center, retrospective, observational study to evaluate hair regrowth [using Severity of Alopecia Tool (SALT)] with dupilumab in 20 children with both AD and AA (age range 5–16 years, mean 10.8 years; baseline SALT range 3–100, mean 54.4). Patient demographics, atopic history, IgE and SALT scores were collected at 12wk follow-up visits, up to > 72wks, to evaluate hair regrowth. Spearman correlations with clinical data were performed. Patients showed clinical improvement over the follow-up period (range 24 to > 72wks, mean 67.6wks) with significant mean(± SD) reduction in SALT at 48wks versus baseline [20.4(± 35.1) vs 54.4(± 37.6), respectively; p < 0.01] and continued improvement up to > 72wks [2.2(± 4.9), p < 0.01]. Baseline SALT positively correlated with disease duration (r = 0.54, p < 0.01), and negatively correlated with improvement in SALT at weeks 24, 36, and 48 (|r|≥ 0.65, p < 0.01 for all comparisons). Baseline IgE positively correlated with improvement in SALT at week 36 (r > 0.60, p < 0.05). Dupilumab was well-tolerated, with no new safety concerns. These real-world data support the utility of dupilumab to safely treat pediatric AA patients, corroborating the role of Th2 skewing in children with AA and associated atopy, warranting larger clinical trials.

Comparison of efficacy and safety of tofacitinib and azathioprine in patients with alopecia areata and variants: a double-blind, randomized controlled trial.

Alopecia areata (AA) is an autoimmune pathology manifested by loss of hair. To evaluate and compare the efficacy and safety of tofacitinib and azathioprine in patients with AA and variants. In this double-blind randomized controlled trail (RCT) carried out at the Department of Dermatology, Medical Teaching Institute-Lady Reading Hospital (MTI-LRH), Peshawar, Pakistan, patients aged ≥ 12 years diagnosed with AA, alopecia totalis (AT) or alopecia universalis (AU) with minimum 50% scalp hair loss for a period ≥ 06 years were included. Patients were randomly assigned to receive oral tofacitinib 5mg twice daily (Group I) or oral azathioprine 2mg/kg body weight once daily (Group II). The primary endpoint was Severity of Alopecia Tool (SALT) score, evaluated at baseline and 06 months follow-up. Safety was consistently assessed during the study. A total of 104 patients underwent random allocation into either the tofacitinib group (n = 52) or the azathioprine group (n = 52). The mean (SD) age of patients was 20.23 (7.14) years and 22.26 (8.07) years, while the mean (SD) disease duration was 6.59 (4.01) years and 7.98 (4.40) years in in Group I and II, respectively. Overall, 40 (38.5%) patients were adolescents while 70 (67.3%) were male. 52 (50%) had AA, 37 (35.5%) had AT and 15 (14.5%) had AU. Mean baseline SALT score in tofacitinib group was 91.02 ± 10.21 and azathioprine group was 91.02 ± 10.63, which at 06 months follow-up improved to 14.1 ± 24.6 and 63.9 ± 33.9, respectively (difference, 11.5 points; 95% confidence interval, 38.3-61.3, p < 0.0001). Overall, no major adverse effects and no difference among the minor adverse effects in the two groups (04 adverse events for tofacitinib group and 08 for azathioprine group: p = 0.23) was observed. Efficacy of tofacitinib was significantly higher than azathioprine, whilst both drugs were well-tolerated in patients with AA and variants.

Real-world effectiveness and safety of tofacitinib for alopecia areata: A retrospective cohort study of 202 patients.

Alopecia areata (AA) is an autoimmune hair loss disorder characterised by collapse of hair follicle immune privilege and mediated by autoreactive CD8+ T lymphocytes and natural killer cells. Treatment is often unsatisfactory. The Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway is implicated in the pathogenesis of AA and Janus Kinase inhibitor (JAKi) medications are promising emerging treatments for AA. We evaluated the safety and effectiveness of tofacitinib in a real-world setting over 18 months of treatment. A retrospective cohort study of all patients with scalp AA commenced on tofacitinib between 1 November 2016 and 31 May 2019. The primary endpoint was the percent change in Severity of Alopecia Tool (SALT) score at 18 months. Two hundred and two patients were included. After 18 months of treatment, 55.9%, 42.6% and 29.2% achieved 50%, 75% and 90% reductions in their SALT scores respectively. Increased duration of AA was a negative predictor of hair regrowth. Males and patients with baseline SALT ≥90 were slower to respond to treatment in the first 12 months. One hundred and twenty-four patients and 168 patients received concomitant systemic corticosteroids or low-dose oral minoxidil during tofacitinib therapy respectively. There were no serious adverse events. Tofacitinib was a safe and effective treatment for patients with moderate-to-severe AA. Further randomised controlled studies are needed to establish the optimal treatment regimen.