Expanding the role of CAR T-cell therapy: From B-cell hematological malignancies to autoimmune rheumatic diseases.

Chimeric antigen receptor (CAR) T-cell therapy is a form of immunotherapy where the lymphocytes, mostly T-cells, are redirected to specifically recognize and eliminate a target antigen by coupling them with CARs. The binding of CAR and target cell surface antigens leads to vigorous T cell activation and robust anti-tumor immune responses. Areas of implication of CAR T-cell therapies include mainly hematological malignancies (i.e., advanced B-cell cancers); however, recent studies have proven the unprecedented success of the new immunotherapy also in autoimmune rheumatic diseases. We aim to review the recent advances in CAR T-cell therapies in rheumatology but also to address the limitations of their use in the real clinical practice based on the data on their efficacy and safety.

Rehabilitation of patients with inflammatory rheumatic diseases and comorbidities: unmet needs.

Comorbidities may contribute to inadequate response to therapy and accelerate disability in various rheumatic diseases such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and psoriatic arthritis (PsA). Cardiovascular, oncological, and infectious comorbidities are common in rheumatic patients. The rehabilitation of patients with inflammatory rheumatic diseases (IRDs) with comorbidities requires a multidisciplinary approach to improving patients' functional mobility, slowing down the disease progression and minimizing the risks of complications. The evidence suggests that cardiac rehabilitation can be implemented in daily practice in patients with IRDs to reduce mortality for those with established risk factors. Physical exercises reduce the severity, improve the clinical course, and reduce hospitalization rates in patients with rheumatic diseases. A rehabilitation program with focused physical therapy can lead to functional improvements and reduction of disease activity in patients with lowered quality of life (QoL). Health professionals should provide evidence-based recommendations for patients with rheumatic diseases and comorbidities to initiate the self-management of their diseases and prevent complications.

[Occupational balance, disability and functionality in people with rheumatic disease]. / Equilibrio ocupacional, discapacidad y funcionalidad en personas con enfermedades reumáticaS

BACKGROUND: We aimed to assess the occupational balance of people with rheumatic disease, analyze its relationship with participation, performance, and satisfaction with daily life activities, and evaluate whether age or receiving non-pharmacological treatment affects the outcome. METHODS: Cross-sectional study carried out between March and November 2021; patients with non-advanced stage of rheumatic disease from the ConArtritis Association - selected through simple random sampling -, were included. Sociodemographic data and scores from the OBQ, IMPACT-S, COPM questionnaires, and a questionnaire created ad hoc for daily life activities were collected online and/or by telephone. RESULTS: The occupational balance of the 47 participants was low (OBQ: 34.2; SD: 13.7). Despite a high participation in daily life activities (IMPACT-S: 76.8; SD: 13.1), the degree of performance and satisfaction with these activities was far from optimal (COPM-R: 3.9; SD: 2.0 and COPM-S: 4.3; SD: 2.5); 46.8% of the participants found limitations in at least four daily life activities (basic and instrumental) and 61.7% used at least one support product in their daily lives. These limitations reduced their resting time and affected their jobs, hobbies, and personal relationships. The level of performance was negatively related to age (p=0.04); No changes in the scores were found in patients who received non-pharmacological treatment. CONCLUSIONS: Our results suggest that individuals with non- advanced stage of a rheumatic disease perceive that their occupational balance may be improved should they have fewer limitations in daily life activities.

Mesenchymal Stem/Stromal Cell-Based Therapies in Systemic Rheumatic Disease: From Challenges to New Approaches for Overcoming Restrictions.

Systemic rheumatic diseases, such as rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis, are chronic autoimmune diseases affecting multiple organs and tissues. Despite recent advances in treatment, patients still experience significant morbidity and disability. Mesenchymal stem/stromal cell (MSC)-based therapy is promising for treating systemic rheumatic diseases due to the regenerative and immunomodulatory properties of MSCs. However, several challenges need to be overcome to use MSCs in clinical practice effectively. These challenges include MSC sourcing, characterization, standardization, safety, and efficacy issues. In this review, we provide an overview of the current state of MSC-based therapies in systemic rheumatic diseases, highlighting the challenges and limitations associated with their use. We also discuss emerging strategies and novel approaches that can help overcome the limitations. Finally, we provide insights into the future directions of MSC-based therapies for systemic rheumatic diseases and their potential clinical applications.

Current State of Platelet-rich Plasma in the Treatment of Rheumatic Disease: A Retrospective Review of the Literature.

