An Observational Study of MabThera/Rituxan (Rituximab) and Alternative TNF-Inhibitors in Patients With Rheumatoid Arthritis and an Inadequate Response to a Single Previous TNF-Inhibitor

Completed

• Conditions: Rheumatoid Arthritis

• Registration Number: NCT01557348
• Lead Sponsor: Hoffmann-La Roche

Brief Summary

This multicenter, prospective, observational study will assess the efficacy of MabThera/Rituxan (rituximab) and alternative TNF-inhibitors in patients with rheumatoid arthritis who are non-responders or intolerant to a single previous TNF-inhibitor. Data will be collected from each patient from the time of change in biologic therapy for 12 months.

Detailed Description

Not available

Study Timeline

• Study Start: 2009-06
• Primary Completion: 2012-03
• Study Completion: 2012-03
• Study First Submitted: 2012-03-13
• Study First Submitted QC: 2012-03-16
• Study First Posted: 2012-03-19
• Status Verified: 2016-11
• Results First Submitted: 2016-11-28
• Results First Submitted QC: 2016-11-28
• Last Update Submitted: 2016-11-28
• Results First Posted: 2017-01-24
• Last Update Posted: 2017-01-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 1239

Inclusion Criteria

• Adult patients, >/= 18 years of age
• Patients with rheumatoid arthritis (RA) who have not responded or have been intolerant to a single TNF-inhibitor therapy
• Initiated on treatment with MabThera/Rituxan or an alternative TNF-inhibitor therapy, in accordance with the relevant Summary of Product Characteristics

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Exclusion Criteria

• Patients whose second biologic therapy is given as part of a clinical trial studying RA treatment

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Least Squares Mean Change From Baseline in Disease Activity Score (3 Variables)-Erythrocyte Sedimentation Rate at Month 6	Baseline (Day of change in biologic therapy [<=Day 1]) and Month 6	The DAS28-3 (ESR) is a measure of disease activity in rheumatoid arthritis. It is calculated from the number of swollen joint count (SJC) and tender joint count (TJC) using the 28 joints count, and ESR (millimeters per hour \[mm/hr\]). Total score ranges from 0 to 9.4, where higher score indicated more disease activity. Decrease in score indicated improvement in disease activity.

