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American College of Rheumatology White Paper on Antimalarial Cardiac Toxicity
Julianna Desmarais,James T. Rosenbaum,Karen H. Costenbader,Ellen M. Ginzler,Nicole Fett,Susan Goodman,James O’Dell,Christian A. Pineau,Gabriela Schmajuk,Victoria P. Werth,Mark S. Link,Richard Kovacs
doi : 10.1002/art.41934
Volume 73, Issue 12 p. 2151-2160
Hydroxychloroquine (HCQ) and chloroquine (CQ) are well-established medications used in treating systemic lupus erythematosus and rheumatoid arthritis, as well as skin conditions such as cutaneous lupus erythematosus. In rare cases, arrhythmias and conduction system abnormalities, as well as cardiomyopathy, have been reported in association with HCQ/CQ use. Recently, however, the corrected QT interval (QTc)–prolonging potential of these medications, and risk of torsade de pointes (TdP) in particular, have been highlighted in the setting of their experimental use for COVID-19 infection. This report was undertaken to summarize the current understanding of HCQ/CQ cardiac toxicity, describe QTc prolongation and TdP risks, and discuss areas of priority for future research. A working group of experts across rheumatology, cardiology, and dermatology performed a nonsystematic literature review and offered a consensus-based expert opinion. Current data clearly indicate that HCQ and CQ are invaluable medications in the management of rheumatic and dermatologic diseases, but they are associated with QTc prolongation by directly affecting cardiac repolarization. Prescribing clinicians should be cognizant of this small effect, especially in patients taking additional medications that prolong the QTc interval. Long-term use of HCQ/CQ may lead to a cardiomyopathy associated with arrhythmias and heart failure. Risk and benefit assessment should be considered prior to initiation of any medication, and both initial and ongoing risk–benefit assessments are important with regard to prescription of HCQ/CQ. While cardiac toxicity related to HCQ/CQ treatment of rheumatic diseases is rarely reported, it can be fatal. Awareness of the potential adverse cardiac effects of HCQ and CQ can increase the safe use of these medications. There is a clear need for additional research to allow better understanding of the cardiovascular risk and safety profile of these therapies used in the management of rheumatic and cutaneous diseases.
Where There’s Smoke, There’s a Joint: Passive Smoking and Rheumatoid Arthritis
Milena A. Gianfrancesco,Cynthia S. Crowson
doi : 10.1002/art.41940
Volume 73, Issue 12 p. 2161-2162
Targeting the Myddosome in Systemic Autoimmunity: Ready for Prime Time?
Mariana J. Kaplan
doi : 10.1002/art.41951
Volume 73, Issue 12 p. 2163-2165
A Decade of JAK Inhibitors: What Have We Learned and What May Be the Future?
Christine Liu BS,Jacqueline Kieltyka BS,Roy Fleischmann MD,Massimo Gadina PhD,John J. O’Shea MD
doi : 10.1002/art.41906
Volume 73, Issue 12 p. 2166-2178
The discovery of cytokines and their role in immune and inflammatory disease led to the development of a plethora of targeted biologic therapies. Later, efforts to understand mechanisms of cytokine signal transduction led to the discovery of JAKs, which themselves were quickly identified as therapeutic targets. It has been a decade since the first JAK inhibitors (jakinibs) were approved, and there are now 9 jakinibs approved for the treatment of rheumatic, dermatologic, hematologic, and gastrointestinal indications, along with emergency authorization for COVID-19. In this review, we will summarize relevant discoveries that led to first-generation jakinibs and review their efficacy and safety as demonstrated in pivotal clinical studies. We will discuss the next generation of more selective jakinibs, along with agents that target kinase families beyond JAKs. Finally, we will reflect on both the opportunities and challenges ahead as we enter the second decade of the clinical use of jakinibs.
