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Trial record 88 of 116 for:    "Connective Tissue Disease" | "Methylprednisolone"

A Study of MabThera (Rituximab) in Combination With Methotrexate in Patients With Rheumatoid Arthritis Who Have Had an Inadequate Response to Anti-TNF Therapies.

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ClinicalTrials.gov Identifier: NCT00462345
Recruitment Status : Completed
First Posted : April 19, 2007
Results First Posted : November 4, 2014
Last Update Posted : November 4, 2014
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Rheumatoid Arthritis
Interventions Drug: rituximab
Drug: Methotrexate
Drug: Corticosteroid or NSAID
Dietary Supplement: Folate
Enrollment 40
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Rituximab, Methotrexate
Hide Arm/Group Description Participants received rituximab 1000 milligrams (mg), intravenously (IV), on Day 1 and Day 15; methylprednisolone 100 mg, IV, was administered 30 minutes before each infusion of rituximab. Participants also received methotrexate (MTX) 10 to 25 milligrams per week (mg/week), orally (PO) or parenterally, and folate at a stable dose of greater than or equal to (≥) 5 mg/week, PO, either as a single dose or as divided daily doses from Day 1 through Week 24. Participants also received prednisone less than or equal to (≤) 10 milligrams per day (mg/day), PO, OR equivalent corticosteroid, OR non-steroidal anti-inflammatory drugs (NSAIDs), PO, from Day 1 through Week 24. Eligible participants who completed the first 24-week course were entered into a second course.
Period Title: Overall Study
Started 40
Completed First Course 38
Completed 37
Not Completed 3
Reason Not Completed
Withdrawal by Subject             2
Did not complete second course             1
Arm/Group Title Rituximab, Methotrexate
Hide Arm/Group Description Participants received rituximab 1000 mg, IV, on Day 1 and Day 15; methylprednisolone 100 mg, IV, was administered 30 minutes before each infusion of rituximab. Participants also received MTX 10 to 25 mg/week, PO or parenterally, and folate at a stable dose of ≥5 mg/week, PO, either as a single dose or as divided daily doses from Day 1 through Week 24. Participants also received prednisone ≤10 mg/day, PO, OR equivalent corticosteroid, OR NSAIDs, PO, from Day 1 through Week 24. Eligible participants who completed the first 24-week course were entered into a second course.
Overall Number of Baseline Participants 40
Hide Baseline Analysis Population Description
Intent to treat (ITT) population included all enrolled participants who received the investigational treatment.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 40 participants
49.9  (11.4)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 40 participants
Female
34
  85.0%
Male
6
  15.0%
1.Primary Outcome
Title Percentage of Participants With An American College of Rheumatology 20 Percent (%) Improvement Criteria (ACR20) Response at Week 24
Hide Description ACR20 response: ≥20% improvement in tender joint count; ≥20% improvement in swollen joint count; and ≥20% improvement in at least 3 of 5 remaining ACR core measures: Patient Assessment of Pain; Patient Global Assessment of Disease Activity (PtGA); Physician Global Assessment of Disease Activity (PGA); self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ-DI]); and either C-Reactive Protein (CRP) or erythrocyte sedimentation rate (ESR).
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population
Arm/Group Title Rituximab, Methotrexate
Hide Arm/Group Description:
Participants received rituximab 1000 mg, IV, on Day 1 and Day 15; methylprednisolone 100 mg, IV, was administered 30 minutes before each infusion of rituximab. Participants also received MTX 10 to 25 mg/week, PO or parenterally, and folate at a stable dose of ≥5 mg/week, PO, either as a single dose or as divided daily doses from Day 1 through Week 24. Participants also received prednisone ≤10 mg/day, PO, OR equivalent corticosteroid, OR NSAIDs, PO, from Day 1 through Week 24. Eligible participants who completed the first 24-week course were entered into a second course.
