Topical Ruxolitinib Evaluation in Chronic Hand Eczema

The Investigator's Global Assessment-Chronic Hand Eczema (IGA-CHE) is an instrument used to rate the severity of the participant's global CHE and is based on a 5-point scale ranging from 0 (clear) to 4 (severe) (1, almost clear; 2, mild eczema; 3, moderate eczema). IGA-CHE TS is defined as an IGA-CHE score of 0 (clear) or 1 (almost clear) with a ≥2-step improvement from Baseline.

Time frame: Baseline; Week 16

Population: Intent-to-Treat (ITT) Population: all participants who were randomized to the study. Treatment groups were defined according to the treatment assignment at the time of randomization regardless of the actual study treatment the participant might have applied during their participation in the study. Missing post-Baseline values were imputed as nonresponders.

The CHE-related Itch NRS is a once-per-24 hours (daily) participant-reported measure of the worst itch severity of their CHE assessed using an 11-point scale (0=no itch to 10=worst imaginable itch). Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

Time frame: Baseline; Weeks 1-32

Population: ITT Population. Only participants with available data were analyzed.

The CHE-related Pain NRS is a once-per-24 hours (daily) participant-reported measure of the worst pain severity of their CHE assessed using an 11-point scale (0=no pain to 10=worst imaginable pain). Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

Time frame: Baseline; Weeks 1-32

Population: ITT Population. Only participants with available data were analyzed.

The DLQI is a simple, 10-question validated questionnaire to measure how much the skin problem has affected the participant over the previous 7 days. The questionnaire was analyzed under 6 subscales as follows: 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); and treatment (Question 10). Scoring of each question is as follows: very much = 3; a lot = 2; a little = 1; not at all = 0; not relevant = 0 (Question 7: Prevented work or studying = Yes = 3). The DLQI was calculated by summing the score of each question, resulting in a maximum of 30 and a minimum of 0. The higher the score, the more quality of life was impaired.

Time frame: Baseline; up to Week 32

Population: ITT Population. Only participants with available data were analyzed.

The EQ-5D-5L questionnaire is a standardized, validated instrument for use as a measure of health outcome. The EQ-5D-5L questionnaire consists of the following 2 sections: the EQ-5D descriptive system and the EQ Visual Analog Scale (VAS). The descriptive system comprises 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: Level 1 = no problems; Level 2 = slight problems; Level 3 = moderate problems; Level 4 = severe problems; and Level 5 = extreme problems. The EQ VAS records the participant's self-rated health on a vertical VAS (0-100), where the endpoints are labeled the best health you can imagine (100 score) and the worst health you can imagine (0 score). Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

Time frame: Baseline; up to Week 32

Population: ITT Population. Only participants with available data were analyzed.

The QOLHEQ is a validated disease-specific instrument to assess disease-specific health-related quality of life in participants suffering from CHE over the past 7 days. It consists of 30 items that are summarized according to impairments for 4 subscales: symptoms, emotions, limitations in functioning, and treatment and prevention. Each item is scored on a scale of never, rarely, sometimes, often, and all the time. The overall score is calculated by summing all items and ranges from 0 to 117. Higher scores indicate a greater impact on quality of life. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

Time frame: Baseline; up to Week 36

Population: ITT Population. Only participants with available data were analyzed.

The WPAI-ChHD questionnaire is a patient-reported quantitative assessment of the amount of absenteeism (measured as percentage of work time missed \[PWTM\] due to CHE), presentism, and daily activity impairment (percentage of impairment while working \[PIWW\] due to CHE, percentage of overall work impairment \[POWI\] due to CHE, percentage of activity impairment \[PAI\] due to CHE) attributable to a specific health problem. The WPAI-ChHD is a 6-item questionnaire used to assess the impact of chronic hand dermatitis (ChHD, the same as CHE in this context) on job performance and productivity in the last 7 days. WPAI outcomes are expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity. Scores range from 0% (no impairment) to 100% (complete impairment). Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

Time frame: Baseline; up to Week 36

Population: ITT Population. Only participants with available data were analyzed.

A TEAE was defined as any AE either reported for the first time or the worsening of a pre-existing event after the first dose of study drug until the end of the safety follow-up. The severity of AEs was based on the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 using Grades 1 through 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.

Time frame: up to Week 16

Population: Safety Population

A TEAE was defined as any AE either reported for the first time or the worsening of a pre-existing event after the first dose of study drug until the end of the safety follow-up. The severity of AEs was based on the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 using Grades 1 through 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.

Time frame: up to Week 36

Population: Open-label Evaluable Population

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 drug. A TEAE was defined as any AE either reported for the first time or the worsening of a pre-existing event after the first dose of study drug until the end of the safety follow-up.

Time frame: up to Week 36

Population: Open-label Evaluable Population: all participants who applied study treatment at least once during the OLE Period

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 drug. A TEAE was defined as any AE either reported for the first time or the worsening of a pre-existing event after the first dose of study drug until the end of the safety follow-up.

Time frame: up to Week 16

Population: Safety Population: all randomized participants who applied study treatment at least once. Treatment groups were determined according to the actual treatment the participant applied on Day 1 regardless of assigned study treatment.

The investigator determined whether a change was clinically meaningful.

