AzTrials
AzTrials

Arthritis, RheumatoidPhase 4NCT02092467

Safety Study Of Tofacitinib Versus Tumor Necrosis Factor (TNF) Inhibitor In Subjects With Rheumatoid Arthritis

A Phase 4 study testing tofacitinib, adalimumab and etanercept in people with Arthritis, Rheumatoid, run by Pfizer at 345 sites in 30 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This post-marketing study is designed to compare the safety of tofacitinib versus TNF inhibitor with respect to major cardiovascular adverse events and malignancies, excluding non-melanoma skin cancers when given to subjects with rheumatoid arthritis. Read more about this study

Who is it for?
Ages 50 years and older
Conditions the study is for
Arthritis, Rheumatoid
What is being tested?
tofacitinib, adalimumab and etanercept
Could I receive a placebo?
No, everyone receives an active treatment
How many people
4,372 participants
Where
345 sitesin 30 countries
Study dates
14 Mar 2014to 22 Jul 2020
Phase
Phase 4
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 50 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Moderate to severe rheumatoid arthritis
  • Taking methotrexate without adequate control of symptoms
  • Have at least one cardiovascular risk factor (eg, current smoker, high blood pressure, high cholesterol levels, diabetes mellitus, history of heart attack, family history of coronary heart disease, extra-articular RA disease)

Who cannot join

  • Current or recent infection
  • Clinically significant laboratory abnormalities
  • Pregnancy

Trial locations and contacts

345 sites in 30 countries.

345 sites in 30 countries

United States142 sites

  • Amarillo Center for Clinical Research, Ltd.

    Amarillo, Texas, 79124

  • Arthritis and Rheumatology of GA, P.C.

    Atlanta, Georgia, 30342

  • Austin Regional Clinic

    Austin, Texas, 78731

  • Bronson Healthcare Group

    Battle Creek, Michigan, 49015

  • University of Alabama at Birmingham (UAB), Arthritis Clinical Intervention Program

    Birmingham, Alabama, 35294-7201

  • St. Alexius Medical Center

    Bismarck, North Dakota, 58501

  • RASF-Clinical Research Center, Inc

    Boca Raton, Florida, 33486

  • Bay Area Arthritis and Osteoporosis

    Brandon, Florida, 33511

  • Weill Cornell Physicians at Brooklyn Heights

    Brooklyn, New York, 11201

  • Medical Associates of North Georgia - Rheumatology

    Canton, Georgia, 30115

  • Trinity Universal Research Associates, Inc

    Carrollton, Texas, 75007

  • Rheumatology Associates, P.A.

    Charleston, South Carolina, 29407

  • Center for Arthritis and Rheumatic Diseases, PC

    Chesapeake, Virginia, 23320

  • Cincinnati Rheumatic Disease Study Group, Inc.

    Cincinnati, Ohio, 45242

  • Arthritis & Rheumatism Associates (Private Practice)

    Clearwater, Florida, 33756

  • Florida Clinical Research Group (Administrative Office)

    Clearwater, Florida, 33759

  • Dr.Robert W. Levin MDOffice of

    Clearwater, Florida, 33765

  • Summit Medical Group

    Clifton, New Jersey, 07012

  • Coeur D'Alene Arthritis Clinic

    Coeur d'Alene, Idaho, 83814

  • Arthritis Associates and Osteoporosis Center of Colorado Springs

    Colorado Springs, Colorado, 80920

  • Medvin Clinical Research

    Covina, California, 91722

  • Klein & Associates, M.D.,P.A.

    Cumberland, Maryland, 21502

  • Pioneer Research Solutions, Inc.

    Cypress, Texas, 77429

  • Baylor Scott and White Research Institute / Arthritis Care and Research Center

    Dallas, Texas, 75231

  • Arthritis Centers of Texas

    Dallas, Texas, 75246

  • UT Southwestern Medical Center

    Dallas, Texas, 75390

  • STAT Research, Inc.

    Dayton, Ohio, 45417

  • International Medical Research

    Daytona Beach, Florida, 32117

  • Office of Jefrey D. Lieberman, MD, PC

    Decatur, Georgia, 30033

  • Altoona Center for Clinical Research

    Duncansville, Pennsylvania, 16635

  • EmergeOrtho,P.A.

    Durham, North Carolina, 27704

  • St. Paul Rheumatology, PA

    Eagan, Minnesota, 55121

  • Med Investigations, Inc.

    Fair Oaks, California, 95628

  • Phase III Clinical Research

    Fall River, Massachusetts, 02720

  • Centre for Rheumatology, Immunology and Arthritis

    Fort Lauderdale, Florida, 33309

  • Arthritis Treatment Center

    Frederick, Maryland, 21702

  • Rheumatic Disease Center

    Glendale, Wisconsin, 53217

  • Northwell Health Division of Rheumatology

    Great Neck, New York, 11021

  • Physicians East, PA

    Greenville, North Carolina, 27834

  • Innovative Clinical Research, LLC

    Greenville, South Carolina, 29601

  • Piedmont Arthritis Clinic, PA

    Greenville, South Carolina, 29601

  • Klein & Associates, MD, PA

    Hagerstown, Maryland, 21740

  • PMG Research of Hickory LLC

    Hickory, North Carolina, 28601

  • Frycare outpatient imaging Center

    Hickory, North Carolina, 28602

  • PMG Research of Hickory, LLC

    Hickory, North Carolina, 28602

  • CHI St. Vincent Medical Group Hot Springs

    Hot Springs, Arkansas, 71913

  • Accurate Clinical Management, LLC

    Houston, Texas, 77004

  • Rheumatic Disease Clinical Research Center

    Houston, Texas, 77004

  • Accurate Clinical Research, Inc.

    Houston, Texas, 77034

  • Houston Institute for Clinical Research

    Houston, Texas, 77074

  • Accurate Clinical Management, LLC

    Houston, Texas, 77084

  • Medical Center Research, LLC

    Houston, Texas, 77089

  • Talbert Medical Group

    Huntington Beach, California, 92646

  • Rheumatology Associates of North Alabama, PC

    Huntsville, Alabama, 35801

  • Diagnostic Rheumatology and Research PC

    Indianapolis, Indiana, 46227

  • West Tennessee Research Institute

    Jackson, Tennessee, 38305

  • University of Florida - Rheumatology at ACC

    Jacksonville, Florida, 32207

  • University of Florida College of Medicine, Jacksonville - Rheumatology Research

    Jacksonville, Florida, 32207

  • Arthritis And Rheumatism Associates LLC

    Jonesboro, Arkansas, 72401

  • Bronson Rheumatology Specialists

    Kalamazoo, Michigan, 49007

  • Jasper Clinic, Inc.

    Kalamazoo, Michigan, 49007

  • Western Michigan University Homer Stryker M.D. School of Medicine Center for Clinical Research

    Kalamazoo, Michigan, 49008

  • Borgess Medical Center

    Kalamazoo, Michigan, 49048

  • Borgess Research Institute

    Kalamazoo, Michigan, 49048

  • Glacier View Research Institute

    Kalispell, Montana, 59901

  • Kansas City Internal Medicine

    Kansas City, Missouri, 64114

  • Rheumatology Consultants, PLLC

    Knoxville, Tennessee, 37909

  • University of California, San Diego (UCSD)- Perlman Ambulatory Clinic

    La Jolla, California, 92037

  • NYU Langone Rheumatology Associates Long Island.

    Lake Success, New York, 11042

  • June DO,PC

    Lansing, Michigan, 48910

  • University of Nevada School of Medicine

    Las Vegas, Nevada, 89102

  • Steinberg Diagnostics

    Las Vegas, Nevada, 89109

  • EKSAKTI, LLC (dba: Eksakti Clinical Research)

    Las Vegas, Nevada, 89128

  • Accurate Clinical Research, Inc.

    League City, Texas, 77573

  • Physician Research Collaboration, LLC

    Lincoln, Nebraska, 68516

  • Valerius Medical Group And Research Center Of Greater Long Beach, Inc.

