A Study of the Efficacy and Safety of Tocilizumab in Adults With Rheumatoid Arthritis.

Clinical Disease Activity Index (CDAI) is an index for measuring disease activity in rheumatoid arthritis (RA). The index was calculated using the following formula: CDAI = number of swollen joints using the 28-joint count (SJC28) + number of tender joints using the 28-joint count (TJC28) + patient global assessment of disease (PGA) based on 10 centimeter [cm] Visual Analog Scale [VAS] + physician global assessment of disease (PhGA) based on 10 cm VAS. VAS assessments involved a 10 cm horizontal scale from 0 (no disease activity) to 10 (maximum disease activity). Total CDAI scores ranged from 0 to 76, with higher scores indicating increased disease activity. Remission is defined as CDAI ≤2.8 and Low Disease Activity (LDA) is defined as 2.8< CDAI ≤10.

Clinical Disease Activity Index (CDAI) is an index for measuring disease activity in rheumatoid arthritis (RA). The index was calculated using the following formula: CDAI = number of swollen joints using the 28-joint count (SJC28) + number of tender joints using the 28-joint count (TJC28) + patient global assessment of disease (PGA) based on 10 centimeter [cm] Visual Analog Scale [VAS] + physician global assessment of disease (PhGA) based on 10 cm VAS. VAS assessments involved a 10 cm horizontal scale from 0 (no disease activity) to 10 (maximum disease activity). Total CDAI scores ranged from 0 to 76, with higher scores indicating increased disease activity. A negative change from baseline indicates an improvement.

Simplified Disease Activity Index (SDAI) was an index for measuring disease activity in RA and had a good correlation with the DAS28. The index was calculated using the following formula: SDAI: SJC28 + TJC28 + PGA (10 cm VAS) + PhGA (10 cm VAS + C-Reactive Protein (CRP) in milligram/liter (mg/L). VAS assessments involved a 10 cm horizontal scale from 0 (no disease activity) to 10 (maximum disease activity). Scores ranged from 0 to 86, with higher scores also indicating increased disease activity. An SDAI score of ≤ 3.3 represents clinical remission, a score of ≤ 11.0 represents low disease activity.

Simplified Disease Activity Index (SDAI) was an index for measuring disease activity in RA and had a good correlation with the DAS28. The index was calculated using the following formula: SDAI: SJC28 + TJC28 + PGA (10 cm VAS) + PhGA (10 cm VAS + C-Reactive Protein (CRP) in mg/L. VAS assessments involved a 10 cm horizontal scale from 0 (no disease activity) to 10 (maximum disease activity). Scores ranged from 0 to 86, with higher scores also indicating increased disease activity. A negative change from baseline indicates an improvement.

The DAS28-ESR score is a measure of the patient's disease activity calculated using the tender joint count on 28 joints (TJC28), swollen joint count on 28 joints (SJC28), patient's global assessment (PGA) of disease activity based on visual analog scale (VAS) and the erythrocyte sedimentation rate (ESR) in millimeter/hour (mm/hr). VAS assessments involved a 10 cm horizontal scale from 0 (no disease activity) to 10 (maximum disease activity). Total possible score ranged from 0 to 10. Higher scores represent higher disease activity. A negative change from baseline indicates an improvement.

An ACR20 response requires at least 20% improvement compared to baseline in SJC (based on 66 joints) and TJC (based on 68 joints) as well as at least 20% improvement in 3 of the following 5 assessments: 1) PGA pain VAS, 2) PGA VAS; 3) physician's global assessment of disease activity VAS, 4) Health Assessment Questionnaire-Disability Index (HAQ-DI) with 20 questions consisting of 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do; and 5) CRP in mg/L or ESR in mm/hr. ACR50 and ACR70 responses are defined in a similar way except that they required a 50% and 70% improvement from baseline, respectively. VAS assessments involved a 10 cm horizontal scale from 0 (no disease activity) to 10 (maximum disease activity).

Response was determined using EULAR criteria based upon DAS28 absolute scores at the assessment visit and the DAS28 reduction from the reference visit. Participants with a score lesser than or equal to (</=) 3.2 and reduction of greater than (>) 1.2 points were assessed as having a 'good' response. Participants with a score >3.2 with reduction of >1.2 points, or a score <=5.1 with reduction of >0.6 to <=1.2 points, were assessed as having a 'moderate' response. Participants with a score >5.1 with reduction of >0.6 to <=1.2 points, or any score with reduction <=0.6 points, were assessed as non-responders with response recorded as 'none.'

The number of tender joints (based on 68 joints) and swollen joints (based on 66 joints) were counted at each visit. TJC was determined by identifying the joints that were painful under pressure or to passive motion; no tenderness =0, tenderness =1. SJC was determined by identifying swelling; no swelling =0, swelling =1. A negative change from baseline indicates an improvement.

Participants were either on tocilizumab monotherapy or tocilizumab plus non-biologic disease modifying anti-rheumatic drugs (DMARDs). Reported here is the percentage of participants on tocilizumab monotherapy at baseline and the change from baseline at Week 24. A positive change from baseline at Week 24 indicates the percentage of participants, who discontinued DMARDs during the study.

PGA VAS represents the participant's overall assessment of their current disease activity on a 100 millimeter (mm) horizontal VAS scale from 0 (no disease activity) to 100 (maximum disease activity). A negative change from baseline indicates an improvement.

Patient Pain VAS represents the participant's assessment of his/her current level of pain on a 100 mm horizontal VAS scale from 0 (no disease activity) to 100 (maximum disease activity). A negative change from baseline indicates an improvement.

The HAQ-DI evaluates participant-reported quality of life using 8 categories: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and other common activities and 20 questions. Each category contains multiple questions, which were answered using a 4-point scale from 0 (without any difficulty) to 3 (unable to do). The overall index score was an average of the individual item responses and may range from 0 to 3, where higher scores indicate more difficulty in daily living activities. A negative change from baseline indicates an improvement.

The symptom-specific measure FACIT-F assesses chronic illness therapy with special emphasis on fatigue in the past 7 days and consists of 5 dimensions: 1) physical well- being, 2) social/family well-being, 3) emotional well-being, 4) functional well-being, and 5) additional concerns. Each of the questions is categorically answered using the scales 0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, and 4=very much for a total possible FACIT-F score of 0 to 52. The figures are reversed during score calculations, so that higher score values indicate more favorable conditions. A positive change from baseline indicates an improvement.

The HDRS is a clinician-administered depression assessment and consists of 17 items with a total score range from 0 to 54. A higher score indicates a worse outcome. HAS is a clinician-administered assessment to measure the severity of anxiety symptoms and consists of 14 items with a total score range from 0 to 56. A higher score indicates a worse outcome.

An AE is any untoward medical occurrence in a participant administered a drug and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a drug, whether or not considered related to the drug. Preexisting conditions which worsen during a study are also considered as AEs. AESIs are AEs that occur in categories of special interest with regard to the benefit-risk profile and overall safety of a drug. The following nine categories of AESIs were identified for tocilizumab: 1) serious and/or medically significant infections, 2) myocardial infarction/acute coronary syndrome, 3) gastrointestinal perforations, 4) malignancies, 5) anaphylaxis/hypersensitivity reactions, 6) demyelinating disorders, 7) stroke, 8) serious and/or medically significant bleeding events, and 9) serious and/or medically significant hepatic events.

Reported is the percentage of participants positive for anti-tocilizumab antibodies in the confirmatory anti-tocilizumab antibody assay, which followed an initial anti-tocilizumab screen. Participants, who withdrew from the study

A positive change from Week 1 indicates an increase in sIL-6R levels.