Therapeutic Advances in Musculoskeletal Disease最新文献

Background: Previous meta-analyses have demonstrated osteoarthritis (OA) is associated with an increased risk of dementia, but these studies were prone to bias based on residual confounding factors and reverse causality.

Objectives: We aimed to investigate associations between OA and cognitive function using data from the National Health and Nutrition Examination Survey (NHANES) and to investigate the causality using Mendelian randomization (MR).

Design: This is a cross-sectional study and MR study.

Methods: Data from the NHANES 2011-2014 were used. Multiple linear, logistic regressions and stratified analyses were used to determine the association between OA status and cognitive function. Sample weights were used to ensure result generalizability. Two-sample MR analysis was conducted to examine the association between OA and dementia. Mediation analyses were performed to investigate the mediating effects of depression.

Results: We did not demonstrate a significant association between OA and cognitive performance after adjusting for relevant covariates (p > 0.05), and the population of individuals with both OA and depression was associated with higher odds of low total word recall cognitive performance (odds ratio (OR) = 4.74, 95% confidence interval (CI): 1.09-20.63; p = 0.04). Genetically predicted specific-site OA was not significantly associated with the risk of dementia (OR = 1.12; 95% CI: 0.96-1.32; p = 0.16), Alzheimer's disease (OR = 0.95, 95% CI: 0.68-1.31, p = 0.74), vascular dementia (OR = 1.32, 95% CI: 0.82-2.13, p = 0.25) with accepted heterogeneity and no evidence of directional pleiotropy. Furthermore, major depression was found to mediate the pathway between OA and vascular dementia (β = 0.044, 95% CI: -0.391 to 0.479, p < 0.05).

Conclusion: Our findings indicate that there is no significant association or causal relationship between OA and cognitive decline. However, depression may serve as an important factor influencing cognitive outcomes. Future research should further explore the bidirectional causal relationship and underlying mechanisms.

Psoriatic arthritis (PsA) presents various clinical manifestations, including skin lesions, peripheral arthritis, axial involvement, enthesitis, nail involvement, dactylitis, and uveitis. In addition, it causes a high incidence of lifestyle-related diseases and an increase in cerebrovascular and cardiovascular events. As the pathology of PsA has been clarified, molecular-targeted drugs targeting tumor necrosis factor-α, interleukin (IL)-17A, IL-17A/F, IL-17 receptor, IL-12/23(p40), IL-23p19, Cytotoxic T-lymphocyte Antigen-4 (CTLA-4), Janus kinase, and phosphodiesterase-4 have been developed and are widely used in clinical practice. PsA is clinically and molecularly heterogeneous, and it is necessary to improve various clinical symptoms with limited treatment options simultaneously; therefore, rheumatologists sometimes encounter difficult situations in clinical practice. Hence, the development of precision medicine may improve treatment outcomes. Recently, the strategic use of molecular-targeted drugs based on the stratification of patients with PsA by peripheral blood lymphocyte phenotyping and serum cytokine concentrations has been reported to possibly lead to a higher therapeutic response. A randomized controlled trial was initiated to verify the efficacy of this treatment strategy. However, to make precision medicine in PsA feasible, shifting from conventional clinical trials to clinical trials based on biomarker profiles and accumulating further data are necessary.

Background: Rheumatology has experienced notable changes in the last decades. New drugs, including biologic agents and Janus kinase (JAK) inhibitors, have blossomed. Concepts such as window of opportunity, arthralgia suspicious for progression, or difficult-to-treat rheumatoid arthritis (RA) have appeared; and new management approaches and strategies such as treat-to-target have become popular. Statistical learning methods, gene therapy, telemedicine, or precision medicine are other advancements that have gained relevance in the field. To better characterize the research landscape and advances in rheumatology, automatic and efficient approaches based on natural language processing (NLP) should be used.

Objectives: The objective of this study is to use topic modeling (TM) techniques to uncover key topics and trends in rheumatology research conducted in the last 23 years.

Design: Retrospective study.

Methods: This study analyzed 96,004 abstracts published between 2000 and December 31, 2023, drawn from 34 specialized rheumatology journals obtained from PubMed. BERTopic, a novel TM approach that considers semantic relationships among words and their context, was used to uncover topics. Up to 30 different models were trained. Based on the number of topics, outliers, and topic coherence score, two of them were finally selected, and the topics were manually labeled by two rheumatologists. Word clouds and hierarchical clustering visualizations were computed. Finally, hot and cold trends were identified using linear regression models.

