A Study of Tocilizumab in Combination With DMARDs in Patients With Moderate to Severe Rheumatoid Arthritis

Improvement must be seen in tender and swollen joint counts and in at least 3 of the following 5 parameters. Patient and physician assessment of patient disease activity (DA) in previous 24 hours on a visual analog scale (VAS, no DA to maximum DA); patient assessment of pain in previous 24 hours on a VAS (none to unbearable); Health Assessment Questionnaire-Disability Index (20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do); and C-reactive protein or, if missing, erythrocyte sedimentation rate.

Time frame: Baseline to Week 24

Population: Intent-to-treat population: All randomized patients who received at least 1 dose of study medication. In determining ACR status, a last observation carried forward (LOCF) approach was used for missing joint count data. Patients with missing data or who escaped were classified as non-responders.

The SF-12 is a self-report measure of general health status with 1 or 2 items for each of 8 domains: Physical functioning, role limitations due to physical health problems, bodily pain, general health, vitality, social functioning, role limitations due to emotional problems, and mental health. Two component summaries, physical (PCS-12) and mental (MCS-12) were calculated using norm-based scoring, resulting in means of 50 and standard deviations of 10 in the 1998 general United States population. Higher scores represent better health and a positive change from baseline represents improvement.

Time frame: Baseline to Weeks 4, 8, 12, 16, 20, and 24

Population: Intent-to-treat population: All randomized patients who received at least 1 dose of study medication. No imputation of missing data was made; only observed data are reported.

Serum concentration of CRP (high-sensitivity CRP \[hsCRP\] test) was analyzed by a central laboratory.

Time frame: Baseline to Days 3 and 7

Population: C-reactive protein (CRP) population: A subset of patients enrolled at designated study sites who met the CRP entry criteria (CRP ≥ 1 mg/dL), received at least 1 dose of study medication, and attended the Day 3 or Day 7 visit. No imputation of missing data was made; only observed data are reported.

DAS28 was calculated using the following formula: 0.56 × sqrt(TJC) + 0.28 × sqrt(SJC) + 0.70 × ln(ESR) + 0.014 × GH, where TJC = tender joint count on 28 joints, SJC = swollen joint count on 28 joints, ESR = erythrocyte sedimentation rate at the current visit (mm/hr), and GH = general health, ie, the patient's global assessment of disease activity (DA) in the previous 24 hours on a 100 mm visual analog scale (no DA to maximum DA). The DAS28 score ranges from 0 to 10, with higher scores indicating more rheumatoid arthritis. A negative change score indicates improvement.

Time frame: Baseline to Weeks 4, 8, 12, 16, 20, 24

Population: Intent-to-treat population: All randomized patients who received at least 1 dose of study medication. No imputation of missing data was made; only observed data are reported.

The FACIT-F is a 13-item patient self-report questionnaire that assesses fatigue over the previous 7 days by scoring each item on a 5-point scale (0=Not at all, 1=A little bit, 2=Somewhat, 3=Quite a bit, 4=Very much). An overall FACIT-F score was obtained by summing the scores of all 13 items. The overall score ranged from 0 to 52. A lower score indicates less fatigue. A negative change score indicates improvement.

Time frame: Baseline to Weeks 4, 8, 12, 16, 20, and 24

Population: Intent-to-treat population: All randomized patients who received at least 1 dose of study medication. No imputation of missing data was made; only observed data are reported.

Derived from the Multidimensional Health Assessment Questionnaire (MDHAQ), the RAPID includes 3 domains that assess disease activity in rheumatoid arthritis: A physical function score (0-10), a pain visual analog scale score (VAS, 0-100), and a global assessment of disease activity VAS score (0-100). Each domain was assessed with the Patient Take Home Form (PTHF). Higher scores indicate more disease activity. A negative change score indicates improvement.

Time frame: Baseline through Day 7

Population: Intent-to-treat population: All randomized patients who received at least 1 dose of study medication. No imputation of missing data was made; only observed data are reported.

