A Long-term Extension Study of Tocilizumab (Myeloma Receptor Antibody [MRA]) in Patients With Rheumatoid Arthritis · Source last updated 2013-11-28
Results reported by the registry submitting party. Population, time horizon, units and missing values must be read together.
Measure
NUMBER
Unit
Adverse Events per 100 Patient Years
Interval / dispersion
95% Confidence Interval
Time frame
through 264 Weeks
What was measured
Patient year (PY) refers to duration in study, calculated from first active drug intake to last safety assessment available + 1. Patient year rates with confidence interval were calculated for adverse events of interest in evaluating the long-term safety of the product being studied.
Abbreviations include the following: adverse event (AE), adverse event of special interest (AESI), gastrointestinal (GI), serious adverse event (SAE), and investigational product (IP). Hypersensitivity events were defined as AEs that occurred during or within 24 hours of IP infusion and were not deemed "unrelated" to trial treatment by the investigator. This definition includes all types of AEs, regardless of whether or not they were consistent with hypersensitivity.
Medical confirmation of the AESI "GI perforation" was based on medical adjudication of events captured by the GI Perforation Standardised MedDRA Queries (SMQs).
Analysis population: All exposure population, which includes all participants who entered the study and received at least one dose of tocilizumab at any time.
Groups in this outcome
Months 0 - 12
Participants with scores during Months 0-12, which equates to baseline through Week 48 (Total PY=486.34).
Months 13 - 24
Participants with scores during Months 13 - 24, which equates to Weeks 49-96 (Total PY=444.49).
Months 25 - 36
Participants with scores during Months 25 - 36, which equates to Weeks 97-144 (Total PY=410.93).
Months 37 - 48
Participants with scores during Months 37 - 48, which equates to Weeks 145-192 (Total PY=388.25).
Months Greater Than 48
Participants with scores during Months greater than 48, which equates to Weeks 193-264 (Total PY=731.93).
Group identifiers and denominators belong to this outcome only. They may differ in another outcome or in safety reporting.
Analysis denominator · Participants
Group
Source count
Months 0 - 12
538
Months 13 - 24
509
Months 25 - 36
463
Months 37 - 48
434
Months Greater Than 48
414
Reported measurements
Total AE rate
Values in Adverse Events per 100 Patient Years · Interval/dispersion: 95% Confidence Interval
Group
Value
Spread
Lower
Upper
Comment
Months 0 - 12
393.76
Not reported
376.32
411.80
Not reported
Months 13 - 24
286.17
Not reported
270.66
302.34
Not reported
Months 25 - 36
260.14
Not reported
244.78
276.22
Not reported
Months 37 - 48
249.84
Not reported
234.36
266.07
Not reported
Months Greater Than 48
212.04
Not reported
201.62
222.86
Not reported
Total SAE rate
Values in Adverse Events per 100 Patient Years · Interval/dispersion: 95% Confidence Interval
Group
Value
Spread
Lower
Upper
Comment
Months 0 - 12
12.54
Not reported
9.59
16.11
Not reported
Months 13 - 24
13.05
Not reported
9.91
16.87
Not reported
Months 25 - 36
18.74
Not reported
14.79
23.42
Not reported
Months 37 - 48
12.62
Not reported
9.34
16.69
Not reported
Months Greater Than 48
13.12
Not reported
10.62
16.02
Not reported
Rate for AEs leading to withdrawal
Values in Adverse Events per 100 Patient Years · Interval/dispersion: 95% Confidence Interval
Group
Value
Spread
Lower
Upper
Comment
Months 0 - 12
5.14
Not reported
3.33
7.59
Not reported
Months 13 - 24
3.82
Not reported
2.23
6.12
Not reported
Months 25 - 36
5.35
Not reported
3.36
8.11
Not reported
Months 37 - 48
2.06
Not reported
0.89
4.06
Not reported
Months Greater Than 48
4.37
Not reported
2.99
6.17
Not reported
AESI All Infections
Values in Adverse Events per 100 Patient Years · Interval/dispersion: 95% Confidence Interval
Group
Value
Spread
Lower
Upper
Comment
Months 0 - 12
92.94
Not reported
84.57
101.92
Not reported
Months 13 - 24
87.52
Not reported
79.03
96.66
Not reported
Months 25 - 36
87.36
Not reported
78.56
96.88
Not reported
Months 37 - 48
87.32
Not reported
78.27
97.12
Not reported
Months Greater Than 48
72.82
Not reported
66.77
79.27
Not reported
AESI Serious Infections
Values in Adverse Events per 100 Patient Years · Interval/dispersion: 95% Confidence Interval
Group
Value
Spread
Lower
Upper
Comment
Months 0 - 12
3.29
Not reported
1.88
5.34
Not reported
Months 13 - 24
2.47
Not reported
1.24
4.43
Not reported
Months 25 - 36
5.60
Not reported
3.55
8.40
Not reported
Months 37 - 48
3.35
Not reported
1.78
5.73
Not reported
Months Greater Than 48
3.55
Not reported
2.32
5.20
Not reported
AESI Opportunistic infections
Values in Adverse Events per 100 Patient Years · Interval/dispersion: 95% Confidence Interval
Group
Value
Spread
Lower
Upper
Comment
Months 0 - 12
0
Not reported
NA
NA
There were no opportunistic infections in this period.
