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Lupus Science & Medicine Sep 2021Immune dysregulation in SLE and the corresponding immune-modulating and immunosuppressive nature of the treatments may play key roles in infection risk. We compared...
OBJECTIVE
Immune dysregulation in SLE and the corresponding immune-modulating and immunosuppressive nature of the treatments may play key roles in infection risk. We compared serious infection rates among individuals with incident SLE with the general population, and examined the role of treatment initiation in SLE.
METHODS
Newly diagnosed patients with SLE (2006-2013) and general population comparators from the Swedish Lupus Linkage cohort were followed for serious infection through 2016. Adjusted Cox and frailty models estimated the relative risk of first and recurrent infections, respectively. Using a new-user design, rates of serious infections were compared between disease-modifying antirheumatic drugs (DMARDs) and hydroxychloroquine (HCQ) initiators. We then evaluated three DMARDs (azathioprine, mycophenolate mofetil and methotrexate) in multivariable-adjusted models.
RESULTS
Individuals with SLE experienced more infections (22% vs 6%), especially during the first year of follow-up, and recurrent serious infections were also more common (HR=2.22, 95% CI 1.93 to 2.56). DMARDs were associated with a higher rate of serious infection versus HCQ (HR=1.82, 95% CI 1.27 to 2.60), which attenuated after multivariable-adjustment (HR=1.30, 95% CI 0.86 to 1.95). Among DMARDs, azathioprine was associated with infection (HR=2.19, 95% CI 1.14 to 4.21) and mycophenolate mofetil yielded an HR=1.39 (95% CI 0.65 to 2.96) in multivariable-adjusted models compared with methotrexate. Results were comparable across numerous sensitivity analyses.
CONCLUSION
Individuals with incident SLE were 2-4 times more likely to be hospitalised for infection and experienced more recurrent infections than the general population. Among DMARD initiators, azathioprine was associated with the highest rate.
Topics: Antirheumatic Agents; Azathioprine; Hospitalization; Humans; Hydroxychloroquine; Sweden
PubMed: 34526357
DOI: 10.1136/lupus-2021-000510 -
Biomedicine & Pharmacotherapy =... Jul 2022Rheumatoid arthritis (RA) is one of more than 100 types of arthritis. This chronic autoimmune disorder affects the lining of synovial joints in about 0.5% of people and... (Review)
Review
Rheumatoid arthritis (RA) is one of more than 100 types of arthritis. This chronic autoimmune disorder affects the lining of synovial joints in about 0.5% of people and may induce severe joints deformity and disability. RA impacts health life of people from all sexes and ages with more prevalence in elderly and women people. Significant improvement has been noted in the last two decades revealing the mechanisms of the development of RA, the improvement of the early diagnosis and the development of new treatment options. Non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, and disease-modifying antirheumatic drugs (DMARDs) remain the most known treatments used against RA. However, not all patients respond well to these drugs and therefore, new solutions are of immense need to improve the disease outcomes. In the present review, we discuss and highlight the recent findings concerning the different classes of RA therapies including the conventional and modern drug therapies, as well as the recent emerging options including the phyto-cannabinoid and cell- and RNA-based therapies. A better understanding of their mechanisms and pathways might help find a specific target against inflammation, cartilage damage, and reduce side effects in arthritis.
Topics: Aged; Anti-Inflammatory Agents, Non-Steroidal; Antirheumatic Agents; Arthritis, Rheumatoid; Female; Humans; Inflammation
PubMed: 35643074
DOI: 10.1016/j.biopha.2022.113126 -
RMD Open Apr 2023
Topics: Humans; Methotrexate; Immunosuppressive Agents; Antirheumatic Agents; Vaccination
PubMed: 37015758
DOI: 10.1136/rmdopen-2022-002798 -
Polish Archives of Internal Medicine Feb 2021The progress in the understanding of the pathophysiology of rheumatic diseases provided a rational basis for the development of biologic disease‑modifying...