The MOS Sleep Scale is a 12-item patient self-report instrument that assesses the quality and quantity of sleep over the previous 4 weeks. A sleep problems index (SLP9) was generated using 9 of the 12 items (1, 3, 4, 5, 6, 7, 8, 9, 12). Each item was normalized so that the lowest and highest possible scores were set to 0 and 100, respectively. The SLP9 score is the average of the recoded 9 items. The SLP9 score ranged from 0 to 100. Higher scores represent greater sleep problems. A negative change score indicates improvement.

Time frame: Baseline to Weeks 4, 8, 12, 16, 20, and 24

Population: Intent-to-treat population: All randomized patients who received at least 1 dose of study medication. No imputation of missing data was made; only observed data are reported.

Derived from the Multidimensional Health Assessment Questionnaire (MDHAQ), the RAPID includes 3 domains that assess disease activity in rheumatoid arthritis: A physical function score (MDHAQ items 1a-j), a pain visual analog scale score (VAS, item 2 in the MDHAQ), and a global assessment of disease activity VAS score (item 6 in the MDHAQ). Each domain is scored on a scale of 0-10. The RAPID score is the sum of the 3 domain scores divided by 3 resulting in a total score on a scale of 0-10. Higher scores indicate more disease activity and a negative change from baseline indicates improvement.

Time frame: Baseline to Weeks 4, 8, 12, 16, 20, and 24

Population: Intent-to-treat population: All randomized patients who received at least 1 dose of study medication. No imputation of missing data was made; only observed data are reported.

Improvement must be seen in tender and swollen joint counts and in at least 3 of the following 5 parameters. Patient and physician assessment of patient disease activity (DA) in previous 24 hours on a visual analog scale (VAS, no DA to maximum DA); patient assessment of pain in previous 24 hours on a VAS (none to unbearable); Health Assessment Questionnaire-Disability Index (20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do); and C reactive protein or, if missing, erythrocyte sedimentation rate.

Time frame: Baseline to Day 7

Population: C-reactive protein (CRP) population: A subset of patients enrolled at designated study sites who met the CRP entry criteria (CRP ≥ 1 mg/dL), received at least 1 dose of study medication, and attended the Day 3 or Day 7 visit. LOCF was used for missing joint count data. Patients with missing data or who escaped were classified as non-responders.

Improvement must be seen in tender and swollen joint counts and in at least 3 of the following 5 parameters. Patient and physician assessment of patient disease activity (DA) in previous 24 hours on a visual analog scale (VAS, no DA to maximum DA); patient assessment of pain in previous 24 hours on a VAS (none to unbearable); Health Assessment Questionnaire-Disability Index (20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do); and C reactive protein or, if missing, erythrocyte sedimentation rate.

Time frame: Baseline to Weeks 4, 8, 12, 16, 20, 24

Population: Intent-to-treat population: All randomized patients who received at least 1 dose of study medication. In determining ACR status, a last observation carried forward (LOCF) approach was used for missing joint count data. Patients with missing data or who escaped were classified as non-responders.

Change of the DAS28 score from baseline was used to determine the EULAR responses of good, moderate, or no response. For a post-baseline score ≤ 3.2, a change from baseline of \< -1.2 was a good response, \< -0.6 to ≥ -1.2 was a moderate response, and ≥ -0.6 was no response. For a post-baseline score \> 3.2 to ≤ 5.1, a change from baseline of \< -0.6 was a moderate response and ≥ -0.6 was no response. For a post-baseline score \> 5.1, a change from baseline \< -1.2 was a moderate response and ≥ -1.2 was no response. A good response could not be achieved for post-baseline scores \> 3.2.

Time frame: Baseline to Weeks 4, 8, 12, 16, 20, and 24

Population: Intent-to-treat population: All randomized patients who received at least 1 dose of study medication. Missing data was imputed as no response.