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Global Rheumatology Research: Frontiers, Challenges, and Opportunities
Joshua B. Bilsborrow,Ingris Peláez-Ballestas,Bernardo Pons-Estel,Christiaan Scott,Xinping Tian,Graciela S. Alarcon,Richard Bucala,Laura B. Lewandowski,Evelyn Hsieh
doi : 10.1002/art.41980
Volume 74, Issue 1 p. 1-4
Reexamining Remission Definitions in Rheumatoid Arthritis: Considering the Twenty-Eight–Joint Disease Activity Score, C-Reactive Protein Level, and Patient Global Assessment
David T. Felson,Diane Lacaille,Michael P. LaValley,Daniel Aletaha
doi : 10.1002/art.41959
Volume 74, Issue 1 p. 5-9
Lung Inflammation, NETosis, and the Pulmonary Initiation of Anti–Citrullinated Protein Antibody Response: What Came First, the Chicken or the Egg?
Jeremy Sokolove
doi : 10.1002/art.41947
Volume 74, Issue 1 p. 10-12
Systemic Sclerosis–Associated Interstitial Lung Disease: How to Incorporate Two Food and Drug Administration–Approved Therapies in Clinical Practice
Dinesh Khanna,Alain Lescoat,David Roofeh,Elana J. Bernstein,Ella A. Kazerooni,Michael D. Roth,Fernando Martinez,Kevin R. Flaherty,Christopher P. Denton
doi : 10.1002/art.41933
Volume 74, Issue 1 p. 13-27
Systemic sclerosis (SSc; scleroderma) has the highest individual mortality of all rheumatic diseases, and interstitial lung disease (ILD) is among the leading causes of SSc-related death. Two drugs are now approved by the US Food and Drug Administration (FDA) and indicated for slowing the rate of decline in pulmonary function in patients with SSc-associated ILD (SSc-ILD): nintedanib (a tyrosine kinase inhibitor) and tocilizumab (the first biologic agent targeting the interleukin-6 pathway in SSc). In addition, 2 generic drugs with cytotoxic and immunoregulatory activity, mycophenolate mofetil and cyclophosphamide, have shown comparable efficacy in a phase II trial but are not FDA-approved for SSc-ILD. In light of the heterogeneity of the disease, the optimal therapeutic strategy for the management of SSc-ILD is still to be determined. The objectives of this review are 2-fold: 1) review the body of research focused on the diagnosis and treatment of SSc-ILD; and 2) propose a practical approach for diagnosis, stratification, management, and therapeutic decision-making in this clinical context. This review presents a practical classification of SSc patients in terms of disease severity (subclinical versus clinical ILD) and associated risk of progression (low versus high risk). The pharmacologic and nonpharmacologic options for first- and second-line therapy, as well as potential combination approaches, are discussed in light of the recent approval of tocilizumab for SSc-ILD.
Disease Flare and Reactogenicity in Patients With Rheumatic and Musculoskeletal Diseases Following Two-Dose SARS–CoV-2 Messenger RNA Vaccination
Caoilfhionn M. Connolly,Jake A. Ruddy,Brian J. Boyarsky,Iulia Barbur,William A. Werbel,Duvuru Geetha,Jacqueline M. Garonzik-Wang,Dorry L. Segev,Lisa Christopher-Stine,Julie J. Paik
doi : 10.1002/art.41924
Volume 74, Issue 1 p. 28-32
To evaluate disease flare and postvaccination reactions (reactogenicity) in patients with rheumatic and musculoskeletal diseases (RMDs) following 2-dose SARS–CoV-2 messenger RNA (mRNA) vaccination.
Humoral and Cellular Immune Responses to SARS–CoV-2 Infection and Vaccination in Autoimmune Disease Patients With B Cell Depletion
David Simon,Koray Tascilar,Katja Schmidt,Bernhard Manger,Leonie Weckwerth,Maria Sokolova,Laura Bucci,Filippo Fagni,Karin Manger,Florian Schuch,Monika Ronneberger,Axel Hueber,Ulrike Steffen,Dirk Mielenz,Martin Herrmann,Thomas Harrer,Arnd Kleyer,Gerhard Krönke,Georg Schett
doi : 10.1002/art.41914
Volume 74, Issue 1 p. 33-37
B cell depletion is an established therapeutic principle in a wide range of autoimmune diseases. However, B cells are also critical for inducing protective immunity after infection and vaccination. We undertook this study to assess humoral and cellular immune responses after infection with or vaccination against SARS–CoV-2 in patients with B cell depletion and controls who are B cell–competent.
