Clinical Trial Results:
A Phase 3b, Randomized, Active Controlled Trial to Evaluate the Efficacy and Safety of Abatacept SC in Combination with Methotrexate in Inducing Clinical Remission Compared to Methotrexate Monotherapy in Adults with Very Early RA
Summary
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EudraCT number |
2010-018674-20 |
Trial protocol |
FR DE BE SE FI DK IT |
Global end of trial date |
27 Oct 2014
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Results information
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Results version number |
v1(current) |
This version publication date |
01 Apr 2016
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First version publication date |
01 Apr 2016
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
IM101-226
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01142726 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Bristol Myers Squibb
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Sponsor organisation address |
Chaussee de la Hulpe 185, Brussels, Belgium,
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Public contact |
Bristol Myers Squibb Study Director, Bristol Myers Squibb, clinical.trials@bms.com
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Scientific contact |
Bristol Myers Squibb Study Director, Bristol Myers Squibb, clinical.trials@bms.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
27 Oct 2014
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
27 Oct 2014
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The main objectives of the study were to compare the clinical efficacy of abatacept in combination with methotrexate (MTX) to MTX alone on the following:
• The proportion of randomized and treated subjects with Disease Activity Score 28 based on C-reactive protein (DAS28-CRP) <2.6 at Month 12
• The proportion of randomized and treated subjects with DAS28-CRP <2.6 at both Month 12 and Month 18.
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Protection of trial subjects |
The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Conference on Harmonization Good Clinical Practice Guidelines. All the local regulatory requirements pertinent to safety of trial subjects were followed.
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Background therapy |
- | ||
Evidence for comparator |
MTX is a standard of care for early treatment of Rheumatoid arthritis. Hence MTX was selected as the active comparator and Based on the results of study NCT00989235, it was hypothesized that the addition of abatacept to MTX will be superior to MTX in inducing DAS28 clinical remission after a year of treatment in subjects who have serologically positive early RA and are MTX naive. MTX was supplied as 2.5 mg tablets for weekly oral administration during the Treatment Period, and was titrated over a period of 6 to 8 weeks based on tolerability. | ||
Actual start date of recruitment |
10 Dec 2010
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
South Africa: 66
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Country: Number of subjects enrolled |
Sweden: 23
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Country: Number of subjects enrolled |
United States: 73
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Country: Number of subjects enrolled |
Australia: 42
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Country: Number of subjects enrolled |
Belgium: 32
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Country: Number of subjects enrolled |
Canada: 6
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Country: Number of subjects enrolled |
Denmark: 2
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Country: Number of subjects enrolled |
Finland: 4
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Country: Number of subjects enrolled |
France: 18
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Country: Number of subjects enrolled |
Germany: 46
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Country: Number of subjects enrolled |
Italy: 4
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Country: Number of subjects enrolled |
Korea, Republic of: 40
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Country: Number of subjects enrolled |
Mexico: 102
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Country: Number of subjects enrolled |
Poland: 53
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Worldwide total number of subjects |
511
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EEA total number of subjects |
182
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
458
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From 65 to 84 years |
53
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85 years and over |
0
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Recruitment
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Recruitment details |
Subjects were enrolled from 73 sites in 14 countries. | ||||||||||||||||||||||||||||||||||||||||||||
Pre-assignment
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Screening details |
A total of 511 subjects were enrolled in the study, and 351 were randomized. Reasons that 160 enrolled subjects were not randomized were failure to meet study criteria (130/160), withdrawal of consent (20/160), poor/non-compliance (3/160), administrative reason by sponsor (2/160), lost to follow-up (1/160), and other reasons (4/160). | ||||||||||||||||||||||||||||||||||||||||||||
Period 1
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Period 1 title |
Treatment Phase: Day 1 Through Month 12
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | ||||||||||||||||||||||||||||||||||||||||||||
Roles blinded |
Subject, Investigator | ||||||||||||||||||||||||||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Abatacept, 125 mg, Plus Methotrexate, 2.5 mg | ||||||||||||||||||||||||||||||||||||||||||||
Arm description |
Subjects received abatacept, 125 mg subcutaneously, plus methotrexate (MTX), 2.5 mg orally as tablets, with a target dose range of 10-20 mg weekly, during the 12-month Treatment Period. Subjects with a Low Disease Activity Score (LDAS) defined as DAS28-CRP score of <3.2 at Month 12 (end of Treatment Period) entered the Withdrawal Period for up to 12 months, during which all study medication was withdrawn. Subjects with a DAS28-CRP score of >3.2 were discontinued from the study. All MTX and corticosteroids, if not already discontinued, were to be tapered off during the first month of the Withdrawal Period. Subjects who experienced a worsening of rheumatoid arthritis (RA) symptoms or a RA flare after at least 3 months in the Withdrawal Period were eligible to enroll into a 6-month Re-exposure Period, during which they received open-label treatment with abatacept subcutaneous (SC) 125 mg/week and MTX. | ||||||||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Methotrexate
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Investigational medicinal product code |
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Other name |
Rheumatrex
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Methotrexate 2.5 mg orally as tablets, with a target dose range of 10-20 mg weekly during the 12-month Treatment Period.
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Investigational medicinal product name |
Abatacept
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Investigational medicinal product code |
BMS 188667
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Other name |
Orencia
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Pharmaceutical forms |
Injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Abatacept 125 mg was administered as subcutaneous injection once weekly during the 12-month Treatment Period.
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Arm title
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Abatacept, 125 mg, Plus Methotrexate Placebo | ||||||||||||||||||||||||||||||||||||||||||||
Arm description |
Subjects received abatacept, 125 mg subcutaneously, plus methotrexate placebo tablets orally, once weekly during the 12-month Treatment Period. Subjects with a Low Disease Activity Score (LDAS) defined as DAS28-CRP score of <3.2 at Month 12 (end of Treatment Period) entered the Withdrawal Period for up to 12 months, during which all study medication was withdrawn. Subjects with a DAS28-CRP score of >3.2 were discontinued from the study. Subjects who experienced a worsening of rheumatoid arthritis (RA) symptoms or a RA flare after at least 3 months in the Withdrawal Period were eligible to enroll into a 6-month Re-exposure Period, during which they received open-label treatment with abatacept SC (125 mg/week) and MTX. | ||||||||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Methotrexate placebo
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Investigational medicinal product code |
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Other name |
Rheumatrex
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Methotrexate matching placebo 2.5 mg tablet was administered orally once weekly during the 12-month Treatment Period.
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Investigational medicinal product name |
Abatacept
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Investigational medicinal product code |
BMS 188667
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Other name |
Orencia
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Pharmaceutical forms |
Injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Abatacept 125 mg was administered as subcutaneous injection once weekly during the 12-month Treatment Period.
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Arm title
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Methotrexate, 2.5 mg, Plus Abatacept Placebo | ||||||||||||||||||||||||||||||||||||||||||||
Arm description |
Subjects received methotrexate, 2.5 mg orally as tablets, with a target dose range of 10-20 mg weekly, plus abatacept placebo subcutaneously, once weekly during the 12-month Treatment Period. Subjects with a Low Disease Activity Score (LDAS) defined as DAS28-CRP score of < 3.2 at Month 12 (end of Treatment Period) entered the Withdrawal Period for up to 12 months, during which all study medication was withdrawn. Subjects with a DAS28-CRP score of >3.2 were discontinued from the study. All MTX and corticosteroids, if not already discontinued, were to be tapered off during the first month of the Withdrawal Period. Subjects who experienced a worsening of rheumatoid arthritis (RA) symptoms or a RA flare after at least 3 months in the Withdrawal Period were eligible to enroll into a 6-month Re-exposure Period, during which they received open-label treatment with abatacept SC (125 mg/week) and MTX. | ||||||||||||||||||||||||||||||||||||||||||||
Arm type |
Active comparator | ||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Methotrexate
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Investigational medicinal product code |
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Other name |
Rheumatrex
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
2.5 mg orally as tablets, with a target dose range of 10-20 mg weekly during the 12-month Treatment Period.
