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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT01646385
First received: April 12, 2012
Last updated: July 7, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention
Rheumatoid Arthritis
Drug: etanercept
Drug: non-biologic anti-rheumatic drugs

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Retrospective
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Crude Incidence Rate of Malignancy [ Time Frame: Baseline up to last follow-up, assessed every 6 month for first 3 years and thereafter annually up to 10 years ] [ Designated as safety issue: Yes ]
    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.

  • Crude Incidence Rate of Lymphoproliferative Malignancy (LM) [ Time Frame: Baseline up to last follow-up, assessed every 6 month for first 3 years and thereafter annually up to 10 years ] [ Designated as safety issue: Yes ]
    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.

  • Crude Incidence Rate of Serious Infections [ Time Frame: Baseline up to last follow-up, assessed every 6 month for first 3 years and thereafter annually up to 10 years ] [ Designated as safety issue: Yes ]
    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.

  • Crude Incidence Rate of Other Serious Adverse Events [ Time Frame: Baseline up to last follow-up, assessed every 6 month for first 3 years and thereafter annually up to 10 years ] [ Designated as safety issue: Yes ]
    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.

  • Crude Incidence Rate of All-Cause Mortality [ Time Frame: Baseline up to last follow-up, assessed every 6 month for first 3 years and thereafter annually up to 10 years ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Percentage of Participants Who Switched to Other Therapy Following Etanercept Discontinuation [ Time Frame: Baseline up to last follow-up, assessed every 6 month for first 3 years and thereafter annually up to 10 years ] [ Designated as safety issue: No ]
    Participants who switched from etanercept to either DMARDs or alternative biologic drug are reported.

  • Time on Etanercept Therapy [ Time Frame: Baseline up to last follow-up, assessed every 6 month for first 3 years and thereafter annually up to 10 years ] [ Designated as safety issue: No ]
    Time on etanercept therapy was calculated by Kaplan-Meier survival analysis.

  • Disease Activity Score Based on 28-Joints Count (DAS28) at Baseline [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Disease Activity Score Based on 28-Joints Count (DAS28) at Year 1, 2, 3, 4, and 5 [ Time Frame: Baseline, Year 1, 2, 3, 4, 5 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With Remission and Low Disease Activity as Assessed by Disease Activity Score Based on 28-Joints Count (DAS28) [ Time Frame: Year 1, 2, 3, 4, 5 ] [ Designated as safety issue: No ]
    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 Remission [ Time Frame: Baseline up to last follow-up, assessed every 6 month for first 3 years and thereafter annually up to 10 years ] [ Designated as safety issue: No ]
    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.

  • Health Assessment Questionnaire (HAQ) Score at Baseline [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Health Assessment Questionnaire (HAQ) Score at Year 1, 2, and 3 [ Time Frame: Baseline, Year 1, 2, 3 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With Remission Based on Health Assessment Questionnaire (HAQ) Score [ Time Frame: Year 1, 2, 3 ] [ Designated as safety issue: No ]
    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.

  • Health Assessment Questionnaire (HAQ) Score 6 Months Prior to And 6 Months Post-Switching Etanercept [ Time Frame: 6 months prior to and 6 months post switching etanercept ] [ Designated as safety issue: No ]
    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.


Enrollment: 6393
Study Start Date: February 2012
Study Completion Date: August 2012
Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
etanercept
adult rheumatoid arthritis patients initiating therapy with etanercept as their first biologic therapy
Drug: etanercept
use as per routine clinical practice
nbDMARD
biologic-naive adult rheumatoid arthritis patients with DAS28 >4.2 treated with non-biologic anti-rheumatic drugs(s).
Drug: non-biologic anti-rheumatic drugs
use as per routine clinical practice (methotrexate, azathioprine, cyclophosphamide, cyclosporine, leflunomide, other)

Detailed Description:

patients recruited sequentially as seen in clinical practice

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

adult patients with a diagnosis of rheumatoid arthritis

Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01646385

Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided

Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01646385     History of Changes
Other Study ID Numbers: B1801348
Study First Received: April 12, 2012
Results First Received: April 3, 2014
Last Updated: July 7, 2014
Health Authority: United Kingdom: Research Ethics Committee

Keywords provided by Pfizer:
observational
non-interventional
cohort
retrospective
register
rheumatoid arthritis

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
TNFR-Fc fusion protein
Antirheumatic Agents
Therapeutic Uses
Pharmacologic Actions
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Gastrointestinal Agents
Immunologic Factors
Immunosuppressive Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on August 26, 2014