    Long Beach, California, 90806

  • ProHealth Partners

    Long Beach, California, 90808

  • Keck Medicine of USC

    Los Angeles, California, 90033

  • Arthritis and Osteoporosis Associates, LLP

    Lubbock, Texas, 79424

  • Dr. Ramesh C. Gupta MD, Office of

    Memphis, Tennessee, 38119

  • Center for Diagnostic Imaging

    Mendota Heights, Minnesota, 55118

  • Southwest Rheumatology Research, LLC

    Mesquite, Texas, 75150

  • Doctors Research Institute

    Miami, Florida, 33145

  • Center for Arthritis and Rheumatic Diseases

    Miami, Florida, 33173

  • San Marcus Research Clinic

    Miami Lakes, Florida, 33014

  • Trinity Health Center - Medical Arts

    Minot, North Dakota, 58701

  • Arthritis and Diabetes Clinic, Inc.

    Monroe, Louisiana, 71203

  • Nashua Rheumatology

    Nashua, New Hampshire, 03060

  • Center For Inflammatory Disease

    Nashville, Tennessee, 37203

  • California Medical Research Associates Inc

    Northridge, California, 91324

  • Ocala Rheumatology Research Center

    Ocala, Florida, 34474

  • Advanced Clinical Research of Orlando

    Ocoee, Florida, 34761

  • Health Research of Oklahoma

    Oklahoma City, Oklahoma, 73103

  • Oklahoma Medical Research Foundation (OMRF)

    Oklahoma City, Oklahoma, 73104

  • Lynn Health Science Institute

    Oklahoma City, Oklahoma, 73112

  • Westroads Clinical Research, Inc.

    Omaha, Nebraska, 68114

  • Arthritis & osteoporosis treatment center,PA

    Orange Park, Florida, 32073

  • Articluaris Healthcare Group d/b/a ACME Research

    Orangeburg, South Carolina, 29118

  • Rheumatology Associates of Central Florida, PA

    Orlando, Florida, 32806

  • Omega Research Consultants, LLC

    Orlando, Florida, 32810

  • Millennium Research

    Ormond Beach, Florida, 32174

  • MidWest Clinical Research, LLC

    Overland Park, Kansas, 66209

  • Desert Medical Advances

    Palm Desert, California, 92260

  • Arthritis Center, Inc.

    Palm Harbor, Florida, 34684

  • Arthritis Research of Florida, Inc.

    Palm Harbor, Florida, 34684

  • The Arthritis Group

    Philadelphia, Pennsylvania, 19152

  • UPMC Arthritis and Autoimmunity Clinic

    Pittsburgh, Pennsylvania, 15213

  • UPMC Lupus Center of Excellence

    Pittsburgh, Pennsylvania, 15213

  • Medvin Clinical Research

    Placentia, California, 92870

  • Trinity Universal Research Associates, Inc.

    Plano, Texas, 75024

  • Advanced Medical Research Center

    Port Orange, Florida, 32127

  • Advanced Urgent Care

    Port Orange, Florida, 32127

  • Quincy Medical Group

    Quincy, Illinois, 62301

  • Arthritis Center Of Reno

    Reno, Nevada, 89502

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • Sierra Rheumatology, Inc.

    Roseville, California, 95661

  • Shores Rheumatology P.C.

    Saint Clair Shores, Michigan, 48081

  • San Diego Arthritis Medical Clinic

    San Diego, California, 92108

  • Dr. Orrin M. Troum, Md And Medical Associates

    Santa Monica, California, 90404

  • Springfield Clinic

    Springfield, Illinois, 62702

  • Clinvest Research, LLC

    Springfield, Missouri, 65810

  • PMG Research Inc., d/b/a PMG Research of Piedmont HealthCare

    Statesville, North Carolina, 28625

  • Center for Arthritis and Rheumatic Diseases, P.C.

    Suffolk, Virginia, 23435

  • Articularis Healthcare Group, Inc d/b/a Low Country Rheumatology

    Summerville, South Carolina, 29486

  • USF Health Morsani Center for Advanced Healthcare

    Tampa, Florida, 33612

  • Los Angeles Biomedical Research Institute at Harbor UCLA Medical Center

    Torrance, California, 90502

  • Harbor UCLA Medical Center

    Torrance, California, 90509

  • Southern Arizona VA Health Care System (SAVAHCS)

    Tucson, Arizona, 85723

  • University of Arizona Clinical and Translational Science Research Center

    Tucson, Arizona, 85724

  • Clinical and Translational Research Center of Alabama, PC

    Tuscaloosa, Alabama, 35406

  • Robin K. Dore M.D., Inc.

    Tustin, California, 92780

  • Medvin Clinical Research

    Van Nuys, California, 91405

  • Ventura Clinical Trials

    Ventura, California, 93003

  • Desert Valley Medical Group

    Victorville, California, 92395

  • Howard University Hospital

    Washington D.C., District of Columbia, 20060

  • The Center for Rheumatology and Bone Research, a division of Arthritis and Rheumatism Associates, PC

    Wheaton, Maryland, 20902

  • Medvin Clinical Research

    Whittier, California, 90602

  • Professional Research Network of Kansas, LLC

    Wichita, Kansas, 67205-1138

  • Carolina Arthritis Associates

    Wilmington, North Carolina, 28401

  • UMass Memorial Medical Center, Memorial Campus

    Worcester, Massachusetts, 01605

  • Clinical Research Center of Reading, LLC

    Wyomissing, Pennsylvania, 19610

  • Florida Medical Clinic, P.A.

    Zephyrhills, Florida, 33542

Other trials in United States

Poland18 sites

  • Zdrowie Osteo-Medic s.c. Lidia i Artur Racewicz, Agnieszka i Jerzy Supronik

    Bialystok, Podlaskie Voivodeship, 15-351

  • Szpital Uniwersytecki nr 2 im. dr Jana Biziela w Bydgoszczy

    Bydgoszcz, 85-168

  • Centrum Kliniczno-Badawcze J.Brzezicki, B.Gornikiewicz-Brzezicka Lekarze Spolka Partnerska

    Elblag, 82-300

  • Centrum Medyczne Pratia Gdynia

    Gdynia, 81-338

  • Synexus Polska Sp. z o.o. Oddzial w Gdyni

    Gdynia, 81-537

  • Centrum Medyczne Pratia Katowice

    Katowice, 40-081

  • Indywidualna Praktyka lekarska Dr hab. med. Anna Szczepańska - Szerej

    Lublin, 20-022

  • Zespol Poradni Specjalistycznych Reumed Filia Onyksowa

    Lublin, 20-582

  • NZOZ Lecznica MAK-MED

    Nadarzyn, Masovian Voivodeship, 05-830

  • PROFMEDICUS Sp. z o.o., Osrodek Badan Klinicznych

    Olsztyn, 10-357

  • Prywatna Praktyka Lekarska Prof. UM dr hab. med. Pawel Hrycaj

    Poznan, 61-397

  • Pomorskie Centrum Reumatologiczne im. Dr Jadwigi Titz-Kosko w Sopocie, Spolka. z o.o.

    Sopot, 81-759

  • KO-MED Centra Kliniczne Sp. zo.o.

    Staszów, 28-200

  • NASZ LEKARZ Przychodnie Medyczne

    Torun, 87-100

  • Centrum Medyczne Pratia Warszawa

    Warsaw, 01-868

  • Rheuma Medicus Zaklad Opieki Zdrowotnej

    Warsaw, 02-118

  • Synexus Polska Sp. z o.o.

    Wroclaw, 50-281

  • NZOZ Biogenes Sp. z o.o.

    Wroclaw, 53-224

Other trials in Poland

Brazil16 sites

  • Hospital das Clinicas Universidade Federal de Minas Gerais

    Belo Horizonte, Minas Gerais, 30130-100

  • Clinica Medica Bonfliglioli Ltda.

