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The main objective of this study was to determine the ability to maintain response after discontinuation of adalimumab treatment and the secondary objective was to determine radiographic progression in participants participating in the study, including the percentage who displayed minimal progression.
This was a two-arm, multi-center, Post Marketing Observational Study (PMOS) conducted in Japanese participants with Rheumatoid Arthritis (RA) who continued the one year observational period of study P12-069 (HOPEFUL II study; NCT01163292) and provided informed consent to participate in study P12-707 (HOPEFUL III study; NCT01346501), after completion of study M06-859 (HOPEFUL I study; NCT00870467). The study P12-707 provided an additional two years of observation for those participants who participated in study P12-069.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Adalimumab | Participants with Rheumatoid Arthritis (RA) who continued adalimumab treatment after completion of study M06-859, participated in the observational period of studies P12-069 and P12-707. Other name for adalimumab is Humira. | ||
| Non-adalimumab | Patients who discontinued adalimumab treatment after completion of the study M06-859. |
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| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With Disease Activity Score 28 - C-Reactive Protein (DAS28-CRP) Score < 3.2 After Discontinuation of Adalimumab Treatment | The DAS28-CRP, a combined index that measured Rheumatoid Arthritis (RA) disease activity, was calculated based on the number of tender joint count (28 joints), the number of swollen joint count (28 joints), overall disease activity (using visual analog scale (VAS)), erythrocyte sedimentation rate (ESR), and C-Reactive protein (CRP). The DAS28-CRP scores ranged from 0 (no disease activity) to 9 (maximal disease activity); decrease in DAS28-CRP score indicated improvement of disease. In participants who discontinued treatment with adalimumab after sustained low disease activity (defined as DAS28-CRP score <3.2) in study M06-859, the percentage of participants who maintained DAS28-CRP score < 3.2 without disease flare (defined as DAS28-CRP score ≥ 3.2) during studies P12-069 and P12-707 was calculated. | At Week 0, Week 26, Week 52, Week 78, Week 104, Week 130, and Week 156 |
| Percentage of Participants With Positive Serum Level of Matrix Metalloprotease-3 (MMP-3) | MMP-3, a proteolytic enzyme that plays a pivotal role in joint destruction in RA was assessed during the study. MMP-3 serum level < 121 ng/mL in men and < 59.7 ng/mL in women was considered as the normal value. Data are presented as the percentage of participants with MMP-3 serum level greater than the normal value. | At Week 0, Week 26, Week 52, Week 78, Week 104, Week 130, Week 156, Week 182, and Week 208 |
| Mean Health Assessment Questionnaire (HAQ) Score | The HAQ score was a participant-reported questionnaire that measured quality of life in terms of physical function of participants with rheumatoid arthritis. It consisted 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 seven days using the following response categories (score): without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). The scores on each task were summed and averaged to provide an overall score from 0 to 3, where 0-1 represented mild disability and 2-3 represented severe disability. Data are presented as mean HAQ score +/- standard deviation with negative scores indicating improvement. |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With Modified Total Sharp Score (mTSS) ≤ 0.5 and ≤ 1.5 | The mTSS, a method of assessing radiographs, was used to evaluate the level of joint destruction by disease. Digitized X-rays of hands and feet were obtained and scored on a scale ranging from 0 [no damage] to 5 [complete collapse or total destruction of joint] for erosion and 0 [no damage] to 4 [complete luxation of joint] for joint space narrowing. The scores on each task were summed and averaged to derive the total mTSS score ranging from 0 [normal] to 380 [maximal disease]. Large positive change in mTSS indicated disease progression; small positive/no change indicated slowing/halting of disease progression. The mTSS score ≤ 0.5 was defined as minimal radiographic progression. Data are presented as the percentage of the participants with mTSS ≤ 0.5 and ≤ 1.5 at the end of third year of the observation period (at Week 104 of P12-707). |
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Inclusion Criteria:
Participants with RA who continued the one year observational period of study P12-069 and provided informed consent to participate in study P12-707.
