A Study of the Impact of Methotrexate (MTX) Discontinuation on the Efficacy of Subcutaneous (SC) Tocilizumab (TCZ) With MTX

A Randomized, Double-Blind Trial Assessing the Impact of Methotrexate Discontinuation on the Efficacy of Subcutaneous Tocilizumab With Methotrexate Therapy

This randomized, multicenter, double-blind, parallel group study will evaluate the impact of MTX discontinuation on the efficacy of SC TCZ in participants with moderate to severe active rheumatoid arthritis who have an inadequate response to current MTX therapy. Participants will initiate treatment with TCZ weekly or every 2 weeks along with MTX at a stable dose orally in an open-label manner for 24 weeks. Participants with a disease activity score based on 28 joints (DAS28) less than or equal to (</=) 3.2 at Week 24, will be randomized to either continue receiving a stable dose of MTX or to switch to matching placebo up to Week 52. Participants without a DAS28 score </=3.2 at Week 24, will continue the same treatment in a non-randomized open-label manner up to Week 52.

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: Tocilizumab (TCZ); Drug: Methotrexate (MTX); Drug: Placebo (PBO)

• Study Type: Interventional
• Enrollment (Actual): 718
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Anniston, Alabama, United States, 36207
      • Pinnacle Research Group; Llc, Central
    • Birmingham, Alabama, United States, 35294
      • Uni Of Alabama,Birmingham; Medicine - Rheumatology
    • Huntsville, Alabama, United States, 35801
      • Rheumatology Associates of North Alabama
    • Tuscaloosa, Alabama, United States, 35406
      • Clnical & Translational Reseach Center for Alabama, PC
  • Arizona
    • Glendale, Arizona, United States, 85306
      • Arizona Arthritis & Rheumatology Associates, P.C.
    • Mesa, Arizona, United States, 85202
      • Arizona Arthritis & Rheumatology Research, PLLC
    • Mesa, Arizona, United States, 85202
      • Arizona Arthritis and Rheuma
    • Phoenix, Arizona, United States, 85027
      • Valley Arthritis Care
    • Scottsdale, Arizona, United States, 85258
      • Advanced Arthritis Care & Research
  • Arkansas
    • Fort Smith, Arkansas, United States, 72903
      • Fort Smith Rheumatology, PC
    • Hot Springs, Arkansas, United States, 71913
      • CHI St. Vincent Medical Group Hot Springs
    • Jonesboro, Arkansas, United States, 72401
      • NEA Baptist Clinic
    • Little Rock, Arkansas, United States, 72205
      • Little Rock Diagnostic Clinic
  • California
    • Covina, California, United States, 91723
      • Medvin Clinical Research
    • El Cajon, California, United States, 92020
      • TriWest Research Associates, LLC
    • Fullerton, California, United States, 92835
      • St. Jude Hospital Yorba Linda DBA St. Joseph
    • Hemet, California, United States, 92543
      • CV Mehta MD Medical Corp
    • Los Alamitos, California, United States, 90720
      • Valerius Medical Group
    • Orange, California, United States, 92868
      • NRC Research Institute
    • San Diego, California, United States, 92108
      • San Diego Arthritis Med Clnc
    • San Leandro, California, United States, 94578
      • C Michael Neuwelt MD Inc
    • Upland, California, United States, 91785-1141
      • Inland Rheumatology; Clinical Trials, Inc.
    • Whittier, California, United States, 90606
      • Medvin Clinical Research
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Hospital
    • Colorado Springs, Colorado, United States, 80920
      • Arthritis Assoc & Osteoporosis; Ctr of Colorado Springs
    • Denver, Colorado, United States, 80230-7127
      • Denver Arthritis Clinic
  • Connecticut
    • Bridgeport, Connecticut, United States, 06606
      • Joao Nascimento
    • Danbury, Connecticut, United States, 06810
      • Clinical Research Center of CT/NY
