Use In Rheumatic Diseases Research Articles

JAK Inhibitors - Pros and Cons Learned from Their Use in Rheumatic Diseases

JAK Inhibitors - Pros and Cons Learned from Their Use in Rheumatic Diseases

Dehydroepiandrosterone (DHEA) Supplementation in Rheumatic Diseases: A Systematic Review.

Dehydroepiandrosterone (DHEA) is an adrenal hormone used to treat rheumatic conditions such as systemic lupus erythematosus (SLE), Sjogren's syndrome (SS), rheumatoid arthritis (RA) with controversial results. To review the results of DHEA use in rheumatic diseases. PubMed, Scielo, Scopus, and Embase databases were systematically searched for articles on the treatment of rheumatic diseases with DHEA between 1966 and April 2023. Twenty-one studies were identified: 13 in SLE, 5 in SS, 2 in RA, and 1 in fibromyalgia. DHEA use in SLE has shown a mild to moderate effect on disease activity, a positive effect on bone mineral density (BMD), and improved fatigue. The studies on SS showed a decrease in symptoms of dry mouth, but its performance did not differ from placebo in disease activity. In RA, a questionable effect on disease activity was noted. The only study on fibromyalgia failed to show any improvement. The drug was well tolerated; mild androgenic effects were the most common complaints. DHEA seems to have a place in SLE treatment, where it improves BMD and disease activity. The use in RA, SS, and FM is questionable.

An introduction to machine learning and analysis of its use in rheumatic diseases.

Machine learning (ML) is a computerized analytical technique that is being increasingly employed in biomedicine. ML often provides an advantage over explicitly programmed strategies in the analysis of multidimensional information by recognizing relationships in the data that were not previously appreciated. As such, the use of ML in rheumatology is increasing, and numerous studies have employed ML to classify patients with rheumatic autoimmune inflammatory diseases (RAIDs) from medical records and imaging, biometric or gene expression data. However, these studies are limited by sample size, the accuracy of sample labelling, and absence of datasets for external validation. In addition, there is potential for ML models to overfit or underfit the data and, thereby, these models might produce results that cannot be replicated in an unrelated dataset. In this Review, we introduce the basic principles of ML and discuss its current strengths and weaknesses in the classification of patients with RAIDs. Moreover, we highlight the successful analysis of the same type of input data (for example, medical records) with different algorithms, illustrating the potential plasticity of this analytical approach. Altogether, a better understanding of ML and the future application of advanced analytical techniques based on this approach, coupled with the increasing availability of biomedical data, may facilitate the development of meaningful precision medicine for patients with RAIDs.

Therapeutic implications of extracorporeal photopheresis for rheumatic diseases

Extracorporeal photopheresis (ECP) procedure is based on mononuclear cells (MNC) apheresis and their extracorporeal UVA exposure. It has been applied mainly in hematology and transplantation. Over thirty years of experience confirmed its effectiveness, outstanding safety profile and good tolerance. These observations encourage the implementation of ECP in the treatment of autoimmune connective tissue diseases. The procedure might be considered in refractory cases, when the first line treatment strategies do not control disease activity or immunosuppressants are contraindicated and in the group of patients with high risk of infections. Current literature about using ECP in rheumatology is scarce and most data come from case reports and small observational studies. Systemic sclerosis is the most studied rheumatic disease in the field of ECP use. The disease appeared on the list of clinical applications of ECP therapy according to American Society for Apheresis. However, no European or American guidelines, or recommendations for the treatment in rheumatology suggest ECP as the treatment option. There are no standards in performing ECP in rheumatic diseases concerning indications, length of therapy, concomitant immunosuppressive treatment, follow up or patients characteristic. In this review, we have searched literature concerning ECP use in rheumatic diseases.

Pharmacovigilance of Biopharmaceuticals in Rheumatic Diseases, Adverse Events, Evolution, and Perspective: An Overview.

Since we have gained an understanding of the immunological pathophysiology of rheumatic diseases such as rheumatoid arthritis and systemic lupus erythematosus, treatment based on biological drugs has become a fundamental axis. These therapies are oriented towards the regulation of cytokines such as tumour necrosis factor-alpha (TNF-α), interleukin (IL)-6, IL-1, and the modulation of cell-mediated immunity (B cells and T cells) by anti CD20 or anti CTAL-4 agents, and can increase the risk of associated infections or adverse events (AE). In this context, the entry of biotherapeutics represented a challenge for pharmacovigilance, risk management and approval by the main global regulatory agencies regarding biosimilars, where efficacy and safety are based on comparability exercises without being an exact copy in terms of molecular structure. The objective of this review is divided into three fundamental aspects: (i) to illustrate the evolution and focus of pharmacovigilance at the biopharmaceutical level, (ii) to describe the different approved recommendations of biopharmaceuticals (biological and biosimilars) and their use in rheumatic diseases (RDs) such as rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), systemic lupus erythematosus (SLE) and other less frequent RD like cryopyrin-associated autoinflammatory syndromes (CAPS), and (iii) to identify the main AE reported in the post-marketing phase of RD biopharmaceuticals.