Risk of COVID-19 in Rheumatoid Arthritis: A National Veterans Affairs Matched Cohort Study in At-Risk Individuals
Bryant R. England,Punyasha Roul,Yangyuna Yang,Andre C. Kalil,Kaleb Michaud,Geoffrey M. Thiele,Brian C. Sauer,Joshua F. Baker,Ted R. Mikuls
doi : 10.1002/art.41800
Volume 73, Issue 12 p. 2179-2188
Rheumatoid arthritis (RA) and its treatments are associated with an increased risk of infection, but it remains unclear whether these factors have an impact on the risk or severity of COVID-19. The present study was undertaken to assess the risk and severity of COVID-19 in a US Department of Veterans Affairs (VA) cohort of patients with RA and those without RA.
Leukocytoclastic Vasculitis After Vaccination With a SARS-CoV-2 Vaccine
Anne Erler,John Fiedler,Anna Koch,Frank Heldmann,Alexander Schütz
doi : 10.1002/art.41910
Volume 73, Issue 12 p. 2188-2188
Incident Rheumatoid Arthritis in HIV Infection: Epidemiology and Treatment
Jennifer S. Hanberg,Evelyn Hsieh,Kathleen M. Akgün,Erica Weinstein,Liana Fraenkel,Amy C. Justice,the VACS Project Team
doi : 10.1002/art.41802
Volume 73, Issue 12 p. 2189-2199
To assess the incidence, presentation, and management of rheumatoid arthritis (RA) in patients with HIV, including the use of disease-modifying antirheumatic drugs (DMARDs) in this immunosuppressed population.
Identification of Novel, Immunogenic HLA–DR-Presented Prevotella copri Peptides in Patients With Rheumatoid Arthritis
Annalisa Pianta,Geena Chiumento,Kristina Ramsden,Qi Wang,Klemen Strle,Sheila Arvikar,Catherine E. Costello,Allen C. Steere
doi : 10.1002/art.41807
Volume 73, Issue 12 p. 2200-2205
We previously identified HLA–DR-presented epitopes from a 27-kd protein of Prevotella copri (Pc) obtained from peripheral blood mononuclear cells (PBMCs) from 1 rheumatoid arthritis (RA) patient. Herein, we sought to identify other HLA–DR-presented Pc peptides and source proteins in PBMCs from additional patients to better understand Pc immune responses and RA disease pathogenesis.
The Interleukin-1 Receptor–Associated Kinase 4 Inhibitor PF-06650833 Blocks Inflammation in Preclinical Models of Rheumatic Disease and in Humans Enrolled in a Randomized Clinical Trial
Aaron Winkler,Weiyong Sun,Saurav De,Aiping Jiao,M. Nusrat Sharif,Peter T. Symanowicz,Shruti Athale,Julia H. Shin,Ju Wang,Bruce A. Jacobson,Simeon J. Ramsey,Ken Dower,Tatyana Andreyeva,Heng Liu,Martin Hegen,Bruce L. Homer,Joanne Brodfuehrer,Mera Tilley,Steven A. Gilbert,Spencer I. Danto,Jean J. Beebe,Betsy J. Barnes,Virginia Pascual,Lih-Ling Lin,Iain Kilty,Margaret Fleming,Vikram R. Rao
doi : 10.1002/art.41953
Volume 73, Issue 12 p. 2206-2218
To investigate the role of PF-06650833, a highly potent and selective small-molecule inhibitor of interleukin-1–associated kinase 4 (IRAK4), in autoimmune pathophysiology in vitro, in vivo, and in the clinical setting.
Passive Smoking Throughout the Life Course and the Risk of Incident Rheumatoid Arthritis in Adulthood Among Women
Kazuki Yoshida,Jiaqi Wang,Susan Malspeis,Nathalie Marchand,Bing Lu,Lauren C. Prisco,Lily W. Martin,Julia A. Ford,Karen H. Costenbader,Elizabeth W. Karlson,Jeffrey A. Sparks
doi : 10.1002/art.41939
Volume 73, Issue 12 p. 2219-2228
To investigate passive smoking throughout the life course and the risk of rheumatoid arthritis (RA), while accounting for personal smoking.
