Observational Study of Tocilizumab in Participants With Rheumatoid Arthritis in Australia

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01683604
First received: September 5, 2012
Last updated: June 10, 2016
Last verified: June 2016
  Purpose
This multi-center, observational study will evaluate the treatment patterns in clinical practice, efficacy and safety of tocilizumab in participants with rheumatoid arthritis (RA) who have had an inadequate response (or were intolerant to) treatment with non-biological disease-modifying anti-rheumatic drugs (DMARDs) or with one biological agent. Data will be collected from each eligible participant initiated on tocilizumab treatment by their treating physician according to approved label for 6 months from start of treatment.

Condition Intervention
Rheumatoid Arthritis
Other: Observational study

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: A Multi-National, Multi-Center Non-Interventional Study in Rheumatoid Arthritis (RA) Patients Treated With Tocilizumab (ACT-UP)

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Percentage of Participants on Tocilizumab Treatment at Month 6 After Treatment Initiation [ Time Frame: Month 6 ] [ Designated as safety issue: No ]
    Percentage of participants on tocilizumab treatment at Month 6 was calculated as: [(participants on tocilizumab treatment at Month 6) divided by (participants evaluable for primary objective)] multiplied by 100.

  • Patient Assessment of Pain Using Visual Analog Scale (VAS) at Baseline [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Participants measured the pain intensity due to RA on a 100 millimeter (mm) VAS, where the responses were on a continuous range from 0 = no pain to 100 = unbearable pain.

  • Patient Global Assessment of Disease Activity Using VAS at Baseline [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    The patient's global assessment of disease activity was measured using a 100 mm VAS, where the responses were on a continuous range from 0 = managing very well to 100 = managing very poorly.

  • Physician Global Assessment of Disease Activity Using VAS at Baseline [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Physician global assessment of disease activity was assessed on a 100 mm VAS, where 0 = no arthritis activity to 100 = extremely active arthritis.

  • Health Assessment Questionnaire Disability Index (HAQ-DI) Scores at Baseline [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    The HAQ-DI is a questionnaire that measures functional status (disability) and health-related quality of life. It measures the participant's ability to perform everyday tasks. The index consists of 20 questions regarding the function of the upper and lower extremities. These questions are summarized in 8 categories: dressing and grooming, arising, eating, walking, hygiene, reach, grip, and common activities over past week. Each question is evaluated according to the degree of severity on a 4-point scale. Total score for HAQ-DI is the average of all questions and ranges from 0 = without any difficulty to 3 = unable to do.

  • Tender Joint Count (TJC) and Swollen Joint Count (SJC) at Baseline [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    TJC was determined by examining 28 and 68 joints and identifying the joints that were painful under pressure or to passive motion. Tenderness was recorded on the joint assessment form at baseline, no tenderness = 0, tenderness = 1. SJC was determined by examining 28 and 66 joints and identifying when swelling was present. Swelling was recorded on the joint assessment form at baseline, no swelling = 0, swelling =1.

  • Erythrocyte Sedimentation Rate (ESR) at Baseline [ Time Frame: Baseline ] [ 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 millimeters per hour (mm/hr). A decrease in the level indicates reduction in inflammation and therefore improvement.

  • C-Reactive Protein (CRP) at Baseline [ Time Frame: Baseline ] [ 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 ultrasensitive assay. A decrease in the level of CRP indicates reduction in inflammation and therefore improvement.


Secondary Outcome Measures:
  • Percentage of Participants Starting Tocilizumab After Stopping a Biologic Treatment or After Failing DMARDs [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  • Median Dose at Month 6 [ Time Frame: Month 6 ] [ Designated as safety issue: No ]
  • Percentage of Participants With Tocilizumab Dose Changed According to the Reason for Change [ Time Frame: Baseline up to Month 6 ] [ Designated as safety issue: No ]
    Percentage of participants with increase or decrease in tocilizumab administration according to the reason for dose modification was reported.

  • Mean Dosing Interval at Month 6 [ Time Frame: Month 6 ] [ Designated as safety issue: No ]
    The time interval between two successive doses in days was reported.

  • Percentage of Participants With Reasons Who Discontinued Tocilizumab [ Time Frame: Baseline up to Month 6 ] [ Designated as safety issue: No ]
  • Time to Restoration of Initial Dosing Regimen [ Time Frame: Baseline up to Month 6 ] [ Designated as safety issue: No ]
  • Percentage of Participants by Reason for Choice of Monotherapy at Baseline [ Time Frame: Baseline up to Month 6 ] [ Designated as safety issue: No ]
  • Percentage of Participants on Tocilizumab Monotherapy (8 mg/Kg) at Baseline and at Month 6 [ Time Frame: Baseline, Month 6 ] [ Designated as safety issue: No ]
  • Duration of Tocilizumab Treatment [ Time Frame: Baseline up to Month 6 ] [ Designated as safety issue: No ]
  • Percentage of Participants by Duration of Morning Stiffness [ Time Frame: Baseline, Month 3, Month 6 ] [ Designated as safety issue: No ]
    Duration of morning stiffness was defined as the time elapsed between the time of usual awakening (even if not in the morning) and the time the participant was able to resume normal activities without stiffness. The participant assessment of morning stiffness was measured using a ruler on a 100 mm VAS by 1 of the six categories: less than (<) 30 minutes, between 30 and 240 minutes, greater than (>) 240 minutes and whole day.

  • Percentage of Participants With and Without Morning Stiffness [ Time Frame: Baseline, Month 3, Month 6 ] [ Designated as safety issue: No ]

    Morning stiffness was defined by the time elapsed between the time of usual awakening (even if not in the morning) and the time the participant was able to resume normal activities without stiffness. The participant assessed morning stiffness based on the following criteria:

    1. Presence of participant's joints stiff when woke up that day, measured as yes or no
    2. Duration of morning stiffness, measured using a ruler on a 100 mm VAS by 1 of the six categories: < 30 minutes, between 30 and 240 minutes, > 240 minutes, and the whole day.
    3. Severity of morning stiffness measured using a ruler on a 100 mm VAS where the responses were on a continuous range from 0 = no stiffness to 100 = maximum stiffness.

  • Percentage of Participants Adhering to Local Label for Adverse Events [ Time Frame: Baseline up to Month 6 ] [ Designated as safety issue: No ]
    Percentage of participants who adhered to local label/protocol for the management of adverse events is reported.

  • Disease Activity Score Based on 28 Joint Count (DAS28) Score by Visit [ Time Frame: Baseline, Month 3, Month 6 ] [ Designated as safety issue: No ]
    The DAS28 score is a measurement of RA activity on a 0 to 10 scale, with higher scores representing higher disease activity, and calculated as DAS28 = 0.56 x √TJC28 + 0.28 x √SJC28 + 0.70 x natural logarithm (ln) (CRP + 1) + 0.014 x PGH + 0.96, where TJC28 = tender joint count on 28 units, SJC28 = swollen joint count on 28 units, CRP = serum concentration of c-reactive protein (after converting units to mg/dL), PGH = patient global assessment of disease activity, which was measured on a 100 mm VAS, where 0 = managing very well and 100 = managing very poorly. A score of less than 2.6 represents clinical remission, a score of greater than or equal to 2.6 and less than or equal to 3.2 represents low disease activity, a score of greater than 3.2 and less than or equal to 5.1 represents moderate disease activity, and a score of greater than 5.1 represents high (or severe) disease.

  • Percentage of Participants Achieving Good European League Against Rheumatism (EULAR) Response at Month 3 and Month 6 [ Time Frame: Month 3 and Month 6 ] [ Designated as safety issue: No ]
    Clinical response was assessed according to EULAR criteria that classified the participant according to individual changes in DAS28 score as good, moderate, or no response. The DAS28 score is a measurement of RA activity on a 0 to 10 scale, with higher scores represent higher disease activity, and calculated as DAS28 = 0.56 x √TJC28 + 0.28 x √SJC28 + 0.36 x ln(CRP + 1) + 0.014 x PGH + 0.96, where TJC28 = tender joint count on 28 units, SJC28 = swollen joint count on 28 units, CRP = serum concentration of c-reactive protein (after converting units to mg/dL), PGH = patient's global assessment of disease activity, which was measured on a 100 mm VAS, where 0 = managing very well and 100 = managing very poorly. Good responders experienced a change from baseline of greater than 1.2 with a DAS28 score less than or equal to 3.2.

  • Clinical Disease Activity Index (CDAI) Score by Visit [ Time Frame: Baseline, Month 3, Month 6 ] [ Designated as safety issue: No ]
    The CDAI is a combined index for measuring disease activity in RA and calculated as CDAI = TJC28 + SJC28 + PGH (in centimeters) + PhGH (in centimeters), where TJC28 = tender joint count on 28 units, SJC28 = swollen joint count on 28 units, PGH = patient's global assessment of disease activity, assessed on a 100 mm VAS, where 0 = managing very well and 100 = managing very poorly, and PhGH = physician global assessment of disease activity, assessed on a 100 mm VAS, where 0 = no arthritis activity and 100 = extremely active arthritis; with a total score ranged from 0-76. Higher scores indicate greater disease activity. CDAI score of less than or equal to 2.8 represents clinical remission, score of less than or equal to 10.0 represents low disease activity, score of less than or equal to 22.0 represents moderate disease activity, and score of greater than 22.0 represents high (or severe) disease.

  • Change From Baseline in TJC and SJC at Month 3 and Month 6 [ Time Frame: Baseline, Month 3, Month 6 ] [ Designated as safety issue: No ]
    TJC was determined by examining 28 and 68 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 baseline, no tenderness = 0, tenderness = 1. SJC was determined by examination of 28 and 66 joints and identifying when swelling was present. The number of swollen joints was recorded on the joint assessment form at baseline, no swelling = 0, swelling =1.

  • Simplified Disease Activity Index (SDAI) Score by Visit [ Time Frame: Baseline, Month 3, Month 6 ] [ Designated as safety issue: No ]
    The SDAI is a combined index for measuring disease activity in RA and calculated as SDAI = TJC28 + SJC28 + PGH (in centimeters) + PhGH (in centimeters) + CRP (in mg/dL), where TJC28 = tender joint count on 28 units, SJC28 = swollen joint count on 28 units, PGH = patient's global assessment of disease activity, assessed on a 100 mm VAS, where 0 = managing very well and 100 = managing very poorly, PhGH = physician global assessment of disease activity, assessed on a 100 mm VAS, where 0 = no arthritis activity and 100 = extremely active arthritis, CRP = serum concentration of c-reactive protein; with a total SDAI score ranged from 0-86. Higher scores indicate greater disease activity. SDAI scores of less than or equal to 3.3 represents clinical remission, less than or equal to 11.0 represents low disease activity, less than or equal to 26.0 represents moderate disease activity, and greater than 26.0 represents high (or severe) disease.

  • Percentage of Participants With an American College of Rheumatology (ACR) 20%, 50%, or 70% (ACR20/50/70) Response at Month 3 and Month 6 From the Start of Tocilizumab Treatment [ Time Frame: Month 3 and Month 6 ] [ Designated as safety issue: No ]
    ACR 20,50 or 70 response=an improvement of ≥ 20%, ≥ 50% or ≥ 70% respectively, as compared to baseline in TJC28 and SJC28, and 20%, 50% or 70% improvement in at least 3 of the 5 following measures: Patient's Assessment of Pain over the previous 24 hours, PGA, PhGA, HAQ, and acute phase reactant (either CRP or ESR). TJC and SJC, based on 28-joint assessments. Number of tender joints and swollen joints were recorded on the joint assessment form at baseline, no tenderness = 0 and tenderness = 1, no swelling = 0 and swelling =1, respectively. HAQ measures functional status (disability) and health-related quality of life with 20 questions, summarized in 8 categories: dressing and grooming, arising, eating, walking, hygiene, reach, grip and common activities over past week, 0=without difficulty to 3=unable to do. Patient's assessment of pain assessed using a VAS; 0=no pain, 100=unbearable pain; PGA and PhGA, assessed using VAS ; 0= no disease activity, 100=maximum disease activity.

  • Change From Baseline in Physician Global Assessment of Disease Activity at Months 3 and 6 [ Time Frame: Baseline, Month 3, Month 6 ] [ Designated as safety issue: No ]
    The physician global assessment of disease activity was evaluated using a 100 mm VAS where 0 = no arthritis activity and 100 = extremely active arthritis. Higher scores indicated increased level of disease.

