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Medical Principles and Practice :... 2018Rheumatoid arthritis (RA) is a chronic, inflammatory, systemic autoimmune disease, affecting the joints with varying severity among patients. The risk factors include... (Review)
Review
Rheumatoid arthritis (RA) is a chronic, inflammatory, systemic autoimmune disease, affecting the joints with varying severity among patients. The risk factors include age, gender, genetics, and environmental exposure (cigarette smoking, air pollutants, and occupational). Many complications can follow, such as permanent joint damage requiring arthroplasty, rheumatoid vasculitis, and Felty syndrome requiring splenectomy if it remains unaddressed. As there is no cure for RA, the treatment goals are to reduce the pain and stop/slow further damage. Here, we present a brief summary of various past and present treatment modalities to address the complications associated with RA.
Topics: Adrenal Cortex Hormones; Analgesics, Opioid; Anti-Inflammatory Agents, Non-Steroidal; Antibodies, Monoclonal, Humanized; Antirheumatic Agents; Arthritis, Rheumatoid; Humans; Immunosuppressive Agents; Interleukin 1 Receptor Antagonist Protein; Leflunomide; Physical Therapy Modalities; Risk Factors; Tumor Necrosis Factor-alpha
PubMed: 30173215
DOI: 10.1159/000493390 -
Joint Bone Spine May 2021The vagus nerve is the main nerve of the parasympathetic autonomic nervous system. Beyond its vegetative functions, the vagus nerve possesses anti-inflammatory and... (Randomized Controlled Trial)
Randomized Controlled Trial
The vagus nerve is the main nerve of the parasympathetic autonomic nervous system. Beyond its vegetative functions, the vagus nerve possesses anti-inflammatory and analgesic properties. Initially developed in the treatment of refractory epilepsy, vagus nerve stimulation (VNS) is currently being evaluated in several musculoskeletal diseases. VNS can be invasive by placing an electrode around the cervical vagus nerve and connected to a generator implanted subcutaneously or non-invasive stimulating the cervical vagus nerve branch percutaneously (auricular or cervical). In rheumatoid arthritis (RA) patients, VNS has been shown to dampen the inflammatory response of circulatory peripheral cells. Several open-labeled small pilot studies have demonstrated that VNS, either invasive or transcutaneous, is associated with a significant decrease of RA disease activity. As well, other studies have shown that VNS could limit fatigue in Sjogren's syndrome and systemic lupus, or decrease pain in fibromyalgia as well as in erosive hand osteoarthritis. However, some questions remain, such as the settings of stimulation, the duration of treatment, or the optimal stimulation route. Finally, randomized controlled trials versus sham stimulation with large samples of patients are mandatory to definitively conclude about the efficacy of VNS.
Topics: Arthritis, Rheumatoid; Fatigue; Humans; Vagus Nerve; Vagus Nerve Stimulation
PubMed: 33548494
DOI: 10.1016/j.jbspin.2021.105149 -
Aging May 2021Many observation studies have demonstrated a close relationship between rheumatoid arthritis (RA) and osteoporosis (OP). However, the causal genetic correlation between...
Many observation studies have demonstrated a close relationship between rheumatoid arthritis (RA) and osteoporosis (OP). However, the causal genetic correlation between RA and OP remains unclear. In this study, we performed bi-directional Mendelian randomization (MR) analyses to explore causal inference between these two traits. The instrumental variables for RA were selected from a large-scale genome-wide association study (GWAS) (1,523 cases and 461,487 controls). Bone mineral density (BMD) at five different sites (heel (n=265,627), forearm (FA) (n=8,143), femoral neck (FN) (n=32,735), lumbar spine (LS) (n=28,498), and total body (n=28,498)) were used as phenotypes for OP. The inverse variance weighted (IVW) method did not detect any causal effect of BMDs on RA except heel BMD (beta = -7.57 × 10-4, p = 0.02). However, other methods (MR-Egger, weighted median, weighted mode, MR-PRESSO, and MR-RAPS) showed no causal association between heel BMD and RA. Likewise, we did not find a causal effect of RA on BMD at any sites. In conclusion, we found no evidence that RA is causally associated with OP/BMD, or vice versa. We suggested that the associations found in previous observational studies between RA and OP/BMD are possibly related to secondary effects such as antirheumatic treatment and reduced physical activity.
