Trial Outcomes & Findings for A Study of MabThera (Rituximab) in Combination With Methotrexate in Patients With Rheumatoid Arthritis Who Have Had an Inadequate Response to Anti-TNF Agents. (NCT NCT00504777)
NCT ID: NCT00504777
Last Updated: 2014-08-04
Results Overview
DAS28 was calculated from the number of swollen joints, or swollen joint count (SJC) and tender joint count (TJC) using the 28 joints count, the erythrocyte sedimentation rate (ESR) (measured in millimeters per hour \[mm/hr\]), and Patient 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 clinically significant improvement in DAS28 was a change of at least 1.2 units.
COMPLETED
PHASE4
36 participants
Week 24
2014-08-04
Participant Flow
Participant milestones
| Measure |
Rituximab + Methotrexate (MTX)
Participants received rituximab 1000 milligrams (mg) intravenously (IV) and 100 mg methylprednisolone IV on Days 1 and 15. Participants were to be receiving background MTX (10-25 mg weekly, oral or parenteral dose).
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|---|---|
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Overall Study
STARTED
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36
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Overall Study
COMPLETED
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35
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Overall Study
NOT COMPLETED
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1
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Reasons for withdrawal
| Measure |
Rituximab + Methotrexate (MTX)
Participants received rituximab 1000 milligrams (mg) intravenously (IV) and 100 mg methylprednisolone IV on Days 1 and 15. Participants were to be receiving background MTX (10-25 mg weekly, oral or parenteral dose).
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Overall Study
Adverse Event
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1
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Baseline Characteristics
A Study of MabThera (Rituximab) in Combination With Methotrexate in Patients With Rheumatoid Arthritis Who Have Had an Inadequate Response to Anti-TNF Agents.
Baseline characteristics by cohort
| Measure |
Rituximab + MTX
n=36 Participants
Participants received rituximab 1000 mg IV, and 100 mg methylprednisolone IV on Days 1 and 15. Participants were to be receiving background MTX (10-25 mg weekly, oral or parenteral dose).
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|---|---|
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Age, Continuous
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50.72 years
STANDARD_DEVIATION 13.42 • n=5 Participants
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|
Sex: Female, Male
Female
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33 Participants
n=5 Participants
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Sex: Female, Male
Male
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3 Participants
n=5 Participants
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PRIMARY outcome
Timeframe: Week 24Population: ITT Population
DAS28 was calculated from the number of swollen joints, or swollen joint count (SJC) and tender joint count (TJC) using the 28 joints count, the erythrocyte sedimentation rate (ESR) (measured in millimeters per hour \[mm/hr\]), and Patient 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 clinically significant improvement in DAS28 was a change of at least 1.2 units.
Outcome measures
| Measure |
Rituximab + MTX
n=36 Participants
Participants received rituximab 1000 mg IV and 100 mg methylprednisolone IV on Days 1 and 15. Participants were to be receiving background MTX (10-25 mg weekly, oral or parenteral dose).
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|---|---|
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Change From Baseline in Disease Activity Score Based on 28-Joint Count (DAS28)
Baseline
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5.51 scores on a scale
Standard Deviation 1.05
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Change From Baseline in Disease Activity Score Based on 28-Joint Count (DAS28)
Week 24
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4.39 scores on a scale
Standard Deviation 1.21
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Change From Baseline in Disease Activity Score Based on 28-Joint Count (DAS28)
Change from Baseline to Week 24
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-1.12 scores on a scale
Standard Deviation 1.19
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SECONDARY outcome
Timeframe: Week 24Population: ITT Population
ACR20/50/70 response defined as greater than or equal to (≥)20 percent (%), 50%, or 70% improvement, respectively, in TJC and SJC, and ≥20%/50%/70% improvement in at least 3 of 5 remaining ACR core measures: Patient Assessment of Pain, Patient Global Assessment of Disease Activity, Physician Global Assessment of Disease Activity, self-assessed disability based on the Health Assessment Questionnaire-Disability Index (HAQ-DI), and C-Reactive Protein (CRP).
