Trial Outcomes & Findings for A Study of MabThera (Rituximab) in Patients With Rheumatoid Arthritis Who Have Had an Inadequate Response to a Single Anti-TNF Inhibitor (NCT NCT02079532)
NCT ID: NCT02079532
Last Updated: 2016-07-29
Results Overview
The DAS28 consists of swollen joint count (SJC) and tender joint count (TJC) measurements, the erythrocyte sedimentation rate (ESR) in millimeters per hour (mm/hr), and the Patient's Global Assessment of Disease Activity (participant-ated rheumatoid arthritis \[RA\] activity assessment) with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity). DAS28 less than or equal to (≤)3.2 equals (=) low disease activity, DAS28 greater than (\>)3.2 to 5.1 = moderate to high disease activity.
COMPLETED
PHASE3
302 participants
Week 24
2016-07-29
Participant Flow
Participant milestones
| Measure |
Rituximab Plus Methotrexate (MTX)
Participants received rituximab, 1 gram (g), intravenously (IV), and methylprednisolone 100 mg, IV, on Days 1 and 15. Participants should have also been receiving MTX as mandatory background therapy. MTX was to have been started at least 3 months prior to the first infusion and must have been given at stable doses for at least 4 weeks prior to the first infusion.
|
|---|---|
|
Overall Study
STARTED
|
302
|
|
Overall Study
COMPLETED
|
273
|
|
Overall Study
NOT COMPLETED
|
29
|
Reasons for withdrawal
| Measure |
Rituximab Plus Methotrexate (MTX)
Participants received rituximab, 1 gram (g), intravenously (IV), and methylprednisolone 100 mg, IV, on Days 1 and 15. Participants should have also been receiving MTX as mandatory background therapy. MTX was to have been started at least 3 months prior to the first infusion and must have been given at stable doses for at least 4 weeks prior to the first infusion.
|
|---|---|
|
Overall Study
Adverse Event
|
7
|
|
Overall Study
Additional or changed therapy
|
2
|
|
Overall Study
Lack of Efficacy
|
9
|
|
Overall Study
Protocol Violation
|
3
|
|
Overall Study
Withdrawal by Subject
|
1
|
|
Overall Study
Administrative problems
|
1
|
|
Overall Study
Inclusion into ReFIRST
|
3
|
|
Overall Study
Other
|
3
|
Baseline Characteristics
A Study of MabThera (Rituximab) in Patients With Rheumatoid Arthritis Who Have Had an Inadequate Response to a Single Anti-TNF Inhibitor
Baseline characteristics by cohort
| Measure |
Rituximab + MTX
n=302 Participants
Participants received rituximab, 1 g, IV, and methylprednisolone 100 mg, IV, on Days 1 and 15. Participants should have also been receiving MTX as mandatory background therapy. MTX was to have been started at least 3 months prior to the first infusion and must have been given at stable doses for at least 4 weeks prior to the first infusion.
|
|---|---|
|
Age, Continuous
|
54.4 years
STANDARD_DEVIATION 18.77 • n=99 Participants
|
|
Sex: Female, Male
Female
|
228 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
74 Participants
n=99 Participants
|
|
Race/Ethnicity, Customized
Caucasian
|
301 participants
n=99 Participants
|
|
Race/Ethnicity, Customized
Asian
|
1 participants
n=99 Participants
|
PRIMARY outcome
Timeframe: Week 24Population: Intent to Treat (ITT) population: all participants who signed informed consent, received at least 1 dose of study drug, and where DAS28 was measured at least once under study medication (Weeks 8, 16, or 24 or unscheduled or withdrawal visit up to Week 24); those with no RA or no DAS28 score at screening were excluded, regardless if treated or not.
The DAS28 consists of swollen joint count (SJC) and tender joint count (TJC) measurements, the erythrocyte sedimentation rate (ESR) in millimeters per hour (mm/hr), and the Patient's Global Assessment of Disease Activity (participant-ated rheumatoid arthritis \[RA\] activity assessment) with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity). DAS28 less than or equal to (≤)3.2 equals (=) low disease activity, DAS28 greater than (\>)3.2 to 5.1 = moderate to high disease activity.
Outcome measures
| Measure |
Rituximab + MTX
n=291 Participants
Participants received rituximab, 1 g, IV, and methylprednisolone 100 mg, IV, on Days 1 and 15. Participants should have also been receiving MTX as mandatory background therapy. MTX was to have been started at least 3 months prior to the first infusion and must have been given at stable doses for at least 4 weeks prior to the first infusion.
|
|---|---|
|
Change From Baseline to Week 24 in Disease Activity Score Based on 28-Joint Count (DAS28)
|
-1.56 scores on a scale
Standard Deviation 1.40
|
SECONDARY outcome
Timeframe: Screening and Weeks 8, 16, and 24Population: ITT population; n (number) = number of participants assessed at a given visit.
The DAS28 consists of SJC and TJC measurements, the ESR in mm/hr, and the Patient's Global Assessment of Disease Activity (participant-rated RA assessment) with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity). DAS28 ≤3.2 = low disease activity, DAS28 \>3.2 to 5.1 = moderate to high disease activity.
