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Annals of the Rheumatic Diseases Mar 2024
Topics: Humans; Arthritis, Rheumatoid; Spondylitis, Ankylosing; Spondylitis; Arthritis
PubMed: 38242638
DOI: 10.1136/ard-2023-225115 -
Best Practice & Research. Clinical... Sep 2023Over the recent years the wider availability and application of state-of-the-art immunological technologies greatly advanced the insight into the mechanisms that play an... (Review)
Review
Over the recent years the wider availability and application of state-of-the-art immunological technologies greatly advanced the insight into the mechanisms that play an important role in axial spondyloarthritis (axSpA) pathophysiology. This increased understanding has facilitated the development of novel treatments that target disease relevant pathways, hereby improving outcome for axSpA patients. In axSpA pathophysiology genetic and environmental factors as well as immune activation by mechanical or bacterial stress resulting in a chronic inflammatory response have a central role. The TNF and IL-23/IL-17 immune pathways play a pivotal role in these disease mechanisms. This review provides an outline of the immunological basis of axSpA with a focus on key genetic risk factors and their link to activation of the pathological immune response, as well as on the role of the gut and entheses in the initiation of inflammation with subsequent new bone formation in axSpA.
Topics: Humans; Spondylarthritis; HLA-B27 Antigen; Spondylitis, Ankylosing; Axial Spondyloarthritis; Inflammation
PubMed: 38030467
DOI: 10.1016/j.berh.2023.101897 -
Expert Opinion on Pharmacotherapy 2023Axial spondyloarthritis (axSpA) refers to an inflammatory rheumatic disease that mainly affects the axial skeleton and leads to progressive radiographic changes of the... (Review)
Review
INTRODUCTION
Axial spondyloarthritis (axSpA) refers to an inflammatory rheumatic disease that mainly affects the axial skeleton and leads to progressive radiographic changes of the sacroiliac joints and spine. axSpA is currently subdivided into the radiographic (r-axSpA) and non-radiographic (nr-axSpA) form. Both forms are associated with musculoskeletal pain, restriction of spinal mobility, specific extra-musculoskeletal manifestations, and overall, altered quality of life. The therapeutic management of axSpA is currently well standardized.
AREAS COVERED
We reviewed available literature (by using PubMed search) on non-pharmacological and pharmacological treatment options that may be used in axSpA, including r-axSpA and nr-axSpA, as well as the role of non-steroidal anti-inflammatory drugs (NSAIDs), biological agents including TNFalpha (TNFi) and IL-17 (IL-17i) inhibitors. New treatment options such as Janus kinase inhibitors are also reviewed.
EXPERT OPINION
NSAIDs remain the mainstay of initial therapy, and subsequently, biological agents (TNFi and IL-17i) may be envisaged. Four TNFi are licensed for the treatment of both r-axSpA and nr-axSpA, while IL-17i are approved in each indication. The choice between a TNFi and an IL-17i is mainly guided by the presence of extra-articular manifestations. JAKi were more recently introduced for the treatment of r-axSpA, but their use is restricted to specific patients with a safe cardiovascular profile.
Topics: Humans; Spondylitis, Ankylosing; Spondylarthritis; Quality of Life; Non-Radiographic Axial Spondyloarthritis; Anti-Inflammatory Agents, Non-Steroidal; Axial Spondyloarthritis
PubMed: 37318776
DOI: 10.1080/14656566.2023.2226328 -
Best Practice & Research. Clinical... Sep 2023"Disease modification" in axial spondyloarthritis (axSpA) seeks to not only alleviate clinical symptoms but also alter the disease's natural course by impeding new bone... (Review)
Review
"Disease modification" in axial spondyloarthritis (axSpA) seeks to not only alleviate clinical symptoms but also alter the disease's natural course by impeding new bone formation. Recent years have witnessed the effectiveness of treatments, including biologics and nonsteroidal anti-inflammatory drugs, in managing axSpA symptoms. Emerging evidence points toward their potential impact on slowing structural disease progression. This comprehensive review centers on the pivotal role of inhibiting new bone formation in axSpA disease modification. It delves into the significance of imaging techniques for assessing disease progression and explores the disease-modifying properties of available axSpA treatments, encompassing NSAIDs, TNF inhibitors, IL-17 inhibitors, and JAK inhibitors. This article offers valuable insights into the evolving landscape of disease modification strategies in axial spondyloarthritis, highlighting the multifaceted approaches used to attain these objectives.
