Trial Outcomes & Findings for Treatments Against RA and Effect on FDG-PET/CT (NCT NCT02374021)
NCT ID: NCT02374021
Last Updated: 2022-10-26
Results Overview
The primary outcome was the change in the mean of the maximum of the target to background ratio (TBR) in the most diseased segment (MDS) of of the index vessel as measured by FDG-PET/CT scans conducted at baseline and after 24 weeks of randomized treatment allocation (MDS meanmaxTBR). The index vessel is the vessel (either aorta, left carotid, or right carotid) with the highest meanmaxTBR at baseline. Higher values indicate greater vascular inflammation. FDG uptake measurement: PET-CT images were batch-analyzed by an investigator blinded to the patients' clinical information. FDG uptake was evaluated within the wall of the ascending aorta and bilateral carotid arteries (as maximum and mean standardized FDG uptake value \[SUVmax and SUVmean, respectively\]) approximately every 5 mm on axial images. Subsequently, the target-to-background ratio (TBR) was reported (ratio of the average arterial to blood axial slice SUVmax) to correct for the blood compartment contribution.
COMPLETED
PHASE4
159 participants
0, 6 months
2022-10-26
Participant Flow
Participant milestones
| Measure |
Triple Therapy (MTX+SSZ+HCQ)
Sulfasalazine (SSZ) 1 g bid and hydroxychloroquine (HCQ) 200 mg twice daily, not to exceed 6.5mg/kg HCQ (in addition to concomitant methotrexate \[MTX\]).
Methotrexate: Subjects entering trial will continue on MTX dose of at least 15mg MTX/week. At the discretion of the treating rheumatologist, may be switched to SQ route.
Sulfasalazine: 1 gm bid
Hydroxychloroquine: 200 mg twice daily, not to exceed 6.5mg/kg
|
TNF Inhibitor (Etanercept or Adalimumab)
etanercept 50 mg subcutaneously weekly or adalimumab 40 mg subcutaneously every other week (in addition to concomitant methotrexate, plus hydroxychloroquine, for subjects who were taking this at screening). Biologic treatment will be assigned randomly.
Methotrexate: Subjects entering trial will continue on MTX dose of at least 15mg MTX/week. At the discretion of the treating rheumatologist, may be switched to SQ route.
Etanercept: 50 mg SC weekly
Adalimumab: 40 mg SQ every other week
|
|---|---|---|
|
Overall Study
STARTED
|
80
|
79
|
|
Overall Study
COMPLETED
|
57
|
58
|
|
Overall Study
NOT COMPLETED
|
23
|
21
|
Reasons for withdrawal
| Measure |
Triple Therapy (MTX+SSZ+HCQ)
Sulfasalazine (SSZ) 1 g bid and hydroxychloroquine (HCQ) 200 mg twice daily, not to exceed 6.5mg/kg HCQ (in addition to concomitant methotrexate \[MTX\]).
Methotrexate: Subjects entering trial will continue on MTX dose of at least 15mg MTX/week. At the discretion of the treating rheumatologist, may be switched to SQ route.
Sulfasalazine: 1 gm bid
Hydroxychloroquine: 200 mg twice daily, not to exceed 6.5mg/kg
|
TNF Inhibitor (Etanercept or Adalimumab)
etanercept 50 mg subcutaneously weekly or adalimumab 40 mg subcutaneously every other week (in addition to concomitant methotrexate, plus hydroxychloroquine, for subjects who were taking this at screening). Biologic treatment will be assigned randomly.
Methotrexate: Subjects entering trial will continue on MTX dose of at least 15mg MTX/week. At the discretion of the treating rheumatologist, may be switched to SQ route.
Etanercept: 50 mg SC weekly
Adalimumab: 40 mg SQ every other week
|
|---|---|---|
|
Overall Study
Adverse Event
|
1
|
0
|
|
Overall Study
Lost to Follow-up
|
3
|
2
|
|
Overall Study
Physician Decision
|
0
|
3
|
|
Overall Study
Withdrawal by Subject
|
6
|
5
|
|
Overall Study
Poor Adherence
|
0
|
1
|
|
Overall Study
Scan protocol not followed
|
0
|
1
|
|
Overall Study
Poor quality scan/scan not able to be analyzed
|
13
|
9
|
Baseline Characteristics
Treatments Against RA and Effect on FDG-PET/CT
Baseline characteristics by cohort
| Measure |
Triple Therapy (MTX+SSZ+HCQ)
n=57 Participants
Sulfasalazine (SSZ) 1 g bid and hydroxychloroquine (HCQ) 200 mg twice daily, not to exceed 6.5mg/kg HCQ (in addition to concomitant methotrexate \[MTX\]).
