Trial Outcomes & Findings for Infliximab for Treatment of Axial Spondyloarthritis (P05336 AM1) (NCT NCT00844805)

NCT ID: NCT00844805

Last Updated: 2017-04-12

Results Overview

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).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

158 participants

Primary outcome timeframe

Week 28

Results posted on

2017-04-12

Participant Flow

Participant milestones

Participant milestones
Measure
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.
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.
Naproxen
For participants who achieved partial remission during 28-week treatment phase, naproxen was continued at a daily dose of 1000 mg administered orally for an additional 24 weeks in the follow-up phase.
No Treatment
For participants who achieved partial remission during Treatment phase, no treatment was administered for an additional 24 weeks in the follow-up phase.
Treatment Phase
STARTED
106
52
0
0
Treatment Phase
COMPLETED
96
45
0
0
Treatment Phase
NOT COMPLETED
10
7
0
0
Follow-Up Phase
STARTED
0
0
41
41
Follow-Up Phase
COMPLETED
0
0
32
32
Follow-Up Phase
NOT COMPLETED
0
0
9
9

Reasons for withdrawal

Reasons for withdrawal
Measure
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.
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.
Naproxen
For participants who achieved partial remission during 28-week treatment phase, naproxen was continued at a daily dose of 1000 mg administered orally for an additional 24 weeks in the follow-up phase.
No Treatment
For participants who achieved partial remission during Treatment phase, no treatment was administered for an additional 24 weeks in the follow-up phase.
Treatment Phase
Adverse Event
5
1
0
0
Treatment Phase
Withdrawal by Subject
3
4
0
0
Treatment Phase
Noncompliance With Protocol
1
0
0
0
Treatment Phase
Did Not Meet Protocol Eligibility
1
2
0
0
Follow-Up Phase
Adverse Event
0
0
1
0
Follow-Up Phase
Withdrawal by Subject
0
0
6
3
Follow-Up Phase
Noncompliance With Protocol
0
0
0
1
Follow-Up Phase
Relapse/Recurrence
0
0
2
4
Follow-Up Phase
Did Not Meet Protocol Eligibility
0
0
0
1

Baseline Characteristics

Infliximab for Treatment of Axial Spondyloarthritis (P05336 AM1)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Infliximab + Naproxen
n=105 Participants
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.
Placebo + Naproxen
n=51 Participants
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.
Total
n=156 Participants
Total of all reporting groups
Age, Continuous
31.7 years
STANDARD_DEVIATION 8.51 • n=99 Participants
30.7 years
STANDARD_DEVIATION 7.34 • n=107 Participants
31.4 years
STANDARD_DEVIATION 8.12 • n=206 Participants
Sex: Female, Male
Female
33 Participants
n=99 Participants
11 Participants
n=107 Participants
44 Participants
n=206 Participants
Sex: Female, Male
Male
72 Participants
n=99 Participants
40 Participants
n=107 Participants
112 Participants
n=206 Participants

PRIMARY outcome

Timeframe: 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.

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).

Outcome measures

Outcome measures
Measure
Infliximab + Naproxen
n=105 Participants
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
Placebo + Naproxen
n=51 Participants
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.
Number of Participants Achieving the Assessment in Ankylosing Spondylitis (ASAS) Partial Remission Criteria at Week 28
Achieved Partial Remission
65 Participants
18 Participants
Number of Participants Achieving the Assessment in Ankylosing Spondylitis (ASAS) Partial Remission Criteria at Week 28
Did Not Achieve Partial Remission
40 Participants
33 Participants

SECONDARY outcome

Timeframe: 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.

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).

Outcome measures

Outcome measures
Measure
Infliximab + Naproxen
n=40 Participants
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
Placebo + Naproxen
n=40 Participants
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.
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
16 Participants
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
24 Participants

SECONDARY outcome

Timeframe: 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.

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).

Outcome measures

Outcome measures
Measure
Infliximab + Naproxen
n=105 Participants
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
Placebo + Naproxen
n=51 Participants
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.
Percentage of Participants Maintaining the ASAS Partial Remission Criteria at Week 52 By Treatment Assignment in the Treatment Phase
40 Percentage of Participants
55 Percentage of Participants

SECONDARY outcome

Timeframe: Baseline, Week 28

Population: The number of participants represented those with a screening value and a value at treatment 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.

