Showing papers on "Inflammatory arthritis published in 2021"

Cardiovascular risk in inflammatory arthritis: rheumatoid arthritis and gout

Abstract: The increased risk of cardiovascular morbidity and mortality in rheumatoid arthritis and gout has been increasingly acknowledged in past decades, with accumulating evidence that gout, just as with rheumatoid arthritis, is an independent cardiovascular risk factor. Although both diseases have a completely different pathogenesis, the underlying pathophysiological mechanisms in systemic inflammation overlap to some extent. Following the recognition that systemic inflammation has an important causative role in cardiovascular disease, anti-inflammatory therapy in both conditions and urate-lowering therapies in gout are expected to lower the cardiovascular burden of patients. Unfortunately, much of the existing data showing that urate-lowering therapy has consistent beneficial effects on cardiovascular outcomes in patients with gout are of low quality and contradictory. We will discuss the latest evidence in this respect. Cardiovascular disease risk management for patients with rheumatoid arthritis and gout is essential. Clinical guidelines and implementation of cardiovascular risk management in daily clinical practice, as well as unmet needs and areas for further investigation, will be discussed.

COVID-19 and immune-mediated inflammatory diseases: effect of disease and treatment on COVID-19 outcomes and vaccine responses.

Abstract: At the beginning of the COVID-19 pandemic, patients with immune-mediated inflammatory diseases were considered to be at high risk for SARS-CoV-2 infection and the development of severe COVID-19. Data collected over the past year, however, suggest that a diagnosis of inflammatory arthritis, psoriasis, or inflammatory bowel diseases does not increase risk for SARS-CoV-2 infection or severe COVID-19 compared with people without these diseases. Furthermore, substantial data suggest that certain medications frequently used in patients with immune-mediated inflammatory diseases, in particular cytokine inhibitors, might even lower the risk for severe COVID-19. Conversely, glucocorticoids and potentially B-cell-depleting treatments seem to worsen COVID-19 outcomes. Additionally, the first data on SARS-CoV-2 vaccination in patients with these diseases suggest that tolerability of vaccination in patients with immune-mediated inflammatory diseases is good, although the immune response to vaccination can be somewhat reduced in this patient group, particularly those taking methotrexate or CD20-targeted treatment.

Severe COVID-19-associated pneumonia in 3 patients with systemic sclerosis treated with rituximab.

Abstract: The case reported by Guilpain et al attracted our attention. This case of granulomatosis with polyangiitis on immunosuppressants, including recent maintenance therapy with rituximab (RTX), developed a severe and life-threatening coronavirus-2 (SARS-CoV-2) disease 2019 (COVID-19). The particularity of this observation was the occurrence of a more progressive worsening than observed in most series.1 Herein, we report the observation of three patients with systemic sclerosis (SSc) routinely treated with RTX who were affected by COVID-19 and who also experienced a late clinical worsening to severe pneumonia. RTX is often used off-label in patients with SSc mainly for refractory skin, musculoskeletal or interstitial lung disease. Observational studies reported a safety profile similar to that reported in rheumatoid arthritis.2 Their main disease characteristics are presented in table 1. Patient 1 had early diffuse cutaneous SSc, with positive RNA polymerase-3 antibodies, and severe cutaneous involvement (peak modified Rodnan Skin Score at 32/51) as the main clinical involvement. Patient 2 had long-lasting limited cutaneous SSc with recurrent digital ulcers and inflammatory arthritis as the main disease manifestations. Patient 3 had a limited cutaneous subset evolving from 2 years, with positive RNA polymerase-3 antibodies and persisting arthritis. None of these patients had interstitial lung disease and primary or secondary heart involvement. Regarding the main comorbidities, patient 1 was treated for high blood pressure by perindopril, furosemide and lercanidipine, and patient 2 had chronic renal insufficiency and history …

Therapeutic ACPA inhibits NET formation: a potential therapy for neutrophil-mediated inflammatory diseases

Abstract: Excessive release of neutrophil extracellular traps (NETs) is associated with disease severity and contributes to tissue injury, followed by severe organ damage. Pharmacological or genetic inhibition of NET release reduces pathology in multiple inflammatory disease models, indicating that NETs are potential therapeutic targets. Here, we demonstrate using a preclinical basket approach that our therapeutic anti-citrullinated protein antibody (tACPA) has broad therapeutic potential. Treatment with tACPA prevents disease symptoms in various mouse models with plausible NET-mediated pathology, including inflammatory arthritis (IA), pulmonary fibrosis, inflammatory bowel disease and sepsis. We show that citrulline residues in the N-termini of histones 2A and 4 are specific targets for therapeutic intervention, whereas antibodies against other N-terminal post-translational histone modifications have no therapeutic effects. Because citrullinated histones are generated during NET release, we investigated the ability of tACPA to inhibit NET formation. tACPA suppressed NET release from human neutrophils triggered with physiologically relevant human disease-related stimuli. Moreover, tACPA diminished NET release and potentially initiated NET uptake by macrophages in vivo, which was associated with reduced tissue damage in the joints of a chronic arthritis mouse model of IA. To our knowledge, we are the first to describe an antibody with NET-inhibiting properties and thereby propose tACPA as a drug candidate for NET-mediated inflammatory diseases, as it eliminates the noxious triggers that lead to continued inflammation and tissue damage in a multidimensional manner.

