Observational Trial With Enbrel

Study Overview
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Brief Summary
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The diagnosis, evaluation and treatment of rheumatoid arthritis (RA) continue to undergo rapid change. Randomized controlled trials such as the TEMPO study have demonstrated the efficacy and safety of the combination of etanercept and methotrexate. Importantly, the TEMPO study showed that patients treated with etanercept and methotrexate could reach the newer therapeutic goals of low disease activity and remission, and that the physicians, patients, and payers are no longer prepared to accept the goal of Reduction of symptoms. RCT are important and powerful tools in assessing efficacy and safety but have their limitations in terms of generalisability. In order to assess health economics, clinical effectiveness and safety of etanercept, they need to be measured by performing observational studies of unselected patients. This study aims to provide a holistic assessment of patients receiving etanercept in a real world setting. This will include centers that would not normally take part in RCT. The study will assess treatment with etanercept with descriptive statistics of the following parameters: Health economic, Safety, Effectiveness. In addition, there was a previous study of similar design, but of only 3 months duration (101354), which will allow comparison with historical data. Since previous study, there have been a number of significant changes: Introduction of a new formulation for etanercept (Enbrel® 50mg · once weekly), Definition of early RA has been modified to short disease duration (from 3 months to 1 year).

Detailed Description
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Non-interventional study: subjects to be selected according to the usual clinical practice of their physician

Official Title
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A 1 Year Observational Study of the Use of Etanercept in Routine German Clinical Practice to Treat Rheumatoid Arthritis Patients: a Health Economic, Safety and Effectiveness Evaluation

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: etanercept


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of rheumatoid arthritis Exclusion Criteria: Sepsis or risk for sepsis, Acute infection, Hypersensitivity against Etanercept