INTRODUCTION: Rheumatic diseases are a spectrum of autoimmune or inflammatory diseases that cause damage to the musculoskeletal system as well as vital organs, such as the heart, lungs, kidneys, and central nervous system. METHODS: The study of rheumatic disease has made great progress in the understanding and management of these conditions in the last few decades using disease-modifying antirheumatic drugs and synthesized biological immunomodulating therapies. However, one potential treatment that has not been well investigated in rheumatic disease is platelet-rich plasma (PRP). PRP is proposed to facilitate the healing of injured tendons and ligaments through a variety of mechanisms, including mitogenesis, angiogenesis and macrophage activation via cytokine release, although its exact mechanism is unclear. RESULT: There has been a great deal of work in determining the exact preparation method and composition of PRP for regenerative purposes in orthopedic surgery, sports medicine, dentistry, cardiac surgery, pediatric surgery, gynecology, urology, plastic surgery, ophthalmology, and dermatology. Despite this, there is a paucity of research on the impact of PRP on rheumatic disease. CONCLUSION: This study aims to summarize and evaluate the current research concerning the use of PRP in rheumatic disease.

The effectiveness of yoga as a form of exercise in the management of rheumatic diseases.

Yoga, a long-standing Indian tradition, has gained popularity globally, inspiring many different disciplines to employ it as a complementary treatment for various diseases. Yoga is primarily composed of numerous physical poses and positions that are coupled with breathing techniques, profound relaxation, and meditation. There are many types of yoga with varying levels of difficulty. Yoga, consisting of various poses and postures with distinct postural mechanics, is frequently highlighted as an exercise that improves both physical and mental health. Applying the proper techniques to yoga poses can boost balance, strength, and flexibility while also improving general health and quality of life. In addition to its physical benefits, it is recognized that yoga enhances an individual's mood, anxiety, and depression levels and their ability to deal with stress. Rheumatic diseases affect many different organs, particularly the musculoskeletal structures, and negatively impact patients' quality of life. Maintaining a sufficient level of exercise is essential to preserve and enhance physical function in addition to pharmaceutical therapy, the mainstay of rheumatic disease treatment. In treatment guidelines for many rheumatic diseases, exercise, and physiotherapy techniques are stressed as the most substantial component of non-pharmacological treatment. This review considered yoga a form of exercise outside of traditional practices. From this perspective, we aimed to summarize the efficacy of yoga practices on various rheumatic diseases. Additionally, we aimed to highlight possible mechanisms of action.

Rheumatic Immune-Related Adverse Events due to Immune Checkpoint Inhibitors-A 2023 Update.

With the aging of the population, malignancies are becoming common complications in patients with rheumatoid arthritis (RA), particularly in elderly patients. Such malignancies often interfere with RA treatment. Among several therapeutic agents, immune checkpoint inhibitors (ICIs) which antagonize immunological brakes on T lymphocytes have emerged as a promising treatment option for a variety of malignancies. In parallel, evidence has accumulated that ICIs are associated with numerous immune-related adverse events (irAEs), such as hypophysitis, myocarditis, pneumonitis, and colitis. Moreover, ICIs not only exacerbate pre-existing autoimmune diseases, but also cause de novo rheumatic disease-like symptoms, such as arthritis, myositis, and vasculitis, which are currently termed rheumatic irAEs. Rheumatic irAEs differ from classical rheumatic diseases in multiple aspects, and treatment should be individualized based on the severity. Close collaboration with oncologists is critical for preventing irreversible organ damage. This review summarizes the current evidence regarding the mechanisms and management of rheumatic irAEs with focus on arthritis, myositis, and vasculitis. Based on these findings, potential therapeutic strategies against rheumatic irAEs are discussed.

Clinical Visit Frequencies in Rheumatology: A Systematic Literature Review.

OBJECTIVE: Clinical visits are a fundamental aspect of rheumatic disease care, but recommendations for appropriate visit frequencies are largely absent from guidelines, scarcely studied, and inconsistently reported. The aim of this systematic review was to summarize the evidence pertaining to visit frequencies for major rheumatic diseases. METHODS: This systematic review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Title/abstract screening, full-text screening, and extraction were carried out by 2 independent authors. Annual visit frequencies were either extracted or calculated and stratified by disease type and country of study. Weighted mean annual visit frequencies were calculated. RESULTS: A total of 273 relevant manuscript records were screened, and 28 were included after applying selection criteria. The included studies were equally divided between US and non-US and were published between 1985 and 2021. Most (n = 16) focused on rheumatoid arthritis (RA), systemic lupus erythematosus (SLE; n = 5), and fibromyalgia (FM; n = 4). For RA, the average annual visit frequencies were 5.25 for US rheumatologists, 4.80 for US non-rheumatologists, 3.29 for non-US rheumatologists, and 2.74 for non-US non-rheumatologists. For SLE, annual visit frequencies for non-rheumatologists were much higher than for US rheumatologists (12.3 versus 3.24). For FM, annual visit frequencies were 1.80 for US rheumatologists and 0.40 for non-US rheumatologists. There was a decreasing trend of visit frequency to rheumatologists from 1982 to 2019. CONCLUSION: Evidence for rheumatology clinical visits was limited and heterogeneous on a global scale. However, general trends suggest more frequent visits in the US and less frequent visits in recent years.

