Trial Outcomes & Findings for A Study of Adalimumab in Japanese Subjects With Active Ankylosing Spondylitis (NCT NCT00667355)
NCT ID: NCT00667355
Last Updated: 2012-01-26
Results Overview
ASAS measures symptomatic improvement in Ankylosing Spondylitis (AS) subjects. ASAS has 4 domains: patient global assessment of disease activity, pain, function, inflammation. ASAS 20 = at least 20% improvement (vs. baseline) and an absolute improvement ≥ 10 units on a 0 - 100 scale (0 = no disease activity; 100 = high disease activity) for ≥ 3 domains, and no worsening (defined as a worsening of ≥ 20% and a net worsening of ≥ 10 units) in the remaining domain.
COMPLETED
PHASE3
41 participants
Week 12
2012-01-26
Participant Flow
Participant milestones
| Measure |
Adalimumab
Adalimumab 40 mg or 80 mg subcutaneously administered every other week until approval of adalimumab for Ankylosing Spondylitis (AS) in Japan.
|
|---|---|
|
Overall Study
STARTED
|
41
|
|
Overall Study
COMPLETED
|
30
|
|
Overall Study
NOT COMPLETED
|
11
|
Reasons for withdrawal
| Measure |
Adalimumab
Adalimumab 40 mg or 80 mg subcutaneously administered every other week until approval of adalimumab for Ankylosing Spondylitis (AS) in Japan.
|
|---|---|
|
Overall Study
Adverse Event
|
5
|
|
Overall Study
Lost to Follow-up
|
1
|
|
Overall Study
Other reason was not specified
|
5
|
Baseline Characteristics
A Study of Adalimumab in Japanese Subjects With Active Ankylosing Spondylitis
Baseline characteristics by cohort
| Measure |
Adalimumab
n=41 Participants
Adalimumab 40 mg or 80 mg subcutaneously administered every other week until approval of adalimumab for Ankylosing Spondylitis (AS) in Japan.
|
|---|---|
|
Age, Customized
<40 years
|
25 subjects
n=93 Participants
|
|
Age, Customized
Between 40 and 65 years
|
16 subjects
n=93 Participants
|
|
Age, Customized
>65 years
|
0 subjects
n=93 Participants
|
|
Age Continuous
|
37.2 years
STANDARD_DEVIATION 12.17 • n=93 Participants
|
|
Sex: Female, Male
Female
|
9 Participants
n=93 Participants
|
|
Sex: Female, Male
Male
|
32 Participants
n=93 Participants
|
|
Region of Enrollment
Japan
|
41 subjects
n=93 Participants
|
PRIMARY outcome
Timeframe: Week 12Population: For all non-responder imputation (NRI) analyses, subjects with a missing value at a visit were imputed as a non-responder for that visit. Observed cases is based on a total of 40 subjects analyzed (vs. 41 subjects for the study and all other analysis sets) due to 1 subject who discontinued prior to Week 12.
ASAS measures symptomatic improvement in Ankylosing Spondylitis (AS) subjects. ASAS has 4 domains: patient global assessment of disease activity, pain, function, inflammation. ASAS 20 = at least 20% improvement (vs. baseline) and an absolute improvement ≥ 10 units on a 0 - 100 scale (0 = no disease activity; 100 = high disease activity) for ≥ 3 domains, and no worsening (defined as a worsening of ≥ 20% and a net worsening of ≥ 10 units) in the remaining domain.
Outcome measures
| Measure |
Adalimumab
n=41 Participants
Adalimumab 40 mg or 80 mg subcutaneously administered every other week until approval of adalimumab for Ankylosing Spondylitis (AS) in Japan.
|
|---|---|
|
Number of Subjects Achieving Assessment in Ankylosing Spondylitis 20 (ASAS 20) at Week 12
Non-responder imputation (NRI), N = 41
|
30 Subjects
|
|
Number of Subjects Achieving Assessment in Ankylosing Spondylitis 20 (ASAS 20) at Week 12
Last Observation Carried Forward (LOCF), N = 41
|
30 Subjects
|
|
Number of Subjects Achieving Assessment in Ankylosing Spondylitis 20 (ASAS 20) at Week 12
Observed Cases, N = 40
|
30 Subjects
|
SECONDARY outcome
Timeframe: Weeks 12, 24, 48, 72, 96, 120, and Final VisitPopulation: Analysis is based on non-responder imputation (NRI), for which subjects with a missing value at a visit were imputed as a non-responder for that visit.
ASAS measures symptomatic improvement in Ankylosing Spondylitis (AS) subjects. ASAS has 4 domains: patient global assessment of disease activity, pain, function, inflammation. ASAS 20 = 20% improvement (vs. baseline) and an absolute improvement ≥ 10 units on a 0-100 scale (0 = no disease activity; 100 = high disease activity) for ≥ 3 domains, and no worsening (defined as a worsening of ≥ 20% and a net worsening of ≥ 10 units) in the remaining domain.
