Trial Outcomes & Findings for An Observational Study of MabThera in Participants With Severe Active Rheumatoid Arthritis (NCT NCT01613027)
NCT ID: NCT01613027
Last Updated: 2016-10-24
Results Overview
DAS28-ESR is a measure of the participant's disease activity and was calculated using the swollen joint count of 28 joints (SJC28), tender joint count of 28 joints (TJC28), erythrocyte sedimentation rate (ESR) (millimeters per hour \[mm/hour\]) and patient's global assessment of disease activity (100-millimeter \[mm\] horizontal visual analog scale with 0=no disease activity to 100=maximum disease activity). DAS28-ESR scores range from 0 to 10, with higher scores corresponding to greater disease activity.
COMPLETED
135 participants
Baseline, Month 6, Month 12
2016-10-24
Participant Flow
Participant milestones
| Measure |
Rituximab
Rituximab administered according to prescribing information and normal clinical practice.
|
|---|---|
|
Overall Study
STARTED
|
135
|
|
Overall Study
COMPLETED
|
127
|
|
Overall Study
NOT COMPLETED
|
8
|
Reasons for withdrawal
| Measure |
Rituximab
Rituximab administered according to prescribing information and normal clinical practice.
|
|---|---|
|
Overall Study
Lost to Follow-up
|
5
|
|
Overall Study
Switched Physician
|
1
|
|
Overall Study
Lack of Efficacy
|
1
|
|
Overall Study
Patient's Decision Due to Adverse Event
|
1
|
Baseline Characteristics
An Observational Study of MabThera in Participants With Severe Active Rheumatoid Arthritis
Baseline characteristics by cohort
| Measure |
Rituximab
n=135 Participants
Rituximab administered according to prescribing information and normal clinical practice.
|
|---|---|
|
Age, Continuous
|
61.2 years
STANDARD_DEVIATION 12.5 • n=5 Participants
|
|
Sex: Female, Male
Female
|
115 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
20 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline, Month 6, Month 12Population: Intention-to Treat population, defined as all enrolled participants who received at least one dose of rituximab.
DAS28-ESR is a measure of the participant's disease activity and was calculated using the swollen joint count of 28 joints (SJC28), tender joint count of 28 joints (TJC28), erythrocyte sedimentation rate (ESR) (millimeters per hour \[mm/hour\]) and patient's global assessment of disease activity (100-millimeter \[mm\] horizontal visual analog scale with 0=no disease activity to 100=maximum disease activity). DAS28-ESR scores range from 0 to 10, with higher scores corresponding to greater disease activity.
Outcome measures
| Measure |
Rituximab
n=135 Participants
Rituximab administered according to prescribing information and normal clinical practice.
|
|---|---|
|
Change From Baseline in Disease Activity Score Based on 28-joint Count and Erythrocyte Sedimentation Rate (DAS28-ESR) at Month 6 and Month 12
Baseline
|
5.53 units on a scale
Standard Deviation 1.12
|
|
Change From Baseline in Disease Activity Score Based on 28-joint Count and Erythrocyte Sedimentation Rate (DAS28-ESR) at Month 6 and Month 12
Change at Month 12
|
-1.88 units on a scale
Standard Deviation 1.40
|
|
Change From Baseline in Disease Activity Score Based on 28-joint Count and Erythrocyte Sedimentation Rate (DAS28-ESR) at Month 6 and Month 12
Change at Month 6
|
-1.52 units on a scale
Standard Deviation 1.36
|
SECONDARY outcome
Timeframe: Baseline, Month 6, Month 12Population: Intention-to Treat population, defined as all enrolled participants who received at least one dose of rituximab.
EULAR response was calculated as the difference between DAS28-ESR scores at baseline and Month 6, and baseline and Month 12, and reported as the percentage of participants with response overall, good response, moderate response, and no response measured at each time point. Good responders = decrease from baseline \>1.2 with a DAS28 score of ≤3.2; moderate responders = decrease from baseline \>1.2 with a DAS28 score of \>3.2, or decrease from baseline \>0.6 to ≤1.2 with a DAS28 score of ≤5.1; non-responders = decrease from baseline ≤0.6 or decrease from baseline \>0.6 and ≤1.2 with a DAS28 score of \>5.1.
