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A Study to Evaluate the Safety and Efficacy of Rituximab in Combination With Methotrexate Compared to Methotrexate Alone in Patients With Active Rheumatoid Arthritis

Phase 3
Completed
Conditions
Rheumatoid Arthritis
Interventions
Registration Number
NCT00299130
Lead Sponsor
Genentech, Inc.
Brief Summary

This study evaluated the efficacy and safety of rituximab in patients with active rheumatoid arthritis (RA).

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
511
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Placebo + methotrexate (MTX)PlaceboParticipants received placebo intravenous infusion on Days 1 and 15. From Week 16 onwards, participants could switch to receive rituximab 0.5 g (on Days 1 and 15) every 24 weeks for up to 5 years if they were not in clinical remission and safety criteria were met. Placebo and rituximab infusions were preceded with 100 milligrams (mg) intravenous methylprednisolone. Participants also received a stable dose of 10-25 mg/week of MTX and ≥ 5 mg/week folic acid for the duration of their participation in the study. All participants entered a 48-week safety follow-up (SFU) period following the treatment period.
Placebo + methotrexate (MTX)FolateParticipants received placebo intravenous infusion on Days 1 and 15. From Week 16 onwards, participants could switch to receive rituximab 0.5 g (on Days 1 and 15) every 24 weeks for up to 5 years if they were not in clinical remission and safety criteria were met. Placebo and rituximab infusions were preceded with 100 milligrams (mg) intravenous methylprednisolone. Participants also received a stable dose of 10-25 mg/week of MTX and ≥ 5 mg/week folic acid for the duration of their participation in the study. All participants entered a 48-week safety follow-up (SFU) period following the treatment period.
Placebo + methotrexate (MTX)MethotrexateParticipants received placebo intravenous infusion on Days 1 and 15. From Week 16 onwards, participants could switch to receive rituximab 0.5 g (on Days 1 and 15) every 24 weeks for up to 5 years if they were not in clinical remission and safety criteria were met. Placebo and rituximab infusions were preceded with 100 milligrams (mg) intravenous methylprednisolone. Participants also received a stable dose of 10-25 mg/week of MTX and ≥ 5 mg/week folic acid for the duration of their participation in the study. All participants entered a 48-week safety follow-up (SFU) period following the treatment period.
Rituximab 2 x 0.5 g + MTXFolateParticipants received 0.5 g rituximab administered by intravenous infusion on Days 1 and 15. After Week 24, participants received further courses of rituximab every 24 weeks for up to 5 years if they were not in clinical remission and safety criteria were met. Rituximab infusions were preceded with 100 mg intravenous methylprednisolone. Participants also received a stable dose of 10-25 mg/week of methotrexate and ≥ 5 mg/week folic acid for the duration of their participation in the study. All participants entered a 48-week safety follow-up (SFU) period following the treatment period.
Placebo + methotrexate (MTX)RituximabParticipants received placebo intravenous infusion on Days 1 and 15. From Week 16 onwards, participants could switch to receive rituximab 0.5 g (on Days 1 and 15) every 24 weeks for up to 5 years if they were not in clinical remission and safety criteria were met. Placebo and rituximab infusions were preceded with 100 milligrams (mg) intravenous methylprednisolone. Participants also received a stable dose of 10-25 mg/week of MTX and ≥ 5 mg/week folic acid for the duration of their participation in the study. All participants entered a 48-week safety follow-up (SFU) period following the treatment period.
Rituximab 2 x 0.5 g + MTXMethotrexateParticipants received 0.5 g rituximab administered by intravenous infusion on Days 1 and 15. After Week 24, participants received further courses of rituximab every 24 weeks for up to 5 years if they were not in clinical remission and safety criteria were met. Rituximab infusions were preceded with 100 mg intravenous methylprednisolone. Participants also received a stable dose of 10-25 mg/week of methotrexate and ≥ 5 mg/week folic acid for the duration of their participation in the study. All participants entered a 48-week safety follow-up (SFU) period following the treatment period.
