IGA is an assessment scale used to determine severity of hand and foot AD and clinical response to treatment on a 5-point scale (0 = clear; 1 = almost clear; 2 = mild; 3 = moderate; 4 = severe) based on erythema and papulation/infiltration. Higher score is indicative of more severe disease.

Peak esophageal intraepithelial eosinophil count was measured from esophageal biopsies. A total of at least 9 mucosal pinch biopsies were collected from 3 esophageal regions: 3 proximal, 3 mid, and 3 distal. The peak esophageal intraepithelial eosinophil count at each visit was the maximum of the quantities of eosinophils in the most inflamed hpfs across the 3 regions. If the quantity of eosinophils was missing for 1 or 2 esophageal regions, the peak eosinophil count was the maximum of the quantities of eosinophils from the region(s) where eosinophil quantities were available.

Esophageal intraepithelial eosinophil count obtained by esophageal endoscopy with biopsies (all 3 esophageal regions: proximal, mid, and distal).

The DSQ is used to measure the frequency and intensity of dysphagia. DSQ scores can range from 0 to 84, with a lower score indicating less-frequent or less-severe dysphagia.

The IGA was an assessment instrument used in clinical studies to rate the severity of AD globally, based on a 5-point scale ranging from 0 (clear) to 4 (severe). The full analysis set (FAS) included all randomized participants. Efficacy analyses were based on the treatment allocated at randomization (as randomized). Values after first rescue treatment used were set to missing. Participants with missing score at Week 16 were considered as a non-responder.

IGA is an assessment scale used to determine severity of atopic dermatitis (AD) and clinical response to treatment on a 5-point scale (0 = clear; 1 = almost clear; 2 = mild; 3 = moderate; 4 = severe) based on erythema and papulation/infiltration. Therapeutic response was an IGA score of 0 (clear) or 1 (almost clear). Participants with IGA "0" or "1" and a reduction from baseline of ≥2 points at Week 16 were reported. \[Values after first rescue treatment used were set to missing. Participants with missing score at week 16 were considered as a non-responder. Participant considered non-responder after rescue treatment use. Efficacy analyses were based on the treatment allocated at randomization (as randomized).\]

The EASI score was used to measure the severity and extent of AD and measures erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD. EASI--75 responders were the participants who achieved ≥75% overall improvement in EASI score from baseline to Week 16. \[Values after first rescue treatment used were set to missing. Participants with missing score at week 16 were considered as a non-responder. Participant considered nonresponder after rescue treatment use. Efficacy analyses were based on the treatment allocated at randomization (as randomized).\]

The EASI score is used to measure the severity and extent of atopic dermatitis (AD) and measured erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD. EASI-75 responders were the participants who achieved ≥75% overall improvement in EASI score from baseline to Week 16. The analysis population for efficacy analyses is the Full Analysis Set (FAS) which included all randomized participants. Efficacy analyses were based on the treatment allocated (as randomized).

Peak serum concentration after multiple doses of dupilumab administered using the PFP (test) relative to the prefilled syringe (reference)

Drug concentration in serum after multiple doses of dupilumab administered using the PFP (test) relative to the prefilled syringe (reference)

The EASI score was used to measure the severity and extent of AD and measured erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD. Difference of percent change in EASI between current study baseline and week 36 in from parent study baseline (NCT02277743 and NCT02277769) was reported. Values after first rescue treatment used were set to missing before multiple imputation (MI).

The EASI score was used to measure the severity and extent of AD and measured erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD. EASI-75 responders were the participants who achieved \>=75% overall improvement in EASI score at Week 36. Values after first rescue treatment used were set to missing. Patients with missing value at week 36 were considered as a non-responder.

IGA is an assessment scale used to determine severity of AD and clinical response to treatment on a 5-point scale (0 = clear; 1 = almost clear; 2 = mild; 3 = moderate; 4 = severe) based on erythema and papulation/infiltration. Therapeutic response is an IGA score of 0 (clear) or 1 (almost clear). Participants with IGA score of "0" or "1" and a reduction from baseline of ≥2 points at Week 16 were reported. Values after first rescue treatment were set to missing and participants with missing IGA scores at Week 16 were considered as non-responders.

Adverse events of special interest in this study include: Anaphylactic reactions, Systemic hypersensitivity reactions, Helminthic infections, Any severe type of conjunctivitis or blepharitis, Keratitis, Clinically symptomatic eosinophilia (or eosinophilia associated with clinical symptoms)

Changes in the SALT score from baseline compared to week 48. SALT score is the sum of percentage of hair loss in all areas (higher score indicates greater hair loss). The change between baseline and Week 48 will be compared.

