Trial Outcomes & Findings for A Study of Retreatment With Rituximab in Patients With Rheumatoid Arthritis Receiving Background Methotrexate (NCT NCT00266227)
NCT ID: NCT00266227
Last Updated: 2013-10-25
Results Overview
ACR20 response was defined as a ≥ 20% improvement compared with baseline in both tender joint count (TJC) \[68 joints\] and swollen joint count (SJC) \[66 joints\] as well as a ≥ 20% improvement in three of five additional measurements: 1) Physician's Global Assessment of disease activity \[visual analog scale: 0=no disease activity to 100=maximum disease activity\]; 2) Patient's Global Assessment of Disease Activity \[visual analog scale: 0=no disease activity to 100=maximum disease activity\]; 3) Patient's Assessment of Pain \[visual analog scale: 0=no pain to 100=unbearable pain\]; 4) Health Assessment Questionnaire \[20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do\] and 5) erythrocyte sedimentation rate.
COMPLETED
PHASE3
559 participants
48 Weeks
2013-10-25
Participant Flow
559 participants received initial treatment open label rituximab. 84 of these participants were not randomized to Retreatment.
Participant milestones
| Measure |
Arm A: Rituximab Retreatment
1000 mg rituximab intravenous initial treatment on day 1 and day 15 plus 10-25 mg/week methotrexate followed by re-treatment during weeks 24 -40 consisting of two additional doses of 1000 mg rituximab 14 days apart plus 10-25 mg/week methotrexate.
|
Arm B: Placebo Retreatment
1000 mg rituximab intravenous initial treatment on day 1 and day 15 plus 10-25 mg/week methotrexate followed by retreatment during weeks 24 -40 consisting of two doses of placebo 14 days apart plus 10-25 mg/week methotrexate.
|
Rituximab-Not Randomized to Retreatment
1000 mg rituximab intravenous initial treatment on day 1 and day 15 plus 10-25 mg/week methotrexate. Participants were not randomized to Retreatment.
|
|---|---|---|---|
|
Initial Treatment
STARTED
|
0
|
0
|
559
|
|
Initial Treatment
COMPLETED
|
0
|
0
|
482
|
|
Initial Treatment
NOT COMPLETED
|
0
|
0
|
77
|
|
Retreatment: Up to Week 48
STARTED
|
318
|
157
|
0
|
|
Retreatment: Up to Week 48
COMPLETED
|
291
|
134
|
0
|
|
Retreatment: Up to Week 48
NOT COMPLETED
|
27
|
23
|
0
|
|
Retreatment: Week 48 to Week 72
STARTED
|
291
|
134
|
0
|
|
Retreatment: Week 48 to Week 72
COMPLETED
|
227
|
92
|
0
|
|
Retreatment: Week 48 to Week 72
NOT COMPLETED
|
64
|
42
|
0
|
Reasons for withdrawal
| Measure |
Arm A: Rituximab Retreatment
1000 mg rituximab intravenous initial treatment on day 1 and day 15 plus 10-25 mg/week methotrexate followed by re-treatment during weeks 24 -40 consisting of two additional doses of 1000 mg rituximab 14 days apart plus 10-25 mg/week methotrexate.
|
Arm B: Placebo Retreatment
1000 mg rituximab intravenous initial treatment on day 1 and day 15 plus 10-25 mg/week methotrexate followed by retreatment during weeks 24 -40 consisting of two doses of placebo 14 days apart plus 10-25 mg/week methotrexate.
|
Rituximab-Not Randomized to Retreatment
1000 mg rituximab intravenous initial treatment on day 1 and day 15 plus 10-25 mg/week methotrexate. Participants were not randomized to Retreatment.
|
|---|---|---|---|
|
Initial Treatment
Adverse Event
|
0
|
0
|
13
|
|
Initial Treatment
Lost to Follow-up
|
0
|
0
|
6
|
|
Initial Treatment
Subject/Guardian decision to withdraw
|
0
|
0
|
45
|
|
Initial Treatment
Physician decision to withdraw
|
0
|
0
|
12
|
|
Initial Treatment
Pregnancy
|
0
|
0
|
1
|
|
Retreatment: Up to Week 48
Death
|
1
|
0
|
0
|
|
Retreatment: Up to Week 48
Adverse Event
|
7
|
7
|
0
|
|
Retreatment: Up to Week 48
Lost to Follow-up
|
3
|
0
|
0
|
|
Retreatment: Up to Week 48
Subject/Guardian Decision to Withdraw
|
11
|
14
|
0
|
|
Retreatment: Up to Week 48
Physician's Decision to Withdraw
|
4
|
2
|
0
|
|
Retreatment: Up to Week 48
Pregnancy
|
1
|
0
|
0
|
|
Retreatment: Week 48 to Week 72
Death
|
1
|
1
|
0
|
|
Retreatment: Week 48 to Week 72
Adverse Event
|
6
|
2
|
0
|
|
Retreatment: Week 48 to Week 72
Lost to Follow-up
|
1
|
0
|
0
|
|
Retreatment: Week 48 to Week 72
Subject/Guardian Decision to Withdraw
|
41
|
29
|
0
|
|
Retreatment: Week 48 to Week 72
Physician's Decision to Withdraw
|
15
|
10
|
0
|
Baseline Characteristics
A Study of Retreatment With Rituximab in Patients With Rheumatoid Arthritis Receiving Background Methotrexate
Baseline characteristics by cohort
| Measure |
Arm A: Rituximab Retreatment
n=318 Participants
1000 mg rituximab intravenous initial treatment on day 1 and day 15 plus 10-25 mg/week methotrexate followed by re-treatment during weeks 24 -40 consisting of two additional doses of 1000 mg rituximab 14 days apart plus 10-25 mg/week methotrexate.
|
Arm B: Placebo Retreatment
n=157 Participants
1000 mg rituximab initial treatment on day 1 and day 15 plus 10-25 mg/wk methotrexate followed by re-treatment during weeks 24 -40 consisting of two doses of placebo 14 days apart plus 10-25 mg/wk methotrexate.
|
Total
n=475 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
266 Participants
n=5 Participants
|
133 Participants
n=7 Participants
|
399 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
52 Participants
n=5 Participants
|
24 Participants
n=7 Participants
|
76 Participants
n=5 Participants
|
|
Age Continuous
|
54.2 years
STANDARD_DEVIATION 10.57 • n=5 Participants
|
53.9 years
STANDARD_DEVIATION 10.52 • n=7 Participants
|
54.1 years
STANDARD_DEVIATION 10.54 • n=5 Participants
|
|
Sex: Female, Male
Female
|
257 Participants
n=5 Participants
|
124 Participants
n=7 Participants
|
381 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
61 Participants
n=5 Participants
|
33 Participants
n=7 Participants
|
94 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 48 WeeksPopulation: Intent-to-treat population includes all participants randomized to Retreatment.
