-
Arthritis Care & Research Jul 2021To develop updated guidelines for the pharmacologic management of rheumatoid arthritis.
OBJECTIVE
To develop updated guidelines for the pharmacologic management of rheumatoid arthritis.
METHODS
We developed clinically relevant population, intervention, comparator, and outcomes (PICO) questions. After conducting a systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to rate the certainty of evidence. A voting panel comprising clinicians and patients achieved consensus on the direction (for or against) and strength (strong or conditional) of recommendations.
RESULTS
The guideline addresses treatment with disease-modifying antirheumatic drugs (DMARDs), including conventional synthetic DMARDs, biologic DMARDs, and targeted synthetic DMARDs, use of glucocorticoids, and use of DMARDs in certain high-risk populations (i.e., those with liver disease, heart failure, lymphoproliferative disorders, previous serious infections, and nontuberculous mycobacterial lung disease). The guideline includes 44 recommendations (7 strong and 37 conditional).
CONCLUSION
This clinical practice guideline is intended to serve as a tool to support clinician and patient decision-making. Recommendations are not prescriptive, and individual treatment decisions should be made through a shared decision-making process based on patients' values, goals, preferences, and comorbidities.
Topics: Antirheumatic Agents; Arthritis, Rheumatoid; Clinical Decision-Making; Consensus; Decision Support Techniques; Humans; Remission Induction; Rheumatology; Treatment Outcome
PubMed: 34101387
DOI: 10.1002/acr.24596 -
Cells Oct 2021Rheumatoid arthritis (RA) is a multifactorial autoimmune disease of unknown etiology, primarily affecting the joints, then extra-articular manifestations can occur. Due... (Review)
Review
Rheumatoid arthritis (RA) is a multifactorial autoimmune disease of unknown etiology, primarily affecting the joints, then extra-articular manifestations can occur. Due to its complexity, which is based on an incompletely elucidated pathophysiological mechanism, good RA management requires a multidisciplinary approach. The clinical status of RA patients has improved in recent years due to medical advances in diagnosis and treatment, that have made it possible to reduce disease activity and prevent systemic complications. The most promising results were obtained by developing disease-modifying anti-rheumatic drugs (DMARDs), the class to which conventional synthetic, biologic, and targeted synthetic drugs belong. Furthermore, ongoing drug development has led to obtaining molecules with improved efficacy and safety profiles, but further research is needed until RA turns into a curable pathology. In the present work, we offer a comprehensive perspective on the management of RA, by centralizing the existing data provided by significant literature, emphasizing the importance of an early and accurate diagnosis associated with optimal personalized treatment in order to achieve better outcomes for RA patients. In addition, this study suggests future research perspectives in the treatment of RA that could lead to higher efficacy and safety profiles and lower financial costs.
Topics: Antirheumatic Agents; Arthritis, Rheumatoid; Humans; Models, Biological; Protein Kinase Inhibitors
PubMed: 34831081
DOI: 10.3390/cells10112857 -
Immunity Dec 2022Significant recent progress in understanding rheumatoid arthritis (RA) pathogenesis has led to improved treatment and quality of life. The introduction of... (Review)
Review
Significant recent progress in understanding rheumatoid arthritis (RA) pathogenesis has led to improved treatment and quality of life. The introduction of targeted-biologic and -synthetic disease modifying anti-rheumatic drugs (DMARDs) has also transformed clinical outcomes. Despite this, RA remains a life-long disease without a cure. Unmet needs include partial response and non-response to treatment in many patients, failure to achieve immune homeostasis or drug free remission, and inability to repair damaged tissues. RA is now recognized as the end of a multi-year prodromal phase in which systemic immune dysregulation, likely beginning in mucosal surfaces, is followed by a symptomatic clinical phase. Inflammation and immune reactivity are primarily localized to the synovium leading to pain and articular damage, but is also associated with a broader series of comorbidities. Here, we review recently described immunologic mechanisms that drive breach of tolerance, chronic synovitis, and remission.
