A Study of MabThera (Rituximab) in Combination With Methotrexate in Patients With Rheumatoid Arthritis Who Have Had an Inadequate Response to Anti-TNF Therapies.
Study Details
Study Description
Brief Summary
This single arm study will evaluate the efficacy and safety of MabThera in combination with methotrexate in patients with rheumatoid arthritis who have had an inadequate response to one or more anti-TNF therapies. Patients will receive MabThera 1000mg i.v. on days 1 and 15, and methotrexate (10-25mg/week p.o. or parenteral), together with methylprednisolone 100mg i.v. prior to infusion of MabThera. After week 24, eligible patients may receive re-treatment. The anticipated time on study treatment is 3-12 months, and the target sample size is <100 individuals.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 4 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Rituximab, Methotrexate Participants received rituximab 1000 milligrams (mg), intravenously (IV), on Day 1 and Day 15. Participants also received methylprednisolone 100 mg, IV, 30 minutes before the infusion of rituximab. Participants also received methotrexate (MTX) 10 to 25 milligrams per week (mg/week), orally (PO) or parenterally, and folate greater than or equal to (≥) 5 mg/week, PO, folate 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. |
Drug: rituximab
1000 mg i.v. on Days 1 and 15
Other Names:
Drug: Methotrexate
10 to 25 mg/week p.o. or parenteral from Day 1 through Week 24
Drug: Corticosteroid or NSAID
≤10 mg/day prednisone p.o., or equivalent corticosteroid, or NSAIDs p.o. from Day 1 through Week 24
Dietary Supplement: Folate
≥5 mg/week, once daily or b.i.d. from Day 1 through Week 24
|
Outcome Measures
Primary Outcome Measures
- Percentage of Participants With An American College of Rheumatology 20 Percent (%) Improvement Criteria (ACR20) Response at Week 24 [Week 24]
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).
Secondary Outcome Measures
- Percentage of Participants With An American College of Rheumatology 50% Improvement Criteria (ACR50) Response at Week 24 [Week 24]
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.
- Percentage of Participants With An American College of Rheumatology 70% Improvement Criteria (ACR70) Response at Week 24 [Week 24]
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.
- Disease Activity Score Based on 28-Joint Count (DAS-28) [Baseline and Week 24]
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.
- Percentage of Participants With Change in DAS-28 From BL to Week 24 of ≥1.2 [Baseline, Week 24]
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.
- Percentage of Participants With DAS Response by European League Against Rheumatism (EULAR) Category at Week 24 [Week 24]
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.
- Swollen Join Count (SJC) [Baseline, Weeks 24 and 48]
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.
- Tender Joint Count (TJC) [Baseline, Weeks 24 and 48]
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.
- Patient Global Assessment of Disease Activity (VAS) [Baseline, Weeks 24 and 48]
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.
- Physician Global Assessment of Disease Activity (VAS) [Baseline, Weeks 24 and 48]
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.
- Patient Assessment of Pain (VAS) [Baseline, Weeks 24 and 48]
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.
- C-reactive Protein (CRP) Level [Baseline, Weeks 24 and 48]
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.
- Erythrocyte Sedimentation Rate (ESR) [Baseline, Weeks 24 and 48]
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.
- HAQ-DI Score [Baseline, Weeks 24 and 48]
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.
- Physical Function as Assessed by Short Form 36 (SF-36) [Screening, Weeks 24 and 48]
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).
- SF-36 Mental Component Scores [Screening, Weeks 24 and 48]
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).
- Modified Total Sharp-Genant Score (mTSS) [Screening and Weeks 24 and 48]
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.
- Modified Sharp Radiographic Erosion Score (ES) [Screening, Weeks 24 and 48]
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.
- Modified Sharp Radiographic Joint Space Narrowing Score (JSN) [Screening, Weeks 24 and 48]
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.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
adult patients, 18-80 years of age;
-
rheumatoid arthritis for >=6 months;
-
receiving outpatient treatment;
-
an inadequate response to at least one anti-TNF therapy;
-
stable methotrexate for >=12 weeks.
