A Study to Evaluate the Efficacy, and Safety Study of Ruxolitinib Cream in Adults With Moderate Atopic Dermatitis

ITCH4 is defined as achieving a ≥4-point improvement from baseline in Itch NRS score. The Itch NRS is a once-daily patient-reported measure of itch intensity assessed using an 11-point scale (0 = no itch to 10 = worst imaginable itch) that best describes their worst level of itching in the past 24 hours. The Itch NRS score for baseline was determined by averaging the 7 daily NRS scores directly before Day 1 (Day -7 to Day -1). The by-visit Itch NRS score for postbaseline visits was determined by averaging the 7 daily NRS scores directly before the visit day.

ITCH4 is defined as achieving a ≥4-point improvement from baseline in Itch NRS score. The Itch NRS is a once-daily patient-reported measure of itch intensity assessed using an 11-point scale (0 = no itch to 10 = worst imaginable itch) that best describes their worst level of itching in the past 24 hours. The Itch NRS score for baseline was determined by averaging the 7 daily NRS scores directly before Day 1 (Day -7 to Day -1). The by-visit Itch NRS score for postbaseline visits was determined by averaging the 7 daily NRS scores directly before the visit day.

An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not it was considered drug related. An AE could therefore have been any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study cream. A TEAE was defined as any AE either reported for the first time or the worsening of a pre-existing event after the first application of study cream and no later than 30 days after the Week 24 or early termination visit.

An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not it was considered drug related. An AE could therefore have been any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study cream. A TEAE was defined as any AE either reported for the first time or the worsening of a pre-existing event after the first application of study cream and no later than 30 days after the Week 24 or early termination visit.

An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not it was considered drug related. An AE could therefore have been any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study cream. A TEAE was defined as any AE either reported for the first time or the worsening of a pre-existing event after the first application of study cream and no later than 30 days after the Week 24 or early termination visit.

An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not it was considered drug related. A TEAE was defined as any AE either reported for the first time or the worsening of a pre-existing event after the first application of study cream and no later than 30 days after the Week 24 or early termination visit. The severity of TEAEs was assessed using Common Terminology Criteria for Adverse Events (CTCAE) v5.0 Grades 1-5. Grade 1: mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; treatment not indicated. Grade 2: moderate; minimal, local, or noninvasive treatment indicated; limiting age-appropriate activities of daily living. Grade 3: severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living. Grade 4: life-threatening consequences; urgent treatment indicated. Grade 5: fatal.

An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not it was considered drug related. A TEAE was defined as any AE either reported for the first time or the worsening of a pre-existing event after the first application of study cream and no later than 30 days after the Week 24 or early termination visit. The severity of TEAEs was assessed using CTCAE v5.0 Grades 1-5. Grade 1: mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; treatment not indicated. Grade 2: moderate; minimal, local, or noninvasive treatment indicated; limiting age-appropriate activities of daily living. Grade 3: severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living. Grade 4: life-threatening consequences; urgent treatment indicated. Grade 5: fatal.

An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not it was considered drug related. A TEAE was defined as any AE either reported for the first time or the worsening of a pre-existing event after the first application of study cream and no later than 30 days after the Week 24 or early termination visit. The severity of TEAEs was assessed using CTCAE v5.0 Grades 1-5. Grade 1: mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; treatment not indicated. Grade 2: moderate; minimal, local, or noninvasive treatment indicated; limiting age-appropriate activities of daily living. Grade 3: severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living. Grade 4: life-threatening consequences; urgent treatment indicated. Grade 5: fatal.

EASI75 was defined as achieving a ≥75% improvement in the EASI score compared to the baseline score. The EASI scoring system is a validated scoring system that grades the physical signs of atopic dermatitis (AD) to provide a measure of AD severity (ranging from 0 to 72). The disease severity strata for the EASI are: 0 = clear; 0.1 to 1.0 = almost clear; 1.1 to 7.0 = mild; 7.1 to 21.0 = moderate; 21.1 to 50.0 = severe; 50.1 to 72.0 = very severe.