Rituximab 2 x 0.5 g + MTXRituximabParticipants received 0.5 g rituximab administered by intravenous infusion on Days 1 and 15. After Week 24, participants received further courses of rituximab every 24 weeks for up to 5 years if they were not in clinical remission and safety criteria were met. Rituximab infusions were preceded with 100 mg intravenous methylprednisolone. Participants also received a stable dose of 10-25 mg/week of methotrexate and ≥ 5 mg/week folic acid for the duration of their participation in the study. All participants entered a 48-week safety follow-up (SFU) period following the treatment period.
Rituximab 2 x 1.0 g + MTXMethotrexateParticipants received 1.0 g rituximab administered by intravenous infusion on Days 1 and 15. After Week 24, participants received further courses of rituximab every 24 weeks for up to 5 years if they were not in clinical remission and safety criteria were met. Rituximab infusions were preceded with 100 mg intravenous methylprednisolone. Participants also received a stable dose of 10-25 mg/week of methotrexate and ≥ 5 mg/week folic acid for the duration of their participation in the study. All participants entered a 48-week safety follow-up (SFU) period following the treatment period.
Rituximab 2 x 1.0 g + MTXFolateParticipants received 1.0 g rituximab administered by intravenous infusion on Days 1 and 15. After Week 24, participants received further courses of rituximab every 24 weeks for up to 5 years if they were not in clinical remission and safety criteria were met. Rituximab infusions were preceded with 100 mg intravenous methylprednisolone. Participants also received a stable dose of 10-25 mg/week of methotrexate and ≥ 5 mg/week folic acid for the duration of their participation in the study. All participants entered a 48-week safety follow-up (SFU) period following the treatment period.
Rituximab 2 x 1.0 g + MTXRituximabParticipants received 1.0 g rituximab administered by intravenous infusion on Days 1 and 15. After Week 24, participants received further courses of rituximab every 24 weeks for up to 5 years if they were not in clinical remission and safety criteria were met. Rituximab infusions were preceded with 100 mg intravenous methylprednisolone. Participants also received a stable dose of 10-25 mg/week of methotrexate and ≥ 5 mg/week folic acid for the duration of their participation in the study. All participants entered a 48-week safety follow-up (SFU) period following the treatment period.
Placebo + methotrexate (MTX)MethylprednisoloneParticipants received placebo intravenous infusion on Days 1 and 15. From Week 16 onwards, participants could switch to receive rituximab 0.5 g (on Days 1 and 15) every 24 weeks for up to 5 years if they were not in clinical remission and safety criteria were met. Placebo and rituximab infusions were preceded with 100 milligrams (mg) intravenous methylprednisolone. Participants also received a stable dose of 10-25 mg/week of MTX and ≥ 5 mg/week folic acid for the duration of their participation in the study. All participants entered a 48-week safety follow-up (SFU) period following the treatment period.
Rituximab 2 x 0.5 g + MTXMethylprednisoloneParticipants received 0.5 g rituximab administered by intravenous infusion on Days 1 and 15. After Week 24, participants received further courses of rituximab every 24 weeks for up to 5 years if they were not in clinical remission and safety criteria were met. Rituximab infusions were preceded with 100 mg intravenous methylprednisolone. Participants also received a stable dose of 10-25 mg/week of methotrexate and ≥ 5 mg/week folic acid for the duration of their participation in the study. All participants entered a 48-week safety follow-up (SFU) period following the treatment period.
Rituximab 2 x 1.0 g + MTXMethylprednisoloneParticipants received 1.0 g rituximab administered by intravenous infusion on Days 1 and 15. After Week 24, participants received further courses of rituximab every 24 weeks for up to 5 years if they were not in clinical remission and safety criteria were met. Rituximab infusions were preceded with 100 mg intravenous methylprednisolone. Participants also received a stable dose of 10-25 mg/week of methotrexate and ≥ 5 mg/week folic acid for the duration of their participation in the study. All participants entered a 48-week safety follow-up (SFU) period following the treatment period.
Primary Outcome Measures
NameTimeMethod
Percentage of Participants With American College of Rheumatology (ACR) 20 Response at Week 24Baseline and Week 24