    • Hamden, Connecticut, United States, 06518
      • Arthritis & Osteoporosis Center Pc
    • Trumbull, Connecticut, United States, 06611
      • New England Research Associates
  • Delaware
    • Lewes, Delaware, United States, 19958
      • Rheumatolgy Consultants of Deleware
    • Newark, Delaware, United States, 19713
      • Javed Rheumatology Associates, Inc.
  • Florida
    • Aventura, Florida, United States, 33180
      • Arthritis & Rheumatism; Disease Specialities
    • Dunedin, Florida, United States, 34698
      • Robert Levin, Md; Research Dept
    • Miami, Florida, United States, 33136
      • South Coast Research Center, Inc.
    • Miami, Florida, United States, 33135
      • Suncoast Research Group LLC
    • Miami Lakes, Florida, United States, 33016
      • Precision Research Organization
    • Naples, Florida, United States, 34102
      • Jeffrey Alper M.D Research
    • Orlando, Florida, United States, 32806
      • Rheumatology Associates of Central Florida
    • Orlando, Florida, United States, 32836
      • Arthritis and Rheumatology Clinic
    • Palm Harbor, Florida, United States, 34684
      • Arthritis Center Palm Harbor
    • Palm Harbor, Florida, United States, 34684
      • Arthritis Rsrch of Florida, Inc.
    • Saint Petersburg, Florida, United States, 33708
      • Pinellas Medical Research - Allegry & Rheumatology Associates, LLC
    • Sarasota, Florida, United States, 34239
      • Sarasota Arthritis Res Center
    • Tamarac, Florida, United States, 33321
      • West Broward Rheumatology Associates, Inc.
    • Tampa, Florida, United States, 33614
      • Burnette & Silverfield, MDS
    • Tampa, Florida, United States, 33613
      • McIlwain Medical Group
    • Winter Garden, Florida, United States, 34787
      • Advanced Clinical Research of Orlando, Inc.
  • Georgia
    • Duluth, Georgia, United States, 30096
      • North Georgia Rheumatology
    • Gainesville, Georgia, United States, 30501
      • Arthritis Center of North Georgia
    • Lawrenceville, Georgia, United States, 30046
      • North Georgia Rheumatology Group, PC
  • Idaho
    • Idaho Falls, Idaho, United States, 83404
      • Institute of Arthritis Research
  • Illinois
    • Springfield, Illinois, United States, 62703
      • Springfield Clinic
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana Uni Medical Center
    • Indianapolis, Indiana, United States, 46227
      • Diagnostic Rheumatology & Research
  • Kansas
    • Overland Park, Kansas, United States, 66209
      • Kansas City Internal Medicine
  • Kentucky
    • Lexington, Kentucky, United States, 40515
      • Bluegrass Comm Research, Inc.
  • Louisiana
    • Monroe, Louisiana, United States, 71203
      • Arthritis & Diabetes Clinic, Inc
  • Maryland
    • Hagerstown, Maryland, United States, 21740
      • Klein & Associates, M.D., P.A.
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • New England Medical Center; Dept. of Medicine, Div. of Rheumatology
    • Fall River, Massachusetts, United States, 02720
      • Phase III Clinical Research
    • Mansfield, Massachusetts, United States, 02048
      • Mansfield Medical Center
    • Worcester, Massachusetts, United States, 01610
      • Clinical Pharmacology Study Group
    • Worcester, Massachusetts, United States, 01605
      • UMass Memorial Medical Center
    • Worcester, Massachusetts, United States, 01605
      • Reliant Medical Group, Inc; Rheumatology
  • Michigan
    • Lansing, Michigan, United States, 48910
      • Advanced Rheumatology, PC
    • Lansing, Michigan, United States, 48910
      • Fiechtner Research Inc
    • Petoskey, Michigan, United States, 49770
      • Nisus Research/Northern Michigan Hospital
    • Saint Clair Shores, Michigan, United States, 48081
      • Shores Rheumatology
  • Minnesota
    • Duluth, Minnesota, United States, 55805
      • St. Luke's Hospital Association of Duluth