EASI75 was defined as achieving a ≥75% improvement in the EASI score compared to the baseline score. The EASI scoring system is a validated scoring system that grades the physical signs of atopic dermatitis (AD) to provide a measure of AD severity (ranging from 0 to 72). The disease severity strata for the EASI are: 0 = clear; 0.1 to 1.0 = almost clear; 1.1 to 7.0 = mild; 7.1 to 21.0 = moderate; 21.1 to 50.0 = severe; 50.1 to 72.0 = very severe.

IGA-TS was defined as achieving an IGA score of 0 or 1 with a ≥2-grade improvement from baseline. The IGA is an overall eczema severity rating on a 0 to 4 scale. 0: clear; no erythema or induration/papulation, no oozing/crusting; there may be minor residual discoloration. 1: almost clear; may be trace faint pink erythema, with almost no induration/papulation, and no oozing/crusting. 2: mild; may be faint pink erythema, with mild induration/papulation and no oozing/crusting. 3: moderate; may be pink-red erythema with moderate induration/papulation and may be some oozing/crusting. 4: severe; may be deep or bright red erythema with severe induration/papulation and with oozing/crusting.

IGA-TS was defined as achieving an IGA score of 0 or 1 with a ≥2-grade improvement from baseline. The IGA is an overall eczema severity rating on a 0 to 4 scale. 0: clear; no erythema or induration/papulation, no oozing/crusting; there may be minor residual discoloration. 1: almost clear; may be trace faint pink erythema, with almost no induration/papulation, and no oozing/crusting. 2: mild; may be faint pink erythema, with mild induration/papulation and no oozing/crusting. 3: moderate; may be pink-red erythema with moderate induration/papulation and may be some oozing/crusting. 4: severe; may be deep or bright red erythema with severe induration/papulation and with oozing/crusting.

ITCH4 is defined as achieving a ≥4-point improvement from baseline in Itch NRS score. The Itch NRS is a once-daily patient-reported measure of itch intensity assessed using an 11-point scale (0 = no itch to 10 = worst imaginable itch) that best describes their worst level of itching in the past 24 hours. The Itch NRS score for baseline was determined by averaging the 7 daily NRS scores directly before Day 1 (Day -7 to Day -1). The by-visit Itch NRS score for postbaseline visits was determined by averaging the 7 daily NRS scores directly before the visit day.

ITCH4 is defined as achieving a ≥4-point improvement from baseline in Itch NRS score. The Itch NRS is a once-daily patient-reported measure of itch intensity assessed using an 11-point scale (0 = no itch to 10 = worst imaginable itch) that best describes their worst level of itching in the past 24 hours. The Itch NRS score for baseline was determined by averaging the 7 daily NRS scores directly before Day 1 (Day -7 to Day -1). The by-visit Itch NRS score for postbaseline visits was determined by averaging the 7 daily NRS scores directly before the visit day.

ITCH2 is defined as achieving a ≥2-point improvement from baseline in Itch NRS score. The Itch NRS is a once-daily patient-reported measure of itch intensity assessed using an 11-point scale (0 = no itch to 10 = worst imaginable itch) that best describes their worst level of itching in the past 24 hours. The Itch NRS score for baseline was determined by averaging the 7 daily NRS scores directly before Day 1 (Day -7 to Day -1). The by-visit Itch NRS score for postbaseline visits was determined by averaging the 7 daily NRS scores directly before the visit day.

The Itch NRS is a once-daily patient-reported measure of itch intensity assessed using an 11-point scale (0 = no itch to 10 = worst imaginable itch) that best describes their worst level of itching in the past 24 hours. The Itch NRS score for baseline was determined by averaging the 7 daily NRS scores directly before Day 1 (Day -7 to Day -1). The by-visit Itch NRS score for postbaseline visits was determined by averaging the 7 daily NRS scores directly before the visit day. Change from baseline was calculated as the post-baseline value minus the baseline value.

The Itch NRS is a once-daily patient-reported measure of itch intensity assessed using an 11-point scale (0 = no itch to 10 = worst imaginable itch) that best describes their worst level of itching in the past 24 hours. The Itch NRS score for baseline was determined by averaging the 7 daily NRS scores directly before Day 1 (Day -7 to Day -1). The by-visit Itch NRS score for postbaseline visits was determined by averaging the 7 daily NRS scores directly before the visit day.

