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

Study Overview
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Brief Summary
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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.

Official Title
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A Global Comparative Observational Study In Rheumatoid Arthritis (RA) Patients Who Are Treated With A TNF Inhibitor Or Tocilizumab As The First Biologic Therapy

Conditions
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Rheumatoid Arthritis

Participation Criteria
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Eligibility Criteria
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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

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 |
| --- | --- |
| Cohort<br> | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline in Calculated Disease Activity Score Based on 28 Joint Count Erythrocyte Sedimentation Rate at Week 24 | 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. | Baseline and Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline in Disease Activity Score Based on 28 Joint Count Erythrocyte Sedimentation Rate at Week 52 | 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. | Baseline and Week 52 | 
| Mean Change From Baseline in Erythrocyte Sedimentation Rate | Blood samples were collected for ESR, which is an acute phase reactant and a measure of inflammation. BL = baseline. | Baseline, Week 24, Week 52 | 
| Mean Change From Baseline in C-reactive Protein | 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. | Baseline, Week 24, Week 52 | 
| Mean Change From Baseline in Swollen Joint Count | 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. | Baseline, Week 24, Week 52 | 
| Mean Change From Baseline in Tender Joint Count | 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. | Baseline, Week 24, Week 52 | 
| Mean Change From Baseline in Clinical Disease Activity Index and Simplified Disease Activity Index Score | 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. | Baseline, Week 24, Week 52 | 
| Mean Change From Baseline in Physician Global Assessment Score | 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. | Baseline, Week 24, Week 52 | 
| Loss of Efficacy or Development of Intolerance to Biologic Therapy | 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. | Up to Week 52 | 
| Proportion of Participants Who Terminated Biologic Treatment | The proportion of participants who discontinued biologic treatment was compared between tocilizumab-treated and TNF inhibitor-treated participants. | Up to Week 52 | 
| Reasons for Treatment Discontinuation | The reasons for discontinuation of tocilizumab or TNF inhibitor is presented. | Up to Week 52 | 
| Cumulative Number of Participants Who Discontinued Biologic Therapy at the End of Each Study Period | 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. | Up to end of treatment | 
| Number of Participants of Infusion Reactions or Injection Site Reactions During the Study Following the Start of the First Biologic Therapy | 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. | Up to Week 52 | 
| Number of Participants With Adverse Events, Serious Adverse Events and Non-serious Adverse Events | 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. | Up to Week 52 | 
| Number of Participants With Serious and Non-serious Adverse Events of Special Interest, Including Infections, During the Study | 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. | Up to Week 52 | 
| Mean Change From Baseline in Health Assessment Questionnaire Disability Index Score | 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. | Baseline, Week 24, Week 52 | 
| Mean Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue Score | 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. | Baseline, Week 24, Week 52 | 
| Mean Change From Baseline in Visual Analogue Scale Pain Score | 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. | Baseline, Week 24, Week 52 | 
| Shift From Baseline in Morning Stiffness | 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 | Baseline, Week 24, Week 52 | 
| Change From Baseline in Patient Global Assessment of Disease Activity | 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. | Baseline, Week 24, Week 52 |