Efficacy and Safety Study of Sirukumab in Patients With Giant Cell Arteritis

Participants who remained in sustained remission without requirement for rescue therapy or treatment change at each scheduled visit of Part B were defined as participants having achieved all of the following criteria: 1. Participants in sustained remission at the Week 52 visit of Part A, 2. Absence of disease flare, 3. No requirement for rescue therapy at any time through Week 24 of Part B, 4. No requirement for treatment change at any time through Week 24 of Part B. Remission was defined as absence of clinical signs and symptoms of GCA and normalization of ESR [<30 millimeters per hour] and CRP [<1 milligram/deciliter]) and flare was defined as recurrence of symptoms attributable to active GCA, with or without elevations in ESR and/or CRP.

Cumulative prednisone is the dose from the taper (both open-label and blinded) as well as from the corticosteroid rescue therapies. Cumulative dose at the specified Week was derived as the sum of all the doses from Baseline to the specified Week at each visit was calculated based on the number of participants who attended that visit. For the main analysis of cumulative prednisone dose over time. Data for Prednisone Dose- Study Drug and Prednisone Equivalent Concomitant Therapy for part A is presented. ITT population and the number of participants included at specific time points were based on the participants who attended a scheduled or unscheduled visit mapped to that time point and received a total prednisone dose greater than 0 mg.

Sustained remission was defined as having achieved all of the following: 1) remission at Week 12 (absence of signs and symptoms of GCA and normalization of ESR and CRP), 2) absence of disease flare Week 12 through Week 52 with or without elevations in ESR and/or CRP, 3) completion of the assigned prednisone taper, and 4) no requirement for rescue therapy through Week 52. Remission was defined as absence of clinical signs and symptoms of GCA and normalization of ESR [<30millimeters per hour] and CRP [<1milligram/deciliter]) and Flare was defined as recurrence of symptoms attributable to active GCA, with or without elevations in ESR and/or CRP. Data for number of participants in sustained remission over time for Part B is presented. Only participants who were in sustained remission at Week 52 of Part A, who Completed the Week X Visit of Part B or who Withdraw before 10th of October 2017 were included in the analysis.

Clinical remission was defined as absence of clinical signs and symptoms of GCA, which was determined by a lack of flare for the participant. If a participant had a flare, they had one or more signs and symptoms, and therefore are not considered as being in clinical remission. Time to first disease flare (days) was calculated as (Date of First Flare - Date of Clinical Remission + 1 day). Data for Time to first disease flare after clinical remission for part A is presented.

Clinical remission was defined as absence of clinical signs and symptoms of GCA. If a participant had a flare, they had one or more signs and symptoms, and therefore are not considered as being in clinical remission. Time to event (days) is defined as the duration in days from the date of the Week 52 visit of Part A to the start date of Event (Date of First Flare - Date of Week 52 visit of Part A + 1). Data for Time to first disease flare after clinical remission for part B is presented.

This summarizes disease flares over time with no adjustment for exposure to study drugs, calculated by taking the last visit before a participant withdrew and then counting the number of participants with at least 1 flare up to that point and summing up the total number of flares experienced by each of these participants; participants who did not reach Week 2 were not included in this analysis. Data for number of disease flares per participant over time for part A were presented.

Number of participants with at least one hospitalization for disease flare at a given visit is the number of participants with at least one hospitalization for disease flare between first SC IP intake and the day of the given visit. Data for participants requiring at least one hospitalization for disease flare for part A is presented.

Number of hospitalizations for disease flare at given visit is the number of hospitalizations for disease flare between first SC IP intake and the day of the of the given visit.. Data for number of hospitalizations for disease flare over time for part A was presented.

SF-36v2 acute health survey questionnaire consists of the following 8 multi-item scales: 1. Limitations in physical functioning due to health problems, 2. Limitations in usual role activities due to physical health problems, 3. Bodily pain, 4. General mental health (psychological distress and well-being), 5. Limitations in usual role activities due to personal or emotional problems, 6. Limitations in social functioning due to physical or mental health problems. 7. Vitality (energy and fatigue) and 8. General health perception. These 8 scales were scored from 0 to 100, 0 (worst score) to 100 (best score) where higher scores indicates better health. Data for Physical Component Summary (PCS), Mental Component Summary (MCS) scores was presented.