To achieve an ACR20 required at least a 20% improvement compared with Baseline in both tender joint counts (68 joints assessed for tenderness) and swollen joint counts (66 joints assessed for swelling), as well as a 20% improvement in three of the following five additional measurements:

* Physician's global assessment of disease activity (assessed using a 100 mm Visual Analog Scale \[VAS\]);

* Patient's global assessment of disease activity (assessed using a 100 mm VAS);

* Patient's assessment of pain (assessed using a 100 mm VAS);

* Health Assessment Questionnaire (HAQ; a patient completed questionnaire consisting of 20 questions, scored from 0-3);

* Acute phase reactant: C-reactive protein (CRP) or, if CRP was missing, erythrocyte sedimentation rate (ESR).

Participants who withdrew prematurely from the study prior to Week 24, who received rescue therapy or had insufficient data in order to calculate a clinical response were considered to be non-responders.

Secondary Outcome Measures
NameTimeMethod
Percent Change From Baseline in Tender Joint CountBaseline, Week 24 and Week 48

Sixty-eight joints were assessed and classified as tender/not tender by pressure and joint manipulation on physical examination.

The percentage change from baseline at each post-baseline visit was calculated as:

\[(post-baseline value minus baseline value) divided by Baseline value\]\*100.

A negative percentage change from baseline score indicates an improvement.

Percentage of Participants With European League Against Rheumatism (EULAR) Response at Week 24Baseline and Week 24

A EULAR response reflects an improvement in disease activity and an attainment of a lower degree of disease activity based on the DAS28 score. The DAS28 score ranges from 0-10, with higher scores indicating more disease activity.

A Good Response is defined as an improvement (decrease) in the DAS28 of more than 1.2 compared with Baseline and attainment of a DAS28 score of less than or equal to 3.2.

A Moderate Response is defined as either:

* an improvement (decrease) in the DAS28 of greater than 0.6 and less than or equal to 1.2 from Baseline and attainment of a DAS28 score of less than or equal to 5.1 or,

* an improvement (decrease) in the DAS28 of more than 1.2 from Baseline and attainment of a DAS28 score of greater than 3.2.

No Response is defined as either an improvement (decrease) in the DAS28 of less than or equal to 0.6, or an improvement (decrease) in the DAS28 of greater than 0.6 and less than or equal to 1.2 and attainment of a DAS28 of more than 5.1.

Percent Change From Baseline in Patient's Pain AssessmentBaseline, Week 24 and Week 48

The participant's assessment of their current level of pain on a 100 mm horizontal visual analog scale (VAS), where the left-hand extreme of the line (0 mm) was described as "no pain" and the right-hand extreme (100 mm) as "unbearable pain".

The percentage change from baseline at each post-baseline visit was calculated as:

\[(post-baseline value minus baseline value) divided by Baseline value\]\*100.

A negative percentage change from baseline score indicates an improvement.

Change From Baseline in Short Form 36 Health Survey (SF-36) Bodily Pain Domain ScoreBaseline, Week 24 and Week 48

The SF-36 measures the impact of disease on overall quality of life and consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). The individual domain scores are calculated and transformed to range from 0 to 100, with higher scores indicating a better level of functioning.

A positive change from baseline score indicates an improvement.

Change From Baseline in Short Form 36 Health Survey (SF-36) Physical Functioning Domain ScoreBaseline, Week 24 and Week 48

The SF-36 measures the impact of disease on overall quality of life and consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). The individual domain scores are calculated and transformed to range from 0 to 100, with higher scores indicating a better level of functioning.

A positive change from baseline score indicates an improvement.

Change From Baseline in Short Form 36 Health Survey (SF-36) Mental Health Domain ScoreBaseline, Week 24 and Week 48

The SF-36 measures the impact of disease on overall quality of life and consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). The individual domain scores are calculated and transformed to range from 0 to 100, with higher scores indicating a better level of functioning.

A positive change from baseline score indicates an improvement.

Percentage of Participants With an ACR50 Response at Week 24Baseline and Week 24

To achieve an ACR50 required at least a 50% improvement compared with Baseline in both tender joint counts (68 joints assessed for tenderness) and swollen joint counts (66 joints assessed for swelling), as well as a 50% improvement in three of the following five additional measurements:

* Physician's global assessment of disease activity (assessed using a 100 mm Visual Analog Scale \[VAS\]);

* Patient's global assessment of disease activity (assessed using a 100 mm VAS);

* Patient's assessment of pain (assessed using a 100 mm VAS);

* Health Assessment Questionnaire (HAQ; a patient completed questionnaire consisting of 20 questions, scored from 0-3);

* Acute phase reactant: C-reactive protein (CRP) or, if CRP was missing, erythrocyte sedimentation rate (ESR).

Participants who withdrew prematurely from the study prior to Week 24, who received rescue therapy or had insufficient data in order to calculate a clinical response were considered to be non-responders.