Ages Eligible for Study
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Minimum Age: 18 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 |
| --- | --- |
| Patients with Rheumatoid Arthritis<br> | Drug: etanercept<br>* The patients will be treated in accordance with the requirements of the labelling of Enbrel® in Germany. The dosage and duration of therapy is to be determined by the physician to meet the patients' individual needs for treatment.<br>* Other names: Enbrel;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving Functional Remission Determined by Hannover Functional Ability Questionnaire (FFbH) at Week 26 | Hannover Functional Ability Questionnaire (FFbH) consists 18 questions to assess daily activities in last 7 days. Each question is answered by the participant as Yes, I can perform the activity without difficulty (score assigned = 2), Yes, but with some difficulties (score assigned = 1) and No or only with help (score assigned = 0). Final FFbH score (FFbH functional capacity) is then computed according to formula: (Sum of all single scores * 100% [percent]) / (2 * number of answered questions) ranging between 0-100; higher score indicates better daily activities. FFbH functional remission is defined as FFbH functional capacity of >= 83%. | Week 26 | 
| Percentage of Participants Achieving Functional Remission Determined by Hannover Functional Ability Questionnaire (FFbH) at Week 52 | Hannover Functional Ability Questionnaire (FFbH) consists 18 questions to assess daily activities in last 7 days. Each question is answered by the participant as Yes, I can perform the activity without difficulty (score assigned = 2), Yes, but with some difficulties (score assigned = 1) and No or only with help (score assigned = 0). Final FFbH score (FFbH functional capacity) is then computed according to formula: (Sum of all single scores * 100%) / (2 * number of answered questions), ranging between 0-100; higher score indicates better daily activities. FFbH functional remission is defined as FFbH functional capacity of >= 83%. | Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Euro Quality of Life-5 Dimensions (EQ-5D) Visual Analog Scale (VAS) | EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single index value. The VAS component rates current health state on a scale from 0 millimeter (mm) (worst imaginable health state) to 100 mm (best imaginable health state); higher scores indicate a better health state. | Baseline, Week 26, Week 52 | 
| Euro Quality of Life-5 Dimensions (EQ-5D) Time Trade Off (TTO) | EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single utility score. Health state profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain or discomfort, and anxiety or depression; 1 indicates better health state (no problems); 3 indicates worst health state (confined to bed). Scoring formula developed by EuroQol group assigns a utility value for each domain in the profile. EQ-5D score is transformed to EQ-5D-TTO score ranging from -0.205 to 0.999; higher score indicates a better health state. | Baseline, Week 26, Week 52 | 
| Work Productivity and Activity Impairment - Special Health Problems (WPAI:SHP) | WPAI:SHP is 6-question participant rated questionnaire to determine the amount of absenteeism, presenteeism, work productivity loss and daily activity impairment attributable to rheumatoid arthritis for a period of 7 days prior to each visit. It yields 4 sub-scores: work time missed (absenteeism), impairment while working (presenteeism or reduced on-the-job effectiveness), overall work impairment (work productivity loss or absenteeism plus presenteeism) and activity impairment (daily activity impairment). These sub-scores are transformed to impairment percentages (range from 0 to 100), with higher numbers indicating greater impairment and less productivity. | Baseline, Week 26, Week 52 | 
| Healthcare Resource Utilization | Participants' utilization of healthcare resources was evaluated as number of events for healthcare resources utilization including: number of visits to general practitioners, visits to rheumatologist, visits to other medical specialists, inpatient hospitalizations, inpatient rehabilitations, inpatient follow-up treatment, outpatient rehabilitations, physiotherapy, and other healthcare utilizations. At baseline, number of events for participants' healthcare resources utilization during last 12 months before enrollment into the study were documented. After enrollment, number of events for participants' healthcare resources utilization were documented for last 6 months after previous documentation. | Baseline, Week 26, Week 52 | 
| Duration of Healthcare Resources Utilization | Participants' duration of healthcare resources utilization was evaluated as number of days for healthcare resources utilization including: duration of visits to general practitioners, to rheumatologist, to other medical specialists, inpatient hospitalizations, inpatient rehabilitations, inpatient follow-up treatment, outpatient rehabilitations, physiotherapy, and other healthcare utilizations. At baseline, number of days for participants' healthcare resources utilizations during last 12 months before enrollment into the study were documented. After enrollment, number of days for participants' healthcare resources utilization were documented for last 6 months after previous documentation. | Baseline, Week 26, Week 52 | 
| Duration of Working Disability | Duration of working disability was assessed as number of days a participant was disable to work. Duration of work disability was considered as 0 if participant was not disable to work during period of assessment. At baseline, participants' duration of working disability during last 12 months before enrollment into the study was documented. After enrollment, participants' duration of working disability was documented for last 6 months after previous documentation. | Baseline, Week 26, Week 52 | 
| Disease Activity Score Based on 28-Joints Count (DAS28) | DAS28 calculated from the number of swollen joints (SJC) and tender joints (TJC) using the 28 joints count, the erythrocyte sedimentation rate (ESR) (millimeters per hour [mm/hour]) and Patient global assessment of disease activity (recorded on a VAS of 0 mm [very good] to 100 mm [very bad]). Total score range: 0 to 10, higher score indicated more disease activity. DAS28 less than (<) 2.6 = remission, DAS28 less than or equal to (<=) 3.2 = low disease activity, DAS28 greater than or equal to (>=) 3.2 to <=5.1 = moderate disease activity, DAS28 greater than (>) 5.1 = high disease activity. | Baseline, Week 2, 6, 12, 26, 38, 52 | 
| Swollen Joints Count (SJC) | Number of swollen joints was determined by examination of 28 joints and identifying when swelling was present. The number of swollen joints was recorded on the joint assessment form at each visit, no swelling = 0, swelling =1. | Baseline, Week 2, 6, 12, 26, 38, 52 | 
| Tender Joints Count (TJC) | Number of tender joints was determined by examining 28 joints and identified the joints that were painful under pressure or to passive motion. The number of tender joints was recorded on the joint assessment form at each visit, no tenderness = 0, tenderness = 1. | Baseline, Week 2, 6, 12, 26, 38, 52 | 
| Erythrocyte Sedimentation Rate (ESR) | ESR is a laboratory test that provides a non-specific measure of inflammation. The test assesses the rate at which red blood cells fall in a test tube. Normal range is 0-30 mm/hour. A higher rate is consistent with inflammation. | Baseline, Week 2, 6, 12, 26, 38, 52 | 
| Percentage of Participants With Remission Determined by Disease Activity Score Based on 28-Joints Count (DAS 28) | DAS28 calculated from the number of swollen joints (SJC) and tender joints (TJC) using the 28 joints count, the erythrocyte sedimentation rate (ESR) (millimeters per hour [mm/hour]) and Patient global assessment of disease activity (recorded on a VAS of 0 mm [very good] to 100 mm [very bad]). Total score range: 0 to 10, higher score indicated more disease activity. DAS28 defined remission was classified as a score of <2.6. | Week 2, 6, 12, 26, 38, 52 | 
| Percentage of Participants With Response Determined by Disease Activity Score Based on 28-Joints Count (DAS 28) | The DAS28-based European League Against Rheumatism (EULAR) response criteria was used to measure individual response as none, good, and moderate, depending on the extent of change from baseline and level of disease activity reached (final values). Good responders: change from baseline >1.2 with DAS28 final value <=3.2; moderate responders: change from baseline >1.2 with DAS28 final values >3.2 to <=5.1 and >5.1 or change from baseline >0.6 to <=1.2 with DAS28 final values <=3.2 and >3.2 to <=5.1; non-responders: change from baseline <=0.6 with DAS28 final values <=3.2, >3.2 to <=5.1 and >5.1 or change from baseline >0.6 to <=1.2 with DAS28 final values >5.1. Good and moderate responders were considered to have DAS28 response. | Week 2, 6, 12, 26, 38, 52 | 
| Duration of Morning Stiffness | Duration of morning stiffness was defined as the time elapsed when participant woke up in the morning and was able to resume normal activities without stiffness in minutes (If none was present = 0; If stiffness persisted the entire day, 999 minutes was recorded [largest value possible to document] which may also include values up to 1440 minutes [= complete day]). | Baseline, Week 2, 6, 12, 26, 38, 52 | 
| Patient Global Assessment of Arthritis Pain | Participants assessed arthritis pain using a 0 mm - 100 mm Visual Analog Scale (VAS) where 0 mm = minimum possible pain (best) and 100 mm = maximum possible pain (worst). | Baseline, Week 2, 6, 12, 26, 38, 52 | 
| Physician Global Assessment of Disease Activity | Physician global assessment of disease activity was measured on a 0 mm to 100 mm Visual Analog Scale (VAS), with 0 mm = no disease activity and 100mm = maximum possible disease activity. | Baseline, Week 2, 6, 12, 26, 38, 52 | 
| Patient Global Assessment of Disease Activity | Patient global assessment of disease activity was measured using a 100 mm Visual Analog Scale (VAS) ranging from 0 mm= very good to 100 mm = very bad. | Baseline, Week 2, 6, 12, 26, 38, 52 | 
| C-Reactive Protein (CRP) | The test for CRP is a laboratory measurement for evaluation of an acute phase reactant of inflammation through the use of an ultrasensitive assay. A decrease in the level of CRP indicates reduction in inflammation and therefore improvement. | Baseline, Week 2, 6, 12, 26, 38, 52 | 
| Fatigue Visual Analog Scale (VAS) | Participants assessed their fatigue during the last 7 days using a 0 mm - 100 mm VAS, where 0 mm = no fatigue and 100 mm = worst possible fatigue. | Baseline, Week 26, 52 |