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Arthritis Research & Therapy Aug 2023Tofacitinib is an oral Janus kinase inhibitor for the treatment of psoriatic arthritis (PsA). This post hoc analysis assessed tofacitinib efficacy on enthesitis by...
BACKGROUND
Tofacitinib is an oral Janus kinase inhibitor for the treatment of psoriatic arthritis (PsA). This post hoc analysis assessed tofacitinib efficacy on enthesitis by baseline location and severity, and impact on disease activity and patient-reported outcomes (PROs), in patients with PsA.
METHODS
Data were pooled from two phase 3 studies (NCT01877668/NCT01882439) in patients with PsA receiving tofacitinib 5 or 10 mg twice daily to month (M)6 or placebo to M3. Endpoints were: change from baseline in Leeds Enthesitis Index (LEI) or Spondyloarthritis Research Consortium of Canada Enthesitis Index (SPARCC); proportions of patients with enthesitis, relapsed enthesitis after resolution, de novo enthesitis, low disease activity (LDA) or remission (minimal disease activity/very low disease activity; Psoriatic Arthritis Disease Activity Score; Disease Activity Index for Psoriatic Arthritis, and Composite Psoriatic Disease Activity in Psoriatic Arthritis); and PROs (Functional Assessment of Chronic Illness Therapy-Fatigue [FACIT-F] total and arthritis pain Visual Analog Scale scores). Descriptive statistics were generated by visit and treatment. Change from baseline in PROs was evaluated by multivariate linear regression.
RESULTS
Seven hundred ten patients from two studies were included: 479 had LEI > 0; 545 had SPARCC > 0; and 136 had LEI = 0 and SPARCC = 0 at baseline. At baseline, among patients with LEI > 0 or SPARCC > 0, mean LEI and SPARCC across treatments and enthesitis locations/severities ranged from 1.0-4.4 and 1.3-9.4, respectively. Across several baseline enthesitis locations/severities, changes from baseline in LEI and SPARCC up to M3 were greater with tofacitinib (-2.0-0.4 and -3.5-0.2) vs placebo (-0.9-0.4 and -1.5-1.1). Enthesitis at M6 was more common in patients with greater baseline enthesitis severity. At M6, ≤ 40% of patients with baseline LEI > 0 or SPARCC > 0 whose enthesitis had resolved by M1/M3 experienced a relapse, and < 14% of patients with baseline LEI = 0 and SPARCC = 0 had de novo enthesitis. LDA/remission rates generally increased with tofacitinib over time. Baseline LEI location was significantly associated with change from baseline in arthritis pain score, while baseline SPARCC severity was significantly associated with change from baseline in FACIT-F total and arthritis pain scores.
CONCLUSION
Tofacitinib treatment resulted in improvements in enthesitis in patients with PsA, regardless of baseline location or severity.
TRIAL REGISTRATION
NCT01877668;NCT01882439.
Topics: Humans; Arthritis, Psoriatic; Enthesopathy; Pain; Piperidines; Spondylarthritis
PubMed: 37608391
DOI: 10.1186/s13075-023-03108-5 -
RMD Open Sep 2023To estimate the incidence of infections among patients with psoriatic arthritis (PsA) or axial spondyloarthritis (axSpA), two distinct phenotypes included in the large... (Meta-Analysis)
Meta-Analysis
Incidence of infections in patients with psoriatic arthritis and axial spondyloarthritis treated with biological or targeted disease-modifying agents: a systematic review and meta-analysis of randomised controlled trials, open-label studies and observational studies.
OBJECTIVE
To estimate the incidence of infections among patients with psoriatic arthritis (PsA) or axial spondyloarthritis (axSpA), two distinct phenotypes included in the large group of spondyloarthritis (SpA), treated with tumour necrosis-factor-inhibitors, interleukin-17-inhibitors, Janus kinase-inhibitors, IL-23 or IL-12/23-inhibitors (IL-12/23i), phosphodiesterase 4-inhibitors or cytotoxic T-lymphocyte associated protein 4-Ig.