Outcome measures
| Measure |
Rituximab + MTX
n=36 Participants
Participants received rituximab 1000 mg IV and 100 mg methylprednisolone IV on Days 1 and 15. Participants were to be receiving background MTX (10-25 mg weekly, oral or parenteral dose).
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Percentage of Participants Achieving American College of Rheumatology (ACR) Response
ACR20
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2.78 percentage of participants
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Percentage of Participants Achieving American College of Rheumatology (ACR) Response
ACR50
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0 percentage of participants
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Percentage of Participants Achieving American College of Rheumatology (ACR) Response
ACR70
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0 percentage of participants
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SECONDARY outcome
Timeframe: Week 24Population: ITT Population
Percentage of participants with a EULAR response at Week 24 based on a scale of good response, moderate response, or no response. The 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 have a change from baseline greater than (\>)1.2 with DAS28 less than or equal to (≤)3.2; moderate responders have a 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 have a change from baseline ≤0.6 or change from baseline \>0.6 and ≤1.2 with DAS28 \>5.1.
Outcome measures
| Measure |
Rituximab + MTX
n=36 Participants
Participants received rituximab 1000 mg IV and 100 mg methylprednisolone IV on Days 1 and 15. Participants were to be receiving background MTX (10-25 mg weekly, oral or parenteral dose).
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|---|---|
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Percentage of Participants Achieving a Response by European League Against Rheumatism (EULAR) Category
Good response
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0 percentage of participants
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Percentage of Participants Achieving a Response by European League Against Rheumatism (EULAR) Category
Moderate response
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58.33 percentage of participants
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Percentage of Participants Achieving a Response by European League Against Rheumatism (EULAR) Category
No response
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41.67 percentage of participants
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SECONDARY outcome
Timeframe: Week 24Population: ITT Population
The Stanford HAQ-DI is a patient-reported questionnaire specific for rheumatoid arthritis. It consists of 20 questions referring to 8 component sets: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. Responses in each component set are scored from 0 (without any difficulty) to 3 (unable to do). The highest score recorded for any question in a category determines the score for the category, unless aids, devices, or help from another person is required. The HAQ-DI score is calculated as the sum of the category scores divided by the number of categories scored, giving a possible range of scores from 0 to 3. Scores of 0 to 1 are generally considered to represent "mild to moderate difficulty", 1 to 2 as "moderate to severe disability", and 2 to 3 as "severe to very severe disability".
Outcome measures
| Measure |
Rituximab + MTX
n=36 Participants
Participants received rituximab 1000 mg IV and 100 mg methylprednisolone IV on Days 1 and 15. Participants were to be receiving background MTX (10-25 mg weekly, oral or parenteral dose).
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Change From Baseline in HAQ-DI Score
Baseline
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1.07 scores on a scale
Standard Deviation 0.69
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Change From Baseline in HAQ-DI Score
Week 24
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0.81 scores on a scale
Standard Deviation 0.65
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Change From Baseline in HAQ-DI Score
Change from Baseline to Week 24
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-0.26 scores on a scale
Standard Deviation 0.52
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Adverse Events
Rituximab + MTX
Serious adverse events
| Measure |
Rituximab + MTX
n=36 participants at risk
Participants received rituximab 1000 mg IV and 100 mg methylprednisolone IV on Days 1 and 15. Participants were to be receiving background MTX (10-25 mg weekly, oral or parenteral dose).
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Musculoskeletal and connective tissue disorders
Spinal column stenosis
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2.8%
1/36 • 24 weeks
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Hepatobiliary disorders
Cholelithiasis
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2.8%
1/36 • 24 weeks
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Musculoskeletal and connective tissue disorders
Back pain
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2.8%
1/36 • 24 weeks
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Other adverse events
| Measure |
Rituximab + MTX
n=36 participants at risk
Participants received rituximab 1000 mg IV and 100 mg methylprednisolone IV on Days 1 and 15. Participants were to be receiving background MTX (10-25 mg weekly, oral or parenteral dose).
