Trial Outcomes & Findings for MTX Discontinuation and Vaccine Response (NCT NCT02748785)
NCT ID: NCT02748785
Last Updated: 2018-10-04
Results Overview
Seroresponse is defined as serconversion or ≥4-fold increase in antibody titers
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
277 participants
Primary outcome timeframe
8 weeks
Results posted on
2018-10-04
Participant Flow
Participant milestones
| Measure |
Group 1
Group 1 will continue MTX
Methotrexate: Methotrexate will be continued
Seasonal Influenza vaccine: all subjects will be vaccinated with a seasonal influenza vaccine
|
Group 2
Group 2 will hold MTX 4 weeks before vaccination and resume MTX on the day of vaccination
Methotrexate: Methotrexate will be continued
Seasonal Influenza vaccine: all subjects will be vaccinated with a seasonal influenza vaccine
|
Group 3
Group 3 will hold MTX 2 weeks before vaccination and resume MTX 2 weeks after vaccination
Methotrexate: Methotrexate will be continued
Seasonal Influenza vaccine: all subjects will be vaccinated with a seasonal influenza vaccine
|
Group 4
Group 4 will hold MTX on day of vaccination and resume MTX 4 weeks after vaccination.
Methotrexate: Methotrexate will be continued
Seasonal Influenza vaccine: all subjects will be vaccinated with a seasonal influenza vaccine
|
|---|---|---|---|---|
|
Visit 1- Visit 2
STARTED
|
69
|
68
|
71
|
69
|
|
Visit 1- Visit 2
COMPLETED
|
59
|
49
|
57
|
63
|
|
Visit 1- Visit 2
NOT COMPLETED
|
10
|
19
|
14
|
6
|
|
Visit 2-Visit 3
STARTED
|
59
|
49
|
57
|
63
|
|
Visit 2-Visit 3
COMPLETED
|
54
|
44
|
49
|
52
|
|
Visit 2-Visit 3
NOT COMPLETED
|
5
|
5
|
8
|
11
|
|
Visit 3- Visit 4
STARTED
|
54
|
44
|
49
|
52
|
|
Visit 3- Visit 4
COMPLETED
|
53
|
43
|
47
|
50
|
|
Visit 3- Visit 4
NOT COMPLETED
|
1
|
1
|
2
|
2
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
MTX Discontinuation and Vaccine Response
Baseline characteristics by cohort
| Measure |
Group 1
n=54 Participants
Group 1 will continue MTX
Methotrexate: Methotrexate will be continued
Seasonal Influenza vaccine: all subjects will be vaccinated with a seasonal influenza vaccine
|
Group 2
n=44 Participants
Group 2 will hold MTX 4 weeks before vaccination and resume MTX on the day of vaccination
Methotrexate: Methotrexate will be continued
Seasonal Influenza vaccine: all subjects will be vaccinated with a seasonal influenza vaccine
|
Group 3
n=49 Participants
Group 3 will hold MTX 2 weeks before vaccination and resume MTX 2 weeks after vaccination
Methotrexate: Methotrexate will be continued
Seasonal Influenza vaccine: all subjects will be vaccinated with a seasonal influenza vaccine
|
Group 4
n=52 Participants
Group 4 will hold MTX on day of vaccination and resume MTX 4 weeks after vaccination.