Secondary Outcome Measures

Name	Time	Method
Least Squares Mean Change From Baseline in Disease Activity Score (3 Variables)-Erythrocyte Sedimentation Rate at Month12	Baseline (Day of change in biologic therapy [<=Day 1]) and Month 12	The DAS28-3 (ESR) is a measure of disease activity in rheumatoid arthritis. It is calculated from the number of swollen joint count (SJC) and tender joint count (TJC) using the 28 joints count, and ESR (millimeters per hour \[mm/hr\]). Total score ranges from 0 to 9.4, where higher score indicated more disease activity. Decrease in score indicated improvement in disease activity.
Least Squares Mean Change From Baseline in TJC at Months 6 and 12	Baseline, Month 6, and Month 12	The TJC is the most specific clinical method to quantify abnormalities in participants with rheumatoid arthritis (RA). A total of 28 joints were assessed for tenderness. Decrease in score indicated an improvement in disease activity.
Least Squares Mean Change From Baseline in SJC at Months 6 and 12	Baseline, Month 6, and Month 12	The SJC is the most specific clinical method to quantify abnormalities in participants with RA. A total of 28 joints were assessed for swelling. Decrease in the score indicated improvement in disease activity.
Least Squares Mean Change From Baseline in C-reactive Protein at Months 6 and 12	Baseline, Month 6, and Month 12	C-reactive protein (CRP) is an inflammation marker. Normal range is from 0-10 milligram/Liter. A decrease in the level of CRP indicates reduction in inflammation and therefore improvement in disease activity.
Least Squares Mean Change From Baseline in ESR at Months 6 and 12	Baseline, Month 6, and Month 12	The ESR is a laboratory test that provides a non-specific measure of inflammation. The test assesses the rate at which red blood cells sediment in a period of one hour. Normal range is 0-30 mm/hr. A reduction in the level of ESR is considered as an improvement in disease activity.
Least Squares Mean Change From Baseline in Physician Global Assessment of Disease at Months 6 and 12	Baseline, Month 6, and Month 12	Physician global assessment of disease was measured on a 0 to 100 millimeter (mm) visual analog scale (VAS), with 0 mm = no disease activity and 100 mm = highest possible disease activity. Higher scores indicate worsening of disease.
Least Squares Mean Change From Baseline in Patient Global Assessment of Disease at Months 6 and 12	Baseline, Month 6, and Month 12	Patient Global Assessment of Disease was measured on a 0 to 100 mm VAS, with 0 mm = no disease activity and 100 mm = highest possible disease activity. Higher scores indicate worsening of disease.
Least Squares Mean Change From Baseline in Participant's VAS Pain Score at Months 6 and 12	Baseline, Month 6, and Month 12	Participants were asked to assess their pain intensity (severity of pain) on a 100-millimeter (mm) VAS with the left edge (0 mm) defined as "no pain" and the right edge (100 mm) defined as "severest pain". Higher scores indicate worsening of disease.
Least Squares Mean Change From Baseline in Health Assessment Questionnaire-Disability Index at Months 6 and 12	Baseline, Month 6, and Month 12	Health Assessment Questionnaire-Disability Index (HAQ-DI) is participant reported assessment of ability to perform tasks in 8 categories of daily living activities as dress/groom, arise, eat, walk, reach, grip, hygiene, and common activities over past week. Each item was scored on a 4-point scale from 0 to 3, where 0=no difficulty, 1=some difficulty, 2=much difficulty, and 3=unable to do. Overall score was computed as the sum of domain scores divided by the number of domains answered. Total possible score range was 0-3, where 0 = least difficulty and 3 = extreme difficulty.
Least Squares Mean Change From Baseline in Duration of Morning Stiffness at Months 6 and 12	Baseline, Month 6, and Month 12	Duration of morning stiffness is defined as the time elapsed when participant woke up in the morning and was able to resume normal activities without stiffness in minutes. Participants with available data at the time of assessment were included in the analysis.
Percentage of Participants Who Remained on Their Second Biologic Therapy at Months 6 and 12 After Start of Second Biologic Therapy	Month 6 and Month 12	Percentage of participants who remained on their second biologic therapy at 6 and 12 months after start of second biologic therapy were reported.
Reasons for Stopping the Second Biologic Therapy and Subsequent Therapy Choice	Up to 12 months
Number of Participants With Any Adverse Events, Any Serious Adverse Event, Adverse Events Leading to Withdrawal, and Death	Up to 12 Months	An Adverse event is defined as any unfavorable and unintended medical occurrence/sign (including an abnormal laboratory finding), symptom or disease in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. A serious adverse event is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, or is medically significant or requires intervention to prevent one or other of the outcomes listed above.
Number of Participants With Reasons for Discontinuation of the First TNFi Therapy	Day 1 (Study entry visit)	The reasons for discontinuation of first TNFi therapy included inefficacy, intolerance and other reasons. The other reasons included complete remission and participants' non-compliance.
Number of Participants With Previous TNFi Therapy	Day 1 (Study entry visit)	The previous TNFi therapy included adalimumab, etanercept, infliximab, and others (certolizumab, and golimumab). Number of participants with previous TNFi therapy history was reported.
Number of Participants With Previous Non-biologic Disease-modifying Anti-rheumatic Drugs Therapy	Day 1 (Study entry visit)	The previous disease-modifying anti-rheumatic drugs therapy included auranofin, aurothioglucose, aurotioprol, azathioprine, chloroquine, ciclosporin, gold, hydroxychloroquine, infliximab, leflunomide, methotrexate, methotrexate sodium, minocycline, penicillamine, sodium aurothiomalate, sodium aurotiosulfate, sulfasalazine, and tiopronin. Number of participants with previous disease-modifying anti-rheumatic drugs therapy was reported.
Factors Related to Selection of Second Biologic Therapy Following an Insufficient Response or Intolerance to a Single Previous TNFi	Baseline	The factors included participant characteristics and the reasons that led to the selection of second biologic therapy following an insufficient response or intolerance to a single previous TNFi. The participant characteristics included participant's option for treatment and option for follow-up. The other reasons included RA disease (rheumatoid factor \[RF\] and cyclic citrullinated peptide \[CCP\] status), primary failure, and new treatment characteristics (rapidity of action, route of administration, frequency of administration, low infectious risk, and no lymphoma risk). Participants were included in more than one of these factors.