Outcome measures
| Measure |
Rituximab + MTX
n=291 Participants
Participants received rituximab, 1 g, IV, and methylprednisolone 100 mg, IV, on Days 1 and 15. Participants should have also been receiving MTX as mandatory background therapy. MTX was to have been started at least 3 months prior to the first infusion and must have been given at stable doses for at least 4 weeks prior to the first infusion.
|
|---|---|
|
DAS28 Score
Screening (n=291)
|
5.87 scores on a scale
Standard Deviation 1.05
|
|
DAS28 Score
Week 8 (n=277)
|
4.57 scores on a scale
Standard Deviation 1.30
|
|
DAS28 Score
Week 16 (n=271)
|
4.17 scores on a scale
Standard Deviation 1.31
|
|
DAS28 Score
Week 24 (n=266)
|
4.30 scores on a scale
Standard Deviation 1.47
|
SECONDARY outcome
Timeframe: Weeks 8, 16, and 24Population: ITT population; n=number of participants assessed at a given visit
The DAS28-based EULAR response criteria were used to measure individual responses as none, good, and moderate, depending on the extent of change from baseline and the level of disease activity reached. Good responders experienced a change from baseline of \>1.2 with a DAS28 score ≤3.2 and moderate responders experienced a change from baseline \>1.2 with DAS28 \>3.2 to ≤5.1 or a change from baseline \>0.6 to ≤1.2 with a DAS28 score of ≤5.1.
Outcome measures
| Measure |
Rituximab + MTX
n=291 Participants
Participants received rituximab, 1 g, IV, and methylprednisolone 100 mg, IV, on Days 1 and 15. Participants should have also been receiving MTX as mandatory background therapy. MTX was to have been started at least 3 months prior to the first infusion and must have been given at stable doses for at least 4 weeks prior to the first infusion.
|
|---|---|
|
Percentage of Participants With European League Against Rheumatism (EULAR) Response of Good or Moderate
Week 8 (n=172)
|
59.1 percentage of participants
|
|
Percentage of Participants With European League Against Rheumatism (EULAR) Response of Good or Moderate
Week 16 (n=198)
|
68.0 percentage of participants
|
|
Percentage of Participants With European League Against Rheumatism (EULAR) Response of Good or Moderate
Week 24 (n=188)
|
64.6 percentage of participants
|
SECONDARY outcome
Timeframe: Week 24Population: ITT population
Percentage of participants with low disease activity defined as DAS28 ≤3.2 at follow-up Week 24. The DAS28 consists of SJC and TJC measurements, the ESR in mm/hr, and the Patient's Global Assessment of Disease Activity (participant rated arthritis activity assessment) with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity).
Outcome measures
| Measure |
Rituximab + MTX
n=291 Participants
Participants received rituximab, 1 g, IV, and methylprednisolone 100 mg, IV, on Days 1 and 15. Participants should have also been receiving MTX as mandatory background therapy. MTX was to have been started at least 3 months prior to the first infusion and must have been given at stable doses for at least 4 weeks prior to the first infusion.
|
|---|---|
|
Percentage of Participants With Low Disease Activity (DAS28 ≤3.2) at Week 24
|
21.6 percentage of participants
|
SECONDARY outcome
Timeframe: Week 24Population: ITT population
Percentage of participants with remission defined as DAS28 \<2.6 at follow-up Week 24. The DAS28 consists of SJC and TJC measurements, the ESR in mm/hr, and the Patient's Global Assessment of Disease Activity (participant rated arthritis activity assessment) with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity). DAS28 ≤3.2 = low disease activity, DAS28 \>3.2 to 5.1 = moderate to high disease activity.
Outcome measures
| Measure |
Rituximab + MTX
n=291 Participants
Participants received rituximab, 1 g, IV, and methylprednisolone 100 mg, IV, on Days 1 and 15. Participants should have also been receiving MTX as mandatory background therapy. MTX was to have been started at least 3 months prior to the first infusion and must have been given at stable doses for at least 4 weeks prior to the first infusion.
|
|---|---|
|
Percentage of Participants Achieving Remission (DAS28 <2.6) at Week 24
|
11.7 percentage of participants
|
SECONDARY outcome
Timeframe: Weeks 8, 16, and 24Population: ITT population
Percentage of participants achieving a response by EULAR category, including 'moderate', 'good', or no response at follow-up Weeks 8, 16, and 24. The DAS28-based EULAR response criteria were used to measure individual response as none, good, and moderate, depending on the extent of change from baseline and the level of disease activity reached. Good responders had a change from baseline \>1.2 with a DAS28 score ≤ 3.2; moderate responders had a change from baseline \>1.2 with a DAS28 score of \>3.2 to ≤5.1 or a change from baseline \>0.6 to ≤1.2 with a DAS28 score of ≤5.1; non-responders had a change from baseline ≤0.6 or change from baseline \>0.6 and ≤1.2 with a DAS28 score of \>5.1.