Results: Abstracts were classified into 45 and 47 topics. The most frequent topics were RA, systemic lupus erythematosus, and osteoarthritis. Expected topics such as COVID-19 or JAK inhibitors were identified after conducting dynamic TM. Topics such as spinal surgery or bone fractures have gained relevance in recent years; however, antiphospholipid syndrome or septic arthritis have lost momentum.

Conclusion: Our study utilized advanced NLP techniques to analyze the rheumatology research landscape and identify key themes and emerging trends. The results highlight the dynamic and varied nature of rheumatology research, illustrating how interest in certain topics has shifted over time.

Background: Recent studies have shown the impact of obesity on achieving low disease activity or remission in rheumatoid arthritis (RA) patients treated with tumor necrosis factor inhibitors. However, there is limited research on the effects of obesity on clinical responses to non-TNF-targeted treatments.

Objectives: This study investigated the influence of body mass index (BMI) on clinical response to non-TNF-targeted treatments in RA patients.

Design: We used data from the KOrean nationwide BIOlogics & targeted therapy (KOBIO) registry, a multicenter, prospective, observational cohort that included RA patients in South Korea.

Methods: Patients who received at least one prescription for non-TNF-targeted treatments, including abatacept, tocilizumab, and Janus kinase inhibitors, were included. They were categorized into three BMI groups: under 25 kg/m² (434 patients), between 25 and 30 kg/m² (146 patients), and over 30 kg/m² (22 patients). After 1 year of treatment, treatment continuation rates and clinical responses among these BMI groups were compared. Time on treatment for each category was analyzed using Kaplan-Meier curves and Cox regression, adjusting for confounders.

Results: The 1-year continuation rate of the targeted treatment was significantly lower in the obese group (81.8%) compared to the normal BMI (93.8%) and overweight (89.0%) groups (p = 0.033). Disease Activity Score of 28 joints-erythrocyte sedimentation rate score improvement was less in the obese group (2.06 ± 2.14) than in the normal BMI group (2.76 ± 1.55) (p = 0.045). Multivariable Cox proportional hazard analysis showed a higher discontinuation rate in the obese group (hazard ratio: 3.407, 95% confidence interval: 1.157-10.211; p = 0.029).

Conclusion: Higher BMI in RA patients was associated with poorer clinical response and higher discontinuation rates for non-TNF-targeted treatments.

Background: Psoriatic arthritis (PsA) is a chronic inflammatory condition that can affect individuals of all ages. Patients may experience a range of physical and psychological issues.

Objective: To examine the impact of PsA on an individual's quality of life (QoL) and physical function.

Design: A systematic review of the literature.

Data sources and methods: A comprehensive search was conducted across seven electronic databases (Cochrane Central Register of Controlled Trials (CENTRAL), CINAHL, AMED, EMBASE, Global Health, MEDLINE and PsycINFO) to retrieve articles related to QoL and lifestyle in adults with PsA. The inclusion criteria were studies published between 2010 and 2021 that used outcomes validated in patients with PsA. The methodological quality was assessed using Joanna Briggs Institute Critical Appraisal Tools. Our primary outcomes were patient-reported outcomes (PROs) measuring QoL and the impact of disease on physical function. The secondary outcomes were assessments of fatigue, anxiety, depression, sleep, work productivity and employment.

Results: The study included 37 comprehensive studies that examined the impact of PsA on QoL and physical function. The findings revealed that the impact of PsA extends to various aspects of life, including activities of daily living, physical, and emotional aspects, such as fatigue, sleep disturbance, anxiety and depression. Notably, people with PsA experience reduced health-related quality of life (HRQoL), particularly in emotional, social and mental health aspects. The severity of pain and/or fatigue is directly linked to decreased HRQoL. Importantly, those who fail to achieve minimal disease activity face challenges in work productivity and employment status.

Conclusion: To conclude, our review underscores the significant impact of PsA on patients' HRQoL beyond joint disease. The emotional, social, and mental aspects of PsA require compassionate and holistic management.

Trial registration: The PROSPERO international prospective register of systematic reviews - CRD42021257395.

Background: Osteoarthritis (OA) is the leading cause of disability among US adults and most commonly affects the knee. Guidelines for knee OA treatment include behavioral, nonpharmacological, pharmacological, and surgical interventions. While emerging knee OA treatments show promise for pain control, data gaps remain regarding the efficacy, safety, comparative effectiveness, and real-world value of treatments.