Outcome measures
| Measure |
Rituximab
n=135 Participants
Rituximab administered according to prescribing information and normal clinical practice.
|
|---|---|
|
Percentage of Participants With European League Against Rheumatism (EULAR) Response at Month 6 and Month 12
Overall - Month 6
|
75.6 percentage of participants
Interval 67.4 to 82.5
|
|
Percentage of Participants With European League Against Rheumatism (EULAR) Response at Month 6 and Month 12
Good Response - Month 6
|
45.2 percentage of participants
Interval 36.6 to 54.0
|
|
Percentage of Participants With European League Against Rheumatism (EULAR) Response at Month 6 and Month 12
Moderate Response - Month 6
|
30.4 percentage of participants
Interval 22.8 to 38.9
|
|
Percentage of Participants With European League Against Rheumatism (EULAR) Response at Month 6 and Month 12
No Response - Month 6
|
24.4 percentage of participants
Interval 17.5 to 32.6
|
|
Percentage of Participants With European League Against Rheumatism (EULAR) Response at Month 6 and Month 12
Overall - Month 12
|
77.0 percentage of participants
Interval 69.0 to 83.8
|
|
Percentage of Participants With European League Against Rheumatism (EULAR) Response at Month 6 and Month 12
Good Response - Month 12
|
40.0 percentage of participants
Interval 31.7 to 48.8
|
|
Percentage of Participants With European League Against Rheumatism (EULAR) Response at Month 6 and Month 12
Moderate Response - Month 12
|
37.0 percentage of participants
Interval 28.9 to 45.8
|
|
Percentage of Participants With European League Against Rheumatism (EULAR) Response at Month 6 and Month 12
No Response - Month 12
|
23.0 percentage of participants
Interval 16.2 to 31.0
|
SECONDARY outcome
Timeframe: Baseline, Month 6, Month 12Population: Intention-to Treat population, defined as all enrolled participants who received at least one dose of rituximab.
SJC was determined by examining 28 and 66 joints and identifying when swelling was present. Swelling was recorded on the joint assessment form at baseline, no swelling = 0, swelling =1. The sum of swollen joints, each, ranged from 0 to 28 with 0 as best possible health status and 28 as worst health status. A decrease from baseline indicates improvement.
Outcome measures
| Measure |
Rituximab
n=135 Participants
Rituximab administered according to prescribing information and normal clinical practice.
|
|---|---|
|
Change From Baseline in Swollen Joint Count (SJC) at Month 6 and Month 12
Change at Month 12
|
-3.8 swollen joints
Standard Deviation 4.5
|
|
Change From Baseline in Swollen Joint Count (SJC) at Month 6 and Month 12
Baseline
|
6.4 swollen joints
Standard Deviation 4.6
|
|
Change From Baseline in Swollen Joint Count (SJC) at Month 6 and Month 12
Change at Month 6
|
-3.1 swollen joints
Standard Deviation 4.3
|
SECONDARY outcome
Timeframe: Baseline, Month 6, Month 12Population: Intention-to Treat population, defined as all enrolled participants who received at least one dose of rituximab.
TJC was determined by examining 28 and 68 joints and identifying the joints that were painful under pressure or to passive motion. Tenderness was recorded on the joint assessment form at baseline, no tenderness = 0, tenderness = 1. A decrease from baseline indicates improvement.
Outcome measures
| Measure |
Rituximab
n=135 Participants
Rituximab administered according to prescribing information and normal clinical practice.
|
|---|---|
|
Change From Baseline in Tender Joint Count (TJC) at Month 6 and Month 12
Baseline
|
8.2 tender joints
Standard Deviation 5.5
|
|
Change From Baseline in Tender Joint Count (TJC) at Month 6 and Month 12
Change at Month 6
|
-4.4 tender joints
Standard Deviation 5.3
|
|
Change From Baseline in Tender Joint Count (TJC) at Month 6 and Month 12
Change at Month 12
|
-5.1 tender joints
Standard Deviation 5.3
|
SECONDARY outcome
Timeframe: Baseline, Month 6, Month 12Population: Intention-to Treat population, defined as all enrolled participants who received at least one dose of rituximab.
ESR is an direct measure of how much inflammation is in the body. The normal range is 0-22 mm/hour for men and 0-29 mm/hour for women. A decrease from baseline indicates improvement.
Outcome measures
| Measure |
Rituximab
n=135 Participants
Rituximab administered according to prescribing information and normal clinical practice.
|
|---|---|
|
Change From Baseline in Erythrocyte Sedimentation Rate (ESR) at Month 6 and Month 12
Change at Month 6
|
-14.1 mm/hour
Standard Deviation 22.2
|
|
Change From Baseline in Erythrocyte Sedimentation Rate (ESR) at Month 6 and Month 12
Baseline
|
43.1 mm/hour
Standard Deviation 23.4
|
|
Change From Baseline in Erythrocyte Sedimentation Rate (ESR) at Month 6 and Month 12
Change at Month 12
|
-16.3 mm/hour
Standard Deviation 24.1
|
SECONDARY outcome
Timeframe: Baseline, Month 6, Month 12Population: Intention-to Treat population, defined as all enrolled participants who received at least one dose of rituximab. Data at Month 6 and Month 12 are included for participants who had assessments for CRP.
