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JOURNAL ARTICLE
Jonathan Kay, Nikolay P Nikolov, Michael H Weisman
On May 17-18, 2022, the ACR and the FDA co-sponsored a public meeting to address topics of mutual interest and importance in assessing long-term safety and clinical efficacy, as well as novel approaches to clinical trials in rheumatoid arthritis (RA) and psoriatic arthritis (PsA). During the two-day consensus-building summit, rheumatologists, other health care professionals, and FDA staff provided a broad perspective on current clinical development challenges and potential approaches to address them. Key takeaways are summarized in this document, including issues related to innovative clinical trial designs, use of novel outcome measures such as magnetic resonance imaging (MRI) and patient-reported outcomes (PROs), and use of innovative approaches to collecting data including registries and digital health technology (DHT)...
April 15, 2024: Arthritis & Rheumatology
#2
REVIEW
David S Pisetsky
Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease that primarily affects young women and causes a wide range of inflammatory manifestations. The hallmark of SLE is the production of antibodies to components of the cell nucleus (antinuclear antibodies or ANAs). These antibodies can bind to DNA, RNA and protein complexes with nucleic acids. Among ANAs, antibodies to DNA (anti-DNA) are markers for classification and disease activity, waxing and waning in many patients. In the blood, anti-DNA antibodies can bind DNA to form immune complexes with two distinct roles in pathogenesis: renal deposition to provoke nephritis and stimulation of cytokine production following uptake into innate immune cells and interaction with internal nucleic acid sensors...
April 15, 2024: Arthritis & Rheumatology
#3
JOURNAL ARTICLE
Yuzhou Gan, Haotian Zhou, Yixue Guo, Bo Huang, Hongjiang Liu, Ziye Wang, Zijun Li, Xiaozhen Zhao, Huaqun Zhu, Qimao Han, Hua Ye, Jing He, Qingwen Wang, Zhanguo Li, Xiaolin Sun
OBJECTIVES: Glucocorticoid-induced Tumor-Necrosis-Factor-Receptor Family-related Protein (GITR), with its ligand (GITRL), plays an important role in CD4+ T-cell-mediated autoimmunity. This study aimed to investigate the underlying mechanisms of GITRL in primary Sjögren's Syndrome (pSS). METHODS: pSS patients and healthy controls were recruited. Serum GITRL and Th17-related cytokines were determinated. RNA-Sequencing was performed to decipher key signal pathways...
April 8, 2024: Arthritis & Rheumatology
#4
JOURNAL ARTICLE
Erika Sa Egal, Severin Donald Kamdem, Masaaki Yoshigi, Ching-Chu Yang, Sarah Pellizzari, Ernest M Kameni, My N Helms, Shervin Assassi, Mark Henkemeyer, Tracy M Frech, Patrice N Mimche
OBJECTIVES: Eph/Ephrin cell-cell signaling is emerging as a key player in tissue fibrogenesis. The aim of this study was to test the hypothesis that the receptor tyrosine kinase EphB2 mediates dermal fibrosis in systemic sclerosis (SSc). METHODS: We assessed normal and SSc human skin biopsies for EphB2 expression. The in vivo role of EphB2 in skin fibrosis was investigated by subjecting Ephb2-knockout mice to both bleomycin-induced and tight skin (Tsk1/+) genetic mouse models of skin fibrosis...
April 8, 2024: Arthritis & Rheumatology
#5
JOURNAL ARTICLE
Daniel H Solomon, Mariana J Kaplan, Peter A Nigrovic, Richard Bucala
No abstract text is available yet for this article.
April 4, 2024: Arthritis & Rheumatology
#6
JOURNAL ARTICLE
Sarah McGrath, Kristoffer Grimstad, Katrin Thorarinsdottir, Kristina Forslind, Daniel Glinatsi, Monica Leu Agelii, Alaitz Aranburu, Timothy Sundell, Charlotte A Jonsson, Alessandro Camponeschi, Anna-Karin Hultgård Ekwall, Andreas Tilevik, Inger Gjertsson, Inga-Lill Mårtensson
OBJECTIVE: Subsets of CD21-/low memory B cells (MBCs), including double-negative (DN, CD27- IgD- ) and Tbet+ CD11c+ cells, are expanded in chronic inflammatory diseases. In rheumatoid arthritis (RA), CD21-/low MBCs correlate with joint destruction. However, whether this is due to the Tbet+ CD11c+ subset, its function and pathogenic contribution to RA are unknown. This study aims to investigate the association between CD21-/low Tbet+ CD11c+ MBCs and joint destruction as well as other clinical parameters and to elucidate their functional properties in untreated RA patients (uRA)...