Prediction of the Progression of Undifferentiated Arthritis to Rheumatoid Arthritis Using DNA Methylation Profiling
Carlos de la Calle-Fabregat,Ellis Niemantsverdriet,Juan D. Cañete,Tianlu Li,Annette H. M. van der Helm-van Mil,Javier Rodríguez-Ubreva,Esteban Ballestar
doi : 10.1002/art.41885
Volume 73, Issue 12 p. 2229-2239
The term “undifferentiated arthritis (UA)” is used to refer to all cases of arthritis that do not fit a specific diagnosis. A significant percentage of UA patients progress to rheumatoid arthritis (RA), others to a different definite rheumatic disease, and the rest undergo spontaneous remission. Therapeutic intervention in patients with UA can delay or halt disease progression and its long-term consequences. It is therefore of inherent interest to identify those UA patients with a high probability of progressing to RA who would benefit from early appropriate therapy. This study was undertaken to investigate whether alterations in the DNA methylation profiles of immune cells may provide information on the genetically or environmentally determined status of patients and potentially discriminate between disease subtypes.
Cerebral Autosomal-Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy Syndrome, a Central Nervous System Vasculitis Mimic
Mithu Maheswaranathan,Anne F. Buckley,Andrew B. Cutler,Lisa Criscione-Schreiber,Ankoor Shah
doi : 10.1002/art.41922
Volume 73, Issue 12 p. 2239-2239
Subchondral Bone Length in Knee Osteoarthritis: A Deep Learning–Derived Imaging Measure and Its Association With Radiographic and Clinical Outcomes
Gary H. Chang,Lisa K. Park,Nina A. Le,Ray S. Jhun,Tejus Surendran,Joseph Lai,Hojoon Seo,Nuwapa Promchotichai,Grace Yoon,Jonathan Scalera,Terence D. Capellini,David T. Felson,Vijaya B. Kolachalama
doi : 10.1002/art.41808
Volume 73, Issue 12 p. 2240-2248
To develop a bone shape measure that reflects the extent of cartilage loss and bone flattening in knee osteoarthritis (OA) and test it against estimates of disease severity.
Amelioration of Posttraumatic Osteoarthritis in Mice Using Intraarticular Silencing of Periostin via Nanoparticle-Based Small Interfering RNA
Xin Duan,Lei Cai,Christine T. N. Pham,Yousef Abu-Amer,Hua Pan,Robert H. Brophy,Samuel A. Wickline,Muhammad Farooq Rai
doi : 10.1002/art.41794
Volume 73, Issue 12 p. 2249-2260
Recent evidence delineates an emerging role of periostin in osteoarthritis (OA), since its expression after knee injury is detrimental to the articular cartilage. We undertook this study to examine whether intraarticular (IA) knockdown of periostin would ameliorate posttraumatic OA in a murine model.
Osteoarthritis Care and Risk of Total Knee Arthroplasty Among Medicare Beneficiaries: A Population-Based Study of Regional Covariation
Michael M. Ward
doi : 10.1002/art.41878
Volume 73, Issue 12 p. 2261-2270
To examine health care utilization among patients with knee osteoarthritis (OA) and assess whether utilization differs among residents of regions with high and low rates of total knee arthroplasty (TKA).
Targeting the CCR6/CCL20 Axis in Entheseal and Cutaneous Inflammation
Zhenrui Shi,Emma Garcia-Melchor,Xuesong Wu,Anthony E. Getschman,Mimi Nguyen,Douglas J. Rowland,Machelle Wilson,Flavia Sunzini,Moeed Akbar,Mindy Huynh,Timothy Law,Smriti K. Raychaudhuri,Siba P. Raychaudhuri,Brian F. Volkman,Neal L. Millar,Sam T. Hwang
doi : 10.1002/art.41882
Volume 73, Issue 12 p. 2271-2281
To assess the involvement of the CCR6/CCL20 axis in psoriatic arthritis (PsA) and psoriasis (PsO) and to evaluate its potential as a therapeutic target.