The overall (longitudinal) change in the ACC HDM exposure-induced nasal airway gene expression profiles observed during the first HDM exposure (visit 3; pre-randomization) and during the three on-treatment HDM exposures (visits 7, 11, and 15)

Sino-Nasal Outcome Test (SNOT-22) survey score after six months treatment (range 0-110). Higher score means worse symptoms.

The SALT is a validated instrument for measuring the amount of scalp hair loss at a single point in time The SALT is a validated instrument for measuring the amount of scalp hair loss at a single point in time SALT - Scalp divided into four areas: vertex (40% of scalp surface area), right profile (18% of scalp surface area), left profile (18% of scalp surface area), and posterior scalp (24% of scalp surface area). Percentage of hair loss in these areas is multiplied by percent surface area of the scalp in that area. SALT score is the sum of percentage of hair loss in all areas. SALT scores range from 0 (no hair loss) to 100 (complete scalp hair loss) with lower score indicating better health outcomes/less hair loss. Primary Outcome is baseline minus Week 24 value.

Sustained remission at week 36, defined as: (1) Complete remission (absence of new lesions \& epithelialization of old lesions) \& off oral corticosteroids (OCS) no later than week 16 \& (2) Absence of disease relapse (appearance of ≥3 new lesions a month \[blisters, eczematous lesions, or urticarial plaques\] or at least 1 large eczematous lesion or urticarial plaque that does not heal within 1 week) after completion of OCS taper, no later than week 16, to week 36 \& (3) Absence of need for rescue therapy during 36 weeks (rescue therapy includes increase of OCS dose during the taper, re-initiation of OCS after completion of the OCS taper, or initiation of any BP-directed therapy). Participants with missing sustained remission data at week 36 due to discontinuation due to lack of efficacy, treatment-related AE, or death were considered non-responders \& those with missing data due to other reasons were handled using multiple imputation.

Symptoms considered to be allergic were graded using the Consortium of Food Allergy Research (CoFAR) Grading Scale for Systemic Allergic Reactions. The scale is Grade 1 (Mild) through 5, the higher the grade, the more severe the allergic reaction. Participants were considered to have passed the DBPCFC if they did not experience any objective Grade 1 reaction. Percentage of participants treated with dupilumab who passed the DBPCFC with at least 444 mg (cumulative) peanut protein at Week 24 was reported.

Symptoms considered to be allergic were graded using the Consortium of Food Allergy Research (CoFAR) Grading Scale for Systemic Allergic Reactions. The allergic reaction is measured on a 1-5 scale, with grade 1 being mild, grade 2 being moderate, grade 3 being severe, grade 4 being life threatening, and grade 5 as death. the higher the grade, the more severe the allergic reaction. Participants were considered to have passed the DBPCFC if they did not experience any objective Grade 1 reaction. Percentage of participants treated with dupilumab plus AR101 vs placebo plus AR101 who passed a post up-dosing DBPCFC with 2044 mg (Cumulative) peanut protein at Visit 16 (Week 28 to 40) was reported. Cumulative data during the specified period was calculated as the average of all available post-randomization values during the specified time period (Week 28 to Week 40).

TNSS was participant-reported composite symptom assessment of 4 symptoms (rhinorrhea, nasal congestion, nasal itching \& sneezing), each scored on a scale from 0 to 3 where 0 = none, 3 = severe. TNSS total score was calculated as the sum of the response for all 4 individual nasal symptom scores and ranged from 0 to 12, where higher score indicated more severe symptoms. AUC of TNSS/component from time of the first observation to time of the last observation (AUC \[0-1 hr\]) was calculated by using the trapezoid rule. Data was reported for Dupilumab + SCIT and placebo matched to Dupilumab + SCIT monotherapy group in this outcome measure.

Serum concentration of functional dupilumab was reported.

Dose normalized was calculated as Cmax obtained directly from the concentration versus time curve divided by dose. Cmax/dose was measured in Milligrams per Liter/Milligrams per Kilogram (\[mg/L\]/\[mg/kg\]).

Tmax was obtained directly from the concentration versus time curve.

Clast is the last measurable serum concentration of dupilumab.

Tlast was defined as the last time point with a measurable serum concentration of dupilumab.

