![](https://assets.reachrx.ai/images/10.1111%E2%98%8Dijd.70035/_page_0_Picture_0.jpeg) **ORIGINAL ARTICLE [OPEN ACCESS](https://doi.org/10.1111/ijd.70035)** # **Improvement in Patient-Reported Emotional Symptoms and Activity Limitations due to Hair Loss in Patients With Alopecia Areata Treated With Ritlecitinib: Additional Analyses From ALLEGRO-2b/3** Ernest H. Law[1](#page-0-0) | [Bintu](https://orcid.org/0000-0002-2705-7002) Sherif[2](#page-0-1) | Arash [Mo](https://orcid.org/0000-0002-7201-3324)staghimi[3](#page-0-2) | [Bret](https://orcid.org/0009-0007-1147-7532)t King[4](#page-0-3) | Rod[ney](https://orcid.org/0000-0002-7495-382X) Sinclair[5](#page-0-4) | Natasha Mesinkovska[6](#page-0-5) | Kent A. Hanson[1,7](#page-0-0) | Dane Korver[2](#page-0-1) | Costel Chirila[2](#page-0-1) 1Pfizer, Inc., New York, New York, USA | 2RTI Health Solutions, North Carolina, USA | 3Department of Dermatology, Brigham & Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA | 4Department of Dermatology, Yale University, New Haven, Connecticut, USA | 5Sinclair Dermatology, East Melbourne, Victoria, Australia | 6Department of Dermatology, University of California, Irvine, California, USA | 7Department of Pharmacy Systems, Outcomes and Policy, University of Illinois Chicago, Chicago, Illinois, USA **Correspondence:** Ernest H. Law [\(ernest.law@pfizer.com](mailto:ernest.law@pfizer.com)) **Received:** 5 June 2025 | **Revised:** 5 June 2025 | **Accepted:** 13 August 2025 **Funding:** This work was supported by Pfizer. **Keywords:** activity limitations | ALLEGRO-2b/3 | alopecia areata | alopecia areata patient priority outcomes | emotional symptoms | hair loss | patient-reported outcomes | ritlecitinib | treatment ### **ABSTRACT** **Background:** Patients with alopecia areata (AA) in ALLEGRO-2b/3 (NCT03732807) had clinically significant hair regrowth and patient-reported improvements with ritlecitinib versus placebo, but patient-reported improvements in AA Patient Priority Outcomes (AAPPO) emotional symptoms (ES) or activity limitations (AL) were not observed during the 24-week placebocontrolled phase. This study compared AAPPO scores between the 50-mg ritlecitinib maintenance dose (+/−200-mg 4-week loading dose) and subtherapeutic 10-mg ritlecitinib through Week 48 of ALLEGRO-2b/3. **Methods:** Least squares mean (LSM) changes from baseline (CFBs) in domain scores were estimated for the full analysis population and for participants with baseline domain scores ≥1. Item-level responses (scores <2) were evaluated for participants with baseline item scores ≥2, since lower baseline item scores (measured on 5-point response scales; range, 0–4) indicated less frequent/severe impacts from hair loss. **Results:** There were 325 participants (200/50-mg [*n*=132] and 50-mg [*n*=130], combined and as subgroups; 10-mg [*n*=63]). LSM CFBs in ES and AL domain scores generally improved through Week 48 for all 50-mg groups, with significant differences versus 10-mg starting at Week 34 for ES and Week 40 for AL. The proportion of responders for all ES and AL items generally increased through Week 48 for all 50-mg groups. The largest improvements versus 10-mg were for ES items 5 and 6 (selfconsciousness and embarrassment) and AL item 11 (interactions with others). **Conclusions:** ALLEGRO-2b/3 participants reported greater improvements in ES and AL due to hair loss by Week 48 with the 50-mg ritlecitinib maintenance dose (+/−200-mg loading dose) versus subtherapeutic 10-mg ritlecitinib. This article is an original publication and has not been submitted elsewhere for publication. This is an open access article under the terms of the [Creative Commons Attribution-NonCommercial](http://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. © 2025 Pfizer Inc. *International Journal of Dermatology* published by Wiley Periodicals LLC on behalf of the International Society of Dermatology. - Using the Alopecia Areata Patient Priority Outcomes measure, this study evaluated patient-reported improvements in emotional symptoms (ES; selfconsciousness, embarrassment, sadness, frustration) and activity limitations (AL; outdoor activity, exercise, interactions with others) due to hair loss among patients with alopecia areata who participated in a randomized controlled trial (ALLEGRO-2b/3) of ritlecitinib. - By trial Week 48, participants receiving 50-mg ritlecitinib (+/−200-mg 4-week loading dose) reported greater improvements in ES and AL due to hair loss than did participants receiving subtherapeutic 10-mg ritlecitinib. - The findings indicate that patients with alopecia areata may experience improvement in psychosocial burden following hair regrowth with ritlecitinib. ### **1 | Introduction** Alopecia areata (AA), a complex autoimmune disease, targets hair follicles and causes nonscarring hair loss in approximately 2% of adults and children worldwide [\[1–3](#page-7-0)]. People with AA often experience sudden patches of hair loss, typically on the scalp, that can progress to total loss of scalp hair (alopecia totalis [AT]) or body hair (alopecia universalis [AU]) [\[1, 2, 4, 5\]](#page-7-0). Rates of spontaneous AA remission are low (particularly among patients with more severe AA), and many people with AA experience chronicrelapsing disease, making sustainable hair growth uncertain [\[2, 4–8](#page-7-1)]. Hair loss due to AA can have devastating effects on individuals' quality of life (QOL) beyond hair loss, with significant impacts on patients' emotional well-being and activities of daily living [\[9–13](#page-7-2)]. In 2023, the United States Food