Methotrexate: Methotrexate will be continued
Seasonal Influenza vaccine: all subjects will be vaccinated with a seasonal influenza vaccine
|
Total
n=199 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
59.1 years
STANDARD_DEVIATION 13.1 • n=5 Participants
|
58.5 years
STANDARD_DEVIATION 113.3 • n=7 Participants
|
58.1 years
STANDARD_DEVIATION 10.9 • n=5 Participants
|
58.1 years
STANDARD_DEVIATION 11.7 • n=4 Participants
|
58.5 years
STANDARD_DEVIATION 11.7 • n=21 Participants
|
|
Sex: Female, Male
Female
|
45 Participants
n=5 Participants
|
39 Participants
n=7 Participants
|
42 Participants
n=5 Participants
|
43 Participants
n=4 Participants
|
169 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
9 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
9 Participants
n=4 Participants
|
30 Participants
n=21 Participants
|
|
Disease duration
|
5.2 years
STANDARD_DEVIATION 4.5 • n=5 Participants
|
6.1 years
STANDARD_DEVIATION 4.9 • n=7 Participants
|
4.9 years
STANDARD_DEVIATION 4.4 • n=5 Participants
|
6.2 years
STANDARD_DEVIATION 5.5 • n=4 Participants
|
6.2 years
STANDARD_DEVIATION 5.5 • n=21 Participants
|
|
Disease Activity Score (DAS)-28
|
2.5 units on a scale (0-10)
STANDARD_DEVIATION 1.1 • n=5 Participants
|
2.8 units on a scale (0-10)
STANDARD_DEVIATION 1.2 • n=7 Participants
|
2.6 units on a scale (0-10)
STANDARD_DEVIATION 1.0 • n=5 Participants
|
2.6 units on a scale (0-10)
STANDARD_DEVIATION 1.0 • n=4 Participants
|
2.6 units on a scale (0-10)
STANDARD_DEVIATION 1.1 • n=21 Participants
|
PRIMARY outcome
Timeframe: 8 weeksPopulation: Per Protocol
Seroresponse is defined as serconversion or ≥4-fold increase in antibody titers
Outcome measures
| Measure |
Group 1
n=54 Participants
Group 1 will continue MTX
Methotrexate: Methotrexate will be continued
Seasonal Influenza vaccine: all subjects will be vaccinated with a seasonal influenza vaccine
|
Group 2
n=44 Participants
Group 2 will hold MTX 4 weeks before vaccination and resume MTX on the day of vaccination
Methotrexate: Methotrexate will be continued
Seasonal Influenza vaccine: all subjects will be vaccinated with a seasonal influenza vaccine
|
Group 3
n=49 Participants
Group 3 will hold MTX 2 weeks before vaccination and resume MTX 2 weeks after vaccination
Methotrexate: Methotrexate will be continued
Seasonal Influenza vaccine: all subjects will be vaccinated with a seasonal influenza vaccine
|
Group 4
n=52 Participants
Group 4 will hold MTX on day of vaccination and resume MTX 4 weeks after vaccination.
Methotrexate: Methotrexate will be continued
Seasonal Influenza vaccine: all subjects will be vaccinated with a seasonal influenza vaccine
|
|---|---|---|---|---|
|
Satisfactory Vaccination Responses Against 3 Antigens
|
31.5 percentage of responders
|
22.7 percentage of responders
|
51 percentage of responders
|
46.2 percentage of responders
|
PRIMARY outcome
Timeframe: 8 weeksPopulation: Per Protocol
Seroresponse is defined as serconversion or ≥4-fold increase in antibody titers
Outcome measures
| Measure |
Group 1
n=54 Participants
Group 1 will continue MTX
Methotrexate: Methotrexate will be continued
Seasonal Influenza vaccine: all subjects will be vaccinated with a seasonal influenza vaccine
|
Group 2
n=44 Participants
Group 2 will hold MTX 4 weeks before vaccination and resume MTX on the day of vaccination
Methotrexate: Methotrexate will be continued
Seasonal Influenza vaccine: all subjects will be vaccinated with a seasonal influenza vaccine
|
Group 3
n=49 Participants
Group 3 will hold MTX 2 weeks before vaccination and resume MTX 2 weeks after vaccination
Methotrexate: Methotrexate will be continued
Seasonal Influenza vaccine: all subjects will be vaccinated with a seasonal influenza vaccine
|
Group 4
n=52 Participants
Group 4 will hold MTX on day of vaccination and resume MTX 4 weeks after vaccination.
