Journal Logo

STUDIES

Patient-Reported Symptoms and Disease Impacts in Adults With Moderate-to-Severe Atopic Dermatitis: Results From a Phase 2b Study With Abrocitinib

Simpson, Eric L. MD; Wollenberg, Andreas MD; Bissonnette, Robert MD; Silverberg, Jonathan I. MD, PhD, MPH§; Papacharalambous, Jocelyne MD; Zhu, Linda MD, PhD; Zhang, Weidong PhD#; Beebe, Jean S. PhD#; Vincent, Michael MD, PhD#; Peeva, Elena MD#; Bushmakin, Andrew G. MS; Cappelleri, Joseph C. PhD; Chen, Linda MPH∗∗; Sikirica, Vanja PharmD, MPH; Xenakis, Jason BS∗∗

Author Information
doi: 10.1097/DER.0000000000000725

Abstract

Atopic dermatitis (AD) is a chronic inflammatory condition affecting 10% of adults or less and 10% to 20% of children worldwide and is associated with high symptom and comorbidity burden.1–3 Moderate-to-severe AD profoundly impacts patient health-related quality of life (HRQoL) and imposes significant burdens on patients, their finances, and society.4–6

For many adults with moderate-to-severe disease, AD is often inadequately controlled by traditional topical or systemic treatments, underscoring a need for novel therapies.7 Abrocitinib (PF-04965842) is an oral Janus kinase 1 selective inhibitor under investigation for the treatment of AD.8,9 Results from a phase 2b study in adults with moderate-to-severe AD (ClinicalTrials.gov NCT02780167) demonstrated the efficacy and safety of abrocitinib in reducing signs/symptoms of AD as measured by clinician-evaluated end points.10

Clinician-evaluated end points are used in drug development, but they may underestimate disease severity and overestimate treatment response compared with patient-reported assessments.11 Furthermore, clinician-evaluated end points may not be aligned with patient treatment expectations.12 Patient-reported outcome (PRO) measures are increasingly used to evaluate new treatments or compare the efficacy of different treatments.13 Accordingly, the Harmonising Outcome Measures for Eczema initiative recommends inclusion of patient-reported symptoms, HRQoL, clinician-evaluated end points, and long-term disease control as core outcomes in AD clinical trials.14 This report evaluates the effect of abrocitinib on PRO measures in the phase 2b study and uses a novel PRO—the Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD) daily symptom diary—a scale developed in accordance with the US Food and Drug Administration's PRO guidance.15

METHODS

Study Design, Treatment, and Patients

A phase 2b, multicenter, randomized, double-blind, parallel-group study was performed to assess the efficacy and safety of abrocitinib in patients aged 18 to 75 years with moderate-to-severe AD per the Investigator’s Global Assessment (IGA) scale. Patients were randomly assigned 1:1:1:1:1 to receive abrocitinib (200, 100, 30, or 10 mg) or placebo once daily for 12 weeks, followed by 4 weeks of treatment-free follow-up. Full inclusion/exclusion criteria and washout periods have been published.10 Permitted concomitant AD medications were oral antihistamines and sponsor-provided emollient and sunscreen. Prohibited therapies included oral immunosuppressants, phototherapy, and topical treatments (eg, corticosteroids, calcineurin inhibitors). The study protocol and informed consent documents were reviewed and approved by the institutional review board and/or independent ethics committee at each of the investigational sites. All patients provided written informed consent. The study was conducted in accordance with the ethical principles of the Declaration of Helsinki, the International Council for Harmonisation Good Clinical Practice guidelines, and all local regulatory requirements.

Patient-Reported Outcome Assessments/End Points

Patient-reported outcome measures included pruritus numeric rating scale (NRS [average]), Patient Global Assessment (PtGA), Patient-Oriented Eczema Measure (POEM), PSAAD, Dermatology Life Quality Index (DLQI), and Hospital Anxiety and Depression Scale (HADS, Supplemental Table 1 https://links.lww.com/DER/A53).15–19 Patient-reported outcomes were measured at in-clinic visits during treatment and follow-up, except for PSAAD (completed daily via electronic diary by patients enrolled at US sites beginning 3 days before the first dose of study drug) and pruritus NRS (assessed daily from days 1–15 and subsequently at in-clinic visits).