Topics: Arthritis, Rheumatoid; Bone Density; Humans; Mendelian Randomization Analysis; Osteoporosis
PubMed: 34015765
DOI: 10.18632/aging.203029 -
Nature Reviews. Rheumatology Apr 2013Osteoarthritis (OA) of the spine involves the facet joints, which are located in the posterior aspect of the vertebral column and, in humans, are the only true synovial... (Review)
Review
Osteoarthritis (OA) of the spine involves the facet joints, which are located in the posterior aspect of the vertebral column and, in humans, are the only true synovial joints between adjacent spinal levels. Facet joint osteoarthritis (FJ OA) is widely prevalent in older adults, and is thought to be a common cause of back and neck pain. The prevalence of facet-mediated pain in clinical populations increases with increasing age, suggesting that FJ OA might have a particularly important role in older adults with spinal pain. Nevertheless, to date FJ OA has received far less study than other important OA phenotypes such as knee OA, and other features of spine pathoanatomy such as degenerative disc disease. This Review presents the current state of knowledge of FJ OA, including relevant anatomy, biomechanics, epidemiology, and clinical manifestations. We present the view that the modern concept of FJ OA is consonant with the concept of OA as a failure of the whole joint, and not simply of facet joint cartilage.
Topics: Aged; Aged, 80 and over; Back Pain; Biomechanical Phenomena; Cervical Vertebrae; Diagnostic Imaging; Female; Humans; Lumbar Vertebrae; Male; Middle Aged; Neck Pain; Osteoarthritis; Pain Measurement; Prevalence; Prognosis; Risk Assessment; Severity of Illness Index; Spinal Diseases; Treatment Outcome; Zygapophyseal Joint
PubMed: 23147891
DOI: 10.1038/nrrheum.2012.199 -
Frontiers in Endocrinology 2022Investigating the causal relationship between rheumatoid arthritis (RA) and atlantoaxial subluxation (AAS) and identifying and quantifying the role of C-reactive protein...
OBJECTIVE
Investigating the causal relationship between rheumatoid arthritis (RA) and atlantoaxial subluxation (AAS) and identifying and quantifying the role of C-reactive protein (CRP) as a potential mediator.
METHODS
Using summary-level data from a genome-wide association study (GWAS), a two-sample Mendelian randomization (MR) analysis of genetically predicted rheumatoid arthritis (14,361 cases, and 43,923 controls) and AAS (141 cases, 227,388 controls) was performed. Furthermore, we used two-step MR to quantitate the proportion of the effect of c-reactive protein-mediated RA on AAS.
RESULTS
MR analysis identified higher genetically predicted rheumatoid arthritis (primary MR analysis odds ratio (OR) 0.61/SD increase, 95% confidence interval (CI) 1.36-1.90) increased risk of AAS. There was no strong evidence that genetically predicted AAS had an effect on rheumatoid arthritis risk (OR 1.001, 95% CI 0.97-1.03). The proportion of genetically predicted rheumatoid arthritis mediated by C-reactive protein was 3.7% (95%CI 0.1%-7.3%).
CONCLUSION
In conclusion, our study identified a causal relationship between RA and AAS, with a small proportion of the effect mediated by CRP, but a majority of the effect of RA on AAS remains unclear. Further research is needed on additional risk factors as potential mediators. In clinical practice, lesions of the upper cervical spine in RA patients need to be given more attention.
Topics: Humans; Arthritis, Rheumatoid; Atlanto-Axial Joint; C-Reactive Protein; Cervical Vertebrae; Genome-Wide Association Study; Joint Dislocations; Joint Instability
PubMed: 36589832
DOI: 10.3389/fendo.2022.1054206 -
Nature Communications Apr 2022Immune checkpoint inhibitors are associated with immune-related adverse events (irAEs), including arthritis (arthritis-irAE). Management of arthritis-irAE is challenging...
Immune checkpoint inhibitors are associated with immune-related adverse events (irAEs), including arthritis (arthritis-irAE). Management of arthritis-irAE is challenging because immunomodulatory therapy for arthritis should not impede antitumor immunity. Understanding of the mechanisms of arthritis-irAE is critical to overcome this challenge, but the pathophysiology remains unknown. Here, we comprehensively analyze peripheral blood and/or synovial fluid samples from 20 patients with arthritis-irAE, and unmask a prominent Th1-CD8 T cell axis in both blood and inflamed joints. CX3CR1 CD8 T cells in blood and CXCR3 CD8 T cells in synovial fluid, the most clonally expanded T cells, significantly share TCR repertoires. The migration of blood CX3CR1 CD8 T cells into joints is possibly mediated by CXCL9/10/11/16 expressed by myeloid cells. Furthermore, arthritis after combined CTLA-4 and PD-1 inhibitor therapy preferentially has enhanced Th17 and transient Th1/Th17 cell signatures. Our data provide insights into the mechanisms, predictive biomarkers, and therapeutic targets for arthritis-irAE.