Methotrexate: Methotrexate will be continued
Seasonal Influenza vaccine: all subjects will be vaccinated with a seasonal influenza vaccine
|
|---|---|---|---|---|
|
Satisfactory Vaccination Responses Against > 2/3 Antigens
|
53.7 percentage of responders
|
52.3 percentage of responders
|
71.4 percentage of responders
|
65.4 percentage of responders
|
PRIMARY outcome
Timeframe: 8 weeksPopulation: Per Protocol
Seroresponse is defined as serconversion or ≥4-fold increase in antibody titers
Outcome measures
| Measure |
Group 1
n=54 Participants
Group 1 will continue MTX
Methotrexate: Methotrexate will be continued
Seasonal Influenza vaccine: all subjects will be vaccinated with a seasonal influenza vaccine
|
Group 2
n=44 Participants
Group 2 will hold MTX 4 weeks before vaccination and resume MTX on the day of vaccination
Methotrexate: Methotrexate will be continued
Seasonal Influenza vaccine: all subjects will be vaccinated with a seasonal influenza vaccine
|
Group 3
n=49 Participants
Group 3 will hold MTX 2 weeks before vaccination and resume MTX 2 weeks after vaccination
Methotrexate: Methotrexate will be continued
Seasonal Influenza vaccine: all subjects will be vaccinated with a seasonal influenza vaccine
|
Group 4
n=52 Participants
Group 4 will hold MTX on day of vaccination and resume MTX 4 weeks after vaccination.
Methotrexate: Methotrexate will be continued
Seasonal Influenza vaccine: all subjects will be vaccinated with a seasonal influenza vaccine
|
|---|---|---|---|---|
|
Satisfactory Vaccination Responses Against > 1/3 Antigens
|
77.8 percentage of responders
|
81.8 percentage of responders
|
87.8 percentage of responders
|
88.5 percentage of responders
|
SECONDARY outcome
Timeframe: 8 weeksSeroprotection is defined as antibody titers of ≥40
Outcome measures
| Measure |
Group 1
n=55 Participants
Group 1 will continue MTX
Methotrexate: Methotrexate will be continued
Seasonal Influenza vaccine: all subjects will be vaccinated with a seasonal influenza vaccine
|
Group 2
n=44 Participants
Group 2 will hold MTX 4 weeks before vaccination and resume MTX on the day of vaccination
Methotrexate: Methotrexate will be continued
Seasonal Influenza vaccine: all subjects will be vaccinated with a seasonal influenza vaccine
|
Group 3
n=49 Participants
Group 3 will hold MTX 2 weeks before vaccination and resume MTX 2 weeks after vaccination
Methotrexate: Methotrexate will be continued
Seasonal Influenza vaccine: all subjects will be vaccinated with a seasonal influenza vaccine
|
Group 4
n=52 Participants
Group 4 will hold MTX on day of vaccination and resume MTX 4 weeks after vaccination.
Methotrexate: Methotrexate will be continued
Seasonal Influenza vaccine: all subjects will be vaccinated with a seasonal influenza vaccine
|
|---|---|---|---|---|
|
Proportion of Seroprotection Against H1N1
|
74 percentage of patients
|
86 percentage of patients
|
96 percentage of patients
|
86 percentage of patients
|
SECONDARY outcome
Timeframe: 8 weeksSeroprotection is defined as antibody titers of ≥40
Outcome measures
| Measure |
Group 1
n=54 Participants
Group 1 will continue MTX
Methotrexate: Methotrexate will be continued
Seasonal Influenza vaccine: all subjects will be vaccinated with a seasonal influenza vaccine
|
Group 2
n=44 Participants
Group 2 will hold MTX 4 weeks before vaccination and resume MTX on the day of vaccination
Methotrexate: Methotrexate will be continued
Seasonal Influenza vaccine: all subjects will be vaccinated with a seasonal influenza vaccine
|
Group 3
n=49 Participants
Group 3 will hold MTX 2 weeks before vaccination and resume MTX 2 weeks after vaccination
Methotrexate: Methotrexate will be continued
Seasonal Influenza vaccine: all subjects will be vaccinated with a seasonal influenza vaccine
|
Group 4
n=52 Participants
Group 4 will hold MTX on day of vaccination and resume MTX 4 weeks after vaccination.