Methotrexate: Subjects entering trial will continue on MTX dose of at least 15mg MTX/week. At the discretion of the treating rheumatologist, may be switched to SQ route.
Sulfasalazine: 1 gm bid
Hydroxychloroquine: 200 mg twice daily, not to exceed 6.5mg/kg
|
TNF Inhibitor (Etanercept or Adalimumab)
n=58 Participants
etanercept 50 mg subcutaneously weekly or adalimumab 40 mg subcutaneously every other week (in addition to concomitant methotrexate, plus hydroxychloroquine, for subjects who were taking this at screening). Biologic treatment will be assigned randomly.
Methotrexate: Subjects entering trial will continue on MTX dose of at least 15mg MTX/week. At the discretion of the treating rheumatologist, may be switched to SQ route.
Etanercept: 50 mg SC weekly
Adalimumab: 40 mg SQ every other week
|
Total
n=115 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
59.0 years
n=93 Participants
|
58.0 years
n=4 Participants
|
58.0 years
n=27 Participants
|
|
Sex: Female, Male
Female
|
43 Participants
n=93 Participants
|
39 Participants
n=4 Participants
|
82 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
14 Participants
n=93 Participants
|
19 Participants
n=4 Participants
|
33 Participants
n=27 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
16 Participants
n=93 Participants
|
15 Participants
n=4 Participants
|
31 Participants
n=27 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
41 Participants
n=93 Participants
|
43 Participants
n=4 Participants
|
84 Participants
n=27 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
DAS28-CRP
|
4.6 units on a scale
n=93 Participants
|
4.9 units on a scale
n=4 Participants
|
4.8 units on a scale
n=27 Participants
|
PRIMARY outcome
Timeframe: 0, 6 monthsPopulation: Participants with a FDG-PET/CT at baseline and six months for whom the primary outcome could be assessed
The primary outcome was the change in the mean of the maximum of the target to background ratio (TBR) in the most diseased segment (MDS) of of the index vessel as measured by FDG-PET/CT scans conducted at baseline and after 24 weeks of randomized treatment allocation (MDS meanmaxTBR). The index vessel is the vessel (either aorta, left carotid, or right carotid) with the highest meanmaxTBR at baseline. Higher values indicate greater vascular inflammation. FDG uptake measurement: PET-CT images were batch-analyzed by an investigator blinded to the patients' clinical information. FDG uptake was evaluated within the wall of the ascending aorta and bilateral carotid arteries (as maximum and mean standardized FDG uptake value \[SUVmax and SUVmean, respectively\]) approximately every 5 mm on axial images. Subsequently, the target-to-background ratio (TBR) was reported (ratio of the average arterial to blood axial slice SUVmax) to correct for the blood compartment contribution.
Outcome measures
| Measure |
Triple Therapy (MTX+SSZ+HCQ)
n=57 Participants
Sulfasalazine (SSZ) 1 g bid and hydroxychloroquine (HCQ) 200 mg twice daily, not to exceed 6.5mg/kg HCQ (in addition to concomitant methotrexate \[MTX\]).
Methotrexate: Subjects entering trial will continue on MTX dose of at least 15mg MTX/week. At the discretion of the treating rheumatologist, may be switched to SQ route.
Sulfasalazine: 1 gm bid
Hydroxychloroquine: 200 mg twice daily, not to exceed 6.5mg/kg
|
TNF Inhibitor (Etanercept or Adalimumab)
n=58 Participants
etanercept 50 mg subcutaneously weekly or adalimumab 40 mg subcutaneously every other week (in addition to concomitant methotrexate, plus hydroxychloroquine, for subjects who were taking this at screening). Biologic treatment will be assigned randomly.
Methotrexate: Subjects entering trial will continue on MTX dose of at least 15mg MTX/week. At the discretion of the treating rheumatologist, may be switched to SQ route.