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Investigational medicinal product name |
Abatacept Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Abatacept matching placebo 125-mg was administered as subcutaneous injection once weekly during the 12-month Treatment Period.
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Notes [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same. Justification: The number of subjects reported in the baseline period are different from the worldwide number enrolled in the trial, as 160 enrolled subjects were not randomized. Reasons were failure to meet study criteria (130/160), withdrawal of consent (20/160), poor/non-compliance (3/160), administrative reason by sponsor (2/160), lost to follow-up (1/160), and other reasons (4/160). |
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Period 2
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Period 2 title |
Withdrawal Phase: Month 12 up to 24
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Is this the baseline period? |
No | ||||||||||||||||||||||||||||||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||||||||||||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Abatacept, 125 mg, Plus Methotrexate, 2.5 mg | ||||||||||||||||||||||||||||||||||||||||||||
Arm description |
Subjects received abatacept, 125 mg subcutaneously, plus methotrexate (MTX), 2.5 mg orally as tablets, with a target dose range of 10-20 mg weekly, during the 12-month Treatment Period. Subjects with a Low Disease Activity Score (LDAS) defined as DAS28-CRP score of <3.2 at Month 12 (end of Treatment Period) entered the Withdrawal Period for up to 12 months, during which all study medication was withdrawn. Subjects with a DAS28-CRP score of >3.2 were discontinued from the study. All MTX and corticosteroids, if not already discontinued, were to be tapered off during the first month of the Withdrawal Period. Subjects who experienced a worsening of rheumatoid arthritis (RA) symptoms or a RA flare after at least 3 months in the Withdrawal Period were eligible to enroll into a 6-month Re-exposure Period, during which they received open-label treatment with abatacept subcutaneous (SC) 125 mg/week and MTX. | ||||||||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Methotrexate
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Investigational medicinal product code |
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Other name |
Rheumatrex
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
2.5 mg orally as tablets, with a target dose range of 10-20 mg weekly during the 12-month Treatment Period.
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Investigational medicinal product name |
Abatacept
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Investigational medicinal product code |
BMS 188667
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Other name |
Orencia
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Pharmaceutical forms |
Injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Abatacept 125 mg was administered as subcutaneous injection once weekly during the 12-month Treatment Period.
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Arm title
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Abatacept, 125 mg, Plus Methotrexate Placebo | ||||||||||||||||||||||||||||||||||||||||||||
Arm description |
Subjects received abatacept, 125 mg subcutaneously, plus methotrexate placebo tablets orally, once weekly during the 12-month Treatment Period. Subjects with a Low Disease Activity Score (LDAS) defined as DAS28-CRP score of <3.2 at Month 12 (end of Treatment Period) entered the Withdrawal Period for up to 12 months, during which all study medication was withdrawn. Subjects with a DAS28-CRP score of >3.2 were discontinued from the study. Subjects who experienced a worsening of rheumatoid arthritis (RA) symptoms or a RA flare after at least 3 months in the Withdrawal Period were eligible to enroll into a 6-month Re-exposure Period, during which they received open-label treatment with abatacept SC (125 mg/week) and MTX. | ||||||||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Methotrexate placebo
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Investigational medicinal product code |
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Other name |
Rheumatrex
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Methotrexate matching placebo 2.5 mg tablet was administered orally once weekly during the 12-month Treatment Period.
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Investigational medicinal product name |
Abatacept
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Investigational medicinal product code |
BMS 188667
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Other name |
Orencia
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Pharmaceutical forms |
Injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Abatacept 125 mg was administered as subcutaneous injection once weekly during the 12-month Treatment Period.
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Arm title
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Methotrexate, 2.5 mg, Plus Abatacept Placebo | ||||||||||||||||||||||||||||||||||||||||||||
Arm description |
Subjects received methotrexate, 2.5 mg orally as tablets, with a target dose range of 10-20 mg weekly, plus abatacept placebo subcutaneously, once weekly during the 12-month Treatment Period. Subjects with a Low Disease Activity Score (LDAS) defined as DAS28-CRP score of < 3.2 at Month 12 (end of Treatment Period) entered the Withdrawal Period for up to 12 months, during which all study medication was withdrawn. Subjects with a DAS28-CRP score of >3.2 were discontinued from the study. All MTX and corticosteroids, if not already discontinued, were to be tapered off during the first month of the Withdrawal Period. Subjects who experienced a worsening of rheumatoid arthritis (RA) symptoms or a RA flare after at least 3 months in the Withdrawal Period were eligible to enroll into a 6-month Re-exposure Period, during which they received open-label treatment with abatacept SC (125 mg/week) and MTX. | ||||||||||||||||||||||||||||||||||||||||||||
Arm type |
Active comparator | ||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Methotrexate
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Investigational medicinal product code |
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Other name |
Rheumatrex
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
2.5 mg orally as tablets, with a target dose range of 10-20 mg weekly during the 12-month Treatment Period.
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Investigational medicinal product name |
Abatacept Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Abatacept matching placebo 125-mg was administered as subcutaneous injection once weekly during the 12-month Treatment Period.
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Notes [2] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period. Justification: Out of all subjects who completed treatment period 67 subjects did not enter the withdrawal period. 2 subjects in the MTX monotherapy arm entered the Withdrawal Period after the data cutoff date for the first analysis. |
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Period 3
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Period 3 title |
Re-Exposure Phase: Months 24 up to 30
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Is this the baseline period? |
No | ||||||||||||||||||||||||||||||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||||||||||||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Abatacept, 125 mg, Plus Methotrexate, 2.5 mg | ||||||||||||||||||||||||||||||||||||||||||||
Arm description |
Subjects received abatacept, 125 mg subcutaneously, plus methotrexate (MTX), 2.5 mg orally as tablets, with a target dose range of 10-20 mg weekly, during the 12-month Treatment Period. Subjects with a Low Disease Activity Score (LDAS) defined as DAS28-CRP score of <3.2 at Month 12 (end of Treatment Period) entered the Withdrawal Period for up to 12 months, during which all study medication was withdrawn. Subjects with a DAS28-CRP score of >3.2 were discontinued from the study. All MTX and corticosteroids, if not already discontinued, were to be tapered off during the first month of the Withdrawal Period. Subjects who experienced a worsening of rheumatoid arthritis (RA) symptoms or a RA flare after at least 3 months in the Withdrawal Period were eligible to enroll into a 6-month Re-exposure Period, during which they received open-label treatment with abatacept subcutaneous (SC) 125 mg/week and MTX. | ||||||||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Methotrexate
|
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Investigational medicinal product code |
|||||||||||||||||||||||||||||||||||||||||||||
Other name |
Rheumatrex
|
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Pharmaceutical forms |
Tablet
|
||||||||||||||||||||||||||||||||||||||||||||
Routes of administration |
Oral use
|
||||||||||||||||||||||||||||||||||||||||||||
Dosage and administration details |
2.5 mg orally as tablets, with a target dose range of 10-20 mg weekly during the 12-month Treatment Period.
