Clinical trial NCT02675426: A Study Comparing Upadacitinib (ABT-494) to Placebo in Adults With Rheumatoid Arthritis on a Stable Dose of Conventional Synthetic Disease-Modifying Antirheumatic Drugs (csDMARDs) Who Have an Inadequate Response to csDMARDs Alone
Official title: A Phase 3, Randomized, Double-Blind Study Comparing Upadacitinib (ABT-494) to Placebo in Subjects With Moderately to Severely Active Rheumatoid Arthritis Who Are on a Stable Dose of Conventional Synthetic Disease-Modifying Anti-Rheumatic Drugs (csDMARDs) and Have an Inadequate Response to csDMARDs
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Rheumatoid Arthritis
Keywords: Musculoskeletal Disease
Arthritis
Joint Disease
Anti-inflammatory agents
Antirheumatic agents
Upadacitinib
ABT-494
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2016-02-05
Enrollment: 661
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objectives of this study are to compare the efficacy, safety, and tolerability of upadacitinib 30 mg once daily (QD) and 15 mg QD versus placebo for the treatment of signs and symptoms of adults with moderately to severely active rheumatoid arthritis who were on a stable dose of csDMARDs and had an inadequate response to csDMARDs.

Detailed description: This Phase 3 multicenter study includes two periods. Period 1 is a 12-week, randomized, double-blind, parallel-group, placebo-controlled period designed to compare the safety and efficacy of upadacitinib 30 mg once daily and upadacitinib 15 mg once daily versus placebo for the treatment of signs and symptoms of adults with moderately to severely active rheumatoid arthritis (RA) who were on a stable dose of csDMARDs and had an inadequate response to csDMARDs.

Period 2 is a 248-week blinded long-term extension period to evaluate the long-term safety, tolerability, and efficacy of upadacitinib 30 mg once daily and upadacitinib 15 mg once daily in participants who completed Period 1.

Participants were to be randomized in a 2:2:1:1 ratio using interactive response technology (IRT) to receive double-blind study drug in one of the following treatment groups:

* Group 1: Upadacitinib 30 mg QD in Period 1 → Upadacitinib 30 mg QD in Period 2
* Group 2: Upadacitinib 15 mg QD in Period 1 → Upadacitinib 15 mg QD in Period 2
* Group 3: Placebo in Period 1 → Upadacitinib 30 mg QD in Period 2
* Group 4: Placebo in Period 1 → Upadacitinib 15 mg QD in Period 2

Randomization was stratified by prior exposure to biological disease-modifying anti-rheumatic drug (bDMARD) (yes/no) and geographic region.

Following Protocol Amendment 6.0 approval in December 2019, all participants still on study received open-label upadacitinib 15 mg QD, including those on upadacitinib 30 mg QD, with the earliest switch occurring at the Week 168 visit.

Eligibility criteria: Inclusion Criteria:

* Adult male or female, at least 18 years old.
* Diagnosis of rheumatoid arthritis (RA) for greater than or equal to 3 months.
* Subjects have been receiving conventional synthetic DMARD (csDMARD) therapy for greater than or equal to 3 months and on a stable dose for greater than or equal to 4 weeks prior to the first dose of study drug. The following csDMARDs are allowed: methotrexate (MTX), sulfasalazine, hydroxychloroquine, chloroquine, and leflunomide.
* Meets the following minimum disease activity criteria: greater than or equal to 6 swollen joints (based on 66 joint counts) and greater than or equal to 6 tender joints (based on 68 joint counts) at Screening and Baseline Visits.
* Subjects with prior exposure to at most one biologic DMARD (bDMARD) may be enrolled (up to 20% of study population) if they have documented evidence of intolerance to bDMARDs or limited exposure (less than 3 months) and have satisfied required washout periods.

Exclusion Criteria:

* Prior exposure to any Janus kinase (JAK) inhibitor (including but not limited to tofacitinib, baricitinib, and filgotinib).
* History of inflammatory joint disease other than RA. History of secondary Sjogren's Syndrome is permitted.
* Subjects who are considered inadequate responders to bDMARD therapy as determined by the Investigator.