ACR20 response was defined as a ≥ 20% improvement compared with baseline in both tender joint count (TJC) \[68 joints\] and swollen joint count (SJC) \[66 joints\] as well as a ≥ 20% improvement in three of five additional measurements: 1) Physician's Global Assessment of disease activity \[visual analog scale: 0=no disease activity to 100=maximum disease activity\]; 2) Patient's Global Assessment of Disease Activity \[visual analog scale: 0=no disease activity to 100=maximum disease activity\]; 3) Patient's Assessment of Pain \[visual analog scale: 0=no pain to 100=unbearable pain\]; 4) Health Assessment Questionnaire \[20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do\] and 5) erythrocyte sedimentation rate.
Outcome measures
| Measure |
Arm A: Rituximab Retreatment
n=318 Participants
1000 mg rituximab intravenous initial treatment on day 1 and day 15 plus 10-25 mg/week methotrexate followed by re-treatment during weeks 24 -40 consisting of two additional doses of 1000 mg rituximab 14 days apart plus 10-25 mg/week methotrexate.
|
Arm B: Placebo Retreatment
n=157 Participants
1000 mg rituximab initial treatment on day 1 and day 15 plus 10-25 mg/wk methotrexate followed by re-treatment during weeks 24 -40 consisting of two doses of placebo 14 days apart plus 10-25 mg/wk methotrexate.
|
|---|---|---|
|
Retreated Subjects With an American College of Rheumatology 20% (ACR20) Response at Week 48 Relative to Baseline
|
170 Participants
Interval 48.0 to 58.9
|
70 Participants
|
SECONDARY outcome
Timeframe: Baseline, Week 48Population: Intent-to-treat population includes all participants randomized to Retreatment.
ACR50 or ACR70 response was defined as a ≥ 50% or 70% improvement compared with baseline in both tender joint count (TJC) \[68 joints\] and swollen joint count (SJC) \[66 joints\] as well as a ≥ 50% or 70% improvement in three of five additional measurements: 1) Physician's Global Assessment of disease activity \[visual analog scale: 0=no disease activity to 100=maximum disease activity\]; 2) Patient's Global Assessment of Disease Activity \[visual analog scale: 0=no disease activity to 100=maximum disease activity\]; 3) Patient's Assessment of Pain \[visual analog scale: 0=no pain to 100=unbearable pain\]; 4) Health Assessment Questionnaire \[20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do\] and 5) erythrocyte sedimentation rate.
Outcome measures
| Measure |
Arm A: Rituximab Retreatment
n=318 Participants
1000 mg rituximab intravenous initial treatment on day 1 and day 15 plus 10-25 mg/week methotrexate followed by re-treatment during weeks 24 -40 consisting of two additional doses of 1000 mg rituximab 14 days apart plus 10-25 mg/week methotrexate.
|
Arm B: Placebo Retreatment
n=157 Participants
1000 mg rituximab initial treatment on day 1 and day 15 plus 10-25 mg/wk methotrexate followed by re-treatment during weeks 24 -40 consisting of two doses of placebo 14 days apart plus 10-25 mg/wk methotrexate.
|
|---|---|---|
|
Retreated Subjects With American College of Rheumatology 50% (ACR50) Response and American College of Rheumatology 70% (ACR70) Response at Week 48 Relative to Baseline
ACR50
|
92 Participants
Interval 23.9 to 33.9
|
41 Participants
|
|
Retreated Subjects With American College of Rheumatology 50% (ACR50) Response and American College of Rheumatology 70% (ACR70) Response at Week 48 Relative to Baseline
ACR70
|
44 Participants
Interval 10.0 to 17.6
|
21 Participants
|
SECONDARY outcome
Timeframe: 48 weeksPopulation: Participants from the Intent-to-treat population, that includes all participants randomized to Retreatment, with data available for analyses.
The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) \[28 joints\], swollen joint count (SJC) \[28 joints\], patient's global assessment of disease activity \[visual analog scale: 0=no disease activity to 100=maximum disease activity\] and the erythrocyte sedimentation rate (ESR) for a total possible score of 2 to 10. Higher values indicate higher disease activity. A negative change from baseline indicates improvement.
Outcome measures
| Measure |
Arm A: Rituximab Retreatment
n=312 Participants
1000 mg rituximab intravenous initial treatment on day 1 and day 15 plus 10-25 mg/week methotrexate followed by re-treatment during weeks 24 -40 consisting of two additional doses of 1000 mg rituximab 14 days apart plus 10-25 mg/week methotrexate.
|
Arm B: Placebo Retreatment
n=157 Participants
1000 mg rituximab initial treatment on day 1 and day 15 plus 10-25 mg/wk methotrexate followed by re-treatment during weeks 24 -40 consisting of two doses of placebo 14 days apart plus 10-25 mg/wk methotrexate.
|
|---|---|---|
|
Change From Baseline in the Disease Activity Score Using 28 Joint Counts (DAS28-ESR) at Week 48
|
-2.1 Units on a scale
Standard Deviation 1.55
|
-1.8 Units on a scale
Standard Deviation 1.69
|
SECONDARY outcome
Timeframe: Baseline, Week 48Population: Participants from the Intent-to-treat population that includes all participants randomized to Retreatment with data available for analyses.
