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A Study to Evaluate the Effects of Rituximab on Immune Responses in Subjects With Active Rheumatoid Arthritis Receiving Background Methotrexate (SIERRA)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00282308
Recruitment Status : Completed
First Posted : January 26, 2006
Results First Posted : October 21, 2013
Last Update Posted : August 10, 2017
Sponsor:
Information provided by (Responsible Party):
Genentech, Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Rheumatoid Arthritis
Interventions Drug: Rituximab
Drug: Methotrexate
Drug: Methylprednisone
Biological: C. albicans
Biological: Tetanus toxoid adsorbed booster vaccine
Biological: 23-valent pneumococcal polysaccharide vaccine
Biological: Keyhole limpet hemocyanin
Enrollment 103
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Rituximab + Methotrexate (Group A) Methotrexate (Group B) All Patients (Combined Groups A and B)
Hide Arm/Group Description Patients received 2 intravenous infusions of rituximab 1000 mg, 14 days apart + methotrexate 10-25 mg/wk orally or subcutaneously during the Treatment Period. Patients received methotrexate 10-25 mg/wk orally or subcutaneously during the Treatment Period. Patients who qualified for re-treatment received 2 intravenous infusions of rituximab 1000 mg, 14 days apart + methotrexate 10-25 mg/week orally or subcutaneously. Patients received methylprednisolone 100 mg intravenously before each infusion of rituximab. Patients received no treatment during the Safety Follow-up Period.
Period Title: Treatment Period
Started 69 34 0 [1]
Completed 65 28 0
Not Completed 4 6 0
Reason Not Completed
Lost to Follow-up             1             0             0
Subject/Guardian Decision to Withdraw             2             4             0
Adverse Event             0             2             0
Not Treated with Study Drug             1             0             0
[1]
Participant Flow is reported separately for the treatment groups for this Period.
Period Title: Optional Extension Re-treatment Period
Started 0 [1] 0 [1] 78 [2]
Completed 0 0 72
Not Completed 0 0 6
Reason Not Completed
Adverse Event             0             0             4
Physician's Decision to Withdraw             0             0             1
Subject/Guardian Decision to Withdraw             0             0             1
[1]
Participant Flow is reported for the combined treatment groups for this Period.
[2]
Not all patients who completed the Treatment Period entered this Optional Re-treatment Period.
Period Title: Safety Follow-up Period
Started 0 [1] 0 [1] 100 [2]
Completed 0 0 81
Not Completed 0 0 19
Reason Not Completed
Adverse Event             0             0             1
Lost to Follow-up             0             0             5
Physician Decision to Withdraw             0             0             1
Subject/Guardian Decision to Withdraw             0             0             12
[1]
Participant Flow is reported for the combined treatment groups for this Period.
[2]
Some patients entered this Safety Follow-up Period directly from the Treatment Period.
Arm/Group Title Rituximab + Methotrexate (Group A) Methotrexate (Group B) Total
Hide Arm/Group Description Patients received 2 intravenous infusions of rituximab 1000 mg, 14 days apart + methotrexate 10-25 mg/wk orally or subcutaneously during the Treatment Period. Patients received methotrexate 10-25 mg/wk orally or subcutaneously during the Treatment Period. Total of all reporting groups
Overall Number of Baseline Participants 68 32 100
Hide Baseline Analysis Population Description
Safety population: All patients who received any amount of rituximab or any vaccine.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 68 participants 32 participants 100 participants
49.7  (9.60) 49.7  (10.51) 49.7  (9.85)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 68 participants 32 participants 100 participants
Female
51
  75.0%
25
  78.1%
76
  76.0%
Male
17
  25.0%
7
  21.9%
24
  24.0%
1.Primary Outcome
Title Percentage of Patients With a Positive Immune Response to Tetanus Toxoid Adsorbed Booster Vaccine
Hide Description The immune response to tetanus toxoid adsorbed booster vaccine was measured in serum samples immediately prior to and 4 weeks after vaccine administration. The tetanus antibody test was an ELISA that used tetanus toxoid as a capturing reagent and alkaline phosphatase-conjugated anti-human IgG (γ) for detection. For patients with pre-vaccination tetanus antibody titers < 0.1 IU/mL, a positive immune response was defined as an antibody titer ≥ 0.2 IU/mL. For patients with pre-vaccination tetanus antibody titers ≥ 0.1 IU/mL, a positive immune response to the booster immunization was defined as a 4-fold increase in antibody titer.