Topics: Humans; Spondylitis, Ankylosing; Antirheumatic Agents; Spondylarthritis; Anti-Inflammatory Agents, Non-Steroidal; Axial Spondyloarthritis; Disease Progression
PubMed: 38042689
DOI: 10.1016/j.berh.2023.101898 -
Frontiers in Immunology 2023Epidemiologic evidence has demonstrated a correlation between ankylosing spondylitis and psychiatric disorders. However, little is known about the common genetics and...
BACKGROUND
Epidemiologic evidence has demonstrated a correlation between ankylosing spondylitis and psychiatric disorders. However, little is known about the common genetics and causality of this association. This study aimed to investigate the common genetics and causality between ankylosing spondylitis (AS) and psychiatric disorders.
METHODS
A two-sample Mendelian Randomization (MR) analysis was carried out to confirm causal relationships between ankylosing spondylitis and five mental health conditions including major depressive disorder (MDD), anxiety disorder (AXD), schizophrenia (SCZ), bipolar disorder (BIP), and anorexia nervosa (AN). Genetic instrumental variables associated with exposures and outcomes were derived from the largest available summary statistics of genome-wide association studies (GWAS). Bidirectional causal estimation of MR was primarily obtained using the inverse variance weighting (IVW) method. Other MR methods include MR-Egger regression, Weighted Median Estimator (WME), Weighted Mode, Simple Mode, and Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO). Sensitivity analyses are conducted to estimate the robustness of MR results.
RESULTS
The findings suggest that AS may be causally responsible for the risk of developing SCZ (OR = 1.18, 95% confidence interval = (1.06, 1.31), P = 2.58 × 10) and AN (OR = 1.32, 95% confidence interval = (1.07, 1.64), P = 9.43 × 10). In addition, MDD, AXD, SCZ, AN, and BIP were not inversely causally related to AS (all p > 0.05).
CONCLUSION
Our study provides fresh insights into the relationship between AS and psychiatric disorders (SCZ and AN). Furthermore, it may provide new clues for risk management and preventive interventions for mental disorders in patients with AS.
Topics: Humans; Spondylitis, Ankylosing; Depressive Disorder, Major; Genome-Wide Association Study; Mendelian Randomization Analysis; Mental Disorders
PubMed: 37954601
DOI: 10.3389/fimmu.2023.1277959 -
Clinical Rheumatology Oct 2023Cardiovascular manifestations are common in patients suffering axial spondyloarthritis and can result in substantial morbidity and disease burden. To give an overview of... (Review)
Review
Cardiovascular manifestations are common in patients suffering axial spondyloarthritis and can result in substantial morbidity and disease burden. To give an overview of this important aspect of axial spondyloarthritis, we conducted a systematic literature search of all articles published between January 2000 and 25 May 2023 on cardiovascular manifestations. Using PubMed and SCOPUS, 123 out of 6792 articles were identified and included in this review. Non-radiographic axial spondyloarthritis seems to be underrepresented in studies; thus, more evidence for ankylosing spondylitis exists. All in all, we found some traditional risk factors that led to higher cardiovascular disease burden or major cardiovascular events. These specific risk factors seem to be more aggressive in patients with spondyloarthropathies and have a strong connection to high or long-standing disease activity. Since disease activity is a major driver of morbidity, diagnostic, therapeutic, and lifestyle interventions are crucial for better outcomes. Key Points • Several studies on axial spondyloarthritis and associated cardiovascular diseases have been conducted in the last few years addressing risk stratification of these patients including artificial intelligence. • Recent data suggest distinct manifestations of cardiovascular disease entities among men and women which the treating physician needs to be aware of. • Rheumatologists need to screen axial spondyloarthritis patients for emerging cardiovascular disease and should aim at reducing traditional risk factors like hyperlipidemia, hypertension, and smoking as well as disease activity.