Targeted apoptosis of macrophages and osteoclasts in arthritic joints is effective against advanced inflammatory arthritis

Abstract: Insufficient apoptosis of inflammatory macrophages and osteoclasts (OCs) in rheumatoid arthritis (RA) joints contributes toward the persistent progression of joint inflammation and destruction. Here, we deliver celastrol (CEL) to selectively induce apoptosis of OCs and macrophages in arthritic joints, with enzyme-responsive nanoparticles (termed PRNPs) composed of RGD modified nanoparticles (termed RNPs) covered with cleavable PEG chains. CEL-loaded PRNPs (CEL-PRNPs) dually target OCs and inflammatory macrophages derived from patients with RA via an RGD-αvβ3 integrin interaction after PEG cleavage by matrix metalloprotease 9, leading to increased apoptosis of these cells. In an adjuvant-induced arthritis rat model, PRNPs have an arthritic joint-specific distribution and CEL-PRNPs efficiently reduce the number of OCs and inflammatory macrophages within these joints. Additionally, rats with advanced arthritis go into inflammatory remission with bone erosion repair and negligible side effects after CEL-PRNPs treatment. These findings indicate potential for targeting chemotherapy-induced apoptosis in the treatment of advanced inflammatory arthritis.

TNF in the era of immune checkpoint inhibitors: friend or foe?

Abstract: Immune checkpoint inhibitors (ICIs) are effective in the treatment of patients with advanced cancer and have emerged as a pillar of standard cancer care. However, their use is complicated by adverse effects known as immune-related adverse events (irAEs), including ICI-induced inflammatory arthritis. ICI-induced inflammatory arthritis is distinguished from other irAEs by its persistence and requirement for long-term treatment. TNF inhibitors are commonly used to treat inflammatory diseases such as rheumatoid arthritis, spondyloarthropathies and inflammatory bowel disease, and have also been adopted as second-line agents to treat irAEs refractory to glucocorticoid treatment. Experiencing an irAE is associated with a better antitumour response after ICI treatment. However, whether TNF inhibition can be safely used to treat irAEs without promoting cancer progression, either by compromising ICI therapy efficacy or via another route, remains an open question. In this Review, we discuss clinical and preclinical studies that address the relationship between TNF, TNF inhibition and cancer. The bulk of the evidence suggests that at least short courses of TNF inhibitors are safe for the treatment of irAEs in patients with cancer undergoing ICI therapy. Data from preclinical studies hint that TNF inhibition might augment the antitumour effect of ICI therapy while simultaneously ameliorating irAEs.

Autoimmune inflammatory rheumatic diseases and COVID-19 outcomes in South Korea: a nationwide cohort study.

Abstract: Summary Background Real-world evidence on the association between autoimmune inflammatory rheumatic diseases, therapies related to these diseases, and COVID-19 outcomes are inconsistent. We aimed to investigate the potential association between autoimmune inflammatory rheumatic diseases and COVID-19 early in the COVID-19 pandemic. Methods We did an exposure-driven, propensity score-matched study using a South Korean nationwide cohort linked to general health examination records. We analysed all South Korean patients aged older than 20 years who underwent SARS-CoV-2 RT-PCR testing between Jan 1 and May 30, 2020, and received general health examination results from the Korean National Health Insurance Service. We defined autoimmune inflammatory rheumatic diseases (inflammatory arthritis and connective tissue diseases) based on the relevant ICD-10 codes, with at least two claims (outpatient or inpatient) within 1 year. The outcomes were positive SARS-CoV-2 RT-PCR test, severe COVID-19 (requirement of oxygen therapy, intensive care unit admission, application of invasive ventilation, or death), and COVID-19-related death. Adjusted odds ratios (ORs) with 95% CIs were estimated after adjusting for the potential confounders. Findings Between Jan 1 and May 30, 2020, 133 609 patients (70 050 [52·4%] female and 63 559 [47·6%] male) completed the general health examination and were tested for SARS-CoV-2; 4365 (3·3%) were positive for SARS-CoV-2, and 8297 (6·2%) were diagnosed with autoimmune inflammatory rheumatic diseases. After matching, patients with an autoimmune inflammatory rheumatic disease showed an increased likelihood of testing positive for SARS-CoV-2 (adjusted OR 1·19, 95% CI 1·03–1·40; p=0·026), severe COVID-19 outcomes (1·26, 1·02–1·59; p=0·041), and COVID-19-related death (1·69, 1·01–2·84; p=0·046). Similar results were observed in patients with connective tissue disease and inflammatory arthritis. Treatment with any dose of systemic corticosteroids or disease-modifying antirheumatic drugs (DMARDs) were not associated with COVID-19-related outcomes, but those receiving high dose (≥10 mg per day) of systemic corticosteroids had an increased likelihood of a positive SARS-CoV-2 test (adjusted OR 1·47, 95% CI 1·05–2·03; p=0·022), severe COVID-19 outcomes (1·76, 1·06–2·96; p=0·031), and COVID-19-related death (3·34, 1·23–8·90; p=0·017). Interpretation Early in the COVID-19 pandemic, autoimmune inflammatory rheumatic diseases were associated with an increased likelihood of a positive SARS-CoV-2 PCR test, worse clinical outcomes of COVID-19, and COVID-19-related deaths in South Korea. A high dose of systemic corticosteroid, but not DMARDs, showed an adverse effect on SARS-CoV-2 infection and COVID-19-related clinical outcomes. Funding National Research Foundation of Korea.