    • Eagan, Minnesota, United States, 55121
      • St. Paul Rheumatology
  • Mississippi
    • Flowood, Mississippi, United States, 39232
      • Jackson Arthritis Clinic
    • Flowood, Mississippi, United States, 39232
      • Arthritis and Osteoporosis; Treatment and Research Center
  • Missouri
    • Florissant, Missouri, United States, 63031
      • David S Rosenberg
    • Kansas City, Missouri, United States, 64111
      • Clinical Research Consultants,LLC
    • Saint Louis, Missouri, United States, 63117
      • Clayton Medical Research
    • Saint Louis, Missouri, United States, 63141
      • Arthritis Consultants
  • Nevada
    • Las Vegas, Nevada, United States, 89128
      • G. T. Kelly, MD
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Rheumatology Research Group
    • Nashua, New Hampshire, United States, 03060
      • Nashua Rheumatology - Foundation Medical Partners
  • New Jersey
    • Manalapan, New Jersey, United States, 07726
      • Arthritis and Osteoporosis Associates
    • Toms River, New Jersey, United States, 08775
      • Ocean Rheumatology
    • Toms River, New Jersey, United States, 08755
      • Atlantic Coast Rheumatology
    • Voorhees, New Jersey, United States, 08043
      • Arthritis Rheumatic & Back Disease Associates
    • Voorhees, New Jersey, United States, 08043
      • Cooper Cancer Institute
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • Albuquerque Clinical Trials
    • Las Cruces, New Mexico, United States, 88011
      • Arthritis and Osteoporosis Associates of New Mexico
  • New York
    • Albany, New York, United States, 12203
      • The Center for Rheumatology
    • Brooklyn, New York, United States, 11201
      • Arthritis & Osteoporosis Center
    • Manhasset, New York, United States, 11030
      • Manhasset Rheumatology
    • New York, New York, United States, 10016
      • Manhattan Medical Reserach
    • Orchard Park, New York, United States, 14127
      • Buffalo Rheumatology Associates
    • Plainview, New York, United States, 11803
      • Office of Premier Chatpar Md
    • Smithtown, New York, United States, 11787
      • Rheumatology Associates of Long Island
    • Syracuse, New York, United States, 13210
      • Arthritis Health Associates
  • North Carolina
    • Asheville, North Carolina, United States, 28803
      • Asheville Arthritis & Osteoporosis Center, PA
    • Charlotte, North Carolina, United States, 28210
      • Carolina Bone & Joint P.A.
    • Durham, North Carolina, United States, 27704
      • Triangle Orthopaedics Associates, P.A.
    • Greensboro, North Carolina, United States, 27408
      • Medication Management
    • Hickory, North Carolina, United States, 28602
      • PMG Research of Hickory LLC
    • Leland, North Carolina, United States, 28451
      • Cape Fear Arthritis Care
    • Raleigh, North Carolina, United States, 27617
      • Shanahan Rheumatology & Immunology, PLLC
  • North Dakota
    • Bismarck, North Dakota, United States, 58501
      • St. Alexius Medical Center; Arthritis Clinic
    • Bismarck, North Dakota, United States, 58507
      • Odyssey Research Services; Main Medical Building
  • Ohio
    • Akron, Ohio, United States, 44333
      • Crystal Arthritis Center, Inc.
    • Cincinnati, Ohio, United States, 45219
      • Cincinnati Rheumatic Disease Study Group
    • Cleveland, Ohio, United States, 44109
      • University Hospitals Case Medical Center
    • Columbus, Ohio, United States, 43203
      • Ohio State University; Rheumatology; Immun/Rheum
    • Columbus, Ohio, United States, 43215
      • Columbus Arthritis Center
    • Dayton, Ohio, United States, 45417
      • STAT Research Inc
    • Middleburg Heights, Ohio, United States, 44130
      • Paramount Medical Research
    • Toledo, Ohio, United States, 43606
      • Clinical Research Source, Inc.
  • Oklahoma