Methotrexate: Methotrexate will be continued
Seasonal Influenza vaccine: all subjects will be vaccinated with a seasonal influenza vaccine
|
|---|---|---|---|---|
|
Proportion of Seroprotection Against H3N2
|
100 percentage of patients w/ seroprotection
|
96 percentage of patients w/ seroprotection
|
98 percentage of patients w/ seroprotection
|
96 percentage of patients w/ seroprotection
|
SECONDARY outcome
Timeframe: 8 weeksSeroprotection is defined as antibody titers of ≥40
Outcome measures
| Measure |
Group 1
n=54 Participants
Group 1 will continue MTX
Methotrexate: Methotrexate will be continued
Seasonal Influenza vaccine: all subjects will be vaccinated with a seasonal influenza vaccine
|
Group 2
n=44 Participants
Group 2 will hold MTX 4 weeks before vaccination and resume MTX on the day of vaccination
Methotrexate: Methotrexate will be continued
Seasonal Influenza vaccine: all subjects will be vaccinated with a seasonal influenza vaccine
|
Group 3
n=49 Participants
Group 3 will hold MTX 2 weeks before vaccination and resume MTX 2 weeks after vaccination
Methotrexate: Methotrexate will be continued
Seasonal Influenza vaccine: all subjects will be vaccinated with a seasonal influenza vaccine
|
Group 4
n=52 Participants
Group 4 will hold MTX on day of vaccination and resume MTX 4 weeks after vaccination.
Methotrexate: Methotrexate will be continued
Seasonal Influenza vaccine: all subjects will be vaccinated with a seasonal influenza vaccine
|
|---|---|---|---|---|
|
Proportion of Seroprotection Against B-Yamagata
|
72 percentage of patients w/ seroprotection
|
71 percentage of patients w/ seroprotection
|
94 percentage of patients w/ seroprotection
|
81 percentage of patients w/ seroprotection
|
SECONDARY outcome
Timeframe: Day of and 4 weeks after vaccinationFold change = post-vaccination titer/pre-vaccination titer
Outcome measures
| Measure |
Group 1
n=54 Participants
Group 1 will continue MTX
Methotrexate: Methotrexate will be continued
Seasonal Influenza vaccine: all subjects will be vaccinated with a seasonal influenza vaccine
|
Group 2
n=44 Participants
Group 2 will hold MTX 4 weeks before vaccination and resume MTX on the day of vaccination
Methotrexate: Methotrexate will be continued
Seasonal Influenza vaccine: all subjects will be vaccinated with a seasonal influenza vaccine
|
Group 3
n=49 Participants
Group 3 will hold MTX 2 weeks before vaccination and resume MTX 2 weeks after vaccination
Methotrexate: Methotrexate will be continued
Seasonal Influenza vaccine: all subjects will be vaccinated with a seasonal influenza vaccine
|
Group 4
n=52 Participants
Group 4 will hold MTX on day of vaccination and resume MTX 4 weeks after vaccination.
Methotrexate: Methotrexate will be continued
Seasonal Influenza vaccine: all subjects will be vaccinated with a seasonal influenza vaccine
|
|---|---|---|---|---|
|
Change From Baseline in Antibody Titer Against H1N1
|
5.1 Fold change
Interval 3.4 to 7.8
|
5.0 Fold change
Interval 3.2 to 7.8
|
8.7 Fold change
Interval 5.3 to 14.5
|
8.1 Fold change
Interval 5.3 to 12.4
|
SECONDARY outcome
Timeframe: Day of and 4 weeks after vaccinationFold change = post-vaccination titer/pre-vaccination titer
Outcome measures
| Measure |
Group 1
n=54 Participants
Group 1 will continue MTX
Methotrexate: Methotrexate will be continued
Seasonal Influenza vaccine: all subjects will be vaccinated with a seasonal influenza vaccine
|
Group 2
n=44 Participants
Group 2 will hold MTX 4 weeks before vaccination and resume MTX on the day of vaccination
Methotrexate: Methotrexate will be continued
Seasonal Influenza vaccine: all subjects will be vaccinated with a seasonal influenza vaccine
|
Group 3
n=49 Participants
Group 3 will hold MTX 2 weeks before vaccination and resume MTX 2 weeks after vaccination
Methotrexate: Methotrexate will be continued
Seasonal Influenza vaccine: all subjects will be vaccinated with a seasonal influenza vaccine
|
Group 4
n=52 Participants
Group 4 will hold MTX on day of vaccination and resume MTX 4 weeks after vaccination.