Primary outcomes:
measure: Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 12
timeFrame: Baseline and Week 12
measure: Percentage of Participants Achieving Low Disease Activity (LDA) Based on DAS28(CRP) at Week 12
timeFrame: Week 12
Secondary outcomes:
measure: Change From Baseline in in Disease Activity Score 28 (CRP) at Week 12
timeFrame: Baseline and Week 12
measure: Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 12
timeFrame: Baseline and Week 12
measure: Change From Baseline in Short-Form 36 (SF-36) Physical Component Summary (PCS) Score at Week 12
timeFrame: Baseline and Week 12
measure: Percentage of Participants Achieving Clinical Remission Based on DAS28 (CRP) at Week 12
timeFrame: Week 12
measure: Percentage of Participants Achieving Low Disease Activity Based on CDAI at Week 12
timeFrame: Week 12
measure: Change From Baseline in Duration of Morning Stiffness at Week 12
timeFrame: Baseline and Week 12
measure: Change From Baseline in in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) at Week 12
timeFrame: Baseline and week 12
measure: Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response at Week 12
timeFrame: Baseline and Week 12
measure: Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response at Week 12
timeFrame: Baseline and Week 12
measure: Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 1
timeFrame: Baseline and Week 1
Other outcomes:
Locations:
city: Mesa
country: United States
facility: AZ Arthritis and Rheum Assoc /ID# 148651
state: Arizona
city: Peoria
country: United States
facility: SunValley Arthritis Center, Lt /ID# 140452
state: Arizona
city: Phoenix
country: United States
facility: AZ Arthritis and Rheum Researc /ID# 138500
state: Arizona
city: Phoenix
country: United States
facility: AZ Arthritis and Rheum Researc /ID# 139286
state: Arizona
city: Phoenix
country: United States
facility: AZ Arthritis & Rheuma Research /ID# 138598
state: Arizona
city: Phoenix
country: United States
facility: Arizona Research Center, Inc. /ID# 140448
state: Arizona
city: Tucson
country: United States
facility: University of Arizona Cancer Center - North Campus /ID# 140451
state: Arizona
city: Covina
country: United States
facility: Covina Arthritis Clinic /ID# 139881
state: California
city: Encino
country: United States
facility: T. Joseph Raoof, MD, Inc. /ID# 140964
state: California
city: La Jolla
country: United States
facility: Allergy and Rheum Med Clin /ID# 146082
state: California
city: Los Angeles
country: United States
facility: Pacific Arthritis Ctr Med Grp /ID# 138744
state: California
city: Tustin
country: United States
facility: Robin K. Dore MD, Inc /ID# 138688
state: California
city: Upland
country: United States
facility: Inland Rheum Clin Trials Inc. /ID# 138853
state: California
city: Denver
country: United States
facility: Denver Arthritis Clinic /ID# 139876
state: Colorado
city: Clearwater
country: United States
facility: Clinical Res of West FL, Inc. /ID# 138854
state: Florida
city: Miami
country: United States
facility: Ctr Arthritis & Rheumatic Dise /ID# 141696
state: Florida
city: Naples
country: United States
facility: Medallion Clinical Research Institute, LLC /ID# 140074
state: Florida
city: New Port Richey
country: United States
facility: Suncoast Clinical Research /ID# 138633
state: Florida
city: Orlando
country: United States
facility: Omega Research Consultants /ID# 139877
state: Florida
city: Palm Harbor
country: United States
facility: Arthritis Center, Inc. /ID# 141363
state: Florida
city: Idaho Falls
country: United States
facility: Institute of Arthritis Res /ID# 138548
state: Idaho
city: Rockford
country: United States
facility: OrthoIllinois /ID# 139695
state: Illinois
city: Skokie
country: United States
facility: Clinical Investigation Special /ID# 139696
state: Illinois
city: Springfield
country: United States
facility: Springfield Clinic /ID# 138602
state: Illinois
city: Vernon Hills
country: United States
facility: Deerbrook Medical Associates /ID# 139694
state: Illinois
city: Indianapolis
