Rheumatoid Arthritis
Conditions
Keywords
Rheumatoid Arthritis
Brief summary
The purpose of this study was to collect data on the incidence of adverse drug reactions, infections and malignant tumors, as well as factors that might affect the safety and effectiveness of Humira® (adalimumab; 40mg/0.8 mL) in Japanese participants who received the drug for the treatment of rheumatoid arthritis.
Detailed description
Rheumatoid arthritis is a chronic autoimmune disease which requires long-term treatment. Due to the need of long-term safety data in Japanese participants and to fulfil the conditions of approval of adalimumab by the Japanese regulatory authority, this post-marketing observational study (PMOS) was conducted. The study investigated the long-term safety of adalimumab, particularly associated with the development of infections and malignant tumors. Data was collected once every 6 months up to 3 years.
Interventions
None listed
Sponsors
AbbVie (prior sponsor, Abbott)
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
15 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Participants who received adalimumab in accordance with its indications for treatment and dosage regimens. 2. Participants who used adalimumab continuously. 3. Participants without current or past history of malignant tumors. 4. Participants evaluated for Disease Activity Score 28 - 4 Erythrocyte Sedimentation Rate (DAS28-4ESR). 5. Participants evaluated by Health Assessment Questionnaire (HAQ) or Modified Health Assessment Questionnaire (MHAQ) prior to the initiation of adalimumab treatment in the all-case PMOS.
Exclusion criteria
1. Contraindications according to the package insert. 2. Participants with serious infections. 3. Participants with tuberculosis. 4. Participants with a history of hypersensitivity to any ingredient of adalimumab. 5. Participants with demyelinating disease or a history of demyelinating disease. 6. Participants with congestive cardiac failure.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Adverse Drug Reactions (ADRs) | From the initiation of adalimumab treatment, every 6 months up to 3 years. | An ADR was any unfavourable or unintended response (adverse event) that could possibly be related to adalimumab treatment. ADRs were assessed and data are presented as percentage of participants. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Infections and Malignant Tumors | From the initiation of adalimumab treatment, every 6 months up to 3 years. | Participants were evaluated for the presence/absence of malignant tumors and infections. Data are presented as percentage of participants. |
| Percentage of Participants With Disease Activity Score 28 - 4 Erythrocyte Sedimentation Rate (DAS28-4ESR) < 2.6 by Visit | Baseline (Week 0), Week 4, Week 12, Week 24, Year 1, Year 1.5, Year 2, Year 2.5, and Year 3 | DAS28-4ESR, a combined index that measured activity of rheumatoid arthritis, was calculated based on: (1) the number of tender joints among 28 joints evaluated; (2) the number of swollen joints among 28 joints evaluated; (3) general health evaluated by a visual analog scale (VAS); and (4) ESR. DAS28-4ESR scores ranged from 0 (no disease activity) to 10 (maximal disease activity); decrease in DAS28-4ESR scores indicate improvement of disease. DAS28-4ESR score \< 2.6 was defined as clinical remission of rheumatoid arthritis. Data are presented as percentage of participants. |
| Percentage of Participants With Modified Health Assessment Questionnaire (MHAQ) Score ≤ 0.5 by Visit | Baseline (Week 0), Week 24, Year 1, Year 1.5, Year 2, Year 2.5, and Year 3 | MHAQ was a participant-reported questionnaire that measured quality of life in terms of physical function of participants with rheumatic diseases. Participants assessed their ability to do each task over the past 6 months using the following response categories (score): 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 from 0 to 3, where 0 represented no disability and 3 very severe, high-dependency disability. MHAQ score ≤ 0.5 was defined as clinical remission, signifying normal physical function. Data are presented as percentage of participants. |
Participant flow
Pre-assignment details
The primary reason for discontinuation was not collected for 224 participants listed under the category of 'multiple reasons per participant' (Insufficient effect (n=76), other reasons (n=43), economic reasons (n=2), AEs (n=41), no further visits (including change of hospital) (n=39), discontinued by the patient request (n=17), and unknown (n=8)).