|
||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Abatacept
|
||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product code |
BMS 188667
|
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Other name |
Orencia
|
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Pharmaceutical forms |
Injection
|
||||||||||||||||||||||||||||||||||||||||||||
Routes of administration |
Subcutaneous use
|
||||||||||||||||||||||||||||||||||||||||||||
Dosage and administration details |
Abatacept 125 mg was administered as subcutaneous injection once weekly during the 12-month Treatment Period.
|
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Arm title
|
Abatacept, 125 mg, Plus Methotrexate Placebo | ||||||||||||||||||||||||||||||||||||||||||||
Arm description |
Subjects received abatacept, 125 mg subcutaneously, plus methotrexate placebo tablets orally, once weekly during the 12-month Treatment Period. Subjects with a Low Disease Activity Score (LDAS) defined as DAS28-CRP score of <3.2 at Month 12 (end of Treatment Period) entered the Withdrawal Period for up to 12 months, during which all study medication was withdrawn. Subjects with a DAS28-CRP score of >3.2 were discontinued from the study. Subjects who experienced a worsening of rheumatoid arthritis (RA) symptoms or a RA flare after at least 3 months in the Withdrawal Period were eligible to enroll into a 6-month Re-exposure Period, during which they received open-label treatment with abatacept SC (125 mg/week) and MTX. | ||||||||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Methotrexate placebo
|
||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||||||||||||||||||||||||||||
Other name |
Rheumatrex
|
||||||||||||||||||||||||||||||||||||||||||||
Pharmaceutical forms |
Tablet
|
||||||||||||||||||||||||||||||||||||||||||||
Routes of administration |
Oral use
|
||||||||||||||||||||||||||||||||||||||||||||
Dosage and administration details |
Methotrexate matching placebo 2.5 mg tablet was administered orally once weekly during the 12-month Treatment Period.
|
||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Abatacept
|
||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product code |
BMS 188667
|
||||||||||||||||||||||||||||||||||||||||||||
Other name |
Orencia
|
||||||||||||||||||||||||||||||||||||||||||||
Pharmaceutical forms |
Injection
|
||||||||||||||||||||||||||||||||||||||||||||
Routes of administration |
Subcutaneous use
|
||||||||||||||||||||||||||||||||||||||||||||
Dosage and administration details |
Abatacept 125 mg was administered as subcutaneous injection once weekly during the 12-month Treatment Period.
|
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Arm title
|
Methotrexate, 2.5 mg, Plus Abatacept Placebo | ||||||||||||||||||||||||||||||||||||||||||||
Arm description |
Subjects received methotrexate, 2.5 mg orally as tablets, with a target dose range of 10-20 mg weekly, plus abatacept placebo subcutaneously, once weekly during the 12-month Treatment Period. Subjects with a Low Disease Activity Score (LDAS) defined as DAS28-CRP score of < 3.2 at Month 12 (end of Treatment Period) entered the Withdrawal Period for up to 12 months, during which all study medication was withdrawn. Subjects with a DAS28-CRP score of >3.2 were discontinued from the study. All MTX and corticosteroids, if not already discontinued, were to be tapered off during the first month of the Withdrawal Period. Subjects who experienced a worsening of rheumatoid arthritis (RA) symptoms or a RA flare after at least 3 months in the Withdrawal Period were eligible to enroll into a 6-month Re-exposure Period, during which they received open-label treatment with abatacept SC (125 mg/week) and MTX. | ||||||||||||||||||||||||||||||||||||||||||||
Arm type |
Active comparator | ||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Methotrexate
|
||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||||||||||||||||||||||||||||
Other name |
Rheumatrex
|
||||||||||||||||||||||||||||||||||||||||||||
Pharmaceutical forms |
Tablet
|
||||||||||||||||||||||||||||||||||||||||||||
Routes of administration |
Oral use
|
||||||||||||||||||||||||||||||||||||||||||||
Dosage and administration details |
2.5 mg orally as tablets, with a target dose range of 10-20 mg weekly during the 12-month Treatment Period.
|
||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Abatacept Placebo
|
||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||||||||||||||||||||||||||||
Other name |
|||||||||||||||||||||||||||||||||||||||||||||
Pharmaceutical forms |
Injection
|
||||||||||||||||||||||||||||||||||||||||||||
Routes of administration |
Subcutaneous use
|
||||||||||||||||||||||||||||||||||||||||||||
Dosage and administration details |
Abatacept matching placebo 125-mg was administered as subcutaneous injection once weekly during the 12-month Treatment Period.
|
||||||||||||||||||||||||||||||||||||||||||||
|
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Baseline characteristics reporting groups
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Abatacept, 125 mg, Plus Methotrexate, 2.5 mg
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Subjects received abatacept, 125 mg subcutaneously, plus methotrexate (MTX), 2.5 mg orally as tablets, with a target dose range of 10-20 mg weekly, during the 12-month Treatment Period. Subjects with a Low Disease Activity Score (LDAS) defined as DAS28-CRP score of <3.2 at Month 12 (end of Treatment Period) entered the Withdrawal Period for up to 12 months, during which all study medication was withdrawn. Subjects with a DAS28-CRP score of >3.2 were discontinued from the study. All MTX and corticosteroids, if not already discontinued, were to be tapered off during the first month of the Withdrawal Period. Subjects who experienced a worsening of rheumatoid arthritis (RA) symptoms or a RA flare after at least 3 months in the Withdrawal Period were eligible to enroll into a 6-month Re-exposure Period, during which they received open-label treatment with abatacept subcutaneous (SC) 125 mg/week and MTX. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Abatacept, 125 mg, Plus Methotrexate Placebo
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Subjects received abatacept, 125 mg subcutaneously, plus methotrexate placebo tablets orally, once weekly during the 12-month Treatment Period. Subjects with a Low Disease Activity Score (LDAS) defined as DAS28-CRP score of <3.2 at Month 12 (end of Treatment Period) entered the Withdrawal Period for up to 12 months, during which all study medication was withdrawn. Subjects with a DAS28-CRP score of >3.2 were discontinued from the study. Subjects who experienced a worsening of rheumatoid arthritis (RA) symptoms or a RA flare after at least 3 months in the Withdrawal Period were eligible to enroll into a 6-month Re-exposure Period, during which they received open-label treatment with abatacept SC (125 mg/week) and MTX. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Methotrexate, 2.5 mg, Plus Abatacept Placebo