April 3, 2024: Arthritis & Rheumatology
#7
JOURNAL ARTICLE
Sho Sendo, Camilla R L Machado, David L Boyle, Robert J Benschop, Narayanan B Perumal, Eunice Choi, Wei Wang, Gary S Firestein
OBJECTIVE: Fibroblast-like synoviocytes (FLS) contribute to the pathogenesis of rheumatoid arthritis (RA), in part due to activation of the pro-inflammatory transcription factor NF-κB. Neddylation is modulated by the negative regulator of ubiquitin-like proteins-1 (NUB1). We determined whether NUB1 and neddylation are aberrant in RA FLS thereby contributing to their aggressive phenotype. METHODS: RA or osteoarthritis (OA) FLS were obtained from arthroplasty synovia...
April 2, 2024: Arthritis & Rheumatology
#8
JOURNAL ARTICLE
Kate Gregory, Dylan Hansen, Ross Penglase, Diane Apostolopoulos, Gene-Siew Ngian, Wendy Stevens, Kathleen Morrisroe, Nava Ferdowsi, Laura Ross, Jennifer Walker, Helen Cooley, Peter Youssef, Kathleen Tymms, Lauren Host, Susanna Proudman, John Moore, Mandana Nikpour, Joanne Sahhar
OBJECTIVE: To determine the event-free survival of Australian patients with diffuse systemic sclerosis (dcSSc), who meet eligibility criteria for autologous stem cell transplant (ASCT) in previously published randomised controlled trials (RCTs), but were managed without ASCT. METHODS: Patients who met inclusion criteria for the ASTIS (Autologous Stem Cell Transplantation International Scleroderma)(1) and SCOT (Scleroderma: Cyclophosphamide Or Transplantation)(2) trials were identified from the multicentre Australian Scleroderma Cohort Study (ASCS)...
April 1, 2024: Arthritis & Rheumatology
#9
LETTER
Megan Kay Wood, Taejoon Won, Daniela Čiháková
No abstract text is available yet for this article.
April 1, 2024: Arthritis & Rheumatology
#10
LETTER
Wang-Dong Xu, An-Fang Huang
No abstract text is available yet for this article.
April 1, 2024: Arthritis & Rheumatology
#11
EDITORIAL
Dana Kidder, Neil Basu
No abstract text is available yet for this article.
March 31, 2024: Arthritis & Rheumatology
#12
JOURNAL ARTICLE
Xenofon Baraliakos, Mikkel Østergaard, Denis Poddubnyy, Désirée van der Heijde, Atul Deodhar, Pedro M Machado, Victoria Navarro-Compán, Kay Geert A Hermann, Mitsumasa Kishimoto, Eun Young Lee, Lianne S Gensler, Uta Kiltz, Marco F Eigenmann, Patricia Pertel, Aimee Readie, Hanno B Richards, Brian Porter, Juergen Braun
INTRODUCTION: Spinal radiographic progression is an important outcome in radiographic axial spondyloarthritis (r-axSpA). SURPASS is the first head-to-head phase IIIb study comparing such changes in patients with r-axSpA treated with secukinumab (IL-17A inhibitor) versus adalimumab biosimilar (Sandoz adalimumab [SDZ-ADL]; TNF inhibitor). METHODS: Biologic-naïve patients with active r-axSpA, at high risk of radiographic progression (high-sensitivity C-reactive protein [hsCRP] ≥5 mg/L and/or ≥1 syndesmophyte[s] on spinal radiographs) were randomized (1:1:1) to secukinumab (150/300 mg) or SDZ-ADL (40 mg)...