Outcome measures
| Measure |
Adalimumab
n=41 Participants
Adalimumab 40 mg or 80 mg subcutaneously administered every other week until approval of adalimumab for Ankylosing Spondylitis (AS) in Japan.
|
|---|---|
|
Number of Subjects Achieving ASAS 20
Week 12
|
30 Subjects
|
|
Number of Subjects Achieving ASAS 20
Week 24
|
30 Subjects
|
|
Number of Subjects Achieving ASAS 20
Week 48
|
32 Subjects
|
|
Number of Subjects Achieving ASAS 20
Week 72
|
32 Subjects
|
|
Number of Subjects Achieving ASAS 20
Week 96
|
27 Subjects
|
|
Number of Subjects Achieving ASAS 20
Week 120
|
21 Subjects
|
|
Number of Subjects Achieving ASAS 20
Final Visit
|
32 Subjects
|
SECONDARY outcome
Timeframe: Weeks 12, 24, 48, 72, 96, 120, and Final VisitPopulation: Analysis is based on NRI, for which subjects with a missing value at a visit were imputed as a non-responder for that visit.
ASAS measures symptomatic improvement in Ankylosing Spondylitis (AS) subjects. ASAS has 4 domains: patient global assessment of disease activity, pain, function, inflammation. ASAS 50 = at least 50% improvement (vs. baseline) and an absolute improvement ≥ 20 units on a 0-100 scale (0 = no disease activity; 100 = high disease activity) for ≥ 3 domains, and no worsening (defined as a worsening of ≥ 20% and a net worsening of ≥ 10 units) in the remaining domain.
Outcome measures
| Measure |
Adalimumab
n=41 Participants
Adalimumab 40 mg or 80 mg subcutaneously administered every other week until approval of adalimumab for Ankylosing Spondylitis (AS) in Japan.
|
|---|---|
|
Number of Subjects Achieving ASAS 50
Week 12
|
23 Subjects
|
|
Number of Subjects Achieving ASAS 50
Week 24
|
26 Subjects
|
|
Number of Subjects Achieving ASAS 50
Week 48
|
26 Subjects
|
|
Number of Subjects Achieving ASAS 50
Week 72
|
25 Subjects
|
|
Number of Subjects Achieving ASAS 50
Week 96
|
19 Subjects
|
|
Number of Subjects Achieving ASAS 50
Week 120
|
17 Subjects
|
|
Number of Subjects Achieving ASAS 50
Final Visit
|
27 Subjects
|
SECONDARY outcome
Timeframe: Weeks 12, 24, 48, 72, 96, 120, and Final VisitPopulation: Analysis is based on NRI, for which subjects with a missing value at a visit were imputed as a non-responder for that visit.
ASAS measures symptomatic improvement in Ankylosing Spondylitis (AS) subjects. ASAS has 4 domains: patient global assessment of disease activity, pain, function, inflammation. ASAS 70 = at least 70% improvement (vs. baseline) and an absolute improvement ≥ 30 units on a 0-100 scale (0 = no disease activity; 100 = high disease activity) for ≥ 3 domains, and no worsening (defined as a worsening of ≥ 20% and a net worsening of ≥ 10 units) in the remaining domain.
Outcome measures
| Measure |
Adalimumab
n=41 Participants
Adalimumab 40 mg or 80 mg subcutaneously administered every other week until approval of adalimumab for Ankylosing Spondylitis (AS) in Japan.
|
|---|---|
|
Number of Subjects Achieving ASAS 70
Week 12
|
13 Subjects
|
|
Number of Subjects Achieving ASAS 70
Week 24
|
16 Subjects
|
|
Number of Subjects Achieving ASAS 70
Week 48
|
18 Subjects
|
|
Number of Subjects Achieving ASAS 70
Week 72
|
17 Subjects
|
|
Number of Subjects Achieving ASAS 70
Week 96
|
15 Subjects
|
|
Number of Subjects Achieving ASAS 70
Week 120
|
13 Subjects
|
|
Number of Subjects Achieving ASAS 70
Final Visit
|
19 Subjects
|
SECONDARY outcome
Timeframe: Weeks 12, 24, 48, 72, 96, 120, and Final VisitPopulation: Analysis is based on NRI, for which subjects with a missing value at a visit were imputed as a non-responder for that visit.
BASDAI is a validated self assessment tool used to determine disease activity in subjects with Ankylosing Spondylitis (AS). Utilizing a Visual Analog Scale (VAS) of 0-10 (0=none and 10=very severe) subjects answered 6 questions measuring discomfort, pain, fatigue, and morning stiffness. BASDAI 50 = at least 50% improvement (vs. baseline) in BASDAI.