Significance of Interleukin (IL)-4 and IL-13 in Inflammatory Arthritis.

Abstract: Interleukin (IL)-4 and IL-13 belong to the T helper 2 (Th2) cytokine family, along with IL-3, IL-5, and IL-9. These cytokines are key mediators of allergic inflammation. They have important immunomodulatory activities and exert influence on a wide variety of immune cells, such as B cells, eosinophils, basophils, monocytes, fibroblasts, endothelial cells, airway epithelial cells, smooth muscle cells, and keratinocytes. Recent studies have implicated IL-4 and IL-13 in the development of various autoimmune diseases. Additionally, these cytokines have emerged as potential players in pathogenesis of inflammatory arthritis. Recent findings suggest that the IL-4 and IL-13 might play a significant role in the downregulation of inflammatory processes underlying RA pathology, and beneficially modulate the course of the disease. This review summarizes the biological features of the IL-4 and IL-13 and provides current knowledge regarding the role of these cytokines in inflammatory arthritis.

Methotrexate and glucocorticoids, but not anticytokine therapy, impair the immunogenicity of a single dose of the BNT162b2 mRNA COVID-19 vaccine in patients with chronic inflammatory arthritis.

Abstract: Strategies aimed at expediting immunisation campaigns against COVID-19 include providing single vaccine doses to individuals with previous exposure to SARS-CoV-2 and delaying second doses. While such approaches are effective at the population level, immunogenicity yielded by one dose of vaccines in immunocompromised patients may be alarmingly low.1 2 Biological (b) and targeted synthetic (ts) disease-modifying antirheumatic drugs (DMARDs) interfere with the immune system at multiple levels and may variably reduce response to viral vaccines.3 Limited data on small numbers of rheumatic patients with variable diagnoses and treatments hamper definitive conclusions on the possible impact of immune-mediated inflammatory diseases, immunomodulatory drugs or both on the efficacy of the new generation of mRNA vaccines.4 5 Here we present interim data analysis on the immunogenicity of the BNT162b2 COVID-19 vaccine in 140 patients with chronic inflammatory arthritis all treated with b/tsDMARDs at the Division of Rheumatology of the IRCCS Policlinico San Matteo University Hospital of Pavia, receiving the first dose of vaccine between 24 and 31 March 2021. Patients were advised to discontinue both the b/tsDMARD and concomitant methotrexate around vaccination. In particular, the following suggestions were made: (1) for all the bDMARDs and methotrexate, withholding of therapy in the 7 days before and after vaccination; and (2) for tsDMARDs, withholding of therapy from the day before until day 7 after vaccination. For glucocorticoids and conventional synthetic DMARDs other than methotrexate, no modifications were advised. Blood samples were obtained immediately before vaccination and at day 21 after the first dose. Serum samples were tested using chemiluminescent immunoassay (LIAISON SARS-CoV-2 S1/S2 IgG; DiaSorin) for the quantitative characterisation of SARS-CoV-2 anti-S1 and anti-S2 IgG antibodies, with values >15 AU/mL indicating a positive result. Demographic and clinical variables were retrieved from the last available rheumatological assessment (median (IQR) 14 (5–19) days before vaccination) …

Coronavirus disease 19 (Covid-19) and non-steroidal anti-inflammatory drugs (NSAID).

Abstract: We have read with interest the report by Monti et al 1 concerning the clinical course of coronavirus disease (Covid-19) in patients with chronic inflammatory arthritis. However, we could not find data about the use of non-steroidal anti-inflammatory drugs (NSAID) among their patients. Whether concomitant NSAID treatment may be harmful or safe in patients with Covid-19 is unknown. However, anti-inflammatory therapies might prevent fatal cytokine storm of Covid-19. Ibuprofen, a commonly prescribed NSAID, was found to reduce interleukin-6 (IL-6) in human tissues,2 and in sputum. …

Biological classification of childhood arthritis: roadmap to a molecular nomenclature.

