An Observational Study of MabThera (Rituximab) in Patients With Rheumatoid Arthritis And Inadequate Response Or Intolerance to a First Anti-TNF Alpha Therapy

Study Overview
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Brief Summary
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This prospective, multi-center, observational study will evaluate the efficacy and the safety of MabThera (rituximab) in participants with rheumatoid arthritis who have not responded or have been intolerant to a first anti-TNF alpha therapy. Participants have commenced MabThera or an alternative anti-TNF alpha treatment as a second biological therapy. Data will be collected for 12 months.

Official Title
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A Non-interventional Study for Relative Efficacy Outcome of Rituximab Treatment in RA Patients Who Have Inadequate Response or Have Been Intolerant to a First Anti-TNF Agent

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: Rituximab
* Drug: Adalimumab
* Drug: Etanercept
* Drug: Infliximab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult participants, >/=20 years of age Participants with rheumatoid arthritis, who have not responded or have been intolerant to a single anti-TNF alpha therapy and who have initiated MabThera or an alternative anti-TNF alpha therapy Exclusion Criteria: Participants whose first anti-TNF alpha treatment was, or second biological therapy is given as part of a clinical trial studying rheumatoid arthritis Participants who have not signed the informed consent form

Ages Eligible for Study
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Minimum Age: 20 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 |
| --- | --- |
| Rituximab<br>Participants who have inadequate response or were intolerant to the first anti-tumor necrosis factor (anti-TNF) agent in rheumatoid arthritis (RA), receiving rituximab as per physician's discretion for RA treatment were observed for 12 months. | Drug: Rituximab<br>* Rituximab as per physician's discretion.<br>* Other names: Mabthera;|
| Other anti-TNF agent<br>Participants who have inadequate response or were intolerant to the first anti-TNF agent in RA, receiving other anti-TNF agent, including adalimumab, etanercept and infliximab, as per physician's discretion for RA treatment were observed for 12 months. | Drug: Adalimumab<br>* Adalimumab as per physician's discretion.<br>Drug: Etanercept<br>* Etanercept as per physician's discretion.<br>Drug: Infliximab<br>* Infliximab as per physician's discretion.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy: Mean Change From Baseline in DAS28 at Month 6 in Intention to Treat (ITT) Population | DAS28 is calculated from the number of swollen joints and tender joints using the 28-joints count, the erythrocyte sedimentation rate (ESR) (millimeters per hour [mm/hr]) and patient's global assessment of disease activity (participant-rated arthritis activity assessment) with transformed scores ranging 0 (minimum score) to 10 (maximum score); higher scores indicated greater affectation due to 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 Month 6 | 
| Efficacy: Mean Change From Baseline in DAS28 at Month 6 in Standard Population Set (SPS) | DAS28 is calculated from the number of swollen joints and tender joints using the 28-joints count, the erythrocyte sedimentation rate (ESR) (millimeters per hour [mm/hr]) and Patient's Global Assessment of Disease Activity (participant-rated arthritis activity assessment) with transformed scores ranging 0 (minimum score) to 10 (maximum score); higher scores indicated greater affectation due to 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 Month 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy: Mean Change From Baseline in Swollen Joint Count (SJC) at Month 6 and 12 in Standard Population Set (SPS) | SJC is a clinical method to quantify abnormalities in participants with RA. It reflects the amount of inflamed synovial tissue. The number of swollen joints were scored as swollen=1 and not swollen=0, and counted. A negative change from baseline represents an improvement (a reduction in the number of swollen joints). | Baseline, Month 6 and 12 | 
| Efficacy: Mean Change From Baseline in Erythrocyte Sedimentation Rate (ESR) at Month 6 and 12 in Intention to Treat (ITT) Population | ESR is an acute phase reactant and a measure of inflammation. A negative change from baseline represents a reduction in inflammation. | Baseline, Month 6 and 12 | 
