Safety and Effect on Quality of Life/Work Productivity of Humira in Patients With Rheumatoid Arthritis

Study Overview
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Brief Summary
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The AGIL study was designed to evaluate the effectiveness and safety of adalimumab over 5 years in routine daily clinical practice in Germany, with a focus on the impact of therapy on employment-related outcomes.

Official Title
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Long Term Documentation of the Safety and Efficacy as Well as the Effects on Quality of Life and Work Productivity in Patients With Rheumatoid Arthritis Under HUMIRA® (Adalimumab) in Routine Clinical Practice (AGIL)

Conditions
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Rheumatoid Arthritis

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Moderate to severe active rheumatoid arthritis in adults with insufficient response to disease-modifying antirheumatic drugs Inclusive methotrexate Moderate to severe active rheumatoid arthritis in adults who have not been treated with methotrexate before; In case of incompatibility with methotrexate, Humira can be used as monotherapy. Exclusion Criteria: Hypersensitivity against the drug or one of the other ingredients Active tuberculosis or other severe infections (e.g. sepsis and opportunistic infections) Moderate to severe cardiac insufficiency

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Adalimumab<br>Adults with moderate to severe active rheumatoid arthritis (RA) who initiated adalimumab therapy during routine clinical care. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Disease Activity Score - 28 Joints (DAS28) | The DAS28 is a validated index of rheumatoid arthritis disease activity. Twenty-eight tender joint counts, 28 swollen joint counts, erythrocyte sedimentation rate (ESR), and the patient's assessment of global disease activity are included in the DAS28 score. Scores on the DAS28 range from 0 to 10. 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. | Baseline and 3, 6, 12, 24, 36, 48, and 60 months | 
| Change From Baseline in Tender Joint Count | Twenty-eight joints were assessed and classified as tender/not tender by pressure and joint manipulation on physical examination. | Baseline and 3, 6, 12, 24, 36, 48, and 60 months | 
| Change From Baseline in Swollen Joint Count | Twenty-eight joints were assessed and classified as swollen/not swollen by pressure and joint manipulation on physical examination. | Baseline and 3, 6, 12, 24, 36, 48, and 60 months | 
| Change From Baseline in Erythrocyte Sedimentation Rate |  | Baseline and 3, 6, 12, 24, 36, 48, and 60 months | 
| Change From Baseline in C-reactive Protein |  | Baseline and 3, 6, 12, 24, 36, 48, and 60 months | 
| Change From Baseline in Health-Assessment Questionnaire-Disability Index (HAQ-DI) | The HAQ-DI is a patient-reported assessment of physical function that includes 20 items in eight categories representing a comprehensive set of functional activities, including dressing, eating, walking, and hygiene. Patients are asked about their ability to complete these tasks in the past week using the following 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 (best) to 3 (worst), with a higher score representing a high-dependency disability. | Baseline and 3, 6, 12, 24, 36, 48, and 60 months | 
| EuroQol-5 Dimensions (EQ-5D) Scores | The EuroQol-5 Dimensions (EQ-5D) is a generic instrument for measuring health-related quality of life. The patient questionnaire consists of two parts. The first part includes statements for the following five areas (dimensions): agility/mobility self-care usual activities pain, bodily discomfort anxiety, depression For each dimension the patient is asked for a three-level assessment of their health on the current day: no problems (1), some problems (2), extreme problems (3). | Baseline and 3, 6, 12, 24, 36, 48, and 60 months | 
| Change From Baseline in Euroqol Visual Analog Scale (VAS) | EuroQol-5 Dimensions (EQ-5D): The EQ-5D is a generic instrument for measuring health-related quality of life. The patient questionnaire consists of two parts. The second part is a vertical, thermometer-like, VAS ranging from 0 to 100 that provides a patient-reported assessment of overall health. Patients are asked to mark how good or bad their health is on that day, with 100 meaning the best health you can imagine and 0 meaning the worst health you can imagine. | Baseline and 3, 6, 12, 24, 36, 48, and 60 months | 
| Change From Baseline in Number of Missed Working Days Due to Sick Leave in the Past 6 Months | Primary effectiveness outcomes related to employment were performed in patients who were employed part- or full-time at baseline. Sick leave days were based on patient recall. | Baseline and 6, 12, 24, 36, 48, and 60 months | 
| Percentage of Participants With > 5 Missed Working Days Due to Sick Leave in the Past 6 Months | Primary effectiveness outcomes related to employment were performed in patients who were employed part- or full-time at baseline. Sick leave days were based on patient recall. | Baseline, 6, 12, 24, 36, 48, and 60 months | 
