Ankylosing Spondylitis, Axial Spondyloarthritis
Conditions
Brief summary
The primary objective of this study was to assess the proportion of participants in the infliximab plus naproxen arm versus the placebo plus naproxen arm, in a population of participants with moderate-to-severe active axial spondyloarthritis and disease duration of ≤3 years, who achieve the Assessment in Ankylosing Spondylitis (ASAS) partial remission criteria.
Detailed description
In the 28-week treatment phase, participants were randomized to receive either infliximab plus naproxen or placebo plus naproxen. After 28-weeks of treatment, participants that achieved partial remission in the treatment phase were randomized to continued treatment with naproxen or to receive no treatment and were followed for an additional 24 weeks (follow-up phase).
Interventions
DRUGInfliximab
DRUGPlacebo
DRUGNaproxen
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 48 Years
Healthy volunteers
No
Inclusion criteria
Participant must: * be 18 to 48 years of age * have diagnosis of active axial spondyloarthritis, with disease duration of less than or equal to 3 years. * have active disease during trial enrollment * have limited treatment history for axial spondyloarthritis (must meet certain criteria) * agree to an acceptable method of contraception (for women of childbearing potential and all men) * must meet certain tuberculosis screening requirements * must meet certain laboratory screening safety requirements * have an x-ray of the sacroiliac joints available from within the previous 12 months (or have one performed during the Screening visit if site is outside of Germany).
Exclusion criteria
Participant will be excluded: * for certain medical conditions and/or recent history of certain medical disorders * for current or recent treatment with certain other medications and certain vaccinations. * for being a woman who is breastfeeding, pregnant, or intending to become pregnant. * if known to have had a substance abuse problem within the previous 3 years prior to screening. * if currently participating in any other clinical study. * for other administrative reasons.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Achieving the Assessment in Ankylosing Spondylitis (ASAS) Partial Remission Criteria at Week 28 | Week 28 | ASAS domains were measured on a visual analog scale (VAS) of 0 to 100 mm (with 0 being the very best situation and 100 being the very worst situation). ASAS partial remission criteria is defined as reaching ≤20 mm in all 4 ASAS domains (i.e., patient global assessment, total back pain, function, and inflammation). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Maintaining the ASAS Partial Remission Criteria at Week 52 By Treatment Assignment in the Treatment Phase | Week 52 | ASAS domains were measured on a VAS of 0 to 100 mm (with 0 being the very best situation and 100 being the very worst situation). ASAS partial remission criteria is defined as reaching ≤20 mm in all 4 ASAS domains (i.e., patient global assessment, total back pain, function, and inflammation). |
| Change From Baseline of Berlin Magnetic Resonance Imaging (MRI) Spine Overall Score at Week 28 | Baseline, Week 28 | MRI scans (T1 for chronic changes and short tau inversion recovery \[STIR\] for active changes) of the whole spine was performed to determine the Berlin MRI Spine Score. The Berlin MRI scoring for the spine was assessed on a scale of 0 (best) to 3 (worst) for a maximum total score of 69, with 0 = no inflammatory lesions; 1 = minor bone marrow edema; 2 = moderate bone marrow edema; 3 = major bone marrow edema; or N = non readable. |
| Change From Baseline in the Sacroiliac Overall Score at Week 28 | Baseline, Week 28 | Each sacroiliac joint was divided into four quadrants. An activity score of 0 (best) to 3 (worst) was assessed for every quadrant of the left and right sacroiliac joint separately for a total maximum score of 24, with with 0 = no inflammatory lesions; 1 = minor bone marrow edema; 2 = moderate bone marrow edema; 3 = major bone marrow edema; or N = non readable. |