Months 13 - 24
0.22
Not reported
0.01
1.25
Not reported
Months 25 - 36
0
Not reported
NA
NA
There were no opportunistic infections in this period.
Months 37 - 48
0.52
Not reported
0.06
1.86
Not reported
Months Greater Than 48
0.27
Not reported
0.03
0.99
Not reported
AESI Hypersensitivity events
Values in Adverse Events per 100 Patient Years · Interval/dispersion: 95% Confidence Interval
Group
Value
Spread
Lower
Upper
Comment
Months 0 - 12
27.35
Not reported
22.90
32.41
Not reported
Months 13 - 24
9.90
Not reported
7.19
13.29
Not reported
Months 25 - 36
5.35
Not reported
3.36
8.11
Not reported
Months 37 - 48
3.86
Not reported
2.16
6.37
Not reported
Months Greater Than 48
4.10
Not reported
2.77
5.85
Not reported
AESI Hepatic events
Values in Adverse Events per 100 Patient Years · Interval/dispersion: 95% Confidence Interval
Group
Value
Spread
Lower
Upper
Comment
Months 0 - 12
0.41
Not reported
0.05
1.49
Not reported
Months 13 - 24
0.90
Not reported
0.25
2.30
Not reported
Months 25 - 36
0.49
Not reported
0.06
1.76
Not reported
Months 37 - 48
1.03
Not reported
0.28
2.64
Not reported
Months Greater Than 48
0.68
Not reported
0.22
1.59
Not reported
AESI Myocardial infarction
Values in Adverse Events per 100 Patient Years · Interval/dispersion: 95% Confidence Interval
Group
Value
Spread
Lower
Upper
Comment
Months 0 - 12
0.62
Not reported
0.13
1.80
Not reported
Months 13 - 24
0
Not reported
NA
NA
There were no myocardial infarctions in this period.
Months 25 - 36
0.24
Not reported
0.01
1.36
Not reported
Months 37 - 48
0.77
Not reported
0.16
2.26
Not reported
Months Greater Than 48
0.27
Not reported
0.03
0.99
Not reported
AESI Stroke, ischemic or hemorrhagic
Values in Adverse Events per 100 Patient Years · Interval/dispersion: 95% Confidence Interval
Group
Value
Spread
Lower
Upper
Comment
Months 0 - 12
0.21
Not reported
0.01
1.15
Not reported
Months 13 - 24
0.22
Not reported
0.01
1.25
Not reported
Months 25 - 36
0.73
Not reported
0.15
2.13
Not reported
Months 37 - 48
0.26
Not reported
0.01
1.44
Not reported
Months Greater Than 48
0.41
Not reported
0.08
1.20
Not reported
AESI GI perforation
Values in Adverse Events per 100 Patient Years · Interval/dispersion: 95% Confidence Interval
Group
Value
Spread
Lower
Upper
Comment
Months 0 - 12
0
Not reported
NA
NA
There were no medically confirmed GI perforations in this period.
Months 13 - 24
0
Not reported
NA
NA
There were no medically confirmed GI perforations in this period.
Months 25 - 36
0.49
Not reported
0.06
1.76
Not reported
Months 37 - 48
0.26
Not reported
0.01
1.44
Not reported
Months Greater Than 48
0
Not reported
NA
NA
There were no medically confirmed GI perforations in this period.
AESI Malignancy
Values in Adverse Events per 100 Patient Years · Interval/dispersion: 95% Confidence Interval
Group
Value
Spread
Lower
Upper
Comment
Months 0 - 12
1.23
Not reported
0.45
2.69
Not reported
Months 13 - 24
1.80
Not reported
0.78
3.55
Not reported
Months 25 - 36
0.97
Not reported
0.27
2.49
Not reported
Months 37 - 48
0.77
Not reported
0.16
2.26
Not reported
Months Greater Than 48
1.50
Not reported
0.75
2.69
Not reported
AESI Demyelinating disorders
Values in Adverse Events per 100 Patient Years · Interval/dispersion: 95% Confidence Interval
Group
Value
Spread
Lower
Upper
Comment
Months 0 - 12
0.21
Not reported
0.01
1.15
Not reported
Months 13 - 24
0
Not reported
NA
NA
There were no demyelinating disorders in this period.
