A Study of RoActemra/Actemra (Tocilizumab) in Patients With Moderate to Severe Rheumatoid Arthritis

An adverse event (AE) was any untoward medical occurrence attributed to study drug in a participant who received study drug. A serious AE (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. An AE was considered treatment emergent if the date of onset of the AE was on or after the date of first dose of study medication. AEs of special interest included Major Adverse Cardiovascular Events (MACE) (including strokes), infections, and infusion reactions. An AE was considered an infection if the preferred term was in the predefined infection AE group term. A serious infection was an infection which was also considered as an AE. An AE was considered an infusion reaction if it occurred during or within 24 hours of an infusion.

Participants who discontinued treatment due to any reason were included in this measure.

Elevations in ALT and AST could indicate hepatotoxicity.

Elevations in ALT and AST could indicate hepatotoxicity.

A serious infection was an infection which was also considered as an SAE. An 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

A serious infection was an infection which was also considered as an SAE. An 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

Elevations in ALT and AST could indicate hepatotoxicity. These enzymes were measured as International Units per Liter (IU/L). The change from baseline was calculated as: baseline value minus the highest value observed post-baseline for each enzyme.

Elevations in LDL and total cholesterol could lead to heart disease. The change from baseline was calculated as: baseline value minus the highest value observed post-baseline and was measured as milligrams per deciliter (mg/dL).

ANC is a measure of number of neutrophil granulocytes. An ANC less than 500 cells per microliter (cells/µL) is defined as neutropenia and significantly increases risk of infection. The change from baseline was calculated as: baseline value minus the highest value observed post-baseline. ANC was measured in cells/µL.

ATP III guidelines classify LDL cholesterol >160 mg/dL, Total cholesterol >240 mg/dL, High Density Lipoprotein (HDL) >60 mg/dL and Triglycerides (TG) >199 as elevated.

ATP III guidelines classify LDL cholesterol >160 mg/dL , Total cholesterol >240 mg/dL, HDL >60 mg/dL and TG >199 as elevated.

The DAS28 is a combined index for measuring disease activity in Rheumatoid Arthritis (RA). The index includes swollen and tender joint counts, acute phase response, and general health status. The DAS28, which uses a 28 joint count, is derived from the original DAS. The index is calculated using the following formula:

DAS28 = 0.56 x (TJC28)^0.5 + 0.28 x (SJC28)^0.5 + 0.70 x In(ESR) + 0.014 x GH Where TJC28 = tender joint count on 28 joints, SJCz8 = swollen joint count on 28 joints, ın = natural log, ESR = erythrocyte sedimentation rate and GH = general health (participant's global assessment of disease activity). DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity. A score of less than (<) 2.6 represents clinical remission, a score of: <3.2 represents low disease activity (LDA), and a score of > 5.1 represents severe disease. A reduction from previous visit of at least 1.2 units in DAS28 is considered to be a clinically meaningful improvement.

The DAS28 is a combined index for measuring disease activity in RA. The index includes swollen and tender joint counts, acute phase response, and general health status. The DAS28, which uses a 28 joint count, is derived from the original DAS. The index is calculated using the following formula:

DAS28 = 0.56 x (TJC28)^0.5 + 0.28 x (SJC28)^0.5 + 0.70 x In(ESR) + 0.014 x GH Where TJC28 = tender joint count on 28 joints, SJCz8 = swollen joint count on 28 joints, ın = natural log, ESR = erythrocyte sedimentation rate and GH = general health (participant's global assessment of disease activity). DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity. A score of < 2.6 represents clinical remission, a score of: < 3.2 represents LDA, and a score of > 5.1 represents severe disease. A reduction of at least 1.2 units from previous visit in DAS28 is considered to be a clinically meaningful improvement.

The DAS28 is a combined index for measuring disease activity in RA. The index includes swollen and tender joint counts, acute phase response, and general health status. The DAS28, which uses a 28 joint count, is derived from the original DAS. The index is calculated using the following formula:

DAS28 = 0.56 x (TJC28)^0.5 + 0.28 x (SJC28)^0.5 + 0.70 x In(ESR) + 0.014 x GH Where TJC28 = tender joint count on 28 joints, SJCz8 = swollen joint count on 28 joints, ın = natural log, ESR = erythrocyte sedimentation rate and GH = general health (participant's global assessment of disease activity). DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity. A score of < 2.6 represents clinical remission, a score of: <3.2 represents LDA, and a score of > 5.1 represents severe disease. A reduction of at least 1.2 units from previous visit in DAS28 is considered to be a clinically meaningful improvement.

TThe DAS28 is a combined index for measuring disease activity in RA. The index includes swollen and tender joint counts, acute phase response, and general health status. The DAS28, which uses a 28 joint count, is derived from the original DAS. The index is calculated using the following formula:

DAS28 = 0.56 x (TJC28)^0.5 + 0.28 x (SJC28)^0.5 + 0.70 x In(ESR) + 0.014 x GH Where TJC28 = tender joint count on 28 joints, SJCz8 = swollen joint count on 28 joints, ın = natural log, ESR = erythrocyte sedimentation rate and GH = general health (participant's global assessment of disease activity). DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity. A score of < 2.6 represents clinical remission, a score of: <3.2 represents LDA, and a score of > 5.1 represents severe disease. A reduction of at least 1.2 units from previous visit in DAS28 is considered to be a clinically meaningful improvement.