METHODS
A meta-analysis of randomised controlled trials (RCTs), open-label extension and observational studies was conducted. Serious infections were defined as infections that were life-threatening, required intravenous antibiotics and/or hospitalisation. Non-serious infections did not meet these severity criteria. The incidence rates (IR) were reported for each diagnosis by treatment class and study type using random-effect model to create a 95% CI.
RESULTS
Among 23 333 PsA patients and 11 457 axSpA patients, there were 1.09 serious infections per 100 patient-years (PY) (95% CI 0.85 to 1.35) with similar IR in PsA (0.96 per 100 PY 95% CI 0.69 to 1.28) and axSpA (1.09 per 100 PY 95% CI 0.76 to 1.46). The IR was lower in RCTs (0.77 per 100 PY 95% CI 0.41 to 1.20) compared with observational studies (1.68 per 100 PY 95% CI 1.03 to 2.47). In PsA patients, the lowest IR value was observed with IL-12/23i (0.29 per 100 PY 95% CI 0.00 to 1.03). There were 53.0 non-serious infections per 100 PY (95% CI 43.47 to 63.55) in 7257 PsA patients and 5638 axSpA patients. The IR was higher in RCTs (69.95 per 100 PY 95% CI 61.59 to 78.84) compared with observational studies (15.37 per 100 PY 95% CI 5.11 to 30.97).
CONCLUSION
Serious infections were rare events in RCTs and real-life studies. Non-serious infections were common adverse events, mainly in RCTs.
PROSPERO REGISTRATION NUMBER
CRD42020196711.
Topics: Humans; Arthritis, Psoriatic; Incidence; Interleukin-12; Axial Spondyloarthritis; Research Design; Randomized Controlled Trials as Topic
PubMed: 37714666
DOI: 10.1136/rmdopen-2023-003064 -
RMD Open Dec 2023This study aims to assess current cardiovascular disease risk and prevalence of risk factors in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and...
OBJECTIVES
This study aims to assess current cardiovascular disease risk and prevalence of risk factors in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthritis (SpA).
METHODS
2050 consecutive patients with inflammatory arthritis (IA) and 939 controls were included, with 1308 patients with RA, 356 patients with PsA and 386 patients with SpA. In a prospective cohort setting, questionnaires regarding previous cardiovascular events and risk factors were used to assess cardiovascular risk and prevalence in patients with IA by calculating ORs using logistic regression models.
RESULTS
'Traditional' cardiovascular (CV) risk factors were significantly elevated in patients with IA compared with controls. Cardiovascular disease (CVD) ORs were increased in patients with RA and PsA compared with controls, 1.61 (95% CI: 1.04 to 2.48) and 2.12 (95% CI: 1.23 to 3.66), respectively, and a trend towards increased odds was observed in patients with SpA (OR 1.43; 95% CI: 0.79 to 2.59). After adjusting for traditional risk factors, CV risk was not increased in patients with RA (OR; 0.95, 95% CI: 0.58 to 1.55), PsA (OR 1.19; 95% CI: 0.64 to 2.22) and SpA (OR; 0.91, 95% CI: 0.47 to 1.77).
CONCLUSION
CVD is currently still more prevalent in patients with IA compared with healthy controls and, more importantly, this elevated risk is highly influenced by an increased prevalence of 'traditional' CV risk factors. More attention to, as well as improvements in, identification and treatment of 'traditional' risk factors, need to be made for not only RA, but other IA conditions as well.
Topics: Humans; Arthritis, Psoriatic; Cardiovascular Diseases; Prospective Studies; Arthritis, Rheumatoid; Risk Factors
PubMed: 38053460
DOI: 10.1136/rmdopen-2023-003485 -
Annals of Nuclear Medicine Mar 2024Rheumatoid Arthritis (RA) is a systemic inflammatory disorder that commonly presents with polyarthritis but can have multisystemic involvement and complications, leading... (Review)
Review
Rheumatoid Arthritis (RA) is a systemic inflammatory disorder that commonly presents with polyarthritis but can have multisystemic involvement and complications, leading to increased morbidity and mortality. The diagnosis of RA continues to be challenging due to its varied clinical presentations. In this review article, we aim to determine the potential of PET/CT to assist in the diagnosis of RA and its complications, evaluate the therapeutic response to treatment, and predict RA remission. PET/CT has increasingly been used in the last decade to diagnose, monitor treatment response, predict remissions, and diagnose subclinical complications in RA. PET imaging with [F]-fluorodeoxyglucose ([F]-FDG) is the most commonly applied radiotracer in RA, but other tracers are also being studied. PET/CT with [F]-FDG, [F]-NaF, and other tracers might lead to early identification of RA and timely evidence-based clinical management, decreasing morbidity and mortality. Although PET/CT has been evolving as a promising tool for evaluating and managing RA, more evidence is required before incorporating PET/CT in the standard clinical management of RA.