Objectives: The Innovations in Genicular Outcomes Registry (IGOR) is prospectively collecting real-world data to assess clinical effectiveness, safety, health-related quality of life, and healthcare resource utilization of knee OA treatments.

Design: The IGOR is a prospective, observational, longitudinal, multicenter registry (NCT05495334) examining knee OA pain treatment outcomes at intervals up to 18 months after treatment.

Methods and analysis: All clinical management decisions are made via shared decision-making involving both the physician and the patient. Index joint-directed treatments may include various intra-articular injections, oral opioid and nonopioid medications (including nonsteroidal anti-inflammatory drugs), cryo nerve blocks, radiofrequency ablations, novel treatment modalities, other physical therapy modalities (including muscle strengthening), and total knee arthroplasties. Patient-reported assessments along with physician-provided medical record data are recorded. Regular data quality assessments are conducted for each site, and an outside monitor ensures data quality and integrity. A steering committee ensures transparency and oversees administrative, legal, ethical, and scientific decisions. Treatment outcomes within and between therapies are compared.

Ethics: Ethical approval was granted by Advarra, Inc. (protocol number, Pro00050981).

Discussion: Data from the IGOR registry study will further elucidate the effectiveness, safety, and real-world value of knee OA treatments individually or in combination. Characterization of real-world treatment patterns will help better understand the impact of specific treatments.

Trial registration: Clinicaltrials.gov, NCT05495334.

Background: The EULAR Sjögren's syndrome (SS) disease activity index (ESSDAI) pulmonary domain is used to assess the activity of respiratory system involvement in Sjögren's disease (SjD). The most unfavorable form of respiratory involvement in SjD, after lymphomas, is interstitial lung disease (ILD).

Objectives: The aim of the study was to assess the involvement of the respiratory system in SjD patients and the occurrence of ILD in high-resolution computed tomography (HRCT), depending on immunological markers, the influence of cigarette smoking, and the age of the patients.

Design: Single-center, registry, cohort study.

Methods: Among all SjD patients, a group with involvement in the pulmonary domain was distinguished. This group was later subjected to a detailed analysis of immunological and serological markers and chest imaging tests.

Results: In all, 64 patients out of 299 with SjD had involvement in the pulmonary domain defined according to the ESSDAI definition. The most frequently reported clinical symptoms of respiratory system involvement included dryness and chronic cough (over 80% of patients), followed by shortness of breath. Nine percent of patients with changes in lungs were asymptomatic. Patients with pulmonary involvement were older (54 vs 48 years, p < 0.05). In the subpopulation of patients with SjD and pulmonary involvement, the presence of rheumatoid factor (73% vs 60%, p < 0.05), and hematological domain involvement according to ESSDAI (54% vs 37%, p < 0.05) were more common. In the group of 64 patients with a positive pulmonary domain, 34 (53%) had ILD on HRCT. A higher incidence of comorbidities was found in the population of patients with ILD. No correlation was found between the type of lung involvement and the immunological profile, inflammatory markers, age, and smoking habit.

Conclusion: Involvement of the pulmonary domain is common in patients with SjD. However, the clinical picture is very heterogeneous, which determines the subsequent personalization of treatment.

Background: Rheumatoid arthritis (RA) increases the risk of premature mortality, primarily due to cardiovascular diseases (CVD). While Systematic Coronary Risk Evaluation (SCORE) and its updated version SCORE2 are used to estimate CVD risk, these tools may not adequately capture the full cardiovascular risk profile in RA patients.

Objectives: This study aims to compare the effectiveness of SCORE2 versus SCORE in predicting the presence of carotid plaques or increased intima-media thickness (IMT), as detected by ultrasound, in RA patients.

Design: This was a single-center cross-sectional study and included adult RA patients with moderate to severe disease who initiated treatment with Janus kinase inhibitors or anti-tumor necrosis factor inhibitors between September 2022 and April 2023.

Methods: Both SCORE and SCORE2 were calculated for each patient. Carotid ultrasound examinations documented the presence of plaques, and IMT was measured.