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Subjects received methotrexate, 2.5 mg orally as tablets, with a target dose range of 10-20 mg weekly, plus abatacept placebo subcutaneously, once weekly during the 12-month Treatment Period. Subjects with a Low Disease Activity Score (LDAS) defined as DAS28-CRP score of < 3.2 at Month 12 (end of Treatment Period) entered the Withdrawal Period for up to 12 months, during which all study medication was withdrawn. Subjects with a DAS28-CRP score of >3.2 were discontinued from the study. All MTX and corticosteroids, if not already discontinued, were to be tapered off during the first month of the Withdrawal Period. Subjects who experienced a worsening of rheumatoid arthritis (RA) symptoms or a RA flare after at least 3 months in the Withdrawal Period were eligible to enroll into a 6-month Re-exposure Period, during which they received open-label treatment with abatacept SC (125 mg/week) and MTX. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
End points reporting groups
|
|||
Reporting group title |
Abatacept, 125 mg, Plus Methotrexate, 2.5 mg
|
||
Reporting group description |
Subjects received abatacept, 125 mg subcutaneously, plus methotrexate (MTX), 2.5 mg orally as tablets, with a target dose range of 10-20 mg weekly, during the 12-month Treatment Period. Subjects with a Low Disease Activity Score (LDAS) defined as DAS28-CRP score of <3.2 at Month 12 (end of Treatment Period) entered the Withdrawal Period for up to 12 months, during which all study medication was withdrawn. Subjects with a DAS28-CRP score of >3.2 were discontinued from the study. All MTX and corticosteroids, if not already discontinued, were to be tapered off during the first month of the Withdrawal Period. Subjects who experienced a worsening of rheumatoid arthritis (RA) symptoms or a RA flare after at least 3 months in the Withdrawal Period were eligible to enroll into a 6-month Re-exposure Period, during which they received open-label treatment with abatacept subcutaneous (SC) 125 mg/week and MTX. | ||
Reporting group title |
Abatacept, 125 mg, Plus Methotrexate Placebo
|
||
Reporting group description |
Subjects received abatacept, 125 mg subcutaneously, plus methotrexate placebo tablets orally, once weekly during the 12-month Treatment Period. Subjects with a Low Disease Activity Score (LDAS) defined as DAS28-CRP score of <3.2 at Month 12 (end of Treatment Period) entered the Withdrawal Period for up to 12 months, during which all study medication was withdrawn. Subjects with a DAS28-CRP score of >3.2 were discontinued from the study. Subjects who experienced a worsening of rheumatoid arthritis (RA) symptoms or a RA flare after at least 3 months in the Withdrawal Period were eligible to enroll into a 6-month Re-exposure Period, during which they received open-label treatment with abatacept SC (125 mg/week) and MTX. | ||
Reporting group title |
Methotrexate, 2.5 mg, Plus Abatacept Placebo
|
||
Reporting group description |
Subjects received methotrexate, 2.5 mg orally as tablets, with a target dose range of 10-20 mg weekly, plus abatacept placebo subcutaneously, once weekly during the 12-month Treatment Period. Subjects with a Low Disease Activity Score (LDAS) defined as DAS28-CRP score of < 3.2 at Month 12 (end of Treatment Period) entered the Withdrawal Period for up to 12 months, during which all study medication was withdrawn. Subjects with a DAS28-CRP score of >3.2 were discontinued from the study. All MTX and corticosteroids, if not already discontinued, were to be tapered off during the first month of the Withdrawal Period. Subjects who experienced a worsening of rheumatoid arthritis (RA) symptoms or a RA flare after at least 3 months in the Withdrawal Period were eligible to enroll into a 6-month Re-exposure Period, during which they received open-label treatment with abatacept SC (125 mg/week) and MTX. | ||
Reporting group title |
Abatacept, 125 mg, Plus Methotrexate, 2.5 mg
|
||
Reporting group description |
Subjects received abatacept, 125 mg subcutaneously, plus methotrexate (MTX), 2.5 mg orally as tablets, with a target dose range of 10-20 mg weekly, during the 12-month Treatment Period. Subjects with a Low Disease Activity Score (LDAS) defined as DAS28-CRP score of <3.2 at Month 12 (end of Treatment Period) entered the Withdrawal Period for up to 12 months, during which all study medication was withdrawn. Subjects with a DAS28-CRP score of >3.2 were discontinued from the study. All MTX and corticosteroids, if not already discontinued, were to be tapered off during the first month of the Withdrawal Period. Subjects who experienced a worsening of rheumatoid arthritis (RA) symptoms or a RA flare after at least 3 months in the Withdrawal Period were eligible to enroll into a 6-month Re-exposure Period, during which they received open-label treatment with abatacept subcutaneous (SC) 125 mg/week and MTX. | ||
Reporting group title |
Abatacept, 125 mg, Plus Methotrexate Placebo
|
||
Reporting group description |
Subjects received abatacept, 125 mg subcutaneously, plus methotrexate placebo tablets orally, once weekly during the 12-month Treatment Period. Subjects with a Low Disease Activity Score (LDAS) defined as DAS28-CRP score of <3.2 at Month 12 (end of Treatment Period) entered the Withdrawal Period for up to 12 months, during which all study medication was withdrawn. Subjects with a DAS28-CRP score of >3.2 were discontinued from the study. Subjects who experienced a worsening of rheumatoid arthritis (RA) symptoms or a RA flare after at least 3 months in the Withdrawal Period were eligible to enroll into a 6-month Re-exposure Period, during which they received open-label treatment with abatacept SC (125 mg/week) and MTX. | ||
Reporting group title |
Methotrexate, 2.5 mg, Plus Abatacept Placebo
|
||
Reporting group description |
Subjects received methotrexate, 2.5 mg orally as tablets, with a target dose range of 10-20 mg weekly, plus abatacept placebo subcutaneously, once weekly during the 12-month Treatment Period. Subjects with a Low Disease Activity Score (LDAS) defined as DAS28-CRP score of < 3.2 at Month 12 (end of Treatment Period) entered the Withdrawal Period for up to 12 months, during which all study medication was withdrawn. Subjects with a DAS28-CRP score of >3.2 were discontinued from the study. All MTX and corticosteroids, if not already discontinued, were to be tapered off during the first month of the Withdrawal Period. Subjects who experienced a worsening of rheumatoid arthritis (RA) symptoms or a RA flare after at least 3 months in the Withdrawal Period were eligible to enroll into a 6-month Re-exposure Period, during which they received open-label treatment with abatacept SC (125 mg/week) and MTX. | ||
Reporting group title |
Abatacept, 125 mg, Plus Methotrexate, 2.5 mg
|
||
Reporting group description |
Subjects received abatacept, 125 mg subcutaneously, plus methotrexate (MTX), 2.5 mg orally as tablets, with a target dose range of 10-20 mg weekly, during the 12-month Treatment Period. Subjects with a Low Disease Activity Score (LDAS) defined as DAS28-CRP score of <3.2 at Month 12 (end of Treatment Period) entered the Withdrawal Period for up to 12 months, during which all study medication was withdrawn. Subjects with a DAS28-CRP score of >3.2 were discontinued from the study. All MTX and corticosteroids, if not already discontinued, were to be tapered off during the first month of the Withdrawal Period. Subjects who experienced a worsening of rheumatoid arthritis (RA) symptoms or a RA flare after at least 3 months in the Withdrawal Period were eligible to enroll into a 6-month Re-exposure Period, during which they received open-label treatment with abatacept subcutaneous (SC) 125 mg/week and MTX. | ||