AUClast was defined as area under the serum concentration time-curve from zero to the last measured concentration.

Dose normalized AUClast was calculated by AUClast/dose.

Adverse Event (AE) was defined as any untoward medical occurrence in a participant administered a study drug which may/may not have a causal relationship with study drug. Serious AE (SAE) was defined as any untoward medical occurrence that resulted in any of following outcomes: death, life-threatening, required initial/prolonged in-participant hospitalization, persistent/significant disability/incapacity, congenital anomaly/birth defect/considered as medically important event. TEAE was defined as AE starting/worsening after first intake of study drug. TEAEs included participants with both SAEs and non-SAEs. Number of participants with TEAEs is reported.

Severity of TEAEs were graded using Qualitative Toxicity Scale, as follows: Mild: Participant is aware of the event or symptom, but the event or symptom is easily tolerated; Moderate: Participant experiences sufficient discomfort to interfere with or reduce his or her usual level of activity; Severe: Significant impairment of functioning: the participant is unable to carry out his or her usual activities. Number of participants with TEAEs by severity were reported.

The IGA is an assessment scale used in clinical studies to rate the severity of AD globally, based on a 5-point scale ranging from 0 to 4 where 0 = clear; 1=almost clear; 2=mild; 3=moderate; 4=severe. A negative change from baseline indicated improvement. Percentage of participants with IGA score of '0' or '1' is reported.

The EASI score is used to measure the severity and extent of AD and measured erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper, and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with the higher scores indicating the worse severity of AD. EASI-75 responders were the participants who achieved ≥75% overall improvement in EASI score from baseline at Week 16.

The SDI is a PRO used to determine frequency/ intensity of dysphagia (recall period 1-wk). Frequency of dysphagia events is graded on a 5-pt scale: 0=none, 1=1x/wk, 2=several/wk, 3=1x/day, 4=several/day; intensity is graded on a 6-pt scale: 0=swallowing unrestricted, 1=slight sensation of resistance, 2=slight retching with delay, 3=short period of obstruction necessitating intervention, 4=longer-lasting period of obstruction removable by vomiting, 5=long-lasting complete obstruction requiring endoscopic intervention. Total score ranges from 0-9 (higher score indicates worsening symptoms).

Peak dupilumab concentration in serum following single dose administration. Analysis was performed on PK analysis set that included all treated subjects who received the study medication and had at least 1 quantified (non-missing) result for dupilumab concentration following the first dose of the study drug.

Mean AUC estimates were calculated using mean concentration data at each time point, using a non-compartmental approach (NCA). Calculated AUClast (computed from time zero to the time of the last positive concentration) are presented. Analysis was performed on PK analysis set that included all treated subjects who received the study medication and had at least 1 quantified (non-missing) result for dupilumab concentration following the first dose of the study drug.

Analysis was performed on PK analysis set that included all treated subjects who received the study medication and had at least 1 quantified (non-missing) result for dupilumab concentration following the first dose of study drug.

A positive response was defined as a ≥ 4-fold increase from pre-vaccination at baseline in anti-tetanus immunoglobulin G (IgG) titer for participants with a pre-vaccination tetanus antibody titers ≥ 0.1 IU/ml or a titer of ≥ 0.2 IU/ml for participants with pre-vaccination titers of \<0.1 IU/ml. There was no planned statistical hypothesis testing regarding the difference in immune response between the 2 treatment groups for this study, therefore no formal statistical hypothesis between groups was performed.

The EASI score was used to measure the severity and extent of atopic dermatitis (AD) and measures erythema (E), infiltration (I), excoriation (Ex) and lichenification (L) on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD. Values after first rescue medication use were set to missing and missing values imputed by last observation carried forward (LOCF).

The EASI score was used to measure the severity and extent of atopic dermatitis (AD) and measures erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score range from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD.

Any untoward medical occurrence in a subject who received investigational medicinal product (IMP) was considered an AE without regard to possibility of causal relationship with this treatment. Treatment-emergent adverse events (TEAEs) were defined as AEs that developed or worsened or became serious during on-treatment period (from start of administration of first dose of study drug to the end of study \[up to Day 78\]). A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in any of following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. Any TEAE included participants with both serious and non-serious AEs.

The EASI score was used to measure the severity and extent of AD and measured erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD. The efficacy data were set to be missing after use of rescue medication and after early termination visit for participants who prematurely discontinued study treatment. All missing values were imputed by LOCF.