Time Frame Week 24 to Week 28 for Group A and Day 1 to Week 4 for Group B
Hide Outcome Measure Data
Hide Analysis Population Description
Immune response per-protocol population: Group A - All patients randomized to Group A who received any rituximab infusion and any vaccine and had pre-vaccination and 4-week post-vaccination blood samples. Group B - All patients randomized to Group B who received any vaccine and had pre-vaccination and 4-week post-vaccination blood samples.
Arm/Group Title Rituximab + Methotrexate (Group A) Methotrexate (Group B)
Hide Arm/Group Description:
Patients received 2 intravenous infusions of rituximab 1000 mg, 14 days apart + methotrexate 10-25 mg/wk orally or subcutaneously during the Treatment Period.
Patients received methotrexate 10-25 mg/wk orally or subcutaneously during the Treatment Period.
Overall Number of Participants Analyzed 64 26
Measure Type: Number
Unit of Measure: Percentage of patients
39.1 42.3
2.Secondary Outcome
Title Percentage of Patients With a 2-fold Increase in Tetanus Antibody Titers or With Tetanus Antibody Titers ≥ 0.2 IU/mL in Response to Tetanus Toxoid Adsorbed Booster Vaccine
Hide Description The immune response to tetanus toxoid adsorbed booster vaccine was measured in serum samples immediately prior to and 4 weeks after vaccine administration. The tetanus antibody test was an ELISA that used tetanus toxoid as a capturing reagent and alkaline phosphatase-conjugated anti-human IgG (γ) for detection.
Time Frame Week 24 to Week 28 for Group A and Day 1 to Week 4 for Group B
Hide Outcome Measure Data
Hide Analysis Population Description
Immune response per-protocol population: Group A - All patients randomized to Group A who received any rituximab infusion and any vaccine and had pre-vaccination and 4-week post-vaccination blood samples. Group B - All patients randomized to Group B who received any vaccine and had pre-vaccination and 4-week post-vaccination blood samples.
Arm/Group Title Rituximab + Methotrexate (Group A) Methotrexate (Group B)
Hide Arm/Group Description:
Patients received 2 intravenous infusions of rituximab 1000 mg, 14 days apart + methotrexate 10-25 mg/wk orally or subcutaneously during the Treatment Period.
Patients received methotrexate 10-25 mg/wk orally or subcutaneously during the Treatment Period.
Overall Number of Participants Analyzed 64 26
Measure Type: Number
Unit of Measure: Percentage of patients
54.7 61.5
3.Secondary Outcome
Title Percentage of Patients With a Positive Immune Response to Each of the 12 Anti-pneumococcal Antibody Serotypes in Response to the 23-valent Pneumococcal Polysaccharide Vaccine
Hide Description The immune response to each of the 12 anti-pneumococcal antibody serotypes was measured in serum samples immediately prior to and 4 weeks after vaccine administration. The pneumococcal antibody assay was a fluoroimmunoassay that used a Luminex Multiplex platform. Purified capsular polysaccharides isolated from 12 serotypes of S. pneumonia were covalently attached to microbeads and used as a capturing reagent. Phycoerythrin conjugated anti-human IgG was used for detection. A positive immune response against a serotype was defined as a 2-fold increase or an increase of > 1 μg/mL from pre-vaccination levels.
Time Frame Week 28 to Week 32 for Group A and Week 4 to Week 8 for Group B
Hide Outcome Measure Data
Hide Analysis Population Description
Immune response per-protocol population: Group A - All patients randomized to Group A who received any rituximab infusion and any vaccine and had pre-vaccination and 4-week post-vaccination blood samples. Group B - All patients randomized to Group B who received any vaccine and had pre-vaccination and 4-week post-vaccination blood samples.
Arm/Group Title Rituximab + Methotrexate (Group A) Methotrexate (Group B)
Hide Arm/Group Description:
Patients received 2 intravenous infusions of rituximab 1000 mg, 14 days apart + methotrexate 10-25 mg/wk orally or subcutaneously during the Treatment Period.