Outcome measures
| Measure |
Adalimumab
n=41 Participants
Adalimumab 40 mg or 80 mg subcutaneously administered every other week until approval of adalimumab for Ankylosing Spondylitis (AS) in Japan.
|
|---|---|
|
Number of Subjects Achieving Bath Ankylosing Spondylitis Disease Activity Index 50 (BASDAI 50)
Week 12
|
27 Subjects
|
|
Number of Subjects Achieving Bath Ankylosing Spondylitis Disease Activity Index 50 (BASDAI 50)
Week 24
|
26 Subjects
|
|
Number of Subjects Achieving Bath Ankylosing Spondylitis Disease Activity Index 50 (BASDAI 50)
Week 48
|
25 Subjects
|
|
Number of Subjects Achieving Bath Ankylosing Spondylitis Disease Activity Index 50 (BASDAI 50)
Week 72
|
28 Subjects
|
|
Number of Subjects Achieving Bath Ankylosing Spondylitis Disease Activity Index 50 (BASDAI 50)
Week 96
|
22 Subjects
|
|
Number of Subjects Achieving Bath Ankylosing Spondylitis Disease Activity Index 50 (BASDAI 50)
Week 120
|
18 Subjects
|
|
Number of Subjects Achieving Bath Ankylosing Spondylitis Disease Activity Index 50 (BASDAI 50)
Final Visit
|
29 Subjects
|
SECONDARY outcome
Timeframe: Baseline, Weeks 12, 24, 48, 72, 96, 120, and Final VisitPopulation: Analysis is based on LOCF.
Subject's assessment of disease activity using a Visual Analog Scale (VAS) of 0 - 100 mm (0 = none and 100 = severe).
Outcome measures
| Measure |
Adalimumab
n=41 Participants
Adalimumab 40 mg or 80 mg subcutaneously administered every other week until approval of adalimumab for Ankylosing Spondylitis (AS) in Japan.
|
|---|---|
|
Mean Change From Baseline in Patient's Global Assessment of Disease Activity
Week 12
|
-34.6 mm on scale
Interval -42.8 to -26.33
|
|
Mean Change From Baseline in Patient's Global Assessment of Disease Activity
Week 24
|
-37.3 mm on scale
Interval -45.99 to -28.69
|
|
Mean Change From Baseline in Patient's Global Assessment of Disease Activity
Week 48
|
-39.5 mm on scale
Interval -47.52 to -31.51
|
|
Mean Change From Baseline in Patient's Global Assessment of Disease Activity
Week 72
|
-39.7 mm on scale
Interval -48.14 to -31.32
|
|
Mean Change From Baseline in Patient's Global Assessment of Disease Activity
Week 96
|
-37.1 mm on scale
Interval -45.96 to -28.34
|
|
Mean Change From Baseline in Patient's Global Assessment of Disease Activity
Week 120
|
-40.1 mm on scale
Interval -48.61 to -31.53
|
|
Mean Change From Baseline in Patient's Global Assessment of Disease Activity
Final Visit
|
-40.6 mm on scale
Interval -48.81 to -32.32
|
SECONDARY outcome
Timeframe: Baseline, Weeks 12, 24, 48, 72, 96, 120, and Final VisitPopulation: Analysis is based on LOCF.
Subject assessed his/her back pain by using a Visual Analog Scale (VAS) of 0 - 100 mm (0 = no pain and 100 = most severe pain).
Outcome measures
| Measure |
Adalimumab
n=41 Participants
Adalimumab 40 mg or 80 mg subcutaneously administered every other week until approval of adalimumab for Ankylosing Spondylitis (AS) in Japan.
|
|---|---|
|
Mean Change From Baseline in Total Back Pain
Week 12
|
-35.6 mm on scale
Interval -43.68 to -27.59
|
|
Mean Change From Baseline in Total Back Pain
Week 24
|
-37.0 mm on scale
Interval -45.05 to -28.85
|
|
Mean Change From Baseline in Total Back Pain
Week 48
|
-38.6 mm on scale
Interval -46.68 to -30.53
|
|
Mean Change From Baseline in Total Back Pain
Week 72
|
-39.3 mm on scale
Interval -47.53 to -31.01
|
|
Mean Change From Baseline in Total Back Pain
Week 96
|
-36.4 mm on scale
Interval -44.33 to -28.4
|
|
Mean Change From Baseline in Total Back Pain
Week 120
|
-39.2 mm on scale
Interval -46.98 to -31.36
|
|
Mean Change From Baseline in Total Back Pain
Final Visit
|
-40.2 mm on scale
Interval -47.8 to -32.64
|
SECONDARY outcome
Timeframe: Baseline, Weeks 12, 24, 48, 72, 96, 120, and Final VisitPopulation: Analysis is based on last observation carried forward (LOCF).
BASFI is a validated self assessment tool that determines the degree of functional limitation in AS subjects. Utilizing a VAS of 0-100 mm (0=easy, 100=impossible), subjects answered 10 questions assessing their ability in completing normal daily activities or physically demanding activities. The BASFI score is a mean score of the 10 questions.
Outcome measures
| Measure |
Adalimumab
n=41 Participants
Adalimumab 40 mg or 80 mg subcutaneously administered every other week until approval of adalimumab for Ankylosing Spondylitis (AS) in Japan.
|
|---|---|
|
Mean Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI)
Week 12
|
-19.4 mm on scale
Interval -24.49 to -14.34
|
|
Mean Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI)
Week 24
|
-20.5 mm on scale
Interval -25.84 to -15.08
|
|
Mean Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI)
Week 48
|
-21.9 mm on scale
Interval -28.39 to -15.51
|
|
Mean Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI)
Week 72
|
-22.2 mm on scale
Interval -29.44 to -14.89
|
|
Mean Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI)
Week 96
|
-22.1 mm on scale
Interval -28.72 to -15.54
|
|
Mean Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI)
Week 120
|
-21.8 mm on scale
Interval -28.07 to -15.51
|
|
Mean Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI)
Final Visit
|
-21.6 mm on scale
Interval -27.65 to -15.49
|
SECONDARY outcome
Timeframe: Baseline, Weeks 12, 24, 48, 72, 96, 120, and Final VisitPopulation: Analysis is based on LOCF.