[Recommendations for the diagnosis and treatment of rheumatic diseases-related hemophagocytic syndrome in China].

Hemophagocytic syndrome (HPS), which is currently named as hemophagocytic lymphohistiocytosis (HLH), is a hyperinflammatory syndrome characterized by persistent fever, hepatosplenomegaly, pancytopenia and hemophagocytosis found in bone marrow, liver, spleen and lymph nodes due to excessive activation of macrophages and cytotoxic T cells. Macrophage activation syndrome (MAS) is a specific form of HLH induced by autoinflammatory/autoimmune disorders which can be life-threatening and requires multiple disciplines. In order to improve clinicians' understanding of MAS and standardize the clinical diagnosis and treatment practice of MAS, the rheumatology branch of Chinese Rheumatology Association organized domestic experts to formulate the diagnosis and treatment standard, in order to improve the diagnosis and treatment level of MAS and improve the prognosis of patients.

Assessment of complementary and alternative medicine methods in the management of ankylosing spondylitis, rheumatoid arthritis, and fibromyalgia syndrome.

A wide variety of musculoskeletal, arthritic, connective tissue, and vasculitic diseases fall under the umbrella of "rheumatic diseases". Ankylosing spondylitis, rheumatoid arthritis, and fibromyalgia syndrome are the three members of this disease group with relatively high prevalence. Pharmacological options are at the center of therapeutic algorithms in treating rheumatic diseases, particularly in reducing inflammation. Despite significant advances in pharmacological treatment in recent years, achieving complete treatment success in a group of patients is impossible. Therefore, patients with rheumatic diseases frequently utilize alternative treatment options, such as complementary and alternative medicine. Complementary and alternative medicine is a broad category of health practices not part of the leading health system. Patients with rheumatic diseases turn to complementary and alternative medicine for various reasons, including restricted access to some treatments due to high prices and rigorous regulations, worries about drug side effects, and symptoms that continue despite pharmacological treatment. In addition, because complementary and alternative medicine options are considered natural, they are frequently accepted as well tolerated and have few harmful effects. Ankylosing spondylitis, rheumatoid arthritis, and fibromyalgia syndrome are the primary foci of this comprehensive review. First, we attempted to summarize the non-traditional physical medicine and complementary and alternative medicine options that can be utilized to manage these diseases. Second, we addressed the link between exercise and inflammation in rheumatic diseases. We briefly discussed the possible benefits of exercise-based approaches. In addition, we highlighted the benefits of cooperation between rheumatology and physical medicine-rehabilitation clinics.

Paraneoplastic musculoskeletal disorders: review and update for radiologists.

Rheumatic paraneoplastic syndromes are rare syndromes that occur at distant sites from the underlying tumor and may involve the bones, joints, fasciae, muscles, or vessels. In the absence of a known tumor, early recognition of a rheumatic syndrome as paraneoplastic permits dedicated work-up for, and potentially early treatment of an occult malignancy. Although there is a continuously growing list of paraneoplastic rheumatic disorders, not all of these disorders have a well-established association with a neoplastic process. The goals of this article are to review the clinical characteristics, diagnostic work-up, and imaging findings of well-documented rheumatic paraneoplastic disorders.

[Management of inflammatory rheumatic diseases during and after malignancies]. / Management von entzündlich rheumatischen Erkrankungen während und nach Malignomen.

The management of inflammatory rheumatic diseases in patients with a simultaneous or previous malignant disease is associated with complex questions. Difficulties and possible solutions in the interpretation of meaningful studies are presented. Recommendations in guidelines on this topic are discussed. National registries and health insurance databases were examined with respect to the risk of tumor recurrence under disease-modifying antirheumatic drugs; however, these analyses mainly refer to tumor necrosis factor (TNF) inhibitors and rituximab. Data on tumor incidence and, if available, risk of tumor recurrence are summarized for commonly used disease-modifying antirheumatic drugs. Finally, an attempt is made to formulate proposals for rheumatological treatment in patients with a history of malignancy.