Outcome measures

Outcome measures
Measure
Infliximab + Naproxen
n=98 Participants
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
Placebo + Naproxen
n=47 Participants
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.
Change From Baseline of Berlin Magnetic Resonance Imaging (MRI) Spine Overall Score at Week 28
-0.5 Units on a Scale
Interval -3.5 to 0.0
0.0 Units on a Scale
Interval -4.7 to 0.0

SECONDARY outcome

Timeframe: Baseline, Week 28

Population: The number of participants represented those with a screening value and a value 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.

Outcome measures

Outcome measures
Measure
Infliximab + Naproxen
n=97 Participants
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
Placebo + Naproxen
n=47 Participants
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.
Change From Baseline in the Sacroiliac Overall Score at Week 28
-2.0 Units on a Scale
Interval -7.0 to -0.5
-3.0 Units on a Scale
Interval -6.5 to -1.0

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: The number of participants represents those with a Week 28 values and those with a Week 52 value.

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.

Outcome measures

Outcome measures
Measure
Infliximab + Naproxen
n=37 Participants
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
Placebo + Naproxen
n=37 Participants
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.
Change From Baseline of Berlin MRI Spine Overall Score at Week 52
0.0 Units on a Scale
Interval 0.0 to 1.0
0.0 Units on a Scale
Interval 0.0 to 2.3

SECONDARY outcome

Timeframe: Baseline, Week 28

Population: The number of participants represented those with a screening value and a value 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.

Outcome measures

Outcome measures
Measure
Infliximab + Naproxen
n=36 Participants
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
Placebo + Naproxen
n=36 Participants
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.
Change From Baseline in the Sacroiliac Overall Score at Week 52
1.1 Units on a Scale
Interval 0.0 to 4.0
1.0 Units on a Scale
Interval 0.0 to 3.3

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure
Infliximab + Naproxen
n=105 Participants
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
Placebo + Naproxen
n=51 Participants
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.
Number of Participants With Complete Absence of Active Inflammatory Lesions at the Spine at Treatment Week 28
63 Participants
23 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure
Infliximab + Naproxen
n=105 Participants
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
Placebo + Naproxen
n=51 Participants
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.
Number of Participants With Complete Absence of Active Inflammatory Lesions at the Sacroiliac Joint at Treatment Week 28
29 Participants
3 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure
Infliximab + Naproxen
n=105 Participants
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
Placebo + Naproxen
n=51 Participants
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.
Number of Participants With Complete Absence of Active Inflammatory Lesions at the Spine and Sacroiliac Joint at Treatment Week 28
19 Participants
0 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure
Infliximab + Naproxen
n=40 Participants
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
Placebo + Naproxen
n=40 Participants
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.
Number of Participants With Complete Absence of Active Inflammatory Lesions at the Spine at Treatment Week 52
20 Participants
16 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure
Infliximab + Naproxen
n=40 Participants
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
Placebo + Naproxen
n=40 Participants
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.
Number of Participants With Complete Absence of Active Inflammatory Lesions at the Sacroiliac Joint at Treatment Week 52
3 Participants
4 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure
Infliximab + Naproxen
n=40 Participants
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
Placebo + Naproxen
n=40 Participants
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.
Number of Participants With Complete Absence of Active Inflammatory Lesions at the Spine and Sacroiliac Joint at Treatment Week 52
1 Participants
1 Participants

SECONDARY outcome

Timeframe: 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.

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).

Outcome measures

Outcome measures
Measure
Infliximab + Naproxen
n=40 Participants
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
Placebo + Naproxen
n=40 Participants
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.
Median Duration of Maintaining ASAS Partial Remission in the Follow-Up Phase
23.00 Weeks
Interval 3.43 to 26.71
12.57 Weeks
Interval 4.71 to 25.14

SECONDARY outcome

Timeframe: 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.

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).

Outcome measures

Outcome measures
Measure
Infliximab + Naproxen
n=40 Participants
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
Placebo + Naproxen
n=40 Participants
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.
Number of Participants Who Achieved ASAS Partial Remission That Experienced Disease Flare With Naproxen Maintenance Treatment in the Follow-Up Phase
1 Participants
3 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure
Infliximab + Naproxen
n=105 Participants
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
Placebo + Naproxen
n=51 Participants
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.
Percentage of Participants That Achieved ASAS-40 Response at Week 28 in the Treatment Phase
79 Percentage of Participants
29 Percentage of Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure
Infliximab + Naproxen
n=105 Participants
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
Placebo + Naproxen
n=51 Participants
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.
Percentage of Participants That Achieved ASAS-20 Response at Week 28 in the Treatment Phase
85 Percentage of Participants
37 Percentage of Participants