Prespecified secondary PRO analyses were changes from baseline in pruritus NRS (average), DLQI, POEM, and HADS and proportion of patients with PtGA of clear (0)/almost clear (1) with 2-point or greater improvement from baseline (ie, PtGA response) at all scheduled time points. The prespecified exploratory PRO end point was change from baseline in weekly average of daily PSAAD total scores at all scheduled time points. Baseline PSAAD total score was defined as an average daily score of the 3 days before the first dose of study drug. For all other PROs, baseline scores were defined as the score before the first dose of study drug.

Responder Analyses

To evaluate the clinical significance of PRO score changes with abrocitinib treatment, proportions of patients achieving predefined responder definitions were calculated for POEM (≥3.4-point improvement), DLQI (≥4-point improvement), and PSAAD (≥1.0-point change).15,20,21 For pruritus NRS, responders were predefined as patients with a baseline NRS score of 4 or greater who achieved 4-point or greater improvement.22 The HADS responders were predefined as patients with “probable” anxiety or depression at baseline (a HADS subscale score ≥11) who achieved a HADS score of less than 11.19,23 The proportion of the patients with “likely” anxiety or depression (a HADS subscale score ≥8) who achieved a HADS score of less than 8 was also calculated.19

Statistics

The safety analysis set included all randomized patients who received 1 dose or more of the study drug. Safety and primary efficacy (non-PRO outcomes) have been published previously.10 Analyses for PRO end points were performed on the full analysis set (FAS), which includes all randomized patients receiving 1 or more doses of study drug except for 4 patients from 1 site. Patients from this site were excluded before unmasking the database because of major protocol deviations.10 The analyses were based on observed cases, except for PSAAD end points, which were performed only for FAS patients enrolled at US sites. Patients who discontinued treatment or received prohibited systemic or topical medication for AD before week 12 were considered nonresponders and were discontinued from treatment. Comparisons were tested at a significance level of 0.05 (2-sided). Multiplicity adjustment was not performed. All analyses were performed in SAS 9.4 (SAS Institute, Inc, Cary, NC).

For the continuous PRO end points (mean change from baseline and/or percentage change from baseline in pruritus NRS, PSAAD, PtGA, DLQI, POEM, and HADS), the primary analysis was performed using the mixed-effects model repeated measure (MMRM), assuming missing at random (MAR). Although it is not possible to definitively demonstrate MAR assumption, this seemed to be a reasonable approximation based on the pattern of discontinuations and sensitivity analysis. The binary PRO end points (eg, proportion of subjects with PtGA response) were analyzed using a generalized linear mixed model (GLMM), assuming MAR and logistic regression models with nonresponder imputation. The GLMM and MMRM included time, treatment, and treatment-by-time interaction as fixed effects and baseline value as a covariate. An unstructured variance-covariance matrix was used to model within-subject variability. Missing values were handled by the GLMM and MMRM without imputation. Because the GLMM did not converge for some binary end points, only logistic regression results are reported.

Associations between PRO end points (pruritus NRS percentage change from baseline, the proportion of the patients who achieved pruritus NRS response, PtGA response, POEM change from baseline, PSAAD percentage change from baseline, DLQI percentage change from baseline, HADS-anxiety, and HADS-depression) and clinical response (IGA response, [defined as clear {0} or almost clear {1} with ≥2-grade improvement] and Eczema Area and Severity Index percentage change from baseline) were analyzed using Pearson correlations.

RESULTS

Demographics and Baseline Disease Characteristics

In total, 267 patients from 58 centers in Australia, Canada, Germany, Hungary, and the United States were randomly assigned and treated and included in the safety analysis set; 263 were included in the FAS and this analysis of PRO end points. Primary efficacy, safety, and patient disposition results have been previously published.10 Baseline disease characteristics were similar across treatment groups (Table 1). As determined by IGA, 57.8% of the patients had moderate AD and 42.2% had severe AD, and the mean SCORing Atopic Dermatitis was 64.2. All 119 US patients were included in the PSAAD exploratory end point; 58.8% had moderate AD, and 41.2% had severe AD (Supplemental Table 2 https://links.lww.com/DER/A53).