[Digitally supported rheumatological screening consultation : How useful is a questionnaire scoring system (RhePort)?] / Digital unterstützte rheumatologische Screeningsprechstunde : Wie hilfreich ist ein Fragebogen-Scoringsystem (RhePort)?

Regarding scarce capacities an early detection consultation (EDC) was established to discriminate patients in an outpatient setting with inflammatory from non-inflammatory rheumatic diseases. A total of 500 patients suspected of having a rheumatic disease received an appointment within 2 weeks. They were interviewed with the help of a digital questionnaire (RhePort), briefly physically examined followed by a determination of CRP. The questionnaire answers were scored using an algorithm within RhePort (from 0 = non-inflammatory to 4 = highly probably inflammatory). Likewise, after completion of the EDC, the rheumatologists scored the overall assessment. The RhePort score and EDC score were compared with the "true" diagnosis made in a detailed second examination after an average of 10 weeks. In 490 evaluable patients 133 inflammatory (27%) and 357 noninflammatory rheumatic diseases (73%) were diagnosed. A classification based solely on the RhePort questionnaire (score > 1) identified 103 out of 129 as inflammatory (sens. 80%) and 125 out of 355 as non-inflammatory (spec. 35%) resulting in an AUC of 0.62 after ROC analysis. With a score > 1, the rheumatological assessment after EDC classified 130 out of 133 patients as inflammatory (sensitivity 98%) and 261 out of 357 as non-inflammatory (specificity 73%). The combined EDC can decisively increase the sensitivity and specificity compared to an "automated" survey by means of a digital questionnaire alone. In addition to the early identification and treatment of inflammatory patients, rapid identification of patients who are not in need of rheumatological treatment can create capacities for care.

Rheumatic Complications of Immune Checkpoint Inhibitors.

Immune checkpoint inhibitors activate the immune system to combat cancer. In doing so, however, they can cause immune-related adverse events (irAEs), including rheumatic syndromes, such as inflammatory arthritis, polymyalgia rheumatica, and myositis. This article reviews rheumatic irAEs that may be encountered in the general medicine practice and provides guidance to support prompt recognition, referral, and treatment of these patients.

[Management of comorbidities in patients suffering from inflammatory rheumatic diseases]. / Prise en charge des comorbidités chez les patients souffrant d'un rhumatisme inflammatoire.

In comparison to the general population, chronic inflammatory rheumatic diseases are more often associated with various comorbidities. Due to the important impact of these pathologies on the quality of life, on the choice of treatment and on the response to the latest, they need to be searched for actively. In this article, we present some of these comorbidities, as well as propositions for their management. We discuss the cardiovascular diseases, neoplasia, infections, interstitial lung disease and osteoporosis.

Les maladies rhumatismales inflammatoires (MRI) sont plus fréquemment associées à certaines comorbidités par rapport à la population générale. Ces pathologies doivent être activement recherchées en raison de leur impact sur la qualité de vie des patients, et car elles peuvent influencer nos choix thérapeutiques. Nous présentons ici cinq comorbidités importantes et leur prise en charge spécifique, à savoir les maladies cardiovasculaires, les néoplasies, les infections, les maladies interstitielles pulmonaires et l'ostéoporose.

Application of extracellular vesicles derived from mesenchymal stem cells as potential therapeutic tools in autoimmune and rheumatic diseases.

Mesenchymal stem cells (MSCs) have been proven to have superior potential to be used astherapeutic candidates in various disorders. Nevertheless, the clinical application of these cells have been restricted because of their tumorigenic properties. Increasing evidence has established that the valuable impacts of MSCs are mainly attributable to the paracrine factors including extracellular vesicles (EVs). EVs are nanosized double-layer phospholipid membrane vesicles contain various proteins, lipids and miRNAs which mediate cell-to-cell communications. Due to their inferior immunogenicity and tumorigenicity, as well as easier management, EVs have drawn attention as potential cell-free replacement therapy to MSCs. For that reason, herein, we reviewed the recent findings of researches on different MSC-EVs and their effectiveness in the treatment of several autoimmune and rheumatic diseases including multiple sclerosis, inflammatory bowel disease, rheumatoid arthritis, osteoarthritis, osteoporosis, and systemic lupus erythematosus as well as Sjogren's syndrome, systemic sclerosis and other autoimmune diseases.

Outcomes of transitional care programs on adolescent chronic inflammatory systemic diseases: systematic review and meta-analyses.