Etanercept: 50 mg SC weekly
Adalimumab: 40 mg SQ every other week
|
|---|---|---|
|
Change From Baseline in Vascular Inflammation as Measured by FDG-PET/CT at 6 Months
|
-0.19 ratio
Standard Deviation 0.51
|
-0.24 ratio
Standard Deviation 0.51
|
SECONDARY outcome
Timeframe: 0, 6 monthsPopulation: Participants with a FDG-PET/CT at baseline and six months for whom the outcome could be assessed
The outcome was the change in the mean of the maximum of the target to background ratio (TBR) in the most diseased segment (MDS) of the aorta as measured by FDG-PET/CT scans conducted at baseline and after 24 weeks of randomized treatment allocation (MDS meanmaxTBR). Higher values indicate greater vascular inflammation. FDG uptake measurement: PET-CT images were batch-analyzed by an investigator blinded to the patients' clinical information. FDG uptake was evaluated within the wall of the ascending aorta and bilateral carotid arteries (as maximum and mean standardized FDG uptake value \[SUVmax and SUVmean, respectively\]) approximately every 5 mm on axial images. Subsequently, the target-to-background ratio (TBR) was reported (ratio of the average arterial to blood axial slice SUVmax) to correct for the blood compartment contribution.
Outcome measures
| Measure |
Triple Therapy (MTX+SSZ+HCQ)
n=52 Participants
Sulfasalazine (SSZ) 1 g bid and hydroxychloroquine (HCQ) 200 mg twice daily, not to exceed 6.5mg/kg HCQ (in addition to concomitant methotrexate \[MTX\]).
Methotrexate: Subjects entering trial will continue on MTX dose of at least 15mg MTX/week. At the discretion of the treating rheumatologist, may be switched to SQ route.
Sulfasalazine: 1 gm bid
Hydroxychloroquine: 200 mg twice daily, not to exceed 6.5mg/kg
|
TNF Inhibitor (Etanercept or Adalimumab)
n=56 Participants
etanercept 50 mg subcutaneously weekly or adalimumab 40 mg subcutaneously every other week (in addition to concomitant methotrexate, plus hydroxychloroquine, for subjects who were taking this at screening). Biologic treatment will be assigned randomly.
Methotrexate: Subjects entering trial will continue on MTX dose of at least 15mg MTX/week. At the discretion of the treating rheumatologist, may be switched to SQ route.
Etanercept: 50 mg SC weekly
Adalimumab: 40 mg SQ every other week
|
|---|---|---|
|
Change From Baseline in the MDS of the Aorta
|
-0.17 Ratio
Standard Deviation 0.39
|
-0.17 Ratio
Standard Deviation 0.52
|
SECONDARY outcome
Timeframe: 0, 6 monthsPopulation: Participants with a FDG-PET/CT at baseline and six months for whom the outcome could be assessed
The outcome was the change in the target to background ratio (TBR) of the aorta as measured by FDG-PET/CT scans conducted at baseline and after 24 weeks of randomized treatment allocation (MDS meanmaxTBR). Higher values indicate greater vascular inflammation. FDG uptake measurement: PET-CT images were batch-analyzed by an investigator blinded to the patients' clinical information. FDG uptake was evaluated within the wall of the ascending aorta and bilateral carotid arteries (as maximum and mean standardized FDG uptake value \[SUVmax and SUVmean, respectively\]) approximately every 5 mm on axial images. Subsequently, the target-to-background ratio (TBR) was reported (ratio of the average arterial to blood axial slice SUVmax) to correct for the blood compartment contribution.
Outcome measures
| Measure |
Triple Therapy (MTX+SSZ+HCQ)
n=52 Participants
Sulfasalazine (SSZ) 1 g bid and hydroxychloroquine (HCQ) 200 mg twice daily, not to exceed 6.5mg/kg HCQ (in addition to concomitant methotrexate \[MTX\]).
Methotrexate: Subjects entering trial will continue on MTX dose of at least 15mg MTX/week. At the discretion of the treating rheumatologist, may be switched to SQ route.
Sulfasalazine: 1 gm bid
Hydroxychloroquine: 200 mg twice daily, not to exceed 6.5mg/kg
|
TNF Inhibitor (Etanercept or Adalimumab)
n=56 Participants
etanercept 50 mg subcutaneously weekly or adalimumab 40 mg subcutaneously every other week (in addition to concomitant methotrexate, plus hydroxychloroquine, for subjects who were taking this at screening). Biologic treatment will be assigned randomly.
