Characterize Patients With Moderately Active Rheumatoid Arthritis (RA)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT01557322
First received: February 8, 2012
Last updated: August 26, 2013
Last verified: August 2013
  Purpose
  1. To assess the baseline (i.e. RA therapy initiation) characteristics in a real-world setting across two moderate RA cohorts: a Test Group of patients newly exposed to etanercept (Enbrel) therapy and a Control Group of patients with similar disease characteristics newly exposed to other, non-biologic therapies.
  2. To assess the change over time (from baseline to the most recent follow-up) in the characteristics described at baseline in 2 British Society for Rheumatology Biologics Register (BSRBR) cohorts (i.e. moderate RA patients treated with Disease modifying anti-rheumatic drugs (DMARDs) alone versus moderate RA patients treated with Enbrel).

Condition Intervention
Rheumatoid Arthritis
Biological: etanercept
Drug: methotrexate (MTX)

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Retrospective
Official Title: Evaluation of the Clinical Characteristics, Real-world Treatment Pathways, and Outcomes of Patients With Moderate Rheumatoid Arthritis

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Number of Participants With American College of Rheumatology (ACR) Criteria [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    ACR criteria: 1) Morning stiffness: in and around joints, lasting at least (>=) 1 hour; 2) Arthritis/deformity of >=3 joint areas: presence of soft tissue swelling or fluid (not bony overgrowth alone), 14 possible areas are right/left proximal interphalangeal (PIP), metacarpophalangeal (MCP), wrist, elbow, knee, ankle, metatarsophalangeal (MTP) joints; 3) Arthritis of hand joints: >=1 area swollen in wrist, MCP, PIP joint; 4) Symmetric arthritis: simultaneous involvement of same joint areas (as defined in 2) on both sides of body; 5): Rheumatoid nodules: subcutaneous nodules over bony prominences or extensor surfaces or in juxtaarticular regions; 6): Rheumatoid factor (RF): abnormal amounts of RF by any method for which result has been positive in <5% of normal control participants; 7) Radiographic changes: typical of RA on posteroanterior hand and wrist radiographs, which must include erosions/unequivocal bony decalcification localized in or most marked adjacent to involved joints.

  • Number of Participants With Systemic Features [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Systemic features included sicca syndrome, serosal involvement (pleurisy/pericarditis), eye involvement, systemic vasculitis, nailfold vasculitis, pulmonary fibrosis, and others (other than those specified).

  • Number of Participants With Prior Joint Replacement or Surgery [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Participants who had prior total knee replacement, total hip replacement, total shoulder replacement, total elbow replacement, wrist/hand/ankle/foot surgery, and neck surgery are reported.

  • Number of Participants With Chest X-Ray Prior to New Therapy [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  • Number of Participants With Comorbidities [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Comorbidities included: hypertension, moderate or severe heart failure, angina, stroke, epilepsy, asthma, chronic bronchitis/emphysema, peptic ulcer, tuberculosis, pre-existing or recent onset of central nervous system demyelinating disorders, chronic infectious disease such as chronic renal infection, chronic chest infection with bronchiectasis or sinusitis, active tuberculosis, renal, hepatic, hematologic, gastrointestinal, endocrine, pulmonary, cardiac, neurologic or cerebral disease, malignancy or history of malignancy, hyperthyroidism, depression and/or anxiety, recent substance abuse (drug or alcohol), human immunodeficiency virus (HIV) infection or active hepatitis B/C infection (including associated chronic active hepatitis). Participants suffering from any of the comorbidity are reported.

  • Body Mass Index (BMI) [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    BMI was calculated by weight divided by height squared and measured as kilogram per square meter (kg/m^2).

  • Blood Pressure (BP) [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    BP is the pressure of the blood within the arteries. It is produced primarily by the contraction of the heart muscle. BP measurement is recorded by 2 numbers: systolic BP (SBP, BP when heart is contracting; it is the maximum arterial pressure during contraction of left ventricle) and diastolic BP (DBP, BP when heart is relaxing; it is the minimum arterial pressure during relaxation and dilation of ventricles).

  • Change From Baseline in Disease Activity Score Based on 28-joints Count (DAS28) at Month 60 [ Time Frame: Baseline, Month 60 ] [ Designated as safety issue: No ]
    DAS28 calculated from the number of swollen joints (SJC) and painful joints (PJC) using the 28 joints count, acute phase reactants (erythrocyte sedimentation rate [ESR, millimeters per hour] or C-reactive protein [CRP, milligram per liter]) and patient's global assessment (PtGA) of disease activity (participant rated arthritis activity assessment with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity). DAS28 <2.6: remission, DAS28 <=3.2: low disease activity, DAS28 >3.2 to <=5.1: moderate disease activity, DAS28 >5.1: progression.

  • Change From Baseline in Tender Joints Count (TJC) at Month 60 [ Time Frame: Baseline, Month 60 ] [ Designated as safety issue: No ]
    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. A negative value in change from baseline indicates an improvement.

  • Change From Baseline in Swollen Joints Count (SJC) at Month 60 [ Time Frame: Baseline, Month 60 ] [ Designated as safety issue: No ]
    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. A negative value in change from baseline indicates an improvement.

