Characterizing the relationships between patient‐reported outcomes and clinician assessments of alopecia areata in a phase 2a randomized trial of ritlecitinib and brepocitinib

Abstract

Background The phase 2a ALLEGRO trial (NCT02974868) investigated the safety and efficacy of ritlecitinib (PF-06651600) and brepocitinib (PF-06700841) in adults with alopecia areata. No randomized controlled trial for alopecia areata has evaluated correlations between clinician-assessed hair loss and patient-reported outcomes. Objectives Report scores from the Alopecia Areata Symptom Impact Scale (AASIS; a patient-reported outcome tool) and explore the relationships of those scores with clinician-assessed Severity of Alopecia Tool (SALT) scores at baseline and week 24 of the ALLEGRO trial. Methods Adults with alopecia areata were randomized to ritlecitinib (n = 48), brepocitinib (n = 47) or placebo (n = 47). After 24 weeks, the mixed-effects model with repeated measures was used to calculate the active treatment groups' AASIS score least-squares mean differences. Relationships between AASIS and SALT scores at baseline and week 24 were evaluated by Pearson's correlation coefficients using pooled data. Results Baseline AASIS and SALT scores were similar among treatment groups. Both active treatment groups reported significant improvements in AASIS scores at week 24 (least-squares mean differences vs. placebo for ritlecitinib, À0.8 to À2.3; brepocitinib, À0.9 to À3.7; P < 0.05 for all). At week 24, the mean SALT scores (standard deviation) improved compared with baseline [ritlecitinib, 54.4 (40.3) vs. 89.4 (15.8); brepocitinib, 31.9 (35.7) vs. 86.4 (18.1)]. The correlation coefficients between AASIS global and subscale scores and SALT scores at week 24 ranged from 0.34 to 0.58; P < 0.05 for all. Conclusions Patients randomized to ritlecitinib or brepocitinib reported significantly improved AASIS and SALT scores at week 24 of the ALLEGRO trial compared to placebo. At week 24, medium-to-large correlations can be seen between AASIS global and subscale scores and SALT scores. Our experience with AASIS instrument highlighted several aspects that suggest new patient-reported outcome tools are needed to accurately assess patients' relevant alopecia areata related signs, symptoms and daily functioning.

Janus Kinase Inhibitors in the Treatment of Alopecia Areata

“…TYK2 is an important regulator of IFNα, IFNγ, IL12/23, IL-6 and IL-10 signalling pathways (Winnette et al, 2022). These cytokines are crucial in the pathogenesis of several autoimmune diseases, including chronic plague psoriasis and alopecia areata.…”

Assessing the efficacy of selective JAK inhibitors for alopecia areata with a patient‐centered approach

“…2 Although there have been interventional trials that have reported AASIS data, this is the first study that correlates AASIS scores with SALT scores. 2 The authors in this study describe their experience using the AASIS score, its limitations such as the ambiguity in the wording of some of the AASIS items, that imply a need to find newer tools to accurately assess patients' relevant AA-related signs, symptoms, and daily functioning.…”

“…The original article published by Dr. Winnette et al in this issue evaluated the relationship between clinician-assessed hair loss with the SALT score and patient-reported outcomes with the Alopecia Areata Symptom Impact Scale (AASIS) tool in patients after 24 weeks of treatment with ritlecitinib and brepocitinib. 2 These authors found a strong positive correlation between SALT scores and AASIS scores after 24-week treatment; in particular, patients with ritlecitinib demonstrated a significant improvement in the patient-reported outcome of "itchy or painful skin", while patients that received brepocitinib, improved in the "interaction with others" and "sexual relationship" items. 2 Although there have been interventional trials that have reported AASIS data, this is the first study that correlates AASIS scores with SALT scores.…”

“…2 These authors found a strong positive correlation between SALT scores and AASIS scores after 24-week treatment; in particular, patients with ritlecitinib demonstrated a significant improvement in the patient-reported outcome of "itchy or painful skin", while patients that received brepocitinib, improved in the "interaction with others" and "sexual relationship" items. 2 Although there have been interventional trials that have reported AASIS data, this is the first study that correlates AASIS scores with SALT scores. 2 The authors in this study describe their experience using the AASIS score, its limitations such as the ambiguity in the wording of some of the AASIS items, that imply a need to find newer tools to accurately assess patients' relevant AA-related signs, symptoms, and daily functioning.…”

“…1 Now, even if we have more insight in the autoimmune nature of AA, this disease is frequently associated with a significant impact on patients' health-related quality of life and adverse psychological effects, such as anxiety and depression. 2 AA affects up to 2% of the population worldwide at some point during their lifetime. 3 Currently, there are no treatments approved by the U.S. Food and Drug Administration (FDA) specific for AA, and there are few effective therapeutic options for widespread and persistent illness.…”