and Drug Administration and the European Medicines Agency approved 50-mg, oncedaily (QD) ritlecitinib for the treatment of adults and adolescents (aged ≥12 years) with severe AA, based on the efficacy and safety results of the ALLEGRO Phase 2b/3 randomized controlled trial (NCT03732807) [[8, 14–16\]](#page-7-3). ALLEGRO-2b/3 was a double-blind, placebo-controlled, dose-ranging pivotal study of ritlecitinib therapy in patients (aged ≥12 years) with a clinical diagnosis of severe AA and ≥50% scalp hair loss [\[8\]](#page-7-3). Overwhelming evidence indicates that patients with AA experience major psychosocial burden due to their disease [\[9, 10, 17–21](#page-7-2)]. However, although patients achieved significant clinician- and patient-reported hair regrowth with ritlecitinib therapy [\[8](#page-7-3)], improvements in patient-reported emotional symptoms (ES) or activity limitations (AL) as measured by the Alopecia Areata Patient Priority Outcomes (AAPPO) questionnaire [\[22](#page-8-0)] were not evident during the 24-week placebocontrolled period of ALLEGRO-2b/3 [\[23](#page-8-1)]. In exploratory analyses of ALLEGRO-2b/3 data [\[24\]](#page-8-2), patients with AA who experienced hair regrowth (i.e., Severity of Alopecia Tool [SALT] score ≤20 or ≤10) on ritlecitinib therapy reported greater improvements in psychosocial impacts and QOL. Since hair regrowth can precede patient-reported outcome (PRO) improvement [\[23\]](#page-8-1), individuals with a clinical response at Week 24 may need additional follow-up time to capture any delayed PRO effects. The ALLEGRO-2b/3 study included a 10-mg study arm for dose-finding purposes. This 10-mg study arm was found to be subtherapeutic and may be viewed as a conservative proxy for placebo to assess the efficacy of clinically active ritlecitinib regimens across the full 48-week double-blinded trial duration. This post hoc analysis of ALLEGRO-2b/3 data compares improvements in AAPPO ES and AL domain and item scores between the ritlecitinib 50-mg QD maintenance dose (+/−200-mg 4-week loading dose) and the subtherapeutic ritlecitinib 10-mg QD dose through Week 48. # **2 | Materials and Methods** ### **2.1 | Study Design** In ALLEGRO-2b/3, eligible participants (*N*=718) were randomized into either placebo or one of five ritlecitinib treatment groups [\[8\]](#page-7-3). The double-blinded trial lasted 48weeks, which comprised a 24-week placebo-controlled phase followed by a 24-week extension phase where participants in placebo groups switched to active ritlecitinib therapy. For this exploratory analysis, there were three treatment groups of interest: (a) participants receiving ritlecitinib 50-mg QD only; (b) participants receiving ritlecitinib 200-mg QD for 4weeks as a loading dose followed by a 50-mg QD maintenance dose (200/50-mg); and (c) all patients who received the 50-mg dose (i.e., pooled group of [a] and [b]). The control group for these analyses included participants who received the subtherapeutic 10-mg ritlecitinib QD dose. ### **2.2 | Alopecia Areata Patient Priority Outcomes (AAPPO) Measure** The AAPPO measure is a validated, self-administered, 11-item questionnaire that evaluates the impact of AA in patients aged ≥12 years [\[22, 25\]](#page-8-0). Items 1 through 4 evaluate current hair loss (scalp, eyebrows, eyelashes, and body) using a 5-point response scale ranging from 0="no hair loss" to 4="complete hair loss (do not have any hair on [insert body area])." Items 5 through 8 assess ES (self-consciousness, embarrassment, sadness, and frustration) over the past week with a 5-point scale ranging from 0="never" to 4="always." Lastly, items 9 through 11 measure AL (outdoor activity, exercise, and interactions with others) over the past week on a 5-point scale ranging from 0="not at all" to 4="completely (did not [insert activity] because of hair loss)." The AAPPO ES domain score is the mean of scores on items 5 through 8, and the AL domain score is the mean of scores on items 9 through 11 (calculations require nonmissing responses on ≥2 domain items). Higher AAPPO scores indicate greater impact on ES and AL due to hair loss. ## **2.3 | Endpoints** Changes from baseline (CFBs) in AAPPO ES and AL domain scores for participants in the full analysis set (FAS) (i.e., all | Abbreviations: AAPPO, Alopecia Areata Patient Priority Outcomes; ES, Emotional symptoms; SD, Standard deviation. | | |------------------------------------------------------------------------------------------------------------------|--| | | | | | | randomized participants excluding placebo) were estimated at Weeks 4, 8, 12, 18, 24, 34, 40, and 48. To evaluate whether participants reporting worse ES/AL status at baseline had different levels of improvement, sensitivity analyses were performed for participants with baseline domain scores ≥1. Among participants with baseline item scores ≥2, AAPPO itemlevel responses (i.e., postbaseline item scores <2) at Weeks 4 through 48 were evaluated. Sensitivity analyses were performed using a more stringent response definition (i.e., postbaseline item score=0) to evaluate item-level improvements. #### **2.4 | Statistical Methods** Exploratory binary endpoints were summarized using descriptive statistics. Summaries of data from all postbaseline visits were based on observed cases and included confidence intervals (CIs) based on the normal approximation. The difference in proportions between treatment groups and the corresponding 95% CIs were based on the Miettinen and Nurminen method. For continuous endpoints, a mixed-effect model with repeated measures (MMRM) was used. The MMRM included the factors (fixed effects) for treatment group, visit (as a categorical variable), treatment-by-visit interaction, and corresponding baseline value. A Toeplitz covariance matrix was used for model errors. For each visit, estimates of least squares mean (LSM) values and differences between the treatment groups and ritlecitinib 10-mg, corresponding *p* values, standard errors, and 95% CIs were derived from the model. *p* values less than 0.05 were considered statistically significant; no adjustments were made for multiple comparisons. | 3