Percentage of Participants With an ACR70 Response at Week 24Baseline and Week 24

To achieve an ACR70 required at least a 70% improvement compared with Baseline in both tender joint counts (68 joints assessed for tenderness) and swollen joint counts (66 joints assessed for swelling), as well as a 70% improvement in three of the following five additional measurements:

* Physician's global assessment of disease activity (assessed using a 100 mm Visual Analog Scale \[VAS\]);

* Patient's global assessment of disease activity (assessed using a 100 mm VAS);

* Patient's assessment of pain (assessed using a 100 mm VAS);

* Health Assessment Questionnaire (HAQ; a patient completed questionnaire consisting of 20 questions, scored from 0-3);

* Acute phase reactant: C-reactive protein (CRP) or, if CRP was missing, erythrocyte sedimentation rate (ESR).

Participants who withdrew prematurely from the study prior to Week 24, who received rescue therapy or had insufficient data in order to calculate a clinical response were considered to be non-responders.

Change From Baseline in Disease Activity Score (DAS28-ESR) at Week 24Baseline and Week 24

The DAS28 is a composite score to measure disease activity in patients with rheumatoid arthritis, derived from the following variables:

* The number of swollen and tender joints assessed using the 28-joint count;

* Erythrocyte sedimentation rate (ESR);

* Patient's global assessment of disease activity measured on a 100 mm visual analog scale.

The DAS28 score ranges from zero to ten. A DAS28 score above 5.1 means high disease activity whereas a DAS28 less than or equal to 3.2 indicates low disease activity. Remission is achieved by a DAS28 lower than 2.6.

Percent Change From Baseline in C-Reactive ProteinBaseline, Week 24 and Week 48

C-Reactive Protein (CRP) was measured from blood samples by a central laboratory as a marker for inflammation.

The percentage change from baseline at each post-baseline visit was calculated as:

\[(post-baseline value minus baseline value) divided by Baseline value\]\*100.

A negative percentage change from baseline score indicates an improvement.

Percent Change From Baseline in Swollen Joint CountBaseline, Week 24 and Week 48

Sixty-six joints were assessed and classified as swollen/not swollen by pressure and joint manipulation on physical examination.

The percentage change from baseline at each post-baseline visit was calculated as:

\[(post-baseline value minus baseline value) divided by Baseline value\]\*100.

A negative percentage change from baseline score indicates an improvement.

Percent Change From Baseline in Patient's Global Assessment of Disease ActivityBaseline, Week 24 and Week 48

The participant's overall assessment of their current disease activity measured on a 100 mm horizontal visual analog scale (VAS). The left-hand extreme of the line (0 mm) was described as "no disease activity" (symptom-free and no arthritis symptoms) and the right-hand extreme (100 mm) as "maximum disease activity" (maximum arthritis disease activity).

The percentage change from baseline at each post-baseline visit was calculated as:

\[(post-baseline value minus baseline value) divided by Baseline value\]\*100.

A negative percentage change from baseline score indicates an improvement.

Percent Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) ScoreBaseline, Week 24 and Week 48

The Stanford Health Assessment Questionnaire disability index is a patient-reported questionnaire specific for rheumatoid arthritis. It consists of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and daily activities. Participants choose from four response categories, ranging from 'without any difficulty' (Score=0) to 'unable to do' (Score=3). The overall score is the average of each of the 8 category scores and ranges from 0 to 3, where zero represents no disability and three very severe, high-dependency disability.

The percentage change from baseline at each post-baseline visit was calculated as:

\[(post-baseline value minus baseline value) divided by Baseline value\]\*100.

A negative percentage change from baseline score indicates an improvement.

Percent Change From Baseline in Short Form 36 Health Survey (SF-36) Summary Scores (Physical and Mental Components)Baseline, Week 24 and Week 48

The SF-36 measures the impact of disease on overall quality of life and consists of 36 questions split into two major components: physical health and mental health. Under physical health are the following four domains: physical health, bodily pain, physical functioning and physical role limitations. Under the mental health domain there are four domains; mental health, vitality, social functioning, and emotional role limitation. The individual domain scores are aggregated to derive a physical-component summary score and a mental-component summary score which range from 0 to 100, with higher scores indicating a better level of functioning.

The percentage change from baseline at each post-baseline visit was calculated as:

\[(post-baseline value minus baseline value) divided by Baseline value\]\*100.

A positive percentage change from baseline score indicates an improvement.