The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) \[28 joints\], swollen joint count (SJC) \[28 joints\], patient's global assessment of disease activity \[visual analog scale: 0=no disease activity to 100=maximum disease activity\] and C-Reactive Protein (CRP) for a total possible score of 2 to 10. Higher values indicate higher disease activity. A negative change from baseline indicates improvement.
Outcome measures
| Measure |
Arm A: Rituximab Retreatment
n=316 Participants
1000 mg rituximab intravenous initial treatment on day 1 and day 15 plus 10-25 mg/week methotrexate followed by re-treatment during weeks 24 -40 consisting of two additional doses of 1000 mg rituximab 14 days apart plus 10-25 mg/week methotrexate.
|
Arm B: Placebo Retreatment
n=157 Participants
1000 mg rituximab initial treatment on day 1 and day 15 plus 10-25 mg/wk methotrexate followed by re-treatment during weeks 24 -40 consisting of two doses of placebo 14 days apart plus 10-25 mg/wk methotrexate.
|
|---|---|---|
|
Change From Baseline in Disease Activity Score (DAS28-CRP) at Week 48
|
-1.8 Units on a scale
Standard Deviation 1.4
|
-1.5 Units on a scale
Standard Deviation 1.5
|
SECONDARY outcome
Timeframe: Baseline, Week 48Population: Intent-to-treat population includes all participants randomized to Retreatment.
Change of the Disease Activity Score 28 score from baseline was used to determine 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.
Outcome measures
| Measure |
Arm A: Rituximab Retreatment
n=318 Participants
1000 mg rituximab intravenous initial treatment on day 1 and day 15 plus 10-25 mg/week methotrexate followed by re-treatment during weeks 24 -40 consisting of two additional doses of 1000 mg rituximab 14 days apart plus 10-25 mg/week methotrexate.
|
Arm B: Placebo Retreatment
n=157 Participants
1000 mg rituximab initial treatment on day 1 and day 15 plus 10-25 mg/wk methotrexate followed by re-treatment during weeks 24 -40 consisting of two doses of placebo 14 days apart plus 10-25 mg/wk methotrexate.
|
|---|---|---|
|
Percentage of Retreated Subjects With a European League Against Rheumatism (EULAR) Response at Week 48
Good Response
|
20.8 Percentage of participants
|
18.5 Percentage of participants
|
|
Percentage of Retreated Subjects With a European League Against Rheumatism (EULAR) Response at Week 48
Moderate Response
|
47.5 Percentage of participants
|
42.7 Percentage of participants
|
SECONDARY outcome
Timeframe: Baseline, Week 48Population: Intent-to-treat population includes all participants randomized to Retreatment.
A Rheumatologist or an skilled arthritis assessor evaluated 66 joints at baseline and at Week 48. A negative change from baseline in Swollen Joint Count indicates improvement.
Outcome measures
| Measure |
Arm A: Rituximab Retreatment
n=318 Participants
1000 mg rituximab intravenous initial treatment on day 1 and day 15 plus 10-25 mg/week methotrexate followed by re-treatment during weeks 24 -40 consisting of two additional doses of 1000 mg rituximab 14 days apart plus 10-25 mg/week methotrexate.
|
Arm B: Placebo Retreatment
n=157 Participants
1000 mg rituximab initial treatment on day 1 and day 15 plus 10-25 mg/wk methotrexate followed by re-treatment during weeks 24 -40 consisting of two doses of placebo 14 days apart plus 10-25 mg/wk methotrexate.
|
|---|---|---|
|
Change From Baseline in American College of Rheumatology (ACR) Core Set Component: Swollen Joint Count at Week 48
|
-12.5 Joint Count
Standard Deviation 12.31
|
-10.2 Joint Count
Standard Deviation 13.30
|
SECONDARY outcome
Timeframe: Baseline, Week 48Population: Intent-to-treat population includes all participants randomized to Retreatment.
A Rheumatologist or an skilled arthritis assessor evaluated 68 joints at baseline and at Week 48. A negative change from baseline in the Tender Joint Count indicates improvement.
Outcome measures
| Measure |
Arm A: Rituximab Retreatment
n=318 Participants
1000 mg rituximab intravenous initial treatment on day 1 and day 15 plus 10-25 mg/week methotrexate followed by re-treatment during weeks 24 -40 consisting of two additional doses of 1000 mg rituximab 14 days apart plus 10-25 mg/week methotrexate.
|
Arm B: Placebo Retreatment
n=157 Participants
1000 mg rituximab initial treatment on day 1 and day 15 plus 10-25 mg/wk methotrexate followed by re-treatment during weeks 24 -40 consisting of two doses of placebo 14 days apart plus 10-25 mg/wk methotrexate.
|
|---|---|---|
|
Change From Baseline in American College of Rheumatology (ACR) Core Set Component: Tender Joint Count at Week 48
|
-15.3 Joint Count
Standard Deviation 15.28
|
-14.7 Joint Count
Standard Deviation 18.71
|
SECONDARY outcome
Timeframe: Baseline, Week 48Population: Participants from the Intent-to-treat population, that includes all participants randomized to Retreatment, with data available for analyses.
The Stanford Health Assessment Questionnaire disability index (HAQ-DI) is a patient completed questionnaire specific for rheumatoid arthritis. It consists of 20 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip,and common daily activities. Each domain has at least two component questions. There are four possible responses for each component ranging from 0(without any difficulty) to 4 (unable to do).HAQ-DI=sum of worst scores in each domain divided by the number of domains answered. A negative change from baseline indicates improvement.
