Rheumatoid Arthritis
Conditions
Keywords
Rheumatoid Arthritis
Brief summary
The purpose of the study was to assess the long-term safety and clinical efficacy following repeated administration of adalimumab in patients with rheumatoid arthritis.
Detailed description
Study DE020 was a multicenter, open-label continuation study for patients with rheumatoid arthritis who had participated in a prior Phase 1, 2, or 3 adalimumab study in the United States or Canada, had a favorable safety and efficacy profile when treated with adalimumab, and met the eligibility criteria for the continuation study. Participants received subcutaneous injections of adalimumab every other week (eow) or monthly based on the adalimumab regimen received in the prior study (i.e., participants who received monthly dosing in the prior study began the continuation study on monthly dosing; all other participants began adalimumab dosing at eow intervals). Participants who maintained an American College of Rheumatology 50% (ACR50) response for 2 consecutive visits could have their dosing interval lengthened to a monthly dosing schedule. Safety and efficacy data were collected over 520 weeks (10 years). Both safety and efficacy data were analyzed using all participants who received at least 1 dose of open-label adalimumab in the 10-year continuation study DE020 (the Full Analysis Set, n=846). Three patients who entered the continuation study but were never dosed were excluded from all analyses.
Interventions
BIOLOGICALAdalimumab
Subcutaneous injection of 40 mg adalimumab every other week (eow) or monthly for up to 520 weeks (10 years)
Sponsors
Abbott
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participant was in a prior D2E7 (adalimumab) study * Participant was age 18 or older and in good health (Investigator discretion) with a recent stable medical history.
Exclusion criteria
* Participant was considered by the investigator, for any reason, to be an unsuitable candidate for the study * Participant was a female subject who is pregnant or breast-feeding or considering becoming pregnant * Participant had any ongoing chronic or active infection
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Disability Index of the Health Assessment Questionnaire (HAQ) at Week 260 | Baseline of prior Phase 1, 2, or 3 adalimumab study and Week 260 | The HAQ-DI is a measure of disability that ranges from 0 to 3. Decrease in score indicates improvement in physical function; a decrease of 0.22 or greater from Baseline score is clinically significant. Participants assessed their ability to perform at least 6 of the following 8 specific tasks (1. dress/groom; 2. arise; 3. eat; 4. walk; 5. reach; 6. grip; 7. maintain hygiene; 8. maintain daily activity) over the past week by marking their response on a questionnaire. Possible responses/scores included the following: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). The 8 task scores are added and the sum is divided by the number of tasks assessed (range = 6 to 8). This yields a HAQ-DI score of 0 to 3. |
| Number of Participants Meeting American College of Rheumatology 20% (ACR20) Response Criteria at Week 520 | Week 520 | ACR20 response criteria were: \>=20% improvement in tender joint count; \>=20% improvement in swollen joint count; and \>=20% improvement in at least 3 of the 5 remaining ACR core measures: patient assessment of pain; patient global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire \[HAQ\]); and C-reactive protein (a laboratory marker of inflammation that is sensitive to acute changes in inflammatory response). All improvements were assessed relative to the baseline of the prior study. |
| Number of Participants Meeting American College of Rheumatology 20% (ACR20) Response Criteria at Week 260 | Week 260 | ACR20 response criteria were: \>=20% improvement in tender joint count; \>=20% improvement in swollen joint count; and \>=20% improvement in at least 3 of the 5 remaining ACR core measures: patient assessment of pain; patient global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire \[HAQ\]); and C-reactive protein (a laboratory marker of inflammation that is sensitive to acute changes in inflammatory response). All improvements were assessed relative to the baseline of the prior study. |
| Number of Participants Meeting American College of Rheumatology 50% (ACR50) Response Criteria at Week 520 | Week 520 | ACR50 response criteria were: \>=50% improvement in tender joint count; \>=50% improvement in swollen joint count; and \>=50% improvement in at least 3 of the 5 remaining ACR core measures: patient assessment of pain; patient global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire \[HAQ\]); and C-reactive protein (a laboratory marker of inflammation that is sensitive to acute changes in inflammatory response). All improvements were assessed relative to the baseline of the prior study. |
| Number of Participants Meeting American College of Rheumatology 50% (ACR50) Response Criteria at Week 260 | Week 260 | ACR50 response criteria were: \>=50% improvement in tender joint count; \>=50% improvement in swollen joint count; and \>=50% improvement in at least 3 of the 5 remaining ACR core measures: patient assessment of pain; patient global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire \[HAQ\]); and C-reactive protein (a laboratory marker of inflammation that is sensitive to acute changes in inflammatory response). All improvements were assessed relative to the baseline of the prior study. |