Results: A total of 122 patients were included. The mean SCORE was 2.48%, while SCORE2 was significantly higher at 4.07% (p < 0.01). SCORE identified 12 (10%) patients as high risk, while SCORE2 identified 99 (81%). Atherosclerotic plaques were present in 34% (n = 42) of participants. Traditional cardiovascular risk factors (dyslipidemia, diabetes, hypertension, and smoking) were significantly associated with ultrasound-detected risk. In 87 cases where SCORE was underestimated, 34 patients (39%) classified as low-moderate risk by SCORE were correctly reclassified as high risk by SCORE2. However, 54 cases classified as high risk by SCORE2 had normal carotid ultrasounds. The sensitivity of SCORE for predicting plaque presence was 21%, compared to 100% for SCORE2. Combining SCORE with carotid ultrasound increased the detection of high-risk patients from 10% to 38%. However, adding carotid ultrasound to SCORE2 did not increase the detection rate beyond 81%.

Conclusion: Our findings highlight the superior performance of SCORE2 compared to SCORE in identifying RA patients with carotid ultrasound abnormalities, thus indicating a higher cardiovascular risk.

Background: Behçet disease (BD) is a rare disease in childhood and its uveitis may lead to blindness if not properly treated.

Objectives: We aim to describe a cohort of paediatric BD patients with uveitis.

Design: This is a multicentric retrospective study.

Methods: Six paediatric rheumatology units in Italy were involved including children with a diagnosis of paediatric BD according to the International Criteria for BD Criteria and/or to the International Study Group Criteria for BD, or Paediatric BD classification criteria if they had uveitis. Demographic, laboratory and clinical data were collected and followed up to March 2023. Ocular characteristics and treatment response were assessed according to Standardization Uveitis Nomenclature.

Results: Among the 97 children with BD followed, 33 (34%) had uveitis (22 males, 66.7%). The median age at onset of BD and uveitis were, respectively, 11.5 years (2.5-17.1) and 11 years (3-17.3). Uveitis preceded BD diagnosis in 18 children (54.5%). Seventeen children had HLA B51 positivity (51.5%). Uveitis was bilateral in 25 (75.8%), and panuveitis in 16 (48.5%). All the patients received at least 1 systemic treatment for uveitis: 25 adalimumab, 2 tocilizumab, 1 abatacept, 3 infliximab, 4 azathioprine, 1 methotrexate and 1 corticosteroid. The remission was achieved with 30/35 treatments (85.7%) after a median time of 8 months (6-24). Six children had a relapse in therapy after the achievement of remission (20%). Fourteen patients stopped the therapy for persistent remission, but 5 relapsed (35.7%) after a median time of 9 months (range 1-48).

Conclusion: Uveitis in BD is a sight-threatening condition, and it is more frequently a panuveitis. Biologic treatments seem to be often required to control ocular inflammation.

Background: Inflammatory bowel disease (IBD) affects 5%-10% of ankylosing spondylitis (AS) patients. Prior data suggest AS patients with IBD may have more severe disease and lower HLA-B27 prevalence. Yet, little is known about potential distinctions in AS with IBD compared to those without IBD.

Objective: To investigate the clinical characteristics and radiographic differences between patients with (AS) with and without concurrent IBD.

Design: This multicenter, observational, cross-sectional study included patients meeting European Spondyloarthropathy Study Group criteria from the Registry of Spondyloarthritis of Spanish Rheumatology (REGISPONSER) and Ibero-American Registry of Spondyloarthropathies (RESPONDIA) registries.

Methods: Characteristics and disease burden were compared between patients with and without IBD. Multivariate logistic regression identified factors independently associated with IBD presence in patients with AS.

Results: We included a total of 2766 patients with AS (1254 from REGISPONSER and 1512 from RESPONDIA), among whom 142 patients (5.13%) presented with concomitant IBD. AS patients with concurrent IBD were less frequently male, had a lower prevalence of HLA-B27 positivity, experienced a lower prolonged diagnostic delay, had a lower frequency of enthesitis, and received more commonly intensified treatment compared to those without IBD. In terms of structural damage, the Bath Ankylosing Spondylitis Radiology Index (BASRI) score for the sacroiliac joints (SIJs), cervical spine, and lumbar spine was lower in patients with AS and IBD than in those without IBD. In the multivariable analysis, the presence of IBD was significantly associated with a lower prevalence of HLA-B27 and enthesitis, with odds ratios (OR) of 0.32 (95% confidence interval (CI): 0.20-0.52) and 0.58 (95% CI: 0.33-0.97), respectively. Furthermore, structural damage in SIJs (BASRI) was significantly decreased in patients with IBD, with an OR of 0.79 (95% CI: 0.64-0.99).

Conclusion: The presence of IBD in AS is associated with lower HLA-B27 positivity, less enthesitis, and less radiographic damage in this large population study.