Outcome measures
| Measure |
Rituximab + MTX
n=291 Participants
Participants received rituximab, 1 g, IV, and methylprednisolone 100 mg, IV, on Days 1 and 15. Participants should have also been receiving MTX as mandatory background therapy. MTX was to have been started at least 3 months prior to the first infusion and must have been given at stable doses for at least 4 weeks prior to the first infusion.
|
|---|---|
|
Percentage of Participants Achieving a Response By EULAR Category
Moderate response, Week 8
|
45.4 percentage of participants
|
|
Percentage of Participants Achieving a Response By EULAR Category
Moderate response, Week 16
|
44.3 percentage of participants
|
|
Percentage of Participants Achieving a Response By EULAR Category
Moderate response, Week 24
|
44.0 percentage of participants
|
|
Percentage of Participants Achieving a Response By EULAR Category
Good response, Week 8
|
13.7 percentage of participants
|
|
Percentage of Participants Achieving a Response By EULAR Category
Good response, Week 16
|
23.7 percentage of participants
|
|
Percentage of Participants Achieving a Response By EULAR Category
Good response, Week 24
|
20.6 percentage of participants
|
|
Percentage of Participants Achieving a Response By EULAR Category
No response, Week 8
|
36.1 percentage of participants
|
|
Percentage of Participants Achieving a Response By EULAR Category
No response, Week 16
|
25.1 percentage of participants
|
|
Percentage of Participants Achieving a Response By EULAR Category
No response, Week 24
|
26.8 percentage of participants
|
SECONDARY outcome
Timeframe: Screening and Weeks 8, 16, and 24Population: ITT population; n=number of participants assessed at a given visit.
The HAQ-DI score consists of questions referring to 8 categories: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and common daily activities. For each of the categories, participants reported the amount of difficulty they had in performing 2 or 3 specific sub-category items. The standard disability score was calculated from the 8 categories by dividing the sum of the individual categories by the number of categories answered, yielding a score from 0 (without any difficulty) to 3 (unable to do).
Outcome measures
| Measure |
Rituximab + MTX
n=291 Participants
Participants received rituximab, 1 g, IV, and methylprednisolone 100 mg, IV, on Days 1 and 15. Participants should have also been receiving MTX as mandatory background therapy. MTX was to have been started at least 3 months prior to the first infusion and must have been given at stable doses for at least 4 weeks prior to the first infusion.
|
|---|---|
|
Health Assessment Questionnaire - Disability Index (HAQ-DI) Score
Week 24 (n=269)
|
1.32 scores on a scale
Standard Deviation 0.70
|
|
Health Assessment Questionnaire - Disability Index (HAQ-DI) Score
Screening (n=288)
|
1.60 scores on a scale
Standard Deviation 0.67
|
|
Health Assessment Questionnaire - Disability Index (HAQ-DI) Score
Week 8 (n=286)
|
1.43 scores on a scale
Standard Deviation 0.66
|
|
Health Assessment Questionnaire - Disability Index (HAQ-DI) Score
Week 16 (n=276)
|
1.33 scores on a scale
Standard Deviation 0.66
|
SECONDARY outcome
Timeframe: Screening and Weeks 8, 16, and 24Population: ITT population; n=number of participants assessed at a given visit.
The FACIT fatigue scale is base on a 13-item questionnaire to assess the therapy-induced fatigue. Participants were requested to score each question on a scale ranging from 0 (best) to 4 (worst). The scoring system of the FACIT fatigue scale adds up to a total scale ranging from 0 (best) to 52 (worst). The assessment was originally developed for chronic illnesses and is now validated for patients with rheumatoid arthritis (RA). The questionnaire was provided in a German translation.
Outcome measures
| Measure |
Rituximab + MTX
n=291 Participants
Participants received rituximab, 1 g, IV, and methylprednisolone 100 mg, IV, on Days 1 and 15. Participants should have also been receiving MTX as mandatory background therapy. MTX was to have been started at least 3 months prior to the first infusion and must have been given at stable doses for at least 4 weeks prior to the first infusion.
|
|---|---|
|
Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Score
Screening (n=286)
|
23.81 scores on a scale
Standard Deviation 11.35
|
|
Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Score
Week 8 (n=282)
|
20.87 scores on a scale
Standard Deviation 11.14
|
|
Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Score
Week 16 (n=272)
|
18.92 scores on a scale
Standard Deviation 11.46
|
|
Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Score
Week 24 (n=262)
|
18.53 scores on a scale
Standard Deviation 11.48
|
SECONDARY outcome
Timeframe: Screening and Weeks 8, 16, and 24Population: ITT population; n=number of participants assessed at a given visit.
The SF-36 is a multi-purpose, short-form health survey with 36 questions. It yields an 8-scale profile of functional health and well-being scores (domains) as well as psychometrically based physical and mental health summary measures. The SF-36 taps 8 health concepts: physical functioning, bodily pain, physical role functioning, emotional role functioning, emotional well-being, social functioning, vitality, and general health perceptions. The 8 scales are further summarized to 2 distinct higher-ordered clusters: the physical and mental composite t-scores (PCS and MCS). The range for all 8 domains as well as for the composite t-scores is from 0 to 100 with 100 as best possible health status and 0 as worst health status.