Time frame: up to Week 16

Population: Safety Population

The investigator determined whether a change was clinically meaningful.

Time frame: up to Week 36

Population: Open-label Evaluable Population

The EQ-5D-5L questionnaire is a standardized, validated instrument for use as a measure of health outcome. The EQ-5D-5L questionnaire consists of the following 2 sections: the EQ-5D descriptive system and the EQ Visual Analog Scale (VAS). The descriptive system comprises 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: Level 1 = no problems; Level 2 = slight problems; Level 3 = moderate problems; Level 4 = severe problems; and Level 5 = extreme problems. The EQ VAS records the participant's self-rated health on a vertical VAS (0-100), where the endpoints are labeled the best health you can imagine (100 score) and the worst health you can imagine (0 score).

Time frame: Baseline; up to Week 32

Population: ITT Population. Only participants with available data were analyzed.

The PGIC is a participants' self-reporting measure that reflects their belief about the efficacy of treatment. The PGIC is a 7-point scale depicting a participant's rating of overall improvement of CHE. Participants were asked to select 1 response from the response options that best described the overall change in their CHE since they started study treatment: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse, and 7, very much worse.

Time frame: Baseline; up to Week 32

Population: ITT Population. Only participants with available data were analyzed.

The HECSI divides the hand into 5 areas for assessment (fingertips, fingers \[except the tips\], palms, back of hands, and wrists). Each of the 5 areas of the hand are assessed separately for erythema, induration/papulation, vesicles, fissuring, scaling, and edema using the following scale: 0, no skin changes; 1, mild disease; 2, moderate disease; and 3, severe disease. To determine the HECSI score, the affected area for each location (total of both hands) is given a score from 0 to 4 (0, 0%; 1, 1%-25%; 2, 26%-50%; 3, 51%-75%; and 4, 76%-100%) based on the extent of clinical symptoms. Finally, the score given for the extent at each location is multiplied by the total sum of the intensity of each clinical feature to calculate the total HECSI score, varying from 0 to a maximum severity score of 360 points. Percentage change was calculated as the (\[post-Baseline value minus the Baseline value\]/\[Baseline value\]) \* 100.

Time frame: Baseline; up to Week 16

Population: ITT Population. Only participants with available data were analyzed.

The CHE-related Pain NRS is a once-per-24 hours (daily) participant-reported measure of the worst pain severity of their CHE assessed using an 11-point scale (0=no pain to 10=worst imaginable pain).

Time frame: Baseline; up to Week 16

Population: ITT Population. Participants with a Baseline Pain NRS Score ≥2 were analyzed. Only participants with available data were analyzed. The 95% confidence interval was calculated using the method by Brookmeyer and Crowley.

ITCH4 response was defined as a ≥4-point improvement in CHE-related Itch Numerical Rating Scale (NRS) score from Baseline. The CHE-related Itch NRS is a once-per-24 hours (daily) participant-reported measure of the worst itch severity of their CHE assessed using an 11-point scale (0=no itch to 10=worst imaginable itch).

Time frame: Baseline; Day 3; Week 1 (Day 7)

Population: ITT Population. Participants with a Baseline Itch NRS Score ≥4 were analyzed. Only participants with available data were analyzed.

ITCH4 response was defined as a ≥4-point improvement in CHE-related Itch Numerical Rating Scale (NRS) score from Baseline. The CHE-related Itch NRS is a once-per-24 hours (daily) participant-reported measure of the worst itch severity of their CHE assessed using an 11-point scale (0=no itch to 10=worst imaginable itch).

Time frame: Baseline; Weeks 4 and 16

Population: ITT Population. Participants with a Baseline Itch NRS Score ≥4 were analyzed. Missing post-Baseline values were imputed as nonresponders at Weeks 4 and 16.

The IGA-CHE is an instrument used to rate the severity of the participant's global CHE and is based on a 5-point scale ranging from 0 (clear) to 4 (severe) (1, almost clear; 2, mild eczema; 3, moderate eczema). IGA-CHE TS is defined as an IGA-CHE score of 0 (clear) or 1 (almost clear) with a ≥2-step improvement from Baseline.

Time frame: Baseline; Weeks 2, 4, 8, 12, 16, 24, and 32

Population: ITT Population. Only participants with available data were analyzed.

The CHE-related Pain NRS is a once-per-24 hours (daily) participant-reported measure of the worst pain severity of their CHE assessed using an 11-point scale (0=no pain to 10=worst imaginable pain).

Time frame: Baseline; up to Week 32

Population: ITT Population. Participants with a Baseline Pain NRS Score ≥2 were analyzed. The 95% confidence interval was calculated using the method by Brookmeyer and Crowley.

ITCH4 response was defined as a ≥4-point improvement in CHE-related Itch Numerical Rating Scale (NRS) score from Baseline. The CHE-related Itch NRS is a once-per-24 hours (daily) participant-reported measure of the worst itch severity of their CHE assessed using an 11-point scale (0=no itch to 10=worst imaginable itch).

Time frame: Baseline; up to Week 32

Population: ITT Population. Participants with a Baseline Itch NRS Score ≥4 were analyzed. The 95% confidence interval was calculated based on the Brookmeyer and Crowley method.