Topics: Male; Humans; Female; Spondylarthritis; Cardiovascular Diseases; Artificial Intelligence; Risk Factors; Spondylitis, Ankylosing; Heart Disease Risk Factors
PubMed: 37418034
DOI: 10.1007/s10067-023-06655-z -
Current Rheumatology Reports Oct 2023Axial spondyloarthritis (AxSpA) is among the rheumatology's most heritable complex diseases, yet precision medicine at clinics still needs to be explored. We reviewed... (Review)
Review
PURPOSE OF REVIEW
Axial spondyloarthritis (AxSpA) is among the rheumatology's most heritable complex diseases, yet precision medicine at clinics still needs to be explored. We reviewed the emerging concepts and recent developments in polygenic risk scores, Mendelian randomization, pharmacogenomics, single-cell sequencing, and spatial transcriptomics.
RECENT FINDINGS
Polygenic risk score has resulted in encouraging results with potential diagnostic utility as it appears to outperform current diagnostic tools. Its performance and generalizability vary with ethnicity. Mendelian randomization has elucidated multiple causal associations, particularly between inflammatory bowel disease and AxSpA. Single-cell transcriptomics (particularly scRNA-seq and scATAC-seq) has identified numerous cell types, including synovial and blood immunological cells, to understand the contribution of both innate and adaptative immunity in AxSpA. Current molecular tools provide an exciting opportunity to advance precision medicine for AxSpA patients. However, extensive research and implementation strategies are still required before they can have an impact in the clinic.
Topics: Humans; Spondylarthritis; Precision Medicine; Spondylitis, Ankylosing; Axial Spondyloarthritis; Risk Factors
PubMed: 37505349
DOI: 10.1007/s11926-023-01113-w -
Revue Medicale Suisse Jan 2024In rheumatology, this year has been characterized by a broader knowledge of the pathogenesis of rheumatoid arthritis and mechanisms involved in the onset and persistence...
In rheumatology, this year has been characterized by a broader knowledge of the pathogenesis of rheumatoid arthritis and mechanisms involved in the onset and persistence of low back pain. Studies relevant to the management of of gout, axial spondyloarthritis, autoinflammatory diseases and systemic vasculitides were published. New data on the safety of JAK inhibitors have been published. The ASAS-EULAR recommendations for the treatment of axial spondyloarthritis were updated, and the 2023 EULAR/PReS guidelines for the diagnosis and treatment of systemic juvenile idiopathic arthritis and adult-onset Still's disease are now available. New molecules and different glucocorticoid sparing strategies were introduced for giant cell arteritis.
Topics: Adult; Humans; Rheumatology; Arthritis, Juvenile; Arthritis, Rheumatoid; Giant Cell Arteritis; Axial Spondyloarthritis
PubMed: 38231111
DOI: 10.53738/REVMED.2024.20.856-7.102 -
RMD Open Nov 2023To provide an integrated analysis of major adverse cardiovascular events (MACEs) and events of venous thromboembolism (VTE) and associated risk factors across rheumatoid...
OBJECTIVES
To provide an integrated analysis of major adverse cardiovascular events (MACEs) and events of venous thromboembolism (VTE) and associated risk factors across rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS) phase 2b/3 upadacitinib clinical programmes.
METHODS
Data were analysed and summarised from clinical trials of RA, PsA and AS treated with upadacitinib 15 mg once daily (QD) and 30 mg QD (as of 30 June 2021). Data from adalimumab (RA and PsA) and methotrexate (RA) arms were included as comparators. Adjudicated MACEs and VTE events were presented as exposure-adjusted rates per 100 patient-years (E/100 PY). Univariable Cox proportional hazard regression analyses assessed potential associations of risk factors for MACE and VTE.