Patients received methotrexate 10-25 mg/wk orally or subcutaneously during the Treatment Period.
Overall Number of Participants Analyzed 63 28
Measure Type: Number
Unit of Measure: Percentage of patients
Serotype 1-146 (1) 12.7 42.9
Serotype 3-146 (3) 9.5 28.6
Serotype 4-146 (4) 12.7 60.7
Serotype 6/26-146 (6B) 38.1 60.7
Serotype 8-146 (8) 33.3 57.1
Serotype 9-146 (9N) 22.2 60.7
Serotype 12-146 (12F) 11.1 50.0
Serotype 14-146 (14) 30.2 60.7
Serotype 19-146 (19F) 25.4 53.6
Serotype 23-146 (23F) 20.6 35.7
Serotype 51-146 (7F) 25.4 60.7
Serotype 56-146 (18C) 20.6 57.1
4.Secondary Outcome
Title Percentage of Patients With a Positive Immune Response to at Least 50% (≥ 6 of 12) of the 12 Anti-pneumococcal Antibody Serotypes in Response to the 23-valent Pneumococcal Polysaccharide Vaccine
Hide Description The immune response to each of the 12 anti-pneumococcal antibody serotypes was measured in serum samples immediately prior to and 4 weeks after vaccine administration. The pneumococcal antibody assay was a fluoroimmunoassay that used a Luminex Multiplex platform. Purified capsular polysaccharides isolated from 12 serotypes of S. pneumonia were covalently attached to microbeads and used as a capturing reagent. Phycoerythrin conjugated anti-human IgG was used for detection. A positive immune response against a serotype was defined as a 2-fold increase or an increase of > 1 μg/mL from pre-vaccination levels.
Time Frame Week 28 to Week 32 for Group A and Week 4 to Week 8 for Group B
Hide Outcome Measure Data
Hide Analysis Population Description
Immune response per-protocol population: Group A - All patients randomized to Group A who received any rituximab infusion and any vaccine and had pre-vaccination and 4-week post-vaccination blood samples. Group B - All patients randomized to Group B who received any vaccine and had pre-vaccination and 4-week post-vaccination blood samples.
Arm/Group Title Rituximab + Methotrexate (Group A) Methotrexate (Group B)
Hide Arm/Group Description:
Patients received 2 intravenous infusions of rituximab 1000 mg, 14 days apart + methotrexate 10-25 mg/wk orally or subcutaneously during the Treatment Period.
Patients received methotrexate 10-25 mg/wk orally or subcutaneously during the Treatment Period.
Overall Number of Participants Analyzed 63 28
Measure Type: Number
Unit of Measure: Percentage of patients
19.0 60.7
5.Secondary Outcome
Title Percentage of Patients With a Positive Immune Response to at Least k (for k = 1, 2, 3, 4, 5) of the 12 Anti-pneumococcal Antibody Serotypes in Response to the 23-valent Pneumococcal Polysaccharide Vaccine
Hide Description The immune response to each of the 12 anti-pneumococcal antibody serotypes was measured in serum samples immediately prior to and 4 weeks after vaccine administration. The pneumococcal antibody assay was a fluoroimmunoassay that used a Luminex Multiplex platform. Purified capsular polysaccharides isolated from 12 serotypes of S. pneumonia were covalently attached to microbeads and used as a capturing reagent. Phycoerythrin conjugated anti-human IgG was used for detection. A positive immune response against a serotype was defined as a 2-fold increase or an increase of > 1 μg/mL from pre-vaccination levels.
Time Frame Week 28 to Week 32 for Group A and Week 4 to Week 8 for Group B
Hide Outcome Measure Data
Hide Analysis Population Description
Immune response per-protocol population: Group A - All patients randomized to Group A who received any rituximab infusion and any vaccine and had pre-vaccination and 4-week post-vaccination blood samples. Group B - All patients randomized to Group B who received any vaccine and had pre-vaccination and 4-week post-vaccination blood samples.