Topics: Humans; Quality of Life; Arthritis, Rheumatoid; Antirheumatic Agents; Synovitis; Synovial Membrane
PubMed: 36516818
DOI: 10.1016/j.immuni.2022.11.009 -
Pediatric Rheumatology Online Journal Aug 2021Juvenile idiopathic arthritis (JIA) is the most common paediatric rheumatological disorder and is classified by subtype according to International League of Associations... (Review)
Review
Juvenile idiopathic arthritis (JIA) is the most common paediatric rheumatological disorder and is classified by subtype according to International League of Associations for Rheumatology criteria. Depending on the number of joints affected, presence of extra-articular manifestations, systemic symptoms, serology and genetic factors, JIA is divided into oligoarticular, polyarticular, systemic, psoriatic, enthesitis-related and undifferentiated arthritis. This review provides an overview of advances in understanding of JIA pathogenesis focusing on aetiology, histopathology, immunological changes associated with disease activity, and best treatment options. Greater understanding of JIA as a collective of complex inflammatory diseases is discussed within the context of therapeutic interventions, including traditional non-biologic and up-to-date biologic disease-modifying anti-rheumatic drugs. Whilst the advent of advanced therapeutics has improved clinical outcomes, a considerable number of patients remain unresponsive to treatment, emphasising the need for further understanding of disease progression and remission to support stratification of patients to treatment pathways.
Topics: Antirheumatic Agents; Arthritis, Juvenile; Child; Disease Progression; Humans; Medication Therapy Management; Risk Assessment
PubMed: 34425842
DOI: 10.1186/s12969-021-00629-8 -
World Journal of Pediatrics : WJP Feb 2020Systemic lupus erythematosis (SLE) is a complex and clinically heterogeneous autoimmune disease. A variety of immunological defects contribute to SLE, including... (Review)
Review
BACKGROUND
Systemic lupus erythematosis (SLE) is a complex and clinically heterogeneous autoimmune disease. A variety of immunological defects contribute to SLE, including dysregulated innate and adaptive immune response. A clearer understanding of the mechanisms driving disease pathogenesis combined with recent advances in medical science is predicted to enable accelerated progress towards improved SLE-personalized approaches to treatment. The aim of this review was to clarify the immunological pathogenesis and treatment of SLE.
DATA SOURCES
Literature reviews and original research articles were collected from database, including PubMed and Wanfang. Relevant articles about SLE were included.
RESULTS
Breakdown of self-tolerance is the main pathogenesis of SLE. The innate and adaptive immune networks are interlinked with each other through cytokines, complements, immune complexes and kinases of the intracellular machinery. Treatments targeted at possible targets of immunity have been assessed in clinical trials. Most of them did not show better safety and efficacy than traditional treatments. However, novel targeting treatments are still being explored.
CONCLUSIONS
Dysregulated immune response plays a critical role in SLE, including innate immunity and adaptive immunity. Biologic agents that aim to specifically target abnormal immune processes were assessing and may bring new hope to SLE patients.
Topics: Adaptive Immunity; Antirheumatic Agents; Child; Humans; Immunity, Innate; Immunosuppressive Agents; Lupus Erythematosus, Systemic
PubMed: 30796732
DOI: 10.1007/s12519-019-00229-3 -
The European Respiratory Journal Oct 2022Interstitial lung disease (ILD) secondary to drug-induced lung injury is an increasingly common cause of morbidity and mortality. The number of drugs associated with the... (Review)
Review
Interstitial lung disease (ILD) secondary to drug-induced lung injury is an increasingly common cause of morbidity and mortality. The number of drugs associated with the development of ILD continues to rise, mainly due to the use of novel monoclonal antibodies and biologicals for neoplastic and rheumatological diseases, and includes, among others, chemotherapeutics, molecular targeting agents, immune checkpoint inhibitors, antibiotics, antiarrhythmics and conventional or biological disease-modifying antirheumatic drugs. Drug-induced ILD (DI-ILD) manifests with a variety of clinical patterns, ranging from mild respiratory symptoms to rapidly progressive respiratory failure and death. In most cases, there are no pathognomonic clinical, laboratory, radiological or pathological features and the diagnosis of DI-ILD is suspected in the presence of exposure to a drug known to cause lung toxicity and after exclusion of alternative causes of ILD. Early identification and permanent discontinuation of the culprit drug are the cornerstones of treatment with systemic glucocorticoids being used in patients with disabling or progressive disease. However, for certain drugs, such as checkpoint inhibitors, the frequency of lung toxicity is such that mitigation strategies are put in place to prevent this complication, and occurrence of DI-ILD is not necessarily synonymous with permanent drug discontinuation, particularly in the absence of valid therapeutic alternatives.
