An Observational Study of MabThera/Rituxan (Rituximab) in Patients With Sero-Positive Rheumatoid Arthritis Who Are Non-Responders or Intolerant to a Single TNF-Inhibitor (PORTSMAB)

Study Overview
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Brief Summary
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This observational study will assess the long-term efficacy and safety of MabThera/Rituxan in routine clinical practice in patients with sero-positive rheumatoid arthritis who are non-responders or intolerant to a single tumour necrosis factor (TNF) inhibitor. Data will be collected from each patient over 2 years.

Official Title
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Portuguese Observational Re-Treatment Study of MabThera (PORTSMAB) - A Two-centre Observational Study in Sero-positive Rheumatoid Arthritis (RA) Patients Who Are Non-responders or Intolerant to a Single Tumor Necrosis Factor (TNF) Inhibitor

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 Rheumatoid arthritis positive for rheumatoid factor and/or anti-CCP Non-responder or intolerant to single TNF-inhibitor therapy Initiating treatment with MabThera/Rituxan Exclusion Criteria: Contra-indications to MabThera/Rituxan therapy

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 |
| --- | --- |
| Rituximab<br>Sero-positive [Rheumatoid Factor (RF) and/or anti-Cyclic Citrullinated Peptide (CCP+)] rheumatoid arthritis (RA) patients, who had initiated therapy with Rituximab (MabThera) following lack of response or intolerance to a single tumour necrosis factor (TNF)-inhibitor will be included in this arm | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline in Disease-activity Score 28-Erythrocyte Sedimentation Rate at Month 24 | The disease-activity score 28 (DAS28) score is a measure of validated instrument for the assessment of the overall severity of RA disease activity calculated using the tender joint count (TJC), swollen joint count (SJC), patient's global assessment of disease activity, and erythrocyte sedimentation rate (ESR) for a total possible score of 2 to 10. Higher values indicate higher disease activity. A negative change from baseline indicates improvement. | Baseline (Day 0) and Month 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline in TJC at Month 24 | 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. A negative change from baseline indicates improvement. | Baseline (Day 0) and Month 24 | 
| Mean Change From Baseline in SJC at Month 24 | 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. A negative change from baseline indicates improvement. | Baseline (Day 0) and Month 24 | 
| Mean Change From Baseline in ESR at Month 24 | The ESR is an acute phase reactant and a measure of inflammation. A negative change from baseline indicates improvement. | Baseline (Day 0) and Month 24 | 
| Mean Change From Baseline in C-reactive Protein at Month 24 | The C-reactive protein is an inflammation marker. High levels of this protein indicate inflammation in diseases such as RA. A negative change from baseline indicates improvement. | Baseline (Day 0) and Month 24 | 
| Mean Change From Baseline in Physician's Global Assessment of Disease Activity At Month 24 | The Physician's Global Assessment of disease activity was assessed using a Visual Analogue Scale (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 = score at observation minus score at Baseline. An increase in score from Baseline represents disease progression and/or joint worsening, no change represents halting of disease progression, and a decrease represents improvement. | Baseline (Day 0) and Month 24 | 
| Mean Change From Baseline in Patient's Global Assessment of Disease Activity at Month 24 | The Patient's Global Assessment of disease activity was assessed using 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 = score at observation minus score at Baseline. An increase in score from Baseline represents disease progression and/or joint worsening, no change represents halting of disease progression, and a decrease represents improvement. | Baseline (Day 0) and Month 24 | 
| Mean Change From Baseline in Severity of Pain at Month 24 | The patient's assessment of pain was performed using a 100 mm VAS ranging from no pain (0) to unbearable pain (100). The distance in mm from the left edge of the scale was measured. A negative change from Baseline score indicates improvement in pain intensity. | Baseline (Day 0) and Month 24 | 
| Mean Change Form Baseline in Functional Capacity at Month 24 | The functional capacity was analyzed using Health Assessment Questionnaire-Disability Index (HAQ-DI). It is a 20-question instrument that assesses the degree of difficulty a person has in accomplishing tasks in 8 domains (dressing, arising, eating, walking, hygiene, reaching, gripping and activities of daily living). Responses in each domain are scored from 0 to 3 (0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do). Overall score was computed as sum of domain scores and divided by the number of domains. A total possible score ranged from 0 (best) to 3 (worst). | Baseline (Day 0) and Month 24 | 
| Reason for Change From First TNF-inhibitor Therapy to Rituximab | Adverse event, primary and secondary insufficient responses and monoclonal gammopathy were the reasons for starting rituximab therapy. | At Screening | 
| Number of Participants on Each Pattern of Re-treatment | There are two patterns of re-treatment, namely treat-to-target and according to the clinic. Treat-to-target: a new cycle every 6 months if not in remission, with the participant receiving no new course of treatment as long as he is in remission. On demand (according to clinic): a new cycle when, in an assessment performed at least 16 weeks after the last treatment cycle, the participant shows moderate or high disease activity [DAS28 > 3.2 or difference in DAS28 (ΔDAS28) > 0.6] | Up to Month 24 | 
| Number of Participants With Incidence of Infusion Reactions or Injection Site Reactions | An infusion reaction or injection site reaction is an event that occurs after infusion or injection which may include hypersensitivity reactions or anaphylactic reactions. | At Months 6, 12 and 24 | 
| Number of Participants With Incidence of Infectious Events | Follow-up of the infectious events was done after Month 6 visit, Month 12 visit and Month 24 visit. | At Months 6, 12 and 24 | 
| Number of Participants Who Experienced Any Adverse Events or Serious Adverse Events | An Adverse Events (AE) is any untoward medical occurrence in a participant or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. 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 Events (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 Month 24 |