Table 1 - Patient Demographics and Disease Characteristics at Randomization
Safety Analysis Set Placebo (n = 56) 10 mg (n = 49) 30 mg (n = 51) 100 mg (n = 56) 200 mg (n = 55)
Age, mean (SD), y 42.6 (15.1) 44.3 (15.9) 37.6 (15.9) 41.1 (15.6) 38.7 (17.6)
Female, n (%) 35 (62.5) 28 (57.1) 29 (56.9) 25 (44.6) 27 (49.1)
Race, n (%)
 White 40 (71.4) 38 (77.6) 39 (76.5) 40 (71.4) 37 (67.3)
 Black 10 (17.9) 5 (10.2) 4 (7.8) 7 (12.5) 13 (23.6)
 Asian 4 (7.1) 5 (10.2) 5 (9.8) 8 (14.3) 5 (9.1)
 Other 2 (3.6) 1 (2.0) 3 (5.9) 1 (1.8) 0
Disease duration, median (range), y 25.6 (1.1–67.1) 30.2 (1.8–60.6) 20.5 (1.2–66.6) 23.8 (1.1–66.7) 19.6 (1.9–68.8)
FAS Placebo (n = 55) 10 mg (n = 49) 30 mg (n = 50) 100 mg (n = 55) 200 mg (n = 54)
SCORAD, mean (SD) 65.0 (12.1) 65.3 (13.2) 62.4 (13.0) 65.4 (13.7) 62.7 (13.8)
EASI, mean (SD) 25.4 (12.9) 28.1 (13.1) 22.1 (10.7) 26.7 (11.8) 24.6 (13.5)
%BSA, mean (SD) 40.1 (22.3) 44.2 (22.7) 34.1 (20.8) 41.9 (22.3) 38.0 (23.3)
IGA, n (%)
 Moderate 34 (61.8) 27 (55.1) 28 (56.0) 29 (52.7) 34 (63.0)
 Severe 21 (38.2) 22 (44.9) 22 (44.0) 26 (47.3) 20 (37.0)
Pruritus NRS, mean (SD) 7.6 (1.8) 7.6 (1.7) 7.6 (1.9) 7.4 (2.2) 6.9 (2.7)
 Pruritus NRS score ≥4, n (%) 51 (92.7) 45 (91.8) 47 (94.0) 51 (92.7) 46 (85.2)
PtGA, n (%)
 Almost clear (score of 1) 1 (1.9) 0 0 1 (1.9) 0
 Mild (score of 2) 5 (9.3) 2 (4.1) 4 (8.2) 6 (11.1) 4 (7.5)
 Moderate (score of 3) 21 (38.9) 16 (32.7) 20 (40.8) 14 (25.9) 18 (34.0)
 Severe (score of 4) 27 (50.0) 31 (63.3) 25 (51.0) 33 (61.1) 31 (58.5)
DLQI, mean (SD) 13.9 (7.3) 14.0 (7.5) 13.7 (6.7) 15.5 (8.0) 12.9 (7.4)
POEM, mean (SD) 21.1 (5.9) 21.7 (5.2) 20.3 (6.2) 20.3 (6.2) 20.5 (5.9)
HADS-depression, mean (SD) 5.3 (4.2) 4.7 (4.6) 3.8 (3.7) 5.5 (4.8) 4.5 (4.0)
HADS-depression score ≥8, n (%) 13 (23.6) 10 (20.4) 9 (18.0) 14 (25.5) 12 (22.2)
HADS-depression score ≥11, n (%) 9 (16.4) 5 (10.2) 4 (8.0) 8 (14.5) 5 (9.3)
HADS-anxiety, mean (SD) 8.2 (4.1) 6.8 (4.1) 5.9 (4.6) 7.9 (4.7) 6.2 (4.3)
HADS-anxiety score ≥8, n (%) 26 (47.3) 18 (36.7) 14 (28.0) 24 (43.6) 21 (38.9)
HADS-anxiety score ≥11, n (%) 14 (25.5) 9 (18.4) 5 (10.0) 14 (25.5) 8 (14.8)
%BSA, percentage of treatable body surface area; DLQI, Dermatology Life Quality Index; EASI, Eczema Area and Severity Index; FAS, full analysis set; HADS, Hospital Anxiety and Depression Scale; IGA, Investigator Global Assessment; NRS, numeric rating scale; POEM, Patient-Oriented Eczema Measure; PtGA, Patient Global Assessment; SCORAD, SCORing Atopic Dermatitis.