Adverse Events

Infliximab + Naproxen

Serious events: 6 serious events
Other events: 24 other events
Deaths: 0 deaths

Placebo + Naproxen

Serious events: 3 serious events
Other events: 8 other events
Deaths: 0 deaths

Naproxen

Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths

No Treatment

Serious events: 3 serious events
Other events: 11 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Infliximab + Naproxen
n=105 participants at risk
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.
Placebo + Naproxen
n=52 participants at risk
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.
Naproxen
n=41 participants at risk
For participants who achieved remission during 28-week treatment phase, naproxen was continued at a daily dose of 1000 mg administered orally for an additional 24 weeks in the follow-up phase.
No Treatment
n=41 participants at risk
For participants who achieved remission during Treatment phase, no treatment was administered for an additional 24 weeks in the follow-up phase.
Blood and lymphatic system disorders
Anaemia
0.00%
0/105 • Up to Week 52.
The Safety Population consisted of all participants who received at least one dose of study medication.
1.9%
1/52 • Number of events 1 • Up to Week 52.
The Safety Population consisted of all participants who received at least one dose of study medication.
0.00%
0/41 • Up to Week 52.
The Safety Population consisted of all participants who received at least one dose of study medication.
2.4%
1/41 • Number of events 1 • Up to Week 52.
The Safety Population consisted of all participants who received at least one dose of study medication.
General disorders
Chest Discomfort
0.95%
1/105 • Number of events 1 • Up to Week 52.
The Safety Population consisted of all participants who received at least one dose of study medication.
0.00%
0/52 • Up to Week 52.
The Safety Population consisted of all participants who received at least one dose of study medication.
0.00%
0/41 • Up to Week 52.
The Safety Population consisted of all participants who received at least one dose of study medication.
0.00%
0/41 • Up to Week 52.
The Safety Population consisted of all participants who received at least one dose of study medication.
Infections and infestations
Pneumonia
0.95%
1/105 • Number of events 1 • Up to Week 52.
The Safety Population consisted of all participants who received at least one dose of study medication.
0.00%
0/52 • Up to Week 52.
The Safety Population consisted of all participants who received at least one dose of study medication.
0.00%
0/41 • Up to Week 52.
The Safety Population consisted of all participants who received at least one dose of study medication.
0.00%
0/41 • Up to Week 52.
The Safety Population consisted of all participants who received at least one dose of study medication.
Infections and infestations
Tuberculosis
0.95%
1/105 • Number of events 1 • Up to Week 52.
The Safety Population consisted of all participants who received at least one dose of study medication.
0.00%
0/52 • Up to Week 52.
The Safety Population consisted of all participants who received at least one dose of study medication.
0.00%
0/41 • Up to Week 52.
The Safety Population consisted of all participants who received at least one dose of study medication.
0.00%
0/41 • Up to Week 52.
The Safety Population consisted of all participants who received at least one dose of study medication.
Investigations
Hepatic Enzyme Increased
0.95%
1/105 • Number of events 1 • Up to Week 52.
The Safety Population consisted of all participants who received at least one dose of study medication.
0.00%
0/52 • Up to Week 52.
The Safety Population consisted of all participants who received at least one dose of study medication.
0.00%
0/41 • Up to Week 52.
The Safety Population consisted of all participants who received at least one dose of study medication.
0.00%
0/41 • Up to Week 52.
The Safety Population consisted of all participants who received at least one dose of study medication.
Musculoskeletal and connective tissue disorders
Ankylosing Spondylitis
0.00%
0/105 • Up to Week 52.
The Safety Population consisted of all participants who received at least one dose of study medication.
1.9%
1/52 • Number of events 1 • Up to Week 52.
The Safety Population consisted of all participants who received at least one dose of study medication.
0.00%
0/41 • Up to Week 52.
The Safety Population consisted of all participants who received at least one dose of study medication.
0.00%
0/41 • Up to Week 52.
The Safety Population consisted of all participants who received at least one dose of study medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast Cancer
0.95%
1/105 • Number of events 1 • Up to Week 52.
The Safety Population consisted of all participants who received at least one dose of study medication.
0.00%
0/52 • Up to Week 52.
The Safety Population consisted of all participants who received at least one dose of study medication.
0.00%
0/41 • Up to Week 52.
The Safety Population consisted of all participants who received at least one dose of study medication.
