Study of Dupilumab and Immune Responses in Adults With Atopic Dermatitis (AD)

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.

Time frame: Week 16

Population: The immune response analysis set (IRS) included all randomized participants who received any study drug, vaccine injection at Week 12, and had 1 measurement for responses to tetanus toxoid vaccine at Week 16.

BSA affected by AD was assessed for each section of the body (the possible highest score for each region was: head and neck \[9%\], anterior trunk \[18%\], back \[18%\], upper limbs \[18%\], lower limbs \[36%\], and genitals \[1%\]). It was reported as a percentage of all major body sections combined. Values after first rescue medication use were set to missing and missing values were imputed by LOCF.

Time frame: Baseline to Week 16

Population: Full analysis set (FAS) that included all randomized participants. Here, number of participants analyzed=participants with available data for this endpoint.

Individual components of the AD lesions (erythema, infiltration/papulation, excoriations, and lichenification) were rated globally (each assessed for the whole body, not by anatomical region) on a 4-point scale (0 = none, 1 = mild, 2 = moderate and 3 = severe) using the EASI severity grading criteria. Total score ranges from 0 (absent disease) to 12 (severe disease). Values after first rescue treatment were set to missing. Analysis was completed using MMRM model which includes treatment, randomization strata, visit, baseline value, treatment-by-visit interaction, and baseline-by-visit interaction as covariates. These results are observed results without imputation.

Time frame: Baseline to Week 16

Population: Full analysis set (FAS) that included all randomized participants. Here, number of participants analyzed=participants with available data for this endpoint.

Pruritus NRS was an assessment tool that was used to report the intensity of participant's pruritus (itch), both maximum and average intensity, during a 24-hour recall period. Participants were asked the following question: how would a participant rate his itch at the worst moment during the previous 24 hours (for maximum itch intensity on a scale of 0 - 10 \[0 = no itch; 10 = worst itch imaginable\]). Weekly average obtained in the 7-day period prior to the baseline visit. Values after first rescue medication use were set to missing and missing values were imputed by Last observation carried forward (LOCF).

Time frame: Baseline to Week 16

Population: Full analysis set (FAS) that included all randomized participants. Here, number of participants analyzed=participants with available data for this endpoint.

The POEM was a 7-item questionnaire that assesses disease symptoms (dryness, itching, flaking, cracking, sleep loss, bleeding and weeping) with a scoring system of 0 (absent disease) to 28 (severe disease) (high score indicative of poor quality of life \[QOL\]). Values after first rescue medication use were set to missing and missing values were imputed by LOCF.

Time frame: Baseline to Week 16

Population: Full analysis set (FAS) that included all randomized participants. Here, number of participants analyzed=participants with available data for this endpoint.

Individual components of the AD lesions (erythema, infiltration/papulation, excoriations, and lichenification) were rated globally (each assessed for the whole body, not by anatomical region) on a 4-point scale (0 = none, 1 = mild, 2 = moderate and 3 = severe) using the EASI severity grading criteria. Total score ranges from 0 (absent disease) to 12 (severe disease). Values after first rescue medication use were set to missing and missing values were imputed by LOCF.

Time frame: Baseline to Week 16

Population: Full analysis set (FAS) that included all randomized participants. Here, number of participants analyzed=participants with available data for this endpoint.

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 ranges from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD. EASI-50 responders were the participants who achieved ≥50% overall improvement in EASI score from baseline to Week 16. Values after first rescue treatment were set to missing and participants with missing EASI score at Week 16 were counted as non-responders.

Time frame: Week 16

Population: Full analysis set (FAS) that included all randomized participants.

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 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 use were set to missing and participants with missing EASI score at Week 16 were considered as non-responders.

Time frame: Week 16

Population: Full analysis set (FAS) that included all randomized participants.

IGA was 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 was an IGA score of 0 (clear) or 1 (almost clear). Values after first rescue treatment were set to missing and participants with missing IGA scores at Week 16 were counted as non-responders.

Time frame: Week 16

Population: Full analysis set (FAS) that included all randomized participants.

Participants with positive response defined as a ≥2-fold increase from pre-vaccination baseline in anti-tetanus IgG titer for participants with 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.

Time frame: Week 16

Population: The immune response analysis set (IRS) included all randomized participants who received any study drug, vaccine injection at Week 12, and had 1 measurement for responses to tetanus toxoid vaccine at Week 16.

A positive response to the Menomune vaccine was a serum bactericidal antibody (SBA) titer of ≥8 for serogroup C.

Time frame: Week 16

Population: The immune response analysis set (IRS) included all randomized participants who received any study drug, vaccine injection at Week 12, and had 1 measurement for responses to tetanus toxoid vaccine at Week 16.