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|---|---|
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Blood and lymphatic system disorders
Leukocytosis
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2.8%
1/36 • 24 weeks
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Blood and lymphatic system disorders
Mononucleosis syndrome
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2.8%
1/36 • 24 weeks
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Cardiac disorders
Dizziness
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5.6%
2/36 • 24 weeks
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Gastrointestinal disorders
Abdominal pain upper
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2.8%
1/36 • 24 weeks
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Gastrointestinal disorders
Diarrhoea
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2.8%
1/36 • 24 weeks
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Gastrointestinal disorders
Gastritis
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2.8%
1/36 • 24 weeks
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|
Gastrointestinal disorders
Gingival bleeding
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2.8%
1/36 • 24 weeks
|
|
Gastrointestinal disorders
Hiatus hernia
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2.8%
1/36 • 24 weeks
|
|
Gastrointestinal disorders
Mouth ulceration
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2.8%
1/36 • 24 weeks
|
|
Gastrointestinal disorders
Oesophageal candidiasis
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2.8%
1/36 • 24 weeks
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Gastrointestinal disorders
Peptic ulcer
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2.8%
1/36 • 24 weeks
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General disorders
Fatigue
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5.6%
2/36 • 24 weeks
|
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General disorders
Oedema peripheral
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2.8%
1/36 • 24 weeks
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|
Hepatobiliary disorders
Hepatic function abnormal
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2.8%
1/36 • 24 weeks
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|
Infections and infestations
Respiratory tract infection
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2.8%
1/36 • 24 weeks
|
|
Infections and infestations
Upper respiratory tract infection
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22.2%
8/36 • 24 weeks
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Investigations
Alanine aminotransferase increased
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2.8%
1/36 • 24 weeks
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Investigations
Blood pressure decreased
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2.8%
1/36 • 24 weeks
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Investigations
Blood pressure increased
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2.8%
1/36 • 24 weeks
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Investigations
Weight increased
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2.8%
1/36 • 24 weeks
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Metabolism and nutrition disorders
Hyperlipidaemia
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2.8%
1/36 • 24 weeks
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|
Musculoskeletal and connective tissue disorders
Arthralgia
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2.8%
1/36 • 24 weeks
|
|
Musculoskeletal and connective tissue disorders
Back pain
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2.8%
1/36 • 24 weeks
|
|
Musculoskeletal and connective tissue disorders
Joint dislocation
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2.8%
1/36 • 24 weeks
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|
Musculoskeletal and connective tissue disorders
Myalgia
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2.8%
1/36 • 24 weeks
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenoma benign
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2.8%
1/36 • 24 weeks
|
|
Psychiatric disorders
Insomnia
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2.8%
1/36 • 24 weeks
|
|
Reproductive system and breast disorders
Menorrhagia
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2.8%
1/36 • 24 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
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2.8%
1/36 • 24 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Cough
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13.9%
5/36 • 24 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Nasal obstruction
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2.8%
1/36 • 24 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Nasopharyngitis
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5.6%
2/36 • 24 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Rhinitis allergic
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2.8%
1/36 • 24 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Wheezing
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2.8%
1/36 • 24 weeks
|
|
Skin and subcutaneous tissue disorders
Acne
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2.8%
1/36 • 24 weeks
|
|
Skin and subcutaneous tissue disorders
Eczema
|
2.8%
1/36 • 24 weeks
|
|
Skin and subcutaneous tissue disorders
Rash
|
5.6%
2/36 • 24 weeks
|
|
Skin and subcutaneous tissue disorders
Seborrhoeic dermatitis
|
2.8%
1/36 • 24 weeks
|
|
Vascular disorders
Hypertension
|
5.6%
2/36 • 24 weeks
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
- Publication restrictions are in place
Restriction type: OTHER