Months 25 - 36
0
Not reported
NA
NA
There were no demyelinating disorders in this period.
Months 37 - 48
0
Not reported
NA
NA
There were no demyelinating disorders in this period.
Months Greater Than 48
0
Not reported
NA
NA
There were no demyelinating disorders in this period.
AESI Serious bleeding disorders
Values in Adverse Events per 100 Patient Years · Interval/dispersion: 95% Confidence Interval
Group
Value
Spread
Lower
Upper
Comment
Months 0 - 12
0.62
Not reported
0.13
1.80
Not reported
Months 13 - 24
0.45
Not reported
0.05
1.63
Not reported
Months 25 - 36
0.49
Not reported
0.06
1.76
Not reported
Months 37 - 48
0.26
Not reported
0.01
1.44
Not reported
Months Greater Than 48
0.68
Not reported
0.22
1.59
Not reported
Complete source fields
classes
categories
measurements
group Id
OG000
lower Limit
376.32
upper Limit
411.80
value
393.76
group Id
OG001
lower Limit
270.66
upper Limit
302.34
value
286.17
group Id
OG002
lower Limit
244.78
upper Limit
276.22
value
260.14
group Id
OG003
lower Limit
234.36
upper Limit
266.07
value
249.84
group Id
OG004
lower Limit
201.62
upper Limit
222.86
value
212.04
title
Total AE rate
categories
measurements
group Id
OG000
lower Limit
9.59
upper Limit
16.11
value
12.54
group Id
OG001
lower Limit
9.91
upper Limit
16.87
value
13.05
group Id
OG002
lower Limit
14.79
upper Limit
23.42
value
18.74
group Id
OG003
lower Limit
9.34
upper Limit
16.69
value
12.62
group Id
OG004
lower Limit
10.62
upper Limit
16.02
value
13.12
title
Total SAE rate
categories
measurements
group Id
OG000
lower Limit
3.33
upper Limit
7.59
value
5.14
group Id
OG001
lower Limit
2.23
upper Limit
6.12
value
3.82
group Id
OG002
lower Limit
3.36
upper Limit
8.11
value
5.35
group Id
OG003
lower Limit
0.89
upper Limit
4.06
value
2.06
group Id
OG004
lower Limit
2.99
upper Limit
6.17
value
4.37
title
Rate for AEs leading to withdrawal
categories
measurements
group Id
OG000
lower Limit
84.57
upper Limit
101.92
value
92.94
group Id
OG001
lower Limit
79.03
upper Limit
96.66
value
87.52
group Id
OG002
lower Limit
78.56
upper Limit
96.88
value
87.36
group Id
OG003
lower Limit
78.27
upper Limit
97.12
value
87.32
group Id
OG004
lower Limit
66.77
upper Limit
79.27
value
72.82
title
AESI All Infections
categories
measurements
group Id
OG000
lower Limit
1.88
upper Limit
5.34
value
3.29
group Id
OG001
lower Limit
1.24
upper Limit
4.43
value
2.47
group Id
OG002
lower Limit
3.55
upper Limit
8.40
value
5.60
group Id
OG003
lower Limit
1.78
upper Limit
5.73
value
3.35
group Id
OG004
lower Limit
2.32
upper Limit
5.20
value
3.55
title
AESI Serious Infections
categories
measurements
comment
There were no opportunistic infections in this period.
group Id
OG000
lower Limit
NA
upper Limit
NA
value
0
group Id
OG001
lower Limit
0.01
upper Limit
1.25
value
0.22
comment
There were no opportunistic infections in this period.