Topics: Humans; Positron Emission Tomography Computed Tomography; Fluorodeoxyglucose F18; Arthritis, Rheumatoid; Positron-Emission Tomography; Radiopharmaceuticals
PubMed: 38277115
DOI: 10.1007/s12149-023-01896-z -
Frontiers in Endocrinology 2023Neutrophil extracellular traps (NETs) are composed of chromatin filaments coated with granular and cytosolic proteins, which contribute to the pathogenesis and...
Neutrophil extracellular traps (NETs) are composed of chromatin filaments coated with granular and cytosolic proteins, which contribute to the pathogenesis and progression of immune-related diseases. NETs are frequently observed in gouty arthritis, but the related mechanisms remain poorly understood. The aim of our study was to systematically elucidate the molecular mechanisms of self-remitting effects in gouty arthritis, and the causative relationship between neutrophil autophagy and NETs. The air pouch and paw edema model were used to simulate gouty arthritis in mice. Neutrophil infiltration and the formation of NETs were found in gouty arthritis. Interestingly, monosodium urate (MSU) crystals could induce the formation of NETs, degrade inflammatory factors, and alleviate the inflammatory response in gouty arthritis. In addition, MSU crystals resulted in profound molecular alterations in neutrophils using RNA-seq analysis, including autophagy activation. MSU crystals could activate neutrophil autophagy , and autophagy activators and inhibitors could regulate the formation of NETs. Furthermore, we explored the mechanism of autophagy-induced NETs. Autophagy related protein 7 (ATG7) produced by neutrophils stimulated with MSU crystals worked synergistically with p53 to enter the nucleus, promoting peptidyl arginine deiminase 4 (PAD4) expression, and inducing the formation of NETs. Finally, we substantiated that neutrophil autophagy regulates the severity of gouty arthritis the formation of NETs in PAD4 mice. Our results indicated that the autophagy of neutrophils regulates the formation of NETs and degrades inflammatory factors. Regulating autophagy and interfering with the formation of NETs represents a potential therapeutic approach against gouty arthritis during clinical practice.
Topics: Mice; Animals; Arthritis, Gouty; Neutrophils; Extracellular Traps; Uric Acid; Inflammation
PubMed: 37810893
DOI: 10.3389/fendo.2023.1071630 -
Medicine Mar 2024Juvenile idiopathic arthritis (JIA) is a chronic clinical condition characterized by arthritic features in children under the age of 16, with at least 6 weeks of active... (Review)
Review
Juvenile idiopathic arthritis (JIA) is a chronic clinical condition characterized by arthritic features in children under the age of 16, with at least 6 weeks of active symptoms. The etiology of JIA remains unknown, and it is associated with prolonged synovial inflammation and structural joint damage influenced by environmental and genetic factors. This review aims to enhance the understanding of JIA by comprehensively analyzing relevant literature. The focus lies on current diagnostic and therapeutic approaches and investigations into the pathoaetiologies using diverse research modalities, including in vivo animal models and large-scale genome-wide studies. We aim to elucidate the multifactorial nature of JIA with a strong focus towards genetic predilection, while proposing potential strategies to improve therapeutic outcomes and enhance diagnostic risk stratification in light of recent advancements. This review underscores the need for further research due to the idiopathic nature of JIA, its heterogeneous phenotype, and the challenges associated with biomarkers and diagnostic criteria. Ultimately, this contribution seeks to advance the knowledge and promote effective management strategies in JIA.