Participants by arm
| Arm | Count |
|---|---|
| Adalimumab 40 mg/0.8 mL Syringe for Subcutaneous Injection Participants with rheumatoid arthritis who received adalimumab, per approved label | 508 |
| Total | 508 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Did Not Continue Use of Adalimumab | 26 |
| Overall Study | History/comorbidity of malignant tumor | 3 |
| Overall Study | Multiple Reasons Per Participant | 224 |
| Overall Study | Off-Label Use of Adalimumab | 8 |
| Overall Study | Participants Without Case Report Form | 7 |
Baseline characteristics
| Characteristic | Adalimumab 40 mg/0.8 mL Syringe for Subcutaneous Injection |
|---|---|
| Age, Continuous | 59.5 Years STANDARD_DEVIATION 13.4 |
| Sex: Female, Male Female | 416 Participants |
| Sex: Female, Male Male | 92 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 211 / 508 |
| serious Total, serious adverse events | 86 / 508 |
Outcome results
Primary
Incidence of Adverse Drug Reactions (ADRs)
An ADR was any unfavourable or unintended response (adverse event) that could possibly be related to adalimumab treatment. ADRs were assessed and data are presented as percentage of participants.
Time frame: From the initiation of adalimumab treatment, every 6 months up to 3 years.
Population: Safety analysis set, defined as participants who did not violate protocol criteria.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Adalimumab 40 mg/0.8 mL Syringe for Subcutaneous Injection | Incidence of Adverse Drug Reactions (ADRs) | 33.3 Percentage of participants |
Secondary
Incidence of Infections and Malignant Tumors
Participants were evaluated for the presence/absence of malignant tumors and infections. Data are presented as percentage of participants.
Time frame: From the initiation of adalimumab treatment, every 6 months up to 3 years.
Population: Safety analysis set, defined as participants who did not violate protocol criteria.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Adalimumab 40 mg/0.8 mL Syringe for Subcutaneous Injection | Incidence of Infections and Malignant Tumors | Infections | 16.1 Percentage of participants |
| Adalimumab 40 mg/0.8 mL Syringe for Subcutaneous Injection | Incidence of Infections and Malignant Tumors | Malignant Tumors | 1.2 Percentage of participants |
Secondary
Percentage of Participants With Disease Activity Score 28 - 4 Erythrocyte Sedimentation Rate (DAS28-4ESR) < 2.6 by Visit
DAS28-4ESR, a combined index that measured activity of rheumatoid arthritis, was calculated based on: (1) the number of tender joints among 28 joints evaluated; (2) the number of swollen joints among 28 joints evaluated; (3) general health evaluated by a visual analog scale (VAS); and (4) ESR. DAS28-4ESR scores ranged from 0 (no disease activity) to 10 (maximal disease activity); decrease in DAS28-4ESR scores indicate improvement of disease. DAS28-4ESR score \< 2.6 was defined as clinical remission of rheumatoid arthritis. Data are presented as percentage of participants.
Time frame: Baseline (Week 0), Week 4, Week 12, Week 24, Year 1, Year 1.5, Year 2, Year 2.5, and Year 3
Population: Efficacy analysis set, defined as safety analysis set excluding participants without evaluable DAS28-4ESR score and lack of Modified Health Assessment Questionnaire (MHAQ) data prior to drug administration.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Adalimumab 40 mg/0.8 mL Syringe for Subcutaneous Injection | Percentage of Participants With Disease Activity Score 28 - 4 Erythrocyte Sedimentation Rate (DAS28-4ESR) < 2.6 by Visit | Baseline (Week 0) | 2.8 Percentage of participants |
| Adalimumab 40 mg/0.8 mL Syringe for Subcutaneous Injection | Percentage of Participants With Disease Activity Score 28 - 4 Erythrocyte Sedimentation Rate (DAS28-4ESR) < 2.6 by Visit | Week 4 | 14.5 Percentage of participants |
| Adalimumab 40 mg/0.8 mL Syringe for Subcutaneous Injection | Percentage of Participants With Disease Activity Score 28 - 4 Erythrocyte Sedimentation Rate (DAS28-4ESR) < 2.6 by Visit | Week 12 | 20.0 Percentage of participants |
