An Exploratory Study of Tocilizumab in Patients With Active Rheumatoid Arthritis (RA) and an Inadequate Response to Current Non-Biologic DMARDs and/or Anti-TNF Therapy.

DAS28 calculated from the number of swollen joints and tender joints using the 28 joints count, the erythrocyte sedimentation rate (ESR) (millimeters per hour [mm/hr]) and Patient's Global Assessment of Disease Activity (participant-rated arthritis activity assessment) with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity. Low disease activity was defined as DAS28 less than or equal to (≤)3.2 and remission was defined as DAS28 less than (<)2.6.

DAS28 calculated from the number of swollen joints and tender joints using the 28 joints count, the ESR (mm/hr) and Patient's Global Assessment of Disease Activity (participant-rated arthritis activity assessment) with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity. Low disease activity was defined as DAS28 ≤3.2 and remission was defined as DAS28 <2.6.

The time to low disease activity or remission was calculated as the number of days from study Day 1 to the first occurrence of low disease activity or remission. Participants who did not achieve low disease activity on or before Week 24 or who withdrew from the study prior to achieving low disease activity were considered censored. DAS28 calculated from the number of swollen joints and tender joints using the 28 joints count, the ESR (mm/hr) and Patient's Global Assessment of Disease Activity (participant-rated arthritis activity assessment) with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity. Low disease activity defined as DAS28 ≤3.2 and remission defined as DAS28 <2.6.

DAS28-based EULAR response criteria were used to measure individual response as none, good, and moderate, depending on the extent of change from baseline and the level of disease activity reached. Good responders: change from baseline >1.2 with DAS28 ≤3.2; moderate responders: change from baseline >1.2 with DAS28 >3.2 to ≤5.1 or change from baseline >0.6 to =<1.2 with DAS28 ≤5.1; non-responders: change from baseline ≤0.6 or change from baseline >0.6 and ≤1.2 with DAS28 >5.1. If the EULAR response could not be determined, it was set to 'No response'.

DAS28 calculated from the number of swollen joints and tender joints using the 28 joints count, the ESR (mm/hr) and Patient's Global Assessment of Disease Activity (participant-rated arthritis activity assessment) with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity. A negative change from baseline indicates improvement.

ACR20, ACR50, ACR70, and ACR90 are defined as ≥20%, ≥50%, ≥70%, or ≥90% improvement, respectively, in: swollen joint count (SJC; 66 joints) and tender joint count (TJC; 68 joints) and ≥20%, ≥50%, ≥70%, or ≥90% improvement, respectively, in 3 of following 5 assessments: Patient's Global Assessment of Pain (visual analog scale [VAS]); Patient's Global Assessment of Disease Activity (VAS); Investigator/Physician's Global Assessment of Disease Activity (VAS); participant's assessment of disability measured by the Health Assessment Questionnaire Disability Index (HAQ-DI); or acute phase reactant (ESR or C-reactive protein [CRP]). Participants who did not have the required data to assess ACR status at a given visit were classified as non-responders.

ACR20, ACR50, ACR70, and ACR90 are defined as ≥20%, ≥50%, ≥70%, or ≥90% improvement, respectively, in: swollen joint count (SJC; 66 joints) and tender joint count (TJC; 68 joints) and ≥20%, ≥50%, ≥70%, or ≥90% improvement, respectively, in 3 of following 5 assessments: Patient's Global Assessment of Pain (VAS); Patient's Global Assessment of Disease Activity (VAS); Investigator/Physician's Global Assessment of Disease Activity (VAS); participant's assessment of disability measured by the HAQ-DI; or acute phase reactant (ESR or CRP).

ACR20, ACR50, ACR70, and ACR90 are defined as ≥20%, ≥50%, ≥70%, or ≥90% improvement, respectively, in: swollen joint count (SJC; 66 joints) and tender joint count (TJC; 68 joints) and ≥20%, ≥50%, ≥70%, or ≥90% improvement, respectively, in 3 of following 5 assessments: Patient's Global Assessment of Pain (VAS); Patient's Global Assessment of Disease Activity (VAS); Investigator/Physician's Global Assessment of Disease Activity (VAS); participant's assessment of disability measured by the HAQ-DI; or acute phase reactant (ESR or CRP). Time to ACR response was calculated as the number of days from day 1 of study to the date of first achievement of ACR response. Data represent median time for responders only.

Number of swollen joints was determined by examination of 66 joints and identifying when swelling was present. 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 66. A negative change from baseline indicates improvement.

Number of tender joints was determined by examining 68 joints and identified the joints that were painful under pressure or to passive motion. 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 68. A negative change from baseline indicates improvement.

The participant's global assessment of disease activity is assessed on a 0 to 100 mm horizontal VAS by the participant. The left-hand extreme of the line=0 mm, and is described as "no disease activity" (symptom-free and no arthritis symptoms) and the right-hand extreme=100 mm, as "maximum disease activity" (maximum arthritis disease activity). The line was marked by the participant and the distance from the left edge was recorded. A negative change from baseline indicated improvement.

The physician's global assessment of disease activity is assessed on a 0 to 100 mm horizontal VAS by the physician. The left-hand extreme of the line=0 mm, and is described as "no disease activity" (symptom-free and no arthritis symptoms) and the right-hand extreme=100 mm as "maximum disease activity" (maximum arthritis disease activity). The physician marked the line and the distance from the left edge was recorded. A negative change from baseline indicated improvement.

The participants assessed their pain using a 0 to 100 mm horizontal VAS. The left-hand extreme of the line=0 mm, and is described as "no pain" and the right-hand extreme=100 mm as "unbearable pain". The participant marked the line and the distance from the left edge was recorded. A negative change from baseline indicated improvement.

The test for CRP (mg per deciliter [mg/dL]) is a laboratory measurement for evaluation of an acute phase reactant of inflammation through the use of an ultrasensitive assay. A decrease in the level of CRP indicates reduction in inflammation and therefore improvement.

ESR (mm/hr) is a blood test used to monitor therapy in inflammatory diseases such as rheumatoid arthritis (RA) and reflects acute phase reactant levels. Active disease in RA is defined by an ESR greater than 30 mm/hr. Change from baseline is computed as the value at each week minus the baseline value. A negative value in change from baseline indicates an improvement.

HAQ-DI includes 20 questions concerning participant's activities of daily life, grouped in 8 scales of 2 to 3 questions for each activity. To respond to each question, a four-level response (score of 0 to 3 points), with higher scores showing larger functional limitations, was chosen. Scoring was as follows with respect to performance of participant's everyday activities: 0 (equals)=without difficulties; 1=with some difficulties; 2=with great difficulties; and 3=unable to perform these actions at all. Minimum score was 0, maximum score was 3.

The SF-36 covers 8 health dimensions including 4 physical subscales (physical function, role-physical, bodily pain, and general health) and 4 mental subscales (vitality, social function, role-emotional, and mental health). The scores range from a minimum of 0 to a maximum of 100, with a higher score indicating better quality of life. Improvements of >3 points were considered clinically meaningful.

The HAQ-DI scale ranges from 0 to 3, where higher scores represent higher disease activity. A score of <0.5 represents clinical remission. A participant achieves a clinically meaningful improvement in HAQ-DI if they had a reduction from baseline of ≥0.22.

FACIT-Fatigue is a 13-item questionnaire; participants scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). The larger the participant's response to the questions (with the exception of 2 negatively stated), the greater the participant's fatigue. The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse score) to 52 (better score). A higher score reflects an improvement in the participant's health status.