Methotrexate: Subjects entering trial will continue on MTX dose of at least 15mg MTX/week. At the discretion of the treating rheumatologist, may be switched to SQ route.
Etanercept: 50 mg SC weekly
Adalimumab: 40 mg SQ every other week
|
|---|---|---|
|
Change From Baseline in the Average TBR of the Aorta
|
-0.06 Ratio
Standard Deviation 0.34
|
-0.02 Ratio
Standard Deviation 0.43
|
SECONDARY outcome
Timeframe: 0, 6 monthsPopulation: Participants with a FDG-PET/CT at baseline and six months for whom the outcome could be assessed
The outcome was the change in the target to background ratio (TBR) of the average of the left and right carotids as measured by FDG-PET/CT scans conducted at baseline and after 24 weeks of randomized treatment allocation (MDS meanmaxTBR). The baseline values of the left and right carotids were averaged and then the follow-up values of the left and right carotids were averaged resulting in one value at each time point. Higher values indicate greater vascular inflammation. FDG uptake measurement: PET-CT images were batch-analyzed by an investigator blinded to the patients' clinical information. FDG uptake was evaluated within the wall of the ascending aorta and bilateral carotid arteries (as maximum and mean standardized FDG uptake value \[SUVmax and SUVmean, respectively\]) approximately every 5 mm on axial images. Subsequently, the target-to-background ratio (TBR) was reported (ratio of the average arterial to blood axial slice SUVmax) to correct for the blood compartment contribution.
Outcome measures
| Measure |
Triple Therapy (MTX+SSZ+HCQ)
n=43 Participants
Sulfasalazine (SSZ) 1 g bid and hydroxychloroquine (HCQ) 200 mg twice daily, not to exceed 6.5mg/kg HCQ (in addition to concomitant methotrexate \[MTX\]).
Methotrexate: Subjects entering trial will continue on MTX dose of at least 15mg MTX/week. At the discretion of the treating rheumatologist, may be switched to SQ route.
Sulfasalazine: 1 gm bid
Hydroxychloroquine: 200 mg twice daily, not to exceed 6.5mg/kg
|
TNF Inhibitor (Etanercept or Adalimumab)
n=45 Participants
etanercept 50 mg subcutaneously weekly or adalimumab 40 mg subcutaneously every other week (in addition to concomitant methotrexate, plus hydroxychloroquine, for subjects who were taking this at screening). Biologic treatment will be assigned randomly.
Methotrexate: Subjects entering trial will continue on MTX dose of at least 15mg MTX/week. At the discretion of the treating rheumatologist, may be switched to SQ route.
Etanercept: 50 mg SC weekly
Adalimumab: 40 mg SQ every other week
|
|---|---|---|
|
Change From Baseline in the Average TBR of the Bilateral Carotids
|
-0.10 Ratio
Standard Deviation 0.51
|
-0.06 Ratio
Standard Deviation 0.48
|
SECONDARY outcome
Timeframe: 0, 6 monthsPopulation: Participants with a FDG-PET/CT at baseline and six months for whom the outcome could be assessed
The outcome was the change in the target to background ratio (TBR) in the index vessel as measured by FDG-PET/CT scans conducted at baseline and after 24 weeks of randomized treatment allocation (MDS meanmaxTBR). Higher values indicate greater vascular inflammation. FDG uptake measurement: PET-CT images were batch-analyzed by an investigator blinded to the patients' clinical information. FDG uptake was evaluated within the wall of the ascending aorta and bilateral carotid arteries (as maximum and mean standardized FDG uptake value \[SUVmax and SUVmean, respectively\]) approximately every 5 mm on axial images. Subsequently, the target-to-background ratio (TBR) was reported (ratio of the average arterial to blood axial slice SUVmax) to correct for the blood compartment contribution.
Outcome measures
| Measure |
Triple Therapy (MTX+SSZ+HCQ)
n=57 Participants
Sulfasalazine (SSZ) 1 g bid and hydroxychloroquine (HCQ) 200 mg twice daily, not to exceed 6.5mg/kg HCQ (in addition to concomitant methotrexate \[MTX\]).
