Study to Assess the Safety and Efficacy of Etanercept in Patients Treated Over the Long-term in Real-world Clinical Practice, Using Data Collected by the British Society of Rheumatology Biologics Registry

Study Overview
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Brief Summary
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This study will assess the rates of serious adverse events and death in adult rheumatoid arthritis patients treated with etanercept over the long-term in real-life clinical practice. It will also assess whether there is any difference in the rate of serious adverse events in patients trated with etanercept in comparision to patients treated with conventional disease-modifying anti-rheumatic drugs (DMARDs). The study will in addition quantify the efficacy of etanercept in this population by assessing the rates of important clinical outcomes such as changes in disease activity and disability/functioning.

Detailed Description
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patients recruited sequentially as seen in clinical practice

Official Title
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Long-term Safety and Efficacy of Etanercept in a UK Observational Cohort Study - a Retrospective Database Analysis of British Society of Rheumatology Biologics Registry (BSRBR) Data

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: etanercept
* Drug: non-biologic anti-rheumatic drugs


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: adult rheumatoid arthritis group 1: initiating etanercept as first biologic therapy group 2: DAS28<4.2, biologic naive and treated with non-biologic DMARDs Exclusion Criteria: diagnosis of other inflammatory arthritis

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 |
| --- | --- |
| etanercept<br>adult rheumatoid arthritis patients initiating therapy with etanercept as their first biologic therapy | Drug: etanercept<br>* use as per routine clinical practice<br>|
| nbDMARD<br>biologic-naive adult rheumatoid arthritis patients with DAS28 >4.2 treated with non-biologic anti-rheumatic drugs(s). | Drug: non-biologic anti-rheumatic drugs<br>* use as per routine clinical practice (methotrexate, azathioprine, cyclophosphamide, cyclosporine, leflunomide, other)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Crude Incidence Rate of Malignancy | Participant-Year estimated by calculating all of the years that participants in a study were followed (number of evaluable participants multiplied by mean follow-up in years). Crude (unadjusted) incidence rate calculated as number of malignancy events divided by Participant-Year, multiplied by 1000. | Baseline up to last follow-up, assessed every 6 month for first 3 years and thereafter annually up to 10 years | 
| Crude Incidence Rate of Lymphoproliferative Malignancy (LM) | Participant-Year estimated by calculating all of years that participants in a study were followed (number of evaluable participants multiplied by mean follow-up in years). Crude (unadjusted) incidence rate calculated as number of LMs divided by Participant-Year, multiplied by 1000. Lymphoproliferative: medical condition characterized by the dysfunction of the immune system often resulting in excessive production of lymphocytes. LMs included lymphoma, myeloma, and leukemia. Adverse outcome was defined as 'lymphoproliferative malignancy' in the field [lymphopro] labeled by BSRBR. | Baseline up to last follow-up, assessed every 6 month for first 3 years and thereafter annually up to 10 years | 
| Crude Incidence Rate of Serious Infections | Participant-Year estimated by calculating all of the years that participants in a study were followed (number of evaluable participants multiplied by total follow-up in years). Crude (unadjusted) incidence rate calculated as number of serious infections divided by Participant-Year, multiplied by 1000. Serious infections included those infections which required intravenous antibiotics, hospitalization, or resulted in death. Adverse outcome was defined as 'serious infection' in the field [serinf] labeled by BSRBR. | Baseline up to last follow-up, assessed every 6 month for first 3 years and thereafter annually up to 10 years | 
| Crude Incidence Rate of Other Serious Adverse Events | Participant-Year estimated by calculating all of the years that participants in a study were followed (number of evaluable participants multiplied by total follow-up in years). Crude (unadjusted) incidence rate calculated as number of other serious adverse events divided by Participant-Year, multiplied by 1000. Other serious adverse events were based on classifications assigned by the BSRBR and included cardiac serious adverse events (SAEs), central nervous system SAEs, and nonmalignant hematological SAEs. | Baseline up to last follow-up, assessed every 6 month for first 3 years and thereafter annually up to 10 years | 
| Crude Incidence Rate of All-Cause Mortality | Participant-Year estimated by calculating all of the years that participants in a study were followed (number of evaluable participants multiplied by total follow-up in years). Crude (unadjusted) incidence rate calculated as number of deaths divided by Participant-Year, multiplied by 1000. Death was recorded in the adverse outcomes table and in the consultant follow-up table. Where multiple events described death for the same participant, date of death was taken as per the earliest record. | Baseline up to last follow-up, assessed every 6 month for first 3 years and thereafter annually up to 10 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Switched to Other Therapy Following Etanercept Discontinuation | Participants who switched from etanercept to either DMARDs or alternative biologic drug are reported. | Baseline up to last follow-up, assessed every 6 month for first 3 years and thereafter annually up to 10 years | 