Methotrexate: Methotrexate will be continued
Seasonal Influenza vaccine: all subjects will be vaccinated with a seasonal influenza vaccine
|
|---|---|---|---|---|
|
Change From Baseline in Antibody Titer Against H3N2
|
5.9 Fold change
Interval 4.3 to 8.1
|
6.1 Fold change
Interval 4.4 to 8.5
|
12.2 Fold change
Interval 8.4 to 17.5
|
10.0 Fold change
Interval 6.8 to 14.8
|
SECONDARY outcome
Timeframe: Day of and 4 weeks after vaccinationFold change = post-vaccination titer/pre-vaccination titer
Outcome measures
| Measure |
Group 1
n=54 Participants
Group 1 will continue MTX
Methotrexate: Methotrexate will be continued
Seasonal Influenza vaccine: all subjects will be vaccinated with a seasonal influenza vaccine
|
Group 2
n=44 Participants
Group 2 will hold MTX 4 weeks before vaccination and resume MTX on the day of vaccination
Methotrexate: Methotrexate will be continued
Seasonal Influenza vaccine: all subjects will be vaccinated with a seasonal influenza vaccine
|
Group 3
n=49 Participants
Group 3 will hold MTX 2 weeks before vaccination and resume MTX 2 weeks after vaccination
Methotrexate: Methotrexate will be continued
Seasonal Influenza vaccine: all subjects will be vaccinated with a seasonal influenza vaccine
|
Group 4
n=52 Participants
Group 4 will hold MTX on day of vaccination and resume MTX 4 weeks after vaccination.
Methotrexate: Methotrexate will be continued
Seasonal Influenza vaccine: all subjects will be vaccinated with a seasonal influenza vaccine
|
|---|---|---|---|---|
|
Change From Baseline in Antibody Titer Against B-Yamagata
|
2.9 Fold change
Interval 2.2 to 3.8
|
2.8 Fold change
Interval 2.1 to 3.7
|
4.7 Fold change
Interval 3.3 to 6.7
|
6.1 Fold change
Interval 4.2 to 8.8
|
SECONDARY outcome
Timeframe: 20 weeks from enrollment.DAS28 flare rate at visit 4 as compared to visit 1. RA flare was defined as an increase in DAS28 of \>1.2 (or \>0.6 if the baseline DAS28 was ≥3.2).
Outcome measures
| Measure |
Group 1
n=54 Participants
Group 1 will continue MTX
Methotrexate: Methotrexate will be continued
Seasonal Influenza vaccine: all subjects will be vaccinated with a seasonal influenza vaccine
|
Group 2
n=44 Participants
Group 2 will hold MTX 4 weeks before vaccination and resume MTX on the day of vaccination
Methotrexate: Methotrexate will be continued
Seasonal Influenza vaccine: all subjects will be vaccinated with a seasonal influenza vaccine
|
Group 3
n=49 Participants
Group 3 will hold MTX 2 weeks before vaccination and resume MTX 2 weeks after vaccination
Methotrexate: Methotrexate will be continued
Seasonal Influenza vaccine: all subjects will be vaccinated with a seasonal influenza vaccine
|
Group 4
n=52 Participants
Group 4 will hold MTX on day of vaccination and resume MTX 4 weeks after vaccination.