Methotrexate: Subjects entering trial will continue on MTX dose of at least 15mg MTX/week. At the discretion of the treating rheumatologist, may be switched to SQ route.
Sulfasalazine: 1 gm bid
Hydroxychloroquine: 200 mg twice daily, not to exceed 6.5mg/kg
|
TNF Inhibitor (Etanercept or Adalimumab)
n=58 Participants
etanercept 50 mg subcutaneously weekly or adalimumab 40 mg subcutaneously every other week (in addition to concomitant methotrexate, plus hydroxychloroquine, for subjects who were taking this at screening). Biologic treatment will be assigned randomly.
Methotrexate: Subjects entering trial will continue on MTX dose of at least 15mg MTX/week. At the discretion of the treating rheumatologist, may be switched to SQ route.
Etanercept: 50 mg SC weekly
Adalimumab: 40 mg SQ every other week
|
|---|---|---|
|
Change From Baseline in the Average TBR of the Index Vessel
|
-0.07 Ratio
Standard Deviation 0.47
|
-0.09 Ratio
Standard Deviation 0.43
|
Adverse Events
Triple Therapy (MTX+SSZ+HCQ)
TNF Inhibitor (Etanercept or Adalimumab)
Serious adverse events
| Measure |
Triple Therapy (MTX+SSZ+HCQ)
n=80 participants at risk
Sulfasalazine (SSZ) 1 g bid and hydroxychloroquine (HCQ) 200 mg twice daily, not to exceed 6.5mg/kg HCQ (in addition to concomitant methotrexate \[MTX\]).
Methotrexate: Subjects entering trial will continue on MTX dose of at least 15mg MTX/week. At the discretion of the treating rheumatologist, may be switched to SQ route.
Sulfasalazine: 1 gm bid
Hydroxychloroquine: 200 mg twice daily, not to exceed 6.5mg/kg
|
TNF Inhibitor (Etanercept or Adalimumab)
n=79 participants at risk
etanercept 50 mg subcutaneously weekly or adalimumab 40 mg subcutaneously every other week (in addition to concomitant methotrexate, plus hydroxychloroquine, for subjects who were taking this at screening). Biologic treatment will be assigned randomly.
Methotrexate: Subjects entering trial will continue on MTX dose of at least 15mg MTX/week. At the discretion of the treating rheumatologist, may be switched to SQ route.
Etanercept: 50 mg SC weekly
Adalimumab: 40 mg SQ every other week
|
|---|---|---|
|
Renal and urinary disorders
Renal Calculi
|
0.00%
0/80 • 24 weeks
|
2.5%
2/79 • Number of events 2 • 24 weeks
|
|
Gastrointestinal disorders
Dysphagia
|
0.00%
0/80 • 24 weeks
|
1.3%
1/79 • Number of events 1 • 24 weeks
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.00%
0/80 • 24 weeks
|
1.3%
1/79 • Number of events 1 • 24 weeks
|
|
Cardiac disorders
Myocardial Infarction
|
0.00%
0/80 • 24 weeks
|
1.3%
1/79 • Number of events 1 • 24 weeks
|
|
Gastrointestinal disorders
Vomiting
|
1.2%
1/80 • Number of events 1 • 24 weeks
|
0.00%
0/79 • 24 weeks
|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
1.2%
1/80 • Number of events 1 • 24 weeks
|
0.00%
0/79 • 24 weeks
|
|
Gastrointestinal disorders
Abdominal Pain
|
1.2%
1/80 • Number of events 1 • 24 weeks
|
0.00%
0/79 • 24 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory Failure
|
0.00%
0/80 • 24 weeks
|
1.3%
1/79 • Number of events 1 • 24 weeks
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms Benign Malignant And Unspecified
|
0.00%
0/80 • 24 weeks
|
1.3%
1/79 • Number of events 1 • 24 weeks
|
|
Renal and urinary disorders
Urinary Tract Infection
|
0.00%
0/80 • 24 weeks
|
1.3%
1/79 • Number of events 1 • 24 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
1.2%
1/80 • Number of events 1 • 24 weeks
|
0.00%
0/79 • 24 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
0.00%
0/80 • 24 weeks
|
2.5%
2/79 • Number of events 2 • 24 weeks
|
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place