Rheumatoid Arthritis
Conditions
Keywords
Rheumatoid Arthritis, Certolizumab Pegol, Cimzia
Brief summary
The objectives of this study are to evaluate the safety and efficacy of certolizumab pegol when administered without coadministration of methotrexate over the long term in Japanese RA patients who transferred from Study 275-08-003 (NCT00791921), and to evaluate the effects of different dosing regimens on the safety and efficacy of certolizumab pegol in American College of Rheumatology 20% (ACR20) responders who completed Study 275-08-003.
Detailed description
This study was initiated by Otsuka Pharmaceutical Co., Ltd and transferred to Astellas on 12/04/2012.
Interventions
DRUGCertolizumab pegol
Subcutaneous (SC) injection
Sponsors
UCB Japan Co. Ltd.
Astellas Pharma Inc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to 74 Years
Healthy volunteers
No
Inclusion criteria
* Subjects who participated in Study 275-08-003 and meet all of the criteria described below. * Patients who did not reach ACR20, and prematurely discontinued Study 275-08-003 at Week 16 or completed Study 275-08-003 by Week 24.
Exclusion criteria
* Patients who experienced an important protocol deviation as mentioned below during Study 275-08-003. * Patients who received live or attenuated vaccines during Study 275-08-003 (Except for influenza or pneumococcal vaccines). * Patients who were found to have tuberculosis on a chest X-ray during Study 275-08-003. * Patients who required treatment for the same infection at two or more different times during Study 275-08-003 * Women who are pregnant, are lactating, of childbearing potential and wish to conceive during the study and post-study 3 months. * Patients whom the investigator has decided to be inappropriate for participation in the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events | From the first dosing of this study up to 12 weeks (84 days) after the last dosing. The dosing was allowed until launch of certolizumab pegol for RA in Japan. The maximum duration on study drug was 204 weeks. | An adverse event (AE) is any untoward medical occurrence in a participant administered study drug which did not necessarily have a causal relationship with the treatment. In this study, events that occurred between the time of informed consent and the start of study medication were included in the adverse events for Study 275-08-003. Any event existing prior to the initiation of study treatment that was aggravated after initiation of study treatment was handled as a new event. The investigator assessed the severity of each AE as follows: Mild: No disruption of normal daily activities; Moderate: Affected normal daily activities; Severe: Inability to perform daily activities. A serious adverse event is an AE that results in death, is life-threatening, requires or prolongs inpatient hospitalization, results in an ongoing or significant incapacity or interferes substantially with normal life functions, or causes a congenital anomaly or birth defect. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With American College of Rheumatology 20% (ACR20) Response | Baseline (of Study 275-08-003), Week 24, Week 52 and at the final assessment (maximum was 208 weeks) | A participant was an ACR20 responder if the following 3 criteria for improvement from Baseline (before study drug administration in Study 275-08-003) were met: * ≥ 20% improvement in 68 tender joint count; * ≥ 20% improvement in 66 swollen joint count; and * ≥ 20% improvement in at least 3 of the 5 following parameters: * Patient's assessment of arthritis pain (measured on a 100 mm visual analog scale \[VAS\]); * Patient's global assessment of disease activity (measured on a 100 mm VAS); * Physician's global assessment of disease activity (measured on a 100 mm VAS); * Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); * C-Reactive Protein (CRP). |
| Percentage of Participants With American College of Rheumatology 50% (ACR50) Response | Baseline (of Study 275-08-003), Week 24, Week 52 and at the final assessment (maximum was 208 weeks) | A participant was an ACR50 responder if the following 3 criteria for improvement from Baseline (before study drug administration in Study 275-08-003) were met: * ≥ 50% improvement in 68 tender joint count; * ≥ 50% improvement in 66 swollen joint count; and * ≥ 50% improvement in at least 3 of the 5 following parameters: * Patient's assessment of arthritis pain (measured on a 100 mm visual analog scale \[VAS\]); * Patient's global assessment of disease activity (measured on a 100 mm VAS); * Physician's global assessment of disease activity (measured on a 100 mm VAS); * Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); * C-Reactive Protein (CRP). |
| Percentage of Participants With American College of Rheumatology 70% (ACR70) Response | Baseline (of Study 275-08-003), Week 24, Week 52 and at the final assessment (maximum was 208 weeks) | A participant was an ACR70 responder if the following 3 criteria for improvement from Baseline (before study drug administration in Study 275-08-003) were met: * ≥ 70% improvement in 68 tender joint count; * ≥ 70% improvement in 66 swollen joint count; and * ≥ 70% improvement in at least 3 of the 5 following parameters: * Patient's assessment of arthritis pain (measured on a 100 mm visual analog scale \[VAS\]); * Patient's global assessment of disease activity (measured on a 100 mm VAS); * Physician's global assessment of disease activity (measured on a 100 mm VAS); * Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); * C-Reactive Protein (CRP). |
| Change From Baseline in Disease Activity Score (DAS) 28 | Baseline (of Study 275-08-003), Week 24, Week 52 and at the final assessment (maximum was 208 weeks) | The DAS28 measures the severity of disease at a specific time and is derived from the following variables: * 28 tender joint count; * 28 swollen joint count; * Erythrocyte sedimentation rate (ESR); * Patient's global assessment of disease activity. To obtain the tender joint count and swollen joint count, 28 joints of the shoulder, elbow, wrist, metacarpophalangeal joints, thumb interphalangeal joints, proximal interphalangeal joints, and knee joints were examined. The data before study drug administration of 275-08-003 Study was utilized for Baseline. DAS28(ESR) scores range from 0 to approximately 10, with the upper bound dependent on the highest possible ESR. A DAS28 score higher than 5.1 indicates high disease activity, a DAS28 score of 3.2 or less indicates low disease activity, and a DAS28 score less than 2.6 indicates clinical remission. |
| Change From Baseline in Modified Total Sharp Score (mTSS) | Baseline (of Study 275-08-003), Week 0 (of this study) and Week 100 | X-ray images of extremities (posteroanterior views of both hands and dorsoplantar views of both feet) were independently assessed by at least two radiographic readers. The degree of joint destruction was graded by assessing bone erosion in 44 joints and joint space narrowing (JSN) in 42 joints. The joint erosion score is a summary of erosion severity in 32 joints of the hands and 12 joints in the feet. Each joint was scored, according to the surface area involved, from 0 (no erosion) to 5 (complete collapse of bone). The score for erosion ranges from 0 to 160 in the hands and from 0 to 120 in the feet (the maximum erosion score for a joint in the foot is 10). The JSN score summarizes the severity of JSN in 30 joints of the hands and 12 joints of the feet. JSN, including subluxation, was scored from 0 (normal) to 4 (complete loss of joint space, bony ankylosis, or luxation), with a maximum JSN score of 168. The mTSS ranges from 0 (normal) to 448 (worst). |
Countries
Japan
Participant flow
Recruitment details
Patients with rheumatoid arthritis (RA) who participated in Study 275-08-003 (NCT00791921) were eligible for this study.
Pre-assignment details
Participants were assigned to treatment groups based on whether they discontinued study 275-08-003 at Week 16 or completed Week 24 and based on American College of Rheumatology 20% (ACR20) response at Week 24.
Participants by arm
| Arm | Count |
|---|---|
| Discontinued Non-responders 200 mg Participants who were ACR20 non-responders and discontinued study 275-08-003 at Week 16 received 200 mg certolizumab pegol by subcutaneous injection once every 2 weeks for up to 52 weeks or until approval of certolizumab pegol for rheumatoid arthritis in Japan. | 110 |
| Completed Non-responders 200 mg Participants who were ACR20 non-responders and completed study 275-08-003 at Week 24 received 200 mg certolizumab pegol by subcutaneous injection once every 2 weeks for up to 52 weeks or until approval of certolizumab pegol for rheumatoid arthritis in Japan. | 12 |
| Completed Responders 200 mg Participants who were ACR20 responders and completed study 275-08-003 at Week 24 received 200 mg certolizumab pegol by subcutaneous injection once every 2 weeks for up to 52 weeks or until approval of certolizumab pegol for rheumatoid arthritis in Japan. | 43 |
| Completed Responders 400 mg Participants who were ACR20 responders and completed study 275-08-003 at Week 24 received 400 mg certolizumab pegol by subcutaneous injection once every 4 weeks for up to 52 weeks or until approval of certolizumab pegol for rheumatoid arthritis in Japan. | 43 |
| Total | 208 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 15 | 2 | 6 | 6 |
| Overall Study | Lack of Efficacy | 17 | 0 | 3 | 2 |
| Overall Study | Non-compliance with Study Procedures | 1 | 0 | 1 | 1 |
| Overall Study | Physician Decision | 2 | 1 | 1 | 1 |
| Overall Study | Pregnancy | 0 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 11 | 0 | 3 | 2 |
Baseline characteristics
| Characteristic | Discontinued Non-responders 200 mg | Completed Non-responders 200 mg | Completed Responders 200 mg | Completed Responders 400 mg | Total |
|---|---|---|---|---|---|
| Age, Continuous | 55.4 years STANDARD_DEVIATION 10.2 | 59.3 years STANDARD_DEVIATION 6.5 | 54.6 years STANDARD_DEVIATION 9.7 | 55.9 years STANDARD_DEVIATION 10.7 | 55.5 years STANDARD_DEVIATION 10 |
| Age, Customized < 65 years | 90 participants | 10 participants | 35 participants | 32 participants | 167 participants |
| Age, Customized ≧ 65 years | 20 participants | 2 participants | 8 participants | 11 participants | 41 participants |
| Body Weight | 56.12 kg STANDARD_DEVIATION 10.84 | 55.92 kg STANDARD_DEVIATION 9.55 | 59.36 kg STANDARD_DEVIATION 11.11 | 58.65 kg STANDARD_DEVIATION 11.83 | 57.30 kg STANDARD_DEVIATION 11.06 |
| Region of Enrollment Japan | 110 participants | 12 participants | 43 participants | 43 participants | 208 participants |
| Sex: Female, Male Female | 91 Participants | 7 Participants | 28 Participants | 28 Participants | 154 Participants |
| Sex: Female, Male Male | 19 Participants | 5 Participants | 15 Participants | 15 Participants | 54 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 102 / 110 | 12 / 12 | 41 / 43 | 40 / 43 |
| serious Total, serious adverse events | 40 / 110 | 3 / 12 | 17 / 43 | 16 / 43 |
Outcome results
Primary
Number of Participants With Adverse Events
An adverse event (AE) is any untoward medical occurrence in a participant administered study drug which did not necessarily have a causal relationship with the treatment. In this study, events that occurred between the time of informed consent and the start of study medication were included in the adverse events for Study 275-08-003. Any event existing prior to the initiation of study treatment that was aggravated after initiation of study treatment was handled as a new event. The investigator assessed the severity of each AE as follows: Mild: No disruption of normal daily activities; Moderate: Affected normal daily activities; Severe: Inability to perform daily activities. A serious adverse event is an AE that results in death, is life-threatening, requires or prolongs inpatient hospitalization, results in an ongoing or significant incapacity or interferes substantially with normal life functions, or causes a congenital anomaly or birth defect.
Time frame: From the first dosing of this study up to 12 weeks (84 days) after the last dosing. The dosing was allowed until launch of certolizumab pegol for RA in Japan. The maximum duration on study drug was 204 weeks.
Population: All participants who received at least one study drug administration were included in the safety analysis population (SAF).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Discontinued Non-responders 200 mg | Number of Participants With Adverse Events | Severe adverse events | 16 participants |
| Discontinued Non-responders 200 mg | Number of Participants With Adverse Events | Infections induced by pathogen in study drug | 0 participants |
| Discontinued Non-responders 200 mg | Number of Participants With Adverse Events | Serious adverse events | 40 participants |
| Discontinued Non-responders 200 mg | Number of Participants With Adverse Events | Serious adverse events leading to death | 0 participants |
| Discontinued Non-responders 200 mg | Number of Participants With Adverse Events | Adverse events leading to withdrawal | 16 participants |
| Discontinued Non-responders 200 mg | Number of Participants With Adverse Events | Any adverse event | 102 participants |
| Discontinued Non-responders 200 mg | Number of Participants With Adverse Events | Overdoses | 0 participants |
| Discontinued Non-responders 200 mg | Number of Participants With Adverse Events | Mild adverse events | 16 participants |
| Discontinued Non-responders 200 mg | Number of Participants With Adverse Events | Moderate adverse events | 70 participants |
| Discontinued Non-responders 200 mg | Number of Participants With Adverse Events | Adverse events occurring within 2 hours of dosing | 0 participants |
| Discontinued Non-responders 200 mg | Number of Participants With Adverse Events | Non-fatal serious adverse events | 40 participants |
| Completed Non-responders 200 mg | Number of Participants With Adverse Events | Any adverse event | 12 participants |
| Completed Non-responders 200 mg | Number of Participants With Adverse Events | Severe adverse events | 2 participants |
| Completed Non-responders 200 mg | Number of Participants With Adverse Events | Adverse events leading to withdrawal | 2 participants |
| Completed Non-responders 200 mg | Number of Participants With Adverse Events | Serious adverse events leading to death | 1 participants |
| Completed Non-responders 200 mg | Number of Participants With Adverse Events | Non-fatal serious adverse events | 2 participants |
| Completed Non-responders 200 mg | Number of Participants With Adverse Events | Serious adverse events | 3 participants |
| Completed Non-responders 200 mg | Number of Participants With Adverse Events | Infections induced by pathogen in study drug | 0 participants |
| Completed Non-responders 200 mg | Number of Participants With Adverse Events | Moderate adverse events | 6 participants |
| Completed Non-responders 200 mg | Number of Participants With Adverse Events | Mild adverse events | 4 participants |
| Completed Non-responders 200 mg | Number of Participants With Adverse Events | Overdoses | 0 participants |
| Completed Non-responders 200 mg | Number of Participants With Adverse Events | Adverse events occurring within 2 hours of dosing | 0 participants |
| Completed Responders 200 mg | Number of Participants With Adverse Events | Non-fatal serious adverse events | 16 participants |
| Completed Responders 200 mg | Number of Participants With Adverse Events | Adverse events leading to withdrawal | 6 participants |
| Completed Responders 200 mg | Number of Participants With Adverse Events | Infections induced by pathogen in study drug | 0 participants |
| Completed Responders 200 mg | Number of Participants With Adverse Events | Any adverse event | 41 participants |
| Completed Responders 200 mg | Number of Participants With Adverse Events | Mild adverse events | 7 participants |
| Completed Responders 200 mg | Number of Participants With Adverse Events | Moderate adverse events | 23 participants |
| Completed Responders 200 mg | Number of Participants With Adverse Events | Severe adverse events | 11 participants |
| Completed Responders 200 mg | Number of Participants With Adverse Events | Serious adverse events | 17 participants |
| Completed Responders 200 mg | Number of Participants With Adverse Events | Serious adverse events leading to death | 2 participants |
| Completed Responders 200 mg | Number of Participants With Adverse Events | Overdoses | 0 participants |
| Completed Responders 200 mg | Number of Participants With Adverse Events | Adverse events occurring within 2 hours of dosing | 0 participants |
| Completed Responders 400 mg | Number of Participants With Adverse Events | Serious adverse events leading to death | 0 participants |
| Completed Responders 400 mg | Number of Participants With Adverse Events | Moderate adverse events | 18 participants |
| Completed Responders 400 mg | Number of Participants With Adverse Events | Mild adverse events | 15 participants |
| Completed Responders 400 mg | Number of Participants With Adverse Events | Any adverse event | 40 participants |
| Completed Responders 400 mg | Number of Participants With Adverse Events | Infections induced by pathogen in study drug | 0 participants |
| Completed Responders 400 mg | Number of Participants With Adverse Events | Adverse events occurring within 2 hours of dosing | 0 participants |
| Completed Responders 400 mg | Number of Participants With Adverse Events | Overdoses | 0 participants |
| Completed Responders 400 mg | Number of Participants With Adverse Events | Adverse events leading to withdrawal | 6 participants |
| Completed Responders 400 mg | Number of Participants With Adverse Events | Serious adverse events | 16 participants |
| Completed Responders 400 mg | Number of Participants With Adverse Events | Severe adverse events | 7 participants |
| Completed Responders 400 mg | Number of Participants With Adverse Events | Non-fatal serious adverse events | 16 participants |
Secondary
Change From Baseline in Disease Activity Score (DAS) 28
The DAS28 measures the severity of disease at a specific time and is derived from the following variables: * 28 tender joint count; * 28 swollen joint count; * Erythrocyte sedimentation rate (ESR); * Patient's global assessment of disease activity. To obtain the tender joint count and swollen joint count, 28 joints of the shoulder, elbow, wrist, metacarpophalangeal joints, thumb interphalangeal joints, proximal interphalangeal joints, and knee joints were examined. The data before study drug administration of 275-08-003 Study was utilized for Baseline. DAS28(ESR) scores range from 0 to approximately 10, with the upper bound dependent on the highest possible ESR. A DAS28 score higher than 5.1 indicates high disease activity, a DAS28 score of 3.2 or less indicates low disease activity, and a DAS28 score less than 2.6 indicates clinical remission.
Time frame: Baseline (of Study 275-08-003), Week 24, Week 52 and at the final assessment (maximum was 208 weeks)
Population: The full analysis set (FAS) included all randomized participants who received at least one dose of study drug with at least one post-baseline efficacy data point. Last observation carried forward (LOCF) was used. N indicates the number of participants with available data at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Discontinued Non-responders 200 mg | Change From Baseline in Disease Activity Score (DAS) 28 | Week 24 [N=110, 12, 43, 43] | -1.87 units on a scale | Standard Deviation 1.31 |
| Discontinued Non-responders 200 mg | Change From Baseline in Disease Activity Score (DAS) 28 | Final Assessment [N=110, 12, 43, 43] | -2.23 units on a scale | Standard Deviation 1.63 |
| Discontinued Non-responders 200 mg | Change From Baseline in Disease Activity Score (DAS) 28 | Week 52 [N=109, 12, 43, 43] | -2.15 units on a scale | Standard Deviation 1.37 |
| Completed Non-responders 200 mg | Change From Baseline in Disease Activity Score (DAS) 28 | Week 24 [N=110, 12, 43, 43] | -2.46 units on a scale | Standard Deviation 1.18 |
| Completed Non-responders 200 mg | Change From Baseline in Disease Activity Score (DAS) 28 | Final Assessment [N=110, 12, 43, 43] | -2.31 units on a scale | Standard Deviation 1.21 |
| Completed Non-responders 200 mg | Change From Baseline in Disease Activity Score (DAS) 28 | Week 52 [N=109, 12, 43, 43] | -2.53 units on a scale | Standard Deviation 0.9 |
| Completed Responders 200 mg | Change From Baseline in Disease Activity Score (DAS) 28 | Week 52 [N=109, 12, 43, 43] | -2.93 units on a scale | Standard Deviation 1.47 |
| Completed Responders 200 mg | Change From Baseline in Disease Activity Score (DAS) 28 | Week 24 [N=110, 12, 43, 43] | -3.10 units on a scale | Standard Deviation 1.28 |