Topics: Humans; Lung Diseases, Interstitial; Antirheumatic Agents; Antibodies, Monoclonal; Biological Factors
PubMed: 35332071
DOI: 10.1183/13993003.02776-2021 -
The New England Journal of Medicine May 2023Peresolimab is a humanized IgG1 monoclonal antibody designed to stimulate the endogenous programmed cell death protein 1 (PD-1) inhibitory pathway. Stimulation of this... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Peresolimab is a humanized IgG1 monoclonal antibody designed to stimulate the endogenous programmed cell death protein 1 (PD-1) inhibitory pathway. Stimulation of this pathway would be a novel approach to the treatment of patients with autoimmune or autoinflammatory diseases.
METHODS
In this phase 2a, double-blind, randomized, placebo-controlled trial, we assigned, in a 2:1:1 ratio, adult patients with moderate-to-severe rheumatoid arthritis who had had an inadequate response to, a loss of response to, or unacceptable side effects with conventional synthetic disease-modifying antirheumatic drugs (DMARDs) or to biologic or targeted synthetic DMARDs to receive 700 mg of peresolimab, 300 mg of peresolimab, or placebo intravenously once every 4 weeks. The primary outcome was the change from baseline to week 12 in the Disease Activity Score for 28 joints based on the C-reactive protein level (DAS28-CRP). The DAS28-CRP ranges from 0 to 9.4, with higher scores indicating more severe disease. The primary comparison was between the 700-mg group and the placebo group. Secondary outcomes included the percentages of patients with American College of Rheumatology 20 (ACR20), ACR50, and ACR70 responses - defined as improvements from baseline of 20%, 50%, and 70% or more, respectively, in the numbers of tender and swollen joints and in at least three of five important domains - at week 12.
RESULTS
At week 12, the change from baseline in the DAS28-CRP was significantly greater in the 700-mg peresolimab group than in the placebo group (least-squares mean change [±SE], -2.09±0.18 vs. -0.99±0.26; difference in change, -1.09 [95% confidence interval, -1.73 to -0.46]; P<0.001). The results of the analyses of secondary outcomes favored the 700-mg dose over placebo with respect to the ACR20 response but not with respect to the ACR50 and ACR70 responses. Adverse events were similar in the peresolimab and placebo groups.
CONCLUSIONS
Peresolimab showed efficacy in a phase 2a trial in patients with rheumatoid arthritis. These results provide evidence that stimulation of the PD-1 receptor has potential efficacy in the treatment of rheumatoid arthritis. (Funded by Eli Lilly; ClinicalTrials.gov number, NCT04634253.).
Topics: Adult; Humans; Antibodies, Monoclonal, Humanized; Antirheumatic Agents; Arthritis, Rheumatoid; Double-Blind Method; Drug Therapy, Combination; Severity of Illness Index; Treatment Outcome; Immunoglobulin G; Administration, Intravenous; Programmed Cell Death 1 Receptor
PubMed: 37195941
DOI: 10.1056/NEJMoa2209856 -
Frontiers in Immunology 2023As a chronic progressive autoimmune disease, rheumatoid arthritis (RA) is characterized by mainly damaging the synovium of peripheral joints and causing joint... (Review)
Review
As a chronic progressive autoimmune disease, rheumatoid arthritis (RA) is characterized by mainly damaging the synovium of peripheral joints and causing joint destruction and early disability. RA is also associated with a high incidence rate and mortality of cardiovascular disease. Recently, the relationship between lipid metabolism and RA has gradually attracted attention. Plasma lipid changes in RA patients are often detected in clinical tests, the systemic inflammatory status and drug treatment of RA patients can interact with the metabolic level of the body. With the development of lipid metabolomics, the changes of lipid small molecules and potential metabolic pathways have been gradually discovered, which makes the lipid metabolism of RA patients or the systemic changes of lipid metabolism after treatment more and more comprehensive. This article reviews the lipid level of RA patients, as well as the relationship between inflammation, joint destruction, cardiovascular disease, and lipid level. In addition, this review describes the effect of anti-rheumatic drugs or dietary intervention on the lipid profile of RA patients to better understand RA.