Overall Number of Participants Analyzed 40
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
47.5
(31.5 to 63.9)
2.Secondary Outcome
Title Percentage of Participants With An American College of Rheumatology 50% Improvement Criteria (ACR50) Response at Week 24
Hide Description ACR50 response: ≥50% improvement in tender joint count; ≥50% improvement in swollen joint count; and ≥50% improvement in at least 3 of 5 remaining ACR core measures: Patient Assessment of Pain; PtGA; PGA; self-assessed disability (HAQ-DI); and either CRP or ESR.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population
Arm/Group Title Rituximab, Methotrexate
Hide Arm/Group Description:
Participants received rituximab 1000 mg, IV, on Day 1 and Day 15; methylprednisolone 100 mg, IV, was administered 30 minutes before each infusion of rituximab. Participants also received MTX 10 to 25 mg/week, PO or parenterally, and folate at a stable dose of ≥5 mg/week, PO, either as a single dose or as divided daily doses from Day 1 through Week 24. Participants also received prednisone ≤10 mg/day, PO, OR equivalent corticosteroid, OR NSAIDs, PO, from Day 1 through Week 24. Eligible participants who completed the first 24-week course were entered into a second course.
Overall Number of Participants Analyzed 40
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
7.5
(1.6 to 20.4)
3.Secondary Outcome
Title Percentage of Participants With An American College of Rheumatology 70% Improvement Criteria (ACR70) Response at Week 24
Hide Description ACR70 response: ≥70% improvement in tender joint count; ≥70% improvement in swollen joint count; and ≥70% improvement in at least 3 of 5 remaining ACR core measures: Patient Assessment of Pain; PtGA; PGA; self-assessed disability (HAQ-DI); and either CRP or ESR.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population
Arm/Group Title Rituximab, Methotrexate
Hide Arm/Group Description:
Participants received rituximab 1000 mg, IV, on Day 1 and Day 15; methylprednisolone 100 mg, IV, was administered 30 minutes before each infusion of rituximab. Participants also received MTX 10 to 25 mg/week, PO or parenterally, and folate at a stable dose of ≥5 mg/week, PO, either as a single dose or as divided daily doses from Day 1 through Week 24. Participants also received prednisone ≤10 mg/day, PO, OR equivalent corticosteroid, OR NSAIDs, PO, from Day 1 through Week 24. Eligible participants who completed the first 24-week course were entered into a second course.
Overall Number of Participants Analyzed 40
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
5.0
(0.6 to 16.9)
4.Secondary Outcome
Title Disease Activity Score Based on 28-Joint Count (DAS-28)
Hide Description DAS28 was calculated from the number of swollen joints and tender joints using the 28 joints count, the ESR (millimeters per hour [mm/hr]) and PtGA of disease activity with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity. DAS28 ≤3.2 equals (=) low disease activity, DAS28 greater than (>)3.2 to 5.1 = moderate to high disease activity.
Time Frame Baseline and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population
Arm/Group Title Rituximab, Methotrexate
Hide Arm/Group Description:
Participants received rituximab 1000 mg, IV, on Day 1 and Day 15; methylprednisolone 100 mg, IV, was administered 30 minutes before each infusion of rituximab. Participants also received MTX 10 to 25 mg/week, PO or parenterally, and folate at a stable dose of ≥5 mg/week, PO, either as a single dose or as divided daily doses from Day 1 through Week 24. Participants also received prednisone ≤10 mg/day, PO, OR equivalent corticosteroid, OR NSAIDs, PO, from Day 1 through Week 24. Eligible participants who completed the first 24-week course were entered into a second course.
Overall Number of Participants Analyzed 40
Mean (Standard Deviation)
Unit of Measure: scores on a scale
Week 0 6.76  (1.02)
Week 24 5.31  (1.16)
Change at Week 24 -1.45  (0.94)
5.Secondary Outcome
Title Percentage of Participants With Change in DAS-28 From BL to Week 24 of ≥1.2
Hide Description DAS28 was calculated from the number of swollen joints and tender joints using the 28 joints count, the ESR (mm/hr) and PtGA of disease activity with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population
Arm/Group Title Rituximab, Methotrexate
Hide Arm/Group Description:
Participants received rituximab 1000 mg, IV, on Day 1 and Day 15; methylprednisolone 100 mg, IV, was administered 30 minutes before each infusion of rituximab. Participants also received MTX 10 to 25 mg/week, PO or parenterally, and folate at a stable dose of ≥5 mg/week, PO, either as a single dose or as divided daily doses from Day 1 through Week 24. Participants also received prednisone ≤10 mg/day, PO, OR equivalent corticosteroid, OR NSAIDs, PO, from Day 1 through Week 24. Eligible participants who completed the first 24-week course were entered into a second course.