Topics: Arthritis; CD8-Positive T-Lymphocytes; Humans; Immune Checkpoint Inhibitors; Immunotherapy; Neoplasms
PubMed: 35413951
DOI: 10.1038/s41467-022-29539-3 -
Annals of the Rheumatic Diseases May 2021MAXIMISE (Managing AXIal Manifestations in psorIatic arthritis with SEcukinumab) trial was designed to evaluate the efficacy of secukinumab in the management of axial... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVES
MAXIMISE (Managing AXIal Manifestations in psorIatic arthritis with SEcukinumab) trial was designed to evaluate the efficacy of secukinumab in the management of axial manifestations of psoriatic arthritis (PsA).
METHODS
This phase 3b, double-blind, placebo-controlled, multi-centre 52-week trial included patients (≥18 years) diagnosed with PsA and classified by ClASsification criteria for Psoriatic Arthritis (CASPAR) criteria, with spinal pain Visual Analogue Score ≥40/100 and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score ≥4 despite use of at least two non-steroidal anti-inflammatory drugs (NSAIDs). Patients were randomised (1:1:1) to secukinumab 300 mg, secukinumab 150 mg or placebo weekly for 4 weeks and every 4 weeks thereafter. At week 12, placebo patients were re-randomised to secukinumab 300/150 mg. Primary endpoint was ASAS20 (Assessment of SpondyloArthritis international Society) response with secukinumab 300 mg at week 12.
RESULTS
Patients were randomly assigned; 167 to secukinumab 300 mg, 165 to secukinumab 150 mg and 166 to placebo. Secukinumab 300 mg and 150 mg significantly improved ASAS20 response versus placebo at week 12 (63% and 66% vs 31% placebo). The OR (95% CI) comparing secukinumab 300 mg and 150 mg versus placebo, using a logistic regression model after multiple imputation, was 3.8 (2.4 and 6.1) and 4.4 (2.7 and 7.0; p<0.0001).
CONCLUSIONS
Secukinumab 300 mg and 150 mg provided significant improvement in signs and symptoms of axial disease compared with placebo in patients with PsA and axial manifestations with inadequate response to NSAIDs.
TRIAL REGISTRATION NUMBER
NCT02721966.
Topics: Adult; Antibodies, Monoclonal, Humanized; Antirheumatic Agents; Arthritis, Psoriatic; Axis, Cervical Vertebra; Double-Blind Method; Female; Humans; Male; Middle Aged; Severity of Illness Index; Treatment Outcome
PubMed: 33334727
DOI: 10.1136/annrheumdis-2020-218808 -
Arthritis Research & Therapy Dec 2022The associations of rheumatoid arthritis (RA) with risk of site-specific cancers beyond lymphohematopoietic cancer have been scarcely explored. We conducted a Mendelian... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The associations of rheumatoid arthritis (RA) with risk of site-specific cancers beyond lymphohematopoietic cancer have been scarcely explored. We conducted a Mendelian randomization investigation of the associations of RA with site-specific cancers in European and East Asian populations.
METHODS
Independent genetic variants strongly associated with RA in European and East Asian populations were selected as instrumental variables from genome-wide association studies of 58,284 European individuals (14,361 cases and 43,923 controls) and 22,515 East Asian individuals (4873 cases and 17,642 controls), respectively. The associations of genetic variants with overall and 22 site-specific cancers were extracted from the UK Biobank study (n = 367,561), the FinnGen study (n = 260,405), Biobank Japan (n = 212,453), and international consortia. The associations for one outcome from different data sources were combined by meta-analysis.
RESULTS
In the European population, the combined odds ratios per 1-unit increase in log odds of genetic liability to RA were 1.06 (95% confidence interval [CI] 1.03-1.10) for head and neck cancer, 1.06 (95% CI 1.02-1.10) for cervical cancer, 0.92 (95% CI 0.87-0.96) for testicular cancer, and 0.94 (95% CI 0.90-0.98) for multiple myeloma. In the East Asian population, the corresponding odds ratios were 1.17 (95% CI 1.06-1.29) for pancreatic cancer, 0.91 (95% CI 0.88-0.94) for breast cancer, and 0.90 (95% CI 0.84-0.96) for ovarian cancer. There were suggestive associations for breast and ovarian cancer and overall cancer in the European population. No other associations were observed.