Percent Change From Baseline in Physician's Global Assessment of Disease ActivityBaseline, Week 24 and Week 48

The physician's assessment of the participant's current disease activity on a 100 mm horizontal VAS, where the left-hand extreme of the line (0 mm) was described as "no disease activity" (symptom-free and no arthritis symptoms) and the right-hand extreme (100 mm) as "maximum disease activity".

The percentage change from baseline at each post-baseline visit was calculated as:

\[(post-baseline value minus baseline value) divided by Baseline value\]\*100.

A negative percentage change from baseline score indicates an improvement.

Percent Change From Baseline in Erythrocyte Sedimentation RateBaseline, Week 24 and Week 48

Erythrocyte sedimentation rate (ESR) indirectly measures how much inflammation is in the body. A higher ESR is indicative of increased inflammation.

The percentage change from baseline at each post-baseline visit was calculated as:

\[(post-baseline value minus baseline value) divided by Baseline value\]\*100.

A negative percentage change from baseline score indicates an improvement.

Change From Baseline in Short Form 36 Health Survey (SF-36) General Health Domain ScoreBaseline, Week 24 and Week 48

The SF-36 measures the impact of disease on overall quality of life and consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). The individual domain scores are calculated and transformed to range from 0 to 100, with higher scores indicating a better level of functioning.

A positive change from baseline score indicates an improvement.

Change From Baseline in Short Form 36 Health Survey (SF-36) Physical Role Limitations Domain ScoreBaseline, Week 24 and Week 48

The SF-36 measures the impact of disease on overall quality of life and consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). The individual domain scores are calculated and transformed to range from 0 to 100, with higher scores indicating a better level of functioning.

A positive change from baseline score indicates an improvement.

Change From Baseline in Short Form 36 Health Survey (SF-36) Social Functioning Domain ScoreBaseline, Week 24 and Week 48

The SF-36 measures the impact of disease on overall quality of life and consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). The individual domain scores are calculated and transformed to range from 0 to 100, with higher scores indicating a better level of functioning.

A positive change from baseline score indicates an improvement.

Change From Baseline in Short Form 36 Health Survey (SF-36) Emotional Role Limitations Domain ScoreBaseline, Week 24 and Week 48

The SF-36 measures the impact of disease on overall quality of life and consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). The individual domain scores are calculated and transformed to range from 0 to 100, with higher scores indicating a better level of functioning.

A positive change from baseline score indicates an improvement.

Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) ScoresBaseline, Week 24 and Week 48

The FACIT-Fatigue questionnaire is a self-administered patient questionnaire that consists of 13 questions designed to measure the degree of fatigue experienced by participants in the previous 7 days. Participants respond to the questions using a value in the range of 0 (not at all) to 4 (very much). The scale score is computed by summing the item scores, after reversing those items that are worded in the negative direction. The FACIT-Fatigue subscale score ranges from 0 to 52, where higher scores represent less fatigue.

A positive change from baseline score indicates an improvement.

Percentage of Participants With DAS28-ESR Low Disease Activity Score and Clinical Remission at Week 24Week 24

The DAS28 is a composite score to measure disease activity in patients with rheumatoid arthritis, derived from the following variables:

* The number of swollen and tender joints assessed using the 28-joint count;

* Erythrocyte sedimentation rate (ESR);

* Patient's global assessment of disease activity measured on a 100 mm visual analog scale.

The DAS28 score ranges from zero to ten. DAS28 above 5.1 indicates high disease activity.

Low disease activity is defined by a DAS28 score less than or equal to 3.2. Remission is defined by a DAS28 score less than 2.6.

Change From Baseline in Short Form 36 Health Survey (SF-36) Vitality Domain ScoreBaseline, Week 24 and Week 48

The SF-36 measures the impact of disease on overall quality of life and consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). The individual domain scores are calculated and transformed to range from 0 to 100, with higher scores indicating a better level of functioning.

A positive change from baseline score indicates an improvement.

Percentage of Participants With HAQ-DI Improved, Unchanged or Worsened at Week 48Baseline and Week 48

The Stanford Health Assessment Questionnaire disability index is a patient-reported questionnaire specific for rheumatoid arthritis. It consists of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and daily activities. Participants choose from four response categories, ranging from 'without any difficulty' (Score=0) to 'unable to do' (Score=3). The overall score is the average of each of the 8 category scores and ranges from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. A negative change from baseline score indicates an improvement.

Improved HAQ-DI is defined as a change from Baseline score less than or equal to -0.22.

An Unchanged HAQ-DI is defined as a change from Baseline score greater than -0.22 and less than 0.22.