Overall Number of Participants Analyzed 40
Measure Type: Number
Unit of Measure: percentage of participants
60.0
6.Secondary Outcome
Title Percentage of Participants With DAS Response by European League Against Rheumatism (EULAR) Category at Week 24
Hide Description The percentage of participants categorized as good, moderate, or nonresponders according to the EULAR response criteria at Week 24. Participants were categorized as good responders if the intensity of their symptoms was in the “low disease activity (DAS28 less than [<]3.2)” category after treatment, and their symptoms significantly decreased to >1.2. Participants were categorized as moderate responders if the intensity of their symptoms was in the “moderate or high disease activity (DAS28 >3.2)” category after treatment, and the symptoms significantly decreased to >1.2; or if the intensity of their symptoms was in the “low or moderate disease activity (DAS28 <5.1)” category, and the DAS28 score changed more than 0.6 or 1.2 or less. Participants were categorized as non-responders if they did not fall into the good or moderate categories.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population
Arm/Group Title Rituximab, Methotrexate
Hide Arm/Group Description:
Participants received rituximab 1000 mg, IV, on Day 1 and Day 15; methylprednisolone 100 mg, IV, was administered 30 minutes before each infusion of rituximab. Participants also received MTX 10 to 25 mg/week, PO or parenterally, and folate at a stable dose of ≥5 mg/week, PO, either as a single dose or as divided daily doses from Day 1 through Week 24. Participants also received prednisone ≤10 mg/day, PO, OR equivalent corticosteroid, OR NSAIDs, PO, from Day 1 through Week 24. Eligible participants who completed the first 24-week course were entered into a second course.
Overall Number of Participants Analyzed 40
Measure Type: Number
Unit of Measure: percentage of participants
Good responders 5.0
Moderate responders 65.0
Nonresponders 30.0
7.Secondary Outcome
Title Swollen Join Count (SJC)
Hide Description Number of swollen joints was determined by examination of 66 joints (as assessed through pressing and palpating during the physical examination) and identifying when swelling was present. The number of swollen joints was recorded on the joint assessment form at each visit as swollen or not swollen.
Time Frame Baseline, Weeks 24 and 48
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population
Arm/Group Title Rituximab, Methotrexate
Hide Arm/Group Description:
Participants received rituximab 1000 mg, IV, on Day 1 and Day 15; methylprednisolone 100 mg, IV, was administered 30 minutes before each infusion of rituximab. Participants also received MTX 10 to 25 mg/week, PO or parenterally, and folate at a stable dose of ≥5 mg/week, PO, either as a single dose or as divided daily doses from Day 1 through Week 24. Participants also received prednisone ≤10 mg/day, PO, OR equivalent corticosteroid, OR NSAIDs, PO, from Day 1 through Week 24. Eligible participants who completed the first 24-week course were entered into a second course.
Overall Number of Participants Analyzed 40
Mean (Standard Deviation)
Unit of Measure: swollen joints
Week 0 16.3  (8.4)
Change at Week 24 -8.9  (6.2)
Change at Week 48 -11.6  (7.2)
8.Secondary Outcome
Title Tender Joint Count (TJC)
Hide Description Number of tender joints was determined by examination of 68 joints (as assessed through pressing and palpating during the physical examination) and identifying when swelling was present. The number of tender joints was recorded on the joint assessment form at each visit as either tender or not tender.
Time Frame Baseline, Weeks 24 and 48
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population
Arm/Group Title Rituximab, Methotrexate
Hide Arm/Group Description:
Participants received rituximab 1000 mg, IV, on Day 1 and Day 15; methylprednisolone 100 mg, IV, was administered 30 minutes before each infusion of rituximab. Participants also received MTX 10 to 25 mg/week, PO or parenterally, and folate at a stable dose of ≥5 mg/week, PO, either as a single dose or as divided daily doses from Day 1 through Week 24. Participants also received prednisone ≤10 mg/day, PO, OR equivalent corticosteroid, OR NSAIDs, PO, from Day 1 through Week 24. Eligible participants who completed the first 24-week course were entered into a second course.
Overall Number of Participants Analyzed 40
Mean (Standard Deviation)
Unit of Measure: tender joints
Week 0 21.9  (14.0)
Change at Week 24 -9.0  (9.3)
Change at Week 48 -13.9  (11.1)
9.Secondary Outcome
Title Patient Global Assessment of Disease Activity (VAS)
Hide Description The mean score of the symptoms of rheumatoid arthritis (RA) at Week 0 (baseline) and the change from Week 0 to Weeks 24 and 48 as assessed by participants using a 100 mm horizontal VAS, where the left endpoint indicated "No disease activity” (no symptom, or no symptom of RA), and the right endpoint indicated “Maximum disease activity” (maximum RA activity). A negative change from Baseline indicated improvement.