International Journal of Dermatology, 2025 | |-------------------------------------------------| |-------------------------------------------------| | | Ritlecitinib | | | | |---------------------------------------------|------------------|------------------|-----------------|--| | | 200/50-mg | 50-mg | 10-mg | | | ES Item 5: Self-consciousness; mean (SD), n | 2.00 (1.20), 131 | 2.10 (1.27), 129 | 2.00 (1.41), 63 | | | Never=0, n (%) | 15 (11.5) | 17 (13.2) | 13 (20.6) | | | Rarely=1, n (%) | 34 (26.0) | 25 (19.4) | 12 (19.0) | | | Sometimes=2, n (%) | 39 (29.8) | 42 (32.6) | 14 (22.2) | | | Often=3, n (%) | 26 (19.8) | 22 (17.1) | 12 (19.0) | | | Always=4, n (%) | 17 (13.0) | 23 (17.8) | 12 (19.0) | | | ES Item 6: Embarrassment; mean (SD), n | 1.70 (1.23), 131 | 1.70 (1.34), 129 | 1.70 (1.39), 63 | | | Never=0, n (%) | 26 (19.8) | 33 (25.6) | 19 (30.2) | | | Rarely=1, n (%) | 36 (27.5) | 27 (20.9) | 10 (15.9) | | | Sometimes=2, n (%) | 37 (28.2) | 31 (24.0) | 16 (25.4) | | | Often=3, n (%) | 19 (14.5) | 23 (17.8) | 10 (15.9) | | | Always=4, n (%) | 13 (9.9) | 15 (11.6) | 8 (12.7) | | | ES Item 7: Sadness; mean (SD), n | 1.60 (1.20), 131 | 1.80 (1.18), 129 | 1.70 (1.32), 63 | | | Never=0, n (%) | 29 (22.1) | 19 (14.7) | 15 (23.8) | | | Rarely=1, n (%) | 32 (24.4) | 36 (27.9) | 11 (17.5) | | | Sometimes=2, n (%) | 41 (31.3) | 39 (30.2) | 22 (34.9) | | | Often=3, n (%) | 19 (14.5) | 23 (17.8) | 6 (9.5) | | | Always=4, n (%) | 10 (7.6) | 12 (9.3) | 9 (14.3) | | | ES Item 8: Frustration; mean (SD), n | 1.50 (1.22), 131 | 1.70 (1.22), 129 | 1.60 (1.28), 63 | | | Never=0, n (%) | 35 (26.7) | 24 (18.6) | 15 (23.8) | | | Rarely=1, n (%) | 27 (20.6) | 37 (28.7) | 14 (22.2) | | | Sometimes=2, n (%) | 39 (29.8) | 36 (27.9) | 22 (34.9) | | | Often=3, n (%) | 22 (16.8) | 19 (14.7) | 4 (6.3) | | | Always=4, n (%) | 8 (6.1) | 13 (10.1) | 8 (12.7) | | ![](https://assets.reachrx.ai/images/10.1111%E2%98%8Dijd.70035/_page_3_Figure_0.jpeg) ![](https://assets.reachrx.ai/images/10.1111%E2%98%8Dijd.70035/_page_3_Figure_1.jpeg) **FIGURE 1** | Improvements in AAPPO ES and AL domain scores—Full analysis population. (a, c) ES and (b, d) AL domain scores were analyzed for all ALLEGRO-2b/3 treatment groups, but only results from groups with the 50-mg maintenance dose and 10-mg (proxy for placebo) dose are shown. Lower values indicate improvement. Values are based on estimated LSM, and significant LSM differences (*p*<0.05) from the 10 mg group are indicated by asterisks (\*). AAPPO, Alopecia Areata Patient Priority Outcomes; AL, Activity limitations; CFB, Change from baseline; CI, Confidence interval; ES, Emotional symptoms; LSM, Least squares mean; Rit, Ritlecitinib; QD, Once daily. ### **3 | Results** ### **3.1 | Study Population** A total of 325 participants were included in the analyses, 262 of whom received the 50-mg maintenance dose (200/50-mg [*n*=132]; 50-mg [*n*=130]) and 63 of whom received the 10-mg dose of ritlecitinib. Baseline demographics and characteristics for ALLEGRO-2b/3 participants have been described previously [\[8](#page-7-3)]. # **3.2 | Emotional Symptoms (ES)** Mean baseline AAPPO ES item-level scores (Table [1](#page-2-0)) were numerically similar across all treatment groups. For the FAS, LSM CFBs in ES domain scores generally improved up to Week 48 for all 50-mg groups but plateaued after Week 12 for the 10 mg group (Figure [1\)](#page-3-0). Compared with LSM CFBs for the 10-mg group, LSM CFBs in ES significantly improved for the combined 50-mg group at Weeks 40 and 48; for the 200/50-mg subgroup at Weeks 34, 40, 48, and across the overall time duration; and for the 50-mg subgroup at Week 48. The largest significant improvements were observed at Week 48 for all 50-mg groups (LSM difference from 10-mg: combined 50-mg group [−0.41; 95% CI, −0.63 to −0.18; *p*=0.0004], 200/50-mg subgroup [−0.49; 95% CI, −0.73 to −0.24; *p*=0.0001], 50-mg subgroup [−0.33; 95% CI, −0.58 to −0.09; *p*=0.0079]). Participants with baseline ES domain scores ≥1 had consistently greater improvements in LSM CFBs to Weeks 4 through 48 than did the FAS (Figure [S1\)](#page-8-3). However, LSM differences from 10-mg were only significant at Week 48 (combined 50-mg group [−0.50; 95% CI, −0.77 to −0.22; *p*=0.0004], 200/50-mg subgroup [−0.56; 95% CI, −0.86 | AAPPO ES | 6 | | Difference (95% CI) | | | Difference (95% CI) | | Difference (95% CI) | |--------------------------------|---------|----------------------|-------------------------|-----------|-------|--------------------------|-----------------|-------------------------| | Item 5
