Trial Outcomes & Findings for Assessment of Clinical Effectiveness and Safety of Adalimumab and High Dose Methotrexate in Routine Clinical Practice (NCT NCT01736189)
NCT ID: NCT01736189
Last Updated: 2019-07-02
Results Overview
The Disease Activity Score 28 (DAS28) is a validated index of rheumatoid arthritis disease activity. Twenty-eight tender joint counts, 28 swollen joint counts, the erythrocyte sedimentation rate (ESR; mm/hr) or C-reactive protein (CRP; mg/dL) level, and the participant's assessment of global disease activity (on a visual analog scale \[VAS\] from 0 to 10 cm) are included in the DAS28 score. Scores on the DAS28 range from 0 to 10; higher scores indicate more disease activity. A DAS28 score \>5.1 indicates high disease activity, a DAS28 score \<3.2 indicates low disease activity, and a DAS28 score \<2.6 indicates clinical remission.
COMPLETED
346 participants
At Week 52
2019-07-02
Participant Flow
All registered participants
Participant milestones
| Measure |
Participants Treated With Adalimumab
40 mg adalimumab via subcutaneous (SC) injection every other week (eow) for 104 weeks
|
|---|---|
|
Overall Study
STARTED
|
346
|
|
Overall Study
COMPLETED
|
300
|
|
Overall Study
NOT COMPLETED
|
46
|
Reasons for withdrawal
| Measure |
Participants Treated With Adalimumab
40 mg adalimumab via subcutaneous (SC) injection every other week (eow) for 104 weeks
|
|---|---|
|
Overall Study
Violation of registration criteria
|
41
|
|
Overall Study
Protocol Violation
|
4
|
|
Overall Study
Criteria and protocol violations
|
1
|
Baseline Characteristics
Race and Ethnicity were not collected from any participant.
Baseline characteristics by cohort
| Measure |
Participants Treated With Adalimumab
n=300 Participants
40 mg adalimumab via subcutaneous (SC) injection every other week (eow) for 104 weeks
|
|---|---|
|
Age, Continuous
|
54.1 years
STANDARD_DEVIATION 13.9 • n=300 Participants
|
|
Sex: Female, Male
Female
|
221 Participants
n=300 Participants
|
|
Sex: Female, Male
Male
|
79 Participants
n=300 Participants
|
PRIMARY outcome
Timeframe: At Week 52Population: Efficacy analysis set: participants with evaluable DAS-28 data
The Disease Activity Score 28 (DAS28) is a validated index of rheumatoid arthritis disease activity. Twenty-eight tender joint counts, 28 swollen joint counts, the erythrocyte sedimentation rate (ESR; mm/hr) or C-reactive protein (CRP; mg/dL) level, and the participant's assessment of global disease activity (on a visual analog scale \[VAS\] from 0 to 10 cm) are included in the DAS28 score. Scores on the DAS28 range from 0 to 10; higher scores indicate more disease activity. A DAS28 score \>5.1 indicates high disease activity, a DAS28 score \<3.2 indicates low disease activity, and a DAS28 score \<2.6 indicates clinical remission.
Outcome measures
| Measure |
Participants Treated With Adalimumab
n=292 Participants
40 mg adalimumab via subcutaneous (SC) injection every other week (eow) for 104 weeks
|
|---|---|
|
Percentage of Participants With a Disease Activity Score 28 (DAS28) Score of <2.6 at Week 52
DAS28-4CRP
|
77.1 percentage of participants
|
|
Percentage of Participants With a Disease Activity Score 28 (DAS28) Score of <2.6 at Week 52
DAS28-4ESR
|
61.1 percentage of participants
|
SECONDARY outcome
Timeframe: At Week 104Population: Efficacy analysis set: participants with evaluable data
The Clinical Disease Activity Index (CDAI) is a composite index for assessing rheumatoid arthritis disease activity. Twenty-eight tender joint counts, 28 swollen joint counts, the participant's global assessment of disease activity (on a visual analog scale \[VAS\] from 0 to 10 cm), and a physician's global assessment of disease activity (measured on a VAS from 0 to 10 cm) are summed to yield the total score. The total CDAI score ranges from 0 to 78 with higher scores indicating higher disease activity. Remission is defined as a CDAI score ≤ 2.8.