Outcome measures
| Measure |
Arm A: Rituximab Retreatment
n=316 Participants
1000 mg rituximab intravenous initial treatment on day 1 and day 15 plus 10-25 mg/week methotrexate followed by re-treatment during weeks 24 -40 consisting of two additional doses of 1000 mg rituximab 14 days apart plus 10-25 mg/week methotrexate.
|
Arm B: Placebo Retreatment
n=157 Participants
1000 mg rituximab initial treatment on day 1 and day 15 plus 10-25 mg/wk methotrexate followed by re-treatment during weeks 24 -40 consisting of two doses of placebo 14 days apart plus 10-25 mg/wk methotrexate.
|
|---|---|---|
|
Change From Baseline in American College of Rheumatology (ACR) Core Set Component: Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 48
|
-0.3 Score on a scale
Standard Deviation 0.53
|
-0.2 Score on a scale
Standard Deviation 0.60
|
SECONDARY outcome
Timeframe: Baseline, Week 48Population: Participants from the Intent-to-treat population, that includes all participants randomized to Retreatment, with data available for analyses.
Participants rated their disease activity at baseline and Week 48 using the Visual Analog Scale (VAS) on a scale of 0 (best) to 100 (worse). A negative change from baseline indicates improvement.
Outcome measures
| Measure |
Arm A: Rituximab Retreatment
n=316 Participants
1000 mg rituximab intravenous initial treatment on day 1 and day 15 plus 10-25 mg/week methotrexate followed by re-treatment during weeks 24 -40 consisting of two additional doses of 1000 mg rituximab 14 days apart plus 10-25 mg/week methotrexate.
|
Arm B: Placebo Retreatment
n=157 Participants
1000 mg rituximab initial treatment on day 1 and day 15 plus 10-25 mg/wk methotrexate followed by re-treatment during weeks 24 -40 consisting of two doses of placebo 14 days apart plus 10-25 mg/wk methotrexate.
|
|---|---|---|
|
Change From Baseline in American College of Rheumatology (ACR) Core Set Component: Subject's Global Assessment of Disease Activity at Week 48
|
-26.9 millimeter (mm)
Standard Deviation 29.04
|
-23.0 millimeter (mm)
Standard Deviation 28.72
|
SECONDARY outcome
Timeframe: Baseline, Week 48Population: Intent-to-treat population includes all participants randomized to Retreatment.
A Rheumatologist or a skilled Arthritis assessor rated the patient's disease activity at baseline and Week 48 using the Visual Analog Scale (VAS) on a scale of 0 (best) to 100 (worse). A negative change from baseline indicates improvement.
Outcome measures
| Measure |
Arm A: Rituximab Retreatment
n=318 Participants
1000 mg rituximab intravenous initial treatment on day 1 and day 15 plus 10-25 mg/week methotrexate followed by re-treatment during weeks 24 -40 consisting of two additional doses of 1000 mg rituximab 14 days apart plus 10-25 mg/week methotrexate.
|
Arm B: Placebo Retreatment
n=157 Participants
1000 mg rituximab initial treatment on day 1 and day 15 plus 10-25 mg/wk methotrexate followed by re-treatment during weeks 24 -40 consisting of two doses of placebo 14 days apart plus 10-25 mg/wk methotrexate.
|
|---|---|---|
|
Change From Baseline in American College of Rheumatology (ACR) Core Set Component: Physician's Global Assessment of Disease Activity at Week 48
|
-31.5 millimeter (mm)
Standard Deviation 27.00
|
-25.5 millimeter (mm)
Standard Deviation 29.59
|
SECONDARY outcome
Timeframe: Baseline, Week 48Population: Participants from the Intent-to-treat population, that includes all participants randomized to Retreatment with data available for analyses.
Patients rated their pain at baseline and Week 48 using the Visual Analog Scale (VAS) on a scale of 0 (none) to 100 (unbearable pain). A negative change from baseline indicates improvement.
Outcome measures
| Measure |
Arm A: Rituximab Retreatment
n=317 Participants
1000 mg rituximab intravenous initial treatment on day 1 and day 15 plus 10-25 mg/week methotrexate followed by re-treatment during weeks 24 -40 consisting of two additional doses of 1000 mg rituximab 14 days apart plus 10-25 mg/week methotrexate.
|
Arm B: Placebo Retreatment
n=157 Participants
1000 mg rituximab initial treatment on day 1 and day 15 plus 10-25 mg/wk methotrexate followed by re-treatment during weeks 24 -40 consisting of two doses of placebo 14 days apart plus 10-25 mg/wk methotrexate.
|
|---|---|---|
|
Change From Baseline in American College of Rheumatology (ACR) Core Set Component: Subject's Assessment of Pain at Week 48
|
-24.0 millimeter (mm)
Standard Deviation 28.99
|
-19.3 millimeter (mm)
Standard Deviation 30.32
|
SECONDARY outcome
Timeframe: Baseline, Week 48Population: Intent-to-treat Population includes all participants randomized to Retreatment.
Blood was collected for C-Reactive Protein, an inflammatory marker, at Baseline and Week 48. A negative change from baseline indicates improvement.
Outcome measures
| Measure |
Arm A: Rituximab Retreatment
n=318 Participants
1000 mg rituximab intravenous initial treatment on day 1 and day 15 plus 10-25 mg/week methotrexate followed by re-treatment during weeks 24 -40 consisting of two additional doses of 1000 mg rituximab 14 days apart plus 10-25 mg/week methotrexate.
|
Arm B: Placebo Retreatment
n=157 Participants
1000 mg rituximab initial treatment on day 1 and day 15 plus 10-25 mg/wk methotrexate followed by re-treatment during weeks 24 -40 consisting of two doses of placebo 14 days apart plus 10-25 mg/wk methotrexate.
|
|---|---|---|
|
Change From Baseline in American College of Rheumatology (ACR) Core Set Component: C-Reactive Protein at Week 48
|
-0.8 mg/dL
Standard Deviation 2.55
|
-0.6 mg/dL
Standard Deviation 2.95
|
SECONDARY outcome
Timeframe: Baseline, Week 48Population: Participants from the Intent-to-treat population, that includes all participants randomized to Retreatment, with data available for analyses.
Blood was collected for Erythrocyte Sedimentation Rate, an inflammatory marker, at Baseline and Week 48. A negative change from baseline indicates improvement.