    • Ardmore, Oklahoma, United States, 73401
      • Arthritis Care Center Oklahoma
    • Oklahoma City, Oklahoma, United States, 73103
      • Health Research of Oklahoma, Llc
    • Oklahoma City, Oklahoma, United States, 73103
      • Arthritis and Rheumatology; Center of Oklahoma PLLC
    • Oklahoma City, Oklahoma, United States, 73112
      • Lynn Health Science Inst.
    • Tulsa, Oklahoma, United States, 74135
      • Healthcare Research Consultants
    • Tulsa, Oklahoma, United States, 74104
      • Oklahoma Center For Arthritis Therapy & Research
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635
      • Altoona Center For Clinical Research
    • Erie, Pennsylvania, United States, 16508
      • Arthritis Associates
    • Philadelphia, Pennsylvania, United States, 19152
      • Arthritis Group
    • Wexford, Pennsylvania, United States, 15090
      • Advanced Rheumatology & Arthritis Research Center
    • Wyomissing, Pennsylvania, United States, 19610
      • Clinical Research Center of Reading
    • Wyomissing, Pennsylvania, United States, 19610
      • Emkey Arthritis & Osteoporosis
  • South Carolina
    • Charleston, South Carolina, United States, 29406
      • Low Country Rheumatology, PA
    • Columbia, South Carolina, United States, 29204
      • Columbia Arthritis Center (Partnership Practice)
    • Greenville, South Carolina, United States, 29601
      • Piedmont Arthritis Clinic
  • Tennessee
    • Jackson, Tennessee, United States, 38305
      • West Tennessee Research Institute
    • Memphis, Tennessee, United States, 38119
      • Ramesh Gupta - PP
  • Texas
    • Amarillo, Texas, United States, 79124
      • Amarillo Center for Clinical Research
    • Austin, Texas, United States, 78731
      • Austin Regional Clinic
    • Austin, Texas, United States, 78758
      • Lovelace Scientific Resources Inc.
    • Beaumont, Texas, United States, 77701
      • Diagnostic Group
    • College Station, Texas, United States, 77845
      • AOCBV
    • Corpus Christi, Texas, United States, 78404
      • Adriana Pop-Moody MD Clinic PA
    • Dallas, Texas, United States, 75231-4406
      • Arthritis Care & Diagnostic Center
    • Dallas, Texas, United States, 75231
      • Metroplex Clinical Research
    • Houston, Texas, United States, 77089
      • Accurate Clinical Research
    • Houston, Texas, United States, 77074
      • Houston Inst. For Clinical Research
    • Houston, Texas, United States, 77004
      • Rheumatic Disease Clin Res Ctr
    • Houston, Texas, United States, 77007
      • IntraFusion Researh Network
    • Mesquite, Texas, United States, 75150
      • Southwest Rheumatology
    • San Antonio, Texas, United States, 78229
      • Accurate Clinical Management
    • San Antonio, Texas, United States, 78229
      • NextGen Clinical Research Inc
    • San Antonio, Texas, United States, 78232
      • Arthiritis & Osteoporosis Centre of South Texas
    • San Marcos, Texas, United States, 78666
      • Arthritis Clinic of Central Texas
    • Victoria, Texas, United States, 77901
      • Crossroads Clinical Research, LLC
    • Waco, Texas, United States, 76710
      • Arthritis & Osteoporosis Clinic
  • Washington
    • Olympia, Washington, United States, 98502
      • South Puget Sound Clinical Research
    • Spokane, Washington, United States, 99204
      • Arthritis Northwest, Spokane
    • Wenatchee, Washington, United States, 98801
      • Wenatchee Valley Hospital & Clinics
  • West Virginia
    • Clarksburg, West Virginia, United States, 26301
      • Mountain State Clinical Research
  • Wisconsin
    • Glendale, Wisconsin, United States, 53217
      • Rheumatic Disease Center
    • Manitowoc, Wisconsin, United States, 54220
      • Lakeshore Orthopedics
    • Onalaska, Wisconsin, United States, 54605
      • Gundersen Clinic Ltd;Sec. Rheumatology/Dept. of Internal Med