Abstract: Chronic inflammatory arthritis in childhood is heterogeneous in presentation and course. Most forms exhibit clinical and genetic similarity to arthritis of adult onset, although at least one phenotype might be restricted to children. Nevertheless, paediatric and adult rheumatologists have historically addressed disease classification separately, yielding a juvenile idiopathic arthritis (JIA) nomenclature that exhibits no terminological overlap with adult-onset arthritis. Accumulating clinical, genetic and mechanistic data reveal the critical limitations of this strategy, necessitating a new approach to defining biological categories within JIA. In this Review, we provide an overview of the current evidence for biological subgroups of arthritis in children, delineate forms that seem contiguous with adult-onset arthritis, and consider integrative genetic and bioinformatic strategies to identify discrete entities within inflammatory arthritis across all ages. Childhood-onset arthritis has historically been treated as a separate entity to adult-onset arthritis, with its own nomenclature and classification system. Biological evidence has revealed the limitations of the current approach, necessitating a fresh look at the classification of paediatric arthritis.

Clinical Heterogeneity of the VEXAS Syndrome: A Case Series.

Abstract: The objective of this study is to describe the clinical features and outcomes of patients with the newly defined vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome. Nine men with somatic mutations in the UBA1 gene were identified; the most frequent variant was p.Met41Thr (7 of 9, 78%). The median age at VEXAS diagnosis was 74 (67, 76.5) years, and patients had a median duration of symptoms for 4 years before diagnosis. Refractory constitutional symptoms (88%), ear and nose chondritis (55%), and inflammatory arthritis (55%) were common clinical features. Vasculitis was noted in 44%. All patients had significantly elevated inflammatory markers and macrocytic anemia. Thrombocytopenia was present in 66% at diagnosis of VEXAS. Eight patients had bone marrow biopsies performed. All bone marrows were hypercellular, and there was vacuolization of the erythroid (100%) or myeloid precursors (75%). Glucocorticoids attenuated symptoms at prednisone doses ≥20 mg per day, but no other immunosuppressive agent showed consistent long-term control of disease. One patient with coexisting plasma-cell myeloma received plasma-cell-directed therapy with improvement of the inflammatory response, which is a novel finding. In conclusion, VEXAS syndrome is a clinically heterogeneous, treatment-refractory inflammatory condition caused by somatic mutation of the UBA1 gene. Patients often present with overlapping rheumatologic manifestations and persistent hematologic abnormalities. As such, internists and subspecialists, including pathologists, should be aware of this condition to avert diagnostic delay, now that the etiology of this syndrome is known.

Axial psoriatic arthritis: An update for dermatologists

Abstract: Psoriasis is a chronic, immune-mediated, systemic, inflammatory disorder characterized by skin plaques and, often, nail disease and arthritis that contribute to reduced quality of life. Psoriatic arthritis—a heterogeneous, inflammatory, musculoskeletal disease that can cause permanent damage to both peripheral and axial joints—is the most common comorbidity of psoriasis. Axial disease occurs in 25% to 70% of patients with PsA, with some patients exclusively experiencing axial joint involvement. Early therapeutic intervention is important for preventing permanent joint and spine damage and loss of functionality in these patients. Because skin symptoms associated with psoriasis often precede psoriatic arthritis, dermatologists are uniquely positioned to play an important role in identifying and treating patients with psoriatic arthritis. Proactive screening of patients with all severities of psoriasis for the signs and symptoms of psoriatic arthritis is key to early diagnosis and intervention. In this review, we discuss the clinical presentation, risk factors, and treatment options for psoriatic arthritis with axial involvement, with the aim of helping dermatologists understand the disease and identify patients who might benefit from further assessment, treatment, and/or referral to a rheumatology practice.

Cigarette smoke induces miR-132 in Th17 cells that enhance osteoclastogenesis in inflammatory arthritis

Abstract: Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by joint destruction and severe morbidity. Cigarette smoking (CS) can exacerbate the incidence and severity of RA. Although Th17 cells and the Aryl hydrocarbon receptor (AhR) have been implicated, the mechanism by which CS induces RA development remains unclear. Here, using transcriptomic analysis, we show that microRNA-132 is specifically induced in Th17 cells in the presence of either AhR agonist or CS-enriched medium. miRNA-132 thus induced is packaged into extracellular vesicles produced by Th17 and acts as a proinflammatory mediator increasing osteoclastogenesis through the down-regulation of COX2. In vivo, articular knockdown of miR-132 in murine arthritis models reduces the number of osteoclasts in the joints. Clinically, RA patients express higher levels of miR-132 than do healthy individuals. This increase is further elevated by cigarette smoking. Together, these results reveal a hitherto unrecognized mechanism by which CS could exacerbate RA and further advance understanding of the impact of environmental factors on the pathogenesis of chronic inflammatory diseases.