CRP is a marker of inflammation and measured in mg/dL. A higher level is consistent with inflammation.
Outcome measures
| Measure |
Adalimumab
n=41 Participants
Adalimumab 40 mg or 80 mg subcutaneously administered every other week until approval of adalimumab for Ankylosing Spondylitis (AS) in Japan.
|
|---|---|
|
Mean Change From Baseline in C-Reactive Protein (CRP)
Week 12
|
-1.2 mg/dL
Interval -1.6 to -0.83
|
|
Mean Change From Baseline in C-Reactive Protein (CRP)
Week 24
|
-1.3 mg/dL
Interval -1.76 to -0.89
|
|
Mean Change From Baseline in C-Reactive Protein (CRP)
Week 48
|
-1.4 mg/dL
Interval -1.78 to -0.95
|
|
Mean Change From Baseline in C-Reactive Protein (CRP)
Week 72
|
-1.3 mg/dL
Interval -1.74 to -0.83
|
|
Mean Change From Baseline in C-Reactive Protein (CRP)
Week 96
|
-1.4 mg/dL
Interval -1.84 to -0.94
|
|
Mean Change From Baseline in C-Reactive Protein (CRP)
Week 120
|
-1.3 mg/dL
Interval -1.76 to -0.76
|
|
Mean Change From Baseline in C-Reactive Protein (CRP)
Final Visit
|
-1.2 mg/dL
Interval -1.67 to -0.64
|
SECONDARY outcome
Timeframe: Weeks 12, 24, 48, 72, 96, 120, and Final VisitPopulation: Analysis is based on NRI, for which subjects with a missing value at a visit were imputed as a non-responder for that visit.
ASAS 5/6 consists of 6 domains: the 4 used in ASAS 20 (patient global assessment of disease activity, pain, function, inflammation) plus spinal mobility and an acute phase reactant, C Reactive Protein (CRP). Achieving ASAS 5/6 requires a 20% improvement compared to baseline in ≥ 5 domains (each domain measured on a 0 - 100 scale \[0 = no disease activity; 100 = high disease activity\]).
Outcome measures
| Measure |
Adalimumab
n=41 Participants
Adalimumab 40 mg or 80 mg subcutaneously administered every other week until approval of adalimumab for Ankylosing Spondylitis (AS) in Japan.
|
|---|---|
|
Number of Subjects Achieving Assessment in Ankylosing Spondylitis (ASAS) 5/6.
Week 12
|
28 Subjects
|
|
Number of Subjects Achieving Assessment in Ankylosing Spondylitis (ASAS) 5/6.
Week 24
|
29 Subjects
|
|
Number of Subjects Achieving Assessment in Ankylosing Spondylitis (ASAS) 5/6.
Week 48
|
31 Subjects
|
|
Number of Subjects Achieving Assessment in Ankylosing Spondylitis (ASAS) 5/6.
Week 72
|
28 Subjects
|
|
Number of Subjects Achieving Assessment in Ankylosing Spondylitis (ASAS) 5/6.
Week 96
|
25 Subjects
|
|
Number of Subjects Achieving Assessment in Ankylosing Spondylitis (ASAS) 5/6.
Week 120
|
20 Subjects
|
|
Number of Subjects Achieving Assessment in Ankylosing Spondylitis (ASAS) 5/6.
Final Visit
|
29 Subjects
|
SECONDARY outcome
Timeframe: Weeks 12, 24, 48, 72, 96, 120, and Final VisitPopulation: Analysis is based on NRI, for which subjects with a missing value at a visit were imputed as a non-responder for that visit.
ASAS measures symptomatic improvement in Ankylosing Spondylitis (AS) subjects. ASAS = 4 domains: patient global assessment of disease activity, pain, function, inflammation. ASAS 40 = at least 40% improvement (vs. baseline) and an absolute improvement ≥ 20 units on a 0-100 scale (0 = no disease activity; 100 = high disease activity) for ≥ 3 domains, and no worsening in remaining domain.
Outcome measures
| Measure |
Adalimumab
n=41 Participants
Adalimumab 40 mg or 80 mg subcutaneously administered every other week until approval of adalimumab for Ankylosing Spondylitis (AS) in Japan.
|
|---|---|
|
Number of Subjects Achieving Assessment in Ankylosing Spondylitis 40 (ASAS 40)
Week 12
|
26 Subjects
|
|
Number of Subjects Achieving Assessment in Ankylosing Spondylitis 40 (ASAS 40)
Week 24
|
26 Subjects
|
|
Number of Subjects Achieving Assessment in Ankylosing Spondylitis 40 (ASAS 40)
Week 48
|
27 Subjects
|
|
Number of Subjects Achieving Assessment in Ankylosing Spondylitis 40 (ASAS 40)
Week 72
|
28 Subjects
|
|
Number of Subjects Achieving Assessment in Ankylosing Spondylitis 40 (ASAS 40)
Week 96
|
24 Subjects
|
|
Number of Subjects Achieving Assessment in Ankylosing Spondylitis 40 (ASAS 40)
Week 120
|
18 Subjects
|
|
Number of Subjects Achieving Assessment in Ankylosing Spondylitis 40 (ASAS 40)
Final Visit
|
26 Subjects
|
SECONDARY outcome
Timeframe: Weeks 12, 24, 48, 72, 96, 120, and Final VisitPopulation: Analysis is based on NRI, for which subjects with a missing value at a visit were imputed as a non-responder for that visit.