    Campinas, São Paulo, 13015-001

  • EDUMED - Educacao em Saude SS Ltda

    Curitiba, Paraná, 80440-080

  • CMIP- Centro Mineiro de Pesquisa Ltda/CETAL- Centro de Estudos e Tratamento do Aparelho Locomotor

    Juiz de Fora, Minas Gerais, 36010-570

  • Hospital de Clinicas de Porto Alegre - UFRGS

    Porto Alegre, Rio Grande do Sul, 90035-903

  • CCBR Brasil - Centro de Pesquisas e Analises Clinicas LTDA

    Rio de Janeiro, Rio de Janeiro, 22271-100

  • Hospital Moinhos de Vento

    Rio Grande de Sul, 90560-030

  • SER - Servicos Especializados em Reumatologia da Bahia

    Salvador, Estado de Bahia, 40150-150

  • Fundacao Faculdade Regional de Medicina de Sao Jose do Rio Preto

    São Jose Do Rio Preto, São Paulo, 15090-000

  • CPCLin - Centro de Pesquisas Clinicas Ltda. / Clinica Dr. Freddy Goldberg Eliaschewitz LTDA EPP

    São Paulo, São Paulo, 01244-030

  • AACD- Lar Escola\ Associacao de Assistencia a Crianca Deficiente

    São Paulo, São Paulo, 04032-060

  • Instituto de Assistencia Medica do Hospital do Servidor Publico Estadual

    São Paulo, São Paulo, 04039-901

  • Fundacao Faculdade de Medicina MECMPAS - Hospital das Clinicas da FMUSP

    São Paulo, São Paulo, 05403-900

  • Hospital Israelita Albert Einstein

    São Paulo, São Paulo, 05652-900

  • CEPIC - Centro Paulista de Investigacao Clinica e Servicos Medicos Ltda

    São Paulo, 04266-010

  • CEDOES - Centro de Diagnostico e Pesquisa da Osteoporose do Espirito Santo

    Vitória, Espírito Santo, 29055-450

Other trials in Brazil

Mexico13 sites

  • Investigacion y Biomedicina de Chihuahua SC

    Chihuahua City, 31000

  • Centro de Investigacion de Tratamientos Innovadores de Sinaloa, S.C

    Culiacán, Sinaloa, 80000

  • Centro Integral en Reumatologia SA de CV

    Guadalajara, Jalisco, 44160

  • Hospital Civil de Guadalajara Fray Antonio Alcalde

    Guadalajara, Jalisco, 44280

  • Unidad Reumatologica Las Americas S.C.P.

    Mérida, Yucatán, 97000

  • Consultorio de Reumatologia

    Mexico City, Mexico City, 07760

  • Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

    Mexico City, Mexico City, 14080

  • CINTRE, Centro de Investigacion y Tratamiento Reumatologico S.C.

    Mexico City, 11850

  • Centro de Investigacion Clinica de Morelia. S.C

    Morelia, Michoacán, 58070

  • Clinica de Enfermedades Cronicas y Procedimientos Especiales, SC

    Morelia, Michoacán, 58249

  • Centro de Alta Especialidad en Reumatologia e Investigacion del Potosi, S.C.

    San Luis Potosí City, 78213

  • Unidad de Investigaciones Reumatologicas

    San Luis Potosí City, 78290

  • Unidad de Enfermedades Reumaticas y Cronico Degenerativas S. C.

    Torreón, Coahuila, 27000

Other trials in Mexico

Argentina11 sites

  • OMI- Organizacion Medica de Investigacion

    Buenos Aires, Buenos Aires F.D., C1015ABO

  • Consultorios Reumatologicos Pampa.

    Buenos Aires, 1428

  • Centro de Educacion Medica e Investigaciones Clinicas Norberto Quirno (CEMIC)

    C.a.b.a., Buenos Aires F.D., 1431

  • CIER - Centro de Investigaciones en Enfermedades Reumaticas

    CABA, C1055AAF

  • Centro Privado de Medicina Familiar - Mindout Research S.R.L.

    CABA, C1417EYG

  • Hospital Privado Centro Medico de Cordoba S.A.

    Córdoba, 5016

  • Sanatorio Parque S.A y Consultorios Externos Asociados

    Rosario, Santa Fe Province, 2000

  • Sanatorio Parque S.A y Consultorios Externos Asociados

    Rosario, 2000

  • I.A.R.I. Instituto de Asistencia Reumatologica Integral - Sede IMAC

    San Isidro, 1643

  • CER San Juan

    San Juan, 5400

  • Centro Medico Privado de Reumatologia

    San Miguel de Tucumán, Tucumán Province, 4000

Other trials in Argentina

Russia11 sites

  • SBHI City Clinical Hospital #4 of HD of Moscow

    Moscow, 115093

  • SBHI of Moscow City Clinical Hospital 1 n. a. N.I. Pirogov of the Healthcare Department of Moscow

    Moscow, 119049

  • SBIH of Nizhniy Novgorod region City Clinical Hospital #5 of Nizhniy Novgorod district

    Nizhny Novgorod, 603005

  • Federal State Budgetary Scientific Institution "Research Institute of Fundamental and

    Novosibirsk, 630075

  • Consulting and Diagnostic Rheumatological Center Healthy Joints LLC

    Novosibirsk, 630099

  • GBUZ RK Republic Hospital n. a. V.A. Baranov of the MoH & social development Of The Karelia Republic

    Petrozavodsk, 185000

  • Saint-Petersburg State Budgetary Institution of Healthcare Municipal hospital # 40 of the

    Saint Petersburg, St.petersburg, 197706

  • Saint-Petersburg State Budget Healthcare Institution Consultative-diagnostic Center #85

    Saint Petersburg, 198260

  • Federal State Budgetary Educational Institution of Higher Education

    Smolensk, 214019

  • SBEI of HPE Ural State Medical University of the MoH of the RF

    Yekaterinburg, 620028

  • Municipal Budgetary Institution "Central City Clinical Hospital #6"

    Yekaterinburg, 620149

Other trials in Russia

South Africa11 sites

  • Tiervlei Trial Centre, Karl Bremer Hospital

    Bellville, Cape Town, Western Cape, 7530

  • Arthritis Clinical Research Trials cc

    Cape Town, Western Cape, 7405

  • Panorama Medical Centre

    Cape Town, Western Cape, 7500

  • University of Cape Town

    Cape Town, Western Cape, 7925

  • St. Augustine's Hospital - Chelmsford Medical Centre 2

    Durban, KwaZulu-Natal, 4001

  • Wits Clinical Research Site

    Johannesburg, Gauteng, 2193

  • Clinresco Centres ( Pty ) Ltd

    Kempton Park, Gauteng, 1619

  • Greenacres Hospital

    Port Elizabeth, Eastern Cape, 6045

  • Jakaranda Hospital

    Pretoria, Gauteng, 0002

  • Emmed Research

    Pretoria, Gauteng, 0084

  • Winelands Medical Research Centre-

    Stellenbosch, 7600

Other trials in South Africa

Israel10 sites

  • Barzilai Medical Center - Rheumatology Outpatient Clinic

    Ashkelon, 78278

  • Assaf Harofeh Medical Center

    Beer Yaacov, 70300

  • Bnai Zion Medical Center Rheumatology Unit

    Haifa, 31048

  • Rambam Health Care Campus

    Haifa, 3109601

  • Carmel Medical Center

    Haifa, 34362

  • Hadassah Medical Center - Hebrew University Hospital

    Jerusalem, 91120

  • Meir Medical Center

    Kfar Saba, 44281

  • Rabin Medical Center

    Petah Tikva, 49100

  • Tel Aviv Sourasky Medical Center

    Tel Aviv, 64239

  • The Chaim Sheba Medical Center

    Tel HaShomer, 52621

Other trials in Israel

Peru10 sites

  • Centro de lnvestigacion de la Red Asistencial del Hospital Nacional ESSALUD Carlos Alberto Seguin E.

    Arequipa, 04001

  • ACQ MEDIC S.A.C. - Centro de Investigacion Clinica Inmunoreumatologia

    Lima, 11

  • Unidad de Investigacion de la Clinica Internacional - Clinica Internacional

    Lima, 1

  • ABK REUMA S.R.L. de Medicentro Biociencias- BIO CIENCIAS PERU S.R.L.