The progress in the understanding of the pathophysiology of rheumatic diseases provided a rational basis for the development of biologic disease‑modifying antirheumatic drugs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs), which have completely revolutionized the treatment of inflammatory conditions. These agents differ in terms of their effectiveness for controlling specific rheumatic diseases depending on the pivotal cytokine driving the inflammatory process. Cytokine blockers were the first to be developed and rapidly expanded. They include agents that act against tumor necrosis factor α (TNF‑α) (etanercept, infliximab, adalimumab, golimumab, and certolizumab pegol) and interleukin (IL) 6 (tocilizumab and sarilumab), IL‑1 (anakinra, canakinumab, and rilonacept), IL‑17 (secukinumab and ixekizumab), and IL-12/23 (ustekinumab) receptors. Lymphocyte‑targeting agents include rituximab and belimumab, which act against B cells by different mechanisms, and abatacept, which is a T cell costimulation modulator. tsDMARDs, also known as small‑molecule inhibitors, are oral drugs based on a novel strategy to treat inflammatory diseases. Janus kinase (JAK) inhibitors (tofacitinib, baricitinib, and upadacitinib) and phosphodiesterase 4 inhibitors (apremilast) form this group. The major concern with the use of bDMARDs and tsDMARDs is a higher risk of infections. Performance of blood tests as well as screening for tuberculosis and hepatitis viral infection are mandatory prior to biologic therapy initiation. Adherence to an immunization program is also recommended. Whenever possible, the choice of bDMARDs and tsDMARDs should be guided by the patient's comorbidities. There have been limited data on the use of these drugs during pregnancy, but anti‑TNF‑α therapy, rituximab, and anakinra seem to be safe. Biologic agents are expensive, but biosimilars have emerged as a cost‑effective option with a potential to treat a greater number of patients.
Topics: Antirheumatic Agents; Autoimmune Diseases; Biosimilar Pharmaceuticals; Cytokines; Humans
PubMed: 32550671
DOI: 10.20452/pamw.15438 -
Frontiers in Immunology 2023Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease of undefined etiology, with persistent synovial inflammation and destruction of articular cartilage... (Review)
Review
Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease of undefined etiology, with persistent synovial inflammation and destruction of articular cartilage and bone. Current clinical drugs for RA mainly include non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, disease modifying anti-rheumatic drugs (DMARDs) and so on, which can relieve patients' joint symptoms. If we want to have a complete cure for RA, there are still some limitations of these drugs. Therefore, we need to explore new mechanisms of RA to prevent and treat RA radically. Pyroptosis is a newly discovered programmed cell death (PCD) in recent years, which is characterized by the appearance of holes in cell membranes, cell swelling and rupture, and the release of intracellular pro-inflammatory factors into the extracellular space, resulting in a strong inflammatory response. The nature of pyroptosis is pro-inflammatory, and whether it is participating in the development of RA has attracted a wide interest among scholars. This review describes the discovery and mechanism of pyroptosis, the main therapeutic strategies for RA, and the role of pyroptosis in the mechanism of RA development. From the perspective of pyroptosis, the study of new mechanisms of RA may provide a potential target for the treatment of RA and the development of new drugs in the clinics.
Topics: Humans; Pyroptosis; Arthritis, Rheumatoid; Antirheumatic Agents; Anti-Inflammatory Agents, Non-Steroidal; Glucocorticoids
PubMed: 37426634
DOI: 10.3389/fimmu.2023.1155606 -
Future Medicinal Chemistry Dec 2022Various metals have been complexed with drugs to improve their cellular impact. Inflammatory diseases like rheumatoid arthritis (RA) are characterized by unbalanced... (Review)
Review
Various metals have been complexed with drugs to improve their cellular impact. Inflammatory diseases like rheumatoid arthritis (RA) are characterized by unbalanced production of proinflammatory cytokines (PICs) and prostaglandins with decreased levels of vitamin D and calcium. The inflammation can be suppressed through targeting the formation of PICs or related enzymes by various treatment strategies that involve the use of corticosteroids, disease-modifying antirheumatic drugs and NSAIDs. We present a detailed review on the impact of calcium complexes of oxicams as an advanced treatment strategy for RA. The calcium complexes demonstrate promising capabilities to cure the disease, improve the strength of bones and suppress PICs in RA.
Topics: Humans; Calcium; Arthritis, Rheumatoid; Cyclooxygenase Inhibitors; Anti-Inflammatory Agents, Non-Steroidal; Antirheumatic Agents; Cytokines
PubMed: 36519430
DOI: 10.4155/fmc-2022-0032 -
Zeitschrift Fur Rheumatologie Mar 2021Infections affect morbidity and mortality of patients suffering from rheumatic diseases in an important way. Risk of infection is influenced generally by age and...