Patient-Reported AD Symptoms/Severity

Pruritus NRS

Rapid improvement in pruritus NRS was observed for the 200- and 100-mg groups and maintained through the 12-week treatment period (Fig. 1A). Significant differences from placebo in mean change from baseline in pruritus NRS were observed 1 day after the first dose (day 2) in the 200-mg group (−1.25 vs −0.07, P < 0.01) and 2 days after the first dose (day 3) in the 100-mg group (−1.18 vs −0.21, P < 0.05). Greater percentage reductions in pruritus NRS from baseline versus placebo were observed beginning at day 3 for the 200-mg group (−19.2% vs −1.5%, P < 0.05) and day 5 for the 100-mg group (−19.9% vs −3.2%, P < 0.05; Supplemental Fig. 1A https://links.lww.com/DER/A53).

F1
Figure 1:
Atopic dermatitis. Improvement in PROs measuring AD symptoms and severity at all scheduled time points. A, Least squares mean change from baseline in pruritus NRS. B, Proportion of the patients who achieved improvement in PtGA (PtGA score of clear [0] or almost clear [1] with ≥2-point improvement). C, Least squares mean change from baseline in POEM. D, Least squares mean of change from baseline in PSAAD. Data are shown as mean change or proportion of responders ± 90% CI. *P < 0.05 (200 mg vs placebo). # P < 0.05 (100 mg vs placebo). CI, confidence interval; NRS, numeric rating scale; POEM, Patient-Oriented Eczema Measure; PRO, patient-reported outcome; PSAAD, Pruritus and Symptoms Assessment for Atopic Dermatitis; PtGA, Patient Global Assessment.

Among patients with a pruritus NRS score of 4 or greater at baseline, greater proportions of responders were observed starting at day 2 for the 200-mg group (15.2% vs 2.0%, P < 0.05) and starting at day 5 for the 100-mg group (20.0% vs 2.0%, P < 0.05) compared with placebo. Significant differences continued to be observed for all subsequent time points through the end of treatment for both doses (Supplemental Fig. 2A https://links.lww.com/DER/A53).

Patient Global Assessment

Rapid, persistent improvements in PtGA were observed in the 200- and 100-mg groups and maintained through the end of treatment. Greater proportions of the patients achieved PtGA response in the 200-mg group compared with the placebo group starting at week 1 (16.7% vs 0%, P < 0.05) and in the 100-mg group starting at week 4 (22.2% vs 3.8%, P < 0.05; Fig. 1B). Significant differences in response rates continued to be observed in both dose groups at all subsequent time points until the end of treatment. At week 12, 51.9% and 25.9% of the patients were responders in the 200- and 100-mg groups, respectively, compared with 7.4% in the placebo group (P < 0.0001 and P < 0.05, respectively; Fig. 1B).

Patient-Oriented Eczema Measure

Significant, clinically meaningful improvements in POEM were observed starting at week 1 for the 200- and 100-mg groups and maintained at least through the end of treatment (Fig. 1C). Starting at week 1, improvement from baseline versus placebo in POEM score was observed in the 200-mg (−9.1 vs −0.9, P < 0.0001) and 100-mg (−4.0 vs −0.9, P < 0.0001) groups. Greater percentage improvements from baseline were observed beginning at week 1 for the 200-mg group (−45.5% vs −2.34%, P < 0.0001) and week 2 for the 100-mg group (−27.3% vs −10.5%, P < 0.05; Supplemental Fig. 1B https://links.lww.com/DER/A53). Beginning at week 1, greater proportions of the patients in the 200-mg (82.7% vs 18.9%, P < 0.0001) and 100-mg (46.3% vs 18.9%, P < 0.01) groups achieved response compared with placebo (Supplemental Fig. 2B https://links.lww.com/DER/A53).

Pruritus and Symptoms Assessment for Atopic Dermatitis

Greater changes from baseline in PSAAD total score versus placebo were observed by week 1 for the 200-mg group (−1.6 vs −0.3, P < 0.05) and week 2 for the 100-mg group (−1.8 vs −0.6, P < 0.05; Fig. 1D). Higher percentage improvements were observed by week 1 for the 200-mg group (−27.2% vs −3.0%, P < 0.05) and week 4 for the 100-mg group (−49.6% vs −16.9%, P < 0.05; Supplemental Fig. 1C https://links.lww.com/DER/A53). Greater proportions of the patients achieved clinically important response versus placebo starting at day 2 for the 200-mg and 100-mg groups and continued through week 2 (70.8% vs 34.6%, P < 0.05), week 4 (83.3% vs 50.0%, P < 0.05), and subsequent time points up to week 13 (except week 8) for the 200-mg group, as well as week 2 (65.0% vs 34.6%, P < 0.05), week 9 (71.4% vs 38.5%, P < 0.05), and subsequent time points up to week 12 for the 100-mg group (Supplemental Fig. 2C https://links.lww.com/DER/A53).15