Reporting group title |
Abatacept, 125 mg, Plus Methotrexate Placebo
|
||
Reporting group description |
Subjects received abatacept, 125 mg subcutaneously, plus methotrexate placebo tablets orally, once weekly during the 12-month Treatment Period. Subjects with a Low Disease Activity Score (LDAS) defined as DAS28-CRP score of <3.2 at Month 12 (end of Treatment Period) entered the Withdrawal Period for up to 12 months, during which all study medication was withdrawn. Subjects with a DAS28-CRP score of >3.2 were discontinued from the study. Subjects who experienced a worsening of rheumatoid arthritis (RA) symptoms or a RA flare after at least 3 months in the Withdrawal Period were eligible to enroll into a 6-month Re-exposure Period, during which they received open-label treatment with abatacept SC (125 mg/week) and MTX. | ||
Reporting group title |
Methotrexate, 2.5 mg, Plus Abatacept Placebo
|
||
Reporting group description |
Subjects received methotrexate, 2.5 mg orally as tablets, with a target dose range of 10-20 mg weekly, plus abatacept placebo subcutaneously, once weekly during the 12-month Treatment Period. Subjects with a Low Disease Activity Score (LDAS) defined as DAS28-CRP score of < 3.2 at Month 12 (end of Treatment Period) entered the Withdrawal Period for up to 12 months, during which all study medication was withdrawn. Subjects with a DAS28-CRP score of >3.2 were discontinued from the study. All MTX and corticosteroids, if not already discontinued, were to be tapered off during the first month of the Withdrawal Period. Subjects who experienced a worsening of rheumatoid arthritis (RA) symptoms or a RA flare after at least 3 months in the Withdrawal Period were eligible to enroll into a 6-month Re-exposure Period, during which they received open-label treatment with abatacept SC (125 mg/week) and MTX. |
|
|||||||||||||||||||
End point title |
Percentage of Subjects Who Achieved Remission by Disease Activity Score 28 Based on C-reactive Protein (DAS28-CRP) Criteria at Month 12 and at Both Months 12 and 18 [1] | ||||||||||||||||||
End point description |
DAS28-CRP remission defined as <2.6; TP=treatment phase; WP=withdrawal phase. The DAS 28-CRP is a measure of disease activity in rheumatoid arthritis (RA) that assesses the 28 joints RA commonly affects; the score includes the number of tender and swollen joints (out of 28), CRP level (a measure of inflammation in the blood), and the subject’s global assessment of health (ranging from very good to very bad). These measures are then fed into a complex mathematical formula to produce the overall DAS (a score greater than 5.1 implies active disease; less than 3.2, well controlled disease; and less than 2.6, remission). Analysis was performed in all the randomized subjects who received at least 1 dose of double-blind study medication in the Treatment Period. Percentage calculated as a/b, where a=number of subjects who achieved remission at Month 12 and at both Months 12 and 18, and b=number of subjects in the analysis. n=number of evaluable subjects.
|
||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||
End point timeframe |
Randomization to Months 12 and 18
|
||||||||||||||||||
Notes [1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint was planned to be assessed for these reporting arms only. |
|||||||||||||||||||
|
|||||||||||||||||||
Statistical analysis title |
DAS28-CRP Remission at Month 12 | ||||||||||||||||||
Statistical analysis description |
Power estimate assumed 2-sided alpha level of 5% and that 60% of ABA + MTX subjects would be in DAS28-CRP remission at Month 12 compared with 38% of MTX monotherapy subjects. Also assumed that 48% of abatacept monotherapy subjects would be in DAS28-CRP remission at Month 12, yielding an expected treatment difference from MX of 10% in favor of ABA monotherapy; 116 subjects randomized to ABA monotherapy would yield a half-length of the 95% CI around that 10% treatment difference of 13.5%.
|
||||||||||||||||||
Comparison groups |
Abatacept, 125 mg, Plus Methotrexate, 2.5 mg v Methotrexate, 2.5 mg, Plus Abatacept Placebo
|
||||||||||||||||||
Number of subjects included in analysis |
235
|
||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||
P-value |
= 0.01 | ||||||||||||||||||
Method |
Regression, Logistic | ||||||||||||||||||
Parameter type |
Odds ratio (OR) | ||||||||||||||||||
Point estimate |
2.01
|
||||||||||||||||||
Confidence interval |
|||||||||||||||||||
level |
95% | ||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||
lower limit |
1.18 | ||||||||||||||||||
upper limit |
3.43 | ||||||||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||||||||
Dispersion value |
0.55
|
||||||||||||||||||
Statistical analysis title |
DAS28-CRP Remission at Both Month 12 and 18 | ||||||||||||||||||
Statistical analysis description |
Conditional on statistical significance of the 1st co-primary efficacy analysis (CEA), a sample of 116 subjects per arm would provide 98% power for the 2nd CEA comparison of the percentage of subjects in DAS28-CRP remission at Months 12 and 18 between the abatacept (ABA)+methotrexate (MTX) arm and the MTX monotherapy arm for intent-to treat population. This sample size calculation assumed 30% remission in the ABA+MTX arm and 8% in the monotherapy arm at Month 18 and a 2-sided alpha level of 5%.
|
||||||||||||||||||
Comparison groups |
Abatacept, 125 mg, Plus Methotrexate, 2.5 mg v Methotrexate, 2.5 mg, Plus Abatacept Placebo
|
||||||||||||||||||
Number of subjects included in analysis |
235
|
||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||
P-value |
= 0.045 | ||||||||||||||||||
Method |
Regression, Logistic | ||||||||||||||||||
Parameter type |
Odds ratio (OR) | ||||||||||||||||||
Point estimate |
2.51
|
||||||||||||||||||
Confidence interval |
|||||||||||||||||||
level |
95% | ||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||
lower limit |
1.02 | ||||||||||||||||||
upper limit |
6.18 | ||||||||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||||||||
Dispersion value |
1.15
|
|
|||||||||||||||||||
End point title |
Percentage of Subjects Who Received Monotherapy and Achieved Remission by Disease Activity Score 28 Based on C-reactive Protein (DAS28-CRP) Criteria at Month 12 and at Both Months 12 and 18 [2] | ||||||||||||||||||
End point description |
TP=treatment period; WP=withdrawal period. Remission defined as DAS28-CRP<2.6. The DAS 28-CRP is a measure of disease activity in rheumatoid arthritis (RA) that assesses the 28 joints RA commonly affects; the score includes the number of tender and swollen joints (out of 28), CRP level (a measure of inflammation in the blood), and the subject’s global assessment of health (ranging from very good to very bad). DAS-CRP scores range from 0 to 10, with higher values indicating greater disease activity. Individual measures are fed into a complex mathematical formula to produce the overall DAS (a score >5.1 implies active disease; <3.2, well controlled disease; and <2.6, remission). All randomized subjects who received at least 1 dose of double-blind monotherapy in the Treatment Period. Percentage calculated as a/b, where a=number of subjects who achieved remission at Month 12 and at both Months 12 and 18, and b=number of subjects in the analysis. n=number of evaluable subjects.