The DAS28 is a combined index for measuring disease activity in RA. The index includes swollen and tender joint counts, acute phase response, and general health status. The DAS28, which uses a 28 joint count, is derived from the original DAS. The index is calculated using the following formula:

DAS28 = 0.56 x (TJC28)^0.5 + 0.28 x (SJC28)^0.5 + 0.70 x In(ESR) + 0.014 x GH Where TJC28 = tender joint count on 28 joints, SJCz8 = swollen joint count on 28 joints, ın = natural log, ESR = erythrocyte sedimentation rate and GH = general health (participant's global assessment of disease activity). DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity. A score of < 2.6 represents clinical remission, a score of: <3.2 LDA, and a score of > 5.1 represents severe disease. A reduction of at least 1.2 units from previous visit in DAS28 is considered to be a clinically meaningful improvement.

The DAS28 is a combined index for measuring disease activity in RA. The index includes swollen and tender joint counts, acute phase response, and general health status. The DAS28, which uses a 28 joint count, is derived from the original DAS. The index is calculated using the following formula:

DAS28 = 0.56 x (TJC28)^0.5 + 0.28 x (SJC28)^0.5 + 0.70 x In(ESR) + 0.014 x GH Where TJC28 = tender joint count on 28 joints, SJCz8 = swollen joint count on 28 joints, ın = natural log, ESR = erythrocyte sedimentation rate and GH = general health (participant's global assessment of disease activity). DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity. A score of < 2.6 represents clinical remission, a score of: <3.2 LDA, and a score of > 5.1 represents severe disease. A reduction of at least 1.2 units in DAS28 is considered to be a clinically meaningful improvement.

The DAS28 is a combined index for measuring disease activity in RA. The index includes swollen and tender joint counts, acute phase response, and general health status. The DAS28, which uses a 28 joint count, is derived from the original DAS. The index is calculated using the following formula:

DAS28 = 0.56 x (TJC28)^0.5 + 0.28 x (SJC28)^0.5 + 0.70 x In(ESR) + 0.014 x GH Where TJC28 = tender joint count on 28 joints, SJCz8 = swollen joint count on 28 joints, ın = natural log, ESR = erythrocyte sedimentation rate and GH = general health (participant's global assessment of disease activity). DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity. A score of < 2.6 represents clinical remission, a score of: <3.2 LDA, and a score of > 5.1 represents severe disease. A reduction of at least 1.2 units in DAS28 is considered to be a clinically meaningful improvement.

The DAS28 is a combined index for measuring disease activity in RA. The index includes swollen and tender joint counts, acute phase response, and general health status. The DAS28, which uses a 28 joint count, is derived from the original DAS. The index is calculated using the following formula:

DAS28 = 0.56 x (TJC28)^0.5 + 0.28 x (SJC28)^0.5 + 0.70 x In(ESR) + 0.014 x GH Where TJC28 = tender joint count on 28 joints, SJCz8 = swollen joint count on 28 joints, ın = natural log, ESR = erythrocyte sedimentation rate and GH = general health (participant's global assessment of disease activity). DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity. A score of < 2.6 represents clinical remission, a score of: <3.2 LDA, and a score of > 5.1 represents severe disease. A reduction of at least 1.2 units in DAS28 is considered to be a clinically meaningful improvement.

The DAS28 is a combined index for measuring disease activity in RA. The index includes swollen and tender joint counts, acute phase response, and general health status. The DAS28, which uses a 28 joint count, is derived from the original DAS. The index is calculated using the following formula:

DAS28 = 0.56 x (TJC28)^0.5 + 0.28 x (SJC28)^0.5 + 0.70 x In(ESR) + 0.014 x GH Where TJC28 = tender joint count on 28 joints, SJCz8 = swollen joint count on 28 joints, ın = natural log, ESR = erythrocyte sedimentation rate and GH = general health (participant's global assessment of disease activity). DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity. A score of < 2.6 represents clinical remission, a score of: <3.2 LDA, and a score of > 5.1 represents severe disease. A reduction of at least 1.2 units in DAS28 is considered to be a clinically meaningful improvement.

ACR20/50/70/90 response: greater than or equal to (≥) 20/50/70/90 percent (%) improvement in TJC; ≥20/50/70/90% improvement in SJC; and ≥20/50/70/90% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and C-Reactive Protein (CRP). Improvements were assessed on the basis of prior visit.

ACR20/50/70/90 response: ≥ 20/50/70/90 % improvement in TJC; ≥20/50/70/90% improvement in SJC; and ≥20/50/70/90% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and C-Reactive Protein (CRP). Improvements were assessed on the basis of prior visit. .

CRP is an inflammatory marker used to measure inflammation in RA and is measured as mg/dL.

ESR is an inflammatory marker used to measure inflammation in RA and is measured as millimeters per hour (mm/hr).

Participants were asked to classify 28 joints as tender or not tender and swollen or not swollen to count the total number of tender and swollen joints by visit.

VAS is a visual scale of 100 mm for the assessment of disease activity by participants or investigator. Disease activity/pain increases while approaching 100 mm. For the screening visit (baseline visit) there's only investigator assessment data, for other visits participant's pain assessment, participant's disease activity assessment and investigator's disease activity assessment parameters were collected.

VAS is a visual scale of 100 mm for the assessment of disease activity by participants or investigator. Disease activity/pain increases while approaching 100 mm. For the screening visit (baseline visit) there's only investigator assessment data, for other visits participant's pain assessment, participant's disease activity assessment and investigator's disease activity assessment parameters were collected.

The Stanford HAQ disability index is a participant completed questionnaire specific for RA. It consists of 20 questions referring to 8 component sections: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. The questionnaire was provided in validated translation into the local languages at the participating sites and was scored. Every question in each section was scored at a scale from 0 to 3 by the participant where 0 = able to perform the activity without any difficulty and 3 = unable to perform the activity. General score was calculated as an average of the 8 sections.