EuroQoL-5 Dimensions consist of 2 elements: the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The EQ-5D descriptive system comprised of following 5 dimensions: 1.Mobility, 2.Self-Care, 3.Usual Activities, 4.Pain/Discomfort and 5.Anxiety/Depression. Each of these 5 dimensions has 5 levels: 1: no problems; 2: slight problems; 3: moderate problems; 4: severe problems; 5: Unable to do. The digits for each of 5 dimensions were combined in a 5-digit number describing the participant's health state: e.g. state 11111 indicates no problem on any of the 5 dimensions. Index score was derived from the 5 dimensions scores using UK tariff. The weights based from the UK population was used for conversion, regardless of the origin country of participant. The score ranged from -0.594 (worst score) to 1.000 (best score).

EQ-5D essentially consists of 2 elements: the EQ-5D descriptive system and the EQ VAS. The EQ-5D descriptive system comprised of the following 5 dimensions: 1.Mobility, 2.Self-Care, 3.Usual Activities, 4.Pain/Discomfort and 5.Anxiety/Depression. Each of these 5 dimensions has 5 levels: 1: no problems; 2: slight problems; 3: moderate problems; 4: severe problems; 5: Unable to do. The digits for each of the 5 dimensions were combined in a 5-digit number describing the participant's health state: e.g. state 11111 indicates no problem on any of the 5 dimensions. The index score was derived from the 5 dimensions scores using UK tariff. The weights based from the UK population was used for the conversion, regardless of the origin country of participant. The score ranged from -0.594 (worst score) to 1 (best score). The EQ VAS records the respondent's self-rated health on a vertical line, VAS where the endpoints are 'Best imaginable health state' and 'Worst imaginable health state'.

The FACIT-Fatigue is a 13-item questionnaire formatted for self-administration that assesses participant reported fatigue and its impact upon daily activities and function over the past seven days. Participants were asked to answer each question using a 5-point Likert-type scale (4 = Not at all; 3 = A little bit; 2 = Somewhat; 3 = Quite a bit; and 0 = Very Much) where 0 is a bad response and 4 is good response. Each of the 13 items of the FACIT-Fatigue Scale ranges from 0-4, with a range of possible total score from 0-52, 0 (Extreme fatigue) to 52 (No fatigue) where 0 being the worst possible score and 52 the best (i.e. less fatigue). Scores below 30 indicate severe fatigue. Each negatively-worded item response was recoded so that 0 is a bad response and 4 is good response. All responses were added with equal weight to obtain the total score. The total score was calculated as the sum of all the individual items after recoding some of the items.

The assessment of pain severity was made using a single pain severity item on which participants were asked to rate the severity of their average pain on a 11-point numeric rating scale ranging from 0, "no pain" to 10, "the worst pain imaginable". Data for NRS scores over time for part A is reported.

Health Assessment Questionnaire-Disability Index (HAQ-DI) indicates the extent of participant's functional ability during the past week, and was assessed for subgroup of participants with symptoms of Polymyalgia Rheumatic (PMR). HAQ-DI included 20 questions in 8 categories of functioning - dressing and grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Each functional area contains at least two questions. For each question, there is a 4-level difficulty scale that is scored from 0 (minimum) to 3 (Maximum), representing "no difficulty" (0), "some difficulty" (1), "much difficulty" (2), and "unable to do" (3) where, lower score indicates less disability and higher scores indicates worse disability. Total score was calculated as average scores of 20 questions which can be interpreted in terms of 3 categories: from 0 to 1: mild difficulties to moderate disability, from 1 to 2: disability moderate to severe, from 2 to 3: severe to very severe disability.

Patient-reported response to treatment was assessed using the PGIC measure, a single item completed by participant to provide a clinically meaningful summary of an individual's response to treatment. The assessment provides an estimate of the magnitude of treatment response at different time points during the study. Responses include: Much Better, Better, Slightly Better, No Change, Slightly Worse, Worse, and Much Worse. The categorical data of participant rating of change is summarized by treatment group, visit and response category.

The Patient's Global Assessments of Disease Activity was recorded on a Visual analog scale (VAS) of 10 centimeter (cm) ranging from 0 ("very well) to 10 ("very poor").