The Itch NRS is a once-daily patient-reported measure of itch intensity assessed using an 11-point scale (0 = no itch to 10 = worst imaginable itch) that best describes their worst level of itching in the past 24 hours. The Itch NRS score for baseline was determined by averaging the 7 daily NRS scores directly before Day 1 (Day -7 to Day -1). The by-visit Itch NRS score for postbaseline visits was determined by averaging the 7 daily NRS scores directly before the visit day.

EASI50 was defined as achieving a ≥50% improvement in the EASI score compared to the baseline score. The EASI scoring system is a validated scoring system that grades the physical signs of atopic dermatitis (AD) to provide a measure of AD severity (ranging from 0 to 72). The disease severity strata for the EASI are: 0 = clear; 0.1 to 1.0 = almost clear; 1.1 to 7.0 = mild; 7.1 to 21.0 = moderate; 21.1 to 50.0 = severe; 50.1 to 72.0 = very severe.

EASI90 was defined as achieving a ≥90% improvement in the EASI score compared to the baseline score. The EASI scoring system is a validated scoring system that grades the physical signs of atopic dermatitis (AD) to provide a measure of AD severity (ranging from 0 to 72). The disease severity strata for the EASI are: 0 = clear; 0.1 to 1.0 = almost clear; 1.1 to 7.0 = mild; 7.1 to 21.0 = moderate; 21.1 to 50.0 = severe; 50.1 to 72.0 = very severe.

EASI75=a ≥75% improvement in the EASI score compared to the baseline score. The EASI scoring system grades the physical signs of AD to provide a measure of severity (range=0-72). EASI disease severity strata: 0 = clear; 0.1-1.0 = almost clear; 1.1-7.0 = mild; 7.1-21.0 = moderate; 21.1-50.0 = severe; 50.1 to 72.0 = very severe. IGA-TS = an IGA score of 0 or 1 with a ≥2-grade improvement from baseline. The IGA is an overall eczema severity rating on a 0 to 4 scale. 0: clear; no erythema or induration/papulation, no oozing/crusting; there may be minor residual discoloration. 1: almost clear; may be trace faint pink erythema, with almost no induration/papulation, and no oozing/crusting. 2: mild; may be faint pink erythema, with mild induration/papulation and no oozing/crusting. 3: moderate; may be pink-red erythema with moderate induration/papulation and may be some oozing/crusting. 4: severe; may be deep or bright red erythema with severe induration/papulation and with oozing/crusting.

BSA assessment was approximated to the nearest 0.1% using the handprint (Palmar) method as a guide. The approximate size of the participant's entire palmar surface (i.e., the palm plus 5 digits, with fingers tucked together and thumb tucked to the side) was considered as 1% BSA, and the approximate size of the participant's thumb was considered as 0.1% BSA. Change from baseline was calculated as the post-baseline value minus the baseline value.

BSA assessment was approximated to the nearest 0.1% using the handprint (Palmar) method as a guide. The approximate size of the participant's entire palmar surface (i.e., the palm plus 5 digits, with fingers tucked together and thumb tucked to the side) was considered as 1% BSA, and the approximate size of the participant's thumb was considered as 0.1% BSA. Change from baseline was calculated as the post-baseline value minus the baseline value.

The EASI scoring system is a validated scoring system that grades the physical signs of atopic dermatitis (AD) to provide a measure of AD severity (ranging from 0 to 72). The disease severity strata for the EASI are: 0 = clear; 0.1 to 1.0 = almost clear; 1.1 to 7.0 = mild; 7.1 to 21.0 = moderate; 21.1 to 50.0 = severe; 50.1 to 72.0 = very severe. Change from baseline was calculated as the post-baseline value minus the baseline value.

The EASI scoring system is a validated scoring system that grades the physical signs of atopic dermatitis (AD) to provide a measure of AD severity (ranging from 0 to 72). The disease severity strata for the EASI are: 0 = clear; 0.1 to 1.0 = almost clear; 1.1 to 7.0 = mild; 7.1 to 21.0 = moderate; 21.1 to 50.0 = severe; 50.1 to 72.0 = very severe. Change from baseline was calculated as the post-baseline value minus the baseline value.