| Change From Baseline of Berlin MRI Spine Overall Score at Week 52 | Baseline, Week 52 | MRI scans (T1 for chronic changes and STIR for active changes) of the whole spine was performed to determine the Berlin MRI Spine Score. The Berlin MRI scoring for the spine was assessed on a scale of 0 (best) to 3 (worst) for a maximum total score of 69, with 0 = no inflammatory lesions; 1 = minor bone marrow edema; 2 = moderate bone marrow edema; 3 = major bone marrow edema; or N = non readable. |
| Change From Baseline in the Sacroiliac Overall Score at Week 52 | Baseline, Week 28 | Each sacroiliac joint was divided into four quadrants. An activity score of 0 (best) to 3 (worst) was assessed for every quadrant of the left and right sacroiliac joint separately for a total maximum score of 24, with with 0 = no inflammatory lesions; 1 = minor bone marrow edema; 2 = moderate bone marrow edema; 3 = major bone marrow edema; or N = non readable. |
| Number of Participants With Complete Absence of Active Inflammatory Lesions at the Spine at Treatment Week 28 | Week 28 | MRI scans (T1 for chronic changes and STIR for active changes) of the whole spine was performed to determine the Berlin MRI Spine Score. The Berlin MRI scoring for the spine was assessed on a scale of 0 (best) to 3 (worst) for a maximum total score of 69, with 0 = no inflammatory lesions; 1 = minor bone marrow edema; 2 = moderate bone marrow edema; 3 = major bone marrow edema; or N = non readable. Complete absence of active inflammatory lesions was defined as a Berlin MRI Score = 0. |
| Number of Participants With Complete Absence of Active Inflammatory Lesions at the Sacroiliac Joint at Treatment Week 28 | Week 28 | Each sacroiliac joint was divided into four quadrants. An activity score of 0 (best) to 3 (worst) was assessed for every quadrant of the left and right sacroiliac joint separately for a total maximum score of 24, with with 0 = no inflammatory lesions; 1 = minor bone marrow edema; 2 = moderate bone marrow edema; 3 = major bone marrow edema; or N = non readable. Complete absence of active inflammatory lesions at the sacroiliac joints was defined as a Score = 0. |
| Number of Participants Maintaining the ASAS Partial Remission Criteria at Week 52 By Treatment Assignment in the Follow-Up Phase | Week 52 | ASAS domains were measured on a VAS of 0 to 100 mm (with 0 being the very best situation and 100 being the very worst situation). ASAS partial remission criteria is defined as reaching ≤20 mm in all 4 ASAS domains (i.e., patient global assessment, total back pain, function, and inflammation). |
| Number of Participants With Complete Absence of Active Inflammatory Lesions at the Spine at Treatment Week 52 | Week 52 | MRI scans (T1 for chronic changes and STIR for active changes) of the whole spine was performed to determine the Berlin MRI Spine Score. The Berlin MRI scoring for the spine was assessed on a scale of 0 (best) to 3 (worst) for a maximum total score of 69, with 0 = no inflammatory lesions; 1 = minor bone marrow edema; 2 = moderate bone marrow edema; 3 = major bone marrow edema; or N = non readable. Complete absence of active inflammatory lesions was defined as a Berlin MRI Score = 0. |
| Number of Participants With Complete Absence of Active Inflammatory Lesions at the Sacroiliac Joint at Treatment Week 52 | Week 52 | EaEach sacroiliac joint was divided into four quadrants. An activity score of 0 (best) to 3 (worst) was assessed for every quadrant of the left and right sacroiliac joint separately for a total maximum score of 24, with with 0 = no inflammatory lesions; 1 = minor bone marrow edema; 2 = moderate bone marrow edema; 3 = major bone marrow edema; or N = non readable. Complete absence of active sacroiliac inflammatory lesions was defined as a Score = 0. |