C-reactive protein (CRP) is a blood test marker for inflammation in the body. Normal CRP levels are below 5.0 milligrams per liter (mg/L). A decrease from baseline indicates improvement.
Outcome measures
| Measure |
Rituximab
n=99 Participants
Rituximab administered according to prescribing information and normal clinical practice.
|
|---|---|
|
Change From Baseline in C-reactive Protein (CRP) at Month 6 and Month 12
Baseline
|
21.8 mg/L
Standard Deviation 39.3
|
|
Change From Baseline in C-reactive Protein (CRP) at Month 6 and Month 12
Change at Month 6
|
-10.7 mg/L
Standard Deviation 34.8
|
|
Change From Baseline in C-reactive Protein (CRP) at Month 6 and Month 12
Change at Month 12
|
-14.1 mg/L
Standard Deviation 38.1
|
SECONDARY outcome
Timeframe: Up to 12 monthsPopulation: Intention-to Treat population, defined as all enrolled participants who received at least one dose of rituximab.
Outcome measures
| Measure |
Rituximab
n=135 Participants
Rituximab administered according to prescribing information and normal clinical practice.
|
|---|---|
|
Percentage of Participants Who Remained on Treatment or Discontinued Treatment by Month 6 and Month 12
Remained on treatment - Month 6
|
93.3 percentage of participants
|
|
Percentage of Participants Who Remained on Treatment or Discontinued Treatment by Month 6 and Month 12
Discontinued treatment - Month 6
|
6.7 percentage of participants
|
|
Percentage of Participants Who Remained on Treatment or Discontinued Treatment by Month 6 and Month 12
Remained on treatment - Month 12
|
86.7 percentage of participants
|
|
Percentage of Participants Who Remained on Treatment or Discontinued Treatment by Month 6 and Month 12
Discontinued treatment - Month 12
|
13.3 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline to Month 6Population: Intention-to Treat population, defined as all enrolled participants who received at least one dose of rituximab.
Reasons for discontinuation from baseline to Month 6 are presented as the number of participants who discontinued treatment by category of reason for discontinuation.
Outcome measures
| Measure |
Rituximab
n=135 Participants
Rituximab administered according to prescribing information and normal clinical practice.
|
|---|---|
|
Reasons for Discontinuation of Treatment by Month 6
Disease remission
|
2 participants
|
|
Reasons for Discontinuation of Treatment by Month 6
Lost to follow-up
|
2 participants
|
|
Reasons for Discontinuation of Treatment by Month 6
Adverse reaction (Allergic reaction)
|
1 participants
|
|
Reasons for Discontinuation of Treatment by Month 6
Switched physician
|
1 participants
|
|
Reasons for Discontinuation of Treatment by Month 6
Insurance issues
|
1 participants
|
|
Reasons for Discontinuation of Treatment by Month 6
Lack of response
|
1 participants
|
|
Reasons for Discontinuation of Treatment by Month 6
Investigation of reasons for body weight loss
|
1 participants
|
SECONDARY outcome
Timeframe: Baseline to Month 12Population: Intention-to Treat population, defined as all enrolled participants who received at least one dose of rituximab.
Reasons for discontinuation from baseline to Month 12 are presented as the number of participants who discontinued treatment by category of reason for discontinuation.
Outcome measures
| Measure |
Rituximab
n=135 Participants
Rituximab administered according to prescribing information and normal clinical practice.