Outcome measures
| Measure |
Rituximab + MTX
n=291 Participants
Participants received rituximab, 1 g, IV, and methylprednisolone 100 mg, IV, on Days 1 and 15. Participants should have also been receiving MTX as mandatory background therapy. MTX was to have been started at least 3 months prior to the first infusion and must have been given at stable doses for at least 4 weeks prior to the first infusion.
|
|---|---|
|
Short-Form 36 (SF-36) Physical Composite Scores (PCS) and Mental Composite Scores (MCS)
PCS, Screening (n=287)
|
30.97 scores on a scale
Standard Deviation 8.14
|
|
Short-Form 36 (SF-36) Physical Composite Scores (PCS) and Mental Composite Scores (MCS)
PCS, Week 8 (n=279)
|
34.24 scores on a scale
Standard Deviation 8.56
|
|
Short-Form 36 (SF-36) Physical Composite Scores (PCS) and Mental Composite Scores (MCS)
PCS, Week 16 (n=270)
|
35.92 scores on a scale
Standard Deviation 8.43
|
|
Short-Form 36 (SF-36) Physical Composite Scores (PCS) and Mental Composite Scores (MCS)
PCS, Week 24 (n=264)
|
36.36 scores on a scale
Standard Deviation 9.00
|
|
Short-Form 36 (SF-36) Physical Composite Scores (PCS) and Mental Composite Scores (MCS)
MCS, Screening (n=287)
|
40.88 scores on a scale
Standard Deviation 13.16
|
|
Short-Form 36 (SF-36) Physical Composite Scores (PCS) and Mental Composite Scores (MCS)
MCS, Week 8 (n=279)
|
43.50 scores on a scale
Standard Deviation 12.31
|
|
Short-Form 36 (SF-36) Physical Composite Scores (PCS) and Mental Composite Scores (MCS)
MCS, Week 16 (n=270)
|
45.17 scores on a scale
Standard Deviation 12.32
|
|
Short-Form 36 (SF-36) Physical Composite Scores (PCS) and Mental Composite Scores (MCS)
MCS, Week 24 (n=264)
|
44.92 scores on a scale
Standard Deviation 13.13
|
SECONDARY outcome
Timeframe: Screening and Weeks 8, 16, and 24Population: ITT population; n=number of participants assessed at a given visit.
The SF-36 is a multi-purpose, short-form health survey with 36 questions. It yields an 8-scale profile of functional health and well-being scores (domains) as well as psychometrically based physical and mental health summary measures. The SF-36 taps 8 health concepts: physical functioning, bodily pain, physical role functioning, emotional role functioning, emotional well-being, social functioning, vitality, and general health perceptions. The 8 scales are further summarized to two distinct higher-ordered clusters: the physical and mental composite t-scores (PCS and MCS). The range for all 8 domains as well as for the composite t-scores is from 0 to 100 with 100 as best possible health status and 0 as worst health status.
Outcome measures
| Measure |
Rituximab + MTX
n=291 Participants
Participants received rituximab, 1 g, IV, and methylprednisolone 100 mg, IV, on Days 1 and 15. Participants should have also been receiving MTX as mandatory background therapy. MTX was to have been started at least 3 months prior to the first infusion and must have been given at stable doses for at least 4 weeks prior to the first infusion.
|
|---|---|
|
SF-36 Domain Scores
Physical functioning, Screening (n=289)
|
39.04 scores on a scale
Standard Deviation 24.83
|
|
SF-36 Domain Scores
Physical functioning, Week 8 (n=284)
|
43.60 scores on a scale
Standard Deviation 24.50
|
|
SF-36 Domain Scores
Physical functioning, Week 16 (n=276)
|
44.64 scores on a scale
Standard Deviation 25.13
|
|
SF-36 Domain Scores
Physical functioning, Week 24 (n=268)
|
47.37 scores on a scale
Standard Deviation 26.19
|
|
SF-36 Domain Scores
Bodily pain, Screening (n=290)
|
25.94 scores on a scale
Standard Deviation 17.75
|
|
SF-36 Domain Scores
Bodily pain, Week 8 (n=285)
|
37.24 scores on a scale
Standard Deviation 19.00
|
|
SF-36 Domain Scores
Bodily pain, Week 16 (n=275)
|
44.25 scores on a scale
Standard Deviation 21.60
|
|
SF-36 Domain Scores
Bodily pain, Week 24 (n=267)
|
44.06 scores on a scale
Standard Deviation 22.13
|
|
SF-36 Domain Scores
Physical role functioning, Screening (n=290)
|
35.11 scores on a scale
Standard Deviation 22.42
|
|
SF-36 Domain Scores
Physical role functioning, Week 8 (n=284)
|
43.72 scores on a scale
Standard Deviation 23.95
|
|
SF-36 Domain Scores
Physical role functioning, Week 16 (n=276)
|
48.37 scores on a scale
Standard Deviation 23.48
|
|
SF-36 Domain Scores
Physical role functioning, Week 24 (n=269)
|
49.63 scores on a scale
Standard Deviation 25.04
|
|
SF-36 Domain Scores
Emotional role functioning, Screening (n=289)
|
52.77 scores on a scale
Standard Deviation 31.23
|
|
SF-36 Domain Scores
Emotional role functioning, Week 8 (n=282)
|
59.13 scores on a scale
Standard Deviation 27.26
|
|
SF-36 Domain Scores
Emotional role functioning, Week 16 (n=276)
|
62.41 scores on a scale
Standard Deviation 27.57
|
|
SF-36 Domain Scores
Emotional role functioning, Week 24 (n=268)
|
61.29 scores on a scale
Standard Deviation 27.98
|