A favorable effect of hydroxychloroquine on glucose and lipid metabolism beyond its anti-inflammatory role.

Hydroxychloroquine (HCQ), a commonly used antimalarial drug in rheumatic diseases, has shown favorable metabolic effects on both glucose control and lipid profiles. We describe a case of a young woman with type 1 diabetes whose glycemic control was optimized with the introduction of HCQ as a treatment for her Sjogren syndrome in addition to a subtle yet measurable improvement in her lipid profile. An increasing body of evidence supports the beneficial impacts of HCQ in various ancillary conditions, including diabetes mellitus and dyslipidemia. However, mechanisms of action responsible for these effects remain ill-defined and may include alterations in insulin metabolism and signaling through cellular receptors. These favorable metabolic effects of HCQ and further understanding of underlying mechanisms may provide an additional rational for its use in rheumatic diseases, conditions associated with an elevated cardiovascular risk.

Etanercept: A Review of Its Use in Autoimmune Inflammatory Diseases

With its approval more than 15 years ago, subcutaneous etanercept (Enbrel(®)) was the first biological disease-modifying antirheumatic drug (bDMARD) and the first tumour necrosis factor inhibitor to be approved for use in rheumatic diseases. Etanercept remains an important cost-effective treatment option in adult patients with rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis or plaque psoriasis, and in paediatric patients with juvenile idiopathic arthritis or plaque psoriasis. In all of these populations, etanercept (with or without methotrexate) effectively reduced signs and symptoms, disease activity and disability, and improved health-related quality of life, with these benefits sustained during long-term treatment. The safety profile of etanercept during short- and long-term treatment was consistent with the approved product labelling, with adverse events being of a predictable and manageable nature. The introduction of etanercept and other bDMARDs as therapeutic options for patients with autoimmune rheumatic diseases and spondyloarthropathies revolutionized disease management and these agents continue to have a central role in treatment strategies. This article reviews the extensive clinical experience with etanercept in these patient populations.

Metotrexato y su Uso en el Tratamiento de Enfermedades Reumáticas

Los autores revisan el uso del Metrotexate en el tratamiento de las enfermedades reumáticas, con especial énfasis en los recientes conceptos desarrollados como droga de segunda línea en el tratamiento de la artritis reumatoidea. Se presenta una revisión de los aspectos farmacocinóticos, eficacia, toxicidad y monitoreo del tratamiento de este medicamento.

Systematic review of 2008-2012 literature and update of recommendations for the use of methotrexate in rheumatic diseases, with a focus on rheumatoid arthritis

The objective of this review is to update the recommendations of the 2010 Italian Consensus on the use of methotrexate (MTX) in rheumatoid arthritis (RA) and other rheumatic diseases. The literature published between 2008 and 2012 was systematically reviewed and updated recommendations on MTX use in rheumatic diseases, particularly RA, were formulated. These recommendations were approved by a panel of expert Italian Rheumatologists. A total of 10,238 references were identified, among which 70 studies were selected for critical evaluation. Sufficient evidence had accumulated to warrant changes to several of the recommendations in the new version. A new recommendation for patients with RA who are in MTX-induced clinical remission was also proposed and approved by the panel. Updated recommendations for the use of MTX in patients with RA or other rheumatologic disease are proposed.

Current and future biosimilars: potential practical applications in rheumatology

Current and future biosimilars: potential practical applications in rheumatology Ghaith Noaiseh, Larry Moreland Division of Rheumatology and Clinical Immunology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA Abstract: The use of biologics in the field of rheumatology has dramatically changed the way we treat rheumatic diseases. As the patent-expiration dates for many tumor necrosis-factor inhibitors and other biological agents are approaching, many large pharmaceutical companies are developing and testing their own versions of these agents; this is due to the biologics' huge revenue potential. The potential cost saving is a major incentive for their development. Producing a biosimilar is not an easy task, as minor changes in the production process can have profound immunological and clinical consequences. The European Medicines Agency (EMA) has led the efforts in issuing guidelines to streamline the approval process for applicants interested in developing biosimilars. The US Food and Drug Administration (FDA) has followed the EMA track and has guidelines in place, but the process varies in different countries. The approval process is far more complex than the one used for the approval of small-molecule generic products. Biosimilars should be developed according to the strict rules set forth by the EMA and FDA; other intended copies are available for clinical use in different parts of the world, but should not be considered biosimilars, as they do not fulfill the stringent definition criteria. Biosimilars will soon be in the market, and their use in rheumatic diseases will likely change our treatment approach. Rheumatologists and other health-care professionals will soon be faced with many questions and will have to be familiarized with the concept and the points of debate. Keywords: biosimilar, rheumatology, biologic, generic, TNF inhibitor, rituximab