  • Change From Baseline in C-Reactive Protein (CRP) Level at Month 60 [ Time Frame: Baseline, Month 60 ] [ Designated as safety issue: No ]
    The test for CRP is a laboratory measurement for evaluation of an acute phase reactant of inflammation through the use of an ultra-sensitive assay. Normal range of CRP is <10 milligram/liter (mg/L). A decrease in the level of CRP indicates reduction in inflammation and therefore improvement.

  • Change From Baseline in Erythrocyte Sedimentation Rate (ESR) at Month 60 [ Time Frame: Baseline, Month 60 ] [ Designated as safety issue: No ]
    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 millimeter/hour (mm/hr). A higher rate is consistent with inflammation.

  • Change From Baseline in Patient's Global Assessment (PtGA) of Disease Activity at Month 60 [ Time Frame: Baseline, Month 60 ] [ Designated as safety issue: No ]
    Participants answered: "Considering all the ways your arthritis affects you, how are you feeling today?" Participants responded by using a 0 - 100 mm VAS, where 0 mm = very well and 100 mm = very poorly.

  • Duration of Disease (Rheumatoid Arthritis) [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  • Time Since First Rheumatologist Visit [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  • Time Since Recalled Symptom Onset [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    RA symptoms include joint pain, stiffness, and swelling.

  • Number of Participants With Previous and Current Disease Modifying Anti-Rheumatic Drugs (DMARDs) [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Number of participants who previously received DMARDs or were currently on DMARDs at baseline is reported.

  • Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Score at Month 60 [ Time Frame: Baseline, Month 60 ] [ Designated as safety issue: No ]
    Health Assessment Questionnaire-Disability Index (HAQ-DI): participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week. Each item scored on 4-point scale from 0 to 3: 0 = no difficulty; 1 = some difficulty; 2 = much difficulty; 3 = unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0 to 3 where 0 = least difficulty and 3 = extreme difficulty.

  • Change From Baseline in 36-Item Short-Form Health Survey (SF-36) at Month 60 [ Time Frame: Baseline, Month 60 ] [ Designated as safety issue: No ]
    The 36-Item Short-Form Health Survey (SF-36) is a standardized survey evaluating 8 aspects of functional health and well-being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. These 8 aspects can also be summarized as physical component score (PCS) and mental component score (MCS). Total of 3 variables were analyzed (2 composite subscales and vitality score). The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning).

  • Change From Baseline in Euro Quality of Life - 5 Dimensions (EQ-5D) at Month 60 [ Time Frame: Baseline, Month 60 ] [ Designated as safety issue: No ]
    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 and discomfort, and anxiety and 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. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state.

  • Time to Disease Worsening [ Time Frame: Baseline up to Month 60 ] [ Designated as safety issue: No ]
    Disease worsening (severe RA diagnosis) was defined as DAS28 score >5.1.

  • Time to Therapeutic Goal [ Time Frame: Baseline up to Month 60 ] [ Designated as safety issue: No ]
    Therapeutic goal achievement was based on physician's discretion.

  • Change From Baseline in Pain Visual Analog Scale (VAS) Score at Month 60 [ Time Frame: Baseline, Month 60 ] [ Designated as safety issue: No ]
    The pain VAS is a horizontal line; 100 millimeter (mm) in length, self-administered by the participant to rate pain from 0 mm (no pain) to 100 mm (worst possible pain).Change = mean scores at observation minus mean scores at baseline.

  • Number of Participants Achieving American College of Rheumatology 20% (ACR20) Response at Month 60 [ Time Frame: Month 60 ] [ Designated as safety issue: No ]
    ACR20 response: greater than or equal to (>=) 20 percent (%) improvement in tender joints count (TJC); >= 20% improvement in swollen joints count (SJC); and >= 20% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and C-Reactive Protein (CRP).

  • Number of Participants Achieving American College of Rheumatology 50% (ACR50) Response at Month 60 [ Time Frame: Month 60 ] [ Designated as safety issue: No ]
    ACR50 response: >= 50% improvement in TJC or SJC and 50% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the HAQ); and CRP.

  • Number of Participants Achieving American College of Rheumatology 70% (ACR70) Response at Month 60 [ Time Frame: Month 60 ] [ Designated as safety issue: No ]
    ACR70 response: >=70% improvement in TJC or SJC and 70% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the HAQ); and CRP.

  • Number of Rheumatoid Arthritis (RA) Related Visits [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Number of RA-related visits to doctor/healthcare professional in previous 3 months was to be reported.

  • Direct and Indirect Cost of Rheumatoid Arthritis (RA) Treatment [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Direct costs included: outpatient costs, physician visits, outpatient surgery, emergency room visits, visits to healthcare professionals other than physicians, medications, diagnostic and/or therapeutic procedures, medical devices, inpatient costs, admission to acute-care nonsurgical departments, admission to acute-care surgical departments, admission to extended-care facilities, and other direct costs (travel expenses, home care, home remodeling, medical devices, non-physician healthcare professionals, alternative medicine practitioner, participant time). Indirect cost (related to lost productivity through morbidity and death) included: lost productivity in employed participants (disability, sick-leaves), lost opportunities (lost productivity in family members caring for the patient, disability requiring changes to everyday activities), and lost wages.