    Lima, 21

  • Instituto Peruano del Hueso y la Articulacion - Instituto Peruano del Hueso y la Articulacion S.A.C.

    Lima, 27

  • Investigaciones en Reumatologia - Centro Medico Corpac

    Lima, 27

  • Investigaciones Clinicas S.A.C.

    Lima, 33

  • Centro de Investigacion de Reumatologia - Clinica San Borja

    Lima, 41

  • Centro de Investigacion en Salud - Centro de Excelencia en Reumatologia

    Lima, 41

  • Centro de Investigacion Clinica Trujillo E.I.R.L. Clinica Peruana Americana

    Trujillo, La Libertad, 13001

Other trials in Peru

Spain10 sites

  • Hospital Universitario de Cruces

    Barakaldo, Vizcaya, 48903

  • Hospital Plato

    Barcelona, 08006

  • Hospital De La Santa Creu I Sant Pau

    Barcelona, 08025

  • Hospital Universitario de Basurto

    Bilbao, Vizcaya, 48013

  • Hospital Universitario 12 de Octubre

    Madrid, 28041

  • Hospital Regional Universitario de Malaga

    Málaga, 29009

  • Hospital de Merida

    Mérida, Badajoz, 06800

  • Hospital Universitario Marques de Valdecilla

    Santander, Cantabria, 39008

  • Hospital Nuestra Senora de la Esperanza

    Santiago de Compostela, LA Coruna, 15705

  • Hospital Universitario Virgen de la Macarena

    Seville, 41009

Other trials in Spain

Czechia9 sites

  • REVMACLINIC s.r.o.

    Brno, 61141

  • Revmatologie, s.r.o.

    Brno, 638 00

  • Revmacentrum MUDr. Mostera, s.r.o.

    Brno-Židenice, 615 00

  • Vesalion, s.r.o.

    Ostrava, Czech Republic, 702 00

  • Artroscan, s.r.o.

    Ostrava, 722 00

  • Mediscan Group, s.r.o.

    Prague, Czech Republic, 148 00

  • Revmatologicky ustav.

    Prague, 128 50

  • Revmatologicka Ambulance

    Prague, 140 00

  • PV - MEDICAL s.r.o.

    Zlín, 76001

Other trials in Czechia

Turkey (Türkiye)9 sites

  • Ankara Universitesi Tip Fakultesi Ibn-i Sina Hastanesi

    Ankara, 06100

  • Hacettepe Universitesi Tip Fakultesi

    Ankara, 06100

  • Adnan Menderes Universitesi Tip Fakultesi Hastanesi

    Aydin, 09010

  • Gaziantep Universitesi Tip Fakultesi

    Gaziantep, 27310

  • Istanbul Universitesi Cerrahpasa Tip Fakultesi

    Istanbul, 34098

  • Izmir Tepecik Egitim ve Arastirma Hastanesi

    Izmir, 35180

  • Kocaeli Universitesi Tip Fakultesi Hastanesi

    Kocaeli, 41380

  • Ondokuz Mayis Universitesi Tip Fakultesi Fiziksel Tip ve

    Samsun, 55200

  • Cumhuriyet Universitesi Tip Fakultesi Hastanesi

    Sivas, 58140

Other trials in Turkey (Türkiye)

United Kingdom9 sites

  • The Royal Wolverhampton NHS Trust-Cannock Chase Hospital

    Cannock, WS11 5XY

  • Barking, Havering and Redbridge University Hospitals NHS Trust

    Goodmayes, Essex, IG3 8YB

  • Aintree University Hospital, Liverpool University Hospitals

    Liverpool, L9 7AL

  • Clinical trials, Pharmacy Department, Aintree University Hospitals

    Liverpool, L9 7AL

  • University of Liverpool Academic Rheumatology Unit. Aintree University Hospital. Liverpool Universit

    Liverpool, L9 7AL

  • The Newcastle Upon Tyne Hospitals NHS Foundation Trust, Clinical Research Facility

    Newcastle upon Tyne, NE1 4LP

  • Northumbria Healthcare NHS Foundation Trust

    North Shields, NE29 8NH

  • Poole Hospital, University Hospitals Dorset NHS Foundation Trust

    Poole, Dorset, BH152JB

  • Pharmacy Department

    Wolverhampton, WV10 0QP

Other trials in United Kingdom

Slovakia7 sites

  • Nestatna reumatologicka ambulancia

    Bratislava, 841 04

  • ROMJAN s.r. o. , Specializovana Reumatologicka ambulancia

    Bratislava - Petrzalka, 851 01

  • AAGS, s.r.o., Reumatologicka ambulancia

    Dunajská Streda, 929 01

  • ECCLESIA s.r.o, Reumatologicka ambulancia

    Nové Zámky, 940 01

  • REUMACENTRUM s.r.o., Reumatologicka ambulancia

    Partizánske, 958 01

  • Reumex s.r.o

    Rimavská Sobota, 979 01

  • Reuma-Global s.r.o., Reumatologicka ambulancia

    Trnava, 91701

Other trials in Slovakia

Taiwan7 sites

  • Changhua Christian Hospital

    Changhua, 500

  • Buddhist Dalin Tzu Chi General Hospital

    Chiayi City, 62247

  • China Medical University Hospital

    Taichung, Taiwan (r.o.c), 40447

  • Chung Shan Medical University Hospital

    Taichung

  • National Cheng Kung University Hospital

    Tainan, 704

  • Taipei Veterans General Hospital

    Taipei, 11217

  • Chang Gung Medical Foundation - Linkou Branch

    Taoyuan City, 33305

Other trials in Taiwan

Canada6 sites

  • Rheumatology Research Associates

    Edmonton, Alberta, T5M 0H4

  • Medicine Professional Corporation

    Ottawa, Ontario, K1Y 4G2

  • Centre de Rhumatologie de l'Est du Quebec

    Rimouski, Quebec, G5L 8W1

  • Centre de Recherche Musculo-Squelettique

    Trois-Rivières, Quebec, G8Z 1Y2

  • PerCuro Clinical Research Limited

    Victoria, British Columbia, V8V 3M9

  • Clinical Research and Arthritis Centre

    Windsor, Ontario, N8X2C9

Other trials in Canada

Australia5 sites

  • St. Vincent's Hospital (Melbourne)

    Fitzroy, Victoria, 3065

  • Austin Repatriation Hospital

    Heidelberg, Victoria, 3081

  • Austin Health - Repatriation Hospital

    Heidelberg West, Victoria, 3081

  • RK Will Pty Ltd

    Victoria Park, Western Australia, 6100

  • The Queen Elizabeth Hospital

    Woodville South, South Australia, 5011

Other trials in Australia

Bulgaria5 sites

  • UMBAL "Dr Georgi Stranski" EAD

    Pleven, 5800

  • MBAL Eurohospital Plovdiv OOD

    Plovdiv, 4000

  • MBAL RUSe AD,

    Rousse, 7002

  • UMBAL Sveti Ivan Rilski" EAD

    Sofia, 1612

  • MBAL Sveta Marina EAD

    Varna, 9010

Other trials in Bulgaria

Colombia5 sites

  • Centro de Investigaciones Clinica del Country

    Bogota, Cundinamarca

  • Centro de Investigacion en Reumatologia y Especialidades Medicas S.A.S, CIREEM S.A.S

    Bogota D.C., Cundinamarca, 112201

  • Servimed S.A.S

    Bucaramanga, Santander Department

  • Preventive Care S.A.S.

    Chía, Cundinamarca, 250001

  • Centro Integral de Reumatologia REUMALAB S.A.S.