The Physician's Global Assessments of Disease Activity was recorded on a VAS of 10 cm ranging from 0 ("none") to 10 ("extremely active").

Blood samples were collected for analysis of CRP. Baseline was defined as the last non-missing value before first SC IP intake. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for Change from Baseline in serum CRP over time for part A was reported. The Safety set comprised of all randomized participants who received at least 1 dose of SC IP.

Blood samples were collected for analysis of ESR. Baseline was defined as the last non-missing value before first SC IP intake. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for Change from Baseline in ESR over time for part A was reported.

An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment or all events of possible drug-induced liver injury with hyperbilirubinaemia were categorized as SAE. Number of participants with AEs, SAEs and corticosteroid related AEs have been reported.

SBP and DBP were measured in semi-supine position after 5 minutes rest at indicated time points. Baseline was defined as the last non-missing value before first SC IP intake. Change from Baseline was defined as post-Baseline value minus Baseline value.

Pulse rate was measured in semi-supine position after 5 minutes rest at Baseline and up to 52 weeks. Baseline was defined as the last non-missing value before first SC IP intake. Change from Baseline was defined as post-Baseline value minus Baseline value.

Temperature was measured in semi-supine position after 5 minutes rest at Baseline and up to 52 weeks. Baseline was defined as the last non-missing value before first SC IP intake. Change from Baseline was defined as post-Baseline value minus Baseline value.

Blood samples were collected to analyze the hematology parameters including Eosinophils, Leukocytes, Lymphocytes, Neutrophils and Platelets. Change from Baseline is presented for these parameters. Baseline was defined as the last non-missing value before first SC IP intake. Change from Baseline was defined as post-Baseline value minus Baseline value.

Blood samples were collected to analyze the hematology parameters including MCHC and Hemoglobin. Change from Baseline is presented for these parameters. Baseline was defined as the last non-missing value before first SC IP intake. Change from Baseline was defined as post-Baseline value minus Baseline value.

Blood samples were collected to analyze the hematology parameter Hematocrit. Change from Baseline is presented for this parameter. Baseline was defined as the last non-missing value before first SC IP intake. Change from Baseline was defined as post-Baseline value minus Baseline value.

Blood samples were collected to analyze the hematology parameter Erythrocytes Mean Corpuscular Volume. Change from Baseline is presented for this parameter. Baseline was defined as the last non-missing value before first SC IP intake. Change from Baseline was defined as post-Baseline value minus Baseline value.

Blood samples were collected to analyze the hematology parameter Erythrocytes Mean Corpuscular Hemoglobin. Change from Baseline is presented for this parameter. Baseline was defined as the last non-missing value before first SC IP intake. Change from Baseline was defined as post-Baseline value minus Baseline value.

Blood samples were collected to analyze the hematology parameter Erythrocytes. Change from Baseline is presented for this parameter. Baseline was defined as the last non-missing value before first SC IP intake. Change from Baseline was defined as post-Baseline value minus Baseline value.

Blood samples were collected to analyze the chemistry parameters including Calcium, Carbon Dioxide, Chloride, Glucose, Phosphate, Potassium, Sodium and Urea . Change from Baseline is presented for these parameters. Baseline was defined as the last non-missing value before first SC IP intake. Change from Baseline was defined as post-Baseline value minus Baseline value.

Blood samples were collected to analyze the chemistry parameters including Albumin and Protein. Change from Baseline is presented for these parameters. Baseline was defined as the last non-missing value before first SC IP intake. Change from Baseline was defined as post-Baseline value minus Baseline value.

Blood samples were collected to analyze the chemistry parameters including ALT,ALP and AST. Change from Baseline is presented for these parameters. Baseline was defined as the last non-missing value before first SC IP intake. Change from Baseline was defined as post-Baseline value minus Baseline value.

Blood samples were collected to analyze the chemistry parameters including bilirubin, creatinine, direct bilirubin and indirect bilirubin. Baseline was defined as the last non-missing value before first SC IP intake. Change from Baseline was defined as post-Baseline value minus Baseline value.

Blood samples for Pharmacokinetic analysis of sirukumab serum concentrations were planned to be collected at specified time points.

