Ravulizumab Versus Placebo in Adult Participants With Dermatomyositis

Data are presented for the number of participants with a TIS40 response, defined as an IMACS-TIS score ≥ 40 at Week 26. IMACS-TIS is a clinical instrument that encompasses 6 core set measure (CSMs) (physician, patient, extra-muscular global activity, muscle strength, Health Assessment Questionnaire \[HAQ\], and muscle enzyme levels). A Total Improvement Score (TIS: 0-100), was determined by summing scores in each CSM, and was based on the improvement and relative weight of each CSM. A higher score indicated greater improvement. TIS40 was considered a moderate improvement score.

Time frame: Week 26

Population: Randomized Set, which included all randomized participants grouped by randomized treatment group.

The CDASI is an instrument that separately measures activity and damage in the skin of dermatomyositis (DM) participants. It contains 3 activity measures (erythema, scale, and erosion/ulceration) and 2 damage measures (poikiloderma and calcinosis). CDASI score is calculated by rating the severity of skin disease in 15 anatomical locations on the body based on the activity and damage components. CDASI was completed by the Clinician or Clinician-Investigator while examining the participant. Total CDASI scores ranged from 0-100, with higher scores indicating a greater disease severity. Change from baseline in CDASI Total Activity Score at Week 26 was analyzed using a mixed model repeated measures (MMRM). The MMRM model included the observed Total Activity Score values at post baseline visits (Week 26) as the dependent variable.

Time frame: Baseline, Week 26

Population: Randomized Set, which included all randomized participants grouped by randomized treatment group. Overall number of participants analyzed = participants with evaluable data for the outcome measure.

The MDAAT assesses disease activity of extra-muscular organ systems and muscles in participants with DM. The validated MDAAT tool measures the degree of disease activity of extra-muscular organ systems and muscle on a 0-10 centimeter (cm) visual analog scale (VAS). Extra-muscular activity ranged between 0 and 10, where, 0 cm = absent and 10 cm = maximum disease activity.

Time frame: Baseline, Week 26

Population: Randomized Set, which included all randomized participants grouped by randomized treatment group. Overall number of participants analyzed = participants with evaluable data for the outcome measure.

The HAQ is a brief self-report questionnaire that assesses physical function pertaining to activities of daily living in a variety of domains. The HAQ includes 20 questions relating to 8 domains of function: dressing and grooming, arising, eating, walking, hygiene, reach, grip and usual activities. For each of the categories, participants reported the amount of difficulty they had in performing 2 or 3 specific subcategory items. The standard disability score is calculated from the 8 categories by dividing the sum of the individual categories by the number of categories answered, yielding a score from 0 (without any difficulty) to 3 (unable to do), with higher values indicating higher disability.

Time frame: Baseline, Week 26

Population: Randomized Set, which included all randomized participants grouped by randomized treatment group. Overall number of participants analyzed = participants with evaluable data for the outcome measure.

The purpose of the MMT-8 was to measure muscle strength as part of the physical examination. It included a subset of 8 muscle groups: neck flexors, deltoids, biceps, wrist, extensors, gluteus maximus and medius, quadriceps, and ankle dorsiflexors. Total MMT8 scores ranged from 0 (lowest strength) to 150 (highest strength).

Time frame: Baseline, Week 26

Population: Randomized Set, which included all randomized participants grouped by randomized treatment group. Overall number of participants analyzed = participants with evaluable data for the outcome measure.

The patient global activity assessment provides an overall rating of disease activity related to myositis from the participant's perspective. Participants were asked to consider all of the active inflammation in their own muscles, skin, joints, intestines, heart, lungs, or other parts of the body that can improve with treatment. The patient global disease activity score was recorded on a 10-cm VAS that contained a smiley face at the 0-cm anchor and a sad face at the 10 cm anchor to help participants understand the scale. Scores ranged from 0 (no evidence of disease activity) to 10 (extremely active or severe disease activity).

Time frame: Baseline, Week 26

Population: Randomized Set, which included all randomized participants grouped by randomized treatment group. Overall number of participants analyzed = participants with evaluable data for the outcome measure.

The physician global activity assessment provides an overall rating of disease activity related to myositis. Disease activity is judged by the physician based on all information available at the time of evaluation, including the participant's appearance, medical history, physical examination, laboratory testing, and prescribed medical therapy. The global disease activity score is recorded on a 10-cm VAS, where 0 cm= no evidence of disease activity and 10 cm= extremely severe disease activity.

Time frame: Baseline, Week 26

Population: Randomized Set, which included all randomized participants grouped by randomized treatment group. Overall number of participants analyzed = participants with evaluable data for the outcome measure.

Acute rescue therapy with standard DM treatment included an increased dose of a medication that was being taken for DM or the initiation of a new DM treatment (glucocorticoid and/or immunosuppressive/immunomodulatory therapy \[ISTs\]). Data are presented for the number of participants who received acute rescue therapy with standard DM treatment.

Time frame: Baseline through Week 26

Population: Randomized Set, which included all randomized participants grouped by randomized treatment group.