Time Frame Baseline, Weeks 24 and 48
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population
Arm/Group Title Rituximab, Methotrexate
Hide Arm/Group Description:
Participants received rituximab 1000 mg, IV, on Day 1 and Day 15; methylprednisolone 100 mg, IV, was administered 30 minutes before each infusion of rituximab. Participants also received MTX 10 to 25 mg/week, PO or parenterally, and folate at a stable dose of ≥5 mg/week, PO, either as a single dose or as divided daily doses from Day 1 through Week 24. Participants also received prednisone ≤10 mg/day, PO, OR equivalent corticosteroid, OR NSAIDs, PO, from Day 1 through Week 24. Eligible participants who completed the first 24-week course were entered into a second course.
Overall Number of Participants Analyzed 40
Mean (Standard Deviation)
Unit of Measure: mm
Week 0 72.6  (21.6)
Change at Week 24 -20.5  (25.8)
Change at Week 48 -31.8  (26.9)
10.Secondary Outcome
Title Physician Global Assessment of Disease Activity (VAS)
Hide Description The mean score of the symptoms of RA at Week 0 and the change from Week 0 (baseline) to Weeks 24 and 48 as assessed by investigators using a 100-mm horizontal VAS, where the left endpoint indicated "No disease activity” (no symptom, or no symptom of RA), and the right endpoint indicated “Maximum disease activity” (maximum RA activity). A negative change from Baseline indicated improvement.
Time Frame Baseline, Weeks 24 and 48
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population
Arm/Group Title Rituximab, Methotrexate
Hide Arm/Group Description:
Participants received rituximab 1000 mg, IV, on Day 1 and Day 15; methylprednisolone 100 mg, IV, was administered 30 minutes before each infusion of rituximab. Participants also received MTX 10 to 25 mg/week, PO or parenterally, and folate at a stable dose of ≥5 mg/week, PO, either as a single dose or as divided daily doses from Day 1 through Week 24. Participants also received prednisone ≤10 mg/day, PO, OR equivalent corticosteroid, OR NSAIDs, PO, from Day 1 through Week 24. Eligible participants who completed the first 24-week course were entered into a second course.
Overall Number of Participants Analyzed 40
Mean (Standard Deviation)
Unit of Measure: mm
Week 0 72.8  (13.4)
Change at Week 24 -30.4  (24.1)
Change at Week 48 -42.1  (23.0)
11.Secondary Outcome
Title Patient Assessment of Pain (VAS)
Hide Description The mean score of pain at Week 0 (baseline) and the change from Week 0 to Weeks 24 and 48 as assessed by participants using a 100-mm horizontal VAS, where the left endpoint indicated “No pain,” and the right endpoint indicated “Unbearable pain.” A negative change indicated improvement.
Time Frame Baseline, Weeks 24 and 48
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population
Arm/Group Title Rituximab, Methotrexate
Hide Arm/Group Description:
Participants received rituximab 1000 mg, IV, on Day 1 and Day 15; methylprednisolone 100 mg, IV, was administered 30 minutes before each infusion of rituximab. Participants also received MTX 10 to 25 mg/week, PO or parenterally, and folate at a stable dose of ≥5 mg/week, PO, either as a single dose or as divided daily doses from Day 1 through Week 24. Participants also received prednisone ≤10 mg/day, PO, OR equivalent corticosteroid, OR NSAIDs, PO, from Day 1 through Week 24. Eligible participants who completed the first 24-week course were entered into a second course.
Overall Number of Participants Analyzed 40
Mean (Standard Deviation)
Unit of Measure: mm
Week 0 69.3  (20.7)
Change at Week 24 -16.8  (26.1)
Change at Week 48 -28.2  (26.8)
12.Secondary Outcome
Title C-reactive Protein (CRP) Level
Hide Description The mean level of CRP in milligrams per liter (mg/L), an acute phase reactant, at Week 0 and the change from Week 0 to Weeks 24 and 48.