country: United States
facility: Indiana Univ School of Med /ID# 140077
state: Indiana
city: Lexington
country: United States
facility: Bluegrass Community Research /ID# 138295
state: Kentucky
city: Paducah
country: United States
facility: Four Rivers Clinical Research /ID# 141134
state: Kentucky
city: Portland
country: United States
facility: MMP Women's Health /ID# 141542
state: Maine
city: Wheaton
country: United States
facility: The Center for Rheumatology & /ID# 139203
state: Maryland
city: Mansfield
country: United States
facility: Mansfield Health Center /ID# 141357
state: Massachusetts
city: Lansing
country: United States
facility: Advanced Rheumatology, PC /ID# 140071
state: Michigan
city: Lansing
country: United States
facility: Justus J. Fiechtner, MD, PC /ID# 138697
state: Michigan
city: Lincoln
country: United States
facility: Physician Res. Collaboration /ID# 138533
state: Nebraska
city: Omaha
country: United States
facility: Westroads Clinical Research /ID# 138304
state: Nebraska
city: Albany
country: United States
facility: The Center for Rheumatology /ID# 138746
state: New York
city: Salisbury
country: United States
facility: PMG Research of Salisbury /ID# 141023
state: North Carolina
city: Wilmington
country: United States
facility: PMG Research of Wilmington LLC /ID# 140951
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Rheumatic Disease Study Group, Inc. /ID# 138868
state: Ohio
city: Toledo
country: United States
facility: Arthritis Assoc of NW Ohio /ID# 140953
state: Ohio
city: Oklahoma City
country: United States
facility: Health Research Oklahoma /ID# 138535
state: Oklahoma
city: Duncansville
country: United States
facility: Altoona Ctr Clinical Res /ID# 138741
state: Pennsylvania
city: Summerville
country: United States
facility: Articularis Healthcare Group, Inc d/b/a Low Country Rheumatology /ID# 138689
state: South Carolina
city: Hendersonville
country: United States
facility: Comprehensive Arthritis Care, a division of Comprehensive Rheumatology Care PLLC /ID# 141021
state: Tennessee
city: Austin
country: United States
facility: Tekton Research, Inc. /ID# 141428
state: Texas
city: Carrollton
country: United States
facility: Trinity Universal Res Assoc /ID# 149271
state: Texas
city: College Station
country: United States
facility: Arth and Osteo Clin Brazo Valley /ID# 147809
state: Texas
city: Dallas
country: United States
facility: Metroplex Clinical Research /ID# 138698
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine /ID# 138682
state: Texas
city: Houston
country: United States
facility: Houston Institute for Clin Res /ID# 138716
state: Texas
city: Killeen
country: United States
facility: Arthritis Consultants, P.A. /ID# 141138
state: Texas
city: Plano
country: United States
facility: Trinity Universal Research Association /ID# 148649
state: Texas
city: San Antonio
country: United States
facility: Accurate Clinical Management /ID# 139338
state: Texas
city: Waco
country: United States
facility: Arthritis & Osteoporosis Clinic /ID# 138703
state: Texas
city: Bothell
country: United States
facility: Western Washington Arthritis C /ID# 138728
state: Washington
city: Spokane
country: United States
facility: Arthritis Northwest, PLLC /ID# 138539
state: Washington
city: Franklin
country: United States
facility: Aurora Rheumatology and Immunotherapy Center /ID# 139306
state: Wisconsin
city: Buenos Aires
country: Argentina
facility: Mautalen Salud e Investigacion /ID# 141419
city: Cordoba
country: Argentina
facility: Inst. Rheumatologic Strusberg /ID# 145648
city: Coffs Harbour
country: Australia
facility: Coffs Clinical Trials /ID# 138747
state: New South Wales
city: Kogarah
country: Australia
facility: Optimus Clinical Research Pty. /ID# 138769
state: New South Wales
city: Camberwell
country: Australia
facility: Emeritus Research /ID# 138773
state: Victoria
city: Geelong
country: Australia
facility: Barwon Rheumatology /ID# 138772
state: Victoria
city: Vienna
country: Austria
facility: Rheuma Zentrum Favoriten GmbH /ID# 138787