Health-Related Quality of Life

Significant differences from placebo in change from baseline in DLQI score were evident at week 1 for the 200-mg (−6.7 vs −1.3, P < 0.0001) and 100-mg (−4.4 vs −1.3, P < 0.01) groups and continued through the end of treatment (Fig. 2). Greater percentage improvements versus placebo in DLQI score were observed starting at week 1 for the 200-mg group (−46.4% vs −3.2%, P < 0.05) and week 2 for the 100-mg group (−46.8% vs −13.8%, P < 0.01; Supplemental Fig. 3A https://links.lww.com/DER/A53). Significantly greater proportions of the patients achieved clinically important DLQI response by week 1 in the 200-mg (63.0% vs 32.1%, P < 0.001) and 100-mg (57.4% vs 32.1%, P < 0.05) groups compared with placebo (Fig. 3A).

F2
Figure 2:
Atopic dermatitis. Improvement in PRO measuring HRQoL. Least squares mean change from baseline in DLQI. Data are shown as mean change ± 90% CI. *P < 0.05 (200 mg vs placebo). # P < 0.05 (100 mg vs placebo). AD, atopic dermatitis; CI, confidence interval; DLQI, Dermatology Life Quality Index; PRO, patient-reported outcome.
F3
Figure 3:
Atopic dermatitis. Proportion of the patients achieving clinically meaningful improvement in PROs measuring HRQoL and psychological impact of AD. A, Proportion of the patients achieving a minimum clinically important difference in DLQI (≥4-point improvement). B, Proportion of the patients meeting responder criteria for HADS-depression (HADS-D, baseline HADS-D ≥11 achieving HADS-D <11). C, Proportion of the patients meeting responder criteria for HADS-anxiety (HADS-A, baseline HADS-A ≥11 achieving HADS-A <11). Data are shown as proportion of the patients (observed) ± 90% CI (estimate). *P < 0.05 (200 mg vs placebo). # P < 0.05 (100 mg vs placebo). AD, atopic dermatitis; CI, confidence interval; DLQI, Dermatology Life Quality Index; HADS-A/D, Hospital Anxiety and Depression Scale–anxiety/depression; PRO, patient-reported outcome.

Psychological Impact of AD

Among the patients with HADS data, significant improvements in symptoms of depression/anxiety compared with placebo were largely observed only in the 200-mg group (Supplemental Figs. 4A, B https://links.lww.com/DER/A53). Changes from baseline in HADS-depression score were observed for the 200-mg group at week 2 (−1.9 vs −0.4, P < 0.01), week 4 (−2.2 vs −0.4, P < 0.001), and week 8 (−1.9 vs −0.6, P < 0.01; Supplemental Fig. 4A https://links.lww.com/DER/A53), and larger percentage improvements were observed at week 1 (−17.2 vs 16.5, P < 0.05), week 2 (−47.5 vs −13.0, P < 0.05), week 4 (−47.27 vs −6.7, P < 0.05), and week 8 (−46.1 vs −2.8, P < 0.05; Supplemental Fig. 3B https://links.lww.com/DER/A53). Significant differences for the 200-mg group versus placebo in change from baseline HADS-anxiety score were observed at week 2 (−2.5 vs −1.3, P < 0.05) and week 8 (−2.7 vs −1.2, P < 0.05; Supplemental Fig. 4B https://links.lww.com/DER/A53), although the percentage changes from baseline were not significantly different from placebo at any time point (Supplemental Fig. 3C https://links.lww.com/DER/A53).

