This 2-arm study assessed the safety and efficacy of tocilizumab versus placebo, both in combination with disease modifying antirheumatic drugs (DMARDs), in regard to reduction in signs and symptoms, in patients with moderate to severe active rheumatoid arthritis with an inadequate response to DMARDs. Patients were randomized in a ratio of 2:1 to receive either tocilizumab 8 mg/kg intravenously (IV) or placebo IV every 4 weeks. All patients also received stable antirheumatic therapy, including permitted DMARDs. The anticipated time on study treatment was 3-12 months and the target sample size was 500+ individuals.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
619
Tocilizumab intravenously at a dose of 8 mg/kg over a 1-hour infusion, every 4 weeks, for a total of 6 infusions.
Placebo IV over a 1-hour infusion, every 4 weeks, for a total of 6 infusions.
As prescribed. The following DMARDs were permitted in this study: methotrexate (MTX), chloroquine, hydroxychloroquine, parenteral gold, sulfasalazine, azathioprine, and leflunomide. These DMARDs could be used alone or in combination, except for the combination of MTX and leflunomide, which was not allowed.
Unnamed facility
Birmingham, Alabama, United States
Unnamed facility
Birmingham, Alabama, United States
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Birmingham, Alabama, United States
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Montgomery, Alabama, United States
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Lake Havasu City, Arizona, United States
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Percentage of Patients With an Improvement of at Least 50% in American College of Rheumatology (ACR) Score (ACR50) From Baseline at Week 24
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
Percentage of Patients With an Improvement of at Least 20%, 50%, or 70% in American College of Rheumatology (ACR) Score (ACR20, ACR50, ACR70) From Baseline at Weeks 4, 8, 12, 16, 20, and 24
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
Mean Change From Baseline in Disease Activity Score 28 (DAS28) at Weeks 4, 8, 12, 16, 20, and 24
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
Percentage of Patients With European League Against Rheumatism (EULAR) Good, Moderate, or no Response at Weeks 4, 8, 12, 16, 20, and 24
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
Mean Change From Baseline in the Routine Assessment Patient Index Data (RAPID) Score at Weeks 4, 8, 12, 16, 20, and 24
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
Mean Change From Baseline in 12-Item Short Form Health Survey v2 (SF-12) Scores at Weeks 4, 8, 12, 16, 20, and 24
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
Mean Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score at Weeks 4, 8, 12, 16, 20, and 24
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
Mean Change From Baseline in the Medical Outcomes Study (MOS) Sleep Scale Score at Weeks 4, 8, 12, 16, 20, and 24
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
Mean Change From Baseline in Individual Components of the Routine Assessment Patient Index Data (RAPID) at Each Day During the First 7 Days of Treatment
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
Percentage of Patients With an Improvement of at Least 20%, 50%, or 70% in American College of Rheumatology (ACR) Score (ACR20, ACR50, ACR70) From Baseline at Day 7
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
Mean Change From Baseline in C-reactive Protein (CRP) at Days 3 and 7
Serum concentration of CRP (high-sensitivity CRP \[hsCRP\] test) was analyzed by a central laboratory.
Time frame: Baseline to Days 3 and 7
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Paradise Valley, Arizona, United States
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Peoria, Arizona, United States
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Scottsdale, Arizona, United States
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Scottsdale, Arizona, United States
Unnamed facility
Jonesboro, Arkansas, United States
...and 147 more locations