city: Wien
country: Austria
facility: Wilhelminenspital der Stadt Wien /ID# 138788
city: Charleroi
country: Belgium
facility: Rhumaconsult SPRL /ID# 138813
state: Hainaut
city: Gent
country: Belgium
facility: UZ Gent /ID# 138806
state: Oost-Vlaanderen
city: Brugge
country: Belgium
facility: AZ Sint Lucas /ID# 141338
city: Banja Luka
country: Bosnia and Herzegovina
facility: University Clinical Centre of the Republic of Srpska /ID# 138819
state: Republika Srpska
city: Banja Luka
country: Bosnia and Herzegovina
facility: University Clinical Centre of the Republic of Srpska /ID# 140372
state: Republika Srpska
city: Sofia
country: Bulgaria
facility: Diag Consult Ctr 17 Sofia EOOD /ID# 141006
city: Sofia
country: Bulgaria
facility: Diagnostic Consultative Center /ID# 138882
city: Winnipeg
country: Canada
facility: Manitoba Clinic /ID# 139086
state: Manitoba
city: St. John's
country: Canada
facility: Eastern Health /ID# 140431
state: Newfoundland and Labrador
city: Sainte-foy
country: Canada
facility: Groupe de Recherche en Maladies Osseuses /ID# 138906
state: Quebec
city: Saskatoon
country: Canada
facility: Dr. Latha Naik /ID# 139089
state: Saskatchewan
city: Rijeka
country: Croatia
facility: Klinicki bolnicki centar Rijeka /ID# 138649
state: Primorsko-goranska Zupanija
city: Zagreb
country: Croatia
facility: Klinicka bolnica Sveti Duh /ID# 152812
city: Zagreb
country: Croatia
facility: Medical Center Kuna-Peric /ID# 140365
city: Zagreb
country: Croatia
facility: Poliklinika Bonifarm /ID# 141415
city: Hlučín
country: Czechia
facility: L.K.N. Arthrocentrum, s.r.o /ID# 141340
state: Moravskoslezsky Kraj
city: Brno
country: Czechia
facility: Revmatologie, s.r.o. /ID# 138899
city: Ostrava
country: Czechia
facility: Artroscan s.r.o. /ID# 138833
city: Slany
country: Czechia
facility: Nemocnice Slany /ID# 141112
city: Zlin
country: Czechia
facility: PV-MEDICAL s.r.o. /ID# 138913
city: Tallinn
country: Estonia
facility: Center of Clinical and Basic Research /ID# 141116
state: Harjumaa
city: Pärnu
country: Estonia
facility: Paernu Hospital /ID# 138961
city: Tallinn
country: Estonia
facility: East Tallinn Central Hospital /ID# 140618
city: Helsinki
country: Finland
facility: Helsinki Univ Central Hospital /ID# 140381
city: Hyvinkaa
country: Finland
facility: Kiljava Medical Research /ID# 139260
city: Lappeenranta
country: Finland
facility: South Karelia Central Hospital /ID# 139973
city: Marseille CEDEX 08
country: France
facility: Hopital Saint Joseph /ID# 149188
state: Bouches-du-Rhone
city: Chambray Les Tours
country: France
facility: CHRU Tours - Hopital Trousseau /ID# 138969
city: Köln
country: Germany
facility: Uniklinik Koln /ID# 139084
state: Nordrhein-Westfalen
city: Berlin
country: Germany
facility: Charité Universitätsmedizin Campus Mitte /ID# 139052
city: Berlin
country: Germany
facility: Immanuel-Krankenhaus /ID# 139059
city: Hamburg
country: Germany
facility: Asklepios Klinik Altona /ID# 140466
city: Planegg
country: Germany
facility: Welcker, Planegg, DE /ID# 140467
city: Heraklion
country: Greece
facility: University General Hospital of Heraklion "PA.G.N.I" /ID# 139115
city: Sha Tin
country: Hong Kong
facility: Prince of Wales Hospital /ID# 139314
city: Budapest
country: Hungary
facility: Revita Reumatologiai Rendelo /ID# 140761
city: Szekesfehervar
country: Hungary
facility: Fejer Megyei Szent Gyorgy Korh /ID# 138554
city: Dublin
country: Ireland
facility: St Vincent's University Hosp /ID# 138562
city: Catanzaro
country: Italy
facility: Universita di Catanzaro Magna Graecia /ID# 139316
state: Calabria
city: Astana
country: Kazakhstan
facility: JSC Nat Scientific Med Res Ctr /ID# 140575
city: Incheon
country: Korea, Republic of
facility: Inha University Hospital /ID# 149310
state: Gwang Yeogsi
city: Suwon-si
country: Korea, Republic of
facility: Ajou University Hospital /ID# 149311
state: Gyeonggido
city: Gwangju
country: Korea, Republic of
facility: Chonnam National University Hospital /ID# 138651
state: Jeonranamdo
city: Seoul
country: Korea, Republic of