Time Frame Baseline, Weeks 24 and 48
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population
Arm/Group Title Rituximab, Methotrexate
Hide Arm/Group Description:
Participants received rituximab 1000 mg, IV, on Day 1 and Day 15; methylprednisolone 100 mg, IV, was administered 30 minutes before each infusion of rituximab. Participants also received MTX 10 to 25 mg/week, PO or parenterally, and folate at a stable dose of ≥5 mg/week, PO, either as a single dose or as divided daily doses from Day 1 through Week 24. Participants also received prednisone ≤10 mg/day, PO, OR equivalent corticosteroid, OR NSAIDs, PO, from Day 1 through Week 24. Eligible participants who completed the first 24-week course were entered into a second course.
Overall Number of Participants Analyzed 40
Mean (Standard Deviation)
Unit of Measure: mg/L
Week 0 3.80  (4.32)
Change at Week 24 -1.54  (3.85)
Change at Week 48 -2.23  (3.01)
13.Secondary Outcome
Title Erythrocyte Sedimentation Rate (ESR)
Hide Description The mean level of ESR (in mm/hr), an acute phase reactant, at Week 0 and the change from Week 0 to Weeks 24 and 48.
Time Frame Baseline, Weeks 24 and 48
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population
Arm/Group Title Rituximab, Methotrexate
Hide Arm/Group Description:
Participants received rituximab 1000 mg, IV, on Day 1 and Day 15; methylprednisolone 100 mg, IV, was administered 30 minutes before each infusion of rituximab. Participants also received MTX 10 to 25 mg/week, PO or parenterally, and folate at a stable dose of ≥5 mg/week, PO, either as a single dose or as divided daily doses from Day 1 through Week 24. Participants also received prednisone ≤10 mg/day, PO, OR equivalent corticosteroid, OR NSAIDs, PO, from Day 1 through Week 24. Eligible participants who completed the first 24-week course were entered into a second course.
Overall Number of Participants Analyzed 40
Mean (Standard Deviation)
Unit of Measure: mm/hr
Week 0 77.2  (28.6)
Change at Week 24 -23.4  (27.1)
Change at Week 48 -36.1  (26.0)
14.Secondary Outcome
Title HAQ-DI Score
Hide Description HAQ-DI: participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week. Each item scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty.
Time Frame Baseline, Weeks 24 and 48
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population
Arm/Group Title Rituximab, Methotrexate
Hide Arm/Group Description:
Participants received rituximab 1000 mg, IV, on Day 1 and Day 15; methylprednisolone 100 mg, IV, was administered 30 minutes before each infusion of rituximab. Participants also received MTX 10 to 25 mg/week, PO or parenterally, and folate at a stable dose of ≥5 mg/week, PO, either as a single dose or as divided daily doses from Day 1 through Week 24. Participants also received prednisone ≤10 mg/day, PO, OR equivalent corticosteroid, OR NSAIDs, PO, from Day 1 through Week 24. Eligible participants who completed the first 24-week course were entered into a second course.
Overall Number of Participants Analyzed 40
Mean (Standard Deviation)
Unit of Measure: scores on a scale
Week 0 1.66  (0.70)
Change at Week 24 -0.34  (0.58)
Change at Week 48 -0.53  (0.64)
15.Secondary Outcome
Title Physical Function as Assessed by Short Form 36 (SF-36)
Hide Description SF-36 is a standardized survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning).
Time Frame Screening, Weeks 24 and 48
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population; n (number) = number of participants assessed for the specified parameter at a given visit.
Arm/Group Title Rituximab, Methotrexate
Hide Arm/Group Description:
Participants received rituximab 1000 mg, IV, on Day 1 and Day 15; methylprednisolone 100 mg, IV, was administered 30 minutes before each infusion of rituximab. Participants also received MTX 10 to 25 mg/week, PO or parenterally, and folate at a stable dose of ≥5 mg/week, PO, either as a single dose or as divided daily doses from Day 1 through Week 24. Participants also received prednisone ≤10 mg/day, PO, OR equivalent corticosteroid, OR NSAIDs, PO, from Day 1 through Week 24. Eligible participants who completed the first 24-week course were entered into a second course.
Overall Number of Participants Analyzed 39
Mean (Standard Deviation)
Unit of Measure: scores on a scale
Screening, Physical functioning (n=39) 27.7  (17.2)
Screening, Role-physical (n=39) 26.6  (21.5)
Screening, Bodily pain (n=39) 29.2  (17.5)
Screening, General health (n=39) 31.7  (16.2)
Week 24, Physical functioning (n=39) 35.8  (22.5)
Week 24, Role-physical (n=39) 41.5  (23.1)
Week 24, Bodily pain (n=39) 44.7  (19.7)
Week 24, General health (n=39) 38.1  (17.1)
Week 48, Physical functioning (n=39) 43.4  (26.7)
Week 48, Role-physical (n=38) 49.3  (29.0)
Week 48, Bodily pain (n=38) 50.9  (22.7)
Week 48, General health (n=38) 44.9  (22.7)
16.Secondary Outcome
Title SF-36 Mental Component Scores
Hide Description SF-36 is a standardized survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning).
