Long-term Safety and Efficacy of Sirukumab in Participants With RA Completing Studies CNTO136ARA3002 or CNTO136ARA3003

An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.

MACE was defined as a composite of Myocardial Infarction (MI), stroke, death, hospitalization for unstable angina, and hospitalization for Transient Ischemic Attack (TIA). Adjudication of these events by the Endpoint Adjudication Committee (EAC) was performed in a blinded fashion.

Percentage of participants with one or more malignancy was reported.

Percentage of participants with one or more serious infections was reported.

Percentage of participants with one or more GI perforations was reported. GI perforation is a hole that develops through the entire wall of the stomach, small intestine, large bowel, or gallbladder.

Percentage of participants with hepatobiliary abnormalities was reported.

Percentage of participants with serious or moderate/severe systemic hypersensitivity reactions, or serum sickness adverse events (AEs) was reported.

Percentage of participants with toxicity grade 4 decrease in neutrophils was reported. As per National Cancer Institute's Common Terminology Criteria for Adverse Events, toxicity grade 4 was defined as decrease in neutrophils less than (<) 500 per Cubic Millimeter (mm^3) or < 0.5 * 10^9 per liter.

Percentage of participants with toxicity grade 4 decrease in platelets was reported. As per National Cancer Institute's Common Terminology Criteria for Adverse Events, toxicity grade 4 was defined as decreased in platelets <25000/mm^3 or < 25.0 * 10^9 per liter.

Percentage of participants with Alanine Aminotranserase (ALT) >= 3*Upper Limit of Normal (ULN), ALT >= 5*ULN or ALT >= 8*ULN was reported.

Percentage of participants with Aspartate Aminotransferase (AST) >= 3*ULN, AST >= 5*ULN and AST >= 8*ULN was reported.

Percentage of participants with either ALT >= 3*ULN or AST >= 3*ULN and total bilirubin >= 2*ULN was reported.

Percentage of participants with normal total cholesterol value at baseline and at least 1 abnormal value post-baseline was reported. Abnormal total cholesterol value was defined as total cholesterol value more than (>) 200 milligrams per deciliter (mg/dL).

Percentage of participants with normal LDL value at baseline and at least 1 abnormal value post-baseline was reported. Abnormal LDL value was defined as LDL value > 130 mg/dL.

Percentage of participants with normal HDL value at baseline and at least 1 abnormal value post-baseline was reported. Abnormal HDL value was defined as HDL value < 40 mg/dL.

Percentage of participants with normal triglyceride value at baseline and at least 1 abnormal value post-baseline was reported. Abnormal triglyceride value was defined as triglyceride value > 250 mg/dL.

ACR 50 response is greater than or equal to (>=) 50 percent (%) improvement in both tender joint count (68) and swollen joint count (66) and >= 50% improvement in 3 of following 5 assessments:Participant's assessment of pain using visual analog scale (VAS) (0-10 scale, 0=no pain and 10=worst possible pain),Participant's global assessment of disease activity by using VAS (scale ranges from 0 to 10, [0 = very well to 10 = very poor]), Physician's global assessment of disease activity using VAS (scale ranges from 0 to 10, [0=no arthritis activity to 10=extremely active arthritis]), Participant's assessment of physical function as measured by Health Assessment Questionnaire-Disability Index (HAQ-DI) (scale ranges from 0= no difficulty to 3= inability to perform a task in that area), and Serum C-reactive protein (CRP). Participants were analyzed for efficacy according to assigned treatment groups from the primary studies, regardless of treatments actually received.

Boolean based ACR/EULAR remission is achieved if all of the following 4 criteria at that visit are met: tender joint count (68 joints) <=1; swollen joint count (66 joints) <=1; CRP <=1 milligram per deciliter (mg/dL); and patient's global assessment of disease activity on visual analog scale (VAS) <=1 on a 0 (very well ) to 10 (extremely bad) scale. Higher scores indicates worst health condition. Participants were analyzed for efficacy according to the assigned treatment groups from the primary studies, regardless of the treatments they actually received.

The Disease Activity Index Score 28 (DAS28) based on C-Reactive Protein (CRP) is a statistically derived index combining tender joints (28 joints), swollen joints (28 joints), CRP and patient's global assessment of disease activity. The set of 28 joint count is based on evaluation of the shoulder, elbow, wrist, metacarpophalangeal (MCP) MCP1 to MCP5, proximal interphalangeal (PIP) PIP1 to PIP5 joints of both the upper right extremity and the upper left extremity as well as the knee joints of lower right and lower left extremities. The values are 0=best to 10=worst. DAS28 (CRP) remission is defined as a DAS28 (CRP) value of less than (<) 2.6 at any study visit. Participants were analyzed for efficacy according to the assigned treatment groups from the primary studies, regardless of the treatments they actually received.

The CDAI score is a derived score of 4 components: tender joints (28 joints), swollen joints (28 joints), patient's global assessment of disease activity, and physician's global assessments of disease activity. The total score ranges from 0 to 76 with a lower score indicating less disease activity. A negative change in CDAI score indicates an improvement in disease activity and a positive change in score indicates a worsening of disease activity. Participants were analyzed for efficacy according to the assigned treatment groups from the primary studies, regardless of the treatments they actually received.

Participant having SDAI-based ACR/EULAR remission at a visit if SDAI score is of <= 3.3. SDAI derived by combining 5 disease assessments: tender joint (28), swollen joint (28) counts, participants global assessment of disease activity using VAS (scale ranges from 0 to 10 [0 =very well to 10 = very poor]), physicians global assessment of disease activity using VAS (scale ranges from 0 to 10 [0=no arthritis to 10=extremely active arthritis]) and CRP. 28 joints evaluated for swelling and tenderness are same set of 28 joints used in DAS28 includes shoulder, elbow, wrist, MCP1, MCP2, MCP3, MCP4, MCP5, PIP1, PIP2, PIP3, PIP4, PIP5 joints of upper right and left extremities and knee joints of lower right and left extremities. Participants were analyzed for efficacy according to assigned treatment groups from the primary studies, regardless of treatments actually received.

The Health Assessment Questionnaire-Disability Index (HAQ-DI) score is an evaluation of the functional status for a participant. The 20-question instrument assesses the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and activities of daily living). Responses in each functional area are scored from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area. 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. Participants were analyzed for efficacy according to assigned treatment groups from the primary studies, regardless of treatments actually received.

HAQ-DI response was defined as change of less than -0.22 from baseline in HAQ-DI score. The HAQ-DI score is an evaluation of the functional status for a participant. The 20-question instrument assesses the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and activities of daily living). Responses in each functional area are scored from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area. 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. Participants were analyzed for efficacy according to assigned treatment groups from the primary studies, regardless of treatments actually received.