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Body weight </=150 kg
• Active moderate to severe rheumatoid arthritis (DAS28 >/=4.4) according to the revised 1987 ACR criteria at screening and baseline (prior to treatment on Day 1)
• Currently receiving oral MTX for at least 24 weeks and on a stable oral dose of at least 15 mg/week for at least 6 weeks prior to treatment (Day 1), with the following exception: a stable dose of at least 10 mg/week is allowed for participants with a body weight <50 kg or calculated glomerular filtration rate (or creatinine clearance) <60 milliliters per minute (mL/min)
• History of parenteral (SC or intramuscular [IM]) MTX is allowed, but not within 6 weeks prior to treatment (Day 1). Participants must not have a documented, clinically significant intolerance to oral MTX and must be receiving oral MTX at a dose of 15 mg/week for at least 6 weeks prior to treatment (Day 1)
• Participants who have received one prior anti-tumor necrosis factor (TNF) must have discontinued etanercept, infliximab, certolizumab, adalimumab, or golimumab for at least 6 months prior to screening
• Oral corticosteroids must have been </=10 mg/day prednisone (or equivalent) and stable for at least 25 out of 28 days prior to treatment (Day 1)
• Participants receiving treatment on an outpatient basis

Exclusion Criteria:

• Documented medical history of significant intolerance to oral MTX >/=15 mg/week
• Participants receiving other (non-MTX) disease modifying anti-rheumatic drugs (DMARDs) within 8 weeks of screening
• Previous treatment with abatacept, rituximab, tofacitinib, or anakinra
• Treatment with parenteral corticosteroids within 4 weeks prior to treatment
• Previous treatment with cell-depleting therapies or alkylating agents
• Previous treatment with TCZ
• Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery during the study
• Rheumatic autoimmune disease other than rheumatoid arthritis
• Non-rheumatic active autoimmune diseases (for example, inflammatory bowel diseases, psoriasis, multiple sclerosis)
• Prior history of or current inflammatory joint disease other than rheumatoid arthritis
• Functional Class IV according to the revised (1987) ACR criteria for rheumatoid arthritis
• History of severe allergic or anaphylactic reactions to human, humanized, or murine monoclonal antibodies
• Evidence of significant uncontrolled concomitant diseases; uncontrolled disease states where flares are commonly treated with oral or parenteral corticosteroids
• Active current or history of recurrent infection, or any major episode of infection requiring hospitalization or treatment with intravenous antibiotics within 4 weeks prior to screening or oral antibiotics within 2 weeks prior to screening
• Active tuberculosis requiring treatment within the previous 3 years
• History of or currently active primary or secondary immunodeficiency
• Pregnant or breast-feeding women
• Positive for hepatitis B or hepatitis C infection
• For potential MRI substudy participants: the presence of any metal-containing device or object in the body