Outcome measures
| Measure |
Participants Treated With Adalimumab
n=131 Participants
40 mg adalimumab via subcutaneous (SC) injection every other week (eow) for 104 weeks
|
|---|---|
|
Percentage of Participants With a Clinical Disease Activity Index (CDAI) Score ≤ 2.8 at Week 104
|
69.5 percentage of participants
|
SECONDARY outcome
Timeframe: At Week 104Population: Efficacy analysis set: participants with evaluable data
The SDAI is a validated measure of rheumatoid arthritis disease activity. Twenty-eight tender joint counts, 28 swollen joint counts, global disease activity assessed by the participant on a visual analogue scale from 0 to 10 (cm), global disease activity assessed by an investigator on a visual analogue scale from 0 to 10 (cm), and serum levels of C-reactive protein (CRP; mg/dL) were included in the SDAI score. Scores on the SDAI range from 0 to 86. An SDAI score ≥26.1 indicates high disease activity, an SDAI score between 11.1 and 26.0 indicates moderate disease activity, an SDAI score between 3.4 and 11.0 indicates low disease activity, and an SDAI score ≤3.3 indicates clinical remission.
Outcome measures
| Measure |
Participants Treated With Adalimumab
n=128 Participants
40 mg adalimumab via subcutaneous (SC) injection every other week (eow) for 104 weeks
|
|---|---|
|
Percentage of Participants With a Simplified Disease Activity Index (SDAI) Score ≤ 3.3 at Week 104
|
73.4 percentage of participants
|
SECONDARY outcome
Timeframe: At Week 104Population: Efficacy analysis set: participants with evaluable data
The Health Assessment Questionnaire - Disability Index (HAQ-DI) is a self-reported assessment specific for rheumatoid arthritis. It consists of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and daily activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task were summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. HAQ remission indicating normal physical function is defined as HAQ-DI \< 0.5.
Outcome measures
| Measure |
Participants Treated With Adalimumab
n=105 Participants
40 mg adalimumab via subcutaneous (SC) injection every other week (eow) for 104 weeks
|
|---|---|
|
Percentage of Participants With a Health Assessment Questionnaire Disability Index (HAQ-DI) Score < 0.5 at Week 104
|
90.5 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline and Week 104Population: Efficacy analysis set: participants with evaluable data
The European Quality of Life-5 Dimensions Health Questionnaire (EQ-5D) is a participant-answered questionnaire scoring 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. For each dimension the participant is asked for a three-level assessment of their health on the current day: "no problems" (1), "some problems" (2), "extreme problems" (3). EQ-5D health states, defined by the EQ-5D descriptive system, are converted into a single summary index by applying a formula that essentially attaches values (also called QOL weights or QOL utilities) to each of the levels in each dimension. EQ-5D Summary Index values range from -0.11 (worst health state) to 1.00 (perfect health state). Positive numbers indicate improvement from baseline.
Outcome measures
| Measure |
Participants Treated With Adalimumab
n=95 Participants
40 mg adalimumab via subcutaneous (SC) injection every other week (eow) for 104 weeks
|
|---|---|
|
Mean Change From Baseline in European Quality of Life-5 Dimensions Health Questionnaire (EQ-5D) Index Score at Week 104
|
0.2543 units on a scale
Standard Deviation 0.1950
|
SECONDARY outcome
Timeframe: Baseline and Week 104Population: Efficacy analysis set: participants with evaluable data
The van der Heijde modified Total Sharp Score (mTSS) is a measure of the level of joint damage. X-rays of hands and feet were taken at the visit. Joints were scored for erosions on a scale of 0 (no damage) to 5 (complete collapse) and joint space narrowing on a scale of 0 (no damage) to 4 (ankylosis or complete dislocation). Erosion scores and narrowing scores were added to obtain the mTSS (range = 0 \[normal\] to 398 \[maximal disease\]). An increase in mTSS from Baseline represents disease progression and/or joint worsening, no change represents halting of disease progression, and a decrease represents improvement.
Outcome measures
| Measure |
Participants Treated With Adalimumab
n=70 Participants
40 mg adalimumab via subcutaneous (SC) injection every other week (eow) for 104 weeks
|
|---|---|
|
Percentage of Participants With a Change From Baseline of ≤ 1.0 in Van Der Heijde Modified Total Sharp Score (mTSS) at Week 104
|
84.3 percentage of participants
|
Adverse Events
Participants Treated With Adalimumab
Serious adverse events
| Measure |
Participants Treated With Adalimumab
n=300 participants at risk
40 mg adalimumab via subcutaneous (SC) injection every other week (eow) for 104 weeks
|
|---|---|
|
Infections and infestations
BRONCHOPULMONARY ASPERGILLOSIS
|
0.33%
1/300 • Number of events 1 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the time of study drug administration until the end of the study (up to 104 weeks).
TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is after the first dose of study drug and were collected whether elicited or spontaneously reported by the participant.
|
|
Infections and infestations
CELLULITIS
|
0.33%
1/300 • Number of events 1 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the time of study drug administration until the end of the study (up to 104 weeks).
TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is after the first dose of study drug and were collected whether elicited or spontaneously reported by the participant.
|
|
Infections and infestations
PNEUMONIA
|
0.33%
1/300 • Number of events 1 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the time of study drug administration until the end of the study (up to 104 weeks).
TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is after the first dose of study drug and were collected whether elicited or spontaneously reported by the participant.
|
|
Infections and infestations
PNEUMONIA CYTOMEGALOVIRAL
|
0.33%
1/300 • Number of events 1 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the time of study drug administration until the end of the study (up to 104 weeks).
TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is after the first dose of study drug and were collected whether elicited or spontaneously reported by the participant.
|
|
Infections and infestations
PNEUMONIA LEGIONELLA
|
0.33%
1/300 • Number of events 1 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the time of study drug administration until the end of the study (up to 104 weeks).
TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is after the first dose of study drug and were collected whether elicited or spontaneously reported by the participant.
|
|
Infections and infestations
PNEUMONIA PNEUMOCOCCAL
|
0.67%
2/300 • Number of events 2 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the time of study drug administration until the end of the study (up to 104 weeks).
TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is after the first dose of study drug and were collected whether elicited or spontaneously reported by the participant.
|
|
Infections and infestations
PNEUMONIA STREPTOCOCCAL
|
0.33%
1/300 • Number of events 1 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the time of study drug administration until the end of the study (up to 104 weeks).
TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is after the first dose of study drug and were collected whether elicited or spontaneously reported by the participant.
|
|
Infections and infestations
PNEUMOCYSTIS JIROVECII PNEUMONIA
|
1.3%
4/300 • Number of events 4 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the time of study drug administration until the end of the study (up to 104 weeks).
TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is after the first dose of study drug and were collected whether elicited or spontaneously reported by the participant.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
BASAL CELL CARCINOMA
|
0.33%
1/300 • Number of events 1 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the time of study drug administration until the end of the study (up to 104 weeks).
TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is after the first dose of study drug and were collected whether elicited or spontaneously reported by the participant.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
COLON CANCER
|
0.33%
1/300 • Number of events 1 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the time of study drug administration until the end of the study (up to 104 weeks).
TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is after the first dose of study drug and were collected whether elicited or spontaneously reported by the participant.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
DIFFUSE LARGE B-CELL LYMPHOMA
|
0.33%
1/300 • Number of events 1 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the time of study drug administration until the end of the study (up to 104 weeks).
TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is after the first dose of study drug and were collected whether elicited or spontaneously reported by the participant.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
OVARIAN CANCER METASTATIC
|
0.33%
1/300 • Number of events 1 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the time of study drug administration until the end of the study (up to 104 weeks).
TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is after the first dose of study drug and were collected whether elicited or spontaneously reported by the participant.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
LUNG NEOPLASM MALIGNANT
|
0.33%
1/300 • Number of events 1 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the time of study drug administration until the end of the study (up to 104 weeks).
TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is after the first dose of study drug and were collected whether elicited or spontaneously reported by the participant.
|
|
Blood and lymphatic system disorders
PANCYTOPENIA
|
0.67%
2/300 • Number of events 2 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the time of study drug administration until the end of the study (up to 104 weeks).
TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is after the first dose of study drug and were collected whether elicited or spontaneously reported by the participant.
|
|
Blood and lymphatic system disorders
THROMBOCYTOPENIA
|
0.33%
1/300 • Number of events 1 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the time of study drug administration until the end of the study (up to 104 weeks).
TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is after the first dose of study drug and were collected whether elicited or spontaneously reported by the participant.
|
|
Nervous system disorders
CEREBRAL HAEMORRHAGE
|
0.33%
1/300 • Number of events 1 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the time of study drug administration until the end of the study (up to 104 weeks).
TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is after the first dose of study drug and were collected whether elicited or spontaneously reported by the participant.
|
|
Nervous system disorders
MENINGITIS NONINFECTIVE
|
0.33%
1/300 • Number of events 1 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the time of study drug administration until the end of the study (up to 104 weeks).
TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is after the first dose of study drug and were collected whether elicited or spontaneously reported by the participant.
|
|
Eye disorders
VITREOUS HAEMORRHAGE
|
0.33%
1/300 • Number of events 1 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the time of study drug administration until the end of the study (up to 104 weeks).
TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is after the first dose of study drug and were collected whether elicited or spontaneously reported by the participant.
|
|
Respiratory, thoracic and mediastinal disorders
INTERSTITIAL LUNG DISEASE
|
0.33%
1/300 • Number of events 1 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the time of study drug administration until the end of the study (up to 104 weeks).
TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is after the first dose of study drug and were collected whether elicited or spontaneously reported by the participant.
|
|
Gastrointestinal disorders
COLITIS
|
0.33%
1/300 • Number of events 1 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the time of study drug administration until the end of the study (up to 104 weeks).
TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is after the first dose of study drug and were collected whether elicited or spontaneously reported by the participant.
|
|
Gastrointestinal disorders
INGUINAL HERNIA
|
0.33%
1/300 • Number of events 1 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the time of study drug administration until the end of the study (up to 104 weeks).
TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is after the first dose of study drug and were collected whether elicited or spontaneously reported by the participant.
|
|
Hepatobiliary disorders
LIVER DISORDER
|
0.33%
1/300 • Number of events 1 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the time of study drug administration until the end of the study (up to 104 weeks).
TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is after the first dose of study drug and were collected whether elicited or spontaneously reported by the participant.
|
|
Skin and subcutaneous tissue disorders
RASH
|
0.33%
1/300 • Number of events 1 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the time of study drug administration until the end of the study (up to 104 weeks).
TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is after the first dose of study drug and were collected whether elicited or spontaneously reported by the participant.
|
|
Skin and subcutaneous tissue disorders
URTICARIA
|
0.33%
1/300 • Number of events 1 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the time of study drug administration until the end of the study (up to 104 weeks).
TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is after the first dose of study drug and were collected whether elicited or spontaneously reported by the participant.
|
|
Musculoskeletal and connective tissue disorders
SPONDYLOLISTHESIS
|
0.33%
1/300 • Number of events 1 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the time of study drug administration until the end of the study (up to 104 weeks).
TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is after the first dose of study drug and were collected whether elicited or spontaneously reported by the participant.
|
|
Renal and urinary disorders
RENAL DISORDER
|
0.33%
1/300 • Number of events 1 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the time of study drug administration until the end of the study (up to 104 weeks).
TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is after the first dose of study drug and were collected whether elicited or spontaneously reported by the participant.
|
|
Renal and urinary disorders
RENAL IMPAIRMENT
|
0.33%
1/300 • Number of events 1 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the time of study drug administration until the end of the study (up to 104 weeks).
TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is after the first dose of study drug and were collected whether elicited or spontaneously reported by the participant.
|
|
Renal and urinary disorders
TUBULOINTERSTITIAL NEPHRITIS AND UVEITIS SYNDROME
|
0.33%
1/300 • Number of events 1 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the time of study drug administration until the end of the study (up to 104 weeks).
TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is after the first dose of study drug and were collected whether elicited or spontaneously reported by the participant.
|
|
Reproductive system and breast disorders
UTERINE HAEMORRHAGE
|
0.33%
1/300 • Number of events 1 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the time of study drug administration until the end of the study (up to 104 weeks).
TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is after the first dose of study drug and were collected whether elicited or spontaneously reported by the participant.
|
|
Investigations
BLOOD PRESSURE DECREASED
|
0.33%
1/300 • Number of events 1 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the time of study drug administration until the end of the study (up to 104 weeks).
TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is after the first dose of study drug and were collected whether elicited or spontaneously reported by the participant.
|
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee AbbVie requests that any investigator or institution that plans on presenting/publishing results disclosure, provide written notification of their request 60 days prior to their presentation/publication. AbbVie requests that no presentation/publication will be instituted until 12 months after a study is completed, or after the first presentation/publication whichever occurs first. A delay may be proposed of a presentation/publication if AbbVie needs to secure patent or proprietary protection.
- Publication restrictions are in place
Restriction type: OTHER