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Rheumatoid Arthritis: Clinical Updates on Diagnosis and Treatment
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Rheumatoid Arthritis: Clinical Updates on Diagnosis and Treatment

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Immunology".

Deadline for manuscript submissions: 24 January 2025 | Viewed by 2438

Special Issue Editor

Dr. Shunsuke Mori

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Guest Editor
Department of Rheumatology, Clinical Research Center for Rheumatic Diseases, National Hospital Organization Kumamoto Saishun Medical Center, Kohshi, Kumamoto, Japan
Interests: rheumatoid arthritis; disease-modifying antirheumatic drugs; inflammatory rheumatic disease; interstitial lung disease; bronchietasis; infectious disease

Special Issue Information

Dear Colleagues,

Over the past two decades, significant advances have been made in the management of rheumatoid arthritis (RA). Early diagnosis, the prompt initiation of pharmaceutical therapies, and the application of a treat-to-target strategy with tight disease control have greatly improved the long-term outcomes of patients with RA. A growing array of conventional, biological, and nonbiological targeted disease-modifying antirheumatic drugs (DMARDs) are available in the current pharmaceutical approach.

Despite this remarkable therapeutic revolution, we are confronted by many difficulties in our daily practice of managing patients with RA. Many patients remain unresponsive to current DMARD therapies or experience disease flares after achieving a state of remission or low disease activity. Additionally, the presence of persistent subclinical inflammation may induce the progressive damage of joints, even after patients have achieved clinical remission. It is not clear when a drug can be discontinued or reduced once the remission state is achieved and sustained. We lack the reliable biomarkers by which we can predict patient responses to individual treatments. It is essential that we address these unmet clinical needs in the management of patients with RA.

The aim of this Special Issue is to provide new information concerning diagnosis and treatment strategies using targeted therapies with biological and nonbiological DMARDs. I welcome original research papers, reviews, meta-analyses, and communications that will contribute to optimizing the use of the existing DMARDs and developing new ideas and future research directions.

Dr. Shunsuke Mori
Guest Editor

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Keywords

  • rheumatoid arthritis
  • disease-modifying antirheumatic drugs (DMARDs)
  • biological therapies
  • Janus kinase inhibitors (JAK inhibitors)
  • treatment strategies
  • joint destruction
  • comorbidity
  • drug safety

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Published Papers (3 papers)