| Efficacy: Mean Change From Baseline in Erythrocyte Sedimentation Rate (ESR) at Month 6 and 12 in Standard Population Set (SPS) | ESR is an acute phase reactant and a measure of inflammation. A negative change from baseline represents a reduction in inflammation. | Baseline, Month 6 and 12 | 
| Efficacy: Mean Change From Baseline in C-reactive Protein (CRP) at Month 6 and 12 in Intention to Treat (ITT) Population | CRP is an inflammation marker. High levels of this protein indicate inflammation in diseases such as RA. A negative change from baseline represents a reduction in inflammation. | Baseline, Month 6 and 12 | 
| Efficacy: Mean Change From Baseline in C-reactive Protein (CRP) at Month 6 and 12 in Standard Population Set (SPS) | CRP is an inflammation marker. High levels of this protein indicate inflammation in diseases such as RA. A negative change from baseline represents a reduction in inflammation. | Baseline, Month 6 and 12 | 
| Efficacy: Health Assessment Questionnaire-Disability Index (HAQ-DI) in Intention to Treat (ITT) Population | The HAQ-DI is a participant-completed questionnaire specific for rheumatoid arthritis. It consists of 20 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip and common daily activities. Each domain has at least two component questions. There are four possible responses for each component ranging from 0 (without any difficulty) to 3 (unable to do). The overall HAQ-DI score is the average of each of the 8 category scores and ranges from 0 to 3, where 0 represents no disability and 3 very severe, high-dependency disability. | Month 6 | 
| Efficacy: Health Assessment Questionnaire-Disability Index (HAQ-DI) in Standard Population Set (SPS) | The HAQ-DI is a participant-completed questionnaire specific for rheumatoid arthritis. It consists of 20 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip and common daily activities. Each domain has at least two component questions. There are four possible responses for each component ranging from 0 (without any difficulty) to 3 (unable to do). The overall HAQ-DI score is the average of each of the 8 category scores and ranges from 0 to 3, where 0 represents no disability and 3 very severe, high-dependency disability. | Month 6 | 
| Safety: Number of Participants With Adverse Events (AE), Adverse Drug Reactions (ADR) and Serious Adverse Events | An AE was considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. ADRs were defined as any response to a drug which was noxious and unintended, and which occurred at dose normally used related to the pharmacological properties. A SAE was any experience that: resulted in death, was life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect or was medically significant. | Baseline up to Month 12 | 
| Efficacy: Mean Change From Baseline in DAS28 at Month 12 | DAS28 is calculated from the number of swollen joints and tender joints using the 28-joints count, the erythrocyte sedimentation rate (ESR) (millimeters per hour [mm/hr]) and Patient's Global Assessment of Disease Activity (participant-rated arthritis activity assessment) with transformed scores ranging 0 (minimum score) to 10 (maximum score); higher scores indicated greater affectation due to 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 Month 12 | 
| Efficacy: Mean Change From Baseline in Tender Joint Count (TJC) at Month 6 and 12 in Intention to Treat (ITT) Population | TJC is a clinical method to quantify abnormalities in participants with RA. It is associated with the level of pain. The number of tender joints were scored as tender=1 and not tender=0, and counted. A negative change from baseline represents an improvement (a reduction in the number of tender joints). | Baseline, Month 6 and 12 | 
| Efficacy: Mean Change From Baseline in Tender Joint Count (TJC) at Month 6 and 12 in Standard Population Set (SPS) | TJC is a clinical method to quantify abnormalities in participants with RA. It is associated with the level of pain. The number of tender joints were scored as tender=1 and not tender=0, and counted. A negative change from baseline represents an improvement (a reduction in the number of tender joints). | Baseline, Month 6 and 12 | 
| Efficacy: Mean Change From Baseline in Swollen Joint Count (SJC) at Month 6 and 12 in Intention to Treat (ITT) Population | SJC is a clinical method to quantify abnormalities in participants with RA. It reflects the amount of inflamed synovial tissue. The number of swollen joints were scored as swollen=1 and not swollen=0, and counted. A negative change from baseline represents an improvement (a reduction in the number of swollen joints). | Baseline, Month 6 and 12 |