March 31, 2024: Arthritis & Rheumatology
#13
JOURNAL ARTICLE
Benjamin Van Espen, E Barton Prideaux, Andrew R Wilson, Camilla R L Machado, Sho Sendo, James Parker, Grégory Seumois, Cristiano Sacchetti, Anna C Belongia, Narayanan B Perumal, Pandurangan Vijayanand, Matthew D Linnik, Robert J Benschop, Wei Wang, Nunzio Bottini, Gary S Firestein, Stephanie M Stanford
OBJECTIVE: Rheumatoid arthritis (RA) is an autoimmune disease in which the joint lining, or synovium, becomes highly inflamed and majorly contributes to disease progression. Understanding pathogenic processes in RA synovium is critical for identifying therapeutic targets. We performed laser capture microscopy (LCM) followed by RNA sequencing (LCM-RNAseq) to study regional transcriptomes throughout RA synovium. METHODS: Synovial lining, sublining, and vessels were captured by LCM from seven RA and seven osteoarthritis (OA) patients...
March 31, 2024: Arthritis & Rheumatology
#14
JOURNAL ARTICLE
Jessica D Murillo-Saich, Roxana Coras, Julio Ramirez, Estefania Quesada-Masachs, Marta Sala-Climent, Katharina Eschelbach, Christopher B Mahony, Raquel Celis, Aaron Armando, Oswald Quehenberger, Adam P Croft, Arthur Kavanaugh, Eric Chang, Juan D Cañete, Abha Singh, Monica Guma
OBJECTIVE: Oxylipins are bioactive lipids derived from polyunsaturated fatty acids (PUFAs) that modulate inflammation and may remain overexpressed in refractory synovitis. In plasma, they could also be biomarkers of synovial pathology. The aim of this study is to determine if synovial oxylipins in inflamed joints correlate with plasma oxylipins and with synovial histological patterns. METHODS: Patients with established rheumatoid or psoriatic arthritis with active disease despite treatment were recruited and paired ST and plasma were collected...
March 20, 2024: Arthritis & Rheumatology
#15
REVIEW
Mary K Crow, Mikhail Olferiev, Kyriakos A Kirou
The discovery of interferon in the 1950s represents much more than the identification of the first cytokine and the key mediator of anti-viral host defense. Defining the molecular nature and complexity of the type I interferon family, as well as its inducers and molecular mechanisms of action, was the work of investigators working at the highest level and producing insights of great consequence. Current knowledge of receptor-ligand interactions, cell signaling, and transcriptional regulation derive from studies of type I interferon...
March 18, 2024: Arthritis & Rheumatology
#16
JOURNAL ARTICLE
Piero Ruscitti, Francesco Masedu, Antonio Vitale, Valeria Caggiano, Ilenia Di Cola, Paola Cipriani, Marco Valenti, Henrique A Mayrink Giardini, Isabele Parente de Brito Antonelli, Marilia Ambiel Dagostin, Giuseppe Lopalco, Florenzo Iannone, Morrone Maria, Ibrahim A Almaghlouth, Kazi Nur Asfina, Hebatallah Hamed Ali, Francesco Ciccia, Daniela Iacono, Ilenia Pantano, Daniele Mauro, Petros P Sfikakis, Maria Tektonidou, Katerina Laskari, Onorina Berardicurti, Lorenzo Dagna, Alessandro Tomelleri, Abdurrahman Tufan, Rıza Can Kardas, Andrea Hinojosa-Azaola, Eduardo Martín-Nares, Perla Ayumi Kawakami-Campos, Gaafar Ragab, Mohamed Tharwat Hegazy, Haner Direskeneli, Fatma Alibaz-Oner, Lampros Fotis, Paolo Sfriso, Marcello Govoni, Francesco La Torre, Maria Cristina Maggio, Carlomaurizio Montecucco, Ludovico De Stefano, Serena Bugatti, Silvia Rossi, Joanna Makowska, Emanuela Del Giudice, Giacomo Emmi, Elena Bartoloni, José Hernández-Rodríguez, Giovanni Conti, Alma Nunzia Olivieri, Alberto Lo Gullo, Gabriele Simonini, Ombretta Viapiana, Ewa Wiesik-Szewczyk, Sukran Erten, Francesco Carubbi, Amato De Paulis, Armin Maier, Samar Tharwat, Stefania Costi, Annamaria Iagnocco, Gian Domenico Sebastiani, Antonio Gidaro, Antonio Luca Brucato, Anastasios Karamanakos, Nurullah Akkoç, Francesco Caso, Luisa Costa, Marcella Prete, Federico Perosa, Fabiola Atzeni, Giuliana Guggino, Claudia Fabiani, Bruno Frediani, Roberto Giacomelli, Luca Cantarini
OBJECTIVES: To evaluate the clinical usefulness of the systemic score in the prediction of life-threatening evolution in Still's disease. To assess the clinical relevance of each component of the systemic score in predicting life-threatening evolution and to derive patient subsets accordingly. METHODS: A multicenter, observational, prospective study was designed including patients included in the GIRRCS (Gruppo Italiano Di Ricerca in Reumatologia Clinica e Sperimentale) AOSD-study group and AIDA (AutoInflammatory Disease Alliance) Network Still's Disease Registry...