| Number of Participants With Complete Absence of Active Inflammatory Lesions at the Spine and Sacroiliac Joint at Treatment Week 52 | Week 52 | MRI scans (T1 for chronic changes and STIR for active changes) of the whole spine was performed to determine the Berlin MRI Spine Score. The Berlin MRI scoring for the spine was assessed on a scale of 0 (best) to 3 (worst) for a maximum total score of 69, with 0 = no inflammatory lesions; 1 = minor bone marrow edema; 2 = moderate bone marrow edema; 3 = major bone marrow edema; or N = non readable. Complete absence of active spinal inflammatory lesions was defined as a Berlin MRI Score = 0. Each sacroiliac joint was divided into four quadrants. An activity score of 0 (best) to 3 (worst) was assessed for every quadrant of the left and right sacroiliac joint separately for a total maximum score of 24, with with 0 = no inflammatory lesions; 1 = minor bone marrow edema; 2 = moderate bone marrow edema; 3 = major bone marrow edema; or N = non readable. Complete absence of active sacroiliac inflammatory lesions was defined as a Score = 0. |
| Median Duration of Maintaining ASAS Partial Remission in the Follow-Up Phase | Week 52 | ASAS domains were measured on a VAS of 0 to 100 mm (with 0 being the very best situation and 100 being the very worse situation). ASAS partial remission criteria is defined as reaching ≤20 mm in all 4 ASAS domains (i.e., patient global assessment, total back pain, function, and inflammation). |
| Number of Participants Who Achieved ASAS Partial Remission That Experienced Disease Flare With Naproxen Maintenance Treatment in the Follow-Up Phase | Week 52 | The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) employs a VAS of 0mm (best) to 100mm (worst). Disease flare was defined as reaching a BASDAI of ≥30 mm during two consecutive visits after Week 28 until Week 52. ASAS domains were measured on a VAS of 0 to 100 mm (with 0 being the very best situation and 100 being the very worse situation). ASAS partial remission criteria was defined as reaching ≤20 mm in all 4 ASAS domains (i.e., patient global assessment, total back pain, function, and inflammation). |
| Percentage of Participants That Achieved ASAS-40 Response at Week 28 in the Treatment Phase | Week 28 | ASAS domains were measured on a VAS of 0 to 100 mm (with 0 being the very best situation and 100 being the very worse situation). ASAS-40 response was defined as ASAS achieving ≥40% improvement in 3 of the 4 domains (patient global assessment, total back pain, function, and inflammation), with an absolute improvement of ≥20 mm and no deterioration in the remaining domain. |
| Percentage of Participants That Achieved ASAS-20 Response at Week 28 in the Treatment Phase | Week 28 | ASAS-20 response was defined as ≥20% improvement in response according to following criteria: • An improvement of ≥20% from baseline and an absolute improvement from baseline of ≥10 mm in at least 3 of the following 4 domains (patient global assessment, pain, function,and inflammation) • Absence of deterioration from baseline (≥20% and an absolute change of ≥10 mm) in the potential remaining domain. |
| Number of Participants With Complete Absence of Active Inflammatory Lesions at the Spine and Sacroiliac Joint at Treatment Week 28 | Week 28 | MRI scans (T1 for chronic changes and STIR for active changes) of the whole spine was performed to determine the Berlin MRI Spine Score. The Berlin MRI scoring for the spine was assessed on a scale of 0 (best) to 3 (worst) for a maximum total score of 69, with 0 = no inflammatory lesions; 1 = minor bone marrow edema; 2 = moderate bone marrow edema; 3 = major bone marrow edema; or N = non readable. Complete absence of active inflammatory lesions was defined as a Berlin MRI Score = 0. Each sacroiliac joint was divided into four quadrants. An activity score of 0 (best) to 3 (worst) was assessed for every quadrant of the left and right sacroiliac joint separately for a total maximum score of 24, with with 0 = no inflammatory lesions; 1 = minor bone marrow edema; 2 = moderate bone marrow edema; 3 = major bone marrow edema; or N = non readable. Complete absence of active sacroiliac inflammatory lesions was defined as a Score = 0. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Infliximab + Naproxen Infliximab administered at a dose of 5 mg/kg intravenously on Day 1 of Weeks 0, 2, 6, 12, 18, and 24, combined with naproxen administered at a daily dose of 1000 mg for 28 weeks during the 28-week treatment phase. | 105 |