(self-consciousness) | Week 4 | ⊢∙⊣ | 7.22 (-9.58 to 19.66) | Γ Η | • | 8.06 (-9.88 to 22.98) | ⊢ ⊢ | 6.44 (-11.29 to 21.00) | | | Week 8 | ⊢⊢ | 7.81 (-10.90 to 23.79) | н | | 10.97 (-9.26 to 28.99) | │ ⊢●⊣ | 4.64 (-15.38 to 22.63) | | | Week 12 | ⊢ ⊢ ●-1 | 8.95 (-9.38 to 24.07) | н | | 9.83 (-9.92 to 27.11) | │ ⊢⊷⊣ | 8.09 (-11.56 to 25.30) | | | Week 18 | ┝╼┥ | 15.66 (-2.53 to 30.60) | ( | -●- | 18.8 (-1.04 to 35.98) | │ ⊬●⊣ | 12.68 (-6.85 to 29.68) | | | Week 24 | ⊢–⊣ | 7.22 (-11.32 to 23.88) | н | ● | 6.36 (-13.85 to 25.14) | │ ⊢⊷⊣ | 8.01 (-12.01 to 26.50) | | | Week 34 | ┝┝╼╌┥ | 12.00 (-6.75 to 29.42) | н | | 11.20 (-9.52 to 30.70) | │ ⊬●-1 | 12.70 (-7.61 to 31.74) | | | Week 40 | ⊢●┥ | 22.42 (3.76 to 38.61)* | | | 20.11 (-0.28 to 38.29) | ⊢●- | 24.71 (4.37 to 42.65)* | | | Week 48 | ⊢⊷⊣ | 29.83 (11.00 to 45.27)* | | H | 33.08 (12.48 to 50.40)* | | 26.84 (6.44 to 44.21)* | | | Week 4 | ┣━┥ | 13.95 (-4.62 to 28.17) | H | | 12.45 (-7.47 to 29.28) | ┝┝╋┥ | 15.44 (-4.63 to 32.33) | | t) | Week 8 | ⊢┥ | 6.26 (-13.82 to 24.13) | н | ● | 9.04 (-12.76 to 29.01) | │ ⊢∳→ | 3.34 (-18.42 to 23.53) | | nen | Week 12 | ┝╺┝┥ | -0.08 (-19.44 to 17.98) | | ⊢ | 0.49 (-20.56 to 20.62) | | -0.67 (-21.82 to 19.65) | | n 6
assr | Week 18 | ╞╼┥ | 19.14 (-0.26 to 35.44) | | ⊢∙−┤│ | 23.44 (2.18 to 41.88)* | │ ┞╼-┥ | 14.78 (-6.37 to 33.54) | | Item 6
(embarrassment) | Week 24 | ┝╺┝┥ | -2.55 (-21.39 to 16.88) | | - | -3.33 (-24.18 to 18.03) | | -1.77 (-22.65 to 19.56) | | emt | Week 34 | ┝┼━╌┥ | 9.45 (-10.19 to 28.65) | H | | 13.39 (-8.38 to 34.38) | ++++++ | 5.69 (-15.91 to 26.85) | | ) | Week 40 | ┝━┥ | 21.29 (1.45 to 39.16)* | | ⊢• | 25.08 (3.39 to 44.58)* | │ ╟━┥ | 17.38 (-4.53 to 37.43) | | | Week 48 | ⊢●┥ | 28.93 (8.71 to 46.06)* | | | 35.52 (13.48 to 54.17)* | │ | 22.66 (0.55 to 42.01)* | | | Week 4 | ⊢●┥ | -16.00 (-33.85 to 1.38) | ⊢ | | -17.36 (-36.58 to 2.07) | ⊢●- | -14.73 (-33.99 to 4.59) | | | Week 8 | ⊢┥┥ | -2.40 (-21.37 to 15.61) | | - | -3.75 (-24.45 to 16.45) | │ ⊢∳⊣ | -1.10 (-21.77 to 18.93) | | ( | Week 12 | ⊢∳⊣ | 0.00 (-18.86 to 17.70) | | ⊢ | -1.80 (-22.42 to 18.17) | │ ⊢∳-┥ | 1.69 (-18.87 to 21.42) | | n 7
ness | Week 18 | ⊢┥ | 3.97 (-14.68 to 21.71) | н | ⊢ | 1.91 (-18.71 to 21.93) | │ ⊢●-1 | 5.88 (-14.57 to 25.54) | | ltem 7
(sadness) | Week 24 | ┝╼┥┥ | -5.31 (-23.38 to 13.51) | | - | -10.10 (-30.16 to 10.83) | +++ | -0.81 (-20.87 to 19.74) | | Ű | Week 34 | ┝╼┿┥ | -5.72 (-23.54 to 13.63) | | H | -1.75 (-22.04 to 19.49) | ⊢●┼┥ | -9.38 (-29.23 to 11.82) | | | Week 40 | ⊢┥ | 5.71 (-12.10 to 24.05) | H | - | 3.78 (-16.30 to 24.04) | │ ⊢●1 | 7.62 (-12.37 to 27.64) | | | Week 48 | ┝╼┥ | 18.88 (0.67 to 37.10)* | | ⊢●┥│ | 21.82 (1.48 to 41.40)* | │ ╟─●─┤ | 16.18 (-4.09 to 35.98) | | | Week 4 | ⊢ ● ⊣ | -2.43 (-21.48 to 14.65) | H | | 6.62 (-14.28 to 25.94) | ⊢ ●- 1 | -11.74 (-31.73 to 7.20) | | | Week 8 | ⊨ ⊢• ⊣ | -3.42 (-23.13 to 15.41) | | ⊢ | -1.75 (-23.21 to 19.13) | ⊢●→ | -5.15 (-26.56 to 15.85) | | (L | Week 12 | ⊨∎ ⊢● ⊣ | -9.02 (-27.95 to 9.77) | | ⊣ | -6.20 (-26.99 to 14.67) | │ ⊢● ┼٩ | -11.88 (-32.45 to 9.00) | | ltem 8
(frustration) | Week 18 | ┝┝╋┙ | 8.58 (-10.75 to 26.34) | н | | 12.60 (-8.76 to 32.48) | +++++ | 4.69 (-16.38 to 24.62) | | lten
ustr | Week 24 | ⊢∳⊣ | -0.27 (-19.72 to 18.63) | | H | -2.40 (-23.78 to 18.71) | │ ⊢∳→ | 1.77 (–19.56 to 22.65) | | (fr | Week 34 | ┝┝╋┥ | 12.90 (-7.38 to 30.93) | | | 13.79 (-8.55 to 34.18) | │ ⊢⊷⊣ | 12.07 (-10.00 to 32.23) | | | Week 40 | ┝╺┝╼┥ | 2.11 (-16.83 to 21.27) | H | ● | 6.72 (-14.41 to 27.71) | ⊢+ | -2.43 (-23.39 to 18.80) | | | Week 48 | | 22.40 (2.37 to 39.39)* | | | 30.00 (8.03 to 48.83)* | | 15.05 (-6.74 to 34.43) | | | | -50 - 30 0 30 50 | | -50 -30 0 | 30 50 | | -50 -30 0 30 50 | | | Favors Favors Fa | | | Favors | Favors | | Favors Favors | • | | | | | | | 200/50-mg | g | 10-mg 50-mg | | | | | | - | | 5 | | - | 5 5 | | **FIGURE 2** | In participants with baseline item scores ≥2, difference in the proportion of responders (postbaseline scores <2) in individual AAPPO ES items. AAPPO data were analyzed for all ALLEGRO-2b/3 treatment groups and across all timepoints, but only results from groups with the 50-mg maintenance dose and 10-mg (proxy for placebo) dose are shown. Analyses were conducted for participants with corresponding baseline item scores ≥2. The mean (dots) and 95% CIs (whiskers) are shown, and significant differences (*p*<0.05) in the proportion of responders compared with the 10-mg group are indicated by asterisks (\*). AAPPO, Alopecia Areata Patient Priority Outcomes; CI, Confidence interval; ES, Emotional symptoms; Rit, Ritlecitinib; QD, Once daily. to −0.27; *p*=0.0002], 50-mg subgroup [−0.43; 95% CI, −0.72 to −0.13; *p*=0.0053]). The proportion of participants with baseline ES item scores ≥2 reporting postbaseline scores <2 on individual items generally increased over time for all 50-mg groups, with the largest differences in improvement versus the 10-mg group observed at Week 48 for each item (Figure [2](#page-4-0) and Table [S1\)](#page-8-3). For item 5 (self-consciousness), the proportion of responders was significantly greater in the combined 50-mg group and the 50-mg subgroup at Week 40, and in all 50-mg groups at Week 48, than in the 10-mg group. The proportion of responders for item 6 (embarrassment) was significantly greater for the 200/50-mg subgroup at Week 18, the combined 50-mg group and the 200/50-mg subgroup at Week 40, and for all 50-mg groups at Week 48 versus the 10-mg group. For item 7 (sadness) and item 8 (frustration), the combined 50-mg group and the 200/50-mg subgroup had a significantly greater proportion of responders at Week 48 than did the 10-mg group. In sensitivity analyses, all 50-mg groups, except the 50-mg subgroup for item 8, had a significantly greater proportion of responders (participants with postbaseline item scores=0) across all ES items at Week 48 versus the 10-mg group (Table [S1](#page-8-3) and Figure [S2\)](#page-8-3). Notably, in comparison with the 10-mg group, the 50-mg groups demonstrated significant differences