Time Frame Screening, Weeks 24 and 48
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population; n=number of participants assessed for the specified parameter at a given visit.
Arm/Group Title Rituximab, Methotrexate
Hide Arm/Group Description:
Participants received rituximab 1000 mg, IV, on Day 1 and Day 15; methylprednisolone 100 mg, IV, was administered 30 minutes before each infusion of rituximab. Participants also received MTX 10 to 25 mg/week, PO or parenterally, and folate at a stable dose of ≥5 mg/week, PO, either as a single dose or as divided daily doses from Day 1 through Week 24. Participants also received prednisone ≤10 mg/day, PO, OR equivalent corticosteroid, OR NSAIDs, PO, from Day 1 through Week 24. Eligible participants who completed the first 24-week course were entered into a second course.
Overall Number of Participants Analyzed 39
Mean (Standard Deviation)
Unit of Measure: scores on a scale
Screening, Vitality (n=38) 30.3  (18.6)
Screening, Social functioning (n=39) 41.7  (26.8)
Screening, Role-emotional (n=39) 36.8  (25.3)
Screening, Mental health (n=38) 52.9  (19.5)
Week 24, Vitality (n=39) 35.7  (21.2)
Week 24, Social functioning (n=39) 55.5  (25.6)
Week 24, Role-emotional (n=39) 53.9  (27.6)
Week 24, Mental health (n=39) 56.0  (21.4)
Week 48, Vitality (n=38) 44.2  (26.6)
Week 48, Social functioning (n=38) 63.2  (26.0)
Week 48, Role-emotional (n=38) 55.5  (31.9)
Week 48, Mental health (n=38) 60.7  (23.9)
17.Secondary Outcome
Title Modified Total Sharp-Genant Score (mTSS)
Hide Description Posterior-anterior (PA) radiograph of each hand and anterior-posterior (AP) radiograph of each foot were taken separately and assessed according to Genant’s method as modified from Sharp’s method. The Sharp-Genant score=total of the erosion score and the joint space narrowing (JSN) score of all the hands and feet. Erosion Score: 14 locations in each hand and wrist and 6 joints in the foot were evaluated for erosion using an 8-point scale where 0=Normal to 3.5=very severe erosion. JSN Score:13 locations in each hand and wrist and 6 joints in the foot were evaluated for joint narrowing score using a 9-point scale where 0=Normal to 4.0=definite ankylosis (stiffness or fixation of a joint). Maximum total erosion score in hands=100 and in feet=42; maximum scores for JSN in the hands=100 and in feet=48. Maximum modified Sharp score achievable is 290. A lower number change from Baseline indicated a better score. Change in scores was calculated as change=final score minus initial score.
Time Frame Screening and Weeks 24 and 48
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ITT population
Arm/Group Title Rituximab, Methotrexate
Hide Arm/Group Description:
Participants received rituximab 1000 mg, IV, on Day 1 and Day 15; methylprednisolone 100 mg, IV, was administered 30 minutes before each infusion of rituximab. Participants also received MTX 10 to 25 mg/week, PO or parenterally, and folate at a stable dose of ≥5 mg/week, PO, either as a single dose or as divided daily doses from Day 1 through Week 24. Participants also received prednisone ≤10 mg/day, PO, OR equivalent corticosteroid, OR NSAIDs, PO, from Day 1 through Week 24. Eligible participants who completed the first 24-week course were entered into a second course.
Overall Number of Participants Analyzed 39
Mean (Standard Deviation)
Unit of Measure: scores on a scale
Screening 79.5  (48.5)
Change at Week 24 0.26  (0.55)
Change at Week 48 0.64  (1.16)
18.Secondary Outcome
Title Modified Sharp Radiographic Erosion Score (ES)
Hide Description Erosion Score: A total of 14 locations in each hand and wrist and 6 joints in the foot were evaluated for erosion using an 8-point scale where 0=Normal to 3.5=very severe erosion. Maximum total erosion score in the hands was 100 and in the feet was 42, for a maximum overall score of 142. Total erosion score was for both hands and feet.