group Id
OG002
lower Limit
NA
upper Limit
NA
value
0
group Id
OG003
lower Limit
0.06
upper Limit
1.86
value
0.52
group Id
OG004
lower Limit
0.03
upper Limit
0.99
value
0.27
title
AESI Opportunistic infections
categories
measurements
group Id
OG000
lower Limit
22.90
upper Limit
32.41
value
27.35
group Id
OG001
lower Limit
7.19
upper Limit
13.29
value
9.90
group Id
OG002
lower Limit
3.36
upper Limit
8.11
value
5.35
group Id
OG003
lower Limit
2.16
upper Limit
6.37
value
3.86
group Id
OG004
lower Limit
2.77
upper Limit
5.85
value
4.10
title
AESI Hypersensitivity events
categories
measurements
group Id
OG000
lower Limit
0.05
upper Limit
1.49
value
0.41
group Id
OG001
lower Limit
0.25
upper Limit
2.30
value
0.90
group Id
OG002
lower Limit
0.06
upper Limit
1.76
value
0.49
group Id
OG003
lower Limit
0.28
upper Limit
2.64
value
1.03
group Id
OG004
lower Limit
0.22
upper Limit
1.59
value
0.68
title
AESI Hepatic events
categories
measurements
group Id
OG000
lower Limit
0.13
upper Limit
1.80
value
0.62
comment
There were no myocardial infarctions in this period.
group Id
OG001
lower Limit
NA
upper Limit
NA
value
0
group Id
OG002
lower Limit
0.01
upper Limit
1.36
value
0.24
group Id
OG003
lower Limit
0.16
upper Limit
2.26
value
0.77
group Id
OG004
lower Limit
0.03
upper Limit
0.99
value
0.27
title
AESI Myocardial infarction
categories
measurements
group Id
OG000
lower Limit
0.01
upper Limit
1.15
value
0.21
group Id
OG001
lower Limit
0.01
upper Limit
1.25
value
0.22
group Id
OG002
lower Limit
0.15
upper Limit
2.13
value
0.73
group Id
OG003
lower Limit
0.01
upper Limit
1.44
value
0.26
group Id
OG004
lower Limit
0.08
upper Limit
1.20
value
0.41
title
AESI Stroke, ischemic or hemorrhagic
categories
measurements
comment
There were no medically confirmed GI perforations in this period.
group Id
OG000
lower Limit
NA
upper Limit
NA
value
0
comment
There were no medically confirmed GI perforations in this period.
group Id
OG001
lower Limit
NA
upper Limit
NA
value
0
group Id
OG002
lower Limit
0.06
upper Limit
1.76
value
0.49
group Id
OG003
lower Limit
0.01
upper Limit
1.44
value
0.26
comment
There were no medically confirmed GI perforations in this period.
group Id
OG004
lower Limit
NA
upper Limit
NA
value
0
title
AESI GI perforation
categories
measurements
group Id
OG000
lower Limit
0.45
upper Limit
2.69
value
1.23
group Id
OG001
lower Limit
0.78
upper Limit
3.55
value
1.80
group Id
OG002
lower Limit
0.27
upper Limit
2.49
value
0.97
group Id
OG003
lower Limit
0.16
upper Limit
2.26
value
0.77
group Id
OG004
lower Limit
0.75
upper Limit
2.69
value
1.50
title
AESI Malignancy
denoms
counts
group Id
OG000
value
538
group Id
OG001
value
509
group Id
OG002
value
463
group Id
OG003
value
434
group Id
OG004
value
414
units
Participants
description
Patient year (PY) refers to duration in study, calculated from first active drug intake to last safety assessment available + 1. Patient year rates with confidence interval were calculated for adverse events of interest in evaluating the long-term safety of the product being studied.
Abbreviations include the following: adverse event (AE), adverse event of special interest (AESI), gastrointestinal (GI), serious adverse event (SAE), and investigational product (IP). Hypersensitivity events were defined as AEs that occurred during or within 24 hours of IP infusion and were not deemed "unrelated" to trial treatment by the investigator. This definition includes all types of AEs, regardless of whether or not they were consistent with hypersensitivity.
Medical confirmation of the AESI "GI perforation" was based on medical adjudication of events captured by the GI Perforation Standardised MedDRA Queries (SMQs).
dispersion Type
95% Confidence Interval
groups
description
Participants with scores during Months 0-12, which equates to baseline through Week 48 (Total PY=486.34).
id
OG000
title
Months 0 - 12
description
Participants with scores during Months 13 - 24, which equates to Weeks 49-96 (Total PY=444.49).
id
OG001
title
Months 13 - 24
description
Participants with scores during Months 25 - 36, which equates to Weeks 97-144 (Total PY=410.93).
id
OG002
title
Months 25 - 36
description
Participants with scores during Months 37 - 48, which equates to Weeks 145-192 (Total PY=388.25).
id
OG003
title
Months 37 - 48
description
Participants with scores during Months greater than 48, which equates to Weeks 193-264 (Total PY=731.93).
id
OG004
title
Months Greater Than 48
param Type
NUMBER
population Description
All exposure population, which includes all participants who entered the study and received at least one dose of tocilizumab at any time.
Triangle