    Medellín, Antioquia

Other trials in Colombia

Thailand5 sites

  • Phramongkutklao Hospital

    Bangkok, 10400

  • Ramathibodi Hospital, Mahidol University

    Bangkok, 10400

  • Faculty of Medicine , Siriraj Hospital , Mahidol University

    Bangkok, 10700

  • Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine,Chiang Mai University

    Chiang Mai, 50200

  • Prince of Songkla University

    Songkhla, 90110

Other trials in Thailand

Hong Kong4 sites

  • Pamela Youde Nethersole Eastern Hospital

    Chai Wan, HKG

  • The University of Hong Kong (HKU)-Queen Mary Hospital (QMH)

    Hong Kong, 999077

  • Tuen Mun Hospital

    Hong Kong

  • Prince of Wales Hospital

    Shatin

Other trials in Hong Kong

New Zealand4 sites

  • Middlemore Hospital Middlemore Clinical Trials Trust

    Auckland, 2025

  • Rheumatology Clinic, Waikato Hospital

    Hamilton, 3204

  • Timaru Hospital

    Timaru, 7910

  • Wellington Hospital

    Wellington, 6021

Other trials in New Zealand

Chile3 sites

  • Prosalud

    Santiago, Santiago Metropolitan, 7510047

  • Centro de Investigacion Clinica Universidad Catolica (CICUC)

    Santiago, Santiago Metropolitan, 8330034

  • Centro Medico de Reumatologia Ltda.

    Temuco, Araucania, 4790928

Other trials in Chile

Finland3 sites

  • Helsingin yliopistollinen keskussairaala

    Helsinki, 00290

  • Kiljavan Laaketutkimus Oy

    Hyvinkää, 05800

  • Laakarikeskus Aava Hyvinkaan Pipetti

    Hyvinkää, 05800

Other trials in Finland

Malaysia3 sites

  • Hospital Selayang, Department of Medicine

    Batu Caves, Selangor, 68100

  • Hospital Raja Permaisuri Bainun

    Ipoh, Perak, 30990

  • Sarawak General Hospital

    Kuching, Sarawak, 93586

Other trials in Malaysia

Jordan2 sites

  • Istishari Hospital

    Amman, 11184

  • King Abdullah University Hospital

    Irbid, 22110

Other trials in Jordan

Lebanon2 sites

  • Hotel Dieu de France Hospital

    El Achrafiyé, Beirut

  • Ain Wazein Hospital

    Lebanon

Other trials in Lebanon

Netherlands2 sites

  • Medical Center Leeuwarden

    Leeuwarden, 8934 AD

  • Universitair Medisch Centrum (UMC) Utrecht

    Utrecht, 3584 CX

Other trials in Netherlands

Puerto Rico2 sites

  • Ponce Medical School Foundation, Inc.

    Ponce, 00716

  • Fundacion de Investigaction de Diego

    San Juan, 00927

Other trials in Puerto Rico

China1 site

  • Guangdong General Hospital

    Guangzhou, Guangdong, 510080

Other trials in China

About this study

Official title: PHASE 3B/4 RANDOMIZED SAFETY ENDPOINT STUDY OF 2 DOSES OF TOFACITINIB IN COMPARISON TO A TUMOR NECROSIS FACTOR (TNF) INHIBITOR IN SUBJECTS WITH RHEUMATOID ARTHRITIS

This post-marketing study is designed to compare the safety of tofacitinib versus TNF inhibitor with respect to major cardiovascular adverse events and malignancies, excluding non-melanoma skin cancers when given to subjects with rheumatoid arthritis. Other safety events, including non-melanoma skin cancers, hepatic events, infections, and efficacy parameters will be collected and evaluated in the study.

Being tested
tofacitinib, adalimumab, etanercept
Keywords
Post-marketing, Phase 4, Open-label, Safety Surveillance, CP690550, Xeljanz, oral treatment
Medical subject headings
Arthritis, Rheumatoid

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • tofacitinibDrug

    Oral tablet, 5 mg BID

  • tofacitinibDrug

    Oral tablet, 10 mg BID

  • adalimumabBiological

    Also called Humira

    Pre-filled syringe, 40 mg subcutaneous injection, every other week

  • etanerceptBiological

    Also called Enbrel

    Pre-filled syringe, 50 mg subcutaneous injection, every week

Study groups in NCT02092467
Study groupRoleWhat they receive
Treatment Arm 1ExperimentalNot described
Receives: Drug: tofacitinib
Treatment Arm 2ExperimentalNot described
Receives: Drug: tofacitinib
Treatment Arm 3Active comparatorTNF inhibitor Arm - adalimumab will be used in US, Canada and Puerto Rico; etanercept will be used in all other countries.
Receives: Biological: adalimumab; Biological: etanercept

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence Rate of Adjudicated Malignancies Excluding Non-melanoma Skin Cancers (NMSC)

    Incidence rate (number of participants with event per 100 participant year [PY]) was defined as the total number of participants with admissible events divided by the total (for all qualifying participants) time at risk for the cohort/treatment group of interest. Malignancy events, excluding NMSC were adjudicated by a steering committee. The risk period (RP) was the last contact date. The last contact date was the maximum of (AE start date, AE stop date, last study visit date, withdrawal date, telephone contact date). If a participant died, last contact date was the death date. First events were counted within the RP. If a participant did not have an event or had an event but outside the risk period, the participant was censored at the end of RP.

    Measured: Baseline up to last contact date (maximum up to 72 months)

  2. Incidence Rate of Adjudicated Major Adverse Cardiovascular Events (MACE)

    MACE included the cardiovascular death, non-fatal myocardial infarction (MI) and non-fatal stroke of any classification, including reversible focal neurologic defects with imaging evidence of a new cerebral lesion consistent with ischemia or hemorrhage. Incidence rate was defined as the total number of participants with admissible events divided by the total (for all qualifying participants) time at risk for the cohort/treatment group of interest. The risk period (RP) was the minimum of last contact date or last study treatment dose date + 60 days. The last contact date was the maximum of (AE start date, AE stop date, last study visit date, withdrawal date, telephone contact date). If a participant died, last contact date was the death date. First events were counted within the RP. If a participant did not have an event or had an event but outside the risk period, the participant was censored at the end of RP.

    Measured: Baseline up to last contact date (maximum up to 72 months)

Secondary outcomes (22)

  1. Incidence Rate of Non-fatal Stroke

    Non-fatal stroke included reversible focal neurologic defects with imaging evidence of a new cerebral lesion consistent with ischemia or hemorrhage. Incidence rate was defined as the total number of participants with admissible events divided by the total (for all qualifying participants) time at risk for the cohort/treatment group of interest. The risk period (RP) was the minimum of last contact date or last study treatment dose date + 60 days. The last contact date was the maximum of (AE start date, AE stop date, last study visit date, withdrawal date, telephone contact date). If a participant died, last contact date was the death date. First events were counted within the RP. If a participant did not have an event or had an event but outside the risk period, the participant was censored at the end of RP.

    Measured: Baseline up to last contact date (maximum up to 72 months)

  2. Incidence Rate of Non-fatal Myocardial Infarction

    Incidence rate was defined as the total number of participants with admissible events divided by the total (for all qualifying participants) time at risk for the cohort/treatment group of interest. The risk period (RP) was the minimum of last contact date or last study treatment dose date + 60 days. The last contact date was the maximum of (AE start date, AE stop date, last study visit date, withdrawal date, telephone contact date). If a participant died, last contact date was the death date. First events were counted within the RP. If a participant did not have an event or had an event but outside the risk period, the participant was censored at the end of RP.

    Measured: Baseline up to last contact date (maximum up to 72 months)

  3. Incidence Rate of Adjudicated Opportunistic Infection Events Including Tuberculosis

    Opportunistic infections (OI) were reviewed and adjudicated by the opportunistic infection review committee (OIRC). Incidence rate was defined as the total number of participants with admissible events divided by the total (for all qualifying participants) time at risk for the cohort/treatment group of interest. The risk period (RP) was the minimum of last contact date or last study treatment dose date + 28 days. The last contact date was the maximum of (AE start date, AE stop date, last study visit date, withdrawal date, telephone contact date). If a participant died, last contact date was the death date. First events were counted within the RP. If a participant did not have an event or had an event but outside the risk period, the participant was censored at the end of RP.