Arm/Group Title Rituximab + Methotrexate (Group A) Methotrexate (Group B)
Hide Arm/Group Description:
Patients received 2 intravenous infusions of rituximab 1000 mg, 14 days apart + methotrexate 10-25 mg/wk orally or subcutaneously during the Treatment Period.
Patients received methotrexate 10-25 mg/wk orally or subcutaneously during the Treatment Period.
Overall Number of Participants Analyzed 63 28
Measure Type: Number
Unit of Measure: Percentage of patients
1 serotype 57.1 82.1
2 serotypes 42.9 82.1
3 serotypes 38.1 78.6
4 serotypes 33.3 75.0
5 serotypes 23.8 67.9
6.Secondary Outcome
Title Serum Level of Anti-tetanus Antibody Measured Immediately Prior to and 4 Weeks After Administration of a Tetanus Toxoid Adsorbed Booster Vaccine
Hide Description Anti-tetanus antibody was measured in serum samples immediately prior to and 4 weeks after administration of a tetanus toxoid adsorbed booster vaccine. The tetanus antibody test was an ELISA that used tetanus toxoid as a capturing reagent and alkaline phosphatase-conjugated anti-human IgG (γ) for detection.
Time Frame Week 24 to Week 28 for Group A and Day 1 to Week 4 for Group B
Hide Outcome Measure Data
Hide Analysis Population Description
Immune response per-protocol population: Group A - All patients randomized to Group A who received any rituximab infusion and any vaccine and had pre-vaccination and 4-week post-vaccination blood samples. Group B - All patients randomized to Group B who received any vaccine and had pre-vaccination and 4-week post-vaccination blood samples.
Arm/Group Title Rituximab + Methotrexate (Group A) Methotrexate (Group B)
Hide Arm/Group Description:
Patients received 2 intravenous infusions of rituximab 1000 mg, 14 days apart + methotrexate 10-25 mg/wk orally or subcutaneously during the Treatment Period.
Patients received methotrexate 10-25 mg/wk orally or subcutaneously during the Treatment Period.
Overall Number of Participants Analyzed 64 26
Geometric Mean (95% Confidence Interval)
Unit of Measure: IU/mL
Pre-vaccination
1.2
(0.88 to 1.69)
1.0
(0.49 to 2.14)
4 weeks post-vaccination
4.0
(2.72 to 5.74)
5.2
(2.25 to 12.00)
7.Secondary Outcome
Title Serum Level of Anti-pneumococcal Antibody Measured Immediately Prior to and 4 Weeks After Administration of a 23-valent Pneumococcal Polysaccharide Vaccine
Hide Description Anti-pneumococcal antibody was measured immediately prior to and 4 weeks after administration of a 23-valent pneumococcal polysaccharide vaccine. The pneumococcal antibody assay was a fluoroimmunoassay that used a Luminex Multiplex platform. Purified capsular polysaccharides isolated from 12 serotypes of S. pneumonia were covalently attached to microbeads and used as a capturing reagent. Phycoerythrin conjugated anti-human IgG was used for detection.
Time Frame Week 28 to Week 32 for Group A and Week 4 to Week 8 for Group B
Hide Outcome Measure Data
Hide Analysis Population Description
Immune response per-protocol population: Group A - All patients randomized to Group A who received any rituximab infusion and any vaccine and had pre-vaccination and 4-week post-vaccination blood samples. Group B - All patients randomized to Group B who received any vaccine and had pre-vaccination and 4-week post-vaccination blood samples.
Arm/Group Title Rituximab + Methotrexate (Group A) Methotrexate (Group B)
Hide Arm/Group Description:
Patients received 2 intravenous infusions of rituximab 1000 mg, 14 days apart + methotrexate 10-25 mg/wk orally or subcutaneously during the Treatment Period.
Patients received methotrexate 10-25 mg/wk orally or subcutaneously during the Treatment Period.