‘SMASH’ recommendations for standardised microscopic arthritis scoring of histological sections from inflammatory arthritis animal models

Abstract: Animal models for inflammatory arthritides such as rheumatoid arthritis (RA) and psoriatic arthritis are widely accepted and frequently used to identify pathological mechanisms and validate novel therapeutic strategies. Unfortunately, many publications reporting on these animal studies lack detailed description and appropriate assessment of the distinct histopathological features of arthritis: joint inflammation, cartilage damage and bone erosion. Therefore, the European consortium BeTheCure, consisting of 38 academic and industrial partners from 15 countries, set as goal to standardise the histological evaluation of joint sections from animal models of inflammatory arthritis. The consensual approach of a task force including 16 academic and industrial scientists as well as laboratory technicians has resulted in the development of the Standardised Microscopic Arthritis Scoring of Histological sections (‘SMASH’) recommendations for a standardised processing and microscopic scoring of the characteristic histopathological features of arthritis, exemplified by four different rodent models for arthritis: murine collagen-induced arthritis, collagen–antibody-induced arthritis, human tumour necrosis factor transgenic Tg197 mice and rat pristane-induced arthritis, applicable to any other inflammatory arthritis model. Through standardisation, the SMASH recommendations are designed to improve and maximise the information derived from in vivo arthritis experiments and to promote reproducibility and transparent reporting on such studies. In this manuscript, we will discuss and provide recommendations for analysis of histological joint sections: identification of the regions of interest, sample preparation, staining procedures and quantitative scoring methods. In conclusion, awareness of the different features of the arthritis pathology in animal models of inflammatory arthritis is of utmost importance for reliable research outcome, and the standardised histological processing and scoring methods in these SMASH recommendations will help increase uniformity and reproducibility in preclinical research on inflammatory arthritis.

Lyme arthritis: linking infection, inflammation and autoimmunity.

Abstract: Infectious agents can trigger autoimmune responses in a number of chronic inflammatory diseases. Lyme arthritis, which is caused by the tick-transmitted spirochaete Borrelia burgdorferi, is effectively treated in most patients with antibiotic therapy; however, in a subset of patients, arthritis can persist and worsen after the spirochaete has been killed (known as post-infectious Lyme arthritis). This Review details the current understanding of the pathogenetic events in Lyme arthritis, from initial infection in the skin, through infection of the joints, to post-infectious chronic inflammatory arthritis. The central feature of post-infectious Lyme arthritis is an excessive, dysregulated pro-inflammatory immune response during the infection phase that persists into the post-infectious period. This response is characterized by high amounts of IFNγ and inadequate amounts of the anti-inflammatory cytokine IL-10. The consequences of this dysregulated pro-inflammatory response in the synovium include impaired tissue repair, vascular damage, autoimmune and cytotoxic processes, and fibroblast proliferation and fibrosis. These synovial characteristics are similar to those in other chronic inflammatory arthritides, including rheumatoid arthritis. Thus, post-infectious Lyme arthritis provides a model for other chronic autoimmune or autoinflammatory arthritides in which complex immune responses can be triggered and shaped by an infectious agent in concert with host genetic factors.

Chemokine Receptor 5 Antagonism Causes Reduction in Joint Inflammation in a Collagen-Induced Arthritis Mouse Model.

Abstract: Rheumatoid arthritis (RA) is a chronic inflammatory disease mainly affecting the synovial joints. A highly potent antagonist of C-C chemokine receptor 5 (CCR5), maraviroc (MVC), plays an essential role in treating several infectious diseases but has not yet been evaluated for its potential effects on RA development. This study focused on evaluating the therapeutic potential of MVC on collagen-induced arthritis (CIA) in DBA/1J mice. Following CIA induction, animals were treated intraperitoneally with MVC (50 mg/kg) daily from day 21 until day 35 and evaluated for clinical score and histopathological changes in arthritic inflammation. We further investigated the effect of MVC on Th9 (IL-9, IRF-4, and GATA3) and Th17 (IL-21R, IL-17A, and RORγT) cells, TNF-α, and RANTES in CD8+ T cells in the spleen using flow cytometry. We also assessed the effect of MVC on mRNA and protein levels of IL-9, IL-17A, RORγT, and GATA3 in knee tissues using RT-PCR and western blot analysis. MVC treatment in CIA mice attenuated the clinical and histological severity of inflammatory arthritis, and it substantially decreased IL-9, IRF4, IL-21R, IL-17A, RORγT, TNF-α, and RANTES production but increased GATA3 production in CD8+ T cells. We further observed that MVC treatment decreased IL-9, IL-17A, and RORγt mRNA and protein levels and increased those of GATA3. This study elucidates the capacity of MVC to ameliorate the clinical and histological signs of CIA by reducing pro-inflammatory responses, suggesting that MVC may have novel therapeutic uses in the treatment of RA.