CONCLUSION
This study suggests that RA may play a role in the development of several site-specific cancers.
Topics: Male; Humans; Female; Genome-Wide Association Study; Mendelian Randomization Analysis; Genetic Predisposition to Disease; Polymorphism, Single Nucleotide; Testicular Neoplasms; East Asian People; Arthritis, Rheumatoid; Ovarian Neoplasms; European People
PubMed: 36514134
DOI: 10.1186/s13075-022-02970-z -
Journal of Back and Musculoskeletal... Sep 2017The aim of this study was to evaluate the effectiveness of PNF and manual therapy methods in the treatment of patients with cervical spine osteoarthritis, especially... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
The aim of this study was to evaluate the effectiveness of PNF and manual therapy methods in the treatment of patients with cervical spine osteoarthritis, especially their efficacy in reducing pain and improving functionality in everyday life. Long-term results were also compared in order to determine which method of treatment is more effective.
SUBJECTS AND METHODS
Eighty randomly selected females aged 45-65 were included in the study. They were randomly divided into two groups of 40 persons. One group received PNF treatment and the other received manual therapy (MAN.T). To evaluate functional capabilities, the Functional Rating Index was used. To evaluate changes in pain, a shortened version of the McGill Questionnaire was used.
RESULT
The PNF group achieved a greater reduction in pain than the MAN.T group. The PNF group showed a greater improvement in performing daily activities such as sleeping, personal care, travelling, work, recreation, lifting, walking and standing as well as decreased intensity and frequency of pain compared to the MAN.T group.
CONCLUSION
The PNF method proved to be more effective in both short (after two weeks) and long (after three months) term.
Topics: Aged; Cervical Vertebrae; Chronic Pain; Exercise Therapy; Female; Follow-Up Studies; Humans; Middle Aged; Musculoskeletal Manipulations; Neck Pain; Osteoarthritis, Spine; Pulsed Radiofrequency Treatment; Surveys and Questionnaires; Treatment Outcome
PubMed: 28946528
DOI: 10.3233/BMR-169718 -
Cancer Communications (London, England) May 2022Cancer incidence and mortality have received critical attention during the long-term management of morbidities in patients with autoimmune diseases (AIDs). This study...
BACKGROUND
Cancer incidence and mortality have received critical attention during the long-term management of morbidities in patients with autoimmune diseases (AIDs). This study aimed to investigate and compare the risk of cancer associated with five major AIDs in a large-scale Chinese cohort.
METHODS
A total of 8,120 AID patients consecutively admitted to a national tertiary referral center in China were included and followed-up for 38,726.55 patient-years, including those with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), Sjögren's syndrome (SS), systemic scleroderma (SSc), and idiopathic inflammatory myositis (IIM). Demographic data, cancer incidence, predilecting sites and cancer onset time were recorded and compared among the five AIDs.
RESULTS
Four hundred and thirty (5.3%) patients developed cancer. Their median age was 57.5 years and AID duration was 79.8 months. The estimated total standardized incidence ratio (SIR) of cancer in AIDs patients was 3.37, with the highest SIR observed in IIM (4.31), followed by RA (3.99), SSc (3.77), SS (2.88) and SLE (2.58). The increased SIR of cancers in AID patients showed a female predominance (female vs. male: 3.59 vs. 2.77) and younger patient involvement (age <50 vs. ≥50 years: 4.88 vs. 3.04). Patients with SLE had increased SIRs for developing hematologic malignancies and solid tumors located in the urinary bladder, corpus uteri and cervix uteri. Patients with SS had a significantly high SIR for developing non-Hodgkin's lymphoma. Within 3 years of IIM diagnosis, 74.6% of the patients developed cancer and they had a high risk of ovarian cancer. RA was associated with a wide distribution of scancers, including non-Hodgkin's lymphoma, gynecologic, urinary tract, thyroid gland and lung cancers. SSc patients had increased SIRs for developing cervical uterine, lung, and breast cancers.
CONCLUSION
Patients with five major AIDs in China had an increased risk of developing cancer, with a predominance in women and younger patients, although cancer incidence, predilection sites and cancer onset time may vary greatly in each AID entity.
Topics: Acquired Immunodeficiency Syndrome; Arthritis, Rheumatoid; Autoimmune Diseases; Cohort Studies; Female; Humans; Lupus Erythematosus, Systemic; Lymphoma, Non-Hodgkin; Male; Middle Aged; Neoplasms; Sjogren's Syndrome
PubMed: 35357093
DOI: 10.1002/cac2.12283