Association of Sputum Neutrophil Extracellular Trap Subsets With IgA Anti–Citrullinated Protein Antibodies in Subjects at Risk for Rheumatoid Arthritis
Yuko Okamoto,Stephanie Devoe,Nickie Seto,Valerie Minarchick,Timothy Wilson,Heather M. Rothfuss,Michael P. Mohning,Jaron Arbet,Miranda Kroehl,Ashley Visser,Justin August,Stacey M. Thomas,Laura Lenis Charry,Chelsie Fleischer,Marie L. Feser,Ashley A. Frazer-Abel,Jill M. Norris,Brian D. Cherrington,William J. Janssen,Mariana J. Kaplan,Kevin D. Deane,V. Michael Holers,M. Kristen Demoruelle
doi : 10.1002/art.41948
Volume 74, Issue 1 p. 38-48
Mechanisms leading to anti–citrullinated protein antibody (ACPA) generation in rheumatoid arthritis (RA) are hypothesized to originate in the lung. We undertook this study to understand associations between neutrophil extracellular trap (NET) formation in the lung and local ACPA generation in subjects at risk of developing RA.
Role of Ciliary Protein Intraflagellar Transport Protein 88 in the Regulation of Cartilage Thickness and Osteoarthritis Development in Mice
Clarissa R. Coveney,Linyi Zhu,Jadwiga Miotla-Zarebska,Bryony Stott,Ida Parisi,Vicky Batchelor,Claudia Duarte,Emer Chang,Eleanor McSorley,Tonia L. Vincent,Angus K. T. Wann
doi : 10.1002/art.41894
Volume 74, Issue 1 p. 49-59
Mechanical and biologic cues drive cellular signaling in cartilage development, health, and disease. Primary cilia proteins, which are implicated in the transduction of biologic and physiochemical signals, control cartilage formation during skeletal development. This study was undertaken to assess the influence of the ciliary protein intraflagellar transport protein 88 (IFT88) on postnatal cartilage from mice with conditional knockout of the Ift88 gene (Ift88-KO).
Magnetic Resonance Imaging–Assessed Subchondral Cysts and Incident Knee Pain and Knee Osteoarthritis: Data From the Multicenter Osteoarthritis Study
Thomas A. Perry,Terence W. O'Neill,Irina Tolstykh,John Lynch,David T. Felson,Nigel K. Arden,Michael C. Nevitt
doi : 10.1002/art.41917
Volume 74, Issue 1 p. 60-69
To examine whether knee subchondral cysts, measured on magnetic resonance imaging (MRI), are associated with incident knee osteoarthritis (OA) outcomes.
Safety and Efficacy of Upadacitinib in Patients With Active Ankylosing Spondylitis and an Inadequate Response to Nonsteroidal Antiinflammatory Drug Therapy: One-Year Results of a Double-Blind, Placebo-Controlled Study and Open-Label Extension
Atul Deodhar,Désirée van der Heijde,Joachim Sieper,Filip Van den Bosch,Walter P. Maksymowych,Tae-Hwan Kim,Mitsumasa Kishimoto,Andrew Ostor,Bernard Combe,Yunxia Sui,Alvina D. Chu,In-Ho Song
doi : 10.1002/art.41911
Volume 74, Issue 1 p. 70-80
To report the efficacy and safety of upadacitinib through 1 year in patients with ankylosing spondylitis (AS).
Identification and Evaluation of Serum Protein Biomarkers That Differentiate Psoriatic Arthritis From Rheumatoid Arthritis
Angela Mc Ardle,Anna Kwasnik,Agnes Szentpetery,Belinda Hernandez,Andrew Parnell,Wilco de Jager,Sytze de Roock,Oliver FitzGerald,Stephen R. Pennington
doi : 10.1002/art.41899
Volume 74, Issue 1 p. 81-91
To identify serum protein biomarkers that might distinguish patients with early inflammatory arthritis (IA) with psoriatic arthritis (PsA) from those with rheumatoid arthritis (RA) and may be used to support appropriate early intervention.