Exclusion Criteria:
Participants with RA who used biological agents other than adalimumab in the one year observational period of study P12-069.
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Participants with Rheumatoid Arthritis (RA) who continued the one year observational period of study P12-069 and provided informed consent to participate in study P12-707.
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| Name | Affiliation | Role |
|---|---|---|
| Sarina Kurimoto | AbbVie | Study Director |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28288682 | Derived | Tanaka Y, Yamanaka H, Ishiguro N, Miyasaka N, Kawana K, Kimura J, Agata N, Takeuchi T. Low disease activity for up to 3 years after adalimumab discontinuation in patients with early rheumatoid arthritis: 2-year results of the HOPEFUL-3 Study. Arthritis Res Ther. 2017 Mar 14;19(1):56. doi: 10.1186/s13075-017-1264-6. |
| Label | URL |
|---|---|
| Related Info | View source |
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| ID | Title | Description |
|---|---|---|
| FG000 | Adalimumab | Participants with Rheumatoid Arthritis (RA) who continued adalimumab treatment after completion of study M06-859 (HOPEFUL I study; NCT00870467), participated in the observational period of studies P12-069 (HOPEFUL II study; NCT01163292) and P12-707 (HOPEFUL III study; NCT01346501). |
| FG001 | Non-adalimumab | Participants with RA who discontinued adalimumab treatment after completion of study M06-859, participated in the observational period of studies P12-069 and P12-707. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | Adalimumab | Participants with RA who continued adalimumab treatment after completion of study M06-859, participated in the observational period of studies P12-069 and P12-707. |
| BG001 | Non-adalimumab |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Percentage of Participants With Disease Activity Score 28 - C-Reactive Protein (DAS28-CRP) Score < 3.2 After Discontinuation of Adalimumab Treatment | The DAS28-CRP, a combined index that measured Rheumatoid Arthritis (RA) disease activity, was calculated based on the number of tender joint count (28 joints), the number of swollen joint count (28 joints), overall disease activity (using visual analog scale (VAS)), erythrocyte sedimentation rate (ESR), and C-Reactive protein (CRP). The DAS28-CRP scores ranged from 0 (no disease activity) to 9 (maximal disease activity); decrease in DAS28-CRP score indicated improvement of disease. In participants who discontinued treatment with adalimumab after sustained low disease activity (defined as DAS28-CRP score <3.2) in study M06-859, the percentage of participants who maintained DAS28-CRP score < 3.2 without disease flare (defined as DAS28-CRP score ≥ 3.2) during studies P12-069 and P12-707 was calculated. | The effectiveness analysis set was defined as all participants who had evaluable DAS28-CRP score during studies P12-069 and P12-707. | Posted | Number | Percentage of participants | At Week 0, Week 26, Week 52, Week 78, Week 104, Week 130, and Week 156 |
From signing of informed consent until withdrawal of participant or starting a new biologic agent or up to approximately 2 years
The occurrence, type, severity, and relationship of adverse events to adalimumab were assessed. Safety was assessed in participants who received adalimumab in the observation period of studies P12-069 and P12-707, in routine clinical practice. Refer 'reporting group description' for the definition of safety analysis set.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Adalimumab | Participants with RA who continued adalimumab treatment after completion of study M06-859, participated in the observational period of studies P12-069 and P12-707 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Bronchiolitis | Infections and infestations | MedDRA version 17.1 | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Gastroenteritis viral | Infections and infestations | MedDRA version 17.1 | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Global Medical Services | AbbVie (prior sponsor, Abbott) | 800-633-9110 |
| ID | Term |
|---|---|
| D001172 | Arthritis, Rheumatoid |
| ID | Term |
|---|---|
| D001168 | Arthritis |
| D007592 | Joint Diseases |
| D009140 | Musculoskeletal Diseases |
| D012216 | Rheumatic Diseases |
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| At Week 0, Week 26, Week 52, Week 78, Week 104, Week 130, Week 156, Week 182, and Week 208 |
| 3 years |
| Percentage of Participants With Adverse Drug Reactions and Serious Adverse Drug Reactions | Adverse drug reactions (serious and non-serious) are adverse events for which the causal relationship between adalimumab and the event could not be ruled out. Adverse event was defined as any untoward or unintended medical occurrences (including abnormal laboratory findings), signs/symptoms, or diseases of the participant receiving adalimumab, regardless of causality of adalimumab treatment. Data are presented as percentage of participants. | From signing of informed consent until withdrawal of participant or starting a new biologic agent or up to approximately 2 years |
Participants with RA who discontinued adalimumab treatment after completion of study M06-859, participated in the observational period of studies P12-069 and P12-707.