For HADS-depression, greater proportions of “probable” case responders compared with placebo were observed at week 2 for the 200-mg group (100% vs 22.2%, P < 0.05) and at no other week for any other group (Fig. 3B). For HADS-anxiety, greater proportions of “probable” case responders were observed in the 200-mg group compared with placebo starting at week 1 (87.5% vs 23.1%, P < 0.05) and continuing through week 8 (75.0% vs 21.4%, P < 0.05; Fig. 3C). A similar pattern was observed in patients with “likely” cases of anxiety or depression at baseline. Significantly higher proportions (P < 0.05) of the patients achieved HADS-depression score of less than 8 in the 200-mg group versus placebo at weeks 2 and 4 (Supplemental Fig. 5A https://links.lww.com/DER/A53). For HADS-anxiety, significantly larger proportions (P < 0.05) of the patients achieved HADS-anxiety score of less than 8 in the 200-mg group from weeks 2 through 12 and in the 100-mg group at weeks 8 and 12 (Supplemental Fig. 5B https://links.lww.com/DER/A53). All measured PRO end points significantly correlated with the primary and secondary clinical end points measured in the phase 2b study: IGA response and Eczema Area and Severity Index change from baseline (all P < 0.05; Supplemental Table 3 https://links.lww.com/DER/A53).

DISCUSSION

This study demonstrates that treatment with once-daily abrocitinib 200 or 100 mg results in rapid (2 days to 2 weeks), statistically significant, clinically relevant improvement that was maintained over a period of 12 weeks in patient-reported disease-specific symptoms and impacts in adults with moderate-to-severe AD.

Pruritus is the primary symptom of AD, with 87% of the patients or more reporting daily itch.24,25 In adults with moderate-to-severe AD, blistering, erythema, sleep disturbance, pain, and open sores/oozing were reported as the most burdensome symptoms.26 In the current study, abrocitinib rapidly and persistently alleviated patient-reported itch severity, as measured by the pruritus NRS, and resulted in improvement in other patient-reported symptoms, such as dryness, redness, flaking, discoloration, pain, bleeding, cracking, bumps, swelling, and weeping/oozing, as measured by the PSAAD and POEM. The efficacy of abrocitinib in alleviating itch and other symptoms is potentially mediated by inhibition of multiple Janus kinase 1–modulated cytokines, such as interleukin (IL)-31, IL-2, IL-4, and IL-13, all of which have been implicated in AD-associated pruritus.8,25,27–30 The mean pruritus NRS score increased above baseline after abrocitinib discontinuation, suggesting that patients might experience maximum benefit when abrocitinib is used without interruption.

Treatment benefits go beyond AD symptoms and have other meaningful impacts on patients' lives. Itch intensity correlates significantly with HRQoL and depression symptoms in adults31 and is possibly associated with poor sleep quality.32 Compared with US adults without AD, those with AD have reduced HRQoL and poorer mental health, the magnitude of which is associated with AD severity26 and inadequately controlled disease.7 In this study, PROs measured life-impact concepts, such as daily activities, personal relationships, symptoms and feelings, leisure activities, and work and school productivity via DLQI and more distal concepts from the core symptom of itch, such as sleep as measured by POEM. Treatment with abrocitinib 200 mg or 100 mg resulted in significant and clinically meaningful improvement in HRQoL beginning 1 week after treatment initiation. Significant, clinically meaningful reductions in depression and anxiety symptoms were noted in patients for abrocitinib 200 mg and 100 mg throughout the treatment period. Among the patients who “likely” had anxiety or depression at baseline, treatment with abrocitinib 200 mg led to approximately 50% to 60% no longer meeting this threshold by 12 weeks, emphasizing the broad improvements seen with abrocitinib—not only alleviating key signs and symptoms, but also improving downstream mental health comorbidities. However, significant differences from placebo in the 200-mg group in HADS-depression and HADS-anxiety subscale scores were not as consistently observed as differences with other outcomes reported in this analysis.

Although differences in study design, baseline severity, characteristics of the study population, and treatment duration limit direct comparisons, the reported mean and percentage improvements from baseline at week 12 in pruritus NRS, POEM, DLQI, and HADS scores observed in the 200-mg group were comparable with or numerically greater than those observed with the subcutaneous injection of dupilumab currently approved by the US Food and Drug Administration for moderate-to-severe AD.23 This highlights the potential of abrocitinib 200 mg to also provide clinically relevant outcomes for patients with moderate-to-severe AD with the convenience and flexibility of an oral therapy. Future trials comparing abrocitinib with dupilumab may inform therapeutic decision making when a systemic therapy is considered for AD.

This is the first report of clinical trial data using the validated PSAAD instrument, which was designed to capture symptoms considered most relevant by patients with AD.15 Patients exhibited rapid and lasting improvements in PSAAD total scores with abrocitinib treatment, suggesting that abrocitinib alleviates symptoms considered most important to patients with AD.

