A Long-Term Extension Study of WA19926 on the Safety of Tocilizumab (RoActemra/Actemra) in Participants With Early Moderate to Severe Rheumatoid Arthritis

An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A serious adverse event (SAE) is any AE that is fatal; life-threatening; requires or prolongs inpatient hospitalization; results in persistent or significant disability/incapacity; congenital anomaly/birth defect in a neonate/infant or significant medical event in the Investigator's judgment. AE of special interest (AESI) includes serious and/or medically significant infectious; myocardial infarction(MI) / acute coronary syndrome (ACS); gastrointestinal (GI) perforation; anaphylaxis / hypersensitivity reactions; demyelinating disorders; stroke; serious and/or medically significant bleeding events; serious and/or medically significant hepatic events; malignancies malignant.

Time frame: Up to 160 weeks

Population: Safety population is defined as all included participants who received having at least one tocilizumab administration.

DAS28-ESR was calculated using Swollen Joint Count Based on 28 Joints (SJC28), Tender Joint Count Based on 28 Joints (TJC28), ESR (mm/hour) and patient's global assessment of disease activity (100-millimeter (mm) horizontal visual analog scale with 0=no disease activity to 100=maximum disease activity. DAS28-ESR scores range from 0 to 10, with higher scores corresponding to greater disease activity.

Time frame: Day 1 and Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, 116, 128, 140

Population: The included population includes all participants who entered the study. All included participants were part of safety population. Here, n = number of participants who were evaluable at specific time points.

SDAI was calculated using SJC28, TJC28, C-reactive protein (CRP) (milligrams per liter (mg/L)), and the patient's global assessment of disease activity and physician's global assessment of disease activity; SDAI scores range from 0 to 86, where lower scores indicate less disease activity.

Time frame: Day 1 and Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, 116, 128, 140

Population: The included population includes all participants who entered the study. All included participants were part of safety population. Here, n = number of participants who were evaluable at specific time points.

The number of swollen joints was recorded on the joint assessment form at each visit, no swelling = 0, swelling =1; total was calculated by adding all the joints for a maximum score of 28 swollen joints. Higher scores correspond to greater disease activity.

Time frame: Day 1 and Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, 116, 128, 140

Population: The included population includes all participants who entered the study. All included participants were part of safety population. Here, n = number of participants who were evaluable at specific time points.

The number of tender joints was recorded on the joint assessment form at each visit, no tenderness = 0, tenderness = 1; total was calculated by adding all the joints for a maximum score of 28 tender joints. Higher scores correspond to greater disease activity.

Time frame: Day 1 and Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, 116, 128, 140

Population: The included population includes all participants who entered the study. All included participants were part of safety population. Here, n = number of participants who were evaluable at specific time points.

C-reactive protein (CRP) is a blood test marker for inflammation in the body. Normal CRP levels are below 5 milligrams per liter (mg/L). Higher scores correspond to greater disease activity.

Time frame: Day 1 and Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, 116, 128, 140

Population: The included population includes all participants who entered the study. All included participants were part of safety population. Here, n = number of participants who were evaluable at specific time points.

Clinical remission was defined as DAS28-ESR \<2.6 and/or SDAI ≤3.3 for a period of at least two consecutive assessment visits (every 12 weeks) over the extension study period. DAS28-ESR scores range from 0 to 10, with higher scores corresponding to greater disease activity. SDAI scores range from 0 to 86, where lower scores indicate less disease activity.

Time frame: Up to approximately 148 weeks

Population: The included population includes all participants who entered the study. All included participants were part of safety population.

ESR is an direct measure of how much inflammation is in the body. The normal range is 0-22 mm/hour for men and 0-29 mm/hour for women. Higher scores correspond to greater disease activity.

Time frame: Day 1 and Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, 116, 128, 140

Population: The included population includes all participants who entered the study. All included participants were part of safety population. Here, n = number of participants who were evaluable at specific time points.

The participants' global assessment of disease activity (VAS) was assessed using a 100-mm horizontal VAS with 0=no disease activity to 100=maximum disease.

Time frame: Day 1 and Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, 116, 128, 140

Population: The included population includes all participants who entered the study. All included participants were part of safety population. Here, n = number of participants who were evaluable at specific time points.

The participants' global assessment of pain (VAS) was assessed using a 100-mm horizontal VAS with 0=no pain to 100=maximum pain.

Time frame: Day 1 and Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, 116, 128, 140

Population: The included population includes all participants who entered the study. All included participants were part of safety population. Here, n = number of participants who were evaluable at specific time points.

An RA flare was defined as an increase in DAS28-ESR from the previous available visits of \>1.2, or \>0.6 if current DAS28-ESR ≥3.2. DAS28-ESR scores range from 0 to 10, with higher scores corresponding to greater disease activity.

Time frame: Up to approximately 148 weeks

Population: The included population includes all participants who entered the study. All included participants were part of safety population.

Clinical remission: Disease Activity Score Based on 28-joint Count and Erythrocyte Sedimentation Rate (DAS28-ESR) less than (\<)2.6 and/or Simplified Disease Activity Index (SDAI) less than or equal to (≤)3.3 for a period of at least two consecutive assessment visits (every 12 weeks) over the extension study period. DAS28-ESR was calculated using Swollen Joint Count Based on 28 Joints (SJC28), Tender Joint Count Based on 28 Joints (TJC28), ESR (mm/hour) and patient's global assessment of disease activity (100-millimeter (mm) horizontal visual analog scale with 0=no disease activity to 100=maximum disease activity. DAS28-ESR scores range from 0-10, with higher scores corresponding to greater disease activity. SDAI was calculated using SJC28, TJC28, C-reactive protein (CRP) (milligrams per liter (mg/L)), the patient's global assessment of disease activity and physician's global assessment of disease activity; SDAI scores range from 0-86, where lower scores indicate less disease activity.

Time frame: Up to approximately 148 weeks

Population: The included population includes all participants who entered the study. All included participants were part of safety population.

Drug-free remission period was defined as clinical remission for at least 2 consecutive assessment visits (every 12 weeks) AND without tocilizumab administration during this clinical remission period.

Time frame: Up to approximately 148 weeks

Population: The included population includes all participants who entered the study. All included participants were part of safety population.

Clinically meaningful improvement was defined as an improvement in HAQ-DI score of ≥0.22. HAQ-DI is the participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week. Each item scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty.

Time frame: Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, 116, 128, 140

Population: The included population includes all participants who entered the study. All included participants were part of safety population. Here, n = number of participants who were evaluable at specific time points.

HAQ-DI remission was defined as HAQ-DI score \<0.5. HAQ-DI is the participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week. Each item scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty.

Time frame: Baseline and Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, 116, 128 140

Population: The included population includes all participants who entered the study. All included participants were part of safety population. Here, n = number of participants who were evaluable at specific time points.

The physicians' global assessment of disease activity (VAS) was assessed using a 100-mm horizontal VAS with 0=no disease activity to 100=maximum disease.

Time frame: Day 1 and Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, 116, 128, 140

Population: The included population includes all participants who entered the study. All included participants were part of safety population. Here, n = number of participants who were evaluable at specific time points.

Time to RA flare was defined as period of clinical remission or drug-free remission followed by flare of DAS28-ESR (increase in DAS28-ESR from the previous available visits of \>1.2, or \>0.6 if current DAS28-ESR ≥3.2). In the case of several remission periods for the same participant, the largest period was used.

Time frame: Up to approximately 148 weeks

Population: The included population includes all participants who entered the study. All included participants were part of safety population.