Checkpoint Inhibitor-Associated Arthritis: A Systematic Review of Case Reports and Case Series

Abstract: Objective We performed a systematic literature review to identify all reports of immune checkpoint inhibitor-associated inflammatory arthritis to describe it phenotypically and serologically. Methods PubMed, Embase, and Cochrane databases were searched for reports of musculoskeletal immune-related adverse events secondary to ICI treatment. Publications were included if they provided individual patient level data regarding the pattern of joint involvement. Descriptive statistics were used to summarize results. Results A total of 4339 articles were screened, of which 67 were included, encompassing 372 patients. The majority of patients had metastatic melanoma (57%), and they were treated with anti-PD1 or anti-PDL1 therapy (78%). Median time to onset of arthritis was 4 months (range, 1 day to 53 months). Forty-nine percent had polyarthritis, 17% oligoarthritis, 3% monoarthritis, 10% arthralgia, and 21% polymyalgia rheumatica. More than half of patients were described as having a "rheumatoid arthritis-like" presentation. Nine percent tested positive for rheumatoid factor or anti-cyclic citrullinated peptide antibodies. Seventy-four percent required corticosteroids, and 45% required additional medications. Sixty-three percent achieved arthritis control, and 32% were ultimately able to discontinue antirheumatic treatments. Immune checkpoint inhibitors were continued in 49%, transiently withheld in 11%, and permanently discontinued due to musculoskeletal immune-related adverse events in 13%. Conclusions Half of reported immune checkpoint inhibitor-associated arthritis cases present with polyarthritis (often RA-like), but only 9% are seropositive. Polymyalgia rheumatica is also common. Most patients respond to steroids alone, but about half require additional medications. Further studies are needed to determine long-term musculoskeletal outcomes in these patients, and the impact of arthritis treatment on cancer survival.

Osteoimmunological insights into the pathogenesis of ankylosing spondylitis

Abstract: Ankylosing spondylitis (AS) is inflammatory arthritis predominantly affecting the spine, which is involved in the disorders of both immune and skeletal systems The exact pathogenesis of AS is not fully understood Osteoimmunology is a new subject of study in inflammatory arthritis, in particular the pathogenic events involved in the cross-regulation of both skeletal and immune systems In this review, we discuss osteoimmunological and pathological changes of AS in the spine that are characterized by altered osteogenesis and osteolytic bone destruction, accompanied by the changes of the immune system It was revealed that bone cells like mesenchymal stem cells, osteoblast, and osteoclast in crossing talking with immune cells such as T cells, B cells coregulate to the pathogenesis of AS Further, an array of cytokines and molecules expressed by both skeletal and immune systems contribute to these complex interplays Understanding the cellular and molecular mechanisms underlying the pathogenesis of AS will lay a foundation for the exploration of the potential new treatment to AS

Adipokines and Autoimmunity in Inflammatory Arthritis

Abstract: Adipokines are adipose tissue-derived factors not only playing an important role in metabolism but also influencing other central processes of the body, such as inflammation. In autoimmune diseases, adipokines are involved in inflammatory pathways affecting different cell types. Many rheumatic diseases belong to the group of autoimmune diseases, for example rheumatoid arthritis (RA) and psoriatic arthritis. Due to the autoimmune responses, a chronic inflammatory milieu develops, which affects the whole body, including adipose tissue. Metabolic alterations such as obesity influence inflammatory responses in autoimmune diseases. Adipokines are bioactive mediators mainly produced by adipose tissue. Due to alterations of systemic adipokine levels, their role as biomarkers with diagnostic potential has been suggested in the context of rheumatic diseases. In the affected joints of RA patients, different synoviocytes but also osteoclasts, osteoblasts, and chondrocytes produce several adipokines, contributing to the unique inflammatory microenvironment. Adipokines have been shown to be potent modulatory effectors on different cell types of the immune system but also local cells in synovial tissue, cartilage, and bone. This review highlights the most recent findings on the role of adipokines in the pathophysiology of inflammatory arthritis with a distinct focus on RA in the quickly developing research field.

Nanomaterials for the Diagnosis and Treatment of Inflammatory Arthritis.

Abstract: Nanomaterials have received increasing attention due to their unique chemical and physical properties for the treatment of rheumatoid arthritis (RA), the most common complex multifactorial joint-associated autoimmune inflammatory disorder. RA is characterized by an inflammation of the synovium with increased production of proinflammatory cytokines (IL-1, IL-6, IL-8, and IL-10) and by the destruction of the articular cartilage and bone, and it is associated with the development of cardiovascular disorders such as heart attack and stroke. While a number of imaging tools allow for the monitoring and diagnosis of inflammatory arthritis, and despite ongoing work to enhance their sensitivity and precision, the proper assessment of RA remains difficult particularly in the early stages of the disease. Our goal here is to describe the benefits of applying various nanomaterials as next-generation RA imaging and detection tools using contrast agents and nanosensors and as improved drug delivery systems for the effective treatment of the disease.