|
SF-36 Domain Scores
Emotional well-being, Screening (n=289)
|
56.11 scores on a scale
Standard Deviation 20.07
|
|
SF-36 Domain Scores
Emotional well-being, Week 8 (n=285)
|
60.43 scores on a scale
Standard Deviation 19.82
|
|
SF-36 Domain Scores
Emotional well-being, Week 16 (n=276)
|
63.02 scores on a scale
Standard Deviation 20.51
|
|
SF-36 Domain Scores
Emotional well-being, Week 24 (n=268)
|
64.03 scores on a scale
Standard Deviation 21.03
|
|
SF-36 Domain Scores
Social functioning, Screening (n=291)
|
56.62 scores on a scale
Standard Deviation 27.23
|
|
SF-36 Domain Scores
Social functioning, Week 8 (n=285)
|
64.04 scores on a scale
Standard Deviation 25.87
|
|
SF-36 Domain Scores
Social functioning, Week 16 (n=277)
|
65.93 scores on a scale
Standard Deviation 26.10
|
|
SF-36 Domain Scores
Social functioning, Week 24 (n=270)
|
66.99 scores on a scale
Standard Deviation 28.11
|
|
SF-36 Domain Scores
Vitality, Screening (n=290)
|
38.49 scores on a scale
Standard Deviation 19.41
|
|
SF-36 Domain Scores
Vitality, Week 8 (n=285)
|
43.42 scores on a scale
Standard Deviation 19.76
|
|
SF-36 Domain Scores
Vitality, Week 16 (n=276)
|
48.25 scores on a scale
Standard Deviation 20.32
|
|
SF-36 Domain Scores
Vitality, Week 24 (n=268)
|
48.22 scores on a scale
Standard Deviation 20.75
|
|
SF-36 Domain Scores
General health perceptions, Screening (n=291)
|
39.14 scores on a scale
Standard Deviation 14.49
|
|
SF-36 Domain Scores
General health perceptions, Week 8 (n=285)
|
45.61 scores on a scale
Standard Deviation 15.06
|
|
SF-36 Domain Scores
General health perceptions, Week 16 (n=272)
|
48.54 scores on a scale
Standard Deviation 17.16
|
|
SF-36 Domain Scores
General health perceptions, Week 24 (n=269)
|
48.30 scores on a scale
Standard Deviation 17.53
|
SECONDARY outcome
Timeframe: Weeks 8, 16, and 24Population: ITT population
ACR20/50/70 response: ≥20%, ≥50%, or ≥70% improvement, respectively, in tender or swollen joint counts and ≥20%, ≥50%, or ≥70% improvement, respectively, in 3 of the following 5 criteria: 1) Physician's Global Assessment of Disease Activity, 2) Patient's Global Assessment of Disease Activity, 3) Patient's Assessment of Pain, 4) participant assessment of functional disability via a HAQ-DI, and 5) C-reactive protein or ESR at each visit.
Outcome measures
| Measure |
Rituximab + MTX
n=291 Participants
Participants received rituximab, 1 g, IV, and methylprednisolone 100 mg, IV, on Days 1 and 15. Participants should have also been receiving MTX as mandatory background therapy. MTX was to have been started at least 3 months prior to the first infusion and must have been given at stable doses for at least 4 weeks prior to the first infusion.
|
|---|---|
|
Percentage of Participants Achieving American College of Rheumatology (ACR) 20 Percent (%), 50% or 70% Response (ACR20/ACR50/ACR70)
ACR20, Week 8
|
38.8 percentage of participants
|
|
Percentage of Participants Achieving American College of Rheumatology (ACR) 20 Percent (%), 50% or 70% Response (ACR20/ACR50/ACR70)
ACR20, Week 16
|
47.8 percentage of participants
|
|
Percentage of Participants Achieving American College of Rheumatology (ACR) 20 Percent (%), 50% or 70% Response (ACR20/ACR50/ACR70)
ACR20, Week 24
|
46.4 percentage of participants
|
|
Percentage of Participants Achieving American College of Rheumatology (ACR) 20 Percent (%), 50% or 70% Response (ACR20/ACR50/ACR70)
ACR50, Week 8
|
13.7 percentage of participants
|
|
Percentage of Participants Achieving American College of Rheumatology (ACR) 20 Percent (%), 50% or 70% Response (ACR20/ACR50/ACR70)
ACR50, Week 16
|
19.9 percentage of participants
|
|
Percentage of Participants Achieving American College of Rheumatology (ACR) 20 Percent (%), 50% or 70% Response (ACR20/ACR50/ACR70)
ACR50, Week 24
|
24.4 percentage of participants
|
|
Percentage of Participants Achieving American College of Rheumatology (ACR) 20 Percent (%), 50% or 70% Response (ACR20/ACR50/ACR70)
ACR70, Week 8
|
2.7 percentage of participants
|
|
Percentage of Participants Achieving American College of Rheumatology (ACR) 20 Percent (%), 50% or 70% Response (ACR20/ACR50/ACR70)
ACR70, Week 16
|
8.2 percentage of participants
|
|
Percentage of Participants Achieving American College of Rheumatology (ACR) 20 Percent (%), 50% or 70% Response (ACR20/ACR50/ACR70)
ACR70, Week 24
|
10.0 percentage of participants
|
SECONDARY outcome
Timeframe: Screening and Weeks 8, 16, and 24Population: ITT population; n=number of participants assessed at a given visit.
The 28 joints to be assessed for tenderness and swelling were shoulder, elbow, wrist, metacarpophalangeal (MCP) joints 1-5, proximal interphalangeal (PIP) joints 1-5, and knee on both sides of the body. The sum of swollen joints, each, ranged from 0 to 28 with 0 as best possible health status and 28 as worst health status.