| Time on Etanercept Therapy | Time on etanercept therapy was calculated by Kaplan-Meier survival analysis. | Baseline up to last follow-up, assessed every 6 month for first 3 years and thereafter annually up to 10 years | 
| Disease Activity Score Based on 28-Joints Count (DAS28) at Baseline | DAS28 calculated from the number of swollen joints (SJC) and tender joints (TJC) using the 28 joints count, the serological markers of inflammation (erythrocyte sedimentation rate [ESR, millimeter per hour] or C-reactive protein [CRP, milligram per liter]) and patient's general health assessment (recorded on a Visual Analog Scale [VAS] of 0 millimeter [mm]-100 mm). DAS28 <=1.6 = remission, DAS28 <=2.4 = low disease activity, DAS28 >=3.2 to 5.1 = moderate disease activity, DAS28 >5.1 = severe disease activity. | Baseline | 
| Change From Baseline in Disease Activity Score Based on 28-Joints Count (DAS28) at Year 1, 2, 3, 4, and 5 | DAS28 calculated from SJC and TJC using the 28 joints count, the serological markers of inflammation (ESR [millimeter per hour] or CRP [milligram per liter]) and patient's general health assessment (recorded on a VAS scale of 0 mm-100 mm). DAS28 <=1.6 = remission, DAS28 <=2.4 = low disease activity, DAS28 >=3.2 to 5.1 = moderate disease activity, DAS28 >5.1 = severe disease activity. | Baseline, Year 1, 2, 3, 4, 5 | 
| Percentage of Participants With Remission and Low Disease Activity as Assessed by Disease Activity Score Based on 28-Joints Count (DAS28) | DAS28 calculated from SJC and TJC using the 28 joints count, the serological markers of inflammation (ESR [millimeter per hour] or CRP [milligram per liter]) and patient's general health assessment (recorded on a VAS scale of 0 mm-100 mm). DAS28 <=1.6 = remission, DAS28 <=2.4 = low disease activity, DAS28 >=3.2 to 5.1 = moderate disease activity, DAS28 >5.1 = severe disease activity. | Year 1, 2, 3, 4, 5 | 
| Time to Remission | DAS28 calculated from SJC and TJC using the 28 joints count, the serological markers of inflammation (ESR [millimeter per hour] or CRP [milligram per liter]) and patient's general health assessment (recorded on a VAS scale of 0 mm-100 mm). DAS28 <=1.6 = remission, DAS28 <=2.4 = low disease activity, DAS28 >=3.2 to 5.1 = moderate disease activity, DAS28 >5.1 = severe disease activity. Time to achieve remission was calculated by Kaplan-Meier survival analysis. | Baseline up to last follow-up, assessed every 6 month for first 3 years and thereafter annually up to 10 years | 
| Health Assessment Questionnaire (HAQ) Score at Baseline | HAQ: self-reported, valid assessment of functional disability in rheumatoid arthritis. Assessed based on ability of participants to perform daily activities in 8 categories: dressing, arising, eating, walking, reaching, gripping, hygiene, and carrying out daily activities. HAQ score range: 0-3: without any difficulty=0, with some difficulty=1, with much difficulty=2, unable to do=3. HAQ total scores expressed as overall mean score with range 0-3: 0-0.25=normal functioning; 0.25-0.5=mild functional limitation; 0.5-1=moderate functional limitation; more than 1=significant functional limitation. | Baseline | 
| Change From Baseline in Health Assessment Questionnaire (HAQ) Score at Year 1, 2, and 3 | HAQ: self-reported, valid assessment of functional disability in rheumatoid arthritis. Assessed based on ability of participants to perform daily activities in 8 categories: dressing, arising, eating, walking, reaching, gripping, hygiene, and carrying out daily activities. HAQ score range: 0-3: without any difficulty=0, with some difficulty=1, with much difficulty=2, unable to do=3. HAQ total scores expressed as overall mean score with range 0-3: 0-0.25=normal functioning; 0.25-0.5=mild functional limitation; 0.5-1=moderate functional limitation; more than 1=significant functional limitation. | Baseline, Year 1, 2, 3 | 
| Percentage of Participants With Remission Based on Health Assessment Questionnaire (HAQ) Score | HAQ: self-reported, valid assessment of functional disability in rheumatoid arthritis. Assessed based on ability of participants to perform daily activities in 8 categories: dressing, arising, eating, walking, reaching, gripping, hygiene, and carrying out daily activities. HAQ score range: 0-3: without any difficulty=0, with some difficulty=1, with much difficulty=2, unable to do=3. HAQ total scores expressed as overall mean score with range 0-3. Participants who had HAQ total score <=0.5 were considered in remission state. | Year 1, 2, 3 | 
| Health Assessment Questionnaire (HAQ) Score 6 Months Prior to And 6 Months Post-Switching Etanercept | HAQ: self-reported, valid assessment of functional disability in rheumatoid arthritis. Assessed based on ability of participants to perform daily activities in 8 categories: dressing, arising, eating, walking, reaching, gripping, hygiene, and carrying out daily activities. HAQ score range: 0-3: without any difficulty=0, with some difficulty=1, with much difficulty=2, unable to do=3. HAQ total scores expressed as overall mean score with range 0-3: 0-0.25=normal functioning; 0.25-0.5=mild functional limitation; 0.5-1=moderate functional limitation; more than 1=significant functional limitation. | 6 months prior to and 6 months post switching etanercept | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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observational, non-interventional, cohort, retrospective, register, rheumatoid arthritis