0.00%
0/41 • Up to Week 52.
The Safety Population consisted of all participants who received at least one dose of study medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Carcinoma In Situ
0.95%
1/105 • Number of events 1 • Up to Week 52.
The Safety Population consisted of all participants who received at least one dose of study medication.
0.00%
0/52 • Up to Week 52.
The Safety Population consisted of all participants who received at least one dose of study medication.
0.00%
0/41 • Up to Week 52.
The Safety Population consisted of all participants who received at least one dose of study medication.
2.4%
1/41 • Number of events 1 • Up to Week 52.
The Safety Population consisted of all participants who received at least one dose of study medication.
Nervous system disorders
Dizziness
0.95%
1/105 • Number of events 1 • Up to Week 52.
The Safety Population consisted of all participants who received at least one dose of study medication.
0/0 • Up to Week 52.
The Safety Population consisted of all participants who received at least one dose of study medication.
0.00%
0/41 • Up to Week 52.
The Safety Population consisted of all participants who received at least one dose of study medication.
0.00%
0/41 • Up to Week 52.
The Safety Population consisted of all participants who received at least one dose of study medication.
Pregnancy, puerperium and perinatal conditions
Foetal Distress Syndrome
0.95%
1/105 • Number of events 1 • Up to Week 52.
The Safety Population consisted of all participants who received at least one dose of study medication.
0.00%
0/52 • Up to Week 52.
The Safety Population consisted of all participants who received at least one dose of study medication.
0.00%
0/41 • Up to Week 52.
The Safety Population consisted of all participants who received at least one dose of study medication.
0.00%
0/41 • Up to Week 52.
The Safety Population consisted of all participants who received at least one dose of study medication.
Pregnancy, puerperium and perinatal conditions
Pregnancy
0.95%
1/105 • Number of events 1 • Up to Week 52.
The Safety Population consisted of all participants who received at least one dose of study medication.
0.00%
0/52 • Up to Week 52.
The Safety Population consisted of all participants who received at least one dose of study medication.
0.00%
0/41 • Up to Week 52.
The Safety Population consisted of all participants who received at least one dose of study medication.
0.00%
0/41 • Up to Week 52.
The Safety Population consisted of all participants who received at least one dose of study medication.
Pregnancy, puerperium and perinatal conditions
Uterine Hypotonus
0.95%
1/105 • Number of events 1 • Up to Week 52.
The Safety Population consisted of all participants who received at least one dose of study medication.
0.00%
0/52 • Up to Week 52.
The Safety Population consisted of all participants who received at least one dose of study medication.
0.00%
0/41 • Up to Week 52.
The Safety Population consisted of all participants who received at least one dose of study medication.
0.00%
0/41 • Up to Week 52.
The Safety Population consisted of all participants who received at least one dose of study medication.
Reproductive system and breast disorders
Ovarian Cyst Ruptured
0.00%
0/105 • Up to Week 52.
The Safety Population consisted of all participants who received at least one dose of study medication.
1.9%
1/52 • Number of events 1 • Up to Week 52.
The Safety Population consisted of all participants who received at least one dose of study medication.
0.00%
0/41 • Up to Week 52.
The Safety Population consisted of all participants who received at least one dose of study medication.
2.4%
1/41 • Number of events 1 • Up to Week 52.
The Safety Population consisted of all participants who received at least one dose of study medication.
Respiratory, thoracic and mediastinal disorders
Dyspnoea
0.95%
1/105 • Number of events 1 • Up to Week 52.
The Safety Population consisted of all participants who received at least one dose of study medication.
0.00%
0/52 • Up to Week 52.
The Safety Population consisted of all participants who received at least one dose of study medication.
0.00%
0/41 • Up to Week 52.
The Safety Population consisted of all participants who received at least one dose of study medication.
0.00%
0/41 • Up to Week 52.
The Safety Population consisted of all participants who received at least one dose of study medication.
Skin and subcutaneous tissue disorders
Dermatitis Atopic
0.00%
0/105 • Up to Week 52.
The Safety Population consisted of all participants who received at least one dose of study medication.
1.9%
1/52 • Number of events 1 • Up to Week 52.
The Safety Population consisted of all participants who received at least one dose of study medication.
0.00%
0/41 • Up to Week 52.
The Safety Population consisted of all participants who received at least one dose of study medication.
2.4%
1/41 • Number of events 1 • Up to Week 52.
The Safety Population consisted of all participants who received at least one dose of study medication.