Inflammatory Arthritis Induced by Anti-Programmed Death-1 Shown in 68Ga-FAPI PET/CT in a Patient With Esophageal Carcinoma.

Abstract: A 30-year-old woman with esophageal squamous cell carcinoma experienced joint pain and swelling in bilateral knees, wrists, and hand joints during the course of neoadjuvant immunochemotherapy She underwent 18F-FDG and 68Ga-FAPI PET/CT for response assessment of the tumor and evaluating her arthritis 68Ga-FAPI PET/CT detected intense uptake in multiple joints, consistent with her polyarthritis However, these joints showed only mild FDG uptake The tumor was in complete response, and her polyarthritis was considered as inflammatory arthritis induced by anti-PD1

All-cause mortality in systemic rheumatic diseases under treatment compared with the general population, 2015-2019.

Abstract: Objectives To compare current all-cause mortality rates in rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic arthritis (PsA), systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) versus general population. Methods In this population-based, retrospective cohort study, anonymised data on 11 186 586 citizens, including all patients with RA (42 735, 79% female), AS (9707, 43% female), PsA (13 779, 55% female), SLE (10 440, 89% female) and SSc (2277, 88% female), (median age of 64/47/54/53/59 years at study entry, respectively), under prescribed treatment between 2015 and 2019, were extracted from the electronic database covering nearly 99% of the Greek population. Results After 1:5 (patients:general population) matching for gender/age, we found that survival was worse in SSc, followed by SLE and inflammatory arthritis. Compared with the general population HRs for death increased from the first 3 years to 5 years of observation possibly due to increases in disease duration: RA (from 0.63 to 1.13 (95% CI: 1.05 to 1.22), AS (from 0.62 to 1.01, (95% CI: 0.76 to 1.33)), PsA (from 0.68 to 1.06, (95% CI: 0.88 to 1.28)), SLE (from 1.52 to 1.98, (95% CI: 1.67 to 2.33)) and SSc (from 2.27 to 4.24, (95% CI: 3.19 to 5.63)). In both SLE and SSc mortality was increased in men than women and in patients younger than 50 years. Conclusions Survival rates over 5 years in inflammatory arthritis under treatment are currently becoming comparable (AS/PsA) or slightly higher (RA) than those of the general population. However, all-cause mortality is almost twofold and fourfold higher in SLE and SSc, respectively, being even higher for male and younger patients.

The Emerging Roles of Endocrine Hormones in Different Arthritic Disorders.

Abstract: The relationship between endocrine hormones and the spectrum of rheumatic conditions has long been discussed in the literature, focusing primarily on sexual hormones, such as estrogens, androgens, prolactin (PRL). Estrogens are indeed involved in the pathogenesis of the main inflammatory arthritis thanks to their effects on the immune system, both stimulatory and inhibitory. The PRL system has been discovered in synovial tissue of rheumatoid arthritis (RA) and psoriatic arthritis (PsA), patients and has been propose as a new potential therapeutic target. Besides sexual hormones, in the last years scientific interest about the crosstalk of immune system with other class of hormones has grown. Hormones acting on the bone tissue (i.e. parathyroid hormone, vitamin D) and modulators of the Wnt pathway (i.e. Dickkopf-1) have been demonstrated to play active role in inflammatory arthritis course, defining a new field of research named osteoimmunology. PTH, which is one of the main determinants of Dkkopf-1, plays a crucial role in bone erosions in RA and a correlation between PTH, Trabecular Bone Score (TBS) and disease activity has been found in ankylosing spondylitis (AS). In PSA is under studying the interaction among IL-17 and bone metabolism. The purpose of this review is to discuss and summarize the recent data about the interaction between endocrine hormone and immune system in the main rheumatic disorders, covering in particular the role of bone-related hormones and cytokines. We will describe this relationship from a biochemical, diagnostic and therapeutic perspective, with a particular focus on RA, PsA and AS.

COVID-19: An Emerging Culprit of Inflammatory Arthritis

Abstract: Arthralgia is one of the most common symptoms that occur in patients with COVID-19. About 15% of patients present with arthralgia at some point. Although COVID-19 seems to attack the musculoskeletal system (muscles and joints) in its infective and postinfective stage causing inflammatory arthritis, not much is known about the rheumatic manifestations of this infection. In this case series of 5 patients, we discuss the occurrence of bilaterally symmetrical polyarthritis in patients, previously free from any rheumatic disease, after encountering COVID-19 infection. The musculoskeletal manifestations in these patients phenotypically resembled rheumatoid arthritis. These patients were treated successfully with low-dose glucocorticoids and disease-modifying antirheumatic drugs (DMARDs).