| Placebo + Naproxen Placebo administered intravenously on Day 1 of Weeks 0, 2, 6, 12, 18, and 24, combined with naproxen administered at a daily dose of 1000 mg for 28 weeks, during the 28-week treatment phase. | 51 |
| Total | 156 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Follow-Up Phase | Adverse Event | 0 | 0 | 1 | 0 |
| Follow-Up Phase | Did Not Meet Protocol Eligibility | 0 | 0 | 0 | 1 |
| Follow-Up Phase | Noncompliance With Protocol | 0 | 0 | 0 | 1 |
| Follow-Up Phase | Relapse/Recurrence | 0 | 0 | 2 | 4 |
| Follow-Up Phase | Withdrawal by Subject | 0 | 0 | 6 | 3 |
| Treatment Phase | Adverse Event | 5 | 1 | 0 | 0 |
| Treatment Phase | Did Not Meet Protocol Eligibility | 1 | 2 | 0 | 0 |
| Treatment Phase | Noncompliance With Protocol | 1 | 0 | 0 | 0 |
| Treatment Phase | Withdrawal by Subject | 3 | 4 | 0 | 0 |
Baseline characteristics
| Characteristic | Infliximab + Naproxen | Placebo + Naproxen | Total |
|---|---|---|---|
| Age, Continuous | 31.7 years STANDARD_DEVIATION 8.51 | 30.7 years STANDARD_DEVIATION 7.34 | 31.4 years STANDARD_DEVIATION 8.12 |
| Sex: Female, Male Female | 33 Participants | 11 Participants | 44 Participants |
| Sex: Female, Male Male | 72 Participants | 40 Participants | 112 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 24 / 105 | 8 / 52 | 6 / 41 | 11 / 41 |
| serious Total, serious adverse events | 6 / 105 | 3 / 52 | 0 / 41 | 3 / 41 |
Outcome results
Primary
Number of Participants Achieving the Assessment in Ankylosing Spondylitis (ASAS) Partial Remission Criteria at Week 28
ASAS domains were measured on a visual analog scale (VAS) of 0 to 100 mm (with 0 being the very best situation and 100 being the very worst situation). ASAS partial remission criteria is defined as reaching ≤20 mm in all 4 ASAS domains (i.e., patient global assessment, total back pain, function, and inflammation).
Time frame: Week 28
Population: The Intent-to-Treat Population consisted of all participants who were randomized, took at least one dose of study medication, and had at least one post-baseline efficacy assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Infliximab + Naproxen | Number of Participants Achieving the Assessment in Ankylosing Spondylitis (ASAS) Partial Remission Criteria at Week 28 | Achieved Partial Remission | 65 Participants |
| Infliximab + Naproxen | Number of Participants Achieving the Assessment in Ankylosing Spondylitis (ASAS) Partial Remission Criteria at Week 28 | Did Not Achieve Partial Remission | 40 Participants |
| Placebo + Naproxen | Number of Participants Achieving the Assessment in Ankylosing Spondylitis (ASAS) Partial Remission Criteria at Week 28 | Achieved Partial Remission | 18 Participants |
| Placebo + Naproxen | Number of Participants Achieving the Assessment in Ankylosing Spondylitis (ASAS) Partial Remission Criteria at Week 28 | Did Not Achieve Partial Remission | 33 Participants |
Secondary
Change From Baseline in the Sacroiliac Overall Score at Week 28
Each sacroiliac joint was divided into four quadrants. An activity score of 0 (best) to 3 (worst) was assessed for every quadrant of the left and right sacroiliac joint separately for a total maximum score of 24, with with 0 = no inflammatory lesions; 1 = minor bone marrow edema; 2 = moderate bone marrow edema; 3 = major bone marrow edema; or N = non readable.
Time frame: Baseline, Week 28
Population: The number of participants represented those with a screening value and a value at treatment Week 28.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Infliximab + Naproxen | Change From Baseline in the Sacroiliac Overall Score at Week 28 | -2.0 Units on a Scale |
| Placebo + Naproxen | Change From Baseline in the Sacroiliac Overall Score at Week 28 | -3.0 Units on a Scale |
Secondary
Change From Baseline in the Sacroiliac Overall Score at Week 52
Each sacroiliac joint was divided into four quadrants. An activity score of 0 (best) to 3 (worst) was assessed for every quadrant of the left and right sacroiliac joint separately for a total maximum score of 24, with with 0 = no inflammatory lesions; 1 = minor bone marrow edema; 2 = moderate bone marrow edema; 3 = major bone marrow edema; or N = non readable.