Overall Number of Participants Analyzed 63 28
Geometric Mean (95% Confidence Interval)
Unit of Measure: µg/mL
Pre-vaccination
0.8
(0.64 to 1.06)
1.0
(0.68 to 1.47)
4 weeks post-vaccination
1.0
(0.76 to 1.37)
2.3
(1.39 to 3.89)
8.Secondary Outcome
Title Serum Level of Anti-keyhole Limpet Hemocyanin Antibody Measured Immediately Prior to and 4 Weeks After the First Administration of Keyhole Limpet Hemocyanin
Hide Description Anti-keyhole limpet hemocyanin antibody was measured immediately prior to and 4 weeks after the first administration of keyhole limpet hemocyanin. The keyhole limpet hemocyanin antibody ELISA assay used keyhole limpet hemocyanin as the plate coat and anti-human IgG-horseradish peroxidase for detection.
Time Frame Week 32 to Week 36 for Group A and Week 8 to Week 12 for Group B
Hide Outcome Measure Data
Hide Analysis Population Description
Immune response per-protocol population: Group A - All patients randomized to Group A who received any rituximab infusion and any vaccine and had pre-vaccination and 4-week post-vaccination blood samples. Group B - All patients randomized to Group B who received any vaccine and had pre-vaccination and 4-week post-vaccination blood samples.
Arm/Group Title Rituximab + Methotrexate (Group A) Methotrexate (Group B)
Hide Arm/Group Description:
Patients received 2 intravenous infusions of rituximab 1000 mg, 14 days apart + methotrexate 10-25 mg/wk orally or subcutaneously during the Treatment Period.
Patients received methotrexate 10-25 mg/wk orally or subcutaneously during the Treatment Period.
Overall Number of Participants Analyzed 64 27
Geometric Mean (95% Confidence Interval)
Unit of Measure: IU/mL
Pre-vaccination
345.7
(312.25 to 382.76)
388.0 [1] 
(NA to NA)
4 weeks post-vaccination
539.5
(461.54 to 630.61)
1585.5
(1065.15 to 2360.17)
[1]
The confidence interval could not be calculated as only 1 patient had an anti-body response above the lower limit of quantitation.
9.Secondary Outcome
Title Percentage of Patients Who Maintained a Positive Response to the C. Albicans Skin Test From Day 1 to Week 24 for Group A or From Day 1 to Week 12 for Group B
Hide Description Patients received an intradermal injection of C. albicans on the volar surface of the forearm on Day 1 and Week 24 for Group A or on Day 1 and Week 12 for Group B. Forty-eight to 72 hours after injection, patients were evaluated for a delayed-type hypersensitivity response by measuring the diameter of induration (palpable raised, hardened area of the forearm skin). A positive response to the C. albicans skin test was defined as at least 5 mm in diameter of induration.
Time Frame Day 1 to Week 24 for Group A and Day 1 to Week 12 for Group B
Hide Outcome Measure Data
Hide Analysis Population Description
Skin test per-protocol population: Group A - All patients randomized to Group A who received any rituximab infusion, had Day 1 and Week 24 skin tests, and who provided complete diameter of induration readings. Group B - All patients randomized to Group B who had Day 1 and Week 12 skin tests and who provided complete diameter of induration readings.
Arm/Group Title Rituximab + Methotrexate (Group A) Methotrexate (Group B)
Hide Arm/Group Description:
Patients received 2 intravenous infusions of rituximab 1000 mg, 14 days apart + methotrexate 10-25 mg/wk orally or subcutaneously during the Treatment Period.
Patients received methotrexate 10-25 mg/wk orally or subcutaneously during the Treatment Period.
Overall Number of Participants Analyzed 64 28
Measure Type: Number
Unit of Measure: Percentage of patients
77.4 70.0
10.Secondary Outcome
Title Percentage of Patients in Group A With an Improvement of at Least 20%, 50%, or 70% in American College of Rheumatology (ACR) Score (ACR20/50/70) From Baseline at Week 24
Hide Description Improvement must be seen in tender and swollen joint counts (28 assessed joints) and in at least 3 of the following 5 parameters: Separate patient and physician assessments of patient disease activity in the previous 24 hours on a visual analog scale (VAS, the extreme left end of the line "no disease activity" [symptom-free and no arthritis symptoms] and the extreme right end "maximum disease activity"; patient assessment of pain in previous the 24 hours on a VAS (extreme left end of the line "no pain" and the extreme right end "unbearable pain"); Health Assessment Questionnaire-Disability Index (20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do); and C reactive protein or, if missing, erythrocyte sedimentation rate.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population: All patients who received any amount of rituximab or any vaccine. Since only limited efficacy data were collected in this study, the parameters necessary to calculate the ACR20/50/70 responses were only available for patients in Group A.