Blood samples for Pharmacokinetic analysis of Serum anti-sirukumab antibodies were planned to be collected at specified time points.

Blood samples for Pharmacodynamic analysis were planned but not collected due to early termination of study.

An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment or all events of possible drug-induced liver injury with hyperbilirubinaemia were categorized as SAE. Number of participants with AEs, SAEs and corticosteroid related AEs for part B have been reported.

An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment or all events of possible drug-induced liver injury with hyperbilirubinaemia were categorized as SAE. Number of participants with AEs, SAEs and corticosteroid related AEs for part B have been reported.

SBP and DBP were measured in semi-supine position after 5 minutes rest for the participant. Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who received at least one dose of 100 mg OL sirukumab is presented.

SBP and DBP were measured in semi-supine position after 5 minutes rest for the participant. Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who never received 100 mg open label Sirukumab has been presented.

Pulse rate was measured in semi-supine position after 5 minutes rest. Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who received at least one dose of 100 mg OL sirukumab is presented.

Pulse rate was measured in semi-supine position after 5 minutes rest. Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who never received 100 mg open label Sirukumab is presented.

Temperature was measured in semi-supine position after 5 minutes rest.. Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who received at least one dose of 100 mg OL sirukumab is presented.

Temperature was measured in semi-supine position after 5 minutes rest.. Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who never received 100 mg open label Sirukumab has been presented.

Blood samples were collected to analyze the hematology parameters including Eosinophils, Leukocytes, Lymphocytes, Neutrophils and Platelets. Change from Baseline is presented for these parameters.Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who received at least one dose of 100 mg OL sirukumab is presented.

Blood samples were collected to analyze the hematology parameters including Eosinophils, Leukocytes, Lymphocytes, Neutrophils and Platelets. Change from Baseline is presented for these parameters.Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who never received 100 mg open label Sirukumab has been presented.

Blood samples were collected to analyze the hematology parameters including MCHC and Hemoglobin. Change from Baseline is presented for these parameters. Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who received at least one dose of 100 mg OL sirukumab is presented.

Blood samples were collected to analyze the hematology parameters including MCHC and Hemoglobin. Change from Baseline is presented for these parameters. Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who never received 100 mg open label Sirukumab has been presented.

Blood samples were collected to analyze the hematology parameter Hematocrit. Change from Baseline is presented for this parameter. Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who received at least one dose of 100 mg OL sirukumab is presented.

Blood samples were collected to analyze the hematology parameter Hematocrit. Change from Baseline is presented for this parameter. Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who never received 100 mg open label Sirukumab has been presented.

Blood samples were collected to analyze the hematology parameter Erythrocytes Mean Corpuscular Volume. Change from Baseline is presented for this parameter. Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who received at least one dose of 100 mg OL sirukumab is presented.

Blood samples were collected to analyze the hematology parameter Hematocrit. Change from Baseline is presented for this parameter. Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who never received 100 mg open label Sirukumab has been presented.

Blood samples were collected to analyze the hematology parameter Erythrocytes Mean Corpuscular Hemoglobin. Change from Baseline is presented for this parameter. Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who received at least one dose of 100 mg OL Sirukumab is presented.

Blood samples were collected to analyze the hematology parameter Erythrocytes Mean Corpuscular Hemoglobin. Change from Baseline is presented for this parameter. Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who never received 100 mg open label Sirukumab has been presented.

Blood samples were collected to analyze the hematology parameter Erythrocytes. Change from Baseline is presented for this parameter. Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who received at least one dose of 100 mg OL Sirukumab is presented.

Blood samples were collected to analyze the hematology parameter Erythrocytes. Change from Baseline is presented for this parameter. Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who never received 100 mg open label Sirukumab has been presented.

Blood samples were collected to analyze the chemistry parameters including Calcium, Carbon Dioxide, Chloride, Glucose, Phosphate, Potassium, Sodium and Urea. Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who received at least one dose of 100 mg OL Sirukumab is presented.

Blood samples were collected to analyze the chemistry parameters including Calcium, Carbon Dioxide, Chloride, Glucose, Phosphate, Potassium, Sodium and Urea. Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who never received 100 mg open label Sirukumab has been presented.