Topics: Child; Animals; Humans; Infant; Arthritis, Juvenile; Phenotype; Biomarkers
PubMed: 38552102
DOI: 10.1097/MD.0000000000037567 -
Cell Proliferation Mar 2024This study aims to determine the molecular mechanisms and analgesic effects of transient receptor potential vanilloid 1 (TRPV1) in the treatments of osteoarthritis (OA)... (Review)
Review
This study aims to determine the molecular mechanisms and analgesic effects of transient receptor potential vanilloid 1 (TRPV1) in the treatments of osteoarthritis (OA) and rheumatoid arthritis (RA). We summarize and analyse current studies regarding the biological functions and mechanisms of TRPV1 in arthritis. We search and analyse the related literature in Google Scholar, Web of Science and PubMed databases from inception to September 2023 through the multi-combination of keywords like 'TRPV1', 'ion channel', 'osteoarthritis', 'rheumatoid arthritis' and 'pain'. TRPV1 plays a crucial role in regulating downstream gene expression and maintaining cellular function and homeostasis, especially in chondrocytes, synovial fibroblasts, macrophages and osteoclasts. In addition, TRPV1 is located in sensory nerve endings and plays an important role in nerve sensitization, defunctionalization or central sensitization. TRPV1 is a non-selective cation channel protein. Extensive evidence in recent years has established the significant involvement of TRPV1 in the development of arthritis pain and inflammation, positioning it as a promising therapeutic target for arthritis. TRPV1 likely represents a feasible therapeutic target for the treatment of OA and RA.
Topics: Humans; Antineoplastic Agents; Arthritis, Rheumatoid; Chondrocytes; Inflammation; Osteoarthritis
PubMed: 37994506
DOI: 10.1111/cpr.13569 -
RMD Open Dec 2023Still's disease is more frequently observed in the paediatric context, but a delayed onset is not exceptional both in the adulthood and in the elderly. However, whether...
OBJECTIVE
Still's disease is more frequently observed in the paediatric context, but a delayed onset is not exceptional both in the adulthood and in the elderly. However, whether paediatric-onset, adult-onset and elderly-onset Still's disease represent expressions of the same disease continuum or different clinical entities is still a matter of controversy. The aim of this study is to search for any differences in demographic, clinical features and response to treatment between pediatric-onset, adult-onset and elderly-onset Still's disease.
METHODS
Subjects included in this study were drawn from the International AutoInflammatory Disease Alliance Network registry for patients with Still's disease.
RESULTS
A total of 411 patients suffering from Still's disease were enrolled; the disease occurred in the childhood in 65 (15.8%) patients, in the adult 314 (76.4%) patients and in the elderly in 32 (7.8%) patients. No statistically significant differences at post-hoc analysis were observed in demographic features of the disease between pediatric-onset, adult-onset and elderly-onset Still's disease. The salmon-coloured skin rash (p=0.004), arthritis (p=0.009) and abdominal pain (p=0.007) resulted significantly more frequent among paediatric patients than in adult cases, while pleuritis (p=0.015) and arthralgia (p<0.0001) were significantly more frequent among elderly-onset patients compared with paediatric-onset subjects. Regarding laboratory data, thrombocytosis was significantly more frequent among paediatric patients onset compared with adult-onset subjects (p<0.0001), while thrombocytopenia was more frequent among elderly-onset patients although statistical significance was only bordered. No substantial differences were observed in the response to treatments.
CONCLUSIONS
Despite some minor difference between groups, overall, demographic, clinical, laboratory and treatments aspects of Still's disease were similarly observed in patients at all ages. This supports that pediatric-onset, adult-onset and elderly-onset Still's disease is the same clinical condition arising in different ages.
Topics: Adult; Humans; Child; Aged; Still's Disease, Adult-Onset; Arthritis, Juvenile; Arthralgia
PubMed: 38053457
DOI: 10.1136/rmdopen-2023-003578 -
Seminars in Arthritis and Rheumatism Oct 2023(1) to describe the frequency of minimal disease activity (MDA) in a real-life psoriatic arthritis (PsA) cohort, (2) to longitudinally explore predictors of MDA; (3) to...
OBJECTIVE
(1) to describe the frequency of minimal disease activity (MDA) in a real-life psoriatic arthritis (PsA) cohort, (2) to longitudinally explore predictors of MDA; (3) to examine frequency and predictors of low disease activity (LDA) in patients with axial involvement (axPsA).