Time frame: Baseline, Week 28
Population: The number of participants represented those with a screening value and a value at treatment Week 28.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Infliximab + Naproxen | Change From Baseline in the Sacroiliac Overall Score at Week 52 | 1.1 Units on a Scale |
| Placebo + Naproxen | Change From Baseline in the Sacroiliac Overall Score at Week 52 | 1.0 Units on a Scale |
Secondary
Change From Baseline of Berlin Magnetic Resonance Imaging (MRI) Spine Overall Score at Week 28
MRI scans (T1 for chronic changes and short tau inversion recovery \[STIR\] for active changes) of the whole spine was performed to determine the Berlin MRI Spine Score. The Berlin MRI scoring for the spine was assessed on a scale of 0 (best) to 3 (worst) for a maximum total score of 69, with 0 = no inflammatory lesions; 1 = minor bone marrow edema; 2 = moderate bone marrow edema; 3 = major bone marrow edema; or N = non readable.
Time frame: Baseline, Week 28
Population: The number of participants represented those with a screening value and a value at treatment Week 28.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Infliximab + Naproxen | Change From Baseline of Berlin Magnetic Resonance Imaging (MRI) Spine Overall Score at Week 28 | -0.5 Units on a Scale |
| Placebo + Naproxen | Change From Baseline of Berlin Magnetic Resonance Imaging (MRI) Spine Overall Score at Week 28 | 0.0 Units on a Scale |
Secondary
Change From Baseline of Berlin MRI Spine Overall Score at Week 52
MRI scans (T1 for chronic changes and STIR for active changes) of the whole spine was performed to determine the Berlin MRI Spine Score. The Berlin MRI scoring for the spine was assessed on a scale of 0 (best) to 3 (worst) for a maximum total score of 69, with 0 = no inflammatory lesions; 1 = minor bone marrow edema; 2 = moderate bone marrow edema; 3 = major bone marrow edema; or N = non readable.
Time frame: Baseline, Week 52
Population: The number of participants represents those with a Week 28 values and those with a Week 52 value.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Infliximab + Naproxen | Change From Baseline of Berlin MRI Spine Overall Score at Week 52 | 0.0 Units on a Scale |
| Placebo + Naproxen | Change From Baseline of Berlin MRI Spine Overall Score at Week 52 | 0.0 Units on a Scale |
Secondary
Median Duration of Maintaining ASAS Partial Remission in the Follow-Up Phase
ASAS domains were measured on a VAS of 0 to 100 mm (with 0 being the very best situation and 100 being the very worse situation). ASAS partial remission criteria is defined as reaching ≤20 mm in all 4 ASAS domains (i.e., patient global assessment, total back pain, function, and inflammation).
Time frame: Week 52
Population: The Intent-to-Treat Population consisted of all participants who were randomized to treatment, took at least one dose of study medication, and had at least one post-baseline efficacy assessment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Infliximab + Naproxen | Median Duration of Maintaining ASAS Partial Remission in the Follow-Up Phase | 23.00 Weeks |
| Placebo + Naproxen | Median Duration of Maintaining ASAS Partial Remission in the Follow-Up Phase | 12.57 Weeks |
p-value: =0.3802Log Rank
Secondary
Number of Participants Maintaining the ASAS Partial Remission Criteria at Week 52 By Treatment Assignment in the Follow-Up Phase
ASAS domains were measured on a VAS of 0 to 100 mm (with 0 being the very best situation and 100 being the very worst situation). ASAS partial remission criteria is defined as reaching ≤20 mm in all 4 ASAS domains (i.e., patient global assessment, total back pain, function, and inflammation).
Time frame: Week 52
Population: The Intent-to-Treat Population consisted of all participants who were randomized, took at least one dose of study medication, and had at least one post-baseline efficacy assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Infliximab + Naproxen | Number of Participants Maintaining the ASAS Partial Remission Criteria at Week 52 By Treatment Assignment in the Follow-Up Phase | Achieved Partial Remission | 19 Participants |
| Infliximab + Naproxen | Number of Participants Maintaining the ASAS Partial Remission Criteria at Week 52 By Treatment Assignment in the Follow-Up Phase | Did Not Achieve Partial Remission | 21 Participants |
| Placebo + Naproxen | Number of Participants Maintaining the ASAS Partial Remission Criteria at Week 52 By Treatment Assignment in the Follow-Up Phase | Achieved Partial Remission | 16 Participants |
| Placebo + Naproxen | Number of Participants Maintaining the ASAS Partial Remission Criteria at Week 52 By Treatment Assignment in the Follow-Up Phase | Did Not Achieve Partial Remission | 24 Participants |
Secondary
Number of Participants Who Achieved ASAS Partial Remission That Experienced Disease Flare With Naproxen Maintenance Treatment in the Follow-Up Phase
The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) employs a VAS of 0mm (best) to 100mm (worst). Disease flare was defined as reaching a BASDAI of ≥30 mm during two consecutive visits after Week 28 until Week 52. ASAS domains were measured on a VAS of 0 to 100 mm (with 0 being the very best situation and 100 being the very worse situation). ASAS partial remission criteria was defined as reaching ≤20 mm in all 4 ASAS domains (i.e., patient global assessment, total back pain, function, and inflammation).
