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

A Global Multi-centre Observational Study in RA Patients Who Are Non Responders or Intolerant to a Single TNF Inhibitor.

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.

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis

• Study Type: Observational
• Enrollment (Actual): 1239

Contacts and Locations

Study Locations

• Canada
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3A 1M3
  • New Brunswick
    • Saint John, New Brunswick, Canada, E4L 4L2
  • Ontario
    • Brampton, Ontario, Canada, L6T 3J1
    • Burlington, Ontario, Canada, L7R 1E2
    • Hamilton, Ontario, Canada, L8N 1Y2
    • Kitchener, Ontario, Canada, N2M 5N6
    • London, Ontario, Canada, N6A 4V2
    • Mississauga, Ontario, Canada, L5M 2V8
    • St. Catharines, Ontario, Canada, L2N 7E4
    • Toronto, Ontario, Canada, M5G 1X5
    • Toronto, Ontario, Canada, M9B 1B1
    • Windsor, Ontario, Canada, N8X 5A6
  • Quebec
    • Montreal, Quebec, Canada, H1T 2M4
    • Montreal, Quebec, Canada, H2L 1S6
    • Montreal, Quebec, Canada, H3T 1Y6
    • Rimouski, Quebec, Canada, G5L 8W1
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada, S7K 0H6
• Colombia
  • Barranquilla, Colombia
  • Bogota, Colombia
  • Cali, Colombia
• France
  • Abbeville, France, 80142
  • Aix Les Bains, France, 73106
  • Amiens, France, 80000
  • Amiens, France, 80094
  • Argenteuil, France, 95107
  • Bayonne, France, 64109
  • Belfort, France, 90000
  • Besancon, France, 25030
  • Bonneville, France, 74136
  • Bordeaux, France, 33076
  • Bordeaux, France, 33100
  • Boulogne-billancourt, France, 92104
  • Brest, France, 29609
  • Bruges, France, 33523
  • Bry Sur Marne, France, 94366
  • Caen, France, 14033
  • Cahors, France, 46005
  • Cambrai, France, 59407
  • Cannes, France, 06401
  • Carcassonne, France, 11890
  • Carhaix Plouguer, France, 29835
  • Chambray Les Tours, France, 37171
  • Clermont-Ferrand, France, 63000
  • Clermont-ferrand, France, 63003
  • Colmar, France, 68024
  • Corbeil-essonnes, France, 91106
  • Draguignan, France, 83300
  • Echirolles, France, 38434
  • Evreux, France, 27023
  • Issy Les Moulineaux, France, 92130
  • La Roche Sur Yon, France, 85925
  • La Source, France, 45100
  • Laon, France, 02001
  • Laval, France, 53015
  • Le Coudray, France, 28360
  • Le Kremlin Bicetre, France, 94275
  • Le Mans, France, 72037
  • Libourne, France, 33505
  • Lievin, France, 62801
  • Lille, France, 59037
  • Limoges, France, 87042
  • Limoges, France, 87000
  • Lomme, France, 59160
  • Lorient, France, 56322
  • Lyon, France, 69002
  • Lyon, France, 69275
  • Lyon, France, 69448
  • Maisons Laffitte, France, 78600
  • Mantes La Jolie, France, 78201
  • Marseille, France, 13285
  • Marseille, France, 13385
  • Mennecy, France, 91540
  • Metz, France, 57077
  • Montauban, France, 82017
  • Montauban, France, 82013
  • Montivilliers, France, 76290
  • Montpellier, France, 34295
  • Mulhouse, France, 68070
  • Nantes, France, 44093
  • Nevers, France, 58033
  • Nice, France, 06202
  • Pachuca, France, 42070
  • Paris, France, 75018
  • Paris, France, 75014
  • Paris, France, 75651
  • Paris, France, 75475
  • Paris, France, 75674
  • Paris, France, 75571
  • Paris, France, 75679
  • Paris, France, 75877
  • Paris, France, 75020
  • Perpignan, France, 66046
  • Pierre Benite, France, 69495
  • Reims, France, 51092
  • Reims, France, 51100
  • Rennes, France, 35203
  • Rodez, France, 12027
  • Roubaix, France, 59056
  • St Aubin Les Elbeuf, France, 76410
  • St Brieuc, France, 22027
  • St Priest En Jarez, France, 42277
  • Toulon, France, 83000
  • Toulouse, France, 31059
  • Toulouse, France, 31000
  • Tours, France, 37000
  • Valence, France, 26000
  • Valenciennes, France, 59322
  • Vandoeuvre-les-nancy, France, 54511
  • Vannes, France, 56017