| Number of Participants Meeting American College of Rheumatology 70% (ACR70) Response Criteria at Week 520 | Week 520 | ACR70 response criteria were: \>=70% improvement in tender joint count; \>=70% improvement in swollen joint count; and \>=70% improvement in at least 3 of the 5 remaining ACR core measures: patient assessment of pain; patient global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire \[HAQ\]); and C-reactive protein (a laboratory marker of inflammation that is sensitive to acute changes in inflammatory response). All improvements were assessed relative to the baseline of the prior study. |
| Number of Participants Meeting American College of Rheumatology 70% (ACR70) Response Criteria at Week 260 | Week 260 | ACR70 response criteria were: \>=70% improvement in tender joint count; \>=70% improvement in swollen joint count; and \>=70% improvement in at least 3 of the 5 remaining ACR core measures: patient assessment of pain; patient global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire \[HAQ\]); and C-reactive protein (a laboratory marker of inflammation that is sensitive to acute changes in inflammatory response). All improvements were assessed relative to the baseline of the prior study. |
| Number of Participants in Clinical Remission (Based on Modified Disease Activity Score) at Week 520 | Week 520 | Clinical remission on modified Disease Activity Score (DAS28) was a value \<2.6; \>=2.6 to \<=3.2 indicated low disease activity; \>3.2 to \<=5.1 indicated moderate disease activity; and \>5.1 indicated high disease activity. DAS28 score is calculated using the number of tender joints and swollen joints (out of 28 each), patient global assessment of disease activity, and C-reactive protein (a laboratory marker of inflammation that is sensitive to acute changes in inflammatory response). |
| Number of Participants in Clinical Remission (Based on Modified Disease Activity Score) at Week 260 | Week 260 | Clinical remission on modified Disease Activity Score (DAS28) was a value \<2.6; \>=2.6 to \<=3.2 indicated low disease activity; \>3.2 to \<=5.1 indicated moderate disease activity; and \>5.1 indicated high disease activity. DAS28 score is calculated using the number of tender joints and swollen joints (out of 28 each), patient global assessment of disease activity, and C-reactive protein (a laboratory marker of inflammation that is sensitive to acute changes in inflammatory response). |
| Change From Baseline in the Disability Index of the Health Assessment Questionnaire (HAQ) at Week 520 | Baseline of prior Phase 1, 2, or 3 adalimumab study and Week 520 | The HAQ-DI is a measure of disability that ranges from 0 to 3. Decrease in score indicates improvement in physical function; a decrease of 0.22 or greater from Baseline score is clinically significant. Participants assessed their ability to perform at least 6 of the following 8 specific tasks (1. dress/groom; 2. arise; 3. eat; 4. walk; 5. reach; 6. grip; 7. maintain hygiene; 8. maintain daily activity) over the past week by marking their response on a questionnaire. Possible responses/scores included the following: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). The 8 task scores are added and the sum is divided by the number of tasks assessed (range = 6 to 8). This yields a HAQ-DI score of 0 to 3. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Reported Adverse Events | Duration of study (up to 520 weeks [10 years]) | Adverse events were collected during the course of the study (after the first adalimumab injection in this continuation study DE020 through 70 days after the last adalimumab injection) for all participants who received at least 1 dose of open-label adalimumab in the continuation study (Full Analysis Set). The number of participants experiencing any adverse event (serious and non-serious) are summarized. See the Reported Adverse Events section for details. |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Adalimumab Open-label adalimumab 40 mg | 846 |
| Total | 846 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Administrative reasons | 83 |
| Overall Study | Adverse Event | 194 |
| Overall Study | Death | 23 |
| Overall Study | Lack of Efficacy | 99 |
| Overall Study | Lost to Follow-up | 44 |
| Overall Study | Protocol Violation | 15 |
| Overall Study | Withdrawal by Subject | 67 |
Baseline characteristics
| Characteristic | Adalimumab |
|---|---|
| Age Continuous | 55.6 years STANDARD_DEVIATION 12.19 |
| Sex: Female, Male Female | 661 Participants |
| Sex: Female, Male Male | 185 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 768 / 846 |
| serious Total, serious adverse events | 432 / 846 |
Outcome results
Primary
Change From Baseline in the Disability Index of the Health Assessment Questionnaire (HAQ) at Week 260
The HAQ-DI is a measure of disability that ranges from 0 to 3. Decrease in score indicates improvement in physical function; a decrease of 0.22 or greater from Baseline score is clinically significant. Participants assessed their ability to perform at least 6 of the following 8 specific tasks (1. dress/groom; 2. arise; 3. eat; 4. walk; 5. reach; 6. grip; 7. maintain hygiene; 8. maintain daily activity) over the past week by marking their response on a questionnaire. Possible responses/scores included the following: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). The 8 task scores are added and the sum is divided by the number of tasks assessed (range = 6 to 8). This yields a HAQ-DI score of 0 to 3.