Time frame: Week 52
Population: The Intent-to-Treat Population consisted of all subjects who were randomized, took at least one dose of study medication, and had at least one post-baseline efficacy assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Infliximab + Naproxen | Number of Participants Who Achieved ASAS Partial Remission That Experienced Disease Flare With Naproxen Maintenance Treatment in the Follow-Up Phase | 1 Participants |
| Placebo + Naproxen | Number of Participants Who Achieved ASAS Partial Remission That Experienced Disease Flare With Naproxen Maintenance Treatment in the Follow-Up Phase | 3 Participants |
p-value: =0.615395% CI: [-14.5, 4.5]Fisher Exact
Secondary
Number of Participants With Complete Absence of Active Inflammatory Lesions at the Sacroiliac Joint at Treatment Week 28
Each sacroiliac joint was divided into four quadrants. An activity score of 0 (best) to 3 (worst) was assessed for every quadrant of the left and right sacroiliac joint separately for a total maximum score of 24, with with 0 = no inflammatory lesions; 1 = minor bone marrow edema; 2 = moderate bone marrow edema; 3 = major bone marrow edema; or N = non readable. Complete absence of active inflammatory lesions at the sacroiliac joints was defined as a Score = 0.
Time frame: Week 28
Population: The Intent-to-Treat Population consisted of all participants who were randomized, took at least one dose of study medication, and had at least one post-baseline efficacy assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Infliximab + Naproxen | Number of Participants With Complete Absence of Active Inflammatory Lesions at the Sacroiliac Joint at Treatment Week 28 | 29 Participants |
| Placebo + Naproxen | Number of Participants With Complete Absence of Active Inflammatory Lesions at the Sacroiliac Joint at Treatment Week 28 | 3 Participants |
p-value: =0.001395% CI: [11, 32.5]Fisher Exact
Secondary
Number of Participants With Complete Absence of Active Inflammatory Lesions at the Sacroiliac Joint at Treatment Week 52
EaEach sacroiliac joint was divided into four quadrants. An activity score of 0 (best) to 3 (worst) was assessed for every quadrant of the left and right sacroiliac joint separately for a total maximum score of 24, with with 0 = no inflammatory lesions; 1 = minor bone marrow edema; 2 = moderate bone marrow edema; 3 = major bone marrow edema; or N = non readable. Complete absence of active sacroiliac inflammatory lesions was defined as a Score = 0.
Time frame: Week 52
Population: The Intent-to-Treat Population consisted of all participants who were randomized, took at least one dose of study medication, and had at least one post-baseline efficacy assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Infliximab + Naproxen | Number of Participants With Complete Absence of Active Inflammatory Lesions at the Sacroiliac Joint at Treatment Week 52 | 3 Participants |
| Placebo + Naproxen | Number of Participants With Complete Absence of Active Inflammatory Lesions at the Sacroiliac Joint at Treatment Week 52 | 4 Participants |
p-value: =195% CI: [-14.9, 9.9]Fisher Exact
Secondary
Number of Participants With Complete Absence of Active Inflammatory Lesions at the Spine and Sacroiliac Joint at Treatment Week 28
MRI scans (T1 for chronic changes and STIR for active changes) of the whole spine was performed to determine the Berlin MRI Spine Score. The Berlin MRI scoring for the spine was assessed on a scale of 0 (best) to 3 (worst) for a maximum total score of 69, with 0 = no inflammatory lesions; 1 = minor bone marrow edema; 2 = moderate bone marrow edema; 3 = major bone marrow edema; or N = non readable. Complete absence of active inflammatory lesions was defined as a Berlin MRI Score = 0. Each sacroiliac joint was divided into four quadrants. An activity score of 0 (best) to 3 (worst) was assessed for every quadrant of the left and right sacroiliac joint separately for a total maximum score of 24, with with 0 = no inflammatory lesions; 1 = minor bone marrow edema; 2 = moderate bone marrow edema; 3 = major bone marrow edema; or N = non readable. Complete absence of active sacroiliac inflammatory lesions was defined as a Score = 0.