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
Randomization to Months 12 and 18
|
||||||||||||||||||
Notes [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint was planned to be assessed for these reporting arms only. |
|||||||||||||||||||
|
|||||||||||||||||||
Statistical analysis title |
DAS28-CRP Remission- Month 12 (Monotherapy) | ||||||||||||||||||
Statistical analysis description |
Odds ratio was based on an Adjusted Logistic Regression test, including treatment, baseline DAS28-CRP value as well as the stratification factor (corticosteroid use at baseline (yes/no))
|
||||||||||||||||||
Comparison groups |
Methotrexate, 2.5 mg, Plus Abatacept Placebo v Abatacept, 125 mg, Plus Methotrexate Placebo
|
||||||||||||||||||
Number of subjects included in analysis |
232
|
||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||
Method |
Regression, Logistic | ||||||||||||||||||
Parameter type |
Odds ratio (OR) | ||||||||||||||||||
Point estimate |
0.92
|
||||||||||||||||||
Confidence interval |
|||||||||||||||||||
level |
95% | ||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||
lower limit |
0.55 | ||||||||||||||||||
upper limit |
1.57 | ||||||||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||||||||
Dispersion value |
0.25
|
||||||||||||||||||
Statistical analysis title |
DAS28-CRP Remission- Month 12 and 18 (Monotherapy) | ||||||||||||||||||
Statistical analysis description |
Odds ratio was based on an Adjusted Logistic Regression test, including treatment, baseline DAS28-CRP value as well as the stratification factor (corticosteroid use at baseline (yes/no))
|
||||||||||||||||||
Comparison groups |
Abatacept, 125 mg, Plus Methotrexate Placebo v Methotrexate, 2.5 mg, Plus Abatacept Placebo
|
||||||||||||||||||
Number of subjects included in analysis |
232
|
||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||
Method |
Regression, Logistic | ||||||||||||||||||
Parameter type |
Odds ratio (OR) | ||||||||||||||||||
Point estimate |
2.04
|
||||||||||||||||||
Confidence interval |
|||||||||||||||||||
level |
95% | ||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||
lower limit |
0.81 | ||||||||||||||||||
upper limit |
5.14 | ||||||||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||||||||
Dispersion value |
0.96
|
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Percentage of Subjects With Remission by Disease Activity Score 28 Based on C-reactive Protein (DAS28-CRP) Criteria Over Time - Intent to Treat Population | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
TP=treatment period; WP=withdrawal period. Remission defined as DAS28-CRP<2.6. The DAS 28-CRP is a measure of disease activity in rheumatoid arthritis (RA) and assesses the 28 joints RA commonly affects; the score includes the number of tender and swollen joints (out of 28), CRP level (a measure of inflammation in the blood), and the subject’s global assessment of health (ranging from very good to very bad). DAS-CRP scores range from 0 to 10, with higher values indicating greater disease activity. Individual measures are fed into a complex mathematical formula to produce the overall DAS (a score greater than 5.1 implies active disease; less than 3.2, well controlled disease; and less than 2.6, remission). Analysis was performed in all the randomized subjects who received at least 1 dose of double-blind study medication in Treatment Period. Percentage calculated as a/b, where a=number of subjects who achieved remission, and b=number of subjects in analysis (intent to treat).
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Randomization to Month 24
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||
End point title |
Adjusted Mean Change From Baseline in Disease Activity Score 28 Based on C-reactive Protein (DAS28-CRP) at Months 6, 12, and 18 | ||||||||||||||||||||||||||||
End point description |
TP=treatment period; WP=withdrawal period. The DAS 28-CRP is a measure of disease activity in rheumatoid arthritis (RA) that assesses the 28 joints RA commonly affects; the score includes the number of tender and swollen joints (out of 28), CRP level (a measure of inflammation in the blood), and the subject’s global assessment of health (ranging from very good to very bad). DAS-CRP scores range from 0 to 10, with higher values indicating greater disease activity. Individual measures are fed into a complex mathematical formula to produce the overall DAS (a score greater than 5.1 implies active disease; less than 3.2, well controlled disease; and less than 2.6, remission). Analysis was performed in all the randomized subjects who received at least 1 dose of double-blind study medication in the Treatment Period. n=number of evaluable subjects.
|
||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||
End point timeframe |
Baseline to Month 18
|
||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||
End point title |
Percentage of Subjects Who Achieved Remission by Criteria of the Simplified Disease Activity Index (SDAI) at Months 12 and 18 | ||||||||||||||||||||||||
End point description |
TP=treatment period; WP=withdrawal period. SDAI-defined remission= ≤3.3. The SDAI was the simple linear sum of 5 outcome parameters: tender joint count (TJC) and swollen joint count (SJC) (based on a 28-joint assessment); subject’s and physician's global assessments of disease activity (assessed on 0-10 cm visual analog scale, on which higher scores=greater affection due to disease activity); and C-reactive protein level (mg/dL). SDAI total score=0-86. SDAI <=3.3 indicates disease remission, >3.4 to 11=low, >11 to 26=moderate, and >26=high disease activity. TJC was assessed at each visit as no swelling=0, swelling=1. TJC was assessed at each visit as no tenderness =0, tenderness = 1. Higher score indicates greater affection due to disease activity. Analysis was performed in all randomized subjects who received at least 1 dose of double-blind study medication in TP. Percentage calculated as a/b, where a=number of subjects who achieved remission, and b=number of subjects in analysis.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Randomization to Month 18
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Adjusted Mean Change From Baseline in Scores on Simplified Disease Activity Index (SDAI) Over Time | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
TP=treatment period; WP=withdrawal period. SDAI-defined remission= ≤3.3. The SDAI is the simple linear sum of 5 outcome parameters: swollen joint count (SJC) and tender joint count (TJC) (based on a 28-joint assessment); subject’s and physician's global assessments of disease activity (assessed on 0-10 cm visual analog scale, on which higher scores=greater affection due to disease activity); and C-reactive protein level (mg/dL). SDAI total score=0-86. SDAI score <=3.3 indicates disease remission, >3.4 to 11=low, >11 to 26=moderate, and >26=high disease activity. SJC is assessed with no swelling=0, swelling=1 (higher score indicates greater swelling). TJC is assessed through identification of painful joints under pressure or to passive motion, with no tenderness=0, tenderness=1 (higher score indicates greater affection due to disease activity). The analysis was performed in Intent to Treat (ITT) population. n= number of subjects with both post baseline and baseline measurements.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Randomization to Month 18
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Percentage of Subjects Achieving a Health Assessment Questionnaire (HAQ) Response Over Time | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
HAQ response defined as a reduction of at least 0.3 units from baseline in score on the Health Assessment Questionnaire Disability Index (HAQ-DI), which assesses subject’s functional ability by rating their abilities over the previous week. The HAQ-DI includes at least 2 questions from each of 8 categories: dressing and grooming, hygiene, arising, reach, eating, grip, walking, and common daily activities. Subjects rate difficulty performing specific tasks: 0=without difficulty, 1=with some difficulty, 2=with much difficulty, and 3=unable to do. The sum of the categories score (the highest scored item in the category) is divided by the number of categories answered, yielding a score from 0-3. Analysis was performed in all randomized subjects who received at least 1 dose of double-blind study medication in the Treatment Period. Percentage calculated as a/b, where a=number of subjects who achieved remission, and b=number of subjects in the analysis.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Randomization to Month 24
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Adjusted Mean Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Response Over Time | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
HAQ response defined as a reduction of at least 0.3 units from baseline in score on the Health Assessment Questionnaire Disability Index (HAQ-DI), which assesses subject’s functional ability by rating their abilities over the previous week. The HAQ-DI includes at least 2 questions from each of 8 categories: dressing and grooming, hygiene, arising, reach, eating, grip, walking, and common daily activities. Subjects rate difficulty performing specific tasks: 0=without difficulty, 1=with some difficulty, 2=with much difficulty, and 3=unable to do. The sum of the categories score (the highest scored item in the category) is divided by the number of categories answered, yielding a score from 0-3. Analysis was performed in all randomized subjects who received at least 1 dose of double-blind study medication in the Treatment Period. Percentage calculated as a/b, where a=number of subjects who achieved remission at Day x, and b=number of subjects in the analysis.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Randomization to Month 24
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||
End point title |
Adjusted Mean Change From Baseline at Months 6, 12, and 18 in Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores of Short Form-36 (SF-36) | ||||||||||||||||||||||||||||||||||||||||
End point description |
TP=treatment period; WP=withdrawal period. The SF-36 is a 36-item self-administered questionnaire developed to assess health-related quality of life (QOL) and comprises 8 domains, including 4 physical (physical health, bodily pain, physical functioning and physical role limitations) and 4 mental (mental health, vitality, social functioning, and emotional role limitation) subscales. Responses are used to derive physical and mental component summary scores, ranging from 0 to 100, with higher scores indicating better QOL (0=Poorest Health; 100=Best Health). Mean change from baseline=post baseline value-baseline value; a higher value signifies improvement. Analysis was performed in all randomized subjects who received at least 1 dose of double-blind study medication in the Treatment Period. n=number of subjects evaluable.