Outcome measures
| Measure |
Arm A: Rituximab Retreatment
n=315 Participants
1000 mg rituximab intravenous initial treatment on day 1 and day 15 plus 10-25 mg/week methotrexate followed by re-treatment during weeks 24 -40 consisting of two additional doses of 1000 mg rituximab 14 days apart plus 10-25 mg/week methotrexate.
|
Arm B: Placebo Retreatment
n=157 Participants
1000 mg rituximab initial treatment on day 1 and day 15 plus 10-25 mg/wk methotrexate followed by re-treatment during weeks 24 -40 consisting of two doses of placebo 14 days apart plus 10-25 mg/wk methotrexate.
|
|---|---|---|
|
Change From Baseline in American College of Rheumatology (ACR) Core Set Component: Erythrocyte Sedimentation (ESR) at Week 48
|
-15.0 millimeter/hour (mm/hr)
Standard Deviation 25.03
|
-10.9 millimeter/hour (mm/hr)
Standard Deviation 24.00
|
SECONDARY outcome
Timeframe: Baseline, Week 48Population: Participants from the Intent-to-treat population, that includes all participants randomized to Retreatment, with data available for analyses.
The Stanford Health Assessment Questionnaire disability index (HAQ-DI) is a patient completed questionnaire specific for rheumatoid arthritis. It consists of 20 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip and common daily activities. Each domain has at least two component questions. There are four possible responses for each component ranging from 0(without any difficulty) to 4 (unable to do). HAQ-DI=sum of worst scores in each domain divided by the number of domains answered.
Outcome measures
| Measure |
Arm A: Rituximab Retreatment
n=316 Participants
1000 mg rituximab intravenous initial treatment on day 1 and day 15 plus 10-25 mg/week methotrexate followed by re-treatment during weeks 24 -40 consisting of two additional doses of 1000 mg rituximab 14 days apart plus 10-25 mg/week methotrexate.
|
Arm B: Placebo Retreatment
n=157 Participants
1000 mg rituximab initial treatment on day 1 and day 15 plus 10-25 mg/wk methotrexate followed by re-treatment during weeks 24 -40 consisting of two doses of placebo 14 days apart plus 10-25 mg/wk methotrexate.
|
|---|---|---|
|
Percentage of Retreated Subjects With a Change ≥ 0.22 From Baseline in HAQ-DI at Week 48
|
57.3 Percentage of participants
|
51.0 Percentage of participants
|
SECONDARY outcome
Timeframe: Baseline, Week 48Population: Participants from the Intent-to-treat population, that includes all participants randomized to Retreatment, with data available for analyses.
The Stanford Health Assessment Questionnaire disability index (HAQ-DI) is a patient completed questionnaire specific for rheumatoid arthritis. It consists of 20 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip and common daily activities. Each domain has at least two component questions. There are four possible responses for each component ranging from 0(without any difficulty) to 4 (unable to do).HAQ-DI=sum of worst scores in each domain divided by the number of domains answered.
Outcome measures
| Measure |
Arm A: Rituximab Retreatment
n=316 Participants
1000 mg rituximab intravenous initial treatment on day 1 and day 15 plus 10-25 mg/week methotrexate followed by re-treatment during weeks 24 -40 consisting of two additional doses of 1000 mg rituximab 14 days apart plus 10-25 mg/week methotrexate.
|
Arm B: Placebo Retreatment
n=157 Participants
1000 mg rituximab initial treatment on day 1 and day 15 plus 10-25 mg/wk methotrexate followed by re-treatment during weeks 24 -40 consisting of two doses of placebo 14 days apart plus 10-25 mg/wk methotrexate.
|
|---|---|---|
|
Percentage of Retreated Subjects With a Change ≥ 0.3 From Baseline in HAQ-DI at Week 48
|
45.9 Percentage of participants
|
39.5 Percentage of participants
|
SECONDARY outcome
Timeframe: Baseline, Week 48Population: Participants from the Intent-to-treat population, that includes all participants randomized to Retreatment, with data available for analyses.
The ACRn is calculated for each participant by taking the lowest percentage improvement in (1) swollen joint count or (2) tender joint count or (3) the median of the remaining 5 components of the ACR response (participant's assessment of disease activity; participant's global assessment of pain; physician's assessment of disease activity; participant's assessment of physical function; an acute phase reactant value - CRP). A positive ACRn Score indicates an improvement.
Outcome measures
| Measure |
Arm A: Rituximab Retreatment
n=317 Participants
1000 mg rituximab intravenous initial treatment on day 1 and day 15 plus 10-25 mg/week methotrexate followed by re-treatment during weeks 24 -40 consisting of two additional doses of 1000 mg rituximab 14 days apart plus 10-25 mg/week methotrexate.
|
Arm B: Placebo Retreatment
n=157 Participants
1000 mg rituximab initial treatment on day 1 and day 15 plus 10-25 mg/wk methotrexate followed by re-treatment during weeks 24 -40 consisting of two doses of placebo 14 days apart plus 10-25 mg/wk methotrexate.
|
|---|---|---|
|
ACRn in Retreated Subjects at Week 48
|
22.1 Score on a scale
Standard Deviation 45.29
|
10.7 Score on a scale
Standard Deviation 62.08
|
SECONDARY outcome
Timeframe: Baseline, Week 48Population: Participants from the Intent-to-treat population, that includes all participants randomized to Retreatment, with data available for analyses.
The SF-36 is a questionnaire used to assess physical functioning and is made up of eight domains: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional and Mental Health. Transforming and standardizing these domains leads to the calculation of the Physical (PCS) and Mental (MCS) Component Summary measures. Scores ranging from 0 to 100, with 0=worst score (or quality of life) and 100=best score. A positive change from baseline indicates improvement.