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Research

12 pages, 444 KiB  
Article
Real-World Clinical Effectiveness and Safety of Antifibrotics in Progressive Pulmonary Fibrosis Associated with Rheumatoid Arthritis
by Javier Narváez, Martí Aguilar-Coll, Vanesa Vicens-Zygmunt, Juan José Alegre, Guadalupe Bermudo and María Molina-Molina
J. Clin. Med. 2024, 13(23), 7074; https://doi.org/10.3390/jcm13237074 - 22 Nov 2024
Abstract
Background/Objectives: Interstitial lung disease (ILD) is one of the most severe complications of rheumatoid arthritis (RA). Real-world data on antifibrotic treatment are needed. Our objective was to evaluate the real-world effectiveness and tolerability of antifibrotic agents in patients with progressive fibrosing RA-ILD. [...] Read more.
Background/Objectives: Interstitial lung disease (ILD) is one of the most severe complications of rheumatoid arthritis (RA). Real-world data on antifibrotic treatment are needed. Our objective was to evaluate the real-world effectiveness and tolerability of antifibrotic agents in patients with progressive fibrosing RA-ILD. Methods: A longitudinal, retrospective, observational study was conducted on a cohort of RA-ILD patients treated with either nintedanib or pirfenidone. The data collected included pulmonary function test (PFT) results, adverse events (AEs), tolerability, and drug retention. Results: Twenty-seven patients were included; 25 (92.5%) initiated nintedanib, while two initiated pirfenidone. The median follow-up duration was 25 months (IQR 7–27). The mean decline in %pFVC and %pDLCO from ILD diagnosis to the initiation of antifibrotic therapy were −8.9% and −14.8%, respectively. After 6 months of treatment, most patients achieved stabilization in PFT: a ∆%pFVC of +1.2% (p = 0.611 compared with baseline) and a ∆%pDLCO of +3.9% (p = 0.400). Eighteen patients completed one year of therapy, with a modest improvement in %pFVC (+4.7%; p = 0.023) and stabilization in %pDLCO (−3.8%; p = 0.175). This trend persisted among the nine patients who completed 2 years of treatment (%pFVC +7.7%; p = 0.037 and %pDLCO −2.2%; p = 0.621). During the follow-up period, 15% of patients died, and 4% underwent lung transplantation. Adverse events occurred in 81% of patients, leading to discontinuation in 18.5% of cases. The most frequent adverse events were gastrointestinal events and hepatitis, leading to a permanent dose reduction of 40% for nintedanib and 14% for pirfenidone. A second antifibrotic agent was prescribed for 18.5% of the patients. At the end of the follow-up period, 63% of the total cohort remained on antifibrotic therapy. Conclusions: According to our results, antifibrotic initiation was associated with a modest improvement in the trajectory of %pFVC and stabilization in %pDLCO. The discontinuation rate in our cohort (37%) was higher than that reported in clinical trials but similar to that reported in previously published real-world studies. Full article
(This article belongs to the Special Issue Rheumatoid Arthritis: Clinical Updates on Diagnosis and Treatment)
10 pages, 860 KiB  
Article
Serum Anti-Aminoacyl-Transfer Ribonucleic Acid Synthetase Antibody Levels Are Involved in Rheumatoid Arthritis Complicated with Interstitial Lung Disease
by Shomi Oka, Takashi Higuchi, Hiroshi Furukawa, Kota Shimada, Akira Okamoto, Misuzu Fujimori, Atsushi Hashimoto, Akiko Komiya, Koichiro Saisho, Norie Yoshikawa, Masao Katayama, Toshihiro Matsui, Naoshi Fukui, Kiyoshi Migita and Shigeto Tohma
J. Clin. Med. 2024, 13(22), 6761; https://doi.org/10.3390/jcm13226761 - 10 Nov 2024
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Abstract
Objectives: A common complication in patients with rheumatoid arthritis (RA) is interstitial lung disease (ILD). Antibodies (Abs) to anti-aminoacyl-transfer ribonucleic acid synthetase (ARS) are linked to ILD in patients with idiopathic inflammatory myopathies (IIM). There have been limited studies of anti-ARS Abs in [...] Read more.
Objectives: A common complication in patients with rheumatoid arthritis (RA) is interstitial lung disease (ILD). Antibodies (Abs) to anti-aminoacyl-transfer ribonucleic acid synthetase (ARS) are linked to ILD in patients with idiopathic inflammatory myopathies (IIM). There have been limited studies of anti-ARS Abs in RA. In this study, we examined anti-ARS Abs in ILD in patients with RA. Methods: Anti-ARS Abs in serum from patients with RA were measured. Results: There were higher anti-ARS Ab levels in RA patients with ILD (mean ± SDM, 16.3 ± 32.3 vs. 7.4 ± 7.0 (Index), p = 5.58 × 10−12), usual interstitial pneumonia (14.4 ± 24.4 vs. 7.4 ± 7.0 [Index], p = 3.14 × 10−12), and nonspecific interstitial pneumonia (17.9 ± 37.7 vs. 7.4 ± 7.0 (Index), p = 5.07 × 10−5) compared with patients without chronic lung disease. The area under the curve (AUC) of the receiver operating characteristic curve for anti-ARS Ab was too low to allow for discrimination among RA patients with/without chronic lung disease (0.608, 95% confidence interval (CI) 0.560–0.655, p = 8.69 × 10−6). Multiple logistic regression analyses of age, smoking status, anti-ARS Abs, as well as Steinbrocker stage generated an ARS-index with a high AUC value (0.707, 95%CI 0.662–0.752, p = 2.20 × 10−19). Conclusions: Anti-ARS Abs are related to ILD pathogenesis in RA and may be a biomarker for ILD. Full article