Outcome measures
| Measure |
Rituximab + MTX
n=291 Participants
Participants received rituximab, 1 g, IV, and methylprednisolone 100 mg, IV, on Days 1 and 15. Participants should have also been receiving MTX as mandatory background therapy. MTX was to have been started at least 3 months prior to the first infusion and must have been given at stable doses for at least 4 weeks prior to the first infusion.
|
|---|---|
|
Swollen Joint Count (SJC)
Screening (n=291)
|
10.01 swollen joints
Standard Deviation 5.34
|
|
Swollen Joint Count (SJC)
Week 8 (n=288)
|
5.16 swollen joints
Standard Deviation 4.73
|
|
Swollen Joint Count (SJC)
Week 16 (n=282)
|
4.22 swollen joints
Standard Deviation 4.07
|
|
Swollen Joint Count (SJC)
Week 24 (n=272)
|
4.70 swollen joints
Standard Deviation 4.67
|
SECONDARY outcome
Timeframe: Screening and Weeks 8, 16, and 24Population: ITT population; n=number of participants assessed at a given visit.
The 28 joints to be assessed for tenderness and swelling were shoulder, elbow, wrist, metacarpophalangeal (MCP) joints 1-5, proximal interphalangeal (PIP) joints 1-5, and knee on both sides of the body. The sum of tender joints ranged from 0 to 28 with 0 as best possible health status and 28 as worst health status.
Outcome measures
| Measure |
Rituximab + MTX
n=291 Participants
Participants received rituximab, 1 g, IV, and methylprednisolone 100 mg, IV, on Days 1 and 15. Participants should have also been receiving MTX as mandatory background therapy. MTX was to have been started at least 3 months prior to the first infusion and must have been given at stable doses for at least 4 weeks prior to the first infusion.
|
|---|---|
|
Tender Joint Count (TJC)
Screening (n=291)
|
12.62 tender joints
Standard Deviation 6.31
|
|
Tender Joint Count (TJC)
Week 8 (n=288)
|
7.53 tender joints
Standard Deviation 6.71
|
|
Tender Joint Count (TJC)
Week 16 (n=282)
|
6.04 tender joints
Standard Deviation 6.31
|
|
Tender Joint Count (TJC)
Week 24 (n=272)
|
6.41 tender joints
Standard Deviation 6.37
|
SECONDARY outcome
Timeframe: Screening and Weeks 8, 16, and 24Population: ITT population; n=number of participants assessed at a given visit.
Physicians assessed the disease (RA) activity on a 100 mm horizontal VAS. The left-hand extreme of the line (0 mm) was described as "no disease activity" (symptom-free and no arthritis symptoms) and the right hand extreme (100 mm) as "maximum disease activity" (maximum arthritis disease activity).
Outcome measures
| Measure |
Rituximab + MTX
n=291 Participants
Participants received rituximab, 1 g, IV, and methylprednisolone 100 mg, IV, on Days 1 and 15. Participants should have also been receiving MTX as mandatory background therapy. MTX was to have been started at least 3 months prior to the first infusion and must have been given at stable doses for at least 4 weeks prior to the first infusion.
|
|---|---|
|
Physician's Global Assessment of Disease Activity
Screening (n=291)
|
63.99 mm
Standard Deviation 15.40
|
|
Physician's Global Assessment of Disease Activity
Week 8 (n=286)
|
39.20 mm
Standard Deviation 19.85
|
|
Physician's Global Assessment of Disease Activity
Week 16 (n=280)
|
33.03 mm
Standard Deviation 19.96
|
|
Physician's Global Assessment of Disease Activity
Week 24 (n=271)
|
35.75 mm
Standard Deviation 23.92
|
SECONDARY outcome
Timeframe: Screening and Weeks 8, 16, and 24Population: ITT population; n=number of participants assessed at a given visit.
Participants were to assess the disease (RA) activity on a 100 mm horizontal VAS. The left-hand extreme of the line (0 mm) was described as "no disease activity" (symptom-free and no arthritis symptoms) and the right hand extreme (100 mm) as "maximum disease activity" (maximum arthritis disease activity).
Outcome measures
| Measure |
Rituximab + MTX
n=291 Participants
Participants received rituximab, 1 g, IV, and methylprednisolone 100 mg, IV, on Days 1 and 15. Participants should have also been receiving MTX as mandatory background therapy. MTX was to have been started at least 3 months prior to the first infusion and must have been given at stable doses for at least 4 weeks prior to the first infusion.
|
|---|---|
|
Patient's Assessment of Disease Activity
Screening (n=291)
|
63.49 mm
Standard Deviation 20.88
|
|
Patient's Assessment of Disease Activity
Week 8 (n=286)
|
46.19 mm
Standard Deviation 23.51
|
|
Patient's Assessment of Disease Activity
Week 16 (n=278)
|
41.25 mm
Standard Deviation 24.99
|
|
Patient's Assessment of Disease Activity
Week 24 (n=270)
|
41.47 mm
Standard Deviation 25.50
|
SECONDARY outcome
Timeframe: Screening and Weeks 8, 16, and 24Population: ITT population; n=number of participants assessed at a given visit.