Outcome measures
| Measure |
Arm A: Rituximab Retreatment
n=312 Participants
1000 mg rituximab intravenous initial treatment on day 1 and day 15 plus 10-25 mg/week methotrexate followed by re-treatment during weeks 24 -40 consisting of two additional doses of 1000 mg rituximab 14 days apart plus 10-25 mg/week methotrexate.
|
Arm B: Placebo Retreatment
n=154 Participants
1000 mg rituximab initial treatment on day 1 and day 15 plus 10-25 mg/wk methotrexate followed by re-treatment during weeks 24 -40 consisting of two doses of placebo 14 days apart plus 10-25 mg/wk methotrexate.
|
|---|---|---|
|
Change From Baseline in SF-36 Health Summary Scores at Week 48 in Retreated Subjects
Mental Health Score
|
4.6 Score on a scale
Standard Deviation 11.80
|
3.9 Score on a scale
Standard Deviation 13.50
|
|
Change From Baseline in SF-36 Health Summary Scores at Week 48 in Retreated Subjects
Physical Health Score
|
6.4 Score on a scale
Standard Deviation 8.76
|
4.8 Score on a scale
Standard Deviation 8.97
|
SECONDARY outcome
Timeframe: Baseline, Week 48Population: Participants from the Intent-to-treat population, that includes all randomized participants, with data available for analyses.
FACIT-F is a 13-item questionnaire. Patients scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). The larger the patient's response to the questions (with the exception of 2 negatively stated), the greater the patient's fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as (4 minus the patient's response). 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 patient's health status.
Outcome measures
| Measure |
Arm A: Rituximab Retreatment
n=317 Participants
1000 mg rituximab intravenous initial treatment on day 1 and day 15 plus 10-25 mg/week methotrexate followed by re-treatment during weeks 24 -40 consisting of two additional doses of 1000 mg rituximab 14 days apart plus 10-25 mg/week methotrexate.
|
Arm B: Placebo Retreatment
n=157 Participants
1000 mg rituximab initial treatment on day 1 and day 15 plus 10-25 mg/wk methotrexate followed by re-treatment during weeks 24 -40 consisting of two doses of placebo 14 days apart plus 10-25 mg/wk methotrexate.
|
|---|---|---|
|
Change From Baseline in Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) at Week 48 in Retreated Subjects
|
-5.0 Score on a scale
Interval -29.0 to 27.0
|
-4.0 Score on a scale
Interval -32.0 to 22.0
|
SECONDARY outcome
Timeframe: Week 48Population: Participants from the Intent-to-treat population, that includes all participants randomized to Retreatment, with data available for analyses.
DAS28-ESR remission was defined as a DAS28-ESR \< 2.6
Outcome measures
| Measure |
Arm A: Rituximab Retreatment
n=317 Participants
1000 mg rituximab intravenous initial treatment on day 1 and day 15 plus 10-25 mg/week methotrexate followed by re-treatment during weeks 24 -40 consisting of two additional doses of 1000 mg rituximab 14 days apart plus 10-25 mg/week methotrexate.
|
Arm B: Placebo Retreatment
n=157 Participants
1000 mg rituximab initial treatment on day 1 and day 15 plus 10-25 mg/wk methotrexate followed by re-treatment during weeks 24 -40 consisting of two doses of placebo 14 days apart plus 10-25 mg/wk methotrexate.
|
|---|---|---|
|
Percentage of Retreated Subjects Achieving DAS28-ESR Remission at Week 48
|
10.4 Percentage of participants
|
8.9 Percentage of participants
|
SECONDARY outcome
Timeframe: Week 48Population: Participants from the Intent-to-treat population, that includes all participants randomized to Retreatment, with data available for analyses.
The DAS28-ESR score is a measure of the subject's disease activity. It is based on the tender joint count (28 joints), swollen joint count (28 joints), patient's global assessment of disease activity (mm), and ESR. DAS28-ESR scores range from 0 - 10. Low disease activity is defined as achieving a DAS28-ESR score of less than or equal to 3.2.
Outcome measures
| Measure |
Arm A: Rituximab Retreatment
n=317 Participants
1000 mg rituximab intravenous initial treatment on day 1 and day 15 plus 10-25 mg/week methotrexate followed by re-treatment during weeks 24 -40 consisting of two additional doses of 1000 mg rituximab 14 days apart plus 10-25 mg/week methotrexate.
|
Arm B: Placebo Retreatment
n=157 Participants
1000 mg rituximab initial treatment on day 1 and day 15 plus 10-25 mg/wk methotrexate followed by re-treatment during weeks 24 -40 consisting of two doses of placebo 14 days apart plus 10-25 mg/wk methotrexate.
|
|---|---|---|
|
Percentage of Retreated Subjects Achieving DAS28-ESR Low Disease at Week 48
|
21.1 Percentage of participants
|
18.5 Percentage of participants
|
Adverse Events
Arm A: Rituximab Retreatment
Arm B: Placebo Retreatment
Rituximab-Not Randomized to Retreatment
Serious adverse events
| Measure |
Arm A: Rituximab Retreatment
n=320 participants at risk
1000 mg rituximab intravenous initial treatment on day 1 and day 15 plus 10-25 mg/week methotrexate followed by re-treatment during weeks 24 -40 consisting of two additional doses of 1000 mg rituximab 14 days apart plus 10-25 mg/week methotrexate.
|
Arm B: Placebo Retreatment
n=155 participants at risk
1000 mg rituximab intravenous initial treatment on day 1 and day 15 plus 10-25 mg/week methotrexate followed by retreatment during weeks 24 -40 consisting of two doses of placebo 14 days apart plus 10-25 mg/week methotrexate.
|
Rituximab-Not Randomized to Retreatment
n=84 participants at risk
1000 mg rituximab intravenous initial treatment on day 1 and day 15 plus 10-25 mg/week methotrexate. Participants were not randomized to Retreatment.