The SCORAD assesses the extent and severity (intensity) of eczema. To determine extent, the rule of 9 or handprint method was used to calculate the eczema affected area (A) as a percentage of the whole body. Scores were added to give a possible maximum of 100%. To determine intensity, a representative area of eczema was selected. The intensity of redness, swelling, oozing/crusting, scratch marks, skin thickening (lichenification), dryness was assessed individually: none, 0; mild, 1; moderate, 2; severe, 3. Intensity scores were added together to give "B" (maximum score of 18). Subjective symptoms (itch and sleeplessness) were scored by the participant using a visual analog scale on which "0" was no itch (or no sleeplessness) and "10" was the worst imaginable itch (or sleeplessness). These scores were added to give "C" (maximum score of 20). The total score[KM25.1] (ranging from 0 to 103; a higher score indicates greater extent and severity) was calculated as: A/5 + 7B/2 + C.

The SCORAD assesses the extent and severity (intensity) of eczema. To determine extent, the rule of 9 or handprint method was used to calculate the eczema affected area (A) as a percentage of the whole body. Scores were added to give a possible maximum of 100%. To determine intensity, a representative area of eczema was selected. The intensity of redness, swelling, oozing/crusting, scratch marks, skin thickening (lichenification), dryness was assessed individually: none, 0; mild, 1; moderate, 2; severe, 3. Intensity scores were added together to give "B" (maximum score of 18). Subjective symptoms (itch and sleeplessness) were scored by the participant using a visual analog scale on which "0" was no itch (or no sleeplessness) and "10" was the worst imaginable itch (or sleeplessness). These scores were added to give "C" (maximum score of 20). The total score[KM27.1] (ranging from 0 to 103; a higher score indicates greater extent and severity) was calculated as: A/5 + 7B/2 + C.

The Itch NRS is a once-daily patient-reported measure of itch intensity assessed using an 11-point scale (0 = no itch to 10 = worst imaginable itch) that best describes their worst level of itching in the past 24 hours. The Itch NRS score for baseline was determined by averaging the 7 daily NRS scores directly before Day 1 (Day -7 to Day -1). The by-visit Itch NRS score for postbaseline visits was determined by averaging the 7 daily NRS scores directly before the visit day. Change from baseline was calculated as the post-baseline value minus the baseline value.

The Skin Pain NRS is a daily participant-reported measure (24-hour or 7-day recall) of the worst level of pain intensity from 0 (no pain) to 10 (worst pain imaginable). Participants were asked to rate the pain intensity by selecting a number that best describes the worst level of pain in the past 24 hours during the VC period and in the past 7 days during the VCE period. Change from baseline was calculated as the post-baseline value minus the baseline value.

The Skin Pain NRS is a daily participant-reported measure (24-hour or 7-day recall) of the worst level of pain intensity from 0 (no pain) to 10 (worst pain imaginable). Participants were asked to rate the pain intensity by selecting a number that best describes the worst level of pain in the past 24 hours during the VC period and in the past 7 days during the VCE period.

The study allowed participants to move to an open-label ruxolitinib 1.5% escape arm if they had not met EASI50 (50% improvement in the EASI score from baseline at 2 consecutive visits at least 1 week apart) at Week 8 (end of the double-blind, vehicle-controlled period and the start of the vehicle-controlled extension, double-blind period) or if they lost EASI50 response during the vehicle-controlled extension, double-blind period. Participants who were moved to the open-label ruxolitinib 1.5% escape arm without meeting the criteria were censored.

Only data in the DB treatment period were included in the analysis.

Only data in the DB treatment period were included in the analysis.

Relapse was assessed during the 30-day Safety Follow-up Period for participants who had an EASI75 response from baseline at the end of the VCE DB period at Week 24. Participants who experienced a relapse were those among EASI75 responders who were on study treatment at Week 24 who met relapse criteria (loss of EASI50 from baseline) at the safety follow-up visit.

Time to first retreatment following the participant's first lesion clearance during the VCE DB period was evaluated in participants who had at least 1 occurrence of lesion clearance.

The percentage of time off study treatment was calculated as the total days off study treatment due to lesion clearance divided by the total days between two visits per participant.