Blood samples were collected to analyze the chemistry parameters including Albumin and Protein. Change from Baseline is presented for these parameters. Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who received at least one dose of 100 mg OL sirukumab is presented.

Blood samples were collected to analyze the chemistry parameters including Albumin and Protein. Change from Baseline is presented for these parameters. Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who never received 100 mg open label Sirukumab has been presented.

Blood samples were collected to analyze the chemistry parameters including ALT,ALP and AST. Change from Baseline is presented for these parameters. Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who received at least one dose of 100 mg OL sirukumab is presented.

Blood samples were collected to analyze the chemistry parameters including ALT,ALP and AST. Change from Baseline is presented for these parameters. Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who never received 100 mg open label Sirukumab has been presented

Blood samples were collected to analyze the chemistry parameters including Albumin and Protein. Change from Baseline is presented for these parameters. Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who received at least one dose of 100 mg OL sirukumab is presented.

Blood samples were collected to analyze the chemistry parameters including Albumin and Protein. Change from Baseline is presented for these parameters. Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who never received 100 mg open label Sirukumab has been presented.

Cumulative prednisone dose is the cumulative doses taken from start of Part B. The cumulative prednisone dose at each visit was calculated based on the number of participants who attended that visit. Data for participants who received at least one dose of 100mg open label Sirukumab was presented.

Cumulative prednisone dose is the cumulative doses taken from start of Part B. The cumulative prednisone dose at each visit was calculated based on the number of participants who attended that visit. Data for participants who never received 100 mg open label Sirukumab has been presented.

This summarizes disease flares over time with no adjustment for exposure to study drugs, calculated by taking the last visit before a participant withdrew and then counting the number of participants with at least 1 flare up to that point and summing up the total number of flares experienced by each of these participants. Data for number of disease flares per participant over time for part B were presented.

Number of participants with at least one flare at a given visit was the number of participants with at least one flare between first SC IP intake and the day of the given visit. The hospitalizations for disease flare were planned to be identified through the adjudication of adverse events of special interest, and include events from the category: "Severe Flare including Hospitalizations". Data for participants requiring hospitalizations for disease flare for part B was not available due to early termination of study.

Number of participants with at least one flare at a given visit was the number of participants with at least one flare between first SC IP intake and the day of the given visit. The hospitalizations for disease flare were planned to be identified through the adjudication of adverse events of special interest, and include events from the category: "Severe Flare including Hospitalizations". Data for participants requiring hospitalizations for disease flare for part B was not available due to early termination of study.

SF-36v2 acute health survey questionnaire was developed as part of the Rand Health Insurance Experiment and consists of the following 8 multi-item scales: 1. Limitations in physical functioning due to health problems, 2. Limitations in usual role activities due to physical health problems, 3. Bodily pain, 4. General mental health (psychological distress and well-being), 5. Limitations in usual role activities due to personal or emotional problems, 6. Limitations in social functioning due to physical or mental health problems. 7. Vitality (energy and fatigue) and 8. General health perception. These 8 scales were scored from 0 to 100, 0 (worst score) to 100 (best score) where higher scores indicates better health. Data for participants (Par) who received at least one dose of 100 mg OL Sirukumab has been presented. Baseline was the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value.

SF-36v2 acute health survey questionnaire was developed as part of the Rand Health Insurance Experiment and consists of the following 8 multi-item scales: 1. Limitations in physical functioning due to health problems, 2. Limitations in usual role activities due to physical health problems, 3. Bodily pain, 4. General mental health (psychological distress and well-being), 5. Limitations in usual role activities due to personal or emotional problems, 6. Limitations in social functioning due to physical or mental health problems. 7. Vitality (energy and fatigue) and 8. General health perception. These 8 scales were scored from 0 to 100, 0 (worst score) to 100 (best score) where higher scores indicates better health. Data for participants (Par) who never received 100 mg OL Sirukumab has been presented. Baseline was the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value.