As with any study, there are limitations. This was a relatively small phase 2b study with a relatively short treatment duration for chronic disease. Nevertheless, numerous significant differences were seen within this small window of treatment. Results from ongoing phase 3 trials of abrocitinib will further elucidate the effect of abrocitinib on PRO measures. As the PSAAD symptom diary was implemented only at US study sites, PSAAD results may not reflect the global patient population. Except for HADS-anxiety/-depression subscales, this analysis did not compare individual items or domains within PRO instruments. Future work is needed to determine which symptoms and impacts are most improved with abrocitinib. Data from the ongoing phase 3 program will be critical to further characterize the safety profile and overall benefit-risk profile of abrocitinib.

In conclusion, treatment with abrocitinib 200 mg or 100 mg rapidly (2 days to 2 weeks) and significantly improved AD symptoms and impacts in adults with moderate-to-severe disease.

ACKNOWLEDGMENTS

Medical writing support under the guidance of the authors was provided by Madeline L. Pfau, PhD, Marianna Johnson, PhD, and Jennifer C. Jaworski, MS, at ApotheCom, San Francisco, CA, and was funded by Pfizer Inc, New York, NY, in accordance with Good Publication Practice (GPP3) guidelines (Ann Intern Med. 2015;163:461–464).

The affiliations for L.C., J.P., and W.Z. are provided for the time of research.