  • Villeneuve Sur Lot, France, 47307
  • Vincennes, France, 94300
• Germany
  • Aachen, Germany, 52064
  • Bremen, Germany, 28199
  • Cuxhaven, Germany, 27476
  • Erlangen, Germany, 91054
  • Frankenberg, Germany, 09669
  • Frankfurt, Germany, 60596
  • Gräfelfing, Germany, 82166
  • Halle, Germany, 06128
  • Hannover, Germany, 30625
  • Köln, Germany, 50679
  • Münster, Germany, 48149
  • Neuss, Germany, 41460
  • Rostock, Germany, 18059
  • Villingen-Schwenningen, Germany, 78054
• Greece
  • Athens, Greece, 11527
  • Athens, Greece, 16673
  • Athens, Greece, 14527
  • Athens, Greece, 155 62
  • Athens, Greece, 10676
  • Larissa, Greece, 411 10
• Italy
  • Abruzzo
    • Coppito, Abruzzo, Italy, 67100
  • Basilicata
    • Potenza, Basilicata, Italy, 85100
  • Campania
    • Napoli, Campania, Italy, 80131
    • Telese Terme, Campania, Italy, 82037
  • Emilia-Romagna
    • Ferrara, Emilia-Romagna, Italy, 44100
    • Modena, Emilia-Romagna, Italy, 41100
  • Friuli-Venezia Giulia
    • Udine, Friuli-Venezia Giulia, Italy, 33100
  • Lombardia
    • Milano, Lombardia, Italy, 20157
    • Milano, Lombardia, Italy, 20162
  • Marche
    • Ancona, Marche, Italy, 60020
    • Jesi, Marche, Italy, 60035
  • Puglia
    • Bari, Puglia, Italy, 70124
    • San Cesario Di Lecce, Puglia, Italy, 73016
  • Sicilia
    • Gazzi, Sicilia, Italy, 98125
    • Palermo, Sicilia, Italy, 90127
  • Toscana
    • Firenze, Toscana, Italy, 50139
    • Pisa, Toscana, Italy, 56100
    • Prato, Toscana, Italy, 59100
    • Siena, Toscana, Italy, 53100
  • Veneto
    • Padova, Veneto, Italy, 35128
    • Verona, Veneto, Italy, 37134
• Mexico
  • Chihuahua, Mexico, 31238
  • Mexicali, Mexico, 21100
  • Mexico City, Mexico, 10700
  • Mexico City, Mexico, 11850
  • Mexico City, Mexico, 14141
  • Pozarica, Mexico, 93260
• Monaco
  • Monaco, Monaco, 98012
• Norway
  • Ålesund, Norway, 6026
• Portugal
  • Amadora, Portugal, 3814-501
  • Guimaraes, Portugal, 4835-044
  • Lisboa, Portugal, 1069-639
  • Porto, Portugal, 4050-011
• Spain
  • Cordoba, Spain, 14004
  • Granada, Spain, 18014
  • Granada, Spain, 18003
  • Leon, Spain, 24071
  • Lugo, Spain, 27004
  • Madrid, Spain, 28034
  • Madrid, Spain, 28905
  • Madrid, Spain, 28222
  • Salamanca, Spain, 37007
  • Sevilla, Spain, 41009
  • Torrevieja, Spain, 03186
  • Murcia
    • El Palmar, Murcia, Spain, 30120
    • Lorca, Murcia, Spain, 30800
• United Kingdom
  • Abergavenny, United Kingdom, NP7 7EG
  • Aylesbury, United Kingdom, HP21 8AL
  • Blackburn, United Kingdom, BB2 3HH
  • Cambridge, United Kingdom, CB2 2QQ
  • Cannock, United Kingdom, WS11 5XY
  • Cardiff, United Kingdom, CF14 4XW
  • Cheltenham, United Kingdom, GL53 7AN
  • Chertsey, United Kingdom, KT16 0PZ
  • Cosham, United Kingdom, PO6 3LY
  • Derby, United Kingdom, DE1 2QY
  • Durham, United Kingdom, DH15TW
  • Exeter, United Kingdom, EX2 5DW
  • Glasgow, United Kingdom, G12 0XH
  • Harrogate, United Kingdom, HG2 7SX
  • Inverness, United Kingdom, IV2 3UV
  • Lancaster, United Kingdom, LA1 4RP
  • Leeds, United Kingdom, LS7 4SA
  • Lincoln, United Kingdom, LN2 5QY
  • Liverpool, United Kingdom, L9 7AL
  • London, United Kingdom, SE1 9RT
  • London, United Kingdom, SW17 0QT
  • London, United Kingdom, SE5 9PJ
  • Manchester, United Kingdom, M13 9PT
  • Poole, United Kingdom, BH15 2JB
  • Salford, United Kingdom, M6 8HD
  • Solihull, United Kingdom, B91 2JL
  • Southport, United Kingdom, PR8 6PN
  • St Helens, United Kingdom, WA9 3DA
  • Stockport, United Kingdom, SK2 7JE
  • Sunderland, United Kingdom, SR4 7TP
  • Sutton in Ashfield, United Kingdom, NG17 4JL
  • Torquay, United Kingdom, TQ2 7AA
  • Truro, United Kingdom, TR1 3LJ
  • Warrington, United Kingdom, WA5 1QG
  • Wirral, United Kingdom, CH49 5PE
  • Wolverhampton, United Kingdom, DY1 2HQ
  • Worthing, United Kingdom, BN11 2DH
  • Wrightington, United Kingdom, WN6 9EP