Induction of Interferon-? and Tissue Inflammation by Overexpression of Eosinophil Cationic Protein in T Cells and Exosomes
Huai-Chia Chuang,Ming-Han Chen,Yi-Ming Chen,Yi-Ru Ciou,Chia-Hsin Hsueh,Ching-Yi Tsai,Tse-Hua Tan
doi : 10.1002/art.41920
Volume 74, Issue 1 p. 92-104
T cells play a critical role in the pathogenesis of systemic lupus erythematosus (SLE). Serum-derived exosomes are increased in SLE patients and are correlated with disease severity. This study was undertaken to investigate whether T cell–derived exosomal proteins play a role in SLE pathogenesis.
Anti–Double-Stranded DNA Antibodies Recognize DNA Presented on HLA Class II Molecules of Systemic Lupus Erythematosus Risk Alleles
Hideaki Tsuji,Koichiro Ohmura,Hui Jin,Ryota Naito,Noriko Arase,Masako Kohyama,Tadahiro Suenaga,Shuhei Sakakibara,Yuta Kochi,Yukinori Okada,Kazuhiko Yamamoto,Hitoshi Kikutani,Akio Morinobu,Tsuneyo Mimori,Hisashi Arase
doi : 10.1002/art.41897
Volume 74, Issue 1 p. 105-111
Specific HLA class II alleles are associated with susceptibility to systemic lupus erythematosus (SLE). The role of HLA class II molecules in SLE pathogenesis remains unclear, although anti-DNA antibodies are specific to SLE and correlate with disease activity. We previously demonstrated that misfolded proteins bound to HLA class II molecules are specific targets for the autoantibodies produced in autoimmune diseases. This study was undertaken to validate our hypothesis that DNA binds to HLA class II molecules in a manner similar to that of misfolded proteins and that DNA bound to HLA class II molecules is involved in SLE pathogenesis.
Phase III/IV, Randomized, Fifty-Two–Week Study of the Efficacy and Safety of Belimumab in Patients of Black African Ancestry With Systemic Lupus Erythematosus
Ellen Ginzler,Luiz Sergio Guedes Barbosa,David D'Cruz,Richard Furie,Kathleen Maksimowicz-McKinnon,James Oates,Mittermayer Barreto Santiago,Amit Saxena,Saira Sheikh,Damon L. Bass,Susan W. Burriss,Jennifer A. Gilbride,James G. Groark,Michelle Miller,Amy Pierce,David A. Roth,Beulah Ji
doi : 10.1002/art.41900
Volume 74, Issue 1 p. 112-123
Enrollment of patients of Black African ancestry with systemic lupus erythematosus (SLE) in phase II and phase III of the belimumab trials was not reflective of the racial distribution observed in the lupus population. This study was undertaken to assess the efficacy and safety of intravenous (IV) belimumab plus standard therapy in patients of self-identified Black race.
Phase IIa Global Study Evaluating Rituximab for the Treatment of Pediatric Patients With Granulomatosis With Polyangiitis or Microscopic Polyangiitis
Paul Brogan,Rae S. M. Yeung,Gavin Cleary,Satyapal Rangaraj,Ozgur Kasapcopur,Aimee O. Hersh,Suzanne Li,Dusan Paripovic,Kenneth Schikler,Andrew Zeft,Claudia Bracaglia,Despina Eleftheriou,Pooneh Pordeli,Simone Melega,Candice Jamois,Jacques Gaudreault,Margaret Michalska,Paul Brunetta,Jennifer C. Cooper,Patricia B. Lehane,the PePRS Study Group
doi : 10.1002/art.41901
Volume 74, Issue 1 p. 124-133
To assess the safety, tolerability, pharmacokinetics, and efficacy of rituximab (RTX) in pediatric patients with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA).
A Worldwide Pharmacoepidemiologic Update on Drug-Induced Antineutrophil Cytoplasmic Antibody–Associated Vasculitis in the Era of Targeted Therapies
Samuel Deshayes,Charles Dolladille,Anaël Dumont,Nicolas Martin Silva,Basile Chretien,Hubert De Boysson,Joachim Alexandre,Achille Aouba
doi : 10.1002/art.41902
Volume 74, Issue 1 p. 134-139
The literature supporting the role of a specific drug in the onset of drug-induced antineutrophil cytoplasmic antibody–associated vasculitis (AAV) mainly relies on case reports or short series and implicates old treatments. The advent of new treatments may have modified the epidemiology of these adverse drug reactions. This study was undertaken to update the list of drugs associated with AAV by using a pharmacovigilance-based data mining approach.