RNA Externalized by Neutrophil Extracellular Traps Promotes Inflammatory Pathways in Endothelial Cells
Luz P. Blanco,Xinghao Wang,Philip M. Carlucci,Jose Jiram Torres-Ruiz,Jorge Romo-Tena,Hong-Wei Sun,Markus Hafner,Mariana J. Kaplan
doi : 10.1002/art.41796
Volume 73, Issue 12 p. 2282-2292
Neutrophil extracellular traps (NETs) are extracellular lattices composed of nucleic material bound to neutrophil granule proteins. NETs may play pathogenic roles in the development and severity of autoimmune diseases such as systemic lupus erythematosus (SLE), at least in part, through induction of type I interferon (IFN) responses via externalization of oxidized immunostimulatory DNA. A distinct subset of SLE proinflammatory neutrophils (low-density granulocytes [LDGs]) displays enhanced ability to form proinflammatory NETs that damage the vasculature. We undertook this study to assess whether NET-bound RNA can contribute to inflammatory responses in endothelial cells (ECs) and the pathways that mediate this effect.
Neuropsychiatric Events in Systemic Lupus Erythematosus: Predictors of Occurrence and Resolution in a Longitudinal Analysis of an International Inception Cohort
John G. Hanly,Caroline Gordon,Sang-Cheol Bae,Juanita Romero-Diaz,Jorge Sanchez-Guerrero,Sasha Bernatsky,Ann E. Clarke,Daniel J. Wallace,David A. Isenberg,Anisur Rahman,Joan T. Merrill,Paul R. Fortin,Dafna D. Gladman,Murray B. Urowitz,Ian N. Bruce,Michelle Petri,Ellen M. Ginzler,M. A. Dooley,Rosalind Ramsey-Goldman,Susan Manzi,Andreas Jonsen,Graciela S. Alarcón,Ronald F. van Vollenhoven,Cynthia Aranow,Meggan Mackay,Guillermo Ruiz-Irastorza,S. Sam Lim,Murat Inanc,Kenneth C. Kalunian,Soren Jacobsen,Christine A. Peschken,Diane L. Kamen,Anca Askanase,Vernon Farewell
doi : 10.1002/art.41876
Volume 73, Issue 12 p. 2293-2302
To determine predictors of change in neuropsychiatric (NP) event status in a large, prospective, international inception cohort of patients with systemic lupus erythematosus (SLE).
Lupus Susceptibility Region Containing CDKN1B rs34330 Mechanistically Influences Expression and Function of Multiple Target Genes, Also Linked to Proliferation and Apoptosis
Bhupinder Singh,Guru P. Maiti,Xujie Zhou,Mehdi Fazel-Najafabadi,Sang-Cheol Bae,Celi Sun,Chikashi Terao,Yukinori Okada,Kek Heng Chua,Yuta Kochi,Joel M. Guthridge,Hong Zhang,Matthew Weirauch,Judith A. James,John B. Harley,Gaurav K. Varshney,Loren L. Looger,Swapan K. Nath
doi : 10.1002/art.41799
Volume 73, Issue 12 p. 2303-2313
In a recent genome-wide association study, a significant genetic association between rs34330 of CDKN1B and risk of systemic lupus erythematosus (SLE) in Han Chinese was identified. This study was undertaken to validate the reported association and elucidate the biochemical mechanisms underlying the effect of the variant.
Inositol-Requiring Enzyme 1?–Mediated Synthesis of Monounsaturated Fatty Acids as a Driver of B Cell Differentiation and Lupus-like Autoimmune Disease
Yana Zhang,Ming Gui,Yajun Wang,Nikita Mani,Shuvam Chaudhuri,Beixue Gao,Huabin Li,Yashpal S. Kanwar,Sarah A. Lewis,Sabrina N. Dumas,James M. Ntambi,Kezhong Zhang,Deyu Fang
doi : 10.1002/art.41883
Volume 73, Issue 12 p. 2314-2326
To explore the molecular mechanisms underlying dysregulation of lipid metabolism in the pathogenesis of systemic lupus erythematosus (SLE).
A Distinct Macrophage Subset Mediating Tissue Destruction and Neovascularization in Giant Cell Arteritis: Implication of the YKL-40/Interleukin-13 Receptor ?2 Axis
Yannick van Sleen,William F. Jiemy,Sarah Pringle,Kornelis S. M. van der Geest,Wayel H. Abdulahad,Maria Sandovici,Elisabeth Brouwer,Peter Heeringa,Annemieke M. H. Boots
doi : 10.1002/art.41887
Volume 73, Issue 12 p. 2327-2337
Macrophages mediate inflammation, angiogenesis, and tissue destruction in giant cell arteritis (GCA). Serum levels of the macrophage-associated protein YKL-40 (chitinase 3–like protein 1), previously linked to angiogenesis and tissue remodeling, remain elevated in GCA despite glucocorticoid treatment. This study was undertaken to investigate the contribution of YKL-40 to vasculopathy in GCA.