SARS-CoV-2 infection in patients with systemic autoimmune diseases

Abstract: Systemic autoimmune diseases (SAD) are a heterogeneous group of diseases with a common aetiopathogenic basis affecting all ages characterised by a systemic phenotypic expression with a wide range of severity and outcomes that often require immunosuppressive therapies, leaving patients at high risk of infection. Knowledge of the impact of COVID-19 in patients with SAD is limited because most are included in studies carried out in patients with autoimmune and rheumatic diseases (mainly inflammatory arthritis). Most studies supported an increased risk of SARS-Cov-2 infection in patients with AD and SAD. Although case-control studies reported no significant differences in the rate of poor outcomes between patients with and without AD, large population-based studies analysing baseline risk factors reported a 2-3 times higher rate of poor outcomes in patients with AD, especially in those with SAD. Individual risk factors associated with poor outcomes included gender male, older age, and underlying comorbidities and therapies (glucocorticoids, sulfasalazine, immunosuppressants and rituximab). Patients with SAD had less favourable COVID-19 outcomes than those with inflammatory arthritis, possibly due to a differentiated underlying therapeutic approach (glucocorticoids, immunosuppressants and B-cell depleting agents for most SAD, anti-cytokine therapies and JAK inhibitors for inflammatory arthritis). Despite the limited evidence, most studies suggest that patients with SAD have an increased risk of a worse evolution of SARS-CoV-2 infection, including a greater risk of hospitalisation/ICU admission and worse survival rates and, therefore, should be considered a high-risk group for COVID-19.

Macrophage migration inhibitory factor drives pathology in a mouse model of spondyloarthritis and is associated with human disease.

Abstract: Spondyloarthritis (SpA), a type 3 immunity-mediated inflammatory arthritis, is a systemic rheumatic disease that primarily affects the joints, spine, gut, skin, and eyes. Macrophage migration inhib...

Targeting synovial fibroblast proliferation in rheumatoid arthritis (TRAFIC): an open-label, dose-finding, phase 1b trial.

Abstract: Summary Background Current rheumatoid arthritis therapies target immune inflammation and are subject to ceiling effects. Seliciclib is an orally available cyclin-dependent kinase inhibitor that suppresses proliferation of synovial fibroblasts—cells not yet targeted in rheumatoid arthritis. Part 1 of this phase 1b/2a trial aimed to establish the maximum tolerated dose of seliciclib in patients with active rheumatoid arthritis despite ongoing treatment with TNF inhibitors, and to evaluate safety and pharmacokinetics. Methods Phase 1b of the TRAFIC study was a non-randomised, open-label, dose-finding trial done in rheumatology departments in five UK National Health Service hospitals. Eligible patients (aged ≥18 years) fulfilled the 1987 American College of Rheumatology (ACR) or the 2010 ACR–European League Against Rheumatism classification criteria for rheumatoid arthritis and had moderate to severe disease activity (a Disease Activity Score for 28 joints [DAS28] of ≥3·2) despite stable treatment with anti-TNF therapy for at least 3 months before enrolment. Participants were recruited sequentially to a maximum of seven cohorts of three participants each, designated to receive seliciclib 200 mg, 400 mg, 600 mg, 800 mg, or 1000 mg administered in 200 mg oral capsules. Sequential cohorts received doses determined by a restricted, one-stage Bayesian continual reassessment model, which determined the maximum tolerated dose (the primary outcome) based on a target dose-limiting toxicity rate of 35%. Seliciclib maximum concentration (Cmax) and area under the plasma concentration time curve 0–6 h (AUC0–6) were measured. This study is registered with ISRCTN, ISRCTN36667085. Findings Between Oct 8, 2015, and Aug 15, 2017, 37 patients were screened and 15 were enrolled to five cohorts and received seliciclib, after which the trial steering committee and the data monitoring committee determined that the maximum tolerated dose could be defined. In addition to a TNF inhibitor, ten (67%) enrolled patients were taking conventional synthetic disease modifying antirheumatic drugs. The maximum tolerated dose of seliciclib was 400 mg, with an estimated dose-limiting toxicity probability of 0·35 (90% posterior probability interval 0·18–0·52). Two serious adverse events occurred (one acute kidney injury in a patient receiving the 600 mg dose and one drug-induced liver injury in a patient receiving the 400 mg dose), both considered to be related to seliciclib and consistent with its known safety profile. 65 non-serious adverse events occurred during the trial, 50 of which were considered to be treatment related. Most treatment-related adverse events were mild; 20 of the treatment-related non-serious adverse events contributed to dose-limiting toxicities. There were no deaths. Average Cmax and AUC0–6 were two-times higher in participants developing dose-limiting toxicities. Interpretation The maximum tolerated dose of seliciclib has been defined for rheumatoid arthritis refractory to TNF blockade. No unexpected safety concerns were identified to preclude ongoing clinical evaluation in a formal efficacy trial. Funding UK Medical Research Council, Cyclacel, Research into Inflammatory Arthritis Centre (Versus Arthritis), and the National Institute of Health Research Newcastle and Birmingham Biomedical Research Centres and Clinical Research Facilities.