March 18, 2024: Arthritis & Rheumatology
#17
JOURNAL ARTICLE
Nancy Wareing, Xuan Wang, Lynette Keyes-Elstein, Ellen A Goldmuntz, Marka A Lyons, Peter McSweeney, Daniel E Furst, Richard A Nash, Leslie J Crofford, Beverly Welch, Ashley Pinckney, Maureen D Mayes, Keith M Sullivan, Shervin Assassi
OBJECTIVE: In the randomized Scleroderma: Cyclophosphamide Or Transplantation (SCOT trial), myeloablation, followed by hematopoietic stem cell transplantation (HSCT), led to normalization of systemic sclerosis (SSc) peripheral blood gene cell (PBC) expression signature at the 26-month visit. Herein, we examined long-term molecular changes ensuing 54 months after randomization for individuals receiving an HSCT or 12 months of intravenous cyclophosphamide (CYC). METHOD: Global PBC transcript studies were performed at pretreatment baseline, 38 months, and 54 months post-randomization, as well as in healthy controls using Illumina HT-12 arrays...
March 18, 2024: Arthritis & Rheumatology
#18
JOURNAL ARTICLE
Mats L Junek, Peter A Merkel, Eswari Vilayur, Ron Wald, Nader Khalidi, David Jayne, Michael Walsh
OBJECTIVE: Relapses of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis are important events that can cause organ dysfunction and reduce quality of life. Understanding the effects of the initial treatments for ANCA-associated vasculitis on the subsequent risk of relapse may help guide monitoring and treatment. METHODS: We performed a post hoc analysis of participants with severe ANCA-associated vasculitis enrolled in an international two-by-two factorial randomized controlled trial comparing the effects of plasma exchange (PLEX) to no PLEX and a regimen of reduced glucocorticoid exposure to a standard regimen...
March 14, 2024: Arthritis & Rheumatology
#19
JOURNAL ARTICLE
Christina Charles-Schoeman, Roy Fleischmann, Eduardo Mysler, Maria Greenwald, Steven R Ytterberg, Gary G Koch, Deepak L Bhatt, Cunshan Wang, Ted R Mikuls, All-Shine Chen, Carol A Connell, John C Woolcott, Sujatha Menon, Yan Chen, Kristen Lee, Zoltán Szekanecz
OBJECTIVE: The ORAL Surveillance trial found a dose-dependent increase in venous thromboembolism (VTE) and pulmonary embolism (PE) events with tofacitinib versus tumor necrosis factor inhibitors (TNFi). We aimed to assess VTE incidence over time and explore risk factors of VTE, including disease activity, in ORAL Surveillance. METHODS: Patients with rheumatoid arthritis (RA) aged ≥50 years with ≥1 additional cardiovascular risk factor received tofacitinib 5 or 10 mg twice daily (BID) or TNFi...
March 13, 2024: Arthritis & Rheumatology
#20
JOURNAL ARTICLE
Hiroyuki Nakamura, Tsutomu Tanaka, Changyu Zheng, Sandra A Afione, Tatsuya Atsumi, Masayuki Noguchi, Fabiola Reis Oliveira, Ana Carolina F Motta, Fernando Chahud, Eduardo M Rocha, Blake M Warner, John A Chiorini
OBJECTIVE: Lysosome-associated membrane protein 3 (LAMP3) misexpression in salivary gland epithelial cells plays a causal role in the development of salivary gland dysfunction and autoimmunity associated with Sjögren's disease (SjD). This study aimed to clarify how epithelial LAMP3 misexpression is induced in SjD. METHODS: To explore upstream signaling pathways associated with LAMP3 expression, we conducted multiple RNA sequencing analyses of minor salivary glands from patients with SjD, submandibular glands from a mouse model of SjD, and salivary gland epithelial cell lines...
March 12, 2024: Arthritis & Rheumatology
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