| BG002 | Total | Total of all reporting groups |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| ID | Title | Description |
|---|
| OG000 | Non-adalimumab | Participants with RA who discontinued adalimumab treatment after completion of study M06-859 and sustained low disease activity (defined as DAS28-CRP score <3.2 at Week 46 and Week 52), participated in the observational period of studies P12-069 and P12-707. |
|
|
| Primary | Percentage of Participants With Positive Serum Level of Matrix Metalloprotease-3 (MMP-3) | MMP-3, a proteolytic enzyme that plays a pivotal role in joint destruction in RA was assessed during the study. MMP-3 serum level < 121 ng/mL in men and < 59.7 ng/mL in women was considered as the normal value. Data are presented as the percentage of participants with MMP-3 serum level greater than the normal value. | The effectiveness analysis set was defined as all participants who had evaluable MMP-3 score during studies P12-069 and P12-707. | Posted | Number | Percentage of participants | At Week 0, Week 26, Week 52, Week 78, Week 104, Week 130, Week 156, Week 182, and Week 208 |
|
|
|
| Primary | Mean Health Assessment Questionnaire (HAQ) Score | The HAQ score was a participant-reported questionnaire that measured quality of life in terms of physical function of participants with rheumatoid arthritis. It consisted 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 seven days using the following response categories (score): without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). The scores on each task were summed and averaged to provide an overall score from 0 to 3, where 0-1 represented mild disability and 2-3 represented severe disability. Data are presented as mean HAQ score +/- standard deviation with negative scores indicating improvement. | The effectiveness analysis set was defined as all participants who had evaluable HAQ score during studies P12-069 and P12-707. | Posted | Mean | Standard Deviation | Score on a scale | At Week 0, Week 26, Week 52, Week 78, Week 104, Week 130, Week 156, Week 182, and Week 208 |
|
|
|
| Secondary | Percentage of Participants With Modified Total Sharp Score (mTSS) ≤ 0.5 and ≤ 1.5 | The mTSS, a method of assessing radiographs, was used to evaluate the level of joint destruction by disease. Digitized X-rays of hands and feet were obtained and scored on a scale ranging from 0 [no damage] to 5 [complete collapse or total destruction of joint] for erosion and 0 [no damage] to 4 [complete luxation of joint] for joint space narrowing. The scores on each task were summed and averaged to derive the total mTSS score ranging from 0 [normal] to 380 [maximal disease]. Large positive change in mTSS indicated disease progression; small positive/no change indicated slowing/halting of disease progression. The mTSS score ≤ 0.5 was defined as minimal radiographic progression. Data are presented as the percentage of the participants with mTSS ≤ 0.5 and ≤ 1.5 at the end of third year of the observation period (at Week 104 of P12-707). | The effectiveness analysis set was defined as all participants who had evaluable mTSS score during studies P12-069 and P12-707. | Posted | Number | Percentage of participants | 3 years |
|
|
|
| Secondary | Percentage of Participants With Adverse Drug Reactions and Serious Adverse Drug Reactions | Adverse drug reactions (serious and non-serious) are adverse events for which the causal relationship between adalimumab and the event could not be ruled out. Adverse event was defined as any untoward or unintended medical occurrences (including abnormal laboratory findings), signs/symptoms, or diseases of the participant receiving adalimumab, regardless of causality of adalimumab treatment. Data are presented as percentage of participants. | Safety was assessed in participants who received adalimumab in the observation period of studies P12-069 and P12-707, in routine clinical practice. Refer 'reporting group description' for the definition of safety analysis set. | Posted | Number | Percentage of participants | From signing of informed consent until withdrawal of participant or starting a new biologic agent or up to approximately 2 years |
|
|
|
| 3 |
| 79 |
| 25 |
| 79 |