|
||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Randomization to Months 6, 12, and 18
|
||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Adjusted Mean Change From Baseline Over Time in Findings on Magnetic Resonance Imaging (MRI) | ||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
TP=treatment period; WP=withdrawal period. MRI was used to assess joint damage progression at Months 6, 12, and 18. If >20% of joints with a missing score for a parameter (erosion, osteitis, and synovitis), the MRI score of each parameter was considered missing. If ≤20% of joints had a missing score for a parameter, the MRI score was carried forward from the previous MRI assessment, or carried backward from the next MRI assessment, if missing score occurred at baseline. MRI total score ranged from 0 (best outcome) to 4 (worst outcome). A gadolinium-enhanced MRI of the dominant hand-wrist was performed on all randomized subjects at 5 points. MRI examination was standardized to ensure sufficient image quality for the evaluation of radiographic progression of rheumatoid arthritis. Analysis was performed in all randomized subjects who received at least 1 dose of double-blind study medication in the Treatment Period. n=number of subjects with both baseline and post-baseline measurements.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Randomization to Month 18
|
||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||
End point title |
Number of Subjects With Death as Outcome, Serious Adverse Events (SAEs), Related SAEs, Discontinuations Due to SAEs, Related Adverse Events (AEs), and Discontinuations Due to AEs During the Treatment Period | ||||||||||||||||||||||||||||||||||||
End point description |
AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Related=having certain, probable, possible, or unknown relationship to study drug. Analysis was performed in all the randomized subjects who received at least 1 dose of double-blind study medication in the Treatment Period.
|
||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||
End point timeframe |
Day 1 to up to 56 days following the last dosing day (Day 365); all deaths during study period, including those that occurred >56 days after last dose in Treatment Period
|
||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||
End point title |
Number of Subjects With Adverse Events (AEs) of Interest During the Treatment Period | ||||||||||||||||||||||||||||
End point description |
AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Related=having certain, probable, possible, or unknown relationship to study drug. AEs of special interest are events potentially associated with the drug or disease under study. Analysis was performed in all the randomized subjects who received at least 1 dose of double-blind study medication in the Treatment Period.
|
||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||
End point timeframe |
Day 1 to 56 days following last dosing day (Day 365)
|
||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Number of Subjects With Results on Hematology and Clinical Laboratory Tests Meeting the Criteria for Marked Abnormality During Treatment Period | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Lower limit of normal (LLN); Upper limit of normal (ULN); Pretreatment (preRX). Criteria for marked abnormality: Platelet count (*10^9 c/µL) >1.5*ULN; potassium, serum (mEq) <0.9*LLN, or if preRX <LLN, use <0.9*preRX; blood urea nitrogen (mg/dL) >2*preRX; creatinine (mg/dL) >1.5*preRX; ALT (U/L) >3*ULN, or if preRX>ULN, use >4*preRX; AST (U/L) >3*ULN, or if preRX>ULN, use >4*preRX; ALP (U/L) >2*ULN, or if preRX>ULN, use >3*preRX; GGT (U/L) >2*ULN, or if preRX>ULN, use >3*preRX; glucose, fasting (mg/dL) <0.8*LLN or >1.5*ULN, or if preRX<LLN use <0.8*preRX or >ULN if preRX >ULN, use >2.0*preRX or OR <LLN; glucose, serum (mg/dL) <65 or >220; uric acid (mg/dL)>1.5*ULN, or if preRX, use >2*preRX; albumin (g/dL) <0.9*LLN, or if preRX<LLN, use <0.75*preRX; hemoglobin (g/dL)>3 decrease from preRX; hematocrit (%) <0.75*preRX. Analysis was performed in all randomized subjects who received at least 1 dose in Treatment Period. n=number of evaluable subjects.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Day 1 up to 56 days following the last dosing day in the Treatment Period (Day 365)
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||
End point title |
Percentage of Subjects With Remission by Disease Activity Score 28 Based on C-reactive Protein (DAS28-CRP) Criteria Over Time During Withdrawal Period- Treated subjects in Remission at Month 12 | ||||||||||||||||||||||||||||||||||||||||
End point description |
WP=withdrawal period. Remission defined as DAS28-CRP<2.6. The DAS 28-CRP is a measure of disease activity in rheumatoid arthritis (RA) and assesses the 28 joints RA commonly affects; the score includes the number of tender and swollen joints (out of 28), CRP level (a measure of inflammation in the blood), and the subject’s global assessment of health (ranging from very good to very bad). DAS-CRP scores range from 0 to 10, with higher values indicating greater disease activity. The overall DAS score greater than 5.1 implies active disease; less than 3.2, well controlled disease; and less than 2.6, remission. Percentage= number of subjects with remission divided by number of subjects who were analyzed (all treated subjects who were in remission at end of treatment period and entered the Withdrawal Period). Analysis was performed in all the treated subjects who were in remission at Month 12 (DAS28-CRP<2.6) and entered the Withdrawal Period. (N=number of subjects analyzed).
|
||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||
End point timeframe |
End of Treatment Period (Month 12) to End of Withdrawal Period (Month 24)
|
||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Percentage of Subjects Who Achieved Remission by Criteria of the Simplified Disease Activity Index (SDAI) Over Time in Treatment Period (TP) and Withdrawal Period (WP) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
SDAI-defined remission as ≤3.3. The SDAI is simple linear sum of 5 outcome parameters: tender joint count (TJC); swollen joint count (SJC) (based on a 28-joint assessment); subject’s and physician's global assessments of disease activity (assessed on 0-10 cm visual analog scale, higher score=greater affection due to disease activity); and C-reactive protein level (mg/dL). SDAI total score=0-86. SDAI <=3.3 indicates disease remission, >3.4 to 11=low, >11 to 26=moderate, and >26=high disease activity. TJC was assessed as no swelling=0, swelling=1. SJC is assessed through painful joints under pressure or to passive motion. TJC is assessed as no tenderness =0, tenderness = 1. Higher score=greater affection due to disease activity. Percent=number with remission/number evaluated. Analysis was performed in all randomized subjects who received at least 1 dose in TP. Subjects were grouped according to treatment regimen to which they were randomized. N= number of subject evaluated.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Randomization to Month 24
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||
End point title |
Number of Subjects With Death as Outcome, Serious Adverse Events (SAEs) and Discontinuations Due to AEs During the Full Study (All Periods) | ||||||||||||||||||||||||
End point description |
AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Includes data up to last active dose date +56 days if the subjects discontinued the Treatment Period or did not enter the Withdrawal Period, up to the day of discontinuation in the Withdrawal Period for subjects discontinuing the Withdrawal Period without entering the Re-exposure Period (RP), up to Day 729 visit (Month 24) for subjects who complete the Withdrawal Period, and up to 56 days post last active dose in Re-exposure Period for subjects entering the Re-exposure Period. Analysis was performed in all the randomized subjects who received at least 1 dose of study medication.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Day 1 to 56 days post last dose (TP: Day 365; WP: >56 days after last dose in TP, up to Month 24; RP: first dose to last dose + 56 days, up to Month 30
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||
End point title |
Number of subjects with Adverse Events (AEs) of Interest During the Withdrawal Period AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that | ||||||||||||||||||||||||||||
End point description |
AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. AEs of special interest are events potentially associated with the drug or disease under study. Includes events with an onset date on or after 57 days post last dosing day (active abatacept or active MTX whichever is the later) in the Treatment Period (TP) and up to end of Withdrawal Period. Treatment groups represent treatment received during the TP. Analysis was performed in all the randomized subjects who received at least 1 dose of double-blind study medication in the TP and entered the Withdrawal Period.