BACKGROUND: Patients with juvenile chronic inflammatory systemic diseases (jCID) are vulnerable to many circumstances when transitioning to adult-centered healthcare; this increases the burden of disease and worsen their quality of life. METHODS: MEDLINE, Embase, Web of Science and Scopus were searched from inception to March 16th, 2021. We included observational, randomized controlled trials and quasi-experimental studies that evaluated a transitional care program for adolescents and young adults with jCIDs. We extracted information regarding health-related quality of life, disease activity, drop-out rates, clinical attendance rates, hospital admission rates, disease-related knowledge, surgeries performed, drug toxicity and satisfaction rates. RESULTS: Fifteen studies met our inclusion criteria. The implementation of transition programs showed a reduction on hospital admission rates for those with transition program (OR 0.28; 95% CI 0.13 to 0.61; I 2 = 0%; p = 0.97), rates of surgeries performed (OR 0.26; 95% CI 0.12 to 0.59; I 2 = 0%; p = 0.50) and drop-out rates from the adult clinic (OR 0.23; 95% CI 0.12 to 0.46; I 2 = 0%; p = 0.88). No differences were found in other outcomes. CONCLUSION: The available body of evidence supports the implementation of transition programs as it could be a determining factor to prevent hospital admission rates, surgeries needed and adult clinic attendance rates.

Safety and Efficacy of Mesenchymal Stromal Cells and Other Cellular Therapeutics in Rheumatic Diseases in 2022: A Review of What We Know So Far.

Although a number of new immunosuppressive agents and biologics have been approved for treating various autoimmune inflammatory rheumatic diseases, there remains a substantial number of patients who have no clinical response or limited clinical response to these available treatments. Use of cellular therapies is a novel approach for the treatment of autoimmune inflammatory rheumatic diseases, with perhaps enhanced efficacy and less toxicity than current therapies. Autologous hematopoietic stem cell transplants were the first foray into cellular therapies, with proven efficacy in scleroderma and multiple sclerosis. Newer, yet unproven, cellular therapies include allogeneic mesenchymal stromal cells, which have been shown to be effective in graft-versus-host disease and in healing Crohn's fistulas. Chimeric antigen receptor T cells are effective in various malignancies, with possible application in rheumatic diseases, as shown in preclinical studies in murine lupus and recently in human lupus. Treg cells are one of the master controllers of the immune response and are decreased in number and/or effectiveness in specific autoimmune diseases. Expansion of autologous Treg cells is an attractive approach to controlling autoimmunity. There are a number of other regulatory cells in the immune system, including Breg cells, dendritic cells, macrophages, and other T cell types, that are in early stages of development as treatments. In this review, the current evidence for the efficacy and mechanisms of actions of cellular therapies already in use or in clinical trials in human autoimmune diseases will be discussed, including the limitations of these therapies and potential side effects.

Impact of a Rheumatology Clinic Protocol on Tobacco Cessation Quit Line Referrals.

OBJECTIVE: Smoking increases cardiopulmonary and rheumatic disease risk, yet tobacco cessation intervention is rare in rheumatology clinics. This study aimed to implement a rheumatology staff-driven protocol, Quit Connect, to increase the rate of electronic referrals (e-referrals) to free, state-run tobacco quit lines. METHODS: We conducted a quasi-experimental cohort study of Quit Connect at 3 rheumatology clinics comparing tobacco quit line referrals from 4 baseline years to referrals during a 6-month intervention period. Nurses and medical assistants were trained to use 2 standardized electronic health record (EHR) prompts to check readiness to quit smoking within 30 days, advise cessation, and connect patients using tobacco quit line e-referral orders. Our objective was to use EHR data to examine the primary outcome of tobacco quit line referrals using pre/post design. RESULTS: Across 54,090 pre- and post-protocol rheumatology clinic visits, 4,601 were with current smokers. We compared outcomes between 4,078 eligible pre-implementation visits and 523 intervention period visits. Post-implementation, the odds of tobacco quit line referral were 26-fold higher compared to our pre-implementation rate (unadjusted odds ratio [OR] 26 [95% confidence interval (95% CI) 6-106]). Adjusted odds of checking readiness to quit in the next 30 days increased over 100-fold compared to pre-implementation (adjusted OR 132 [95% CI 99-177]). Intervention led to e-referrals for 71% of quit-ready patients in <90 seconds; 24% of referred patients reported a quit attempt. CONCLUSION: Implementing Quit Connect in rheumatology clinics was feasible and improved referrals to a state-run tobacco quit line. Given the importance of smoking cessation to reduce cardiopulmonary and rheumatic disease risk, future studies should investigate disseminating cessation protocols like Quit Connect that leverage tobacco quit lines.