Anticentromere Antibody Levels and Isotypes and the Development of Systemic Sclerosis
Nina M. van Leeuwen,Maaike Boonstra,Jaap A. Bakker,Annette Grummels,Suzana Jordan,Sophie Liem,Oliver Distler,Anna-Maria Hoffmann-Vold,Karin Melsens,Vanessa Smith,Marie-Elise Truchetet,Hans U. Scherer,René Toes,Tom W. J. Huizinga,Jeska K. de Vries-Bouwstra
doi : 10.1002/art.41814
Volume 73, Issue 12 p. 2338-2347
Little is known on the disease course of very early systemic sclerosis (SSc). Among the information yet to be elucidated is whether anticentromere antibody (ACA) isotype levels can serve as biomarkers for future SSc development and for organ involvement. This study was undertaken to evaluate whether IgG, IgM, and IgA ACA levels in IgG ACA–positive patients are associated with disease severity and/or progression from very early SSc to definite SSc.
Addressing Immeasurable Time Bias in an Observational Study: Comment on the Article by Suissa et al
Alanna Weisman,Gillian A. Hawker,George A. Tomlinson
doi : 10.1002/art.41886
Volume 73, Issue 12 p. 2348-2349
Reply
Samy Suissa,Karine Suissa,Marie Hudson
doi : 10.1002/art.41884
Volume 73, Issue 12 p. 2349-2349
Hypoxia-Induced Synovial Fibroblast Activation in Inflammatory Arthritis and the Role of Notch-1 and Notch-3 Signaling: Comment on the Article by Chen et al
Wang-Dong Xu,An-Fang Huang
doi : 10.1002/art.41909
Volume 73, Issue 12 p. 2349-2350
Reply
Jianhai Chen,Antonia Sun,Jian Li,Wenxiang Cheng,Peng Zhang
doi : 10.1002/art.41904
Volume 73, Issue 12 p. 2350-2351
Disease Activity Assessment in Nonradiographic Axial Spondyloarthritis: Is It Time to Move Beyond the Bath Ankylosing Spondylitis Disease Activity Index or Ankylosing Spondylitis Disease Activity Score? Comment on the Article by Rusman et al
Debashish Mishra,B. V. Harish,Sudhish Gadde,Pradeepta S. Patro
doi : 10.1002/art.41905
Volume 73, Issue 12 p. 2351-2352
Reply
Tamara Rusman,Mignon A. C. van der Weijden,Michael T. Nurmohamed,Carmella M. A. van der Bijl,Conny J. van der Laken,Pierre M. Bet,Robert B. M. Landewé,Janneke J. H. de Winter,Bouke J. H. Boden,Irene E. van der Horst-Bruinsma
doi : 10.1002/art.41908
Volume 73, Issue 12 p. 2352-2353
Clinical and Methodologic Considerations With Regard to a Trial of Nintedanib in Patients With Systemic Sclerosis-Associated Interstitial Lung Disease: Comment on the Reanalysis by Maher et al
Markus Bredemeier
doi : 10.1002/art.41893
Volume 73, Issue 12 p. 2353-2354
Reply
Toby M. Maher,Maureen D. Mayes,Christian Stock,Margarida Alves
doi : 10.1002/art.41895
Volume 73, Issue 12 p. 2354-2355
Suggested Considerations for the Treatment of Rheumatic Diseases in Adult Patients With COVID-19: Comment on the Article by Mikuls et al
Jeffrey Hsu,Chin-Hsiu Liu,James C. Wei
doi : 10.1002/art.41889
Volume 73, Issue 12 p. 2355-2355
Incorrect Frequency of Belimumab Infusions Reported in the Article by Atisha-Fregoso et al (Arthritis Rheumatol, January 2021)
doi : 10.1002/art.42019
Volume 73, Issue 12 p. 2356-2356