RESULTS
In total, 4298 patients received upadacitinib 15 mg (RA n=3209, PsA n=907 and AS n=182) and 2125 patients received upadacitinib 30 mg (RA n=1204 and PsA n=921). In patients with RA and PsA, rates of MACE (0.3-0.6 E/100 PY) and VTE (0.2-0.4 E/100 PY) were similar across upadacitinib doses; in patients with AS, no MACEs and one VTE event occurred. Most patients experiencing MACEs or VTE events had two or more baseline cardiovascular risk factors. Across RA and PsA groups, rates of MACEs and VTE events were similar.
CONCLUSIONS
Rates of MACEs and VTE events with upadacitinib were consistent with previously reported data for patients receiving conventional synthetic and biologic disease-modifying anti-rheumatic drugs and comparable with active comparators adalimumab and methotrexate. Associated patient characteristics are known risk factors for MACEs and VTE events.
TRIAL REGISTRATION NUMBERS
RA (SELECT-NEXT: NCT02675426; SELECT-MONOTHERAPY: NCT02706951; SELECT-BEYOND: NCT02706847; SELECT-COMPARE: NCT02629159; SELECT-EARLY: NCT02706873, SELECT-CHOICE: NCT03086343), PsA (SELECT-PsA 2: NCT03104374; SELECT-PsA 1: NCT03104400), and AS (SELECT-AXIS 1: NCT03178487).
Topics: Humans; Adalimumab; Arthritis, Psoriatic; Arthritis, Rheumatoid; Methotrexate; Spondylitis, Ankylosing; Venous Thromboembolism; Clinical Trials as Topic
PubMed: 37945286
DOI: 10.1136/rmdopen-2023-003392 -
Journal of Translational Medicine Aug 2023Ankylosing spondylitis (AS) is an autoimmune disease with a genetic correlation and is characterized by inflammation in the axial skeleton and sacroiliac joints. Many AS...
BACKGROUND
Ankylosing spondylitis (AS) is an autoimmune disease with a genetic correlation and is characterized by inflammation in the axial skeleton and sacroiliac joints. Many AS patients also have inflammatory bowel diseases (IBD), but the underlying causes of intestinal inflammation and osteoporosis in AS are not well understood. CX3CL1, a protein involved in inflammation, has been found to be up-regulated in AS patients and AS-model mice.
METHODS
The authors investigated the effects of CX3CL1 on AS by studying its impact on macrophage polarization, inflammation factors, and osteoclast differentiation. Furthermore, the effects of inhibiting the NF-κB pathway and blocking CX3CL1 were assessed using BAY-117082 and anti-CX3CL1 mAb, respectively. AS model mice were used to evaluate the effects of anti-CX3CL1 mAb on limb thickness, spine rupture, and intestinal tissue damage.
RESULTS
The authors found that CX3CL1 increased the expression of M1-type macrophage markers and inflammation factors, and promoted osteoclast differentiation. This effect was mediated through the NF-κB signaling pathway. Inhibition of the NF-κB pathway prevented M1-type macrophage polarization, reduced inflammation levels, and inhibited osteoclast differentiation. Injection of anti-CX3CL1 mAb alleviated limb thickness, spine rupture, and intestinal tissue damage in AS model mice by inhibiting M1-type macrophage polarization and reducing intestinal tissue inflammation.
CONCLUSIONS
The study demonstrated that up-regulated CX3CL1 promotes M1-type macrophage polarization and osteoclast differentiation through the NF-κB signaling pathway. Inhibition of this pathway and blocking CX3CL1 can alleviate inflammation and bone destruction in AS. These findings contribute to a better understanding of the pathogenesis of AS and provide a basis for clinical diagnosis and treatment.
Topics: Animals; Mice; Inflammation; NF-kappa B; Osteoclasts; Signal Transduction; Spondylitis, Ankylosing
PubMed: 37626378
DOI: 10.1186/s12967-023-04449-0