in the proportion of responders at some earlier timepoints for all ES items except item 6, with significance noted as early as Week 12 for item 5 (200/50-mg subgroup), Week 48 for item 6 (all 50-mg groups), Week 34 for item 7 (200/50-mg subgroup), and Week 18 for item 8 (200/50-mg subgroup). # **3.3 | Activity Limitations (AL)** Mean baseline AAPPO AL item-level scores (Table [2](#page-5-0)) were numerically similar across all groups. For the FAS, LSM CFBs in | | Ritlecitinib | | | | |---------------------------------------------------------|------------------|------------------|-----------------|--| | | 200/50-mg | 50-mg | 10-mg | | | AL Item 9: Outdoor activities; mean (SD), n | 0.80 (0.97), 131 | 0.80 (1.11), 129 | 0.80 (1.13), 63 | | | Not at all=0, n (%) | 68 (51.9) | 77 (59.7) | 36 (57.1) | | | A little=1, n (%) | 32 (24.4) | 25 (19.4) | 11 (17.5) | | | Moderately=2, n (%) | 23 (17.6) | 13 (10.1) | 8 (12.7) | | | A great deal=3, n (%) | 7 (5.3) | 10 (7.8) | 7 (11.1) | | | Completely=4, n (%) | 1 (0.8) | 4 (3.1) | 1 (1.6) | | | AL Item 10: Exercise or physical activity; mean (SD), n | 0.70 (1.06), 131 | 0.50 (0.89), 129 | 0.60 (0.93), 63 | | | Not at all=0, n (%) | 82 (62.6) | 88 (68.2) | 41 (65.1) | | | A little=1, n (%) | 23 (17.6) | 26 (20.2) | 9 (14.3) | | | Moderately=2, n (%) | 14 (10.7) | 8 (6.2) | 10 (15.9) | | | A great deal=3, n (%) | 9 (6.9) | 5 (3.9) | 3 (4.8) | | | Completely=4, n (%) | 3 (2.3) | 2 (1.6) | 0 (0.0) | | | AL Item 11: Interactions with others; mean (SD), n | 0.60 (0.85), 131 | 0.70 (1.03), 129 | 0.70 (1.07), 63 | | | Not at all=0, n (%) | 83 (63.4) | 79 (61.2) | 39 (61.9) | | | A little=1, n (%) | 28 (21.4) | 28 (21.7) | 11 (17.5) | | | Moderately=2, n (%) | 16 (12.2) | 9 (7.0) | 5 (7.9) | | | A great deal=3, n (%) | 3 (2.3) | 11 (8.5) | 8 (12.7) | | | Completely=4, n (%) | 1 (0.8) | 2 (1.6) | 0 (0.0) | | Abbreviations: AAPPO, Alopecia Areata Patient Priority Outcomes; AL, Activity limitations; SD, Standard deviation. AL domain scores generally improved up to Week 48 for all 50 mg groups but slightly worsened after Week 24 for the 10-mg group (Figure [1\)](#page-3-0). Significant improvements versus the 10-mg group were observed at Week 40 (LSM difference from 10-mg: 200/50-mg subgroup [−0.21; 95% CI, −0.40 to −0.03; *p*=0.0251]) and Week 48 (combined 50-mg group [−0.17; 95% CI, −0.34 to −0.00; *p*=0.0469], 200/50-mg subgroup [−0.24; 95% CI, −0.42 to −0.05; *p*=0.0131]). The largest improvements for the 50-mg subgroup in comparison with the 10-mg group were observed at Week 48 (−0.11; 95% CI, −0.30 to 0.08), although the difference was not significant. The LSM CFBs were more improved for participants with baseline AL domain scores ≥1 than for the FAS (Figure [S1\)](#page-8-3). The largest CFBs occurred at Week 48 for all 50-mg groups (LSM: combined 50-mg group [−1.12; 95% CI, −1.31 to −0.92], 200/50-mg [−1.23; 95% CI, −1.50 to −0.95], 50-mg subgroup [−1.00; 95% CI, −1.28 to −0.72]), but the difference relative to the 10-mg group was only significant for the 200/50-mg subgroup at Week 40 (LSM difference from 10-mg group: −0.52; 95% CI, −0.99 to −0.05; *p*=0.0317). The proportion of participants with baseline AL item scores ≥2 who reported postbaseline scores <2 for items 9 through 11 started high (>42%) at Week 4 and generally increased up to Week 48 for all 50-mg groups (Figure [3](#page-6-0) and Table [S2](#page-8-3)). For all 50-mg groups, the greatest proportion of responders for item 9 (outdoor activities) was observed at Week 40, and for item 10 (exercise or physical activity) at Week 48. The greatest proportion of responders for item 11 (interactions with others) occurred for the 200/50-mg subgroup at Week 40 and for the combined 50-mg group and 50-mg subgroup at Week 48. Among the combined 50-mg group and the 200/50-mg subgroup responses, item 9 at Week 40 and item 11 at Weeks 40 and 48 were significantly different from the corresponding responses in the 10-mg group. While the results of the sensitivity analyses were more variable, the proportion of responders (participants with postbaseline item scores=0) still generally increased up to Week 48 for items 9 through 11 among all 50-mg groups (Table [S2](#page-8-3) and Figure [S3\)](#page-8-3). For item 11, only the combined 50-mg group at Week 48 had significant differences in the proportion of responders versus the 10-mg group. ## **4 | Discussion** In the current study, greater improvements in LSM CFBs in ES and AL domain scores were observed in the ritlecitinib 50-mg groups than the 10-mg group, particularly at Weeks 40 and 48. For ES scores, differences in improvement were observed in all 50-mg groups after Week 12, with significant differences starting at Week 34 (200/50-mg subgroup), when compared with the 10-mg group. For AL scores, differences in improvement in all 50-mg groups were seen after Week 24, with significant differences starting at Week 40 (200/50-mg subgroup). In sensitivity analyses, participants with baseline ES or AL burden scores ≥1 ![](https://assets.reachrx.ai/images/10.1111%E2%98%8Dijd.70035/_page_6_Figure_3.jpeg) **FIGURE 3** | In participants with baseline item scores ≥2, difference in the proportion of responders (postbaseline scores <2) in individual AAPPO AL items. AAPPO data were analyzed for all ALLEGRO-2b/3 treatment groups and across all timepoints, but only results from groups with the 50-mg maintenance dose and 10-mg (proxy for placebo) dose are shown. Analyses were conducted for participants with corresponding baseline item scores ≥2. The mean (dots) and 95% CIs (whiskers) are