EuroQoL-5 Dimensions consist of 2 elements: the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The EQ-5D descriptive system comprised of following 5 dimensions: 1.Mobility, 2.Self-Care, 3.Usual Activities, 4.Pain/Discomfort and 5.Anxiety/Depression. Each of these 5 dimensions has 5 levels: 1: no problems; 2: slight problems; 3: moderate problems; 4: severe problems; 5: Unable to do. The digits for each of 5 dimensions were combined in a 5-digit number describing the participant's health state: e.g. state 11111 indicates no problem on any of the 5 dimensions. Index score was derived from the 5 dimensions scores using UK tariff. The weights based from the UK population was used for conversion, regardless of the origin country of participant. The score ranged from -0.594 (worst score) to 1.000 (best score). Baseline was last measurement done up to and including Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value.

EuroQoL-5 Dimensions consist of 2 elements: the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The EQ-5D descriptive system comprised of following 5 dimensions: 1.Mobility, 2.Self-Care, 3.Usual Activities, 4.Pain/Discomfort and 5.Anxiety/Depression. Each of these 5 dimensions has 5 levels: 1: no problems; 2: slight problems; 3: moderate problems; 4: severe problems; 5: Unable to do. The digits for each of 5 dimensions were combined in a 5-digit number describing the participant's health state: e.g. state 11111 indicates no problem on any of the 5 dimensions. Index score was derived from the 5 dimensions scores using UK tariff. The weights based from the UK population was used for conversion, regardless of the origin country of participant. The score ranged from -0.594 (worst score) to 1.000 (best score). Baseline was last measurement done up to and including Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value.

The FACIT-Fatigue is a 13-item questionnaire formatted for self-administration that assesses participant reported fatigue and its impact upon daily activities and function over the past seven days. Participants were asked to answer each question using a 5-point Likert-type scale (4 = Not at all; 3 = A little bit; 2 = Somewhat; 3 = Quite a bit; and 0 = Very Much) where 0 is a bad response and 4 is good response. Each of the 13 items of the FACIT-Fatigue Scale ranges from 0-4, with a range of possible total score from 0-52, 0 (Extreme fatigue) to 52 (No fatigue) where 0 being the worst possible score and 52 the best (i.e. less fatigue). Scores below 30 indicate severe fatigue. Baseline was the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value.

The FACIT-Fatigue is a 13-item questionnaire formatted for self-administration that assesses participant reported fatigue and its impact upon daily activities and function over the past seven days. Participants were asked to answer each question using a 5-point Likert-type scale (4 = Not at all; 3 = A little bit; 2 = Somewhat; 3 = Quite a bit; and 0 = Very Much) where 0 is a bad response and 4 is good response. Each of the 13 items of the FACIT-Fatigue Scale ranges from 0-4, with a range of possible total score from 0-52, 0 (Extreme fatigue) to 52 (No fatigue) where 0 being the worst possible score and 52 the best (i.e. less fatigue). Scores below 30 indicate severe fatigue. Baseline was the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Participants with post baseline data were reported.

The assessment of pain severity was made using a single pain severity item on which participants were asked to rate the severity of their average pain now on an 11-point numeric rating scale ranging from 0, "no pain" to 10, "the worst pain imaginable". Baseline was the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value.

The assessment of pain severity was made using a single pain severity item on which participants were asked to rate the severity of their average pain now on an 11-point numeric rating scale ranging from 0, "no pain" to 10, "the worst pain imaginable". Baseline was the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Participants with post baseline data were reported.

Health Assessment Questionnaire-Disability Index (HAQ-DI) indicates the extent of participant's functional ability during the past week, and was assessed for subgroup of participants with symptoms of Polymyalgia Rheumatic (PMR). HAQ-DI included 20 questions in 8 categories of functioning - dressing and grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Each functional area contains at least two questions. For each question, there is a 4-level difficulty scale that is scored from 0 (minimum) to 3 (Maximum), representing "no difficulty" (0), "some difficulty" (1), "much difficulty" (2), and "unable to do" (3) where, lower score indicates less disability and higher scores indicates worse disability. Total score was calculated as average scores of 20 questions which can be interpreted in terms of 3 categories: from 0 to 1: mild difficulties to moderate disability, from 1 to 2: disability moderate to severe, from 2 to 3: severe to very severe disability