Bone marrow mesenchymal cells: Promises for use in rheumatic diseases

Bone marrow mesenchymal cells: Promises for use in rheumatic diseases

The Italian contributions to the history of salicylates

It is well-known that the modern history of salicylates began in 1899 when the compound acetylsalicylic acid was registered and introduced commercially as "aspirin" by the Bayer Company of Germany. As a matter of fact, however, remedies made from willow bark had been used to treat fever and rheumatic complaints at least since 1763, when Edward Stone described their efficacy against malarian fever. A number of Italian scientists made significant contributions during the long period of research leading up to the synthesis of acetylsalicylic acid and its widespread use in rheumatic diseases. In this paper we will review the contributions of some of these researchers, beginning with Bartolomeo Rigatelli, who in 1824 used a willow bark extract as a therapeutic agent, denominating it "salino amarissimo antifebbrile" (very bitter antipyretic salt). In the same year, Francesco Fontana described this natural compound, giving it the name "salicina" (salicin). Two other Italian chemists added considerably to current knowledge of the salicylates: Raffaele Piria in 1838, while working as a research fellow in Paris, extracted the chemical compound salicylic acid, and Cesare Bertagnini in 1855 published a detailed description of the classic adverse event associated with salicylate overdoses--tinnitus--which he studied by deliberately ingesting excessive doses himself. Bertagnini and above all Piria also played conspicuous roles in the history of Italy during the period of the Italian Risorgimento, participating as volunteers in the crucial battle of Curtatone and Montanara during the first Italian War of Independence.

O uso de provas de atividade inflamatória em reumatologia

A inflamação, localizada ou sistêmica, é uma das características de doenças reumatológicas. A resposta a uma lesão tecidual desencadeia uma série de modificações que promovem eliminação de patógenos, limitação do dano tecidual e restauração da estrutura lesada. Essas modificações dependem do aumento ou da diminuição da concentração sérica de proteínas, conhecidas como biomarcadores inflamatórios, que atuam na resposta inflamatória. A análise laboratorial desses marcadores permite, juntamente com os dados clínicos e outros exames complementares, acessar a atividade de algumas doenças e monitorar a resposta à terapêutica, assim como pode sugerir presença de infecção. Atualmente, o reumatologista tem à sua disposição algumas opções de exames que avaliam a resposta inflamatória, como a proteína C-reativa, a velocidade de hemossedimentação e a eletroforese de proteínas, entre outros. Este artigo revisa as características de alguns desses biomarcadores e o emprego das provas de atividade inflamatória em doenças reumatológicas.

Evidenzbasierte Empfehlungen einer nationalen Expertenrunde zum Einsatz von Methotrexat bei entzündlich-rheumatischen Erkrankungen

Hintergrund: Methotrexat (MTX) ist eines der am häufigsten eingesetzten Basistherapeutika bei rheumatischen Erkrankungen. In der klinischen Praxis und zahlreichen Therapiestudien ist MTX der Goldstandard für die Behandlung der rheumatoiden Arthritis. Dennoch hat eine Umfrage im Rahmen der internationalen 3e-Initiative (Evidence, Experts, Exchange) unter nationalen und internationalen Experten 10 unzureichend geklärte Fragen zur klinischen Anwendung von MTX erbracht. In diesem Projekt sollten daher evidenzbasierte Empfehlungen für die Anwendung von MTX erarbeitet werden. Die nationalen Empfehlungen der deutschen Expertengruppe werden hier vorgestellt.

Update on Anti-TNF-Alpha Treatment in Rheumatic Diseases

The development of inhibitors of Tumor Necrosis Factor (TNF)α ro-inflammatory cytokine playing a pivotal role in chronic inflammatory diseases, represents a milestone in the therapy of several rheumatic diseases. Currently, three TNFα -blo drugs are available for clinical use in rheumatic diseases: infliximab, etanercept and adalimumab. These drugs rapidly reduce disease activity and probably change the poor outcome of several chronic rheumatic diseases, by preventing the development of bone erosions, joint deformity and disability. Although these drugs have proved to be effective and well tolerated in the short period, some concerns exist about long-term safety and efficacy. In fact, the longterm use of inhibitors of TNFα,a pivota okine in host defense, might result in the development of infections and neoplasms, therefore the long-term safety has to be defined. The most frightening infection to date is tuberculosis, and guidelines for the screening of patient candidates to biological treatment has significantly reduced the risk. Parasitic and viral infections do not contraindicate biological therapy. Lymphoma has been reported in association with TNFα antagonists, h ether or not there is a causal relationship is still debated. The use of biological agents in other rheumatic inflammatory conditions is rapidly increasing, but their cost poses a considerable financial burden on healthcare systems and a careful economic evaluation is needed. /abs > Keywords: Etanercept, infliximab, adalimumab, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis

Biological agents recommended for use in rheumatic diseases

Biological agents recommended for use in rheumatic diseases

Naproxen A Reappraisal of its Pharmacology, and Therapeutic Use in Rheumatic Diseases and Pain States

Naproxen is a nonsteroidal anti-inflammatory drug (NSAID) advocated for use in painful and inflammatory rheumatic and certain nonrheumatic conditions. It may be administered orally or rectally using a convenient once or twice daily regimen. Dosage adjustments are not usually required in the elderly or those with mild renal or hepatic impairment although it is probably prudent to start treatment at a low dosage and titrate upwards in such groups of patients. Numerous clinical trials have confirmed that the analgesic and anti-inflammatory efficacy of naproxen is equivalent to that of the many newer and established NSAIDs with which it has been compared. The drug is effective in many rheumatic diseases such as rheumatoid arthritis, osteoarthritis, ankylosing spondylitis and nonarticular rheumatism, in acute traumatic injury, and in the treatment of and prophylaxis against acute pain such as migraine, tension headache, postoperative pain, postpartum pain and pain associated with a variety of gynaecological procedures. Naproxen is also effective in treating the pain and associated symptoms of primary or secondary dysmenorrhoea, and decreases excessive blood loss in patients with menorrhagia. The adverse effect profile of naproxen is well established, particularly compared with that of many newer NSAIDs, and the drug is well tolerated. Thus, the efficacy and tolerability of naproxen have been clearly established over many years of clinical use, and it can therefore be considered as a first-line treatment for rheumatic diseases and various pain states.

Clinical pharmacology and toxicology of cyclophosphamide: emphasis on use in rheumatic diseases

N UMEROUS cytotoxic drugs are available for the treatment of severe forms of rheumatic diseases-’ Biologic effects of alkylating agents were first reported in 1887,4 and over the years, these agents have been used extensively in the treatment of neoplastic disease.5.6 Intravenous nitrogen mustard, in 195 1, was reported as clinically effective in the management of two patients with rheumatoid arthritis (RA).’ It is only during the past 20 years that the use of alkylating agents has increased dramatically in the management of rheumatic diseases. Chlorambucil and cyclophosphamide (CP) are the two alkylating agents currently used most often in the management of rhematic disease. Cyclophosphamide, a bifunctionally substituted nitrogen mustard compound, was synthesized in 1958.’ The first major report, albeit uncontrolled, suggesting the benefit of CP for treatment of RA appeared in 1968.9 Since then, numerous controlled and uncontrolled studies have been reported which variably support the use of CP for treatment of a number of rheumatic diseases. These diseases include RA,“” systemic lupus erythematosus, (SLE)12,13 and numerous systemic vasculidites2 The purpose of this review is to summarize the clinical pharmacology and toxicology of CP, with special emphasis on its use in rheumatic diseases.

ANTI-INFLAMMATORY, ANALGESIC AND ANTIPYRETIC ACTIVITIES OF 6-CHLORO-5-CYCLOHEXYLINDAN-1-CARBOXYLIC ACID (TAI-284)

Since the discovery of adramatically potent antiphlogistic or antirheumatic effect of cortisone, a number of glucocorticoid derivatives were synthesized for pharmacological evaluation and some of them have been introduced to clinical use in rheumatic diseases and other various inflammatory disorders. The large doses or prolonged use of glucocorticoids, however, produced a variety of clinical side effects such as gastro-intestinal lesion and impaired protection against infection mainly due to adaptative adrenal atrophy and immunosuppression. Enthusiastic efforts to dissociate the therapeutic effects from adverse ones in chemical structure of glucocorticoids have all resulted in failure.

Anti-inflammatory, analgesic and antipyretic activities of 6-chloro-5-cyclohexylindan-1-carboxylic acid (TAI-284).

Since the discovery of adramatically potent antiphlogistic or antirheumatic effect of cortisone, a number of glucocorticoid derivatives were synthesized for pharmacological evaluation and some of them have been introduced to clinical use in rheumatic diseases and other various inflammatory disorders. The large doses or prolonged use of glucocorticoids, however, produced a variety of clinical side effects such as gastro-intestinal lesion and impaired protection against infection mainly due to adaptative adrenal atrophy and immunosuppression. Enthusiastic efforts to dissociate the therapeutic effects from adverse ones in chemical structure of glucocorticoids have all resulted in failure.