Partial remission is defined as a score of less than 20 units (on a scale of 0-100; 0=no disease activity and 100=high disease activity) in each of the 4 Assessments in Ankylosing Spondylitis (ASAS) domains: patient global assessment of disease activity, pain, function, and inflammation.
Outcome measures
| Measure |
Adalimumab
n=41 Participants
Adalimumab 40 mg or 80 mg subcutaneously administered every other week until approval of adalimumab for Ankylosing Spondylitis (AS) in Japan.
|
|---|---|
|
Number of Subjects Achieving Assessment in Ankylosing Spondylitis Partial Remission
Week 12
|
15 Subjects
|
|
Number of Subjects Achieving Assessment in Ankylosing Spondylitis Partial Remission
Week 24
|
16 Subjects
|
|
Number of Subjects Achieving Assessment in Ankylosing Spondylitis Partial Remission
Week 48
|
17 Subjects
|
|
Number of Subjects Achieving Assessment in Ankylosing Spondylitis Partial Remission
Week 72
|
20 Subjects
|
|
Number of Subjects Achieving Assessment in Ankylosing Spondylitis Partial Remission
Week 96
|
15 Subjects
|
|
Number of Subjects Achieving Assessment in Ankylosing Spondylitis Partial Remission
Week 120
|
13 Subjects
|
|
Number of Subjects Achieving Assessment in Ankylosing Spondylitis Partial Remission
Final Visit
|
19 Subjects
|
SECONDARY outcome
Timeframe: Baseline, Weeks 12, 24, 48, 72, 96, 120, and Final VisitPopulation: Analysis is based on LOCF.
BASMI is an objective measure of spinal mobility. The BASMI score is composed of 5 measures: tragus to wall distance, lumbar flexion, cervical rotation, lumbar side flexion, and intermalleolar distance. Each measure was scored 0-2 (0=normal mobility/mild disease involvement, 1=moderate disease involvement, 2=severe disease involvement) to give a final total score ranging from 0 to 10. The higher the BASMI score, the more severe was the subject's limitation of movement due to their AS.
Outcome measures
| Measure |
Adalimumab
n=41 Participants
Adalimumab 40 mg or 80 mg subcutaneously administered every other week until approval of adalimumab for Ankylosing Spondylitis (AS) in Japan.
|
|---|---|
|
Mean Change From Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI)
Final Visit
|
-0.6 units on scale
Interval -1.0 to -0.21
|
|
Mean Change From Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI)
Week 12
|
-0.4 units on scale
Interval -0.79 to -0.02
|
|
Mean Change From Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI)
Week 24
|
-0.5 units on scale
Interval -0.9 to -0.17
|
|
Mean Change From Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI)
Week 48
|
-0.6 units on scale
Interval -1.07 to -0.23
|
|
Mean Change From Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI)
Week 72
|
-0.5 units on scale
Interval -0.95 to -0.06
|
|
Mean Change From Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI)
Week 96
|
-0.6 units on scale
Interval -1.03 to -0.13
|
|
Mean Change From Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI)
Week 120
|
-0.7 units on scale
Interval -1.09 to -0.22
|
SECONDARY outcome
Timeframe: Baseline, Weeks 12, 24, 48, 72, 96, 120, and Final VisitPopulation: Analysis is based on LOCF.
Chest expansion is the difference in centimeters between full expiration and full inspiration, measured at the 4th inter-costal space. An increase in chest expansion represents improvement.
Outcome measures
| Measure |
Adalimumab
n=41 Participants
Adalimumab 40 mg or 80 mg subcutaneously administered every other week until approval of adalimumab for Ankylosing Spondylitis (AS) in Japan.
|
|---|---|
|
Mean Change From Baseline in Chest Expansion
Week 12
|
0.7 cm
Interval 0.3 to 1.03
|
|
Mean Change From Baseline in Chest Expansion
Week 24
|
0.4 cm
Interval 0.16 to 0.66
|
|
Mean Change From Baseline in Chest Expansion
Week 48
|
0.8 cm
Interval 0.4 to 1.17
|
|
Mean Change From Baseline in Chest Expansion
Week 72
|
1.0 cm
Interval 0.56 to 1.46
|
|
Mean Change From Baseline in Chest Expansion
Week 96
|
0.6 cm
Interval 0.19 to 1.11
|
|
Mean Change From Baseline in Chest Expansion
Week 120
|
1.1 cm
Interval 0.55 to 1.72
|
|
Mean Change From Baseline in Chest Expansion
Final Visit
|
1.2 cm
Interval 0.54 to 1.8
|
SECONDARY outcome
Timeframe: Baseline, Weeks 12, 24, 48, 72, 96, 120, and Final VisitPopulation: Analysis is based on LOCF.
