Study Evaluating the Mechanism of Action of PF-04965842 Monotherapy for Moderate-to-severe Atopic Dermatitis

Mean fold-changes from baseline at Week 12 in the biomarkers for general inflammation (Matrix Metallopeptidase [MMP]12), hyperplasia (Keratin [KRT]16), Th2 immune response (C-C motif chemokine ligand [CCL]17, CCL18, CCL26), and Th22 immune response (S100 calcium binding protein A [S100A]8, S100A9, S100A12), in lesional (LS) and non-lesional (NL) skin tissues, respectively. Expression levels from RT-PCR are normalized to the housekeeping gene RPLP0 by negatively transforming the Ct values to -dCt.

Mean fold-changes from baseline in immunohistochemistry analysis in lesional skin endpoints at Week 12 are presented. Fold-changes are computed by obtaining the antilog of log2 fold-changes, retaining the sign for log2 fold-change.

Mean fold-changes from baseline in hyperplasia markers in skin biopsies at Week 12 are presented. Fold-changes are computed by obtaining the antilog of log2 fold-changes, retaining the sign for log2 fold-change.

OLINK Proteomics Microassay was used to analyze biomarkers in serum to assess the effect of abrocitinib on the blood biomarkers. Mean fold-changes at Week 12 from baseline are listed. Baseline is defined as the last observation on or prior to day of first dose (Day 1).

Mean percent changes from baseline at Week 12 in T-cell lymphocyte subset populations (CD3+ T cells, CD4+ T cells, CD8+ T cells, NK cells, B cells) are presented. Baseline is defined as the last observation on or prior to day of first dose (Day 1).

PP-NRS assesses the severity of itch (pruritus) due to AD. Participants were asked to assess their worst itching due to AD on an NRS anchored by the terms "no itch" (0) and "worst itch imaginable" (10). Participants who withdrew from the study were counted as non-responder. Spearman correlation coefficient was calculated to assess the relationship between PP-NRS CFB and fold CFB of IHC and gene expression biomarkers.

The IGA of AD is scored on a 5-point scale (0-4), reflecting a global consideration of the erythema, induration and scaling. The overall severity of AD was assessed according to the 5-point scale: 0=Clear, 1=Almost Clear, 2=Mild, 3=Moderate, and 4=Severe. Participants who withdrew from the study were counted as non-responder.

The EASI quantifies the severity of AD based on both severity of lesion clinical signs and the percent of body surface area (BSA) affected. The EASI score can vary in increments of 0.1 and range from 0.0 to 72.0, with higher scores representing greater severity of AD. Participants who withdrew from the study were counted as non-responder.

PP-NRS assesses the severity of itch (pruritus) due to AD. Participants were asked to assess their worst itching due to AD on an NRS anchored by the terms "no itch" (0) and "worst itch imaginable" (10). Higher scores indicated worse itch. Participants who withdrew from the study were counted as non-responder.

The EASI quantifies the severity of AD based on both severity of lesion clinical signs and the percent of BSA affected. The EASI score can vary in increments of 0.1 and range from 0.0 to 72.0, with higher scores representing greater severity of AD. Participants who withdrew from the study were counted as non-responder.

The EASI quantifies the severity of AD based on both severity of lesion clinical signs and the percent of BSA affected. The EASI score can vary in increments of 0.1 and range from 0.0 to 72.0, with higher scores representing greater severity of AD. Participants who withdrew from the study were counted as non-responder.

BSA efficacy is derived from the sum of the BSA in handprints across 4 body regions assessed as part of the EASI assessment. Handprint refers to that of each individual participant for their own measurement. The BSA efficacy ranges from 0 to 100%, with higher values representing greater severity of AD. The percentage BSA ranges from 0 to 100, with higher scores representing greater severity of AD. Since the scalp, palms, and soles were excluded from the BSA (efficacy) assessment, the maximum possible percentage BSA was less than 100.

An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product; the event did not need to have a causal relationship with the treatment. TEAEs were AEs that occurred following the start of treatment or AEs increasing in severity during treatment. Treatment-related TEAEs were determined by the investigator.

A serious adverse event (SAE) was any untoward medical occurrence at any dose that resulted in death; was life threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect. Treatment-related SAEs were determined by the investigator.

An AE was any untoward medical occurrence in a clinical investigation participant administered a product; the event did not need to have a causal relationship with the treatment. TEAEs were AEs that occurred following the start of treatment or AEs increasing in severity during treatment. Treatment-related TEAEs were determined by the investigator.

Laboratory tests included hematology (including coagulation panel), clinical chemistry, lipid profile panel, and routine urinalysis. LLN is lower limit of normal. ULN is upper limit of normal.

Clinical laboratory tests including red blood cell (erythrocytes) were performed at Week 2, 4, 8, and 12 by collecting blood samples and performing the corresponding analysis per the laboratory manual. Fasting was only required prior to labs that included the lipid profile panel.

Clinical laboratory tests including reticulocytes were performed at Week 2, 4, 8, and 12 by collecting blood samples and performing the corresponding analysis per the laboratory manual. Fasting was only required prior to labs that included the lipid profile panel.

Clinical laboratory tests including platelet counts were performed at Week 2, 4, 8, and 12 by collecting blood samples and performing the corresponding analysis per the laboratory manual. Fasting was only required prior to labs that included the lipid profile panel.

Clinical laboratory tests including hs-CRP were performed at Week 2, 4, 8, and 12 by collecting blood samples and performing the corresponding analysis per the laboratory manual. Fasting was only required prior to labs that included the lipid profile panel.

Clinical laboratory tests including interleukin were performed at Week 2, 4, 8, and 12 by collecting blood samples and performing the corresponding analysis per the laboratory manual. Fasting was only required prior to labs that included the lipid profile panel.

Clinical laboratory tests including erythropoietin were performed at Week 2, 4, 8, and 12 by collecting blood samples and performing the corresponding analysis per the laboratory manual. Fasting was only required prior to labs that included the lipid profile panel.

Clinical laboratory tests including thrombopoietin were performed at Week 2, 4, 8, and 12 by collecting blood samples and performing the corresponding analysis per the laboratory manual. Fasting was only required prior to labs that included the lipid profile panel.

The severity and frequency of itch (pruritus) during the night due to AD was assessed using the Night Time Itch Scale Score. Participants assessed their worst itching due to AD during their most recent night's sleep on an NRS anchored by the terms "no itch" (0) and "worst itch imaginable" (10). Higher scores indicated worse itch. The frequency of itch was assessed using a 5-point qualitative scale, with responses including "Never", "Rarely", "Sometimes", "Often" and "Almost Always".

Pharmacokinetic (PK) samples were collected at Week 4 and 12 for measurement of plasma concentration of PF-04965842.

PK samples were collected at Week 4 and 12 for measurement of plasma concentration of abrocitinib's metabolite PF-06471658 (M1).

PK samples were collected at Week 4 and 12 for measurement of plasma concentration of abrocitinib's metabolite PF-07055087 (M2).

PK samples were collected at Week 4 and 12 for measurement of plasma concentration of abrocitinib's metabolites PF-07054874 (M4).