Exclusion Criteria:
-
other rheumatic autoimmune disease or inflammatory joint disease;
-
previous treatment with MabThera;
-
concurrent treatment with any DMARD (apart from methotrexate), anti-TNF alpha therapy, or other biologic agent.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Seoul | Korea, Republic of | 110-744 | ||
| 2 | Seoul | Korea, Republic of | 133-792 | ||
| 3 | Seoul | Korea, Republic of | 137701 | ||
| 4 | Seoul | Korea, Republic of | 138-736 |
Sponsors and Collaborators
- Hoffmann-La Roche
Investigators
- Study Director: Clinical Trials, Hoffmann-La Roche
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- ML20934
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Rituximab, Methotrexate |
|---|---|
| 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 |
Baseline Characteristics
| Arm/Group Title | Rituximab, Methotrexate |
|---|---|
| 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 Participants | 40 |
| Age (years) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [years] |
49.9
(11.4)
|
| Sex: Female, Male (Count of Participants) | |
| Female |
34
85%
|
| Male |
6
15%
|
Outcome Measures
| Title | Percentage of Participants With An American College of Rheumatology 20 Percent (%) Improvement Criteria (ACR20) Response at Week 24 |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population |
| Arm/Group Title | Rituximab, Methotrexate |
|---|---|
| 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. |
| Measure Participants | 40 |
| Number (95% Confidence Interval) [percentage of participants] |
47.5
118.8%
|
| Title | Percentage of Participants With An American College of Rheumatology 50% Improvement Criteria (ACR50) Response at Week 24 |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population |
| Arm/Group Title | Rituximab, Methotrexate |
|---|---|
| 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. |
| Measure Participants | 40 |
| Number (95% Confidence Interval) [percentage of participants] |
7.5
18.8%
|
| Title | Percentage of Participants With An American College of Rheumatology 70% Improvement Criteria (ACR70) Response at Week 24 |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population |
| Arm/Group Title | Rituximab, Methotrexate |
|---|---|
| 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. |
| Measure Participants | 40 |
| Number (95% Confidence Interval) [percentage of participants] |
5.0
12.5%
|
| Title | Disease Activity Score Based on 28-Joint Count (DAS-28) |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population |
| Arm/Group Title | Rituximab, Methotrexate |
|---|---|
| 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. |
| Measure Participants | 40 |
| Week 0 |
6.76
(1.02)
|
| Week 24 |
5.31
(1.16)
|
| Change at Week 24 |
-1.45
(0.94)
|
| Title | Percentage of Participants With Change in DAS-28 From BL to Week 24 of ≥1.2 |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population |
| Arm/Group Title | Rituximab, Methotrexate |
|---|---|
| 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. |
| Measure Participants | 40 |
| Number [percentage of participants] |
60.0
150%
|
| Title | Percentage of Participants With DAS Response by European League Against Rheumatism (EULAR) Category at Week 24 |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population |
| Arm/Group Title | Rituximab, Methotrexate |
|---|---|
| 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. |
| Measure Participants | 40 |
| Good responders |
5.0
12.5%
|
| Moderate responders |
65.0
162.5%
|
| Nonresponders |
30.0
75%
|
| Title | Swollen Join Count (SJC) |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population |
| Arm/Group Title | Rituximab, Methotrexate |
|---|---|
| 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. |
| Measure Participants | 40 |
| Week 0 |
16.3
(8.4)
|
| Change at Week 24 |
-8.9
(6.2)
|
| Change at Week 48 |
-11.6
(7.2)
|
| Title | Tender Joint Count (TJC) |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population |
| Arm/Group Title | Rituximab, Methotrexate |
|---|---|