Assessment of enthesitis was performed in the following 7 domains: 1) 1st costochondral joint left and right, 2) 7th costochondral joint left and right, 3) posterior superior iliac spine left and right, 4) anterior superior iliac spine left and right, 5) iliac crest left and right, 6) 5th lumbar spinous process and 7) proximal insertion of Achilles tendon left and right. Each domain was graded for the presence (1) and absence (0) of tenderness yielding total MASES ranging from 0 (no tenderness) to 13 (worst possible score; severe tenderness).
Outcome measures
| Measure |
Adalimumab
n=41 Participants
Adalimumab 40 mg or 80 mg subcutaneously administered every other week until approval of adalimumab for Ankylosing Spondylitis (AS) in Japan.
|
|---|---|
|
Mean Change From Baseline in Maastricht Ankylosing Spondylitis Enthesitis Score (MASES)
Week 12
|
-1.0 units on a scale
Interval -1.71 to -0.39
|
|
Mean Change From Baseline in Maastricht Ankylosing Spondylitis Enthesitis Score (MASES)
Week 24
|
-1.1 units on a scale
Interval -1.76 to -0.53
|
|
Mean Change From Baseline in Maastricht Ankylosing Spondylitis Enthesitis Score (MASES)
Week 48
|
-1.3 units on a scale
Interval -1.9 to -0.74
|
|
Mean Change From Baseline in Maastricht Ankylosing Spondylitis Enthesitis Score (MASES)
Week 72
|
-1.1 units on a scale
Interval -1.72 to -0.48
|
|
Mean Change From Baseline in Maastricht Ankylosing Spondylitis Enthesitis Score (MASES)
Week 96
|
-1.4 units on a scale
Interval -1.98 to -0.85
|
|
Mean Change From Baseline in Maastricht Ankylosing Spondylitis Enthesitis Score (MASES)
Week 120
|
-1.4 units on a scale
Interval -1.96 to -0.77
|
|
Mean Change From Baseline in Maastricht Ankylosing Spondylitis Enthesitis Score (MASES)
Final Visit
|
-1.4 units on a scale
Interval -1.96 to -0.77
|
SECONDARY outcome
Timeframe: Baseline, Weeks 12, 24, 48, 72, 96, 120, and Final VisitPopulation: Analysis is based on LOCF.
Nocturnal pain assessed by subjects using a Visual Analog Scale (VAS) of 0 - 100 mm (0 = no pain and 100 = worst possible pain).
Outcome measures
| Measure |
Adalimumab
n=41 Participants
Adalimumab 40 mg or 80 mg subcutaneously administered every other week until approval of adalimumab for Ankylosing Spondylitis (AS) in Japan.
|
|---|---|
|
Mean Change From Baseline in Nocturnal Pain
Week 12
|
-30.0 mm on scale
Interval -39.71 to -20.29
|
|
Mean Change From Baseline in Nocturnal Pain
Week 24
|
-31.7 mm on scale
Interval -41.92 to -21.54
|
|
Mean Change From Baseline in Nocturnal Pain
Week 48
|
-35.8 mm on scale
Interval -45.04 to -26.61
|
|
Mean Change From Baseline in Nocturnal Pain
Week 72
|
-34.6 mm on scale
Interval -43.45 to -25.77
|
|
Mean Change From Baseline in Nocturnal Pain
Week 96
|
-33.4 mm on scale
Interval -43.14 to -23.69
|
|
Mean Change From Baseline in Nocturnal Pain
Week 120
|
-35.0 mm on scale
Interval -44.1 to -25.85
|
|
Mean Change From Baseline in Nocturnal Pain
Final Visit
|
-35.3 mm on scale
Interval -44.52 to -26.07
|
SECONDARY outcome
Timeframe: Baseline, Weeks 12, 24, 48, 72, 96, 120, and Final VisitPopulation: Analysis is based on LOCF.
The number of swollen joints among 22 anatomical joints for both the right and left side of the body were assessed by a joint evaluator where the presence of a swollen joint was scored as 1 and absence as 0. The total SJC was derived by the sum of the scores for a range of SJC from 0 (best possible score; no swollen joints) to 44 (worse possible score; all joints swollen).