    Measured: Baseline up to last contact date (maximum up to 72 months)

  4. Incidence Rate of Adjudicated Hepatic Events

    Hepatic events (adjudicated) included drug-induced liver injury (DILI) - probable, highly likely and definite, DILI - listed separately, DILI - cases meeting classification and severity, participants with elevations of transaminase levels greater than (>) 1* upper limit of normal (ULN), greater than or equal to (>=) 3*ULN, >=5*ULN (based on laboratory values). Incidence rate was the total number of participants with admissible events divided by total (for all qualifying participants) time at risk for the cohort/treatment group of interest. The risk period (RP) was minimum of The risk period (RP) was the minimum of last contact date or last study treatment dose date + 28 days. Last contact date was maximum of (AE start date, AE stop date, last study visit date, withdrawal date, telephone contact date). In case of death, last contact date was death date. First events counted within RP. Participant did not have an event or had an event outside risk period were censored at end of RP.

    Measured: Baseline up to last contact date (maximum up to 72 months)

  5. Incidence Rate of Adjudicated Cardiovascular Events Other Than Major Adverse Cardiovascular Events (MACE)

    Cardiovascular events (adjudicated) were death (coronary and non-coronary), MI, all coronary revascularization, unstable angina, new ischemic heart disease, stroke (fatal and non-fatal), transient ischemic attack (TIA), congestive heart failure (CHF), peripheral arterial vascular disease (PAVD), deep vein thrombosis, pulmonary embolism, arterial embolism, arterial thrombosis. Incidence rate was total number of participants with admissible events divided by total (for all qualifying participants) time at risk for cohort/treatment group of interest. Risk period (RP) was the minimum of last contact date or last study treatment dose date + 28 days. Last contact date was maximum of (AE start date, AE stop date, last study visit date, withdrawal date, telephone contact date). In case of death, last contact date was death date. First events counted within RP. Participant did not have an event or had an event outside risk period were censored at end of RP.

    Measured: Baseline up to last contact date (maximum up to 72 months)

  6. Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

    AE was any untoward medical occurrence post treatment; event need not necessarily had causal relationship with treatment or usage. SAE: any untoward medical occurrence at any dose: resulted in death, life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, resulted in congenital anomaly. TEAE: event that occurred for first time during effective duration of treatment and not seen prior to start of treatment or event seen prior to start of treatment but increase in severity during treatment. Risk period (RP) for AE: minimum of last contact date or last study treatment dose date+28 days. RP for SAEs: last contact date. Last contact date was maximum: AE start, AE stop, last study visit, withdrawal and telephone contact. In case of death, last contact was death date. First events counted within RP. Participant did not have event or had event outside risk period were censored at end of RP.

    Measured: AEs: Baseline up to minimum of last contact date or last study treatment dose date+28 days (maximum up to 72 months); SAEs: Baseline up to minimum of last contact date (maximum up to 72 months)

  7. Number of Participants With Clinically Significant Abnormal Laboratory Parameters

    Clinically significant laboratory abnormalities: Hematology: hemoglobin, hematocrit, erythrocytes with primary criteria as less than [<] 0.8* lower limit of normal [LLN]), platelets (<0.5* LLN; >1.75* ULN), leukocytes (<0.6*LLN; >1.5*ULN), lymphocytes, lymphocytes/leukocytes, neutrophils, neutrophils/leukocytes (<0.8*LLN; >1.2*ULN), eosinophils, eosinophils/leukocytes, monocytes, monocytes/leukocytes (>1.2*ULN); urinalysis: urine glucose, urine protein, urine hemoglobin, and leukocyte esterase (>=1); chemistry: bilirubin, indirect bilirubin (>1.5*ULN) aspartate aminotransferase, alanine aminotransferase (>3.0*ULN), creatinine, triglycerides, cholesterol (>1.3*ULN) and HDL cholesterol (<0.8*LLN). Risk period (RP) was minimum of last contact date or last study treatment dose date+28 days. Last contact date was (date of death or maximum of dates: AE start, AE stop, last study visit, withdrawal, telephone contact). Participants without event or event outside RP were censored at end of RP.

    Measured: Baseline up to last contact date (maximum up to 72 months)

  8. Incidence Rate of Adjudicated All-Cause Deaths

    All-cause death was defined as the death due to any cause during the course of study. Incidence rate was defined as the total number of participants with admissible events divided by the total (for all qualifying participants) time at risk for the cohort/treatment group of interest. Incidence rate of all-cause deaths (adjudicated by Adjudication Committee) was reported in this outcome measure. The risk period (RP) was the minimum of last contact date or last study treatment dose date + 28 days. The last contact date was the maximum of (AE start date, AE stop date, last study visit date, withdrawal date, telephone contact date). If a participant died, last contact date was the death date. First events were counted within the RP. If a participant did not have an event or had an event but outside the risk period, the participant was censored at the end of RP.

    Measured: Baseline up to last contact date (maximum up to 72 months)

  9. Number of Participants With Reasons For Permanent or Temporary Discontinuation of Study Medication

    Number of participants who permanent or temporary discontinued study medication due to any AE, treatment related AEs, Coronavirus disease 2019 (COVID 19) related AEs, and herpes zoster were reported. The risk period (RP) was the minimum of last contact date or last study treatment dose date + 28 days. The last contact date was the maximum of (AE start date, AE stop date, last study visit date, withdrawal date, telephone contact date). If a participant died, last contact date was the death date. First events were counted within the RP. If a participant did not have an event or had an event but outside the risk period, the participant was censored at the end of RP.

    Measured: Baseline up to last contact date (maximum up to 72 months)

  10. Change From Baseline in Disease Activity Score 28-4 (DAS28-4) C-reactive Protein (CRP) at Month 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60 and 63

    DAS28 is a measure of disease activity in participants with rheumatoid arthritis based on a 28-joint assessment. DAS28-4 (CRP) was calculated from number of painful joints out of 28 joints (TJC28) and number of swollen joints out of 28 joints (SJC28), CRP (milligrams per liter [mg/L]) and patient's global assessment of disease activity (PtGA) on a 100 mm Visual Analog Scale (VAS) (scores ranging from 0 millimeter [mm] [very well] to 100 mm [worst], higher scores indicated worse health condition). Total DAS28-4 (CRP) score range: 0 to 9.4, higher score indicated more disease activity. DAS28-4 (CRP) <= 3.2 indicates low disease activity and > 3.2 to <=5.1 indicates moderate disease activity, >5.1 indicates high disease activity, and DAS28-4 (CRP) < 2.6 indicates remission. DAS28-4 (CRP) = 0.56*sqrt(TJC28) + 0.28*sqrt(SJC28) + 0.36*ln(CRP in mg/L +1) + 0.014*PtGA in mm+ 0.96; ln = natural logarithm, sqrt = square root.

    Measured: Baseline, Months 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60 and 63

  11. Change From Baseline in Simplified Disease Activity Index (SDAI) Score at Month 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60 and 63

    SDAI is the numerical sum of five outcome parameters: TJC and SJC both based on a 28-joint assessment, PtGA and physician's global assessment of health (PhyGA) both assessed on a 0 to 100 mm VAS (higher scores indicate greater affection due to disease activity), and CRP (mg/L). SDAI total score ranges from 0 to 86 with higher score indicating greater disease activity. SDAI <=3.3 indicates disease remission, >3.4 to 11 indicates low disease activity >11 to 26 indicates moderate disease activity, and >26 indicates high disease activity. SDAI = (28TJC) + (28SJC) + PhyGA/10 + PtGA/10 + CRP/10.

    Measured: Baseline, Month 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60 and 63

  12. Change From Baseline in Clinical Disease Activity Index (CDAI) Score at Month 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60 and 63

    CDAI is the numerical sum of four outcome parameters: TJC and SJC both based on a 28-joint assessment, PtGA and PhyGA both assessed on a 0 to 100 mm VAS (higher scores indicate greater affection due to disease activity). CDAI total score ranges from 0 to 76 with higher score indicating greater disease activity. CDAI <=2.8 indicates disease remission, >2.8 to 10 indicates low disease activity, >10 to 22 indicates moderate disease activity, and >22 indicates high disease activity. CDAI = (28TJC) + (28SJC) + PhyGA/10 + PtGA/10.