| 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. |
| Measure Participants | 40 |
| Week 0 |
21.9
(14.0)
|
| Change at Week 24 |
-9.0
(9.3)
|
| Change at Week 48 |
-13.9
(11.1)
|
| Title | Patient Global Assessment of Disease Activity (VAS) |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population |
| Arm/Group Title | Rituximab, Methotrexate |
|---|---|
| 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. |
| Measure Participants | 40 |
| Week 0 |
72.6
(21.6)
|
| Change at Week 24 |
-20.5
(25.8)
|
| Change at Week 48 |
-31.8
(26.9)
|
| Title | Physician Global Assessment of Disease Activity (VAS) |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population |
| Arm/Group Title | Rituximab, Methotrexate |
|---|---|
| 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. |
| Measure Participants | 40 |
| Week 0 |
72.8
(13.4)
|
| Change at Week 24 |
-30.4
(24.1)
|
| Change at Week 48 |
-42.1
(23.0)
|
| Title | Patient Assessment of Pain (VAS) |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population |
| Arm/Group Title | Rituximab, Methotrexate |
|---|---|
| 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. |
| Measure Participants | 40 |
| Week 0 |
69.3
(20.7)
|
| Change at Week 24 |
-16.8
(26.1)
|
| Change at Week 48 |
-28.2
(26.8)
|
| Title | C-reactive Protein (CRP) Level |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population |
| Arm/Group Title | Rituximab, Methotrexate |
|---|---|
| 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. |
| Measure Participants | 40 |
| Week 0 |
3.80
(4.32)
|
| Change at Week 24 |
-1.54
(3.85)
|
| Change at Week 48 |
-2.23
(3.01)
|
| Title | Erythrocyte Sedimentation Rate (ESR) |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population |
| Arm/Group Title | Rituximab, Methotrexate |
|---|---|
| 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. |
| Measure Participants | 40 |
| Week 0 |
77.2
(28.6)
|
| Change at Week 24 |
-23.4
(27.1)
|
| Change at Week 48 |
-36.1
(26.0)
|
| Title | HAQ-DI Score |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population |
| Arm/Group Title | Rituximab, Methotrexate |
|---|---|
| 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. |
| Measure Participants | 40 |
| Week 0 |
1.66
(0.70)
|
| Change at Week 24 |
-0.34
(0.58)
|
| Change at Week 48 |
-0.53
(0.64)
|
| Title | Physical Function as Assessed by Short Form 36 (SF-36) |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population; n (number) = number of participants assessed for the specified parameter at a given visit. |
| Arm/Group Title | Rituximab, Methotrexate |
|---|---|
| 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. |
| Measure Participants | 39 |
| 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)
|
| Title | SF-36 Mental Component Scores |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population; n=number of participants assessed for the specified parameter at a given visit. |
| Arm/Group Title | Rituximab, Methotrexate |
|---|---|
| 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. |
| Measure Participants | 39 |
| 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)
|
| Title | Modified Total Sharp-Genant Score (mTSS) |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population |
| Arm/Group Title | Rituximab, Methotrexate |
|---|---|
| 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. |
| Measure Participants | 39 |
| Screening |
79.5
(48.5)
|
| Change at Week 24 |
0.26
(0.55)
|
| Change at Week 48 |
0.64
(1.16)
|
| Title | Modified Sharp Radiographic Erosion Score (ES) |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population |
| Arm/Group Title | Rituximab, Methotrexate |
|---|---|
| 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. |
| Measure Participants | 39 |
| Screening |
25.2
(25.1)
|
| Change at Week 24 |
0.18
(0.42)
|
| Change at Week 48 |
0.49
(0.89)
|
| Title | Modified Sharp Radiographic Joint Space Narrowing Score (JSN) |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population. 39 participants were analyzed for this outcome measure. |