REFERENCES

1. Williams H, Flohr C. How epidemiology has challenged 3 prevailing concepts about atopic dermatitis. J Allergy Clin Immunol 2006;118(1):209–213.
2. Chiesa Fuxench ZC, Block JK, Boguniewicz M, et al. Atopic Dermatitis in America study: a cross-sectional study examining the prevalence and disease burden of atopic dermatitis in the US adult population. J Invest Dermatol 2019;139(3):583–590.
3. Wollenberg A, Oranje A, Deleuran M, et al. ETFAD/EADV Eczema Task Force 2015 position paper on diagnosis and treatment of atopic dermatitis in adult and paediatric patients. J Eur Acad Dermatol Venereol 2016;30(5):729–747.
4. Drucker AM, Wang AR, Li WQ, et al. The burden of atopic dermatitis: summary of a report for the National Eczema Association. J Invest Dermatol 2017;137(1):26–30.
5. Silverberg JI. Public health burden and epidemiology of atopic dermatitis. Dermatol Clin 2017;35(3):283–289.
6. Silverberg JI, Gelfand JM, Margolis DJ, et al. Health utility scores of atopic dermatitis in US adults. J Allergy Clin Immunol Pract 2019;7(4):1246–1252.e1.
7. Wei W, Anderson P, Gadkari A, et al. Extent and consequences of inadequate disease control among adults with a history of moderate to severe atopic dermatitis. J Dermatol 2018;45(2):150–157.
8. Ghoreschi K, Laurence A, O'Shea JJ. Janus kinases in immune cell signaling. Immunol Rev 2009;228(1):273–287.
9. Vazquez ML, Kaila N, Strohbach JW, et al. Identification of N-{cis-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclobutyl}propane-1-sulfonamide (PF-04965842): a selective JAK1 clinical candidate for the treatment of autoimmune diseases. J Med Chem 2018;61(3):1130–1152.
10. Gooderham MJ, Forman SB, Bissonnette R, et al. Efficacy and safety of oral Janus kinase 1 inhibitor abrocitinib for patients with atopic dermatitis: a phase 2 randomized clinical trial. JAMA Dermatol 2019;155(12):1371–1379.
11. Copley-Merriman C, Zelt S, Clark M, et al. Impact of measuring patient-reported outcomes in dermatology drug development. Patient 2017;10(2):203–213.
12. US Department of Health and Human Services. Guidance for industry—patient-reported outcome measures: use in medical product development to support labeling claims. 2009. Available at: https://www.fda.gov/media/77832/download. Accessed February 1, 2021.
13. Brédart A, Marrel A, Abetz-Webb L, et al. Interviewing to develop patient-reported outcome (PRO) measures for clinical research: eliciting patients' experience. Health Qual Life Outcomes 2014;12:15.
14. Chalmers JR, Schmitt J, Apfelbacher C, et al. Report from the third international consensus meeting to harmonise core outcome measures for atopic eczema/dermatitis clinical trials (HOME). Br J Dermatol. 2014;171(6):1318–1325.
15. Lebwohl MG, Simpson EL, Bushmakin AG, et al. Validation of the pruritus and symptoms assessment for atopic dermatitis in adults with moderate to severe atopic dermatitis. Paper presented at The 10th Georg Rajka International Symposium on Atopic Dermatitis; April 11–13, 2018; Utrecht, the Netherlands. Abstract P071.
16. Phan NQ, Blome C, Fritz F, et al. Assessment of pruritus intensity: prospective study on validity and reliability of the visual analogue scale, numerical rating scale and verbal rating scale in 471 patients with chronic pruritus. Acta Derm Venereol 2012;92(5):502–507.
17. Charman CR, Venn AJ, Williams HC. The patient-oriented eczema measure: development and initial validation of a new tool for measuring atopic eczema severity from the patients' perspective. Arch Dermatol 2004;140(12):1513–1519.
18. Finlay AY, Khan GK. Dermatology Life Quality Index (DLQI)—a simple practical measure for routine clinical use. Clin Exp Dermatol 1994;19(3):210–216.
19. Zigmond AS, Snaith RP. The Hospital Anxiety and Depression Scale. Acta Psychiatr Scand 1983;67(6):361–370.
20. Schram ME, Spuls PI, Leeflang MMG, et al. EASI, (objective) SCORAD and POEM for atopic eczema: responsiveness and minimal clinically important difference. Allergy 2012;67(1):99–106.
21. Basra MK, Salek MS, Camilleri L, et al. Determining the minimal clinically important difference and responsiveness of the Dermatology Life Quality Index (DLQI): further data. Dermatology 2015;230(1):27–33.
22. Yosipovitch G, Reaney M, Mastey V, et al. Peak pruritus numerical rating scale: psychometric validation and responder definition for assessing itch in moderate-to-severe atopic dermatitis. Br J Dermatol 2019;181(4):761–769.
23. Simpson EL, Gadkari A, Worm M, et al. Dupilumab therapy provides clinically meaningful improvement in patient-reported outcomes (PROs): a phase IIb, randomized, placebo-controlled, clinical trial in adult patients with moderate to severe atopic dermatitis (AD). J Am Acad Dermatol 2016;75(3):506–515.
24. Dawn A, Papoiu AD, Chan YH, et al. Itch characteristics in atopic dermatitis: results of a web-based questionnaire. Br J Dermatol 2009;160(3):642–644.
25. Mollanazar NK, Smith PK, Yosipovitch G. Mediators of chronic pruritus in atopic dermatitis: getting the itch out?Clin Rev Allergy Immunol 2016;51(3):263–292.
26. Silverberg JI, Gelfand JM, Margolis DJ, et al. Patient burden and quality of life in atopic dermatitis in US adults: a population-based cross-sectional study. Ann Allergy Asthma Immunol 2018;121(3):340–347.
27. Cevikbas F, Wang X, Akiyama T, et al. A sensory neuron-expressed IL-31 receptor mediates T helper cell–dependent itch: involvement of TRPV1 and TRPA1. J Allergy Clin Immunol 2014;133(2):448–460.
28. Wahlgren CF, Tengvall Linder M, Hägermark O, et al. Itch and inflammation induced by intradermally injected interleukin-2 in atopic dermatitis patients and healthy subjects. Arch Dermatol Res 1995;287(6):572–580.
29. Chan LS, Robinson N, Xu L. Expression of interleukin-4 in the epidermis of transgenic mice results in a pruritic inflammatory skin disease: an experimental animal model to study atopic dermatitis. J Invest Dermatol 2001;117(4):977–983.
30. Zheng T, Oh MH, Oh SY, et al. Transgenic expression of interleukin-13 in the skin induces a pruritic dermatitis and skin remodeling. J Invest Dermatol 2009;129(3):742–751.
31. Chrostowska-Plak D, Reich A, Szepietowski JC. Relationship between itch and psychological status of patients with atopic dermatitis. J Eur Acad Dermatol Venereol 2013;27(2):e239–e242.
32. Bender BG, Leung SB, Leung DY. Actigraphy assessment of sleep disturbance in patients with atopic dermatitis: an objective life quality measure. J Allergy Clin Immunol 2003;111(3):598–602.

Supplemental Digital Content

© 2021 American Contact Dermatitis Society. All Rights Reserved.