    Measured: Baseline, Month 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60 and 63

  13. Percentage of Participants Who Achieved Observed American College of Rheumatology-European League Against Rheumatism (ACR-EULAR) Boolean Remission Criteria

    ACR-EULAR Boolean-based definition of remission participant must satisfy all of the following: TJC28 <=1, SJC28 <=1, CRP <=10 mg/L, PtGA on a 0-100 mm scale, higher scores indicate greater affection due to disease activity.

    Measured: Month 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60, 63, 66, 69 and 72

  14. Percentage of Participants With Simplified Disease Activity Index (SDAI) Less Than or Equal to (<=) 3.3

    SDAI is the numerical sum of five outcome parameters: TJC and SJC both based on a 28-joint assessment, PtGA and PhyGA both assessed on a 0 to 100 mm VAS (higher scores indicate greater affection due to disease activity), and CRP (mg/L). SDAI total score ranges from 0 to 86 with higher score indicating greater disease activity. SDAI <=3.3 indicates disease remission, >3.4 to 11 indicates low disease activity >11 to 26 indicates moderate disease activity, and >26 indicates high disease activity. SDAI = (28TJC) + (28SJC) + PhyGA/10 + PtGA/10 + CRP/10.

    Measured: Month 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60, 63, 66, 69 and 72

  15. Percentage of Participants With Clinical Disease Activity Index (CDAI) <=2.8

    CDAI is the numerical sum of four outcome parameters: TJC and SJC both based on a 28-joint assessment, PtGA and PhyGA both assessed on a 0 to 100 mm VAS (higher scores indicate greater affection due to disease activity). CDAI total score ranges from 0 to 76 with higher score indicating greater disease activity. CDAI <=2.8 indicates disease remission, >2.8 to 10 indicates low disease activity, >10 to 22 indicates moderate disease activity, and >22 indicates high disease activity. CDAI = (28TJC) + (28SJC) + PhyGA/10 + PtGA/10.

    Measured: Month 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60, 63, 66, 69 and 72

  16. Percentage of Participants With Simplified Disease Activity Index (SDAI) <=11

    SDAI is the numerical sum of five outcome parameters: TJC and SJC both based on a 28-joint assessment, PtGA and PhyGA both assessed on a 0 to 100 mm VAS (higher scores indicate greater affection due to disease activity), and CRP (mg/L). SDAI total score ranges from 0 to 86 with higher score indicating greater disease activity. SDAI <=3.3 indicates disease remission, >3.4 to 11 indicates low disease activity >11 to 26 indicates moderate disease activity, and >26 indicates high disease activity. SDAI = (28TJC) + (28SJC) + PhyGA/10 + PtGA/10 + CRP/10.

    Measured: Month 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60, 63, 66, 69 and 72

  17. Percentage of Participants With Clinical Disease Activity Index (CDAI) <=10

    CDAI is the numerical sum of four outcome parameters: TJC and SJC both based on a 28-joint assessment, PtGA and PhyGA both assessed on a 0 to 100 mm VAS (higher scores indicate greater affection due to disease activity). CDAI total score ranges from 0 to 76 with higher score indicating greater disease activity. CDAI <=2.8 indicates disease remission, >2.8 to 10 indicates low disease activity, >10 to 22 indicates moderate disease activity, and >22 indicates high disease activity. CDAI = (28TJC) + (28SJC) + PhyGA/10 + PtGA/10.

    Measured: Month 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60, 63, 66, 69 and 72

  18. Percentage of Participants With Disease Activity Score 28-4 (DAS28-4) C-reactive Protein (CRP) <=3.2

    DAS28 is a measure of disease activity in participants with rheumatoid arthritis based on a 28-joint assessment. DAS28-4 (CRP) was calculated from number of painful joints out of 28 joints (TJC28) and number of swollen joints out of 28 joints (SJC28), CRP (mg/L) and PtGA on a 100 mm VAS (VAS: scores ranging from 0 mm [very well] to 100 mm [worst], higher scores indicated worse health condition). Total DAS28-4 (CRP) score range: 0 to 9.4, higher score indicated more disease activity. DAS28-4 (CRP) <= 3.2 indicates low disease activity and > 3.2 to <=5.1 indicates moderate disease activity, >5.1 indicates high disease activity, and DAS28-4 (CRP) < 2.6 indicates remission. DAS28-4 (CRP) = 0.56*sqrt(TJC28) + 0.28*sqrt(SJC28) + 0.36*ln(CRP in mg/L +1) + 0.014*PtGA in mm+ 0.96.

    Measured: Month 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60, 63, 66, 69 and 72

  19. Number of Participants With an American College of Rheumatology 20 Percent (%) (ACR20) Response

    ACR20 response is a >= 20% improvement in TJC (28) and SJC (28) and >=20% improvement in 3 of the 5 remaining ACR-core criteria: 1) PGA of arthritis, 2) PtGA of arthritis, 3) participant's assessment of arthritis pain, 4) participant's assessment of functional disability by HAQ-DI, and 5) CRP (mg/L) at each visit. PGA: physician's global assessment of arthritis on VAS, 0 (very well) to 100 mm (worst arthritis), higher scores=worse condition. PtGA: participant's global assessment of arthritis on VAS, 0 mm (very well) to 100 mm (worst arthritis condition), higher scores = worse condition. Participant's assessment of arthritis pain: assessed on VAS, 0 mm (no pain) to 100 mm (most severe pain), higher score = more pain. HAQ-DI: functional disability evaluation, score: 0 (no difficulty) to 3 (unable to do), higher score=more disability.

    Measured: Month 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60, 63, 66, 69 and 72

  20. Number of Participants With an American College of Rheumatology 50% (ACR50) Response

    ACR50 response is a >= 50% improvement in TJC (28) and SJC (28) and >=50% improvement in 3 of the 5 remaining ACR-core criteria: 1) PGA of arthritis, 2) PtGA of arthritis, 3) participant's assessment of arthritis pain, 4) participant's assessment of functional disability by HAQ-DI, and 5) CRP (mg/L) at each visit. PGA: physician's global assessment of arthritis on VAS, 0 (very well) to 100 mm (worst arthritis), higher scores=worse condition. PtGA: participant's global assessment of arthritis on VAS, 0 mm (very well) to 100 mm (worst arthritis condition), higher scores = worse condition. Participant's assessment of arthritis pain: assessed on VAS, 0 mm (no pain) to 100 mm (most severe pain), higher score = more pain. HAQ-DI: functional disability evaluation, score: 0 (no difficulty) to 3 (unable to do), higher score=more disability.

    Measured: Month 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60, 63, 66, 69 and 72

  21. Number of Participants With an American College of Rheumatology 70% (ACR70) Response

    ACR70 response is a >= 70% improvement in TJC (28) and SJC (28) and >=70% improvement in 3 of the 5 remaining ACR-core criteria: 1) PGA of arthritis, 2) PtGA of arthritis, 3) participant's assessment of arthritis pain, 4) participant's assessment of functional disability by HAQ-DI, and 5) CRP (mg/L) at each visit. PGA: physician's global assessment of arthritis on VAS, 0 (very well) to 100 mm (worst arthritis), higher scores=worse condition. PtGA: participant's global assessment of arthritis on VAS, 0 mm (very well) to 100 mm (worst arthritis condition), higher scores = worse condition. Participant's assessment of arthritis pain: assessed on VAS, 0 mm (no pain) to 100 mm (most severe pain), higher score = more pain. HAQ-DI: functional disability evaluation, score: 0 (no difficulty) to 3 (unable to do), higher score=more disability.

    Measured: Month 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60, 63, 66, 69 and 72

  22. Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) at Months 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60 and 63

    HAQ-DI assesses the degree of difficulty a participant has experienced during the past week in 8 domains of daily living activities: dressing/grooming; arising; eating; walking; reach; grip; hygiene; and other activities. There were total of 30 items distributed in these 8 domains. Each item was scored on a 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 (least difficulty) and 3 (extreme difficulty), where higher scores indicate more difficulty while performing daily living activities.