| Change From Baseline in Work Productivity and Activity Impairment: Absenteeism | The Work Productivity and Activity Impairment (WPAI) questionnaire for general health is a validated tool in RA consisting of 6 questions, based on patient recall of the previous 7 days. WPAI assesses work time missed due to illness (absenteeism), impairment at work due to health (presenteeism), total work productivity impairment due to health (an aggregate measure of both absenteeism and presenteeism), and total non-occupational activity impairment due to health. WPAI scores are expressed as impairment percentages, with higher scores indicating worse outcomes. | Baseline and 3, 6, 12, 24, 36, 48, and 60 months | 
| Change From Baseline in Work Productivity and Activity Impairment: Presenteeism | The Work Productivity and Activity Impairment (WPAI) questionnaire for general health is a validated tool in RA consisting of 6 questions, based on patient recall of the previous 7 days. WPAI assesses work time missed due to illness (absenteeism), impairment at work due to health (presenteeism), total work productivity impairment due to health (an aggregate measure of both absenteeism and presenteeism), and total non-occupational activity impairment due to health. WPAI scores are expressed as impairment percentages, with higher scores indicating worse outcomes. | Baseline and 3, 6, 12, 24, 36, 48, and 60 months | 
| Change From Baseline in Work Productivity and Activity Impairment: Total Work Productivity Impairment | The Work Productivity and Activity Impairment (WPAI) questionnaire for general health is a validated tool in RA consisting of 6 questions, based on patient recall of the previous 7 days. WPAI assesses work time missed due to illness (absenteeism), impairment at work due to health (presenteeism), total work productivity impairment due to health (an aggregate measure of both absenteeism and presenteeism), and total non-occupational activity impairment due to health. WPAI scores are expressed as impairment percentages, with higher scores indicating worse outcomes. | Baseline and 3, 6, 12, 24, 36, 48, and 60 months | 
| Change From Baseline in Work Productivity and Activity Impairment: Total Activity Impairment | The Work Productivity and Activity Impairment (WPAI) questionnaire for general health is a validated tool in RA consisting of 6 questions, based on patient recall of the previous 7 days. WPAI assesses work time missed due to illness (absenteeism), impairment at work due to health (presenteeism), total work productivity impairment due to health (an aggregate measure of both absenteeism and presenteeism), and total non-occupational activity impairment due to health. WPAI scores are expressed as impairment percentages, with higher scores indicating worse outcomes. | Baseline and 3, 6, 12, 24, 36, 48, and 60 months | 
| Change From Baseline in Work Activity Index (WAI) | The WAI is a tool designed to record the work ability of employees and consists of 7 questions. The modified WAI used in this study included Questions 1, 2, 4, 6, and 7 of the WAI. Question 3, which involves the number of current diseases diagnosed by a physician, was omitted because this parameter was unlikely to reflect change due to treatment. Question 5 (sick leave during the past year) was replaced with the previous question concerning sick leave days.WAI scores range from 7 (worst) to 49 (best). | Baseline and 6, 12, 24, 36, 48, and 60 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Physician Visits in Past 6 Months | Participants self-reported the number of physician visits they had in the past 6 months. | Baseline, 6, 12, 24, 36, 48, and 60 months | 
| Number of Inpatient Hospitalizations in Past 6 Months | Participants self-reported the number of hospitalizations they had in the past 6 months. | Baseline, 6, 12, 24, 36, 48, and 60 months | 
| Duration of Inpatient Hospitalizations in Past 6 Months | Participants who had been hospitalized were asked how many days they were hospitalized in the past 6 months. | Baseline, 6, 12, 24, 36, 48, and 60 months | 
| Number of Days With Impairment of Non-Occupational Activities in Past 6 Months | Patients reported the number of days that sickness affected non-occupational activities in four categories: household, child-rearing/parenting, education, and recreational (free-time). Participants with no impairment were considered to have 0 days. | Baseline, 6, 12, 24, 36, 48, and 60 months | 
| Duration of Morning Stiffness |  | Baseline and 3, 6, 12, 24, 36, 48, and 60 months | 
| Participant's Assessment of Pain | Participants were asked to evaluate their level of pain in the past 7 days on a scale from 0 (no pain) to 10 (unbearable pain). | Baseline and 3, 6, 12, 24, 36, 48, and 60 months | 
| Participant's Assessment of Fatigue | Participants were asked to indicate how much they had suffered from abnormal exhaustion and fatigue during the past 7 days on a scale from 0 (none) to 10 (strongly). | Baseline and 3, 6, 12, 24, 36, 48, and 60 months | 
| Percentage of Participants Taking Concomitant RA Medications | Assessment of concomitant medications included disease-modifying antirheumatic drugs (DMARDs) (methotrexate, Leflunomid, sulfasalazine), systemic glucocorticoids, non-steroidal anti-inflammatory drugs (NSAIDs), Cox-2 inhibitors (coxibs), analgesics and others. | Baseline to month 60 | 
| Patient Assessment of Adalimumab Therapy | Participants were asked to rate therapy with adalimumab in comparison with other previous therapies according to the following response options: Considerably better Better About the same Worse Noticeably worse | Months 3, 6, 12, 24, 36, 48, and 60 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Work Productivity, Long-term Observation, Humira, Quality of Life, Rheumatoid Arthritis