Time frame: Baseline of prior Phase 1, 2, or 3 adalimumab study and Week 260
Population: All participants who received at least 1 dose of open-label adalimumab (Full Analysis Set) in the continuation study and had a Week 260 visit. Analysis used observed data (no imputation).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Adalimumab | Change From Baseline in the Disability Index of the Health Assessment Questionnaire (HAQ) at Week 260 | -0.59 units on a scale | Standard Deviation 0.628 |
Primary
Change From Baseline in the Disability Index of the Health Assessment Questionnaire (HAQ) at Week 520
The HAQ-DI is a measure of disability that ranges from 0 to 3. Decrease in score indicates improvement in physical function; a decrease of 0.22 or greater from Baseline score is clinically significant. Participants assessed their ability to perform at least 6 of the following 8 specific tasks (1. dress/groom; 2. arise; 3. eat; 4. walk; 5. reach; 6. grip; 7. maintain hygiene; 8. maintain daily activity) over the past week by marking their response on a questionnaire. Possible responses/scores included the following: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). The 8 task scores are added and the sum is divided by the number of tasks assessed (range = 6 to 8). This yields a HAQ-DI score of 0 to 3.
Time frame: Baseline of prior Phase 1, 2, or 3 adalimumab study and Week 520
Population: All participants who received at least 1 dose of open-label adalimumab in the continuation study (Full Analysis Set) and had a Week 520 visit. Analysis used observed data (no imputation).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Adalimumab | Change From Baseline in the Disability Index of the Health Assessment Questionnaire (HAQ) at Week 520 | -0.52 units on a scale | Standard Deviation 0.662 |
Primary
Number of Participants in Clinical Remission (Based on Modified Disease Activity Score) at Week 260
Clinical remission on modified Disease Activity Score (DAS28) was a value \<2.6; \>=2.6 to \<=3.2 indicated low disease activity; \>3.2 to \<=5.1 indicated moderate disease activity; and \>5.1 indicated high disease activity. DAS28 score is calculated using the number of tender joints and swollen joints (out of 28 each), patient global assessment of disease activity, and C-reactive protein (a laboratory marker of inflammation that is sensitive to acute changes in inflammatory response).
Time frame: Week 260
Population: All participants who received at least 1 dose of open-label adalimumab in the continuation study (Full Analysis Set) and had a Week 260 visit. Analysis used observed data (no imputation).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Adalimumab | Number of Participants in Clinical Remission (Based on Modified Disease Activity Score) at Week 260 | 243 participants |
Primary
Number of Participants in Clinical Remission (Based on Modified Disease Activity Score) at Week 520
Clinical remission on modified Disease Activity Score (DAS28) was a value \<2.6; \>=2.6 to \<=3.2 indicated low disease activity; \>3.2 to \<=5.1 indicated moderate disease activity; and \>5.1 indicated high disease activity. DAS28 score is calculated using the number of tender joints and swollen joints (out of 28 each), patient global assessment of disease activity, and C-reactive protein (a laboratory marker of inflammation that is sensitive to acute changes in inflammatory response).
Time frame: Week 520
Population: All participants who received at least 1 dose of open-label adalimumab in the continuation study (Full Analysis Set) and had a Week 520 visit. Analysis used observed data (no imputation).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Adalimumab | Number of Participants in Clinical Remission (Based on Modified Disease Activity Score) at Week 520 | 135 participants |
Primary
Number of Participants Meeting American College of Rheumatology 20% (ACR20) Response Criteria at Week 260
ACR20 response criteria were: \>=20% improvement in tender joint count; \>=20% improvement in swollen joint count; and \>=20% improvement in at least 3 of the 5 remaining ACR core measures: patient assessment of pain; patient global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire \[HAQ\]); and C-reactive protein (a laboratory marker of inflammation that is sensitive to acute changes in inflammatory response). All improvements were assessed relative to the baseline of the prior study.
Time frame: Week 260
Population: All participants who received at least 1 dose of open-label adalimumab in the continuation study (Full Analysis Set) and had a Week 260 visit. Analysis used observed data (no imputation).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Adalimumab | Number of Participants Meeting American College of Rheumatology 20% (ACR20) Response Criteria at Week 260 | 402 participants |
Primary
Number of Participants Meeting American College of Rheumatology 20% (ACR20) Response Criteria at Week 520
ACR20 response criteria were: \>=20% improvement in tender joint count; \>=20% improvement in swollen joint count; and \>=20% improvement in at least 3 of the 5 remaining ACR core measures: patient assessment of pain; patient global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire \[HAQ\]); and C-reactive protein (a laboratory marker of inflammation that is sensitive to acute changes in inflammatory response). All improvements were assessed relative to the baseline of the prior study.