Arm/Group Title Rituximab + Methotrexate (Group A)
Hide Arm/Group Description:
Patients received 2 intravenous infusions of rituximab 1000 mg, 14 days apart + methotrexate 10-25 mg/wk orally or subcutaneously during the Treatment Period.
Overall Number of Participants Analyzed 66
Measure Type: Number
Unit of Measure: Percentage of patients
ACR 20% 36.4
ACR 50% 21.2
ACR 70% 4.5
Time Frame Adverse events were reported from Weeks 1-36 for Group A and Weeks 1-24 for Group B of the treatment period, Weeks 1-6 of the optional extension retreatment period, and Weeks 1-48 of the safety follow-up period (maximum of up to 90 weeks).
Adverse Event Reporting Description Safety population: All patients who received any amount of rituximab or any vaccine.
 
Arm/Group Title Rituximab + Methotrexate (Group A) - Treatment Period Methotrexate (Group B) - Treatment Period Group A - Optional Extension Re-treatment Period Group B - Optional Extension Re-treatment Period Group A - Safety Follow-up Period Group B - Safety Follow-up Period
Hide Arm/Group Description Patients received 2 intravenous infusions of rituximab 1000 mg, 14 days apart + methotrexate 10-25 mg/wk orally or subcutaneously during the Treatment Period. Patients received methotrexate 10-25 mg/wk orally or subcutaneously during the Treatment Period. Patients who qualified for re-treatment received 2 intravenous infusions of rituximab 1000 mg, 14 days apart + methotrexate 10-25 mg/week orally or subcutaneously. Patients received methylprednisolone 100 mg intravenously before each infusion of rituximab. Patients who qualified for re-treatment received 2 intravenous infusions of rituximab 1000 mg, 14 days apart + methotrexate 10-25 mg/week orally or subcutaneously. Patients received methylprednisolone 100 mg intravenously before each infusion of rituximab. Patients received no treatment during the Safety Follow-up Period. Patients received no treatment during the Safety Follow-up Period.
All-Cause Mortality
Rituximab + Methotrexate (Group A) - Treatment Period Methotrexate (Group B) - Treatment Period Group A - Optional Extension Re-treatment Period Group B - Optional Extension Re-treatment Period Group A - Safety Follow-up Period Group B - Safety Follow-up Period
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/--   --/-- 
Hide Serious Adverse Events
Rituximab + Methotrexate (Group A) - Treatment Period Methotrexate (Group B) - Treatment Period Group A - Optional Extension Re-treatment Period Group B - Optional Extension Re-treatment Period Group A - Safety Follow-up Period Group B - Safety Follow-up Period
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   3/68 (4.41%)   2/32 (6.25%)   2/52 (3.85%)   2/26 (7.69%)   3/68 (4.41%)   1/32 (3.13%) 
Cardiac disorders             
Coronary artery disease   1/68 (1.47%)  0/32 (0.00%)  0/52 (0.00%)  0/26 (0.00%)  0/68 (0.00%)  0/32 (0.00%) 
Eye disorders             
Amaurosis fugax   0/68 (0.00%)  0/32 (0.00%)  1/52 (1.92%)  0/26 (0.00%)  0/68 (0.00%)  0/32 (0.00%) 