Outcome measures
| Measure |
Adalimumab
n=41 Participants
Adalimumab 40 mg or 80 mg subcutaneously administered every other week until approval of adalimumab for Ankylosing Spondylitis (AS) in Japan.
|
|---|---|
|
Mean Change From Baseline in Swollen Joint Count for 44 Joints (SJC 44)
Week 12
|
-1.1 SJC
Interval -1.91 to -0.38
|
|
Mean Change From Baseline in Swollen Joint Count for 44 Joints (SJC 44)
Week 24
|
-1.1 SJC
Interval -1.81 to -0.34
|
|
Mean Change From Baseline in Swollen Joint Count for 44 Joints (SJC 44)
Week 48
|
-1.1 SJC
Interval -1.97 to -0.32
|
|
Mean Change From Baseline in Swollen Joint Count for 44 Joints (SJC 44)
Week 72
|
-1.3 SJC
Interval -2.17 to -0.37
|
|
Mean Change From Baseline in Swollen Joint Count for 44 Joints (SJC 44)
Week 96
|
-1.2 SJC
Interval -1.99 to -0.44
|
|
Mean Change From Baseline in Swollen Joint Count for 44 Joints (SJC 44)
Week 120
|
-1.2 SJC
Interval -2.01 to -0.43
|
|
Mean Change From Baseline in Swollen Joint Count for 44 Joints (SJC 44)
Final Visit
|
-1.2 SJC
Interval -1.94 to -0.4
|
SECONDARY outcome
Timeframe: Baseline, Weeks 12, 24, 48, 72, 96, 120, and Final VisitPopulation: Analysis is based on LOCF.
The number of tender or painful joints among 23 anatomical joints for both the right and left side of the body were assessed by a joint evaluator where the presence of a tender or painful joint was scored as 1 and absence as 0. The total TJC was derived by the sum of the scores for a range of TJC from 0 (best possible score; no tender or painful joints) to 46 (worst possible score; all joints tender or painful).
Outcome measures
| Measure |
Adalimumab
n=41 Participants
Adalimumab 40 mg or 80 mg subcutaneously administered every other week until approval of adalimumab for Ankylosing Spondylitis (AS) in Japan.
|
|---|---|
|
Mean Change From Baseline in Tender Joint Count for 46 Joints (TJC 46)
Week 12
|
-1.5 TJC
Interval -3.86 to 0.94
|
|
Mean Change From Baseline in Tender Joint Count for 46 Joints (TJC 46)
Week 24
|
-1.4 TJC
Interval -3.66 to 0.87
|
|
Mean Change From Baseline in Tender Joint Count for 46 Joints (TJC 46)
Week 48
|
-1.3 TJC
Interval -3.6 to 0.96
|
|
Mean Change From Baseline in Tender Joint Count for 46 Joints (TJC 46)
Week 72
|
-1.6 TJC
Interval -4.0 to 0.88
|
|
Mean Change From Baseline in Tender Joint Count for 46 Joints (TJC 46)
Week 96
|
-1.6 TJC
Interval -3.63 to 0.46
|
|
Mean Change From Baseline in Tender Joint Count for 46 Joints (TJC 46)
Week 120
|
-1.6 TJC
Interval -3.69 to 0.56
|
|
Mean Change From Baseline in Tender Joint Count for 46 Joints (TJC 46)
Final Visit
|
-1.6 TJC
Interval -3.69 to 0.56
|
SECONDARY outcome
Timeframe: Baseline, Weeks 12, 24, 48, 72, 96, 120, and Final VisitPopulation: Analysis is based on LOCF.
SF-36 is a standardized survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. These are summarized in a physical component summary (PCS) and mental component summary (MCS) score. The score for a section is an average of the individual question scores, which are scaled 0-100 (0=lowest level of functioning; 100=highest level of functioning).
Outcome measures
| Measure |
Adalimumab
n=41 Participants
Adalimumab 40 mg or 80 mg subcutaneously administered every other week until approval of adalimumab for Ankylosing Spondylitis (AS) in Japan.
|
|---|---|
|
Mean Change From Baseline in 36-Item Short Form (SF-36) Questionnaire
PCS Week 12
|
9.6 units on scale
Interval 6.81 to 12.4
|
|
Mean Change From Baseline in 36-Item Short Form (SF-36) Questionnaire
PCS Week 24
|
10.6 units on scale
Interval 7.51 to 13.67
|
|
Mean Change From Baseline in 36-Item Short Form (SF-36) Questionnaire
PCS Week 48
|
11.4 units on scale
Interval 8.69 to 14.06
|
|
Mean Change From Baseline in 36-Item Short Form (SF-36) Questionnaire
PCS Week 72
|
11.3 units on scale
Interval 8.29 to 14.3
|
|
Mean Change From Baseline in 36-Item Short Form (SF-36) Questionnaire
PCS Week 96
|
12.3 units on scale
Interval 9.25 to 15.37
|
|
Mean Change From Baseline in 36-Item Short Form (SF-36) Questionnaire
PCS Week 120
|
12.1 units on scale
Interval 9.07 to 15.19
|
|
Mean Change From Baseline in 36-Item Short Form (SF-36) Questionnaire
PCS Final Visit
|
12.6 units on scale
Interval 9.75 to 15.53
|
|
Mean Change From Baseline in 36-Item Short Form (SF-36) Questionnaire
MCS Week 12
|
7.0 units on scale
Interval 3.07 to 10.87
|
|
Mean Change From Baseline in 36-Item Short Form (SF-36) Questionnaire
MCS Week 24
|
7.0 units on scale
Interval 3.62 to 10.34
|
|
Mean Change From Baseline in 36-Item Short Form (SF-36) Questionnaire
MCS Week 48
|
6.1 units on scale
Interval 2.52 to 9.59
|
|
Mean Change From Baseline in 36-Item Short Form (SF-36) Questionnaire
MCS Week 72
|
6.7 units on scale
Interval 2.94 to 10.53
|
|
Mean Change From Baseline in 36-Item Short Form (SF-36) Questionnaire
MCS Week 96
|
5.8 units on scale
Interval 2.55 to 9.09
|
|
Mean Change From Baseline in 36-Item Short Form (SF-36) Questionnaire
MCS Week 120
|
6.1 units on scale
Interval 2.63 to 9.59
|
|
Mean Change From Baseline in 36-Item Short Form (SF-36) Questionnaire
MCS Final Visit
|
5.9 units on scale
Interval 2.44 to 9.42
|
Adverse Events
Adalimumab
Serious adverse events
| Measure |
Adalimumab
n=41 participants at risk
Adalimumab 40 mg or 80 mg subcutaneously administered every other week until approval of adalimumab for Ankylosing Spondylitis (AS) in Japan.