(This article belongs to the Special Issue Rheumatoid Arthritis: Clinical Updates on Diagnosis and Treatment)
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9 pages, 449 KiB  
Article
Influence of Safety Warnings on the Prescribing Attitude of JAK Inhibitors for Rheumatoid Arthritis in Italy
by Marino Paroli, Andrea Becciolini, Alberto Lo Gullo, Simone Parisi, Elena Bravi, Romina Andracco, Valeria Nucera, Francesca Ometto, Federica Lumetti, Antonella Farina, Patrizia Del Medico, Matteo Colina, Viviana Ravagnani, Palma Scolieri, Maddalena Larosa, Marta Priora, Elisa Visalli, Olga Addimanda, Rosetta Vitetta, Alessandro Volpe, Alessandra Bezzi, Francesco Girelli, Aldo Biagio Molica Colella, Rosalba Caccavale, Eleonora Di Donato, Giuditta Adorni, Daniele Santilli, Gianluca Lucchini, Eugenio Arrigoni, Ilaria Platè, Natalia Mansueto, Aurora Ianniello, Enrico Fusaro, Maria Chiara Ditto, Vincenzo Bruzzese, Dario Camellino, Gerolamo Bianchi, Francesca Serale, Rosario Foti, Giorgio Amato, Francesco De Lucia, Ylenia Dal Bosco, Roberta Foti, Massimo Reta, Alessia Fiorenza, Guido Rovera, Antonio Marchetta, Maria Cristina Focherini, Fabio Mascella, Simone Bernardi, Gilda Sandri, Dilia Giuggioli, Carlo Salvarani, Maria Ilenia De Andres, Veronica Franchina, Francesco Molica Colella, Giulio Ferrero, Bernd Raffeiner and Alarico Arianiadd Show full author list remove Hide full author list
J. Clin. Med. 2024, 13(13), 3929; https://doi.org/10.3390/jcm13133929 - 4 Jul 2024
Cited by 1 | Viewed by 1509
Abstract
Background/Objectives: The Janus kinase inhibitors (JAKi) tofacitinib (TOFA), baricitinib (BARI), upadacitinib (UPA), and filgotinib (FILGO) are effective drugs for the treatment of rheumatoid arthritis. However, the US Food and Drug Administration (FDA) raised concerns about the safety of TOFA after its approval. This [...] Read more.
Background/Objectives: The Janus kinase inhibitors (JAKi) tofacitinib (TOFA), baricitinib (BARI), upadacitinib (UPA), and filgotinib (FILGO) are effective drugs for the treatment of rheumatoid arthritis. However, the US Food and Drug Administration (FDA) raised concerns about the safety of TOFA after its approval. This prompted the European Medicines Agency (EMA) to issue two safety warnings for limiting TOFA use, then extended a third warning to all JAKi in patients at high risk of developing serious adverse effects (SAE). These include thrombosis, major adverse cardiac events (MACE), and cancer. The purpose of this work was to analyze how the first two safety warnings from the EMA affected the prescribing of JAKi by rheumatologists in Italy. Methods: All patients with rheumatoid arthritis who had been prescribed JAKi for the first time in a 36-month period from 1 July 2019, to 30 June 2022 were considered. Data were obtained from the medical records of 29 Italian tertiary referral rheumatology centers. Patients were divided into three groups of 4 months each, depending on whether the JAKi prescription had occurred before the EMA’s first safety alert (1 July–31 October 2019, Group 1), between the first and second alerts (1 November 2019–29 February 2020, Group 2), or between the second and third alerts (1 March 2021–30 June 2021, Group 3). The percentages and absolute changes in the patients prescribed the individual JAKi were analyzed. Differences among the three groups of patients regarding demographic and clinical characteristics were also assessed. Results: A total of 864 patients were prescribed a JAKi during the entire period considered. Of these, 343 were identified in Group 1, 233 in Group 2, and 288 in Group 3. An absolute reduction of 32% was observed in the number of patients prescribed a JAKi between Group 1 and Group 2 and 16% between Group 1 and Group 3. In contrast, there was a 19% increase in the prescription of a JAKi in patients between Group 2 and Group 3. In the first group, BARI was the most prescribed drug (227 prescriptions, 66.2% of the total), followed by TOFA (115, 33.5%) and UPA (1, 0.3%). In the second group, the most prescribed JAKi was BARI (147, 63.1%), followed by TOFA (65, 27.9%) and UPA (33, 11.5%). In the third group, BARI was still the most prescribed JAKi (104 prescriptions, 36.1%), followed by UPA (89, 30.9%), FILGO (89, 21.5%), and TOFA (33, 11.5%). The number of patients prescribed TOFA decreased significantly between Group 1 and Group 2 and between Group 2 and Group 3 (p ˂ 0.01). The number of patients who were prescribed BARI decreased significantly between Group 1 and Group 2 and between Group 2 and Group 3 (p ˂ 0.01). In contrast, the number of patients prescribed UPA increased between Group 2 and Group 3 (p ˂ 0.01). Conclusions: These data suggest that the warnings issued for TOFA were followed by a reduction in total JAKi prescriptions. However, the more selective JAKi (UPA and FILGO) were perceived by prescribers as favorable in terms of the risk/benefit ratio, and their use gradually increased at the expense of the other molecules. Full article
(This article belongs to the Special Issue Rheumatoid Arthritis: Clinical Updates on Diagnosis and Treatment)
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