shown, and significant differences (*p*<0.05) in the proportion of responders compared with the 10-mg group are indicated by asterisks (\*). AAPPO, Alopecia Areata Patient Priority Outcomes; AL, Activity limitations; CI, Confidence interval; Rit, Ritlecitinib; QD, Once daily. generally had greater improvements in LSM CFBs than those with baseline scores ≥2, with significant differences at Week 40 for AL and Week 48 for ES, when the 50-mg groups were compared with the 10-mg group. The current recommendation for AAPPO domain scoring is to calculate the mean score across ES (items 5–8) and AL (items 9–11) [\[22](#page-8-0)]. While statistically significant differences across the domain scores were observed in this study, there is no published guidance on thresholds of meaningful within-patient change that can help interpret these differences [\[22](#page-8-0)]. Item-level analyses may improve understanding of how to interpret AAPPO questionnaire data. In this study of each ES and AL item, 50-mg groups generally had a larger proportion of responders through Week 48 than did the 10-mg group. The largest differences from 10-mg were observed for ES item 5 (self-consciousness) and ES item 6 (embarrassment), with significance noted as early as Week 18 for item 6 (200/50-mg subgroup). AL item-level scores at baseline started low (range 0.5–0.8), making it difficult to see improvements in AL. Still, differences from 10-mg were observed for AL item 11 (interactions with others), and significant differences appeared starting at Week 40 for both item 9 and item 11 (combined 50-mg group and 200/50-mg subgroup). While results of the sensitivity analyses were inconsistent, the proportion of responders (those with postbaseline item scores=0) also generally increased up to Week 48 for the 50-mg groups versus the 10-mg group. These results suggest that ritlecitinib indirectly improves ES and AL by stimulating hair regrowth and that the impact of hair regrowth may impact ES items before it impacts AL items. Understanding the ES and AL caused by AA may help inform treatment decisions. Currently, patients with AA have two approved treatment options for severe AA in the United States, the European Union, and other parts of the world [\[26](#page-8-4)]; baricitinib is a Janus kinase (JAK)1 and JAK2 inhibitor indicated for adult patients [\[27, 28\]](#page-8-5), and ritlecitinib is a dual inhibitor of JAK3 and JAK5 members of the tyrosine kinase expressed in hepatocellular carcinoma (TEC) family indicated for adult and adolescent patients [\[14, 29\]](#page-8-6). Both baricitinib and ritlecitinib demonstrated clinically meaningful improvements in hair regrowth for patients with AA [[8, 30](#page-7-3)]. However, there is limited information available on the relationship between hair regrowth with ritlecitinib therapy and the psychological burden of AA. In ALLEGRO-2b/3, there were no psychosocial improvements with ritlecitinib therapy versus placebo by Week 24 [\[23\]](#page-8-1), despite participants experiencing significant hair regrowth (SALT scores ≤20) [[8\]](#page-7-3). It might take time for patients with AA to adjust to their new state of hair regrowth, especially when patients in ALLEGRO-2b/3 had a current episode of hair loss lasting an average of approximately 3 years at baseline [\[8, 31](#page-7-3)]. The results of this study suggest that a longer follow-up period may be needed to observe downstream psychosocial improvement following effective treatment. This study was limited by the constraints of the ALLEGRO-2b/3 trial [\[8\]](#page-7-3). As such, these analyses excluded participants with <50% scalp hair loss and those with duration of current AA episode longer than 10 years at baseline. Thus, it is possible that baseline burden, and therefore improvements from baseline, may differ among patients who have had AA for many years. Additionally, limited sample sizes restricted overall statistical power and made analyses of key subgroups unfeasible (e.g., different age groups; patients with AT or AU, who may have differences in response rates [[8, 22\]](#page-7-3)). Due to limited sample sizes, a combined 50-mg group was included in this study. Results of the combined 50-mg group could have been impacted by the 200-mg 4-week loading dose, though scores of individual 50 mg and 200/50-mg subgroups generally improved up to Week 48. Despite these limitations, randomization was maintained throughout this study, and findings presented here complement those of the primary ALLEGRO-2b/3 trial [\[8](#page-7-3)]. ### **5 | Conclusions** By Week 48, ALLEGRO-2b/3 participants reported greater improvements in ES and AL due to hair loss with the 50-mg ritlecitinib QD maintenance dose (+/−200-mg 4-week loading dose) than with the subtherapeutic 10-mg QD ritlecitinib dose. Overall, these findings show item-level AAPPO differences and may demonstrate improvements in psychosocial burden following hair regrowth with ritlecitinib. #### **Acknowledgments** The authors thank Lacey R. Lopez, PhD, and Gabrielle Dardis, PhD, of RTI Health Solutions for medical writing assistance. Part of this work was presented as a poster at Maui Derm from January 22 to 26 2024, in Wailea, Hawaii, United States. Pfizer Inc. provided the financial support for the study. RTI Health Solutions, an independent nonprofit research organization, received funding under a research contract with Pfizer Inc. to conduct this study and provide publication support in the form of manuscript writing, styling, and submission. ### **Ethics Statement** This was a secondary