Health Assessment Questionnaire-Disability Index (HAQ-DI) indicates the extent of participant's functional ability during the past week, and was assessed for subgroup of participants with symptoms of Polymyalgia Rheumatic (PMR). HAQ-DI included 20 questions in 8 categories of functioning - dressing and grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Each functional area contains at least two questions. For each question, there is a 4-level difficulty scale that is scored from 0 (minimum) to 3 (Maximum), representing "no difficulty" (0), "some difficulty" (1), "much difficulty" (2), and "unable to do" (3) where, lower score indicates less disability and higher scores indicates worse disability. Total score was calculated as average scores of 20 questions which can be interpreted in terms of 3 categories: from 0 to 1: mild difficulties to moderate disability, from 1 to 2: disability moderate to severe, from 2 to 3: severe to very severe disability

The Patient's Global Assessments of Disease Activity was recorded on a Visual analog scale (VAS). of 10 centimeter (cm) ranging from 0 ("very well) to 10 ("very poor"). Baseline was the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value.

The Patient's Global Assessments of Disease Activity was recorded on a Visual analog scale (VAS). of 10 centimeter (cm) ranging from 0 ("very well) to 10 ("very poor"). Baseline was the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Participants with post baseline data were reported.

In PhGA was based on "What is physician's assessment of the participant's current disease activity". PhGA used a 10 cm VAS ranging from 0 ("none") to 10 ("extremely active"). Baseline was the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value.

In PhGA was based on "What is physician's assessment of the participant's current disease activity". PhGA used a 10 cm VAS ranging from 0 ("none") to 10 ("extremely active"). Baseline was the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Participants with post baseline data were reported.

Patient-reported response to treatment was assessed using the PGIC measure, a single item completed by participant to provide a clinically meaningful summary of an individual's response to treatment. The assessment provides an estimate of the magnitude of treatment response at different time points during the study. Responses include: Much Better, Better, Slightly Better, No Change, Slightly Worse, Worse, and Much Worse. The categorical data of participant rating of change is summarized by treatment group, visit and response category.

Patient-reported response to treatment was assessed using the PGIC measure, a single item completed by participant to provide a clinically meaningful summary of an individual's response to treatment. The assessment provides an estimate of the magnitude of treatment response at different time points during the study. Responses include: Much Better, Better, Slightly Better, No Change, Slightly Worse, Worse, and Much Worse. The categorical data of participant rating of change is summarized by treatment group, visit and response category.

Blood samples were collected for analysis of CRP. Data for Change from Baseline in serum CRP over time for part B was reported. Baseline was the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value.

Blood samples were collected for analysis of CRP. Data for Change from Baseline in serum CRP over time for part B was reported. Baseline was the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value.

Blood samples were collected for analysis of ESR. Data for Change from Baseline in ESR over time for part A was reported. Baseline was the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value.

Blood samples were collected for analysis of ESR. Data for Change from Baseline in ESR over time for part A was reported. Baseline was the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value.

EQ-5D essentially consists of 2 elements: the EQ-5D descriptive system and the EQ VAS. The EQ-5D descriptive system comprised of the following 6 dimensions: 1.Mobility, 2.Self, 3.Usual Activities, 4.Pain/Discomfort, 5.Anxiety/Depression; 6.How good or or bad your health is today. Each of these 6 dimensions has 5 levels: 1: no problems; 2: slight problems; 3: moderate problems; 4: severe problems; 5: Unable to do. The EQ VAS records the respondent's self-rated health on a vertical line, VAS where the endpoints are 'Best imaginable health state' and 'Worst imaginable health state'. Answers to 'How good or bad your health is today' were measured on a 100 point VAS scale. Baseline for Part B is the last non-missing measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value.

EQ-5D essentially consists of 2 elements: the EQ-5D descriptive system and the EQ VAS. The EQ-5D descriptive system comprised of the following 6 dimensions: 1.Mobility, 2.Self, 3.Usual Activities, 4.Pain/Discomfort, 5.Anxiety/Depression; 6.How good or or bad your health is today. Each of these 6 dimensions has 5 levels: 1: no problems; 2: slight problems; 3: moderate problems; 4: severe problems; 5: Unable to do. The EQ VAS records the respondent's self-rated health on a vertical line, VAS where the endpoints are 100 (Best imaginable health state) and 0 (Worst imaginable health state). Answers to 'How good or bad your health is today' were measured on a 100 point VAS scale. Baseline for Part B is the last non-missing measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value.