| Adalimumab 40 mg/0.8 mL Syringe for Subcutaneous Injection | Percentage of Participants With Disease Activity Score 28 - 4 Erythrocyte Sedimentation Rate (DAS28-4ESR) < 2.6 by Visit | Week 24 | 29.6 Percentage of participants |
| Adalimumab 40 mg/0.8 mL Syringe for Subcutaneous Injection | Percentage of Participants With Disease Activity Score 28 - 4 Erythrocyte Sedimentation Rate (DAS28-4ESR) < 2.6 by Visit | Year 1 | 33.6 Percentage of participants |
| Adalimumab 40 mg/0.8 mL Syringe for Subcutaneous Injection | Percentage of Participants With Disease Activity Score 28 - 4 Erythrocyte Sedimentation Rate (DAS28-4ESR) < 2.6 by Visit | Year 1.5 | 37.1 Percentage of participants |
| Adalimumab 40 mg/0.8 mL Syringe for Subcutaneous Injection | Percentage of Participants With Disease Activity Score 28 - 4 Erythrocyte Sedimentation Rate (DAS28-4ESR) < 2.6 by Visit | Year 2 | 36.6 Percentage of participants |
| Adalimumab 40 mg/0.8 mL Syringe for Subcutaneous Injection | Percentage of Participants With Disease Activity Score 28 - 4 Erythrocyte Sedimentation Rate (DAS28-4ESR) < 2.6 by Visit | Year 2.5 | 38.2 Percentage of participants |
| Adalimumab 40 mg/0.8 mL Syringe for Subcutaneous Injection | Percentage of Participants With Disease Activity Score 28 - 4 Erythrocyte Sedimentation Rate (DAS28-4ESR) < 2.6 by Visit | Year 3 | 36.4 Percentage of participants |
Secondary
Percentage of Participants With Modified Health Assessment Questionnaire (MHAQ) Score ≤ 0.5 by Visit
MHAQ was a participant-reported questionnaire that measured quality of life in terms of physical function of participants with rheumatic diseases. Participants assessed their ability to do each task over the past 6 months using the following response categories (score): 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 from 0 to 3, where 0 represented no disability and 3 very severe, high-dependency disability. MHAQ score ≤ 0.5 was defined as clinical remission, signifying normal physical function. Data are presented as percentage of participants.
Time frame: Baseline (Week 0), Week 24, Year 1, Year 1.5, Year 2, Year 2.5, and Year 3
Population: Efficacy analysis set, defined as safety analysis set excluding participants without evaluable DAS28-4ESR score and lack of Modified Health Assessment Questionnaire (MHAQ) data prior to drug administration.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Adalimumab 40 mg/0.8 mL Syringe for Subcutaneous Injection | Percentage of Participants With Modified Health Assessment Questionnaire (MHAQ) Score ≤ 0.5 by Visit | Year 3 | 66.2 Percentage of participants |
| Adalimumab 40 mg/0.8 mL Syringe for Subcutaneous Injection | Percentage of Participants With Modified Health Assessment Questionnaire (MHAQ) Score ≤ 0.5 by Visit | Year 2.5 | 65.7 Percentage of participants |
| Adalimumab 40 mg/0.8 mL Syringe for Subcutaneous Injection | Percentage of Participants With Modified Health Assessment Questionnaire (MHAQ) Score ≤ 0.5 by Visit | Baseline (Week 0) | 43.4 Percentage of participants |
| Adalimumab 40 mg/0.8 mL Syringe for Subcutaneous Injection | Percentage of Participants With Modified Health Assessment Questionnaire (MHAQ) Score ≤ 0.5 by Visit | Week 24 | 53.5 Percentage of participants |
| Adalimumab 40 mg/0.8 mL Syringe for Subcutaneous Injection | Percentage of Participants With Modified Health Assessment Questionnaire (MHAQ) Score ≤ 0.5 by Visit | Year 1 | 63.6 Percentage of participants |
| Adalimumab 40 mg/0.8 mL Syringe for Subcutaneous Injection | Percentage of Participants With Modified Health Assessment Questionnaire (MHAQ) Score ≤ 0.5 by Visit | Year 1.5 | 63.6 Percentage of participants |
| Adalimumab 40 mg/0.8 mL Syringe for Subcutaneous Injection | Percentage of Participants With Modified Health Assessment Questionnaire (MHAQ) Score ≤ 0.5 by Visit | Year 2 | 66.0 Percentage of participants |