Topics: Humans; Lipid Metabolism; Cardiovascular Diseases; Arthritis, Rheumatoid; Antirheumatic Agents; Lipids
PubMed: 37325667
DOI: 10.3389/fimmu.2023.1190607 -
The New England Journal of Medicine Apr 2021The Janus kinase inhibitor upadacitinib is a potential treatment for psoriatic arthritis. The efficacy and safety of upadacitinib as compared with adalimumab, a tumor... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
The Janus kinase inhibitor upadacitinib is a potential treatment for psoriatic arthritis. The efficacy and safety of upadacitinib as compared with adalimumab, a tumor necrosis factor α inhibitor, in patients who have an inadequate response to nonbiologic disease-modifying antirheumatic drugs are unclear.
METHODS
In a 24-week, phase 3 trial, we randomly assigned patients in a 1:1:1:1 ratio to receive oral upadacitinib at a dose of 15 mg or 30 mg once daily, placebo, or subcutaneous adalimumab (40 mg every other week). The primary end point was an American College of Rheumatology 20 (ACR20) response (≥20% decrease in the number of tender and swollen joints and ≥20% improvement in at least three of five other domains) at week 12 with upadacitinib as compared with placebo. Secondary end points included comparisons of upadacitinib with adalimumab.
RESULTS
A total of 1704 patients received an active drug or placebo. The percentage of patients who had an ACR20 response at week 12 was 70.6% with 15-mg upadacitinib, 78.5% with 30-mg upadacitinib, 36.2% with placebo (P<0.001 for both upadacitinib doses vs. placebo), and 65.0% with adalimumab. The difference between groups for 15-mg upadacitinib as compared with adalimumab was 5.6 percentage points (95% confidence interval [CI], -0.6 to 11.8) and for 30-mg upadacitinib as compared with adalimumab was 13.5 percentage points (95% CI, 7.5 to 19.4). Both upadacitinib doses were noninferior to adalimumab for the ACR20 response at week 12; the 30-mg dose but not the 15-mg dose was superior to adalimumab. The incidence of adverse events through week 24 was 66.9% with 15-mg upadacitinib, 72.3% with 30-mg upadacitinib, 59.6% with placebo, and 64.8% with adalimumab. There were serious infections in 1.2%, 2.6%, 0.9%, and 0.7% of the patients, respectively. Hepatic disorders occurred in 9.1% of patients in the 15-mg upadacitinib group and 12.3% in the 30-mg upadacitinib group, but grade 3 increases in aminotransferase levels occurred in 2% of patients or fewer in all groups.
CONCLUSIONS
The percentage of patients with psoriatic arthritis who had an ACR20 response at week 12 was significantly higher with 15-mg or 30-mg upadacitinib than with placebo. The 30-mg dose but not the 15-mg dose was superior to adalimumab. Adverse events were more frequent with upadacitinib than with placebo. (Funded by AbbVie; SELECT-PsA 1 ClinicalTrials.gov number, NCT03104400.).
Topics: Adalimumab; Adult; Antirheumatic Agents; Arthritis, Psoriatic; Dose-Response Relationship, Drug; Double-Blind Method; Female; Heterocyclic Compounds, 3-Ring; Humans; Janus Kinase Inhibitors; Least-Squares Analysis; Liver Diseases; Male; Middle Aged
PubMed: 33789011
DOI: 10.1056/NEJMoa2022516 -
Frontiers in Immunology 2021Autoimmune diseases are a worldwide health problem with growing rates of morbidity, and are characterized by breakdown and dysregulation of the immune system. Although... (Review)
Review
Autoimmune diseases are a worldwide health problem with growing rates of morbidity, and are characterized by breakdown and dysregulation of the immune system. Although their etiology and pathogenesis remain unclear, the application of dietary supplements is gradually increasing in patients with autoimmune diseases, mainly due to their positive effects, relatively safety, and low cost. Quercetin is a natural flavonoid that is widely present in fruits, herbs, and vegetables. It has been shown to have a wide range of beneficial effects and biological activities, including anti-inflammation, anti-oxidation, and neuroprotection. In several recent studies quercetin has reportedly attenuated rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, and systemic lupus erythematosus in humans or animal models. This review summarizes the evidence for the pharmacological application of quercetin for autoimmune diseases, which supports the view that quercetin may be useful for their prevention and treatment.
Topics: Animals; Anti-Inflammatory Agents; Antirheumatic Agents; Autoimmune Diseases; Humans; Quercetin
PubMed: 34248976
DOI: 10.3389/fimmu.2021.689044