The percentage of time on study treatment was calculated as the total days intended on study treatment divided by the total days between two visits per participant.

The DLQI is 10-question validated questionnaire measuring how much the skin problem has affected the participant over the previous 7 days. The questionnaire is analyzed under 6 headings: symptoms and feelings (Questions 1 and 2); daily activities (Questions 3 and 4); leisure (Questions 5 and 6); work and school (Question 7); personal relations (Questions 8 and 9); treatment (Question 10). The scoring of each question is: 3, very much; 2, a lot; 1, a little; 0, not at all; not relevant, 0; Question 7, "prevented work or studying," 3. The DLQI is calculated by summing the scores of each question, resulting in a maximum of 30 and a minimum of 0. The higher the score, the more quality of life is impaired. Total DLQI scores can be categorized as: 0-1, no effect; 2-5, small effect; 6-10, moderate effect; 11-20, very large effect; 21-30, extremely large effect.

The DLQI is 10-question validated questionnaire measuring how much the skin problem has affected the participant over the previous 7 days. The questionnaire is analyzed under 6 headings: symptoms and feelings (Questions 1 and 2); daily activities (Questions 3 and 4); leisure (Questions 5 and 6); work and school (Question 7); personal relations (Questions 8 and 9); treatment (Question 10). The scoring of each question is: 3, very much; 2, a lot; 1, a little; 0, not at all; not relevant, 0; Question 7, "prevented work or studying," 3. The DLQI is calculated by summing the scores of each question, resulting in a maximum of 30 and a minimum of 0. The higher the score, the more quality of life is impaired. Total DLQI scores can be categorized as: 0-1, no effect; 2-5, small effect; 6-10, moderate effect; 11-20, very large effect; 21-30, extremely large effect. Change from baseline was calculated as the post-baseline value minus the baseline value.

The DLQI is 10-question validated questionnaire measuring how much the skin problem has affected the participant over the previous 7 days. The questionnaire is analyzed under 6 headings: symptoms and feelings (Questions 1 and 2); daily activities (Questions 3 and 4); leisure (Questions 5 and 6); work and school (Question 7); personal relations (Questions 8 and 9); treatment (Question 10). The scoring of each question is: 3, very much; 2, a lot; 1, a little; 0, not at all; not relevant, 0; Question 7, "prevented work or studying," 3. The DLQI is calculated by summing the scores of each question, resulting in a maximum of 30 and a minimum of 0. The higher the score, the more quality of life is impaired. Total DLQI scores can be categorized as: 0-1, no effect; 2-5, small effect; 6-10, moderate effect; 11-20, very large effect; 21-30, extremely large effect. Change from baseline was calculated as the post-baseline value minus the baseline value.

The POEM is a 7-question quality-of-life assessment used for monitoring atopic eczema severity, focusing on the illness as experienced by the participant. The questionnaire asks how many days the participant has been bothered by various aspects of their skin condition during the past week. The response options and corresponding scoring questionnaires are: no days (0), 1 to 2 days (1), 3 to 4 days (2), 5 to 6 days (3), and every day (4), with total scores ranging from 0 to 28. The meaning of POEM scores can be categorized as: 0 to 2 (clear/almost clear), 3 to 7 (mild eczema), 8 to 16 (moderate eczema), 17 to 24 (severe eczema), and 25 to 28 (very severe eczema). Change from baseline was calculated as the post-baseline value minus the baseline value.

The POEM is a 7-question quality-of-life assessment used for monitoring atopic eczema severity, focusing on the illness as experienced by the participant. The questionnaire asks how many days the participant has been bothered by various aspects of their skin condition during the past week. The response options and corresponding scoring questionnaires are: no days (0), 1 to 2 days (1), 3 to 4 days (2), 5 to 6 days (3), and every day (4), with a range in total score of 0 to 28. The meaning of POEM scores can be categorized as: 0 to 2 (clear/almost clear), 3 to 7 (mild eczema), 8 to 16 (moderate eczema), 17 to 24 (severe eczema), and 25 to 28 (very severe eczema). Change from baseline was calculated as the post-baseline value minus the baseline value.