METHODS
consecutive PsA patients in stable biological/targeted-synthetic Disease-Modifying Anti-Rheumatic Drugs (bDMARDs/tDMARDs) who attended our center were enrolled. Disease activity indices, including MDA and ankylosing spondylitis disease activity score-LDA (ASDAS-LDA) for axPsA, were evaluated at baseline and every 6 months, up to 36 months or bDMARDs/tsDMARDs discontinuation. Patients' history, BMI, comorbidities - including osteoarthritis (OA) and fibromyalgia - were collected. Variables were compared between patients who achieved sustained MDA and those who did not. Multivariable generalized estimating equation (GEE) models were built to identify predictors of MDA and ASDAS-LDA over time. Data were expressed as beta coefficient (95%CI).
RESULTS
104 patients were enrolled, 54% males, mean age 55.7 years; 52% had axPsA. Across all evaluations, 52-61% reached MDA, and 17-24% achieved ASDAS-LDA. AxPsA, fibromyalgia, OA and BMI≥35 were less frequently observed in patients with sustained MDA. The GEE model confirmed the following factors were significantly and independently associated with MDA: age (Beta=-0.05), bDMARDs/tsDMARDs duration (Beta=+0.31), axPsA (Beta=-1.07), fibromyalgia (Beta=-3.35), OA (Beta=-1.87), BMI≥35 (Beta=-2.53). Age (Beta=-0.01), fibromyalgia (Beta=-2.03) and OA (Beta=-1.30) were also independently associated with ASDAS-LDA.
CONCLUSIONS
MDA is an attainable target in real-life. AxPsA represents a difficult-to-treat subset. Sustained MDA depends on disease features (axPsA) as well as patients' characteristics (e.g. age, bDMARDs/tDMARDs duration, comorbidities).
Topics: Male; Humans; Middle Aged; Female; Arthritis, Psoriatic; Fibromyalgia; Antirheumatic Agents; Spondylitis, Ankylosing; Comorbidity; Osteoarthritis; Severity of Illness Index
PubMed: 37453183
DOI: 10.1016/j.semarthrit.2023.152237 -
RMD Open Nov 2023To investigate the relationship between metabolomic profiles, genome-wide polygenic risk scores (PRSs) and risk of rheumatoid arthritis (RA).
OBJECTIVE
To investigate the relationship between metabolomic profiles, genome-wide polygenic risk scores (PRSs) and risk of rheumatoid arthritis (RA).
METHODS
143 nuclear magnetic resonance-based plasma metabolic biomarkers were measured among 93 800 participants in the UK Biobank. The Cox regression model was used to assess the associations between these metabolic biomarkers and RA risk, and genetic correlation and Mendelian randomisation analyses were performed to reveal their causal relationships. Subsequently, a metabolic risk score (MRS) comprised of the weighted sum of 17 clinically validated metabolic markers was constructed. A PRS was derived by assigning weights to genetic variants that exhibited significant associations with RA at a genome-wide level.
RESULTS
A total of 620 incident RA cases were recorded during a median follow-up time of 8.2 years. We determined that 30 metabolic biomarkers were potentially associated with RA, while no further significant causal associations were found. Individuals in the top decile of MRS had an increased risk of RA (HR 3.52, 95% CI: 2.80 to 4.43) compared with those below the median of MRS. Further, significant gradient associations between MRS and RA risk were observed across genetic risk strata. Specifically, compared with the low genetic risk and favourable MRS group, the risk of incident RA in the high genetic risk and unfavourable MRS group has almost elevated by fivefold (HR 6.10, 95% CI: 4.06 to 9.14).
CONCLUSION
Our findings suggested the metabolic profiles comprising multiple metabolic biomarkers contribute to capturing an elevated risk of RA, and the integration of genome-wide PRSs further improved risk stratification.
Topics: Humans; Biological Specimen Banks; Cohort Studies; Risk Factors; Arthritis, Rheumatoid; Biomarkers; United Kingdom
PubMed: 38035758
DOI: 10.1136/rmdopen-2023-003560