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Rheumatoid arthritis patients who are non-responders or intolerant to a single TNF-inhibitor

Description

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

Exclusion Criteria:

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

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Rituximab; Eligible participants will receive rituximab as second biologic therapy in routine clinical practice and were observed for 12 months from the start of the second biologic therapy.
Alternative TNFi; Eligible participants will receive alternative TNFi treatment as second biologic therapy in routine clinical practice and were observed for 12 months from the start of the second biologic therapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Least Squares Mean Change From Baseline in Disease Activity Score (3 Variables)-Erythrocyte Sedimentation Rate at 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.	Baseline (Day of change in biologic therapy [<=Day 1]) and Month 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Least Squares Mean Change From Baseline in Disease Activity Score (3 Variables)-Erythrocyte Sedimentation Rate at Month12	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.	Baseline (Day of change in biologic therapy [<=Day 1]) and Month 12
Least Squares Mean Change From Baseline in TJC at Months 6 and 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.	Baseline, Month 6, and Month 12
Least Squares Mean Change From Baseline in SJC at Months 6 and 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.	Baseline, Month 6, and Month 12
Least Squares Mean Change From Baseline in C-reactive Protein at Months 6 and 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.	Baseline, Month 6, and Month 12
Least Squares Mean Change From Baseline in ESR at Months 6 and 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.	Baseline, Month 6, and Month 12
Least Squares Mean Change From Baseline in Physician Global Assessment of Disease at Months 6 and 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.	Baseline, Month 6, and Month 12
Least Squares Mean Change From Baseline in Patient Global Assessment of Disease at Months 6 and 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.	Baseline, Month 6, and Month 12
Least Squares Mean Change From Baseline in Participant's VAS Pain Score at Months 6 and 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.	Baseline, Month 6, and Month 12
Least Squares Mean Change From Baseline in Health Assessment Questionnaire-Disability Index at Months 6 and 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.	Baseline, Month 6, and Month 12
Least Squares Mean Change From Baseline in Duration of Morning Stiffness at Months 6 and 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.	Baseline, Month 6, and Month 12
Percentage of Participants Who Remained on Their Second Biologic Therapy at Months 6 and 12 After Start of Second Biologic Therapy	Percentage of participants who remained on their second biologic therapy at 6 and 12 months after start of second biologic therapy were reported.	Month 6 and Month 12
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	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.	Up to 12 Months
Number of Participants With Reasons for Discontinuation of the First TNFi Therapy	The reasons for discontinuation of first TNFi therapy included inefficacy, intolerance and other reasons. The other reasons included complete remission and participants' non-compliance.	Day 1 (Study entry visit)
Number of Participants With Previous TNFi Therapy	The previous TNFi therapy included adalimumab, etanercept, infliximab, and others (certolizumab, and golimumab). Number of participants with previous TNFi therapy history was reported.	Day 1 (Study entry visit)
Number of Participants With Previous Non-biologic Disease-modifying Anti-rheumatic Drugs Therapy	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.	Day 1 (Study entry visit)
Factors Related to Selection of Second Biologic Therapy Following an Insufficient Response or Intolerance to a Single Previous TNFi	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.	Baseline

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start: June 1, 2009
• Primary Completion (Actual): March 1, 2012
• Study Completion (Actual): March 1, 2012

Study Registration Dates

• First Submitted: March 13, 2012
• First Submitted That Met QC Criteria: March 16, 2012
• First Posted (Estimate): March 19, 2012

Study Record Updates

• Last Update Posted (Estimate): January 24, 2017
• Last Update Submitted That Met QC Criteria: November 28, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid
• Other Study ID Numbers: MA22401