|
|---|---|
|
Reasons for Discontinuation of Treatment by Month 12
Patient's decision due to adverse event
|
1 participants
|
|
Reasons for Discontinuation of Treatment by Month 12
Disease remission
|
3 participants
|
|
Reasons for Discontinuation of Treatment by Month 12
Lost to follow-up
|
5 participants
|
|
Reasons for Discontinuation of Treatment by Month 12
Lack of efficacy
|
1 participants
|
|
Reasons for Discontinuation of Treatment by Month 12
Lack of response
|
1 participants
|
|
Reasons for Discontinuation of Treatment by Month 12
Non-satisfactory response
|
1 participants
|
|
Reasons for Discontinuation of Treatment by Month 12
Adverse reaction (Allergic reaction)
|
1 participants
|
|
Reasons for Discontinuation of Treatment by Month 12
Adverse reactions (Bradycardia and dermatitis)
|
1 participants
|
|
Reasons for Discontinuation of Treatment by Month 12
Switched physician
|
1 participants
|
|
Reasons for Discontinuation of Treatment by Month 12
Insurance issues
|
1 participants
|
|
Reasons for Discontinuation of Treatment by Month 12
Investigation of reasons for body weight loss
|
1 participants
|
|
Reasons for Discontinuation of Treatment by Month 12
Physician's decision
|
1 participants
|
SECONDARY outcome
Timeframe: Up to 12 monthsPopulation: Intention-to Treat population, defined as all enrolled participants who received at least one dose of rituximab. Data for change from baseline at Month 6 and Month 12 are included for participants with available data at each time point.
The M-HAQ is a participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week. Each item scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty. A negative change from baseline indicates improvement. Clinically meaningful improvement was defined as minimum clinically significant reduction from baseline of ≥0.22 at the respective time point.
Outcome measures
| Measure |
Rituximab
n=135 Participants
Rituximab administered according to prescribing information and normal clinical practice.
|
|---|---|
|
Percentage of Participants With Clinically Meaningful Improvement From Baseline in Modified Health Assessment Questionnaire (M-HAQ)
Baseline to Month 6 (n = 89)
|
65.9 percentage of participants
Interval 57.3 to 73.9
|
|
Percentage of Participants With Clinically Meaningful Improvement From Baseline in Modified Health Assessment Questionnaire (M-HAQ)
Baseline to Month 12 (n = 97)
|
71.9 percentage of participants
Interval 63.5 to 79.2
|
SECONDARY outcome
Timeframe: Up to 12 monthsPopulation: Intention-to Treat population, defined as all enrolled participants who received at least one dose of rituximab.
An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An ADR was defined as any noxious and unintended response to a medicinal product related to any dose. AEs of special interest includes progressive multifocal leukoencephalopathy (PML), any encephalopathy, hepatitis B or hepatitis B reactivation, gastrointestinal perforation, tuberculosis (TB) or TB reactivation, opportunistic infections, and malignancies.
Outcome measures
| Measure |
Rituximab
n=135 Participants
Rituximab administered according to prescribing information and normal clinical practice.
|
|---|---|
|
Percentage of Participants With Adverse Events (AEs) and Adverse Drug Reactions (ADRs)
Any non-serious AE not related to rituximab
|
24.4 percentage of participants
|
|
Percentage of Participants With Adverse Events (AEs) and Adverse Drug Reactions (ADRs)
Any serious AE
|
6.7 percentage of participants
|
|
Percentage of Participants With Adverse Events (AEs) and Adverse Drug Reactions (ADRs)
Any AE
|
37.8 percentage of participants
|
|
Percentage of Participants With Adverse Events (AEs) and Adverse Drug Reactions (ADRs)
Any non-serious AE
|
32.6 percentage of participants
|
|
Percentage of Participants With Adverse Events (AEs) and Adverse Drug Reactions (ADRs)
Any non-serious ADR
|
9.6 percentage of participants
|
|
Percentage of Participants With Adverse Events (AEs) and Adverse Drug Reactions (ADRs)
Any serious AE not related to rituximab
|
3.0 percentage of participants
|
|
Percentage of Participants With Adverse Events (AEs) and Adverse Drug Reactions (ADRs)
Any serious ADR
|
3.7 percentage of participants
|
|
Percentage of Participants With Adverse Events (AEs) and Adverse Drug Reactions (ADRs)
Any AE of special interest related to rituximab
|
2.2 percentage of participants
|
SECONDARY outcome
Timeframe: Up to 12 monthsPopulation: Intention-to Treat population, defined as all enrolled participants who received at least one dose of rituximab.