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
0.31%
1/320
|
0.00%
0/155
|
0.00%
0/84
|
|
Cardiac disorders
Myocardial infarction
|
0.62%
2/320
|
0.00%
0/155
|
1.2%
1/84
|
|
Cardiac disorders
Acute coronary syndrome
|
0.00%
0/320
|
0.65%
1/155
|
0.00%
0/84
|
|
Cardiac disorders
Acute myocardial infarction
|
0.00%
0/320
|
0.65%
1/155
|
0.00%
0/84
|
|
Cardiac disorders
Coronary artery disease
|
0.31%
1/320
|
0.00%
0/155
|
0.00%
0/84
|
|
Cardiac disorders
Coronary artery occlusion
|
0.00%
0/320
|
0.65%
1/155
|
0.00%
0/84
|
|
Cardiac disorders
Atrial fibrillation
|
0.31%
1/320
|
0.00%
0/155
|
0.00%
0/84
|
|
Cardiac disorders
Supraventricular tachycardia
|
0.00%
0/320
|
0.65%
1/155
|
0.00%
0/84
|
|
Cardiac disorders
Cardiac failure congestive
|
0.31%
1/320
|
0.00%
0/155
|
0.00%
0/84
|
|
Cardiac disorders
Pericarditis
|
0.31%
1/320
|
0.00%
0/155
|
0.00%
0/84
|
|
Cardiac disorders
Cardio-respiratory arrest
|
0.31%
1/320
|
0.00%
0/155
|
0.00%
0/84
|
|
Gastrointestinal disorders
Colitis
|
0.31%
1/320
|
0.00%
0/155
|
0.00%
0/84
|
|
Gastrointestinal disorders
Enterocolitis
|
0.31%
1/320
|
0.00%
0/155
|
0.00%
0/84
|
|
Gastrointestinal disorders
Oesophagitis ulcerative
|
0.31%
1/320
|
0.00%
0/155
|
0.00%
0/84
|
|
General disorders
Chest pain
|
0.31%
1/320
|
0.65%
1/155
|
0.00%
0/84
|
|
General disorders
Death
|
0.31%
1/320
|
0.00%
0/155
|
0.00%
0/84
|
|
General disorders
Hernia obstructive
|
0.31%
1/320
|
0.00%
0/155
|
0.00%
0/84
|
|
Hepatobiliary disorders
Cholecystitis
|
0.00%
0/320
|
0.65%
1/155
|
0.00%
0/84
|
|
Hepatobiliary disorders
Biliary dyskinesia
|
0.31%
1/320
|
0.00%
0/155
|
0.00%
0/84
|
|
Infections and infestations
Pneumonia
|
1.9%
6/320
|
0.65%
1/155
|
0.00%
0/84
|
|
Infections and infestations
Abdominal abscess
|
0.00%
0/320
|
0.65%
1/155
|
0.00%
0/84
|
|
Infections and infestations
Abdominal wall abscess
|
0.00%
0/320
|
0.65%
1/155
|
0.00%
0/84
|
|
Infections and infestations
Diverticulitis
|
0.31%
1/320
|
0.00%
0/155
|
0.00%
0/84
|
|
Infections and infestations
Gastroenteritis
|
0.31%
1/320
|
0.00%
0/155
|
0.00%
0/84
|
|
Infections and infestations
Perirectal abscess
|
0.31%
1/320
|
0.00%
0/155
|
0.00%
0/84
|
|
Infections and infestations
Cellulitis
|
0.62%
2/320
|
0.65%
1/155
|
1.2%
1/84
|
|
Infections and infestations
Arthritis bacterial
|
0.31%
1/320
|
0.00%
0/155
|
0.00%
0/84
|
|
Infections and infestations
Osteomyelitis
|
0.31%
1/320
|
0.00%
0/155
|
1.2%
1/84
|
|
Infections and infestations
Clostridium difficile colitis
|
0.31%
1/320
|
0.00%
0/155
|
0.00%
0/84
|
|
Infections and infestations
Human ehrlichiosis
|
0.31%
1/320
|
0.00%
0/155
|
0.00%
0/84
|
|
Infections and infestations
Urosepsis
|
0.31%
1/320
|
0.00%
0/155
|
0.00%
0/84
|
|
Infections and infestations
Pyelonephritis
|
0.00%
0/320
|
0.65%
1/155
|
0.00%
0/84
|
|
Infections and infestations
Viral infection
|
0.31%
1/320
|
0.00%
0/155
|
0.00%
0/84
|
|
Injury, poisoning and procedural complications
Fall
|
0.31%
1/320
|
0.00%
0/155
|
1.2%
1/84
|
|
Injury, poisoning and procedural complications
Road traffic accident
|
0.31%
1/320
|
0.00%
0/155
|
0.00%
0/84
|
|
Injury, poisoning and procedural complications
Device failure
|
0.00%
0/320
|
0.65%
1/155
|
0.00%
0/84
|
|
Metabolism and nutrition disorders
Diabetes mellitus inadequate control
|
0.31%
1/320
|
0.00%
0/155
|
0.00%
0/84
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.62%
2/320
|
0.65%
1/155
|
0.00%
0/84
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
0.31%
1/320
|
0.00%
0/155
|
0.00%
0/84
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
0.00%
0/320
|
1.3%
2/155
|
0.00%
0/84
|
|
Musculoskeletal and connective tissue disorders
Spinal osteoarthritis
|
0.31%
1/320
|
0.00%
0/155
|
0.00%
0/84
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.31%
1/320
|
0.65%
1/155
|
1.2%
1/84
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc degeneration
|
0.31%
1/320
|
0.00%
0/155
|
0.00%
0/84
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion
|
0.31%
1/320
|
0.00%
0/155
|
0.00%
0/84
|
|
Musculoskeletal and connective tissue disorders
Rheumatiod arthritis
|
0.62%
2/320
|
0.00%
0/155
|
0.00%
0/84
|
|
Musculoskeletal and connective tissue disorders
Osteonecrosis
|
0.00%
0/320
|
0.65%
1/155
|
1.2%
1/84
|
|
Musculoskeletal and connective tissue disorders
Bursitis
|
0.31%
1/320
|
0.00%
0/155
|
0.00%
0/84
|
|
Musculoskeletal and connective tissue disorders
Costochondritis
|
0.31%
1/320
|
0.00%
0/155
|
0.00%
0/84
|
|
Musculoskeletal and connective tissue disorders
Joint destruction
|
0.00%
0/320
|
0.65%
1/155
|
0.00%
0/84
|
|
Musculoskeletal and connective tissue disorders