  • Change From Baseline in Patient Global Assessment of Disease Activity at Months 3 and 6 [ Time Frame: Baseline, Month 3, Month 6 ] [ Designated as safety issue: No ]
    The patient's global assessment of disease activity was measured using a 100 mm VAS, where the responses were on a continuous range from 0= managing very well and 100 = managing very poorly.

  • Change From Baseline in HAQ-DI Score at Months 3 and 6 [ Time Frame: Baseline, Month 3, Month 6 ] [ Designated as safety issue: No ]
    The HAQ-DI is a questionnaire that measures functional status (disability) and health-related quality of life. It measures the participant's ability to perform everyday tasks. The index consists of 20 questions regarding the function of the upper and lower extremities. These questions are summarized in 8 categories: dressing and grooming, arising, eating, walking, hygiene, reach, grip and common activities over past week. Each question was evaluated according to the degree of severity on a 4-point scale ranging from 0 = without any difficulty to 3 = unable to do. Total score is the sum of each question, which ranges from 0 to 60, where higher scores represent higher disease activity. The change from baseline in HAQ-DI score at Month 3 and Month 6 was calculated as the difference between HAQ-D1 score reported at baseline and the HAQ-D1 score reported at Month 3 and Month 6.

  • Change From Baseline in VAS-Fatigue at Months 3 and 6 [ Time Frame: Baseline, Month 3, Month 6 ] [ Designated as safety issue: No ]
    Participants measured the level of fatigue due to RA using a 100 mm VAS, where the responses were on a continuous range from 0 = no fatigue to 100 = extreme fatigue.

  • Change From Baseline in Patient's Assessment of Pain at Months 3 and 6 [ Time Frame: Baseline, Month 3, Month 6 ] [ Designated as safety issue: No ]
    Participants measured the pain intensity due to RA using a 100 mm VAS, where the responses were on a continuous range from 0 = no pain to 100 = unbearable pain.

  • Change From Baseline in Participant Assessment of Morning Stiffness Using VAS at Months 3 and 6 [ Time Frame: Baseline, Month 3, Month 6 ] [ Designated as safety issue: No ]
    The participant assessment of morning stiffness was measured using a ruler on a 100 mm VAS, where the responses were on a continuous range from 0 = no stiffness and 100 = maximum stiffness.


Enrollment: 37
Study Start Date: July 2012
Study Completion Date: June 2014
Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Rheumatoid Arthritis (RA) Participants (All Groups)
Participants with severe RA were prescribed with tocilizumab in accordance with routine clinic practice, and were observed for 6 months.
Other: Observational study

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
RA participants treated with tocilizumab
Criteria

Inclusion Criteria:

  • Severe RA.
  • Inadequate response (or intolerant) to non-biological DMARDs or one biologic agent
  • Participants initiating treatment with tocilizumab on their physician's decision (in accordance with the local label), including participants who started treatment with tocilizumab within the 8 weeks prior to the enrolment visit.

Exclusion Criteria:

  • Tocilizumab treatment more than 8 weeks prior to the enrolment visit.
  • Previous tocilizumab treatment in a clinical trial or for compassionate use.
  • Enrolled in an ongoing clinical trial and/or treatment with any investigational agent within 4 weeks (or 5 half-lives of the investigational agent, whichever is longer) before starting treatment with tocilizumab.
  • History of autoimmune disease or any joint inflammatory disease other than RA.
  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: NCT01683604

Locations
Australia, New South Wales
Campsie, New South Wales, Australia, 2194
Coffs Harbour, New South Wales, Australia, 2450
New Lambton, New South Wales, Australia, 2305
Australia, South Australia
Woodville, South Australia, Australia, 5011
Australia, Victoria
Heidelberg, Victoria, Australia, 3084
Morwell, Victoria, Australia, 3842
Australia, Western Australia
Shenton Park, Western Australia, Australia, 6008
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01683604     History of Changes
Other Study ID Numbers: ML28144 
Study First Received: September 5, 2012
Results First Received: April 20, 2016
Last Updated: June 10, 2016
Health Authority: Australia: National Health and Medical Research Council

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases

ClinicalTrials.gov processed this record on July 25, 2016