Percentage of participants with any non-serious AE and any serious AE by intensity (mild, moderate, severe) was reported. An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Outcome measures
| Measure |
Rituximab
n=135 Participants
Rituximab administered according to prescribing information and normal clinical practice.
|
|---|---|
|
Percentage of Participants With Any Non-Serious AE and Any Serious AE by Intensity
Any serious AE (Moderate)
|
3.0 percentage of participants
|
|
Percentage of Participants With Any Non-Serious AE and Any Serious AE by Intensity
Any serious AE (Severe)
|
2.2 percentage of participants
|
|
Percentage of Participants With Any Non-Serious AE and Any Serious AE by Intensity
Any non-serious AE (Mild)
|
25.9 percentage of participants
|
|
Percentage of Participants With Any Non-Serious AE and Any Serious AE by Intensity
Any non-serious AE (Moderate)
|
9.6 percentage of participants
|
|
Percentage of Participants With Any Non-Serious AE and Any Serious AE by Intensity
Any non-serious AE (Severe)
|
0.0 percentage of participants
|
|
Percentage of Participants With Any Non-Serious AE and Any Serious AE by Intensity
Any serious AE (Mild)
|
1.5 percentage of participants
|
SECONDARY outcome
Timeframe: Up to 12 monthsPopulation: Intention-to Treat population, defined as all enrolled participants who received at least one dose of rituximab.
Percentage of non-serious AEs resolved and ongoing at the time of study completion were reported. An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Outcome measures
| Measure |
Rituximab
n=66 Non-Serious AEs
Rituximab administered according to prescribing information and normal clinical practice.
|
|---|---|
|
Percentage of Non-Serious AEs
Resolved
|
84.8 percentage of non-serious AEs
|
|
Percentage of Non-Serious AEs
Ongoing
|
15.2 percentage of non-serious AEs
|
SECONDARY outcome
Timeframe: Up to 12 monthsPopulation: Intention-to Treat population, defined as all enrolled participants who received at least one dose of rituximab.
Percentage of non-serious ADRs at the time of study completion was reported. An ADR was defined as any noxious and unintended response to a medicinal product related to any dose.
Outcome measures
| Measure |
Rituximab
n=16 Non-Serious ADRs
Rituximab administered according to prescribing information and normal clinical practice.
|
|---|---|
|
Percentage of Non-Serious ADRs
|
100.0 percentage of non-serious ADRs
|
SECONDARY outcome
Timeframe: Up to 12 monthsPopulation: Intention-to Treat population, defined as all enrolled participants who received at least one dose of rituximab.
Percentage of serious AEs resolved and ongoing at the time of study completion was reported. An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Outcome measures
| Measure |
Rituximab
n=9 Serious AEs
Rituximab administered according to prescribing information and normal clinical practice.
|
|---|---|
|
Percentage of Serious AEs
Resolved
|
88.9 percentage of serious AEs
|
|
Percentage of Serious AEs
Ongoing
|
11.1 percentage of serious AEs
|
SECONDARY outcome
Timeframe: Up to 12 monthsPopulation: Intention-to Treat population, defined as all enrolled participants who received at least one dose of rituximab.
Percentage of serious ADRs resolved and ongoing at the time of study completion was reported. An ADR was defined as any noxious and unintended response to a medicinal product related to any dose.
Outcome measures
| Measure |
Rituximab
n=5 Serious ADRs
Rituximab administered according to prescribing information and normal clinical practice.
|
|---|---|
|
Percentage of Serious ADRs
Ongoing
|
20.0 percentage of serious ADRs
|
|
Percentage of Serious ADRs
Resolved
|
80.0 percentage of serious ADRs
|
Adverse Events
Rituximab
Serious adverse events
| Measure |
Rituximab
n=135 participants at risk
Rituximab administered according to prescribing information and normal clinical practice.
|
|---|---|
|
Infections and infestations
Bronchitis
|
1.5%
2/135 • Up to 12 months
Safety population, defined as all enrolled participants who received at least one dose of rituximab.
|
|
Infections and infestations
Sinusitis
|
0.74%
1/135 • Up to 12 months
Safety population, defined as all enrolled participants who received at least one dose of rituximab.
|
|
Infections and infestations
Upper respiratory tract infection
|
0.74%
1/135 • Up to 12 months
Safety population, defined as all enrolled participants who received at least one dose of rituximab.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cerebellar tumour
|
0.74%
1/135 • Up to 12 months
Safety population, defined as all enrolled participants who received at least one dose of rituximab.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma
|
0.74%
1/135 • Up to 12 months
Safety population, defined as all enrolled participants who received at least one dose of rituximab.
|
|
Cardiac disorders
Angina pectoris
|
0.74%
1/135 • Up to 12 months
Safety population, defined as all enrolled participants who received at least one dose of rituximab.
|
|
Investigations
Haematocrit decreased
|
0.74%
1/135 • Up to 12 months
Safety population, defined as all enrolled participants who received at least one dose of rituximab.
|
|
Surgical and medical procedures
Hip arthroplasty
|
0.74%
1/135 • Up to 12 months
Safety population, defined as all enrolled participants who received at least one dose of rituximab.
|
Other adverse events
Adverse event data not reported
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