Spinal column stenosis
|
0.00%
0/320
|
0.65%
1/155
|
0.00%
0/84
|
|
Nervous system disorders
Cerebral ischaemia
|
0.31%
1/320
|
0.00%
0/155
|
0.00%
0/84
|
|
Nervous system disorders
Cerebrovascular accident
|
0.31%
1/320
|
0.00%
0/155
|
0.00%
0/84
|
|
Nervous system disorders
Syncope
|
0.31%
1/320
|
0.00%
0/155
|
0.00%
0/84
|
|
Nervous system disorders
Cauda equina syndrome
|
0.31%
1/320
|
0.00%
0/155
|
0.00%
0/84
|
|
Nervous system disorders
Transient ischaemic attack
|
0.00%
0/320
|
0.65%
1/155
|
0.00%
0/84
|
|
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous
|
0.31%
1/320
|
0.00%
0/155
|
0.00%
0/84
|
|
Reproductive system and breast disorders
Rectocele
|
0.31%
1/320
|
0.00%
0/155
|
0.00%
0/84
|
|
Reproductive system and breast disorders
Uterine prolapse
|
0.00%
0/320
|
0.65%
1/155
|
0.00%
0/84
|
|
Reproductive system and breast disorders
Benign prostatic hyperplasia
|
0.31%
1/320
|
0.00%
0/155
|
0.00%
0/84
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome
|
0.31%
1/320
|
0.65%
1/155
|
0.00%
0/84
|
|
Respiratory, thoracic and mediastinal disorders
Interstitial lung disease
|
0.00%
0/320
|
0.65%
1/155
|
0.00%
0/84
|
|
Vascular disorders
Deep vein thrombosis
|
0.31%
1/320
|
1.3%
2/155
|
0.00%
0/84
|
|
Vascular disorders
Iliac artery occlusion
|
0.31%
1/320
|
0.00%
0/155
|
0.00%
0/84
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.31%
1/320
|
0.00%
0/155
|
0.00%
0/84
|
|
General disorders
Pyrexia
|
0.00%
0/320
|
0.00%
0/155
|
1.2%
1/84
|
|
Hepatobiliary disorders
Cholelithiasis
|
0.00%
0/320
|
0.00%
0/155
|
1.2%
1/84
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/320
|
0.00%
0/155
|
1.2%
1/84
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
0.00%
0/320
|
0.00%
0/155
|
1.2%
1/84
|
|
Vascular disorders
Hypotension
|
0.00%
0/320
|
0.00%
0/155
|
1.2%
1/84
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer
|
0.00%
0/320
|
0.00%
0/155
|
1.2%
1/84
|
Other adverse events
| Measure |
Arm A: Rituximab Retreatment
n=320 participants at risk
1000 mg rituximab intravenous initial treatment on day 1 and day 15 plus 10-25 mg/week methotrexate followed by re-treatment during weeks 24 -40 consisting of two additional doses of 1000 mg rituximab 14 days apart plus 10-25 mg/week methotrexate.
|
Arm B: Placebo Retreatment
n=155 participants at risk
1000 mg rituximab intravenous initial treatment on day 1 and day 15 plus 10-25 mg/week methotrexate followed by retreatment during weeks 24 -40 consisting of two doses of placebo 14 days apart plus 10-25 mg/week methotrexate.
|
Rituximab-Not Randomized to Retreatment
n=84 participants at risk
1000 mg rituximab intravenous initial treatment on day 1 and day 15 plus 10-25 mg/week methotrexate. Participants were not randomized to Retreatment.
|
|---|---|---|---|
|
Gastrointestinal disorders
Nausea
|
10.9%
35/320
|
9.7%
15/155
|
6.0%
5/84
|
|
Gastrointestinal disorders
Diarrhoea
|
7.8%
25/320
|
5.8%
9/155
|
9.5%
8/84
|
|
General disorders
Fatigue
|
10.3%
33/320
|
5.8%
9/155
|
9.5%
8/84
|
|
General disorders
Pyrexia
|
6.6%
21/320
|
2.6%
4/155
|
4.8%
4/84
|
|
Infections and infestations
Upper respiratory tract infection
|
22.2%
71/320
|
20.6%
32/155
|
9.5%
8/84
|
|
Infections and infestations
Sinusitis
|
14.1%
45/320
|
10.3%
16/155
|
6.0%
5/84
|
|
Infections and infestations
Nasopharyngitis
|
6.2%
20/320
|
7.1%
11/155
|
4.8%
4/84
|
|
Infections and infestations
Urinary tract infection
|
13.8%
44/320
|
11.0%
17/155
|
7.1%
6/84
|
|
Infections and infestations
Bronchitis
|
6.9%
22/320
|
10.3%
16/155
|
4.8%
4/84
|
|
Musculoskeletal and connective tissue disorders
Rheumatoid arthritis
|
23.1%
74/320
|
38.1%
59/155
|
22.6%
19/84
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
8.4%
27/320
|
7.1%
11/155
|
6.0%
5/84
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
8.4%
27/320
|
13.5%
21/155
|
8.3%
7/84
|
|
Nervous system disorders
Headache
|
15.9%
51/320
|
11.6%
18/155
|
15.5%
13/84
|
|
Nervous system disorders
Dizziness
|
8.1%
26/320
|
1.3%
2/155
|
2.4%
2/84
|
|
Psychiatric disorders
Insomnia
|
6.2%
20/320
|
5.8%
9/155
|
2.4%
2/84
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
6.9%
22/320
|
9.0%
14/155
|
3.6%
3/84
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
6.9%
22/320
|
9.7%
15/155
|
11.9%
10/84
|
|
Skin and subcutaneous tissue disorders
Rash
|
6.6%
21/320
|
6.5%
10/155
|
4.8%
4/84
|
|
Vascular disorders
Flushing
|
6.9%
22/320
|
1.3%
2/155
|
8.3%
7/84
|
Additional Information
Medical Communications Specialist
Genentech, Inc.
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: OTHER