Other adverse events

Other adverse events
Measure
Infliximab + Naproxen
n=105 participants at risk
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.
Placebo + Naproxen
n=52 participants at risk
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.
Naproxen
n=41 participants at risk
For participants who achieved remission during 28-week treatment phase, naproxen was continued at a daily dose of 1000 mg administered orally for an additional 24 weeks in the follow-up phase.
No Treatment
n=41 participants at risk
For participants who achieved remission during Treatment phase, no treatment was administered for an additional 24 weeks in the follow-up phase.
Gastrointestinal disorders
Abdominal Pain Upper
7.6%
8/105 • Number of events 10 • Up to Week 52.
The Safety Population consisted of all participants who received at least one dose of study medication.
3.8%
2/52 • Number of events 2 • Up to Week 52.
The Safety Population consisted of all participants who received at least one dose of study medication.
0.00%
0/41 • Up to Week 52.
The Safety Population consisted of all participants who received at least one dose of study medication.
0.00%
0/41 • Up to Week 52.
The Safety Population consisted of all participants who received at least one dose of study medication.
Gastrointestinal disorders
Dyspepsia
2.9%
3/105 • Number of events 3 • Up to Week 52.
The Safety Population consisted of all participants who received at least one dose of study medication.
5.8%
3/52 • Number of events 7 • Up to Week 52.
The Safety Population consisted of all participants who received at least one dose of study medication.
0.00%
0/41 • Up to Week 52.
The Safety Population consisted of all participants who received at least one dose of study medication.
0.00%
0/41 • Up to Week 52.
The Safety Population consisted of all participants who received at least one dose of study medication.
Gastrointestinal disorders
Diarrhoea
0.00%
0/105 • Up to Week 52.
The Safety Population consisted of all participants who received at least one dose of study medication.
0.00%
0/52 • Up to Week 52.
The Safety Population consisted of all participants who received at least one dose of study medication.
7.3%
3/41 • Number of events 4 • Up to Week 52.
The Safety Population consisted of all participants who received at least one dose of study medication.
2.4%
1/41 • Number of events 3 • Up to Week 52.
The Safety Population consisted of all participants who received at least one dose of study medication.
Infections and infestations
Nasopharyngitis
12.4%
13/105 • Number of events 16 • Up to Week 52.
The Safety Population consisted of all participants who received at least one dose of study medication.
9.6%
5/52 • Number of events 5 • Up to Week 52.
The Safety Population consisted of all participants who received at least one dose of study medication.
9.8%
4/41 • Number of events 4 • Up to Week 52.
The Safety Population consisted of all participants who received at least one dose of study medication.
14.6%
6/41 • Number of events 9 • Up to Week 52.
The Safety Population consisted of all participants who received at least one dose of study medication.
Infections and infestations
Bronchitis
0.00%
0/105 • Up to Week 52.
The Safety Population consisted of all participants who received at least one dose of study medication.
0.00%
0/52 • Up to Week 52.
The Safety Population consisted of all participants who received at least one dose of study medication.
0.00%
0/41 • Up to Week 52.
The Safety Population consisted of all participants who received at least one dose of study medication.
9.8%
4/41 • Number of events 5 • Up to Week 52.
The Safety Population consisted of all participants who received at least one dose of study medication.
Infections and infestations
Rhinitis
0.00%
0/105 • Up to Week 52.
The Safety Population consisted of all participants who received at least one dose of study medication.
0.00%
0/52 • Up to Week 52.
The Safety Population consisted of all participants who received at least one dose of study medication.
7.3%
3/41 • Number of events 3 • Up to Week 52.
The Safety Population consisted of all participants who received at least one dose of study medication.
4.9%
2/41 • Number of events 2 • Up to Week 52.
The Safety Population consisted of all participants who received at least one dose of study medication.
Nervous system disorders
Headache
6.7%
7/105 • Number of events 14 • Up to Week 52.
The Safety Population consisted of all participants who received at least one dose of study medication.
3.8%
2/52 • Number of events 5 • Up to Week 52.
The Safety Population consisted of all participants who received at least one dose of study medication.
0.00%
0/41 • Up to Week 52.
The Safety Population consisted of all participants who received at least one dose of study medication.
0.00%
0/41 • Up to Week 52.
The Safety Population consisted of all participants who received at least one dose of study medication.

Additional Information

Senior Vice President,Global Clinical Development

Merck Sharp & Dohme Corp

Results disclosure agreements

  • Principal investigator is a sponsor employee The investigator agrees to provide to the sponsor 45 days prior to submission for publication or presentation, review copies of abstracts or manuscripts for publication including, without limitation, slides and texts of oral or other public presentations and texts of any transmission through any electronic media. The sponsor shall have the right to review and comment with respect to data analysis and presentation with regard to protected proprietary information, data accuracy, and fair balance.
  • Publication restrictions are in place

Restriction type: OTHER