facility: Hanyang University Seoul Hospi /ID# 138655
state: Seongdong-gu
city: Seoul
country: Korea, Republic of
facility: Cath Univ Seoul St Mary's Hosp /ID# 138652
state: Seoul Teugbyeolsi
city: Daegu
country: Korea, Republic of
facility: Daegu Catholic University Med /ID# 139249
city: Daejeon
country: Korea, Republic of
facility: Chungnam National University Hospital /ID# 138653
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital /ID# 138659
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center /ID# 140579
city: Adazi
country: Latvia
facility: LTD M+M Centers /ID# 138818
city: Klaipeda
country: Lithuania
facility: Klaipeda University Hospital /ID# 141416
city: Vilnius
country: Lithuania
facility: Vilnius University Hospital /ID# 141348
city: Colonia Centro
country: Mexico
facility: Centro Peninsular de Investigación Clínica SCP /ID# 148160
state: Yucatan
city: Mexico City
country: Mexico
facility: Unidad de Investigacion de las Enfermedades Reumatologicas SA de CV /ID# 138841
city: Nelson
country: New Zealand
facility: Porter Rheumatology Ltd /ID# 138347
city: Toruń
country: Poland
facility: NZOZ Nasz Lekarz /ID# 138374
state: Kujawsko-pomorskie
city: Grodzisk Mazowiecki
country: Poland
facility: McBk Sc /Id# 138360
state: Mazowieckie
city: Białystok
country: Poland
facility: Osteo-Medic spolka cywilna /ID# 138371
state: Podlaskie
city: Elblag
country: Poland
facility: NZOZ Centrum Reumatologiczne /ID# 138353
state: Warminsko-mazurskie
city: Warsaw
country: Poland
facility: Rheuma Medicus /ID# 138372
city: Lisbon
country: Portugal
facility: Instituto Portugues De Reumatologia /ID# 148315
state: Lisboa
city: Lisbon
country: Portugal
facility: Centro Hospitalar Lisboa Ocidental, EPE /ID# 140594
state: Lisboa
city: San Juan
country: Puerto Rico
facility: School of Medicine University of Puerto Rico-Medical Sciences Campus /ID# 139328
city: Cluj
country: Romania
facility: Spitalul Clinic Judetean de Urgenta /ID# 138407
city: Ploiesti
country: Romania
facility: Spitalul Municipal Ploiesti /ID# 138405
city: Sibiu
country: Romania
facility: Spitalul Clinic Judetean de Ur /ID# 138393
city: Pyatigorsk
country: Russian Federation
facility: LLC Novaya Klinika /ID# 139269
state: Stavropol Skiy Kray
city: Kazan
country: Russian Federation
facility: Kazan State Medical University /ID# 138413
state: Tatarstan, Respublika
city: Petrozavodsk
country: Russian Federation
facility: Republican Clin Hos n.a. Baran /ID# 139273
city: Samara
country: Russian Federation
facility: Samara Regional Clinical Hosp /ID# 148642
city: Ulyanovsk
country: Russian Federation
facility: Ulyanovsk Regional Clin Hosp /ID# 139279
city: Voronezh
country: Russian Federation
facility: Voronezh State Medical Univers /ID# 148431
city: Yaroslavl
country: Russian Federation
facility: Yaroslavi State Medical Univer /ID# 139908
city: Kosice
country: Slovakia
facility: ARTROMAC n.o. /ID# 138428
city: Kosice
country: Slovakia
facility: Nemocnica Kosice Saca, a.s. /ID# 138918
city: Pieštany
country: Slovakia
facility: Slovak research center Team Member, Thermium s.r.o. /ID# 139924
city: Pieštany
country: Slovakia
facility: Narodny ustav reumatickych chorob Piestany /ID# 138427
city: Trnava
country: Slovakia
facility: REUMA-GLOBAL, s.r.o. /ID# 139912
city: Berea
country: South Africa
facility: St. Augustine's Medical Centre /ID# 141352
state: Kwazulu-Natal
city: Cape Town
country: South Africa
facility: Arthritis Clinical Research Tr /ID# 138945
state: Western Cape
city: Stellenbosch
country: South Africa
facility: Winelands Medical Research Ctr /ID# 138944
state: Western Cape
city: Málaga
country: Spain
facility: Hospital Regional de Malaga /ID# 138975
state: Malaga
city: Elche
country: Spain
facility: Hospital General Univ de Elche /ID# 138991
city: Madrid
country: Spain
facility: Hospital Clin Univ San Carlos /ID# 138993
city: Santiago de Compostela
country: Spain
facility: Hosp Nuestra Senora Esperanza /ID# 138997
city: Fribourg
country: Switzerland
facility: HFR Fribourg - Hopital Canton /ID# 139155
city: Taichung City