TIS20 was defined as a ≥20-point improvement response on IMACS-TIS. IMACS-TIS is a clinical instrument that encompasses 6 CSMs (physician, patient, extra-muscular global activity, muscle strength, HAQ, and muscle enzyme levels). A Total Improvement Score (TIS: 0-100), was determined by summing scores in each CSM, and was based on the improvement and relative weight of each CSM. Higher scores indicated greater improvement/response. TIS20 is considered a mild improvement score.

Time frame: Week 26

Population: Randomized Set, which included all randomized participants grouped by randomized treatment group.

TIS60 was defined as a ≥60-point improvement response on IMACS-TIS. IMACS-TIS is a clinical instrument that encompasses 6 CSMs (physician, patient, extra-muscular global activity, muscle strength, HAQ, and muscle enzyme levels). A Total Improvement Score (TIS: 0-100), was determined by summing scores in each CSM, and was based on the improvement and relative weight of each CSM. Higher scores indicated greater improvement/response. TIS60 is considered a severe improvement score.

Time frame: Week 26

Population: Randomized Set, which included all randomized participants grouped by randomized treatment group.

The CDASI is an instrument that separately measures activity and damage in the skin of dermatomyositis (DM) participants. It contains 3 activity measures (erythema, scale, and erosion/ulceration) and 2 damage measures (poikiloderma and calcinosis). CDASI score is calculated by rating the severity of skin disease in 15 anatomical locations on the body based on the activity and damage components. CDASI was completed by the Clinician or Clinician-Investigator while examining the participant. Total CDASI scores ranged from 0-100, with higher scores indicating a greater disease severity. Data are presented for the number of participants with a CDASI response. Response was defined as a \>=7 point improvement in participants who did not have an intercurrent event at or prior to the relevant timepoint.

Time frame: Week 26

Population: Randomized Set, which included all randomized participants grouped by randomized treatment group.

CW was defined as one of the following: 1. Physician's global activity VAS worsening ≥ 2 cm and MMT-8 worsening ≥ 20% compared to baseline 2. Global extra muscular activity worsening ≥ 2 cm on the MDAAT VAS compared to baseline 3. Any 3 of 5 CSMs (excluding muscle enzymes) worsening by ≥ 30% compared to baseline Data are presented for the number of participants with clinical worsening during the RCP at 2 consecutive visits.

Time frame: Baseline through Week 26

Population: Randomized Set, which included all randomized participants grouped by randomized treatment group.

CDA-IGA is a scale that was created to measure disease severity in participants with skin disease. It is a 5-point scale (0 = clear; 1 = almost clear; 2 = mild; 3 = moderate; 4 = severe) with morphologic descriptors for each score. The CDA-IGA was completed by the Investigator and was used to describe the overall appearance of lesions at a given time point. Data are presented for the number of participants with a CDA-IGA response at Week 26. A response was defined as participants with clear or almost clear skin (score of 0 or 1) who did not have an intercurrent event at or before the relevant timepoint.

Time frame: Week 26

Population: Randomized Set, which included all randomized participants grouped by randomized treatment group.

Laboratory tests were conducted to measure serum activities of muscle associated enzymes including creatine kinase (CK), alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and aldolase. Data are presented for the number of participants who had an abnormal muscle enzyme at baseline that had been normalized at Week 26.

Time frame: Baseline, Week 26

Population: Randomized Set, which included all randomized participants grouped by randomized treatment group.

TIS20, 40 and 60 were defined as a ≥20, ≥40 and ≥60-point improvement response on IMACS-TIS respectively. IMACS-TIS is a clinical instrument that encompasses 6 CSMs (physician, patient, and extra-muscular global activity, muscle strength, HAQ, and muscle enzyme levels). A Total Improvement Score (TIS: 0-100), was determined by summing scores in each CSM, and was based on the improvement and relative weight of each CSM. Higher scores indicated greater improvement/response. TIS20, 40 and 60 were considered mild, moderate and severe improvement scores respectively. Data are presented for the time to first response of TIS20, TIS40, or TIS60. The median time to TIS20, TIS40, and TIS60 was defined at the time in which 50% of the participants experienced TIS20, TIS40, or TIS60, respectively, based on a Kaplan-Meier analysis.

Time frame: Baseline through Week 26

Population: Randomized Set, which included all randomized participants grouped by randomized treatment group. Overall number of participants analyzed = participants evaluable for this outcome measure. Number analyzed = participant evaluable for the specified category.

TIS scores ranged from 0-100 with higher scores indicating a greater improvement. Scores were determined by summing scores in each of the 6 CSMs of the IMAC (physician, patient, extra-muscular global activity, muscle strength, HAQ, and muscle enzyme levels). Clinically meaningful thresholds for improvement were defined as ≥ 20 point improvement response on IMACS-TIS (TIS20; mild), ≥ 40 point improvement response on IMACS TIS (TIS40; moderate) and ≥ 60 point improvement response on IMACS-TIS (TIS60; severe). Scores were based on the improvement and relative weight of each CSM. Data are presented for TIS (least squares mean) at Week 26.

Time frame: Week 26

Population: Randomized Set, which included all randomized participants grouped by randomized treatment group. Overall number of participants analyzed = participants with evaluable data for the outcome measure.