Participants were to assess their current level of pain on a 100 mm horizontal VAS. The left-hand extreme of the line (0 mm) was described as "no pain" and the right-hand (100 mm) as "unbearable pain".
Outcome measures
| Measure |
Rituximab + MTX
n=291 Participants
Participants received rituximab, 1 g, IV, and methylprednisolone 100 mg, IV, on Days 1 and 15. Participants should have also been receiving MTX as mandatory background therapy. MTX was to have been started at least 3 months prior to the first infusion and must have been given at stable doses for at least 4 weeks prior to the first infusion.
|
|---|---|
|
Patient's Assessment of Pain
Screening (n=291)
|
62.78 mm
Standard Deviation 20.80
|
|
Patient's Assessment of Pain
Week 8 (n=287)
|
47.30 mm
Standard Deviation 23.26
|
|
Patient's Assessment of Pain
Week 16 (n=276)
|
42.11 mm
Standard Deviation 25.14
|
|
Patient's Assessment of Pain
Week 24 (n=269)
|
41.76 mm
Standard Deviation 25.52
|
SECONDARY outcome
Timeframe: Screening, Days 1 and 15, and Weeks 8, 16, and 24Population: ITT population; n=number of participants assessed at a given visit.
Mean CRP as measured as an acute phase reactant by mg per deciliter (mg/dL) at screening, Days 1 and 15, and Weeks 8, 16, and 24.
Outcome measures
| Measure |
Rituximab + MTX
n=289 Participants
Participants received rituximab, 1 g, IV, and methylprednisolone 100 mg, IV, on Days 1 and 15. Participants should have also been receiving MTX as mandatory background therapy. MTX was to have been started at least 3 months prior to the first infusion and must have been given at stable doses for at least 4 weeks prior to the first infusion.
|
|---|---|
|
C-Reactive Protein (CRP)
Screening (n=289)
|
1.82 mg/dL
Standard Deviation 2.35
|
|
C-Reactive Protein (CRP)
Day 1 (n=233)
|
1.60 mg/dL
Standard Deviation 1.96
|
|
C-Reactive Protein (CRP)
Day 15 (n=286)
|
1.81 mg/dL
Standard Deviation 2.27
|
|
C-Reactive Protein (CRP)
Week 8 (n=283)
|
1.31 mg/dL
Standard Deviation 1.44
|
|
C-Reactive Protein (CRP)
Week 16 (n=281)
|
1.21 mg/dL
Standard Deviation 1.65
|
|
C-Reactive Protein (CRP)
Week 24 (n=269)
|
1.30 mg/dL
Standard Deviation 1.77
|
SECONDARY outcome
Timeframe: Screening, Days 1 and 15, and Weeks 8, 16, and 24Population: ITT population; n=number of participants assessed at a given visit.
Mean ESR, as an acute phase reactant, measured in mm/hr at screening, Days 1 and 15, and Weeks 8, 16, and 24.
Outcome measures
| Measure |
Rituximab + MTX
n=291 Participants
Participants received rituximab, 1 g, IV, and methylprednisolone 100 mg, IV, on Days 1 and 15. Participants should have also been receiving MTX as mandatory background therapy. MTX was to have been started at least 3 months prior to the first infusion and must have been given at stable doses for at least 4 weeks prior to the first infusion.
|
|---|---|
|
Erythrocyte Sedimentation Rate (ESR)
Screening (n=291)
|
30.20 mm/hr
Standard Deviation 20.56
|
|
Erythrocyte Sedimentation Rate (ESR)
Day 1 (n=225)
|
28.07 mm/hr
Standard Deviation 19.51
|
|
Erythrocyte Sedimentation Rate (ESR)
Day 15 (n=277)
|
30.61 mm/hr
Standard Deviation 21.46
|
|
Erythrocyte Sedimentation Rate (ESR)
Week 8 (n=279)
|
24.85 mm/hr
Standard Deviation 16.68
|
|
Erythrocyte Sedimentation Rate (ESR)
Week 16 (n=276)
|
22.28 mm/hr
Standard Deviation 16.58
|
|
Erythrocyte Sedimentation Rate (ESR)
Week 24 (n=268)
|
23.64 mm/hr
Standard Deviation 17.36
|
SECONDARY outcome
Timeframe: Screening and Weeks 8, 16, and 24Population: ITT population; n=number of participants assessed at a given visit.
Mean RF as measured by international unit per milliliter (IU/mL) at screening and Weeks 8, 16, and 24.
Outcome measures
| Measure |
Rituximab + MTX
n=279 Participants
Participants received rituximab, 1 g, IV, and methylprednisolone 100 mg, IV, on Days 1 and 15. Participants should have also been receiving MTX as mandatory background therapy. MTX was to have been started at least 3 months prior to the first infusion and must have been given at stable doses for at least 4 weeks prior to the first infusion.
|
|---|---|
|
Rheumatoid Factor (RF)
Screening (n=279)
|
178.23 IU/mL
Standard Deviation 352.61
|
|
Rheumatoid Factor (RF)
Week 8 (n=255)
|
109.84 IU/mL
Standard Deviation 213.32
|
|
Rheumatoid Factor (RF)
Week 16 (n=259)
|
88.22 IU/mL
Standard Deviation 174.99
|
|
Rheumatoid Factor (RF)
Week 24 (n=258)
|
87.52 IU/mL
Standard Deviation 187.94
|
Adverse Events
Rituximab + MTX
Serious adverse events
| Measure |
Rituximab + MTX
n=302 participants at risk
Participants received rituximab, 1 g, IV, and methylprednisolone 100 mg, IV, on Days 1 and 15. Participants should have also been receiving MTX as mandatory background therapy. MTX was to have been started at least 3 months prior to the first infusion and must have been given at stable doses for at least 4 weeks prior to the first infusion.
|
|---|---|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal and connective tissue disorders
|
3.0%
9/302 • From first dose of study drug up to 24 weeks of follow up.