|
||||||||||||||||||||||||||||
End point type |
Secondary
|
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End point timeframe |
Last dose in TP + 57 days, up to Month 24
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No statistical analyses for this end point |
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End point title |
Number of subjects with Adverse Events (AEs) of Interest During the Re-exposure Period | ||||||||||||||||||||||||||||
End point description |
AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. AEs of special interest are events potentially associated with the drug or disease under study. Includes data up to 56 days post the last dosing day (active abatacept or active MTX, whichever is the later) in the Re-exposure Period. Treatment groups represent Treatment received during Treatment Period.
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End point type |
Secondary
|
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End point timeframe |
End of Withdrawal Period (up to Month 24) up to last dose of Re-exposure Period + 56 days
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No statistical analyses for this end point |
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End point title |
Number of Subjects With Results on Hematology and Clinical Laboratory Tests Meeting the Criteria for Marked Abnormality in Withdrawal Period | ||||||||||||||||||||||||||||||||||||||||
End point description |
LLN=lower limit of normal; ULN=upper limit of normal; preRX=pretreatment. Criteria for marked abnormality on laboratory test results: creatinine (mg/dL) >1.5*preRX; ALT (U/L) >3*ULN, or if preRX>ULN, use >4*preRX; G-glutamyl transferase (GGT) (U/L) >2*ULN, or if preRX>ULN, use >3*preRX; glucose, fasting (mg/dL) <0.8*LLN or >1.5*ULN, or if preRX<LLN use <0.8*preRX or >ULN if preRX >ULN, use >2.0*preRX or OR <LLN; glucose, serum (mg/dL) <65 or >220; uric acid (mg/dL)>1.5*ULN, or if preRX, use >2*preRX; hemoglobin (g/dL)>3 decrease from preRX. Analysis was performed in all the randomized subjects who received at least 1 dose of study drug in the Treatment Period, entered the Withdrawal Period, and had values available. n=number of subjects evaluable.
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End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||
End point timeframe |
End of Withdrawal Period (up to Month 24) up to last dose of Re-exposure Period + 56 days
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No statistical analyses for this end point |
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|||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Number of Subjects With Results on Hematology and Clinical Laboratory Tests Meeting the Criteria for Marked Abnormality in Re-exposure Period | ||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
LLN=lower limit of normal; ULN=upper limit of normal; preRX=pretreatment. Criteria for marked abnormality on laboratory test results: creatinine (mg/dL) >1.5*preRX; ALT (U/L) >3*ULN, or if preRX>ULN, use >4*preRX; AST (U/L) >3*ULN, or if preRX>ULN, use >4*preRX; ALP (U/L) >2*ULN, or if preRX>ULN, use >3*preRX; G-glutamyl transferase U/L) >2*ULN, or if preRX>ULN, use >3*preRX; glucose, fasting (mg/dL) <0.8*LLN or >1.5*ULN, or if preRX<LLN use <0.8*preRX or >ULN if preRX >ULN, use >2.0*preRX or OR <LLN; glucose, serum (mg/dL) <65 or >220; hemoglobin (g/dL)>3 decrease from preRX; hematocrit (%) < 0.75*preRX. Analysis was performed in all all the treated subjects entering the Re-exposure Period and having measurements available were analyzed. n= number of subjects evaluable. Treatment groups represent Treatment received during Treatment Period.
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End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Start of re-exposure period to 56 days post last dose, up to Month 30
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No statistical analyses for this end point |
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Adverse events information
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Timeframe for reporting adverse events |
Day 1 to last dose + 56 days, up to 30 Months
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
17.1
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Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Abatacept, 125 mg, Plus Methotrexate, 2.5 mg
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Subjects received abatacept, 125 mg subcutaneously, plus methotrexate (MTX), 2.5 mg orally as tablets, with a target dose range of 10-20 mg weekly, during the 12-month Treatment Period. Subjects with a Low Disease Activity Score (LDAS) defined as DAS28-CRP score of <3.2 at Month 12 (end of Treatment Period) entered the Withdrawal Period for up to 12 months, during which all study medication was withdrawn. Subjects with a DAS28-CRP score of >3.2 were discontinued from the study. All MTX and corticosteroids, if not already discontinued, were to be tapered off during the first month of the Withdrawal Period. Subjects who experienced a worsening of rheumatoid arthritis (RA) symptoms or a RA flare after at least 3 months in the Withdrawal Period were eligible to enroll into a 6-month Re-exposure Period, during which they received open-label treatment with abatacept subcutaneous (SC) 125 mg/week and MTX. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Abatacept, 125 mg, Plus Methotrexate Placebo
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Subjects received abatacept, 125 mg subcutaneously, plus methotrexate placebo tablets orally, once weekly during the 12-month Treatment Period. Subjects with a Low Disease Activity Score (LDAS) defined as DAS28-CRP score of <3.2 at Month 12 (end of Treatment Period) entered the Withdrawal Period for up to 12 months, during which all study medication was withdrawn. Subjects with a DAS28-CRP score of >3.2 were discontinued from the study. Subjects who experienced a worsening of rheumatoid arthritis (RA) symptoms or a RA flare after at least 3 months in the Withdrawal Period were eligible to enroll into a 6-month Re-exposure Period, during which they received open-label treatment with abatacept SC (125 mg/week) and MTX. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Methotrexate, 2.5 mg, Plus Abatacept Placebo
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Subjects received methotrexate, 2.5 mg orally as tablets, with a target dose range of 10-20 mg weekly, plus abatacept placebo subcutaneously, once weekly during the 12-month Treatment Period. Subjects with a Low Disease Activity Score (LDAS) defined as DAS28-CRP score of < 3.2 at Month 12 (end of Treatment Period) entered the Withdrawal Period for up to 12 months, during which all study medication was withdrawn. Subjects with a DAS28-CRP score of >3.2 were discontinued from the study. All MTX and corticosteroids, if not already discontinued, were to be tapered off during the first month of the Withdrawal Period. Subjects who experienced a worsening of rheumatoid arthritis (RA) symptoms or a RA flare after at least 3 months in the Withdrawal Period were eligible to enroll into a 6-month Re-exposure Period, during which they received open-label treatment with abatacept SC (125 mg/week) and MTX. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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17 May 2011 |
Incidences of Disease Activity Score was updated to Disease Activity Score 28 using C-reactive protein and time frame for stable oral corticosteroid use as well as routes of administration were updated. |
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Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |