An Global Comparative Observational Study of RoActemra/Actemra (Tocilizumab) in Patients With Rheumatoid Arthritis

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01543503
First received: February 28, 2012
Last updated: January 12, 2016
Last verified: January 2016
  Purpose
This prospective, multi-center, observational study will assess the efficacy and safety of treatment in patients who are treated with a TNF Inhibitor or RoActemra/Actemra (tocilizumab) as the first biologic therapy. Data will be collected for 52 weeks.

Condition
Rheumatoid Arthritis

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: A Global Comparative Observational Study In Rheumatoid Arthritis (RA) Patients Who Are Treated With A TNF Inhibitor Or Tocilizumab As The First Biologic Therapy

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Mean Change From Baseline in Calculated Disease Activity Score Based on 28 Joint Count Erythrocyte Sedimentation Rate at Week 24 [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
    Disease activity score based on 28 joint counts (DAS28) is a composite measure of disease severity and it incorporates four specific measures of disease: swollen joint count (SJC) of 28 joints, tender joint count (TJC) of 28 joints, Patient's Global Assessment of Disease Activity by visual analogue scale (VAS), and acute-phase inflammatory marker [erythrocyte sedimentation rate (ESR) in millimeter/hour (mm/h), or C-reactive protein (CRP) in milligram/liter (mg/L)]. For the purposes of this study, ESR was used whenever possible to calculate the DAS28 (DAS28-ESR). Higher the scores, greater is the disease activity. A DAS28 score of less than or equal to (</=) 3.2 = low disease activity, a DAS28 score of >3.2 to 5.1 = moderate to high disease activity.


Secondary Outcome Measures:
  • Mean Change From Baseline in Disease Activity Score Based on 28 Joint Count Erythrocyte Sedimentation Rate at Week 52 [ Time Frame: Baseline and Week 52 ] [ Designated as safety issue: No ]
    Disease activity score based on 28 joint counts (DAS28) is a composite measure of disease severity and it incorporates four specific measures of disease: swollen joint count (SJC) of 28 joints, tender joint count (TJC) of 28 joints, Patient's Global Assessment of Disease Activity by visual analogue scale (VAS), and acute-phase inflammatory marker (ESR in mm/h, or CRP in mg/L). For the purposes of this study, ESR was used whenever possible to calculate the DAS28 (DAS28-ESR). Higher the scores, greater is the disease activity. A DAS28 score of </= 3.2 = low disease activity, a DAS28 score of >3.2 to 5.1 = moderate to high disease activity.

  • Mean Change From Baseline in Erythrocyte Sedimentation Rate [ Time Frame: Baseline, Week 24, Week 52 ] [ Designated as safety issue: No ]
    Blood samples were collected for ESR, which is an acute phase reactant and a measure of inflammation. BL = baseline.

  • Mean Change From Baseline in C-reactive Protein [ Time Frame: Baseline, Week 24, Week 52 ] [ Designated as safety issue: No ]
    Blood samples were collected for C-reactive protein (CRP). CRP is an inflammation marker. High levels of this protein indicate inflammation in diseases such as RA.

  • Mean Change From Baseline in Swollen Joint Count [ Time Frame: Baseline, Week 24, Week 52 ] [ Designated as safety issue: No ]
    A swollen joint count (SJC) is the most specific clinical method to quantify abnormalities in participants with RA. It reflects the amount of inflamed synovial tissue. Twenty-eight joints were assessed for swelling. Joints were classified as swollen (1)/ not swollen (0) giving a total possible SJC score of 0 to 28.

  • Mean Change From Baseline in Tender Joint Count [ Time Frame: Baseline, Week 24, Week 52 ] [ Designated as safety issue: No ]
    A tender joint count (TJC) is the most specific clinical method to quantify abnormalities in participants with RA. It is associated with the level of pain. Twenty-eight joints were assessed for tenderness. Joints were classified as tender (1)/not tender (0) giving a total possible TJC score of 0 to 28.

  • Mean Change From Baseline in Clinical Disease Activity Index and Simplified Disease Activity Index Score [ Time Frame: Baseline, Week 24, Week 52 ] [ Designated as safety issue: No ]
    Clinical Disease Activity Index (CDAI) was calculated as the sum of the following parameters: SJC + TJC + VAS Patient Global Assessment of Disease Activity + VAS Physician Global Assessment of Disease Activity. VAS assessments involved a 10-cm horizontal scale from 'no disease activity' to 'maximum disease activity'. CDAI scores ranged from 0 to 76, with higher scores indicating increased disease activity. Simplified Disease Activity Index (SDAI) was calculated as the sum of the following parameters: SJC +TJC + Patient Global Assessment of Disease Activity + Physician Global Assessment of Disease Activity + CRP. SDAI scores ranged from 0 to 86, with higher scores also indicating increased disease activity.

  • Mean Change From Baseline in Physician Global Assessment Score [ Time Frame: Baseline, Week 24, Week 52 ] [ Designated as safety issue: No ]
    The Physician's Global Assessment of disease activity was assessed using a 0 to 100 millimeter (mm) horizontal VAS. The left-hand extreme of the line equals 0 mm, and is described as "no disease activity" (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm, as "maximum disease activity" (maximum arthritis disease activity). Change from baseline = scores at observation minus score at baseline. An increase in score from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represented improvement.

  • Loss of Efficacy or Development of Intolerance to Biologic Therapy [ Time Frame: Up to Week 52 ] [ Designated as safety issue: No ]
    Events that are clearly consistent with the expected pattern of progression of the underlying disease may contribute to lack of efficacy. Lack of efficacy was one of the reasons for termination of biology therapy. The number of participants showing lack of efficacy to biologic therapy is presented.

  • Proportion of Participants Who Terminated Biologic Treatment [ Time Frame: Up to Week 52 ] [ Designated as safety issue: No ]
    The proportion of participants who discontinued biologic treatment was compared between tocilizumab-treated and TNF inhibitor-treated participants.

  • Reasons for Treatment Discontinuation [ Time Frame: Up to Week 52 ] [ Designated as safety issue: No ]
    The reasons for discontinuation of tocilizumab or TNF inhibitor is presented.

  • Cumulative Number of Participants Who Discontinued Biologic Therapy at the End of Each Study Period [ Time Frame: Up to end of treatment ] [ Designated as safety issue: No ]
    The total number of participants who discontinued biologic therapy at the end of each study period (Week 0 - 24, Week 24 - 52, Week 52 - 57 and Week 57 - end of treatment) is presented. Participants who did not have a biologic therapy discontinuation or discontinued before having one, were considered as 'censored' at the date study termination.

  • Number of Participants of Infusion Reactions or Injection Site Reactions During the Study Following the Start of the First Biologic Therapy [ Time Frame: Up to Week 52 ] [ Designated as safety issue: No ]
    An infusion reaction was defined as an adverse event (AE) occurring during and within 24 hours after the infusion, which may include hypersensitivity reactions or anaphylactic reactions. Injection site reactions were included in the summaries for infusion reactions.

  • Number of Participants With Adverse Events, Serious Adverse Events and Non-serious Adverse Events [ Time Frame: Up to Week 52 ] [ Designated as safety issue: No ]
    An AE is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A serious adverse event (SAE) is any untoward medical occurrence that at any dose results in death, are life threatening, requires hospitalization or prolongation of hospitalization or results in disability/incapacity, and congenital anomaly/birth defect.

  • Number of Participants With Serious and Non-serious Adverse Events of Special Interest, Including Infections, During the Study [ Time Frame: Up to Week 52 ] [ Designated as safety issue: No ]
    Adverse events of special interest (AESI) for this study included: infections (including opportunistic infections), myocardial infarction/acute coronary syndrome, gastrointestinal perforation and related events, malignancies, anaphylaxis / hypersensitivity reactions, demyelinating disorders, stroke, bleeding events and hepatic events. Based on seriousness criteria, they were categorized as serious and non-serious adverse events of special interest.

  • Mean Change From Baseline in Health Assessment Questionnaire Disability Index Score [ Time Frame: Baseline, Week 24, Week 52 ] [ Designated as safety issue: No ]
    The Health Assessment Questionnaire-Disability Index (HAQ-DI) is a 20-question instrument that assesses the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping and activities of daily living). Responses in each functional area are scored from 0 to 3 (0=no difficulty and 3=inability to perform a task in that area). HAQ-DI 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.

  • Mean Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue Score [ Time Frame: Baseline, Week 24, Week 52 ] [ Designated as safety issue: No ]
    Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) is a 13-item questionnaire. Participants scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). The larger the participant's response to the questions (with the exception of 2 negatively stated), the greater the participant's fatigue. The sum of all responses resulted in the FACIT-F score for a total possible score of 0 (worse score) to 52 (better score). A higher score reflects an improvement in the participant's health status.

  • Mean Change From Baseline in Visual Analogue Scale Pain Score [ Time Frame: Baseline, Week 24, Week 52 ] [ Designated as safety issue: No ]
    VAS is a 100 mm scale. Intensity of pain range: 0 mm=no pain to 100 mm=worst possible pain. Change from baseline =scores at observation minus score at baseline. An increase in score from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represented improvement.

  • Shift From Baseline in Morning Stiffness [ Time Frame: Baseline, Week 24, Week 52 ] [ Designated as safety issue: No ]
    Shift tables presenting the number of participants in each bivariate category Week (W) 0 versus Week 24 and Week 52, with regards to morning stiffness at the different time points, was presented for each treatment arm. For participants who experienced joint stiffness while waking up in the morning, duration of morning stiffness was categorized as follows: Less than 30 minutes (min), Between 30 and 60 minutes, Between 60 and 120 minutes, Between 120 to 240 minutes, More than 240 minutes and the whole day. Baseline = BL

  • Change From Baseline in Patient Global Assessment of Disease Activity [ Time Frame: Baseline, Week 24, Week 52 ] [ Designated as safety issue: No ]
    The patient's global assessment of disease activity is assessed on a 0 to 100 mm horizontal VAS by the participant. The left-hand extreme of the line equals 0 mm, and is described as "no disease activity" (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm, as "maximum disease activity" (maximum arthritis disease activity). A negative change from Baseline indicated improvement.


Enrollment: 1225
Study Start Date: February 2012
Study Completion Date: February 2015
Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Adult patients with rheumatoid arthritis
Criteria

Inclusion Criteria:

  • Adult patients, >/=18 years of age
  • Diagnosis of rheumatoid arthritis
  • Non-respondent or intolerant to non-biologic disease-modifying anti-rheumatic drug (DMARD) therapy
  • Patient has been prescribed a first biologic therapy up to 6 weeks prior to the inclusion visit, irrespective of the treatment prescribed

Exclusion Criteria:

  • Patients whose first biologic therapy is given as part of a clinical trial studying rheumatoid arthritis (RA) treatment
  • Patients who are receiving or have received experimental DMARDs as part of a clinical trial studying RA treatment in the last 12 months
  • Patients whose first biologic is rituximab, abatacept or anakinra.
  • Patients who have received any biologic therapy for more than 6 weeks prior to the inclusion visit
  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: NCT01543503

  Show 154 Study Locations
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01543503     History of Changes
Other Study ID Numbers: MA27950 
Study First Received: February 28, 2012
Results First Received: January 12, 2016
Last Updated: January 12, 2016
Health Authority: United Kingdom: Ministry of Health

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

ClinicalTrials.gov processed this record on April 27, 2016