Time frame: Week 28
Population: The Intent-to-Treat Population consisted of all participants who were randomized, took at least one dose of study medication, and had at least one post-baseline efficacy assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Infliximab + Naproxen | Number of Participants With Complete Absence of Active Inflammatory Lesions at the Spine and Sacroiliac Joint at Treatment Week 28 | 19 Participants |
| Placebo + Naproxen | Number of Participants With Complete Absence of Active Inflammatory Lesions at the Spine and Sacroiliac Joint at Treatment Week 28 | 0 Participants |
p-value: =0.000495% CI: [10.7, 25.5]Fisher Exact
Secondary
Number of Participants With Complete Absence of Active Inflammatory Lesions at the Spine and Sacroiliac Joint at Treatment Week 52
MRI scans (T1 for chronic changes and STIR for active changes) of the whole spine was performed to determine the Berlin MRI Spine Score. The Berlin MRI scoring for the spine was assessed on a scale of 0 (best) to 3 (worst) for a maximum total score of 69, with 0 = no inflammatory lesions; 1 = minor bone marrow edema; 2 = moderate bone marrow edema; 3 = major bone marrow edema; or N = non readable. Complete absence of active spinal inflammatory lesions was defined as a Berlin MRI Score = 0. Each sacroiliac joint was divided into four quadrants. An activity score of 0 (best) to 3 (worst) was assessed for every quadrant of the left and right sacroiliac joint separately for a total maximum score of 24, with with 0 = no inflammatory lesions; 1 = minor bone marrow edema; 2 = moderate bone marrow edema; 3 = major bone marrow edema; or N = non readable. Complete absence of active sacroiliac inflammatory lesions was defined as a Score = 0.
Time frame: Week 52
Population: The Intent-to-Treat Population consisted of all participants who were randomized, took at least one dose of study medication, and had at least one post-baseline efficacy assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Infliximab + Naproxen | Number of Participants With Complete Absence of Active Inflammatory Lesions at the Spine and Sacroiliac Joint at Treatment Week 52 | 1 Participants |
| Placebo + Naproxen | Number of Participants With Complete Absence of Active Inflammatory Lesions at the Spine and Sacroiliac Joint at Treatment Week 52 | 1 Participants |
p-value: =195% CI: [-6.8, 6.8]Fisher Exact
Secondary
Number of Participants With Complete Absence of Active Inflammatory Lesions at the Spine at Treatment Week 28
MRI scans (T1 for chronic changes and STIR for active changes) of the whole spine was performed to determine the Berlin MRI Spine Score. The Berlin MRI scoring for the spine was assessed on a scale of 0 (best) to 3 (worst) for a maximum total score of 69, with 0 = no inflammatory lesions; 1 = minor bone marrow edema; 2 = moderate bone marrow edema; 3 = major bone marrow edema; or N = non readable. Complete absence of active inflammatory lesions was defined as a Berlin MRI Score = 0.