| Completed Responders 200 mg | Change From Baseline in Disease Activity Score (DAS) 28 | Final Assessment [N=110, 12, 43, 43] | -2.98 units on a scale | Standard Deviation 1.58 |
| Completed Responders 400 mg | Change From Baseline in Disease Activity Score (DAS) 28 | Week 24 [N=110, 12, 43, 43] | -2.87 units on a scale | Standard Deviation 1.4 |
| Completed Responders 400 mg | Change From Baseline in Disease Activity Score (DAS) 28 | Final Assessment [N=110, 12, 43, 43] | -2.93 units on a scale | Standard Deviation 1.24 |
| Completed Responders 400 mg | Change From Baseline in Disease Activity Score (DAS) 28 | Week 52 [N=109, 12, 43, 43] | -2.98 units on a scale | Standard Deviation 1.11 |
Secondary
Change From Baseline in Modified Total Sharp Score (mTSS)
X-ray images of extremities (posteroanterior views of both hands and dorsoplantar views of both feet) were independently assessed by at least two radiographic readers. The degree of joint destruction was graded by assessing bone erosion in 44 joints and joint space narrowing (JSN) in 42 joints. The joint erosion score is a summary of erosion severity in 32 joints of the hands and 12 joints in the feet. Each joint was scored, according to the surface area involved, from 0 (no erosion) to 5 (complete collapse of bone). The score for erosion ranges from 0 to 160 in the hands and from 0 to 120 in the feet (the maximum erosion score for a joint in the foot is 10). The JSN score summarizes the severity of JSN in 30 joints of the hands and 12 joints of the feet. JSN, including subluxation, was scored from 0 (normal) to 4 (complete loss of joint space, bony ankylosis, or luxation), with a maximum JSN score of 168. The mTSS ranges from 0 (normal) to 448 (worst).
Time frame: Baseline (of Study 275-08-003), Week 0 (of this study) and Week 100
Population: Full analysis set with available mTSS data. Linear extrapolation method was used.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Discontinued Non-responders 200 mg | Change From Baseline in Modified Total Sharp Score (mTSS) | Change from Baseline to Week 0 | 1.48 units on a scale | Standard Deviation 2.67 |
| Discontinued Non-responders 200 mg | Change From Baseline in Modified Total Sharp Score (mTSS) | Change from Baseline to Week 100 [N=82, 11, 35, 36 | 7.89 units on a scale | Standard Deviation 14.23 |
| Completed Non-responders 200 mg | Change From Baseline in Modified Total Sharp Score (mTSS) | Change from Baseline to Week 100 [N=82, 11, 35, 36 | 8.73 units on a scale | Standard Deviation 11.54 |
| Completed Non-responders 200 mg | Change From Baseline in Modified Total Sharp Score (mTSS) | Change from Baseline to Week 0 | 2.18 units on a scale | Standard Deviation 2.91 |
| Completed Responders 200 mg | Change From Baseline in Modified Total Sharp Score (mTSS) | Change from Baseline to Week 0 | 0.77 units on a scale | Standard Deviation 3 |
| Completed Responders 200 mg | Change From Baseline in Modified Total Sharp Score (mTSS) | Change from Baseline to Week 100 [N=82, 11, 35, 36 | 2.07 units on a scale | Standard Deviation 6.72 |
| Completed Responders 400 mg | Change From Baseline in Modified Total Sharp Score (mTSS) | Change from Baseline to Week 0 | -0.05 units on a scale | Standard Deviation 1.22 |
| Completed Responders 400 mg | Change From Baseline in Modified Total Sharp Score (mTSS) | Change from Baseline to Week 100 [N=82, 11, 35, 36 | 1.85 units on a scale | Standard Deviation 4.24 |
Secondary
Percentage of Participants With American College of Rheumatology 20% (ACR20) Response
A participant was an ACR20 responder if the following 3 criteria for improvement from Baseline (before study drug administration in Study 275-08-003) were met: * ≥ 20% improvement in 68 tender joint count; * ≥ 20% improvement in 66 swollen joint count; and * ≥ 20% improvement in at least 3 of the 5 following parameters: * Patient's assessment of arthritis pain (measured on a 100 mm visual analog scale \[VAS\]); * Patient's global assessment of disease activity (measured on a 100 mm VAS); * Physician's global assessment of disease activity (measured on a 100 mm VAS); * Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); * C-Reactive Protein (CRP).
Time frame: Baseline (of Study 275-08-003), Week 24, Week 52 and at the final assessment (maximum was 208 weeks)
Population: The full analysis set (FAS) included all randomized participants who received at least one dose of study drug with at least one post-baseline efficacy data point. Last observation carried forward (LOCF) was used.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Discontinued Non-responders 200 mg | Percentage of Participants With American College of Rheumatology 20% (ACR20) Response | Week 24 | 60.9 percentage of participants |
| Discontinued Non-responders 200 mg | Percentage of Participants With American College of Rheumatology 20% (ACR20) Response | Final Assessment | 67.3 percentage of participants |
| Discontinued Non-responders 200 mg | Percentage of Participants With American College of Rheumatology 20% (ACR20) Response | Week 52 | 70.0 percentage of participants |
| Completed Non-responders 200 mg | Percentage of Participants With American College of Rheumatology 20% (ACR20) Response | Week 24 | 58.3 percentage of participants |
| Completed Non-responders 200 mg | Percentage of Participants With American College of Rheumatology 20% (ACR20) Response | Final Assessment | 75.0 percentage of participants |
| Completed Non-responders 200 mg | Percentage of Participants With American College of Rheumatology 20% (ACR20) Response | Week 52 | 83.3 percentage of participants |
| Completed Responders 200 mg | Percentage of Participants With American College of Rheumatology 20% (ACR20) Response | Week 52 | 76.7 percentage of participants |
| Completed Responders 200 mg | Percentage of Participants With American College of Rheumatology 20% (ACR20) Response | Week 24 | 90.7 percentage of participants |
| Completed Responders 200 mg | Percentage of Participants With American College of Rheumatology 20% (ACR20) Response | Final Assessment | 86.0 percentage of participants |
| Completed Responders 400 mg | Percentage of Participants With American College of Rheumatology 20% (ACR20) Response | Week 24 | 90.7 percentage of participants |
| Completed Responders 400 mg | Percentage of Participants With American College of Rheumatology 20% (ACR20) Response | Final Assessment | 88.4 percentage of participants |
| Completed Responders 400 mg | Percentage of Participants With American College of Rheumatology 20% (ACR20) Response | Week 52 | 90.7 percentage of participants |
Secondary
Percentage of Participants With American College of Rheumatology 50% (ACR50) Response
A participant was an ACR50 responder if the following 3 criteria for improvement from Baseline (before study drug administration in Study 275-08-003) were met: * ≥ 50% improvement in 68 tender joint count; * ≥ 50% improvement in 66 swollen joint count; and * ≥ 50% improvement in at least 3 of the 5 following parameters: * Patient's assessment of arthritis pain (measured on a 100 mm visual analog scale \[VAS\]); * Patient's global assessment of disease activity (measured on a 100 mm VAS); * Physician's global assessment of disease activity (measured on a 100 mm VAS); * Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); * C-Reactive Protein (CRP).
Time frame: Baseline (of Study 275-08-003), Week 24, Week 52 and at the final assessment (maximum was 208 weeks)
Population: The full analysis set (FAS) included all randomized participants who received at least one dose of study drug with at least one post-baseline efficacy data point. Last observation carried forward (LOCF) was used.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Discontinued Non-responders 200 mg | Percentage of Participants With American College of Rheumatology 50% (ACR50) Response | Week 24 | 29.1 percentage of participants |
| Discontinued Non-responders 200 mg | Percentage of Participants With American College of Rheumatology 50% (ACR50) Response | Final Assessment | 47.3 percentage of participants |
| Discontinued Non-responders 200 mg | Percentage of Participants With American College of Rheumatology 50% (ACR50) Response | Week 52 | 40.9 percentage of participants |
| Completed Non-responders 200 mg | Percentage of Participants With American College of Rheumatology 50% (ACR50) Response | Week 24 | 41.7 percentage of participants |
| Completed Non-responders 200 mg | Percentage of Participants With American College of Rheumatology 50% (ACR50) Response | Final Assessment | 58.3 percentage of participants |
| Completed Non-responders 200 mg | Percentage of Participants With American College of Rheumatology 50% (ACR50) Response | Week 52 | 58.3 percentage of participants |
| Completed Responders 200 mg | Percentage of Participants With American College of Rheumatology 50% (ACR50) Response | Week 52 | 62.8 percentage of participants |
| Completed Responders 200 mg | Percentage of Participants With American College of Rheumatology 50% (ACR50) Response | Week 24 | 69.8 percentage of participants |
| Completed Responders 200 mg | Percentage of Participants With American College of Rheumatology 50% (ACR50) Response | Final Assessment | 67.4 percentage of participants |
| Completed Responders 400 mg | Percentage of Participants With American College of Rheumatology 50% (ACR50) Response | Week 24 | 74.4 percentage of participants |
| Completed Responders 400 mg | Percentage of Participants With American College of Rheumatology 50% (ACR50) Response | Final Assessment | 74.4 percentage of participants |
| Completed Responders 400 mg | Percentage of Participants With American College of Rheumatology 50% (ACR50) Response | Week 52 | 69.8 percentage of participants |
Secondary
Percentage of Participants With American College of Rheumatology 70% (ACR70) Response
A participant was an ACR70 responder if the following 3 criteria for improvement from Baseline (before study drug administration in Study 275-08-003) were met: * ≥ 70% improvement in 68 tender joint count; * ≥ 70% improvement in 66 swollen joint count; and * ≥ 70% improvement in at least 3 of the 5 following parameters: * Patient's assessment of arthritis pain (measured on a 100 mm visual analog scale \[VAS\]); * Patient's global assessment of disease activity (measured on a 100 mm VAS); * Physician's global assessment of disease activity (measured on a 100 mm VAS); * Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); * C-Reactive Protein (CRP).
Time frame: Baseline (of Study 275-08-003), Week 24, Week 52 and at the final assessment (maximum was 208 weeks)
Population: The full analysis set (FAS) included all randomized participants who received at least one dose of study drug with at least one post-baseline efficacy data point. Last observation carried forward (LOCF) was used.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Discontinued Non-responders 200 mg | Percentage of Participants With American College of Rheumatology 70% (ACR70) Response | Week 24 | 14.5 percentage of participants |
| Discontinued Non-responders 200 mg | Percentage of Participants With American College of Rheumatology 70% (ACR70) Response | Final Assessment | 29.1 percentage of participants |
| Discontinued Non-responders 200 mg | Percentage of Participants With American College of Rheumatology 70% (ACR70) Response | Week 52 | 22.7 percentage of participants |
| Completed Non-responders 200 mg | Percentage of Participants With American College of Rheumatology 70% (ACR70) Response | Week 24 | 16.7 percentage of participants |
| Completed Non-responders 200 mg | Percentage of Participants With American College of Rheumatology 70% (ACR70) Response | Final Assessment | 16.7 percentage of participants |
| Completed Non-responders 200 mg | Percentage of Participants With American College of Rheumatology 70% (ACR70) Response | Week 52 | 16.7 percentage of participants |
| Completed Responders 200 mg | Percentage of Participants With American College of Rheumatology 70% (ACR70) Response | Week 52 | 58.1 percentage of participants |
| Completed Responders 200 mg | Percentage of Participants With American College of Rheumatology 70% (ACR70) Response | Week 24 | 46.5 percentage of participants |
| Completed Responders 200 mg | Percentage of Participants With American College of Rheumatology 70% (ACR70) Response | Final Assessment | 60.5 percentage of participants |
| Completed Responders 400 mg | Percentage of Participants With American College of Rheumatology 70% (ACR70) Response | Week 24 | 48.8 percentage of participants |
| Completed Responders 400 mg | Percentage of Participants With American College of Rheumatology 70% (ACR70) Response | Final Assessment | 58.1 percentage of participants |
| Completed Responders 400 mg | Percentage of Participants With American College of Rheumatology 70% (ACR70) Response | Week 52 | 46.5 percentage of participants |