Time-Dependent Analysis of Risk of New-Onset Heart Failure Among Patients With Polymyositis and Dermatomyositis
Chun-Yu Lin,Hung-An Chen,Tsai-Ching Hsu,Chun-Hsin Wu,Yu-Jih Su,Chung-Yuan Hsu
doi : 10.1002/art.41907
Volume 74, Issue 1 p. 140-149
To determine the risk and time trends of heart failure (HF) leading to hospitalization in individuals newly diagnosed as having polymyositis/dermatomyositis (PM/DM) relative to non-PM/DM controls at the general population level.
Effect of Clonally Expanded PD-1highCXCR5–CD4+ Peripheral T Helper Cells on B Cell Differentiation in the Joints of Patients With Antinuclear Antibody–Positive Juvenile Idiopathic Arthritis
Jonas Fischer,Johannes Dirks,Julia Klaussner,Gabriele Haase,Annette Holl-Wieden,Christine Hofmann,Stephan Hackenberg,Hermann Girschick,Henner Morbach
doi : 10.1002/art.41913
Volume 74, Issue 1 p. 150-162
Antinuclear antibody (ANA)–positive juvenile idiopathic arthritis (JIA) is characterized by synovial B cell hyperactivity, but the precise role of CD4+ T cells in promoting local B cell activation is unknown. This study was undertaken to determine the phenotype and function of synovial CD4+ T cells that promote aberrant B cell activation in JIA.
Variants on the UBE2L3/YDJC Autoimmune Disease Risk Haplotype Increase UBE2L3 Expression by Modulating CCCTC-Binding Factor and YY1 Binding
Jaanam Gopalakrishnan,Kandice L. Tessneer,Yao Fu,Satish Pasula,Richard C. Pelikan,Jennifer A. Kelly,Graham B. Wiley,Patrick M. Gaffney
doi : 10.1002/art.41925
Volume 74, Issue 1 p. 163-173
Genetic variants spanning UBE2L3 are associated with increased expression of the UBE2L3-encoded E2 ubiquitin-conjugating enzyme H7 (UbcH7), which facilitates activation of proinflammatory NF-?B signaling and susceptibility to autoimmune diseases. We undertook this study to delineate how genetic variants carried on the UBE2L3/YDJC autoimmune risk haplotype function to drive hypermorphic UBE2L3 expression.
Hypogammaglobulinemia in rheumatoid arthritis patients treated with rituximab: should we switch biologics? Comment on the article by Fraenkel et al
Gerasimos Evangelatos,Melina Moschopoulou,Alexios Iliopoulos,George E. Fragoulis
doi : 10.1002/art.41938
Volume 74, Issue 1 p. 174-175
Reply
Liana Fraenkel,Joan M. Bathon,Bryant R. England,E. William St.Clair,Elie A. Akl,On behalf of the ACR RA guideline author group
doi : 10.1002/art.41942
Volume 74, Issue 1 p. 175-175
Importance of internal and external validity in clinical research: comment on the article by Fatima et al
Yusuke Matsuo,Yoshie Yamada,Jun Miyata,Tetsuro Aita,Takashi Yoshioka
doi : 10.1002/art.41919
Volume 74, Issue 1 p. 175-176
Considerations for a study using the Health Assessment Questionnaire to predict all-cause mortality in early rheumatoid arthritis: comment on the article by Fatima et al
Po-Yun Ko,Da-Ming Yeh,James Cheng-Chung Wei
doi : 10.1002/art.41916
Volume 74, Issue 1 p. 176-177
Functional capacity at 1 year predicts all-cause mortality in patients with rheumatoid arthritis: comment on the article by Fatima et al
Richard K. Jacoby,Johannes J. Rasker
doi : 10.1002/art.41915
Volume 74, Issue 1 p. 177-178
Reply
Safoora Fatima,O. Schieir,E. C. Keystone,M. F. Valois,S. J. Bartlett,L. Bessette,G. Boire,G. Hazlewood,C. Hitchon,D. Tin,C. Thorne,V. P. Bykerk,J. E. Pope,on behalf of the CATCH Investigators
doi : 10.1002/art.41918
Volume 74, Issue 1 p. 178-180