Time frame: Week 28
Population: The Intent-to-Treat Population consisted of all participants who were randomized, took at least one dose of study medication, and had at least one post-baseline efficacy assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Infliximab + Naproxen | Number of Participants With Complete Absence of Active Inflammatory Lesions at the Spine at Treatment Week 28 | 63 Participants |
| Placebo + Naproxen | Number of Participants With Complete Absence of Active Inflammatory Lesions at the Spine at Treatment Week 28 | 23 Participants |
p-value: =0.088495% CI: [-1.7, 31.5]Fisher Exact
Secondary
Number of Participants With Complete Absence of Active Inflammatory Lesions at the Spine at Treatment Week 52
MRI scans (T1 for chronic changes and STIR for active changes) of the whole spine was performed to determine the Berlin MRI Spine Score. The Berlin MRI scoring for the spine was assessed on a scale of 0 (best) to 3 (worst) for a maximum total score of 69, with 0 = no inflammatory lesions; 1 = minor bone marrow edema; 2 = moderate bone marrow edema; 3 = major bone marrow edema; or N = non readable. Complete absence of active inflammatory lesions was defined as a Berlin MRI Score = 0.
Time frame: Week 52
Population: The Intent-to-Treat Population consisted of all participants that were randomized, took at least one dose of study medication, and had at least one post-baseline efficacy assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Infliximab + Naproxen | Number of Participants With Complete Absence of Active Inflammatory Lesions at the Spine at Treatment Week 52 | 20 Participants |
| Placebo + Naproxen | Number of Participants With Complete Absence of Active Inflammatory Lesions at the Spine at Treatment Week 52 | 16 Participants |
p-value: =0.500595% CI: [-11.7, 31.7]Fisher Exact
Secondary
Percentage of Participants Maintaining the ASAS Partial Remission Criteria at Week 52 By Treatment Assignment in the Treatment Phase
ASAS domains were measured on a VAS of 0 to 100 mm (with 0 being the very best situation and 100 being the very worst situation). ASAS partial remission criteria is defined as reaching ≤20 mm in all 4 ASAS domains (i.e., patient global assessment, total back pain, function, and inflammation).
Time frame: Week 52
Population: The Intent-to-Treat Population consisted of all participants who were randomized, took at least one dose of study medication, and had at least one post-baseline efficacy assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Infliximab + Naproxen | Percentage of Participants Maintaining the ASAS Partial Remission Criteria at Week 52 By Treatment Assignment in the Treatment Phase | 40 Percentage of Participants |
| Placebo + Naproxen | Percentage of Participants Maintaining the ASAS Partial Remission Criteria at Week 52 By Treatment Assignment in the Treatment Phase | 55 Percentage of Participants |
Secondary
Percentage of Participants That Achieved ASAS-20 Response at Week 28 in the Treatment Phase
ASAS-20 response was defined as ≥20% improvement in response according to following criteria: • An improvement of ≥20% from baseline and an absolute improvement from baseline of ≥10 mm in at least 3 of the following 4 domains (patient global assessment, pain, function,and inflammation) • Absence of deterioration from baseline (≥20% and an absolute change of ≥10 mm) in the potential remaining domain.
Time frame: Week 28
Population: The Intent-to-Treat Population consisted of all participants who were randomized, took at least one dose of study medication, and had at least one post-baseline efficacy assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Infliximab + Naproxen | Percentage of Participants That Achieved ASAS-20 Response at Week 28 in the Treatment Phase | 85 Percentage of Participants |
| Placebo + Naproxen | Percentage of Participants That Achieved ASAS-20 Response at Week 28 in the Treatment Phase | 37 Percentage of Participants |
p-value: =0.301195% CI: [-6, 22.8]Fisher Exact
Secondary
Percentage of Participants That Achieved ASAS-40 Response at Week 28 in the Treatment Phase
ASAS domains were measured on a VAS of 0 to 100 mm (with 0 being the very best situation and 100 being the very worse situation). ASAS-40 response was defined as ASAS achieving ≥40% improvement in 3 of the 4 domains (patient global assessment, total back pain, function, and inflammation), with an absolute improvement of ≥20 mm and no deterioration in the remaining domain.
Time frame: Week 28
Population: The Intent-to-Treat Population consisted of all participants who were randomized, took at least one dose of study medication, and had at least one post-baseline efficacy assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Infliximab + Naproxen | Percentage of Participants That Achieved ASAS-40 Response at Week 28 in the Treatment Phase | 79 Percentage of Participants |
| Placebo + Naproxen | Percentage of Participants That Achieved ASAS-40 Response at Week 28 in the Treatment Phase | 29 Percentage of Participants |
p-value: =0.026395% CI: [2.5, 34.3]Fisher Exact