| EG001 | Non-adalimumab | Participants with RA who discontinued adalimumab treatment after completion of study M06-859 and re-started adalimumab treatment during the observational period of studies P12-069 and P12-707 | 1 | 22 | 9 | 22 |
| Interstitial lung disease | Respiratory, thoracic and mediastinal disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Ascites | Gastrointestinal disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Hepatic cirrhosis | Hepatobiliary disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Calculus urinary | Renal and urinary disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA version 17.1 | Non-systematic Assessment |
|
| Otitis media | Infections and infestations | MedDRA version 17.1 | Non-systematic Assessment |
|
| Pharyngitis | Infections and infestations | MedDRA version 17.1 | Non-systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA version 17.1 | Non-systematic Assessment |
|
| Pseudomembranous colitis | Infections and infestations | MedDRA version 17.1 | Non-systematic Assessment |
|
| Pulmonary mycosis | Infections and infestations | MedDRA version 17.1 | Non-systematic Assessment |
|
| Sinusitis | Infections and infestations | MedDRA version 17.1 | Non-systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA version 17.1 | Non-systematic Assessment |
|
| Oral herpes | Infections and infestations | MedDRA version 17.1 | Non-systematic Assessment |
|
| Seasonal allergy | Immune system disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Hypercholesterolaemia | Metabolism and nutrition disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Asthenopia | Eye disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Vitreous haemorrhage | Eye disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Palpitations | Cardiac disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Asthma | Respiratory, thoracic and mediastinal disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Dysphonia | Respiratory, thoracic and mediastinal disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Upper respiratory tract inflammation | Respiratory, thoracic and mediastinal disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Abdominal discomfort | Gastrointestinal disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Enterocolitis | Gastrointestinal disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Stomatitis | Gastrointestinal disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Anal haemorrhage | Gastrointestinal disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Eczema | Skin and subcutaneous tissue disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Lumbar spinal stenosis | Musculoskeletal and connective tissue disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Rheumatoid arthritis | Musculoskeletal and connective tissue disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA version 17.1 | Non-systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | MedDRA version 17.1 | Non-systematic Assessment |
|
| Gamma-glutamyltransferase increased | Investigations | MedDRA version 17.1 | Non-systematic Assessment |
|
| Liver function test abnormal | Investigations | MedDRA version 17.1 | Non-systematic Assessment |
|
| Low density lipoprotein increased | Investigations | MedDRA version 17.1 | Non-systematic Assessment |
|
| Platelet count decreased | Investigations | MedDRA version 17.1 | Non-systematic Assessment |
|
| White blood cell count decreased | Investigations | MedDRA version 17.1 | Non-systematic Assessment |
|
| Blood alkaline phosphatase increased | Investigations | MedDRA version 17.1 | Non-systematic Assessment |
|
| Hepatic enzyme increased | Investigations | MedDRA version 17.1 | Non-systematic Assessment |
|
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.
| D003240 |
| Connective Tissue Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
| Week 52 |
|
| Week 78 (N=62, 57) |
|
| Week 104 (N=58, 66) |
|
| Week 130 (N=40, 46) |
|
| Week 156 (N=38, 52) |
|
| Week 182 (N=35, 38) |
|
| Week 208 (N=32, 43) |
|
| Week 52 |
|
| Week 78 (N=45, 48) |
|
| Week 104 (N=55, 62) |
|
| Week 130 (N=30, 44) |
|
| Week 156 (N=28, 51) |
|
| Week 182 (N=26, 33) |
|
| Week 208 (N=24, 39) |
|