Time Frame Screening, Weeks 24 and 48
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population
Arm/Group Title Rituximab, Methotrexate
Hide Arm/Group Description:
Participants received rituximab 1000 mg, IV, on Day 1 and Day 15; methylprednisolone 100 mg, IV, was administered 30 minutes before each infusion of rituximab. Participants also received MTX 10 to 25 mg/week, PO or parenterally, and folate at a stable dose of ≥5 mg/week, PO, either as a single dose or as divided daily doses from Day 1 through Week 24. Participants also received prednisone ≤10 mg/day, PO, OR equivalent corticosteroid, OR NSAIDs, PO, from Day 1 through Week 24. Eligible participants who completed the first 24-week course were entered into a second course.
Overall Number of Participants Analyzed 39
Mean (Standard Deviation)
Unit of Measure: scores on a scale
Screening 25.2  (25.1)
Change at Week 24 0.18  (0.42)
Change at Week 48 0.49  (0.89)
19.Secondary Outcome
Title Modified Sharp Radiographic Joint Space Narrowing Score (JSN)
Hide Description JSN Score: A total of 13 locations in each hand and wrist and 6 joints in the foot were evaluated for joint narrowing score using a 9-point scale where 0=Normal to 4.0=definite ankylosis (stiffness or fixation of a joint). Maximum total scores for JSN in the hands was 100 and in the feet was 48, for a maximum overall score of 148. Total JSN was for both hands and feet.
Time Frame Screening, Weeks 24 and 48
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Hide Analysis Population Description
ITT population. 39 participants were analyzed for this outcome measure.
Arm/Group Title Rituximab, Methotrexate
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Participants received rituximab 1000 mg, IV, on Day 1 and Day 15; methylprednisolone 100 mg, IV, was administered 30 minutes before each infusion of rituximab. Participants also received MTX 10 to 25 mg/week, PO or parenterally, and folate at a stable dose of ≥5 mg/week, PO, either as a single dose or as divided daily doses from Day 1 through Week 24. Participants also received prednisone ≤10 mg/day, PO, OR equivalent corticosteroid, OR NSAIDs, PO, from Day 1 through Week 24. Eligible participants who completed the first 24-week course were entered into a second course.
Overall Number of Participants Analyzed 39
Mean (Standard Deviation)
Unit of Measure: scores on a scale
Screening 54.3  (27.6)
Change at Week 24 0.08  (0.24)
Change at Week 48 0.15  (0.51)
Time Frame Adverse events (AEs) were reported from Screening up through Week 48 or Withdrawal Visit.
Adverse Event Reporting Description All enrolled participants who received study treatment were included in the safety analysis. The study did not include a separate analysis of nonserious AEs, therefore AEs presented in this record include all AEs reported during the study, not just nonserious events.
 
Arm/Group Title Rituximab, Methotrexate
Hide Arm/Group Description Participants received rituximab 1000 mg, IV, on Day 1 and Day 15; methylprednisolone 100 mg, IV, was administered 30 minutes before each infusion of rituximab. Participants also received MTX 10 to 25 mg/week, PO or parenterally, and folate at a stable dose of ≥5 mg/week, PO, either as a single dose or as divided daily doses from Day 1 through Week 24. Participants also received prednisone ≤10 mg/day, PO, OR equivalent corticosteroid, OR NSAIDs, PO, from Day 1 through Week 24. Eligible participants who completed the first 24-week course were entered into a second course.
All-Cause Mortality
Rituximab, Methotrexate
Affected / at Risk (%)
Total   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Rituximab, Methotrexate
Affected / at Risk (%)
Total   6/40 (15.00%) 
Gastrointestinal disorders   
Appendicitis * 1  2/40 (5.00%) 
Infections and infestations   
Arthritis bacterial * 1  1/40 (2.50%) 
Infection * 1  1/40 (2.50%) 
Scrub typhus * 1  1/40 (2.50%) 
Injury, poisoning and procedural complications   
Concussion * 1  1/40 (2.50%) 
Surgical and medical procedures   
Knee arthroplasty * 1  1/40 (2.50%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Rituximab, Methotrexate
Affected / at Risk (%)
Total   38/40 (95.00%) 
Eye disorders   
Iridocyclitis * 1  1/40 (2.50%) 
Keratitis * 1  1/40 (2.50%) 
Visual acuity reduced * 1  1/40 (2.50%) 
Gastrointestinal disorders   
Nausea * 1  3/40 (7.50%) 
Constipation * 1  2/40 (5.00%) 
Dyspepsia * 1  2/40 (5.00%) 
Diarrhoea * 1  1/40 (2.50%) 
Dry mouth * 1  1/40 (2.50%) 
Gingival pain * 1  1/40 (2.50%) 
Mouth ulceration * 1  1/40 (2.50%) 
General disorders   
Feeling hot * 1  4/40 (10.00%) 
Chest discomfort * 1  2/40 (5.00%) 
Face oedema * 1  2/40 (5.00%) 
Pyrexia * 1  2/40 (5.00%) 
Chest pain * 1  1/40 (2.50%) 
Fatigue * 1  1/40 (2.50%) 
Irritability * 1  1/40 (2.50%) 
Infections and infestations   
Upper respiratory tract infection * 1  12/40 (30.00%) 
Onychomycosis * 1  3/40 (7.50%) 
Appendicitis * 1  2/40 (5.00%) 
Arthritis bacterial * 1  1/40 (2.50%) 
Fungal infection * 1  1/40 (2.50%) 
Infection * 1  1/40 (2.50%) 
Scrub typhus * 1  1/40 (2.50%) 
Injury, poisoning and procedural complications   
Concussion * 1  1/40 (2.50%) 
Contusion * 1  1/40 (2.50%) 
Joint dislocation * 1  1/40 (2.50%) 
Neck injury * 1  1/40 (2.50%) 
Wrist fracture * 1  1/40 (2.50%) 
Investigations   
Blood pressure decreased * 1  1/40 (2.50%) 
Gamma-glutamyltransferase increased * 1  1/40 (2.50%) 
Weight decreased * 1  1/40 (2.50%) 
Musculoskeletal and connective tissue disorders   
Arthralgia * 1  5/40 (12.50%) 
Myalgia * 1  3/40 (7.50%) 
Rheumatoid arthritis * 1  3/40 (7.50%) 
Arthritis * 1  1/40 (2.50%) 
Osteopenia * 1  1/40 (2.50%) 
Osteoporosis * 1  1/40 (2.50%) 
Pain in extremity * 1  1/40 (2.50%) 
Rotator cuff syndrome * 1  1/40 (2.50%) 
Urticaria * 1  2/40 (5.00%) 
Nervous system disorders   
Headache * 1  3/40 (7.50%) 
Dizziness * 1  3/40 (7.50%) 
Amnesia * 1  2/40 (5.00%) 
Disturbance in attention * 1  1/40 (2.50%) 
Somnolence * 1  1/40 (2.50%) 
Psychiatric disorders   
Insomnia * 1  2/40 (5.00%) 
Renal and urinary disorders   
Dysuria * 1  1/40 (2.50%) 
Reproductive system and breast disorders   
Breast mass * 1  1/40 (2.50%) 
Galactorrhoea * 1  1/40 (2.50%) 
Menopausal symptoms * 1  1/40 (2.50%) 
Prostatitis * 1  1/40 (2.50%) 
Respiratory, thoracic and mediastinal disorders   
Pharyngolaryngeal pain * 1  4/40 (10.00%) 
Cough * 1  3/40 (7.50%) 
Rhinorrhoea * 1  2/40 (5.00%) 
Dysphonia * 1  1/40 (2.50%) 
Productive cough * 1  1/40 (2.50%) 
Skin and subcutaneous tissue disorders   
Rash * 1  6/40 (15.00%) 
Alopecia * 1  3/40 (7.50%) 
Pruritus * 1  3/40 (7.50%) 
Hyperhidrosis * 1  2/40 (5.00%) 
Swelling face * 1  2/40 (5.00%) 
Erythema * 1  1/40 (2.50%) 
Surgical and medical procedures   
Knee arthroplasty * 1  1/40 (2.50%) 
Vascular disorders   
Vasculitis * 1  1/40 (2.50%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
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Name/Title: Medical Communications
Organization: Hoffman-LaRoche
Phone: 800-821-8590
EMail: genentech@druginfo.com
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Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00462345     History of Changes
Other Study ID Numbers: ML20934
First Submitted: April 18, 2007
First Posted: April 19, 2007
Results First Submitted: May 8, 2014
Results First Posted: November 4, 2014
Last Update Posted: November 4, 2014