Other Outcome Measures:
  • Number of Participants With Adverse Events (AEs) [ Time Frame: Month 6, 12, 18, 24, 30, 36, 48, 60 ] [ Designated as safety issue: Yes ]
    An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Number of participants with AEs is reported by each follow-up time point up to Month 60.

  • Number of Participants With Malignancy [ Time Frame: Month 6, 12, 18, 24, 30, 36, 48, 60 ] [ Designated as safety issue: Yes ]
    Malignancy included lymphoproliferative tumors, Hodgkins lymphoma, myeloma, leukaemia, non-melanoma skin cancer, and solid tumor. Number of participants with each of these malignancies is reported by each follow-up time point up to Month 60.

  • Number of Participants Who Died or Hospitalized Due to Adverse Events [ Time Frame: Month 6, 12, 18, 24, 30, 36, 48, 60 ] [ Designated as safety issue: Yes ]
    Number of participants who died or hospitalized due to AEs is reported by each follow-up time point up to Month 60.

  • Change From Baseline in Disease Activity Score Based on 28-joints Count (DAS28) at Month 6 [ Time Frame: Baseline, Month 6 ] [ Designated as safety issue: No ]
    DAS28 calculated from the SJC and PJC using the 28 joints count, acute phase reactants (ESR, millimeters per hour or CRP, milligram per liter) and PtGA of disease activity (participant rated arthritis activity assessment with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity). DAS28 <2.6: remission, DAS28 <=3.2: low disease activity, DAS28 >3.2 to <=5.1: moderate disease activity, DAS28 >5.1: progression.

  • Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Score at Month 6 [ Time Frame: Baseline, Month 6 ] [ Designated as safety issue: No ]
    Health Assessment Questionnaire-Disability Index (HAQ-DI): participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week. Each item scored on 4-point scale from 0 to 3: 0 = no difficulty; 1 = some difficulty; 2 = much difficulty; 3 = unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0 to 3 where 0 = least difficulty and 3 = extreme difficulty.

  • Change From Baseline in 36-Item Short-Form Health Survey (SF-36) at Month 6 [ Time Frame: Baseline, Month 6 ] [ Designated as safety issue: No ]
    The 36-Item Short-Form Health Survey (SF-36) is a standardized survey evaluating 8 aspects of functional health and well-being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. These 8 aspects can also be summarized as physical component score (PCS) and mental component score (MCS). Total of 3 variables were analyzed (2 composite subscales and vitality score). The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning).

  • Change From Baseline in Euro Quality of Life - 5 Dimensions (EQ-5D) at Month 6 [ Time Frame: Baseline, Month 6 ] [ Designated as safety issue: No ]
    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 and discomfort, and anxiety and 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. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state.


Enrollment: 1754
Study Start Date: October 2011
Study Completion Date: September 2012
Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Biologic Biological: etanercept
This is a Non-interventional study. The data is being analyzed retrospectively. The data consists of 2 cohorts; biologic and non-biologic
Other Name: Enrel
non-biologic DMARD Drug: methotrexate (MTX)
This is a Non-interventional study. The data is being analyzed retrospectively. The data consists of 2 cohorts; biologic and non-biologic
Other Name: non-biologic DMARD

Detailed Description:

Retrospective database analysis

  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

The BSR Biologics Register tracks the progress of patients with severe rheumatoid arthritis and other rheumatic conditions who are taking biologic therapy and those who are biologic naive.

Criteria

Inclusion Criteria:

The Test Group will be patients with rheumatoid arthritis, newly starting therapy with etanercept (Enbrel). Inclusion criteria for the exposed cohort subjects are:

  • Patients aged 18 years and over at the time of diagnosis;
  • Patients from the BSRBR with moderate RA as defined by a DAS28 (>3.2 and ≤5.1);
  • Patients who have given informed consent for long term follow-up and access to all medical records;
  • Patients initiating (i.e. at leats one treatment) treatment with etanercept (Enbrel) for RA.

The Control Group:

  • Patients aged 18 years and over a the time of diagnosis;
  • Patients from the BSRBR with moderate RA as defined by a DAS28 (>3.2 and ≤5.1);
  • Patients who have given informed consent for long term follow-up and access to all medical records; Patients are receiving at least one traditional DMARD and have never been prescribed a biologic agent;

Exclusion Criteria:

Per BSRBR registry since data is retropsectively being analyzed

  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: NCT01557322

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: NCT01557322     History of Changes
Other Study ID Numbers: B1801345
Study First Received: February 8, 2012
Results First Received: August 26, 2013
Last Updated: August 26, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Autoimmune Diseases
Connective Tissue Diseases
Immune System Diseases
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Methotrexate
Abortifacient Agents
Abortifacient Agents, Nonsteroidal
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antirheumatic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Physiological Effects of Drugs
Reproductive Control Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014