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Non-Randomized Participants (TCZ + MTX); All participants will receive initial treatment with open-label TCZ + MTX. Participants who complete 24-week treatment with open-label TCZ + MTX and did not achieve a DAS28 score </=3.2 at Week 24, will continue receiving TCZ + MTX in open label manner up to Week 52.	Drug: Tocilizumab (TCZ); TCZ will be administered at a dose of 162 milligrams (mg) via SC injection weekly (if body weight is greater than or equal to [>/=] 100 kilograms [kg]) or every 2 weeks (if body weight was less than [<] 100 kg).; Other Names: Actemra; Drug: Methotrexate (MTX); MTX will be administered at a stable dose (15 mg to 25 mg per week) orally.
Experimental: Randomized Participants (TCZ + MTX); Participants who complete the initial 24-week treatment with open-label TCZ + MTX and achieve a DAS28 score </=3.2 at Week 24, will be randomized to receive TCZ along with MTX up to Week 52.	Drug: Tocilizumab (TCZ); TCZ will be administered at a dose of 162 milligrams (mg) via SC injection weekly (if body weight is greater than or equal to [>/=] 100 kilograms [kg]) or every 2 weeks (if body weight was less than [<] 100 kg).; Other Names: Actemra; Drug: Methotrexate (MTX); MTX will be administered at a stable dose (15 mg to 25 mg per week) orally.
Active Comparator: Randomized Participants (TCZ + PBO); Participants who complete the initial 24-week treatment with open-label TCZ + MTX and achieve a DAS28 score </=3.2 at Week 24, will be randomized to receive TCZ along with MTX matched placebo (PBO) up to Week 52.	Drug: Tocilizumab (TCZ); TCZ will be administered at a dose of 162 milligrams (mg) via SC injection weekly (if body weight is greater than or equal to [>/=] 100 kilograms [kg]) or every 2 weeks (if body weight was less than [<] 100 kg).; Other Names: Actemra; Drug: Placebo (PBO); PBO matching to MTX will be administered orally.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Week 24 in Disease Activity Score Based on 28 Joints (DAS28) Score at Week 40	The DAS28 was derived from assessments of erythrocyte sedimentation rate (ESR) measured in millimeters per hour (mm/h), tender joint count on 28 joints (TJC28), swollen joint count on 28 joints (SJC28), and Patient's Global Assessment of disease activity according to 100--millimeter (mm) Visual Analog Scale (VAS). DAS28 score was calculated as [0.56 × square root of TJC] + [0.28 × square root of SJC] + [0.70 × natural log (ESR)] + [0.014 × VAS]. DAS28 score could range from 0 to 10, where higher score represented higher disease activity. The change from Week 24 to Week 40 was averaged among all participants, where negative changes indicated an improvement in disease activity.	Week 24, Week 40

