An Observational Study of MabThera in Participants With Severe Active Rheumatoid Arthritis

Completed

• Conditions: Rheumatoid Arthritis
• Interventions: Biological: Rituximab

• Registration Number: NCT01613027
• Lead Sponsor: Hoffmann-La Roche

Brief Summary

This observational study will evaluate the effect on disease activity and the safety in routine clinical practice of MabThera (rituximab) in participants with active seropositive rheumatoid arthritis, who have an inadequate response to one or more tumour necrosis factor inhibitor (anti-TNF) therapies.

Detailed Description

Not available

Study Timeline

• Study Start: 2012-02
• Study First Submitted: 2012-05-25
• Study First Submitted QC: 2012-06-04
• Study First Posted: 2012-06-06
• Primary Completion: 2015-09
• Study Completion: 2015-09
• Status Verified: 2016-08
• Results First Submitted: 2016-08-31
• Results First Submitted QC: 2016-08-31
• Last Update Submitted: 2016-08-31
• Results First Posted: 2016-10-24
• Last Update Posted: 2016-10-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 135

Inclusion Criteria

• Age >18 years with rheumatoid arthritis (RA)
• Seropositive participants with RA (positive for rheumatoid factor (RF) and/or anti-Citrullinated Cyclic Peptide [CCP])
• Active disease despite receiving one or more TNF inhibitors
• Absence of serious or active infection

Exclusion Criteria

• Participants with serious history of heart failure (class New York Heart Association [NYHA] IV) or severe uncontrolled heart disease
• Participants pregnant or lactating
• Prior treatment with Mabthera®
• Participants receiving any other investigational product in the context of other clinical study
• Participants with known hypersensitivity to rituximab or to any of the excipients

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Rituximab	Rituximab	Rituximab administered according to prescribing information and normal clinical practice.

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Disease Activity Score Based on 28-joint Count and Erythrocyte Sedimentation Rate (DAS28-ESR) at Month 6 and Month 12	Baseline, Month 6, Month 12	DAS28-ESR is a measure of the participant's disease activity and was calculated using the swollen joint count of 28 joints (SJC28), tender joint count of 28 joints (TJC28), erythrocyte sedimentation rate (ESR) (millimeters per hour \[mm/hour\]) and patient's global assessment of disease activity (100-millimeter \[mm\] horizontal visual analog scale with 0=no disease activity to 100=maximum disease activity). DAS28-ESR scores range from 0 to 10, with higher scores corresponding to greater disease activity.

Secondary Outcome Measures

Name	Time	Method
Percentage of Serious ADRs	Up to 12 months	Percentage of serious ADRs resolved and ongoing at the time of study completion was reported.; An ADR was defined as any noxious and unintended response to a medicinal product related to any dose.
Change From Baseline in Swollen Joint Count (SJC) at Month 6 and Month 12	Baseline, Month 6, Month 12	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. The sum of swollen joints, each, ranged from 0 to 28 with 0 as best possible health status and 28 as worst health status. A decrease from baseline indicates improvement.
Change From Baseline in Tender Joint Count (TJC) at Month 6 and Month 12	Baseline, Month 6, Month 12	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. A decrease from baseline indicates improvement.
Change From Baseline in Erythrocyte Sedimentation Rate (ESR) at Month 6 and Month 12	Baseline, Month 6, Month 12	ESR is an direct measure of how much inflammation is in the body. The normal range is 0-22 mm/hour for men and 0-29 mm/hour for women. A decrease from baseline indicates improvement.
Percentage of Participants Who Remained on Treatment or Discontinued Treatment by Month 6 and Month 12	Up to 12 months
Percentage of Serious AEs	Up to 12 months	Percentage of serious AEs resolved and ongoing at the time of study completion was reported.; An AE was defined as 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.
Change From Baseline in C-reactive Protein (CRP) at Month 6 and Month 12	Baseline, Month 6, Month 12	C-reactive protein (CRP) is a blood test marker for inflammation in the body. Normal CRP levels are below 5.0 milligrams per liter (mg/L). A decrease from baseline indicates improvement.
Reasons for Discontinuation of Treatment by Month 6	Baseline to Month 6	Reasons for discontinuation from baseline to Month 6 are presented as the number of participants who discontinued treatment by category of reason for discontinuation.
Reasons for Discontinuation of Treatment by Month 12	Baseline to Month 12	Reasons for discontinuation from baseline to Month 12 are presented as the number of participants who discontinued treatment by category of reason for discontinuation.
Percentage of Participants With Clinically Meaningful Improvement From Baseline in Modified Health Assessment Questionnaire (M-HAQ)	Up to 12 months	The M-HAQ is a participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week. Each item scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty. A negative change from baseline indicates improvement.; Clinically meaningful improvement was defined as minimum clinically significant reduction from baseline of ≥0.22 at the respective time point.
Percentage of Participants With Adverse Events (AEs) and Adverse Drug Reactions (ADRs)	Up to 12 months	An AE was defined as 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. An ADR was defined as any noxious and unintended response to a medicinal product related to any dose. AEs of special interest includes progressive multifocal leukoencephalopathy (PML), any encephalopathy, hepatitis B or hepatitis B reactivation, gastrointestinal perforation, tuberculosis (TB) or TB reactivation, opportunistic infections, and malignancies.
Percentage of Participants With European League Against Rheumatism (EULAR) Response at Month 6 and Month 12	Baseline, Month 6, Month 12	EULAR response was calculated as the difference between DAS28-ESR scores at baseline and Month 6, and baseline and Month 12, and reported as the percentage of participants with response overall, good response, moderate response, and no response measured at each time point. Good responders = decrease from baseline \>1.2 with a DAS28 score of ≤3.2; moderate responders = decrease from baseline \>1.2 with a DAS28 score of \>3.2, or decrease from baseline \>0.6 to ≤1.2 with a DAS28 score of ≤5.1; non-responders = decrease from baseline ≤0.6 or decrease from baseline \>0.6 and ≤1.2 with a DAS28 score of \>5.1.
Percentage of Participants With Any Non-Serious AE and Any Serious AE by Intensity	Up to 12 months	Percentage of participants with any non-serious AE and any serious AE by intensity (mild, moderate, severe) was reported.; An AE was defined as 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.
Percentage of Non-Serious AEs	Up to 12 months	Percentage of non-serious AEs resolved and ongoing at the time of study completion were reported.; An AE was defined as 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.
Percentage of Non-Serious ADRs	Up to 12 months	Percentage of non-serious ADRs at the time of study completion was reported.; An ADR was defined as any noxious and unintended response to a medicinal product related to any dose.