Time frame: Week 520
Population: All participants who received at least 1 dose of open-label adalimumab in the continuation study (Full Analysis Set) and had a Week 520 visit. Analysis used observed data (no imputation).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Adalimumab | Number of Participants Meeting American College of Rheumatology 20% (ACR20) Response Criteria at Week 520 | 187 participants |
Primary
Number of Participants Meeting American College of Rheumatology 50% (ACR50) Response Criteria at Week 260
ACR50 response criteria were: \>=50% improvement in tender joint count; \>=50% improvement in swollen joint count; and \>=50% improvement in at least 3 of the 5 remaining ACR core measures: patient assessment of pain; patient global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire \[HAQ\]); and C-reactive protein (a laboratory marker of inflammation that is sensitive to acute changes in inflammatory response). All improvements were assessed relative to the baseline of the prior study.
Time frame: Week 260
Population: All participants who received at least 1 dose of open-label adalimumab in the continuation study (Full Analysis Set) and had a Week 260 visit. Analysis used observed data (no imputation).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Adalimumab | Number of Participants Meeting American College of Rheumatology 50% (ACR50) Response Criteria at Week 260 | 279 participants |
Primary
Number of Participants Meeting American College of Rheumatology 50% (ACR50) Response Criteria at Week 520
ACR50 response criteria were: \>=50% improvement in tender joint count; \>=50% improvement in swollen joint count; and \>=50% improvement in at least 3 of the 5 remaining ACR core measures: patient assessment of pain; patient global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire \[HAQ\]); and C-reactive protein (a laboratory marker of inflammation that is sensitive to acute changes in inflammatory response). All improvements were assessed relative to the baseline of the prior study.
Time frame: Week 520
Population: All participants who received at least 1 dose of open-label adalimumab in the continuation study (Full Analysis Set) and had a Week 520 visit. Analysis used observed data (no imputation).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Adalimumab | Number of Participants Meeting American College of Rheumatology 50% (ACR50) Response Criteria at Week 520 | 132 participants |
Primary
Number of Participants Meeting American College of Rheumatology 70% (ACR70) Response Criteria at Week 260
ACR70 response criteria were: \>=70% improvement in tender joint count; \>=70% improvement in swollen joint count; and \>=70% improvement in at least 3 of the 5 remaining ACR core measures: patient assessment of pain; patient global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire \[HAQ\]); and C-reactive protein (a laboratory marker of inflammation that is sensitive to acute changes in inflammatory response). All improvements were assessed relative to the baseline of the prior study.
Time frame: Week 260
Population: All participants who received at least 1 dose of open-label adalimumab in the continuation study (Full Analysis Set) and had a Week 260 visit. Analysis used observed data (no imputation).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Adalimumab | Number of Participants Meeting American College of Rheumatology 70% (ACR70) Response Criteria at Week 260 | 179 participants |
Primary
Number of Participants Meeting American College of Rheumatology 70% (ACR70) Response Criteria at Week 520
ACR70 response criteria were: \>=70% improvement in tender joint count; \>=70% improvement in swollen joint count; and \>=70% improvement in at least 3 of the 5 remaining ACR core measures: patient assessment of pain; patient global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire \[HAQ\]); and C-reactive protein (a laboratory marker of inflammation that is sensitive to acute changes in inflammatory response). All improvements were assessed relative to the baseline of the prior study.
Time frame: Week 520
Population: All participants who received at least 1 dose of open-label adalimumab in the continuation study (Full Analysis Set) and had a Week 520 visit. Analysis used observed data (no imputation).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Adalimumab | Number of Participants Meeting American College of Rheumatology 70% (ACR70) Response Criteria at Week 520 | 78 participants |
Secondary
Reported Adverse Events
Adverse events were collected during the course of the study (after the first adalimumab injection in this continuation study DE020 through 70 days after the last adalimumab injection) for all participants who received at least 1 dose of open-label adalimumab in the continuation study (Full Analysis Set). The number of participants experiencing any adverse event (serious and non-serious) are summarized. See the Reported Adverse Events section for details.
Time frame: Duration of study (up to 520 weeks [10 years])
Population: All participants who received at least 1 dose of open-label adalimumab in the continuation study (Full Analysis Set).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Adalimumab | Reported Adverse Events | 808 participants |