analysis of deidentified data from the ALLEGRO-2b/3 trial (NCT03732807, which obtained institutional review board/ethics committee approval and written consent for each participant). This current study did not collect or use personal identifying information, so institutional board review was not required. ### **Conflicts of Interest** E.H.L. is an employee of Pfizer Inc. and holds shares and/or stock options in the company. B.S., D.K., and C.C. are full-time employees of RTI Health Solutions, an independent nonprofit research organization, which was retained by Pfizer Inc. to conduct the research that is the subject of this manuscript. A.M. has served as secretary/treasurer for the Medical Dermatology Society and has received consulting fees from hims & hers (holds stock or stock options), AbbVie, Apogee, ACOM, Equillium, ASLAN, Boehringer Ingelheim, Figure 1, and Olaplex. B.K. has received fees from and/or is a clinical trial investigator for Aclaris, Arena Pharmaceuticals, Bristol Meyers Squibb, Celgene, Concert Pharmaceuticals Inc., Dermavant, Eli Lilly and Company, Pfizer Inc., Regeneron, Sanofi Genzyme, TWi Biotechnology Inc., and Viela Bio. R.S. declares no conflicts of interest. N.M. has received fees from and/or held a leadership/advisory position for Eli Lilly and Company, Pfizer Inc., AbbVie, Sun Pharma, L'Oréal, American Hair Research, and Nutrafol. K.A.H. was a paid consultant for Pfizer Inc. during the period in which the work for this manuscript was conducted; the author is no longer affiliated with the company. ### **Data Availability Statement** Upon request, and subject to review, Pfizer will provide the data that support the findings of this study. Subject to certain criteria, conditions and exceptions, Pfizer may also provide access to the related individual deidentified participant data. See [https://www.pfizer.com/](https://www.pfizer.com/science/clinical%E2%80%90trials/trial%E2%80%90data%E2%80%90and%E2%80%90results) [science/clinical-trials/trial-data-and-results](https://www.pfizer.com/science/clinical%E2%80%90trials/trial%E2%80%90data%E2%80%90and%E2%80%90results) for more information. ### **References** 1. A. Gilhar, A. Etzioni, and R. Paus, "Alopecia Areata," *New England Journal of Medicine* 366, no. 16 (2012): 1515–1525, [https://doi.org/10.](https://doi.org/10.1056/NEJMra1103442) [1056/NEJMra1103442](https://doi.org/10.1056/NEJMra1103442). 2. C. H. Pratt, L. E. King, Jr., A. G. Messenger, A. M. Christiano, and J. P. Sundberg, "Alopecia Areata," *Nature Reviews Disease Primers* 3 (2017): 17011, [https://doi.org/10.1038/nrdp.2017.11.](https://doi.org/10.1038/nrdp.2017.11) 3. H. H. Lee, E. Gwillim, K. R. Patel, et al., "Epidemiology of Alopecia Areata, Ophiasis, Totalis, and Universalis: A Systematic Review and Meta-Analysis," *Journal of the American Academy of Dermatology* 82, no. 3 (2020): 675–682, [https://doi.org/10.1016/j.jaad.2019.08.032.](https://doi.org/10.1016/j.jaad.2019.08.032) 4. L. Alhanshali, M. G. Buontempo, K. I. Lo Sicco, and J. Shapiro, "Alopecia Areata: Burden of Disease, Approach to Treatment, and Current Unmet Needs," *Clinical, Cosmetic and Investigational Dermatology* 16 (2023): 803–820, [https://doi.org/10.2147/ccid.S376096.](https://doi.org/10.2147/ccid.S376096) 5. L. C. Strazzulla, E. H. C. Wang, L. Avila, et al., "Alopecia Areata: Disease Characteristics, Clinical Evaluation, and New Perspectives on Pathogenesis," *Journal of the American Academy of Dermatology* 78, no. 1 (2018): 1–12, . 6. A. Tosti, S. Bellavista, and M. Iorizzo, "Alopecia Areata: A Long Term Follow-Up Study of 191 Patients," *Journal of the American Academy of Dermatology* 55, no. 3 (2006): 438–441, [https://doi.org/10.1016/j.jaad.](https://doi.org/10.1016/j.jaad.2006.05.008) [2006.05.008.](https://doi.org/10.1016/j.jaad.2006.05.008) 7. S. A. Walker and S. Rothman, "A Statistical Study and Consideration of Endocrine Influences," *Journal of Investigative Dermatology* 14, no. 6 (1950): 403–413, . 8. B. King, X. Zhang, W. G. Harcha, et al., "Efficacy and Safety of Ritlecitinib in Adults and Adolescents With Alopecia Areata: A Randomised, Double-Blind, Multicentre, Phase 2b-3 Trial," *Lancet* 401, no. 10387 (2023): 1518–1529, [https://doi.org/10.1016/s0140-6736\(23\)00222-2](https://doi.org/10.1016/s0140-6736(23)00222-2). 9. A. Muntyanu, S. Gabrielli, J. Donovan, et al., "The Burden of Alopecia Areata: A Scoping Review Focusing on Quality of Life, Mental Health and Work Productivity," *Journal of the European Academy of Dermatology and Venereology* 37 (2023): 1490–1520, [https://doi.org/10.](https://doi.org/10.1111/jdv.18926) [1111/jdv.18926](https://doi.org/10.1111/jdv.18926). 10. L. J. Burns, N. Mesinkovska, D. Kranz, A. Ellison, and M. M. Senna, "Cumulative Life Course Impairment of Alopecia Areata," *International Journal of Trichology* 12, no. 5 (2020): 197–204, [https://doi.org/](https://doi.org/10.4103/ijt.ijt_99_20) [10.4103/ijt.ijt\\_99\\_20.](https://doi.org/10.4103/ijt.ijt_99_20) 11. S. J. Li, K. P. Huang, C. Joyce, and A. Mostaghimi, "The Impact of Alopecia Areata on Sexual Quality of Life," *International Journal of Trichology* 10, no. 6 (2018): 271–274, [https://doi.org/10.4103/ijt.ijt\\_](https://doi.org/10.4103/ijt.ijt_93_18) [93\\_18.](https://doi.org/10.4103/ijt.ijt_93_18) 12. K. Gandhi, M. E. Shy, M. Ray, M. Fridman, S. Vaghela, and A. Mostaghimi, "The Association of Alopecia Areata-Related Emotional Symptoms With Work Productivity and Daily Activity Among Patients With Alopecia Areata," *Dermatol Ther (Heidelb)* 13, no. 1 (2023): 285– 298, [https://doi.org/10.1007/s13555-022-00864-1.](https://doi.org/10.1007/s13555-022-00864-1) 13. A. Mostaghimi, L. Napatalung, V. Sikirica, et al., "Patient Perspectives of the Social, Emotional and Functional Impact of Alopecia Areata: A Systematic Literature Review," *Dermatol Ther (Heidelb)* 11, no. 3 (2021): 867–883, [https://doi.org/10.1007/s13555-021-00512-0.](https://doi.org/10.1007/s13555-021-00512-0) 14. Pfizer Laboratories Division of Pfizer Inc., "LITFULO-Ritlecitinib Capsule Prescribing Information," (2023), [https://labeling.pfizer.com/](https://labeling.pfizer.com/ShowLabeling.aspx?id=19638) [ShowLabeling.aspx?id=19638.](https://labeling.pfizer.com/ShowLabeling.aspx?id=19638) 15. H. A. Blair, "Ritlecitinib: First Approval," *Drugs* 83, no. 14 (2023): 1315–1321,. 