|
|---|---|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
2.4%
1/41 • All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.
|
|
Infections and infestations
Intervertebral discitis
|
2.4%
1/41 • All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.
|
|
Infections and infestations
Osteomyelitis
|
2.4%
1/41 • All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.
|
|
Infections and infestations
Pneumonia
|
2.4%
1/41 • All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer
|
2.4%
1/41 • All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.
|
|
Eye disorders
Cataract
|
4.9%
2/41 • All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.
|
|
Gastrointestinal disorders
Periodontitis
|
2.4%
1/41 • All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.
|
|
Infections and infestations
Septic shock
|
2.4%
1/41 • All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.
|
|
Reproductive system and breast disorders
Adenomyosis
|
2.4%
1/41 • All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer
|
2.4%
1/41 • All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.
|
Other adverse events
| Measure |
Adalimumab
n=41 participants at risk
Adalimumab 40 mg or 80 mg subcutaneously administered every other week until approval of adalimumab for Ankylosing Spondylitis (AS) in Japan.
|
|---|---|
|
Eye disorders
Cataract
|
9.8%
4/41 • All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.
|
|
Eye disorders
Conjunctivitis allergic
|
7.3%
3/41 • All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.
|
|
Gastrointestinal disorders
Diarrhoea
|
19.5%
8/41 • All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.
|
|
Gastrointestinal disorders
Stomatitis
|
7.3%
3/41 • All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.
|
|
General disorders
Injection site erythema
|
14.6%
6/41 • All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.
|
|
Hepatobiliary disorders
Hepatic function abnormal
|
22.0%
9/41 • All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.
|
|
Hepatobiliary disorders
Hepatic steatosis
|
7.3%
3/41 • All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.
|
|
Infections and infestations
Nasopharyngitis
|
53.7%
22/41 • All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.
|
|
Infections and infestations
Upper respiratory tract infection
|
17.1%
7/41 • All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.
|
|
Infections and infestations
Pharyngitis
|
9.8%
4/41 • All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.
|
|
Infections and infestations
Gastroenteritis
|
7.3%
3/41 • All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.
|
|
Investigations
Weight increased
|
9.8%
4/41 • All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.
|
|
Metabolism and nutrition disorders
Hyperlipidaemia
|
7.3%
3/41 • All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.
|
|
Musculoskeletal and connective tissue disorders
Ankylosing spondylitis
|
14.6%
6/41 • All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
9.8%
4/41 • All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.
|
|
Nervous system disorders
Headache
|
12.2%
5/41 • All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.
|
|
Respiratory, thoracic and mediastinal disorders
Upper respiratory tract inflammation
|
19.5%
8/41 • All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngolaryngeal pain
|
7.3%
3/41 • All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.
|
|
Skin and subcutaneous tissue disorders
Rash
|
12.2%
5/41 • All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.
|
|
Vascular disorders
Hypertension
|
7.3%
3/41 • All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.
|
|
Injury, poisoning and procedural complications
Contusion
|
14.6%
6/41 • All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.
|
|
Infections and infestations
Influenza
|
9.8%
4/41 • All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.
|
|
Gastrointestinal disorders
Nausea
|
9.8%
4/41 • All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.
|
|
General disorders
Pyrexia
|
9.8%
4/41 • All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
7.3%
3/41 • All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.
|
|
Investigations
C-reactive protein increased
|
7.3%
3/41 • All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.
|
|
Skin and subcutaneous tissue disorders
Dermatitis contact
|
7.3%
3/41 • All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.
|
|
Skin and subcutaneous tissue disorders
Erythema
|
7.3%
3/41 • All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.
|
|
General disorders
Malaise
|
7.3%
3/41 • All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
7.3%
3/41 • All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.
|
|
Infections and infestations
Rhinitis
|
7.3%
3/41 • All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.
|
Additional Information
Global Medical Services
Abbott
Results disclosure agreements
- Principal investigator is a sponsor employee Disclosure agreements vary; the Medical Institution shall not disclose any material/information disclosed by Abbott Japan in connection with the Clinical Research or information obtained by conducting the Clinical Research to third parties without Abbott Japan's prior written approval. When Medical Institution intends to publish information obtained by conducting Clinical Research, Institution shall obtain Abbott Japan's prior written approval.
- Publication restrictions are in place
Restriction type: OTHER