    Measured: Baseline, Months 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60 and 63

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Mar 2014 (estimated)
  2. Study start14 Mar 2014
  3. Primary completion22 Jul 2020
  4. Study completion22 Jul 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
4,372 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02092467
Sponsor's protocol ID
A3921133
Other IDs
2013-003177-99
Status last verified
Jul 2021
First submitted
3 Mar 2014
Last updated
17 Aug 2021
Data monitoring committee
Yes
Individual data sharing
Yes: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical\_trials/trial\_data\_and\_results/data\_requests.

Publications

  • Giles JT, Charles-Schoeman C, Buch MH, Dougados M, Szekanecz Z, Mikuls TR, Ytterberg SR, Koch GG, Kwok K, Cadatal MJ, Menon S, Chen Y, Diehl AM, Rivas JL, Yndestad A, Bhatt DL. Use of statins and its association with major adverse cardiovascular events with tofacitinib vs TNF inhibitors in patients with rheumatoid arthritis with and without atherosclerotic cardiovascular disease. Ann Rheum Dis. 2026 Jan;85(1):103-113. doi: 10.1016/j.ard.2025.08.028. Epub 2025 Sep 23.

    PubMed 40992967

  • Hetland ML, Strangfeld A, Bonfanti G, Soudis D, Deuring JJ, Edwards RA. Machine learning prediction and explanatory models of serious infections in patients with rheumatoid arthritis treated with tofacitinib. Arthritis Res Ther. 2024 Aug 27;26(1):153. doi: 10.1186/s13075-024-03376-9.

    PubMed 39192350

  • Batko B, Jeka S, Wiland P, Zielinska A, Stopinska-Polaszewska M, Stajszczyk M, Kosydar-Piechna M, Cadatal MJ, Rivas JL. Geographical Differences in the Safety and Efficacy of Tofacitinib Versus TNFi: A Post Hoc Analysis of ORAL Surveillance. Rheumatol Ther. 2024 Oct;11(5):1217-1235. doi: 10.1007/s40744-024-00693-y. Epub 2024 Jul 26.

    PubMed 39060905

  • Citera G, Mysler E, Kakehasi AM, Pascual-Ramos V, Masson W, Cadatal MJ, Rivas JL, Sheibanie F, Helling C, Ponce de Leon D. Cardiovascular Events, Malignancies, and Efficacy Outcomes in Latin American Patients With Rheumatoid Arthritis Receiving Tofacitinib or Tumor Necrosis Factor Inhibitors: A Post Hoc Analysis of the ORAL Surveillance Study. J Clin Rheumatol. 2024 Aug 1;30(5):208-216. doi: 10.1097/RHU.0000000000002106. Epub 2024 Jun 17.

    PubMed 38880956

  • Buch MH, Bhatt DL, Charles-Schoeman C, Giles JT, Mikuls T, Koch GG, Ytterberg S, Nagy E, Jo H, Kwok K, Connell CA, Masri KR, Yndestad A. Risk of extended major adverse cardiovascular event endpoints with tofacitinib versus TNF inhibitors in patients with rheumatoid arthritis: a post hoc analysis of a phase 3b/4 randomised safety study. RMD Open. 2024 Apr 12;10(2):e003912. doi: 10.1136/rmdopen-2023-003912.

    PubMed 38609322

  • Karpouzas GA, Szekanecz Z, Baecklund E, Mikuls TR, Bhatt DL, Wang C, Sawyerr GA, Chen Y, Menon S, Connell CA, Ytterberg SR, Mortezavi M. Rheumatoid arthritis disease activity and adverse events in patients receiving tofacitinib or tumor necrosis factor inhibitors: a post hoc analysis of ORAL Surveillance. Ther Adv Musculoskelet Dis. 2023 Nov 6;15:1759720X231201047. doi: 10.1177/1759720X231201047. eCollection 2023.

    PubMed 37942277

  • Kristensen LE, Danese S, Yndestad A, Wang C, Nagy E, Modesto I, Rivas J, Benda B. Identification of two tofacitinib subpopulations with different relative risk versus TNF inhibitors: an analysis of the open label, randomised controlled study ORAL Surveillance. Ann Rheum Dis. 2023 Jul;82(7):901-910. doi: 10.1136/ard-2022-223715. Epub 2023 Mar 17.

    PubMed 36931693

  • Hansen KE, Mortezavi M, Nagy E, Wang C, Connell CA, Radi Z, Litman HJ, Adami G, Rossini M. Fracture in clinical studies of tofacitinib in rheumatoid arthritis. Ther Adv Musculoskelet Dis. 2022 Dec 27;14:1759720X221142346. doi: 10.1177/1759720X221142346. eCollection 2022.

    PubMed 36601090

  • Curtis JR, Yamaoka K, Chen YH, Bhatt DL, Gunay LM, Sugiyama N, Connell CA, Wang C, Wu J, Menon S, Vranic I, Gomez-Reino JJ. Malignancy risk with tofacitinib versus TNF inhibitors in rheumatoid arthritis: results from the open-label, randomised controlled ORAL Surveillance trial. Ann Rheum Dis. 2023 Mar;82(3):331-343. doi: 10.1136/ard-2022-222543. Epub 2022 Dec 5.

    PubMed 36600185

  • Weitz JI, Szekanecz Z, Charles-Schoeman C, Vranic I, Sahin B, Paciga SA, Wang Z, Hyde C, Martin DA. Biomarkers to predict risk of venous thromboembolism in patients with rheumatoid arthritis receiving tofacitinib or tumour necrosis factor inhibitors. RMD Open. 2022 Nov;8(2):e002571. doi: 10.1136/rmdopen-2022-002571.

    PubMed 36323490

  • Charles-Schoeman C, Buch MH, Dougados M, Bhatt DL, Giles JT, Ytterberg SR, Koch GG, Vranic I, Wu J, Wang C, Kwok K, Menon S, Rivas JL, Yndestad A, Connell CA, Szekanecz Z. Risk of major adverse cardiovascular events with tofacitinib versus tumour necrosis factor inhibitors in patients with rheumatoid arthritis with or without a history of atherosclerotic cardiovascular disease: a post hoc analysis from ORAL Surveillance. Ann Rheum Dis. 2023 Jan;82(1):119-129. doi: 10.1136/ard-2022-222259. Epub 2022 Sep 22.

    PubMed 36137735

  • Balanescu AR, Citera G, Pascual-Ramos V, Bhatt DL, Connell CA, Gold D, Chen AS, Sawyerr G, Shapiro AB, Pope JE, Schulze-Koops H. Infections in patients with rheumatoid arthritis receiving tofacitinib versus tumour necrosis factor inhibitors: results from the open-label, randomised controlled ORAL Surveillance trial. Ann Rheum Dis. 2022 Nov;81(11):1491-1503. doi: 10.1136/ard-2022-222405. Epub 2022 Aug 3.

    PubMed 35922124

  • Ytterberg SR, Bhatt DL, Mikuls TR, Koch GG, Fleischmann R, Rivas JL, Germino R, Menon S, Sun Y, Wang C, Shapiro AB, Kanik KS, Connell CA; ORAL Surveillance Investigators. Cardiovascular and Cancer Risk with Tofacitinib in Rheumatoid Arthritis. N Engl J Med. 2022 Jan 27;386(4):316-326. doi: 10.1056/NEJMoa2109927.

    PubMed 35081280

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing tofacitinib, adalimumab and etanercept in people with Arthritis, Rheumatoid, run by Pfizer at 345 sites in 30 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 17 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 345 sites in United States, Poland, Brazil, Mexico, Argentina and 25 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 17 Aug 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence Rate of Adjudicated Malignancies Excluding Non-melanoma Skin Cancers (NMSC) (time frame: Baseline up to last contact date (maximum up to 72 months)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02092467, which also lists 13 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Aug 2021.

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