General disorders             
Chest pain   1/68 (1.47%)  0/32 (0.00%)  0/52 (0.00%)  0/26 (0.00%)  0/68 (0.00%)  0/32 (0.00%) 
Infections and infestations             
Hip fracture   1/68 (1.47%)  0/32 (0.00%)  0/52 (0.00%)  0/26 (0.00%)  0/68 (0.00%)  0/32 (0.00%) 
Pyelonephritis   0/68 (0.00%)  0/32 (0.00%)  1/52 (1.92%)  0/26 (0.00%)  1/68 (1.47%)  0/32 (0.00%) 
Musculoskeletal and connective tissue disorders             
Rheumatoid arthritis   0/68 (0.00%)  1/32 (3.13%)  0/52 (0.00%)  0/26 (0.00%)  0/68 (0.00%)  0/32 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)             
Ovarian cancer   0/68 (0.00%)  0/32 (0.00%)  0/52 (0.00%)  1/26 (3.85%)  0/68 (0.00%)  0/32 (0.00%) 
Thyroid cancer   0/68 (0.00%)  0/32 (0.00%)  0/52 (0.00%)  1/26 (3.85%)  0/68 (0.00%)  1/32 (3.13%) 
Basal cell carcinoma   0/68 (0.00%)  0/32 (0.00%)  0/52 (0.00%)  0/26 (0.00%)  1/68 (1.47%)  0/32 (0.00%) 
Psychiatric disorders             
Bipolar disorder   0/68 (0.00%)  0/32 (0.00%)  0/52 (0.00%)  0/26 (0.00%)  1/68 (1.47%)  0/32 (0.00%) 
Reproductive system and breast disorders             
Ovarian cyst   0/68 (0.00%)  1/32 (3.13%)  0/52 (0.00%)  0/26 (0.00%)  0/68 (0.00%)  0/32 (0.00%) 
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Rituximab + Methotrexate (Group A) - Treatment Period Methotrexate (Group B) - Treatment Period Group A - Optional Extension Re-treatment Period Group B - Optional Extension Re-treatment Period Group A - Safety Follow-up Period Group B - Safety Follow-up Period
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   51/68 (75.00%)   19/32 (59.38%)   7/52 (13.46%)   13/26 (50.00%)   19/68 (27.94%)   11/32 (34.38%) 
Ear and labyrinth disorders             
Ear pruritus   1/68 (1.47%)  3/32 (9.38%)  0/52 (0.00%)  0/26 (0.00%)  0/68 (0.00%)  0/32 (0.00%) 
Gastrointestinal disorders             
Nausea   7/68 (10.29%)  1/32 (3.13%)  0/52 (0.00%)  0/26 (0.00%)  0/68 (0.00%)  0/32 (0.00%) 
Diarrhoea   5/68 (7.35%)  1/32 (3.13%)  0/52 (0.00%)  0/26 (0.00%)  0/68 (0.00%)  0/32 (0.00%) 
General disorders             
Fatigue   4/68 (5.88%)  0/32 (0.00%)  0/52 (0.00%)  2/26 (7.69%)  0/68 (0.00%)  0/32 (0.00%) 
Feeling hot   2/68 (2.94%)  2/32 (6.25%)  0/52 (0.00%)  0/26 (0.00%)  0/68 (0.00%)  0/32 (0.00%) 
Oedema peripheral   4/68 (5.88%)  0/32 (0.00%)  0/52 (0.00%)  0/26 (0.00%)  0/68 (0.00%)  0/32 (0.00%) 
Infections and infestations             
Upper respiratory tract infection   7/68 (10.29%)  2/32 (6.25%)  1/52 (1.92%)  4/26 (15.38%)  8/68 (11.76%)  6/32 (18.75%) 
Sinusitis   5/68 (7.35%)  0/32 (0.00%)  2/52 (3.85%)  3/26 (11.54%)  7/68 (10.29%)  2/32 (6.25%) 
Influenza   5/68 (7.35%)  1/32 (3.13%)  0/52 (0.00%)  0/26 (0.00%)  0/68 (0.00%)  0/32 (0.00%) 
Urinary tract infection   0/68 (0.00%)  0/32 (0.00%)  0/52 (0.00%)  0/26 (0.00%)  6/68 (8.82%)  0/32 (0.00%) 
Bronchitis   0/68 (0.00%)  0/32 (0.00%)  0/52 (0.00%)  0/26 (0.00%)  3/68 (4.41%)  3/32 (9.38%) 