Note that available data included a summary of events by system organ class only, no data provided by preferred term.
|
|
Infections and infestations
Infections and infestations
|
2.3%
7/302 • From first dose of study drug up to 24 weeks of follow up.
Note that available data included a summary of events by system organ class only, no data provided by preferred term.
|
|
Injury, poisoning and procedural complications
Injury, poisoning and procedural complications
|
2.3%
7/302 • From first dose of study drug up to 24 weeks of follow up.
Note that available data included a summary of events by system organ class only, no data provided by preferred term.
|
|
Gastrointestinal disorders
Gastrointestinal disorders
|
1.7%
5/302 • From first dose of study drug up to 24 weeks of follow up.
Note that available data included a summary of events by system organ class only, no data provided by preferred term.
|
|
Cardiac disorders
Cardiac disorders
|
0.99%
3/302 • From first dose of study drug up to 24 weeks of follow up.
Note that available data included a summary of events by system organ class only, no data provided by preferred term.
|
|
General disorders
General disorders and administration site conditions
|
0.66%
2/302 • From first dose of study drug up to 24 weeks of follow up.
Note that available data included a summary of events by system organ class only, no data provided by preferred term.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
|
0.66%
2/302 • From first dose of study drug up to 24 weeks of follow up.
Note that available data included a summary of events by system organ class only, no data provided by preferred term.
|
|
Nervous system disorders
Nervous system disorders
|
0.66%
2/302 • From first dose of study drug up to 24 weeks of follow up.
Note that available data included a summary of events by system organ class only, no data provided by preferred term.
|
|
Ear and labyrinth disorders
Ear and labyrinth disorders
|
0.33%
1/302 • From first dose of study drug up to 24 weeks of follow up.
Note that available data included a summary of events by system organ class only, no data provided by preferred term.
|
|
Endocrine disorders
Endocrine disorders
|
0.33%
1/302 • From first dose of study drug up to 24 weeks of follow up.
Note that available data included a summary of events by system organ class only, no data provided by preferred term.
|
|
Immune system disorders
Immune system disorders
|
0.33%
1/302 • From first dose of study drug up to 24 weeks of follow up.
Note that available data included a summary of events by system organ class only, no data provided by preferred term.
|
|
Investigations
Investigations
|
0.33%
1/302 • From first dose of study drug up to 24 weeks of follow up.
Note that available data included a summary of events by system organ class only, no data provided by preferred term.
|
|
Metabolism and nutrition disorders
Metabolism and nutrition disorders
|
0.33%
1/302 • From first dose of study drug up to 24 weeks of follow up.
Note that available data included a summary of events by system organ class only, no data provided by preferred term.
|
|
Psychiatric disorders
Psychiatric disorders
|
0.33%
1/302 • From first dose of study drug up to 24 weeks of follow up.
Note that available data included a summary of events by system organ class only, no data provided by preferred term.
|
|
Renal and urinary disorders
Renal and urinary disorders
|
0.33%
1/302 • From first dose of study drug up to 24 weeks of follow up.
Note that available data included a summary of events by system organ class only, no data provided by preferred term.
|
|
Reproductive system and breast disorders
Reproductive system and breast disorders
|
0.33%
1/302 • From first dose of study drug up to 24 weeks of follow up.
Note that available data included a summary of events by system organ class only, no data provided by preferred term.
|
|
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders
|
0.33%
1/302 • From first dose of study drug up to 24 weeks of follow up.
Note that available data included a summary of events by system organ class only, no data provided by preferred term.
|
|
Vascular disorders
Vascular disorders
|
0.33%
1/302 • From first dose of study drug up to 24 weeks of follow up.
Note that available data included a summary of events by system organ class only, no data provided by preferred term.
|
Other adverse events
| Measure |
Rituximab + MTX
n=302 participants at risk
Participants received rituximab, 1 g, IV, and methylprednisolone 100 mg, IV, on Days 1 and 15. Participants should have also been receiving MTX as mandatory background therapy. MTX was to have been started at least 3 months prior to the first infusion and must have been given at stable doses for at least 4 weeks prior to the first infusion.
|
|---|---|
|
Infections and infestations
Nasopharyngitis
|
12.3%
37/302 • From first dose of study drug up to 24 weeks of follow up.
Note that available data included a summary of events by system organ class only, no data provided by preferred term.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
6.3%
19/302 • From first dose of study drug up to 24 weeks of follow up.
Note that available data included a summary of events by system organ class only, no data provided by preferred term.
|
|
Vascular disorders
Hypertension
|
5.6%
17/302 • From first dose of study drug up to 24 weeks of follow up.
Note that available data included a summary of events by system organ class only, no data provided by preferred term.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
- Publication restrictions are in place
Restriction type: OTHER