Infections affect morbidity and mortality of patients suffering from rheumatic diseases in an important way. Risk of infection is influenced generally by age and existing comorbidities as well as especially by activity of the rheumatic disease and immunosuppressive treatment. Correspondingly best possible reduction of disease activity and elimination or at least successful treatment of comorbidities are able to reduce infection risk. Patients at high risk of infection should be identified and be monitored in an intensified way. Furthermore risk is influenced by antirheumatic treatment, e.g. enhanced by long-term glucocorticoid treatment, reduced by optimisied use of disease-modifying antirheumatic drugs leading to best possible disease control. Finally protective antibiotic or antiviral treatment (e.g. in case of latent tuberculosis or hepatitis) as well as optimised vaccination status are able to reduce risk of infection further.
Topics: Antirheumatic Agents; Antiviral Agents; Glucocorticoids; Humans; Immunosuppressive Agents; Infection Control; Infections; Rheumatic Diseases
PubMed: 33326041
DOI: 10.1007/s00393-020-00938-5 -
The Israel Medical Association Journal... Mar 2020We describe the features of nocebo, and its impact in studies of transition from the originator to the respective biosimilar in inflammatory rheumatic diseases.... (Review)
Review
We describe the features of nocebo, and its impact in studies of transition from the originator to the respective biosimilar in inflammatory rheumatic diseases. Investigations in healthy volunteers as well as in the neurology and anesthesiology fields demonstrated the involved cerebral areas and the neurotransmitter pathways responsible for the nocebo response. Whether these findings are applicable to patients with inflammatory rheumatic diseases remains to be demonstrated. Nocebo may account for part of the after-switching biosimilar failures. However, in the absence of validated classification or diagnostic criteria, specific neurochemical and neuroimaging studies, the lack of data on serum tumor necrosis factor and drug levels, and the disease improvement after the switching back to the originator biologic observed in some patients, the nocebo diagnosis remains the role of the individual clinician. Investigations on nocebo pathophysiology and diagnosis are required to address its impact in after-transition biosimilar studies in rheumatology.
Topics: Antirheumatic Agents; Humans; Nocebo Effect; Rheumatic Diseases; Rheumatology
PubMed: 32147985
DOI: No ID Found -
Frontiers in Immunology 2023Autoimmune diseases are affected by complex pathophysiology involving multiple cell types, cytokines, antibodies and mimicking factors. Different drugs are used to... (Review)
Review
Autoimmune diseases are affected by complex pathophysiology involving multiple cell types, cytokines, antibodies and mimicking factors. Different drugs are used to improve these autoimmune responses, including nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, antibodies, and small molecule drugs (DMARDs), which are prevalent clinically in the treatment of rheumatoid arthritis (RA), etc. However, low cost-effectiveness, reduced efficacy, adverse effects, and patient non-response are unattractive factors driving the development of new drugs such as iguratimod. As a new disease-modifying antirheumatic drug, iguratimod has pharmacological activities such as regulating autoimmune disorders, inflammatory cytokines, regulating immune cell activation, differentiation and proliferation, improving bone metabolism, and inhibiting fibrosis. In recent years, clinical studies have found that iguratimod is effective in the treatment of RA, SLE, IGG4-RD, Sjogren 's syndrome, ankylosing spondylitis, interstitial lung disease, and other autoimmune diseases and rheumatic diseases. The amount of basic and clinical research on other autoimmune diseases is also increasing. Therefore, this review systematically reviews the latest relevant literature in recent years, reviews the research results in recent years, and summarizes the research progress of iguratimod in the treatment of related diseases. This review highlights the role of iguratimod in the protection of autoimmune and rheumatic bone and related immune diseases. It is believed that iguratimod's unique mode of action and its favorable patient response compared to other DMARDs make it a suitable antirheumatic and bone protective agent in the future.
Topics: Humans; Antirheumatic Agents; Arthritis, Rheumatoid; Chromones; Sjogren's Syndrome; Cytokines
PubMed: 37809072
DOI: 10.3389/fimmu.2023.1150661 -
Current Opinion in Rheumatology Sep 2021
Topics: Antirheumatic Agents; COVID-19; Humans; Rheumatic Diseases; Rheumatology; SARS-CoV-2
PubMed: 34175865
DOI: 10.1097/BOR.0000000000000813