Genital herpes   0/68 (0.00%)  0/32 (0.00%)  0/52 (0.00%)  2/26 (7.69%)  0/68 (0.00%)  0/32 (0.00%) 
Viral upper respiratory tract infection   0/68 (0.00%)  0/32 (0.00%)  0/52 (0.00%)  0/26 (0.00%)  1/68 (1.47%)  2/32 (6.25%) 
Musculoskeletal and connective tissue disorders             
Rheumatoid arthritis   12/68 (17.65%)  0/32 (0.00%)  0/52 (0.00%)  2/26 (7.69%)  2/68 (2.94%)  3/32 (9.38%) 
Arthralgia   8/68 (11.76%)  1/32 (3.13%)  2/52 (3.85%)  2/26 (7.69%)  0/68 (0.00%)  0/32 (0.00%) 
Muscle spasms   4/68 (5.88%)  1/32 (3.13%)  0/52 (0.00%)  0/26 (0.00%)  0/68 (0.00%)  0/32 (0.00%) 
Pain in extremity   0/68 (0.00%)  0/32 (0.00%)  2/52 (3.85%)  2/26 (7.69%)  0/68 (0.00%)  0/32 (0.00%) 
Bursitis   4/68 (5.88%)  0/32 (0.00%)  0/52 (0.00%)  0/26 (0.00%)  0/68 (0.00%)  0/32 (0.00%) 
Neck pain   0/68 (0.00%)  0/32 (0.00%)  0/52 (0.00%)  2/26 (7.69%)  0/68 (0.00%)  0/32 (0.00%) 
Nervous system disorders             
Headache   9/68 (13.24%)  3/32 (9.38%)  0/52 (0.00%)  0/26 (0.00%)  0/68 (0.00%)  0/32 (0.00%) 
Dizziness   4/68 (5.88%)  0/32 (0.00%)  0/52 (0.00%)  0/26 (0.00%)  0/68 (0.00%)  0/32 (0.00%) 
Psychiatric disorders             
Insomnia   3/68 (4.41%)  2/32 (6.25%)  0/52 (0.00%)  0/26 (0.00%)  0/68 (0.00%)  0/32 (0.00%) 
Respiratory, thoracic and mediastinal disorders             
Throat irritation   5/68 (7.35%)  2/32 (6.25%)  0/52 (0.00%)  0/26 (0.00%)  0/68 (0.00%)  0/32 (0.00%) 
Oropharyngeal pain   5/68 (7.35%)  1/32 (3.13%)  0/52 (0.00%)  0/26 (0.00%)  0/68 (0.00%)  0/32 (0.00%) 
Cough   7/68 (10.29%)  1/32 (3.13%)  0/52 (0.00%)  3/26 (11.54%)  0/68 (0.00%)  0/32 (0.00%) 
Respiratory tract congestion   0/68 (0.00%)  0/32 (0.00%)  0/52 (0.00%)  3/26 (11.54%)  0/68 (0.00%)  0/32 (0.00%) 
Sinus congestion   0/68 (0.00%)  0/32 (0.00%)  0/52 (0.00%)  2/26 (7.69%)  0/68 (0.00%)  0/32 (0.00%) 
Skin and subcutaneous tissue disorders             
Pruritus   9/68 (13.24%)  3/32 (9.38%)  0/52 (0.00%)  0/26 (0.00%)  0/68 (0.00%)  0/32 (0.00%) 
Erythema   4/68 (5.88%)  2/32 (6.25%)  0/52 (0.00%)  0/26 (0.00%)  0/68 (0.00%)  0/32 (0.00%) 
Urticaria   5/68 (7.35%)  1/32 (3.13%)  0/52 (0.00%)  0/26 (0.00%)  0/68 (0.00%)  0/32 (0.00%) 
Rash macular   1/68 (1.47%)  3/32 (9.38%)  0/52 (0.00%)  0/26 (0.00%)  0/68 (0.00%)  0/32 (0.00%) 
Vascular disorders             
Flushing   4/68 (5.88%)  0/32 (0.00%)  0/52 (0.00%)  0/26 (0.00%)  0/68 (0.00%)  0/32 (0.00%) 
Indicates events were collected by systematic assessment
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
Layout table for Results Point of Contact information
Name/Title: Medical Communications
Organization: Genentech, Inc.
Phone: 800 821-8590
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Responsible Party: Genentech, Inc.
ClinicalTrials.gov Identifier: NCT00282308    
Other Study ID Numbers: U3374g
First Submitted: January 24, 2006
First Posted: January 26, 2006
Results First Submitted: June 5, 2013
Results First Posted: October 21, 2013
Last Update Posted: August 10, 2017