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Achieving 20% Improvement in American College of Rheumatology (ACR20) Response	The ACR20 response at any time was defined as >/=20% improvement compared to baseline in TJC (assessed on 68 joints) and SJC (assessed on 66 joints); and 20% improvement compared to baseline in 3 of the following 5 criteria, respectively: 1) Patient's global assessment of disease activity according to 100-mm VAS, 2) Physician's global assessment of disease activity according to 100-mm VAS, 3) participant's global assessment of pain according to 100-mm VAS, 4) Participant's assessment of functional ability via a Health Assessment Questionnaire-Disability Index (HAQ-DI), and 5) Acute phase reactant (ESR in mm/h or C-Reactive Protein [CRP] in milligrams per deciliter [mg/dL]).	Weeks 24, 40, and 52
Percentage of Participants Achieving 50% Improvement in American College of Rheumatology (ACR50) Response	The ACR50 response at any time was defined as >/=50% improvement compared to baseline in TJC (assessed on 68 joints) and SJC (assessed on 66 joints); and 50% improvement compared to baseline in 3 of the following 5 criteria, respectively: 1) Patient's global assessment of disease activity according to 100-mm VAS, 2) Physician's global assessment of disease activity according to 100-mm VAS, 3) participant's global assessment of pain according to 100-mm VAS, 4) Participant's assessment of functional ability via HAQ-DI, and 5) Acute phase reactant (ESR in mm/h or CRP in mg/dL).	Weeks 24, 40, and 52
Percentage of Participants Achieving 70% Improvement in American College of Rheumatology (ACR70) Response	The ACR70 response at any time was defined as >/=70% improvement compared to baseline in TJC (assessed on 68 joints) and SJC (assessed on 66 joints); and 70% improvement compared to baseline in 3 of the following 5 criteria, respectively: 1) Patient's global assessment of disease activity according to 100-mm VAS, 2) Physician's global assessment of disease activity according to 100-mm VAS, 3) participant's global assessment of pain according to 100-mm VAS, 4) Participant's assessment of functional ability via HAQ-DI, and 5) Acute phase reactant (ESR in mm/h or CRP in mg/dL).	Weeks 24, 40, and 52
Percentage of Participants With >/=1.2 Points Increase (Worsening) From Week 24 in DAS28 Score at Week 40 and 52	The DAS28 was derived from assessments of ESR measured in mm/h, TJC28, SJC28, and Patient's global assessment of disease activity according to 100-mm VAS. DAS28 score was calculated as [0.56 × square root of TJC] + [0.28 × square root of SJC] + [0.70 × natural log (ESR)] + [0.014 × VAS]. DAS28- score could range from 0 to 10, where higher score represented higher disease activity.	Week 24, 40, and 52
Percentage of Participants With DAS28 Score <2.6 (DAS28 Remission)	The DAS28 was derived from assessments of ESR measured in mm/h, TJC28, SJC28, and Patient's global assessment of disease activity according to 100-mm VAS. DAS28 score was calculated as [0.56 × square root of TJC] + [0.28 × square root of SJC] + [0.70 × natural log (ESR)] + [0.014 × VAS]. DAS28 score could range from 0 to 10, where higher score represented higher disease activity.	Week 40, Week 52
Percentage of Participants With DAS28 Score </=3.2 (Low DAS28)	The DAS28 was derived from assessments of ESR measured in mm/h, TJC28, SJC28, and Patient's global assessment of disease activity according to 100-mm VAS. DAS28 score was calculated as [0.56 × square root of TJC] + [0.28 × square root of SJC] + [0.70 × natural log (ESR)] + [0.014 × VAS]. DAS28-ESR score could range from 0 to 10, where higher score represented higher disease activity.	Week 40, Week 52
Change From Week 24 in Bone Erosion Score at Week 40 for Participants in the Magnetic Resonance Imaging (MRI) Substudy	Bones from the wrist regions (carpal bones, distal radius, distal ulna, and metacarpal bases) and the metacarpophalangeal (MCP) joints (metacarpal heads and phalangeal bases) were assessed for erosion via MRI and scored separately based on the proportion of eroded bone compared to the 'assessed bone volume' judged from all available images. Scoring ranged from 0 (no erosion) to 10 (91-100%). Results were summed, resulting in scores from 0 to 80 for the wrist region, 0 to 150 for the MCP joints, and 0 to 230 on aggregate. A negative value for change from Week 24 in bone erosion score indicated an improvement.	Weeks 24, Week 40
Percentage of Participants With Anti-Therapeutic Antibodies (ATA) to TCZ	Percentage of participants with positive results for ATA against TCZ at Baseline and at any of the post-baseline assessment time-points was reported. Participants positive at any post-baseline time points were participants who had no positivity at baseline for the same assay.	Baseline, Post-baseline (assessed at Weeks 12, 24, 36, 52 and at follow up [Week 60])
Mean TCZ Serum Concentration		Baseline, Weeks 12, 24, 36, 52 and follow up (Week 60)
Mean Soluble Interleukin-6 (IL-6) Receptor Concentration		Baseline, Weeks 12, 24, 36, 52 and follow up (Week 60)

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Publications and helpful links

General Publications

• Kremer JM, Rigby W, Singer NG, Birchwood C, Gill D, Reiss W, Pei J, Michalska M. Sustained Response Following Discontinuation of Methotrexate in Patients With Rheumatoid Arthritis Treated With Subcutaneous Tocilizumab: Results From a Randomized, Controlled Trial. Arthritis Rheumatol. 2018 Aug;70(8):1200-1208. doi: 10.1002/art.40493. Epub 2018 Jun 14.

Study record dates

Study Major Dates

• Study Start (Actual): November 7, 2013
• Primary Completion (Actual): October 14, 2016
• Study Completion (Actual): October 14, 2016

Study Registration Dates

• First Submitted: May 14, 2013
• First Submitted That Met QC Criteria: May 14, 2013
• First Posted (Estimate): May 17, 2013

Study Record Updates

• Last Update Posted (Actual): December 26, 2017
• Last Update Submitted That Met QC Criteria: November 30, 2017
• Last Verified: November 1, 2017

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; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Reproductive Control Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Methotrexate
• Other Study ID Numbers: ML28776