country: Taiwan
facility: China Medical University Hosp /ID# 139232
state: Taichung
city: Tainan City
country: Taiwan
facility: National Cheng Kung University Hospital /ID# 140868
state: Tainan
city: Taipei City
country: Taiwan
facility: National Taiwan Univ Hosp /ID# 141443
state: Taipei
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical University Chung-Ho Memorial Hospital /ID# 140869
city: New Taipei City
country: Taiwan
facility: Far Eastern Memorial Hospital /ID# 140871
city: Taipei City
country: Taiwan
facility: Taipei Veterans General Hosp /ID# 139234
city: Ankara
country: Turkey
facility: Ankara Numune Training and Res /ID# 139237
city: Kyiv
country: Ukraine
facility: LLC Revmocentr /ID# 139872
city: Lviv
country: Ukraine
facility: MNCE "Lviv City Clinical Hospital #4" /ID# 139873
city: Odesa
country: Ukraine
facility: Odessa National Medical Univ /ID# 139179
city: Leicester
country: United Kingdom
facility: Leicester Royal Infirmary /ID# 139184
state: England
city: London
country: United Kingdom
facility: Whipps Cross Univ Hospital /ID# 139523
state: London, City Of
city: London
country: United Kingdom
facility: The Royal Free Hospital /ID# 139191
state: London, City Of
city: Edinburgh
country: United Kingdom
facility: Western General Hospital /ID# 139524
city: Southampton
country: United Kingdom
facility: Southampton General Hospital /ID# 139169
city: Warrington
country: United Kingdom
facility: Warrington + Halton Hosp NHS /ID# 139195
Study officials:
affiliation: AbbVie
name: AbbVie Inc.
role: STUDY_DIRECTOR
References:
citation: Burmester GR, Kremer JM, Van den Bosch F, Kivitz A, Bessette L, Li Y, Zhou Y, Othman AA, Pangan AL, Camp HS. Safety and efficacy of upadacitinib in patients with rheumatoid arthritis and inadequate response to conventional synthetic disease-modifying anti-rheumatic drugs (SELECT-NEXT): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2018 Jun 23;391(10139):2503-2512. doi: 10.1016/S0140-6736(18)31115-2. Epub 2018 Jun 18.
citation: Bergman M, Buch MH, Tanaka Y, Citera G, Bahlas S, Wong E, Song Y, Zueger P, Ali M, Strand V. Routine Assessment of Patient Index Data 3 (RAPID3) in Patients with Rheumatoid Arthritis Treated with Long-Term Upadacitinib Therapy in Five Randomized Controlled Trials. Rheumatol Ther. 2022 Dec;9(6):1517-1529. doi: 10.1007/s40744-022-00483-4. Epub 2022 Sep 20.
citation: Bergman M, Tundia N, Yang M, Orvis E, Clewell J, Bensimon A. Economic Benefit from Improvements in Quality of Life with Upadacitinib: Comparisons with Tofacitinib and Methotrexate in Patients with Rheumatoid Arthritis. Adv Ther. 2021 Dec;38(12):5649-5661. doi: 10.1007/s12325-021-01930-4. Epub 2021 Oct 12.
citation: Yamaoka K, Tanaka Y, Kameda H, Khan N, Sasaki N, Harigai M, Song Y, Zhang Y, Takeuchi T. The Safety Profile of Upadacitinib in Patients with Rheumatoid Arthritis in Japan. Drug Saf. 2021 Jun;44(6):711-722. doi: 10.1007/s40264-021-01067-x. Epub 2021 May 27.
citation: Cohen SB, van Vollenhoven RF, Winthrop KL, Zerbini CAF, Tanaka Y, Bessette L, Zhang Y, Khan N, Hendrickson B, Enejosa JV, Burmester GR. Safety profile of upadacitinib in rheumatoid arthritis: integrated analysis from the SELECT phase III clinical programme. Ann Rheum Dis. 2021 Mar;80(3):304-311. doi: 10.1136/annrheumdis-2020-218510. Epub 2020 Oct 28.
citation: Strand V, Pope J, Tundia N, Friedman A, Camp HS, Pangan A, Ganguli A, Fuldeore M, Goldschmidt D, Schiff M. Upadacitinib improves patient-reported outcomes in patients with rheumatoid arthritis and inadequate response to conventional synthetic disease-modifying antirheumatic drugs: results from SELECT-NEXT. Arthritis Res Ther. 2019 Dec 9;21(1):272. doi: 10.1186/s13075-019-2037-1.
citation: Nader A, Mohamed MF, Winzenborg I, Doelger E, Noertersheuser P, Pangan AL, Othman AA. Exposure-Response Analyses of Upadacitinib Efficacy and Safety in Phase II and III Studies to Support Benefit-Risk Assessment in Rheumatoid Arthritis. Clin Pharmacol Ther. 2020 Apr;107(4):994-1003. doi: 10.1002/cpt.1671. Epub 2019 Nov 30.