A worsened HAQ-DI score is defined as a change from Baseline score of greater than or equal to 0.22.

Percentage of Participants With HAQ-DI Improved, Unchanged or Worsened at Week 24Baseline and Week 24

The Stanford Health Assessment Questionnaire disability index is a patient-reported questionnaire specific for rheumatoid arthritis. It consists of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and daily activities. Participants choose from four response categories, ranging from 'without any difficulty' (Score=0) to 'unable to do' (Score=3). The overall score is the average of each of the 8 category scores and ranges from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. A negative change from baseline score indicates an improvement.

Improved HAQ-DI is defined as a change from Baseline score less than or equal to -0.22.

An Unchanged HAQ-DI is defined as a change from Baseline score greater than -0.22 and less than 0.22.

A worsened HAQ-DI score is defined as a change from Baseline score of greater than or equal to 0.22.

Percentage of Participants With an ACR50 Response at Week 48Baseline and Week 48

To achieve an ACR50 required at least a 50% improvement compared with Baseline in both tender joint counts (68 joints assessed for tenderness) and swollen joint counts (66 joints assessed for swelling), as well as a 50% improvement in three of the following five additional measurements:

* Physician's global assessment of disease activity (assessed using a 100 mm Visual Analog Scale \[VAS\]);

* Patient's global assessment of disease activity (assessed using a 100 mm VAS);

* Patient's assessment of pain (assessed using a 100 mm VAS);

* Health Assessment Questionnaire (HAQ; a patient completed questionnaire consisting of 20 questions, scored from 0-3);

* Acute phase reactant: C-reactive protein (CRP) or, if CRP was missing, erythrocyte sedimentation rate (ESR).

Participants who withdrew prematurely from the study prior to week 48, who received rescue therapy or had insufficient data in order to calculate a clinical response were considered to be non-responders.

Percentage of Participants With an ACR70 Response at Week 48Baseline and Week 48

To achieve an ACR70 required at least a 70% improvement compared with baseline in both tender joint counts (68 joints assessed for tenderness) and swollen joint counts (66 joints assessed for swelling), as well as a 70% improvement in three of the following five additional measurements:

* Physician's global assessment of disease activity (assessed using a 100 mm Visual Analog Scale \[VAS\]);

* Patient's global assessment of disease activity (assessed using a 100 mm VAS);

* Patient's assessment of pain (assessed using a 100 mm VAS);

* Health Assessment Questionnaire (HAQ; a patient completed questionnaire consisting of 20 questions, scored from 0-3);

* Acute phase reactant: C-reactive protein (CRP) or, if CRP was missing, erythrocyte sedimentation rate (ESR).

Participants who withdrew prematurely from the study prior to Week 48, who received rescue therapy or had insufficient data in order to calculate a clinical response were considered to be non-responders.

Percentage of Participants With DAS28-ESR Low Disease Activity Score and Clinical Remission at Week 48Week 48

The DAS28 is a composite score to measure disease activity in patients with rheumatoid arthritis, derived from the following variables:

* The number of swollen and tender joints assessed using the 28-joint count;

* Erythrocyte sedimentation rate (ESR);

* Patient's global assessment of disease activity measured on a 100 mm visual analog scale.

The DAS28 score ranges from zero to ten. DAS28 above 5.1 indicates high disease activity.

Low disease activity is defined by a DAS28 score less than or equal to 3.2. Remission is defined by a DAS28 score less than 2.6.

Percentage of Participants With European League Against Rheumatism (EULAR) Response at Week 48Baseline and Week 48

A EULAR response reflects an improvement in disease activity and an attainment of a lower degree of disease activity based on the DAS-28 score.

A Good Response is defined as an improvement (decrease) in the DAS28 of more than 1.2 compared with Baseline and attainment of a DAS28 score less than or equal to 3.2.

A Moderate Response is defined as either:

* an improvement (decrease) in the DAS28 of greater than 0.6 and less than or equal to 1.2 and attainment of a DAS28 score of less than or equal to 5.1 or,

* an improvement (decrease) in the DAS28 of more than 1.2 and attainment of a DAS28 score of greater than 3.2.

No Response is defined as either an improvement (decrease) in the DAS28 of less than or equal to 0.6, or an improvement (decrease) in the DAS28 of greater than 0.6 and less than or equal to 1.2 and attainment of a DAS28 score of 5.1 or higher.

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