Methotrexate: Methotrexate will be continued
Seasonal Influenza vaccine: all subjects will be vaccinated with a seasonal influenza vaccine
|
|---|---|---|---|---|
|
DAS28 Flare Rate at Visit 4
|
7.5 percentage of flare patients
|
14.0 percentage of flare patients
|
19.1 percentage of flare patients
|
12.0 percentage of flare patients
|
Adverse Events
Group 1
Serious events: 0 serious events
Other events: 33 other events
Deaths: 0 deaths
Group 2
Serious events: 2 serious events
Other events: 23 other events
Deaths: 0 deaths
Group 3
Serious events: 0 serious events
Other events: 23 other events
Deaths: 0 deaths
Group 4
Serious events: 0 serious events
Other events: 17 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Group 1
n=54 participants at risk
Group 1 will continue MTX
Methotrexate: Methotrexate will be continued
Seasonal Influenza vaccine: all subjects will be vaccinated with a seasonal influenza vaccine
|
Group 2
n=44 participants at risk
Group 2 will hold MTX 4 weeks before vaccination and resume MTX on the day of vaccination
Methotrexate: Methotrexate will be continued
Seasonal Influenza vaccine: all subjects will be vaccinated with a seasonal influenza vaccine
|
Group 3
n=49 participants at risk
Group 3 will hold MTX 2 weeks before vaccination and resume MTX 2 weeks after vaccination
Methotrexate: Methotrexate will be continued
Seasonal Influenza vaccine: all subjects will be vaccinated with a seasonal influenza vaccine
|
Group 4
n=52 participants at risk
Group 4 will hold MTX on day of vaccination and resume MTX 4 weeks after vaccination.
Methotrexate: Methotrexate will be continued
Seasonal Influenza vaccine: all subjects will be vaccinated with a seasonal influenza vaccine
|
|---|---|---|---|---|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung cancer
|
0.00%
0/54 • At each visit
|
2.3%
1/44 • Number of events 1 • At each visit
|
0.00%
0/49 • At each visit
|
0.00%
0/52 • At each visit
|
|
Injury, poisoning and procedural complications
Fracture
|
0.00%
0/54 • At each visit
|
2.3%
1/44 • Number of events 1 • At each visit
|
0.00%
0/49 • At each visit
|
0.00%
0/52 • At each visit
|
Other adverse events
| Measure |
Group 1
n=54 participants at risk
Group 1 will continue MTX
Methotrexate: Methotrexate will be continued
Seasonal Influenza vaccine: all subjects will be vaccinated with a seasonal influenza vaccine
|
Group 2
n=44 participants at risk
Group 2 will hold MTX 4 weeks before vaccination and resume MTX on the day of vaccination
Methotrexate: Methotrexate will be continued
Seasonal Influenza vaccine: all subjects will be vaccinated with a seasonal influenza vaccine
|
Group 3
n=49 participants at risk
Group 3 will hold MTX 2 weeks before vaccination and resume MTX 2 weeks after vaccination
Methotrexate: Methotrexate will be continued
Seasonal Influenza vaccine: all subjects will be vaccinated with a seasonal influenza vaccine
|
Group 4
n=52 participants at risk
Group 4 will hold MTX on day of vaccination and resume MTX 4 weeks after vaccination.
Methotrexate: Methotrexate will be continued
Seasonal Influenza vaccine: all subjects will be vaccinated with a seasonal influenza vaccine
|
|---|---|---|---|---|
|
Infections and infestations
Upper respiratory infection
|
48.1%
26/54 • Number of events 26 • At each visit
|
40.9%
18/44 • Number of events 18 • At each visit
|
40.8%
20/49 • Number of events 20 • At each visit
|
30.8%
16/52 • Number of events 16 • At each visit
|
|
General disorders
Dizziness
|
1.9%
1/54 • Number of events 1 • At each visit
|
6.8%
3/44 • Number of events 3 • At each visit
|
0.00%
0/49 • At each visit
|
1.9%
1/52 • Number of events 1 • At each visit
|
|
General disorders
Injection site reaction
|
5.6%
3/54 • Number of events 3 • At each visit
|
2.3%
1/44 • Number of events 1 • At each visit
|
4.1%
2/49 • Number of events 2 • At each visit
|
0.00%
0/52 • At each visit
|
|
Nervous system disorders
Headache
|
5.6%
3/54 • Number of events 3 • At each visit
|
2.3%
1/44 • Number of events 1 • At each visit
|
2.0%
1/49 • Number of events 1 • At each visit
|
0.00%
0/52 • At each visit
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place