16. European Medicines Agency (EMA), "Litfulo (Ritlecitinib)," (2023), [https://www.ema.europa.eu/en/medicines/human/EPAR/litfulo.](https://www.ema.europa.eu/en/medicines/human/EPAR/litfulo) 17. N. Mesinkovska, B. King, P. Mirmirani, J. Ko, and J. Cassella, "Burden of Illness in Alopecia Areata: A Cross-Sectional Online Survey Study," *Journal of Investigative Dermatology Symposium Proceedings* 20, no. 1 (2020): S62–S68,. 18. P. Tucker, "Bald Is Beautiful?: The Psychosocial Impact of Alopecia Areata," *Journal of Health Psychology* 14, no. 1 (2009): 142–151, [https://](https://doi.org/10.1177/1359105308097954) [doi.org/10.1177/1359105308097954](https://doi.org/10.1177/1359105308097954). 19. L. H. Wang, S. H. Ma, Y. H. Tai, et al., "Increased Risk of Suicide Attempt in Patients With Alopecia Areata: A Nationwide Population-Based Cohort Study," *Dermatology* 239 (2023): 712–719, [https://doi.org/](https://doi.org/10.1159/000530076) [10.1159/000530076](https://doi.org/10.1159/000530076). 20. A. Creadore, P. Manjaly, S. J. Li, et al., "Evaluation of Stigma Toward Individuals With Alopecia," *JAMA Dermatology* 157, no. 4 (2021): 392–398, . 21. N. Mesinkovska, B. Craiglow, S. G. Ball, et al., "The Invisible Impact of a Visible Disease: Psychosocial Impact of Alopecia Areata," *Dermatol Ther (Heidelb)* 13, no. 7 (2023): 1503–1515, [https://doi.org/10.1007/s1355](https://doi.org/10.1007/s13555-023-00941-z) [5-023-00941-z.](https://doi.org/10.1007/s13555-023-00941-z) 22. K. W. Wyrwich, R. Winnette, R. Bender, et al., "Validation of the Alopecia Areata Patient Priority Outcomes (AAPPO) Questionnaire in Adults and Adolescents With Alopecia Areata," *Dermatol Ther (Heidelb)* 12, no. 1 (2022): 149–166, [https://doi.org/10.1007/s13555-021-00648-z.](https://doi.org/10.1007/s13555-021-00648-z) 23. R. Sinclair, N. Mesinkovska, and D. Mitra, "33280 Improvement in Patient-Reported Hair Loss Outcome Measures in Patients With Alopecia Areata Treated With Ritlecitinib: 48-Week Results From the ALLE-GRO Phase 2b/3 Randomized, Double-Blind, Placebo-Controlled Trial," *Journal of the American Academy of Dermatology* 87, no. 3 (2022): AB69. 24. E. H. Law, B. Sherif, N. J. Williams, et al., "Improvements in Patient-Reported Outcomes Based on Scalp Hair Regrowth Among Patients With Alopecia Areata: Analysis of the ALLEGRO 2b/3 Trial," Paper Presented at: 31st European Academy of Dermatology & Venereology (EADV) Congress (2022). 25. R. Winnette, S. Martin, N. Harris, and L. S. Deal, "Development of the Alopecia Areata Patient Priority Outcomes Instrument: A Qualitative Study," *Dermatol Ther (Heidelb)* 11, no. 2 (2021): 599–613, [https://](https://doi.org/10.1007/s13555-021-00508-w) [doi.org/10.1007/s13555-021-00508-w.](https://doi.org/10.1007/s13555-021-00508-w) 26. L. Rudnicka, M. Arenbergerova, R. Grimalt, et al., "European Expert Consensus Statement on the Systemic Treatment of Alopecia Areata," *Journal of the European Academy of Dermatology and Venereology* 38, no. 4 (2024): 687–694, . 27. US Food and Drug Administration (FDA), "FDA Approves First Systemic Treatment for Alopecia Areata," (2022), [https://www.fda.gov/](https://www.fda.gov/news-events/press-announcements/fda-approves-first-systemic-treatment-alopecia-areata) [news-events/press-announcements/fda-approves-first-systemic-treat](https://www.fda.gov/news-events/press-announcements/fda-approves-first-systemic-treatment-alopecia-areata) [ment-alopecia-areata.](https://www.fda.gov/news-events/press-announcements/fda-approves-first-systemic-treatment-alopecia-areata) 28. B. King, A. Mostaghimi, Y. Shimomura, et al., "Integrated Safety Analysis of Baricitinib in Adults With Severe Alopecia Areata From Two Randomized Clinical Trials," *British Journal of Dermatology* 188, no. 2 (2023): 218–227, [https://doi.org/10.1093/bjd/ljac059.](https://doi.org/10.1093/bjd/ljac059) 29. H. Xu, M. I. Jesson, U. I. Seneviratne, et al., "PF-06651600, a Dual JAK3/TEC Family Kinase Inhibitor," *ACS Chemical Biology* 14, no. 6 (2019): 1235–1242, [https://doi.org/10.1021/acschembio.9b00188.](https://doi.org/10.1021/acschembio.9b00188) 30. B. King, M. Ohyama, O. Kwon, et al., "Two Phase 3 Trials of Baricitinib for Alopecia Areata," *New England Journal of Medicine* 386, no. 18 (2022): 1687–1699, [https://doi.org/10.1056/NEJMoa2110343.](https://doi.org/10.1056/NEJMoa2110343) 31. B. King, X. Zhang, W. G. Harcha, et al., "A Plain Language Summary on Ritlecitinib Treatment for Adults and Adolescents With Alopecia Areata," *Immunotherapy* 15 (2023): 1093–1103, [https://doi.org/10.2217/](https://doi.org/10.2217/imt-2023-0069) [imt-2023-0069.](https://doi.org/10.2217/imt-2023-0069) #### **Supporting Information** Additional supporting information can be found online in the Supporting Information section. **Data S1:** ijd70035-sup-0001-Supinfo. docx.