| Arm/Group Title | Rituximab, Methotrexate |
|---|---|
| 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. |
| Measure Participants | 39 |
| Screening |
54.3
(27.6)
|
| Change at Week 24 |
0.08
(0.24)
|
| Change at Week 48 |
0.15
(0.51)
|
Adverse Events
| 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 | |
| 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 (%) | # Events | |
| Total | / (NaN) | |
Serious Adverse Events |
||
| Rituximab, Methotrexate | ||
| Affected / at Risk (%) | # Events | |
| Total | 6/40 (15%) | |
| Gastrointestinal disorders | ||
| Appendicitis | 2/40 (5%) | |
| Infections and infestations | ||
| Arthritis bacterial | 1/40 (2.5%) | |
| Infection | 1/40 (2.5%) | |
| Scrub typhus | 1/40 (2.5%) | |
| Injury, poisoning and procedural complications | ||
| Concussion | 1/40 (2.5%) | |
| Surgical and medical procedures | ||
| Knee arthroplasty | 1/40 (2.5%) | |
Other (Not Including Serious) Adverse Events |
||
| Rituximab, Methotrexate | ||
| Affected / at Risk (%) | # Events | |
| Total | 38/40 (95%) | |
| Eye disorders | ||
| Iridocyclitis | 1/40 (2.5%) | |
| Keratitis | 1/40 (2.5%) | |
| Visual acuity reduced | 1/40 (2.5%) | |
| Gastrointestinal disorders | ||
| Nausea | 3/40 (7.5%) | |
| Constipation | 2/40 (5%) | |
| Dyspepsia | 2/40 (5%) | |
| Diarrhoea | 1/40 (2.5%) | |
| Dry mouth | 1/40 (2.5%) | |
| Gingival pain | 1/40 (2.5%) | |
| Mouth ulceration | 1/40 (2.5%) | |
| General disorders | ||
| Feeling hot | 4/40 (10%) | |
| Chest discomfort | 2/40 (5%) | |
| Face oedema | 2/40 (5%) | |
| Pyrexia | 2/40 (5%) | |
| Chest pain | 1/40 (2.5%) | |
| Fatigue | 1/40 (2.5%) | |
| Irritability | 1/40 (2.5%) | |
| Infections and infestations | ||
| Upper respiratory tract infection | 12/40 (30%) | |
| Onychomycosis | 3/40 (7.5%) | |
| Appendicitis | 2/40 (5%) | |
| Arthritis bacterial | 1/40 (2.5%) | |
| Fungal infection | 1/40 (2.5%) | |
| Infection | 1/40 (2.5%) | |
| Scrub typhus | 1/40 (2.5%) | |
| Injury, poisoning and procedural complications | ||
| Concussion | 1/40 (2.5%) | |
| Contusion | 1/40 (2.5%) | |
| Joint dislocation | 1/40 (2.5%) | |
| Neck injury | 1/40 (2.5%) | |
| Wrist fracture | 1/40 (2.5%) | |
| Investigations | ||
| Blood pressure decreased | 1/40 (2.5%) | |
| Gamma-glutamyltransferase increased | 1/40 (2.5%) | |
| Weight decreased | 1/40 (2.5%) | |
| Musculoskeletal and connective tissue disorders | ||
| Arthralgia | 5/40 (12.5%) | |
| Myalgia | 3/40 (7.5%) | |
| Rheumatoid arthritis | 3/40 (7.5%) | |
| Arthritis | 1/40 (2.5%) | |
| Osteopenia | 1/40 (2.5%) | |
| Osteoporosis | 1/40 (2.5%) | |
| Pain in extremity | 1/40 (2.5%) | |
| Rotator cuff syndrome | 1/40 (2.5%) | |
| Urticaria | 2/40 (5%) | |
| Nervous system disorders | ||
| Headache | 3/40 (7.5%) | |
| Dizziness | 3/40 (7.5%) | |
| Amnesia | 2/40 (5%) | |
| Disturbance in attention | 1/40 (2.5%) | |
| Somnolence | 1/40 (2.5%) | |
| Psychiatric disorders | ||
| Insomnia | 2/40 (5%) | |
| Renal and urinary disorders | ||
| Dysuria | 1/40 (2.5%) | |
| Reproductive system and breast disorders | ||
| Breast mass | 1/40 (2.5%) | |
| Galactorrhoea | 1/40 (2.5%) | |
| Menopausal symptoms | 1/40 (2.5%) | |
| Prostatitis | 1/40 (2.5%) | |
| Respiratory, thoracic and mediastinal disorders | ||
| Pharyngolaryngeal pain | 4/40 (10%) | |
| Cough | 3/40 (7.5%) | |
| Rhinorrhoea | 2/40 (5%) | |
| Dysphonia | 1/40 (2.5%) | |
| Productive cough | 1/40 (2.5%) | |
| Skin and subcutaneous tissue disorders | ||
| Rash | 6/40 (15%) | |
| Alopecia | 3/40 (7.5%) | |
| Pruritus | 3/40 (7.5%) | |
| Hyperhidrosis | 2/40 (5%) | |
| Swelling face | 2/40 (5%) | |
| Erythema | 1/40 (2.5%) | |
| Surgical and medical procedures | ||
| Knee arthroplasty | 1/40 (2.5%) | |
| Vascular disorders | ||
| Vasculitis | 1/40 (2.5%) | |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
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
| Name/Title | Medical Communications |
|---|---|
| Organization | Hoffman-LaRoche |
| Phone | 800-821-8590 |
| genentech@druginfo.com |
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