The EQ-5D is a validated, self-administered, generic utility questionnaire wherein participants rate their current health state based on the following criteria (dimensions): mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The 5L indicates that, for each dimension, there are 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. The participant was asked to indicate his/her health state over the past 7 days using a scale ranging from 0 (worst imaginable health) to 100 (best imaginable health). Missing values were not imputed. Change from Baseline was calculated as the post-baseline value minus the baseline value.

The EQ-5D is a validated, self-administered, generic utility questionnaire wherein participants rate their current health state based on the following criteria (dimensions): mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The 5L indicates that, for each dimension, there are 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. The participant was asked to indicate his/her health state over the past 7 days using a scale ranging from 0 (worst imaginable health) to 100 (best imaginable health). Missing values were not imputed. Change from Baseline was calculated as the post-baseline value minus the baseline value.

The HADS is a 14-item questionnaire that assesses the levels of anxiety and depression a person is currently experiencing. There are 7 questions each for measuring anxiety and for measuring depression, with 4 possible responses to each question: 0, 1, 2, or 3. Separate scores were calculated for anxiety and depression, both ranging from 0 to 21; a higher score indicates a greater level of anxiety/depression. The recall period was the past 7 days for both the VC and VCE periods. Change from baseline was calculated as the post-baseline value minus the baseline value.

The HADS is a 14-item questionnaire that assesses the levels of anxiety and depression a person is currently experiencing. There are 7 questions each for measuring anxiety and for measuring depression, with 4 possible responses to each question: 0, 1, 2, or 3. Separate scores were calculated for anxiety and depression, both ranging from 0 to 21; a higher score indicates a greater level of anxiety/depression. The recall period was the past 7 days for both the VC and VCE periods. Change from baseline was calculated as the post-baseline value minus the baseline value.

The PROMIS Short Form - Sleep-Related Impairment (8a) is an 8-item questionnaire. Each item is rated on a 5-point scale (never, almost never, sometimes, almost always, and always). Individual items are summed to get a total score ranging from 8 to 40; higher scores indicate greater severity of sleep-related impairment. The recall period was 7 days. Change from baseline was calculated as the post-baseline value minus the baseline value.

The PROMIS Short Form - Sleep-Related Impairment (8a) is an 8-item questionnaire. Each item is rated on a 5-point scale (never, almost never, sometimes, almost always, and always). Individual items are summed to get a total score ranging from 8 to 40; higher scores indicate greater severity of sleep-related impairment. The recall period was 7 days. Change from baseline was calculated as the post-baseline value minus the baseline value.

The PROMIS Short Form - Sleep-Related Disturbance (8b) is an 8-item questionnaire. Each item is rated on a 5-point scale (never, almost never, sometimes, almost always, and always). Individual items are summed to get a total score ranging from 8 to 40; higher scores indicate greater severity of sleep-related disturbance. The recall period was 7 days. Change from baseline was calculated as the post-baseline value minus the baseline value.

The PROMIS Short Form - Sleep-Related Disturbance (8b) is an 8-item questionnaire. Each item is rated on a 5-point scale (never, almost never, sometimes, almost always, and always). Individual items are summed to get a total score ranging from 8 to 40; higher scores indicate greater severity of sleep-related disturbance. The recall period was 7 days. Change from baseline was calculated as the post-baseline value minus the baseline value.

The WPAI-AD questionnaire is a validated 6-item instrument that measures the effect of overall health and specific symptoms on productivity at work and regular activities outside of it during the past 7 days. The WPAI outcomes are expressed as impairment percentages (0% to 100% for all outcomes; higher number indicate greater impairment and less productivity [i.e., worse outcomes]): Questions: 1 = currently employed; 2 = hours missed due to AD; 3 = hours missed other reasons; 4 = hours actually worked; 5 = degree AD-affected productivity while working; 6 = degree AD-affected regular activities. Scores: multiply scores by 100 to express in percentages: percent work time missed due to AD: Q2 / (Q2 + Q4); percent impairment while working due to AD: Q5 / 10; percent overall work impairment due to AD: Q2 / (Q2 + Q4) + ([1 - (Q2 / (Q2+Q4)] × [Q5/10]); percent activity impairment due to AD: Q6 / 10. Change from baseline was calculated as the post-baseline value minus the baseline value.