Arthritis Research & Therapy最新文献

Objectives: The precise contributions of the classical (CP), lectin (LP), and alternative (AP) pathways to systemic lupus erythematosus (SLE) remain incompletely understood. This study aimed to comprehensively investigate complement pathway components in SLE.

Methods: Sixty SLE patients and 20 healthy controls (HC) were recruited. Plasma C1q, C4, C4b, C2, C3, C5, Factor B (FB), Factor P (FP), Factor D (FD), Factor H (FH), Factor I (FI), and Mannose-binding lectin were measured by Multiplex Assay.

Results: Compared to HC and patients with low disease activity, active SLE showed decreased C1q, C4, C4b, C3, and FP, with increased C2, while FB was reduced only relative to HC. Patients with low C3 and C4 showed higher anti-dsDNA and C2, more newly diagnosed SLE, and lower C1q, C5, FP, FB, and FH. SLE patients with isolated low C3 exhibited reduced FP, FB, and FH, with a trend toward longer disease duration. Newly diagnosed SLE showed decreased C1q and C4b, while those with renal involvement had lower C1q and C3 but higher C2. The concurrent infection subgroup presented decreased C1q and increased C2. Regression analysis identified C2 as independently associated with concurrent infection and FD as the strongest negative correlation with renal function. Principal component analysis further delineated three patient clusters with distinct complement signatures.

Conclusion: The CP is predominantly activated at disease onset, whereas the AP contributes to both initiation and progression of SLE. C2 and FD hold potential as biomarkers for SLE complications. Complement-driven stratification informs precision therapy in SLE.

This study aimed to identify subpopulations of patients with hip osteoarthritis who exhibit distinct adaptations in gait biomechanics, and to evaluate subpopulation-specific effects of total hip replacement on gait biomechanics. Three datasets were analyzed: (1) a cohort of 109 unilateral hip osteoarthritis patients before total hip replacement, (2) a subset of the first dataset of 63 patients re-evaluated after total hip replacement and (3) a control group of 56 healthy individuals. For all participants, three-dimensional joint angle and moment waveforms of the pelvis, ipsilateral hip and knee, as well as sagittal-plane ankle motion and the foot progression angle, were obtained. The analytical framework integrated k-means clustering, support vector machine classifiers, Shapley Additive exPlanations, and statistical waveform analyses. Clustering of the pre-operative dataset revealed three distinct subpopulations characterized by unique patterns in gait kinematics and joint moments. These subpopulations also differed in age, Kellgren-Lawrence score, and walking speed. Prior to total hip replacement, between 51.4% and 85.2% of hip osteoarthritis patients were classified as pathologic; following surgery, this proportion decreased to 27.8% - 51.8%. Hip flexion and rotation angles and moments were identified as the most important features for patient classification. The magnitude of gait improvement after total hip replacement varied across subpopulations, indicating subpopulation-specific responses to surgical intervention. In conclusion, patients with hip osteoarthritis demonstrate distinct subpopulation-specific gait adaptations, both before and after total hip replacement. Preoperative classification of patients into the identified subpopulations using machine learning approaches may facilitate the prediction of postoperative gait recovery and support the development of personalized treatment and rehabilitation strategies.

Chronic inflammatory arthritis of childhood, known as juvenile idiopathic arthritis (JIA), exhibits distinct and shared features with adult-onset disease. Recent advances in minimally invasive synovial biopsy, high resolution imaging and sequencing technologies have enabled detailed characterisation of the inflamed synovium in JIA, facilitating insights into the underlying immunopathology. In this review we draw on these findings to consider how the developing immunological and structural context of the joint impacts the presentation and consequence of inflammatory joint disease in children and young adults.

Background: Treatment of rheumatoid arthritis (RA) frequently requires Janus kinase inhibitors (JAKi) and biologic DMARDs (bDMARDs) with other mechanisms of action (OMA) after tumour necrosis factor inhibitors (TNFi) failure. Comparative safety data between JAKis and OMA in TNFi-inadequate responders (TNFi-IR) remain limited.

Objectives: To evaluate and compare safety profiles of JAKis versus OMA in TNFi-IR RA patients.

Methods: A retrospective cohort study followed 305 RA patients (163 JAKis; 142 OMA) previously treated with TNFi for up to 24 months. Incidence rates (IR) of adverse events (AEs) per 100 patient-years (PY) and incidence rate ratios (IRR) adjusted for disease activity and previous bDMARD exposure were calculated using Poisson regression.

Results: At baseline, OMA patients had higher disease activity (DAS28-CRP = 4.5 vs. 3.8), whereas comorbidities and other baseline characteristics were similar. Overall, AE incidence was higher with OMA (IR 111.6/100 PY) compared to JAKis (IR 65.3/100 PY; adjusted IRR 1.67, 95% CI 1.22-2.31). Serious AEs occurred more frequently with OMA (IR 11.7/100 PY) versus JAKis (IR 7.9/100 PY; adjusted IRR 0.41, 95% CI 0.18-0.95). Infection rates were comparable; herpes zoster occurred exclusively in the JAKi group during the initial year. Venous thromboembolism, cardiovascular events, and malignancies were rare and similar between groups.

Conclusion: In RA patients with inadequate response to TNFis, JAKis and OMA showed comparable safety profiles over 24 months. Serious AEs were numerically higher with OMA; herpes zoster was more frequent with JAKis. No new significant safety signals emerged.

Background: Psoriatic arthritis with inflammatory axial involvement (PsA-ax) and axial spondyloarthritis (axSpA) are distinct entities within the spectrum of spondyloarthritides. Despite overlapping clinical and imaging features, the extent and pattern of radiographic spinal progression in PsA-ax relative to axSpA remain insufficiently characterized.

Objective: To describe and analyse differences in radiographic spinal progression between axSpA and PsA-ax.

Methods: In this retrospective cohort study, 246 patients (axSpA: n=172; PsA-ax: n=74) with lateral radiographs of the cervical, thoracic, and/or lumbar spine were included. Radiographic progression was quantified using the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). An adjusted linear mixed-effects model was used to analyse differences in the longitudinal association with mSASSS between axSpA and PsA-ax. The estimated β-coefficient along with the 95% confidence interval (CI) is reported.

Results: The mSASSS differed substantially at baseline, averaging 6 (SD 14) in axSpA and 0.96 (SD 2.12) in PsA-ax. The patient-level mean MSASSS change over 2 years was small overall, but higher in patients with axSpA than in those with PsA-ax, averaging 0.39 (SD 1.83) and 0.07 (SD 0.29), respectively. A total of 27% of axSpA and 5% of PsA-ax had a patient-level mean MSASSS change over 2 years >0 units. In the adjusted linear mixed-effects model, the estimated mean progression in mSASSS over two years was slightly lower in PsA-ax compared to axSpA (adjusted β = -0.088, 95% CI: -0.446 to 0.271).

Conclusion: Patients with PsA-ax were found to have slightly lower mean progression in mSASSS over two years than patients with axSpA. However, the wide CI crossing zero indicates large uncertainty and compatibility with no difference in mSASSS progression between PsA with axial involvement and axSpA, warranting further studies.

Background: Arthritis imposes serious health consequences, including substantial disability and increased risk of all-cause mortality. Prior studies have reported that pain was associated with decreased health-related quality of life (HRQoL) among individuals with arthritis, yet the association between joint pain severity and HRQoL remains unclear.

Methods: This study analyzed pooled data from 362,366 U.S. adults with arthritis in the 2015-2019 Behavioral Risk Factor Surveillance Survey, categorizing joint pain severity as no/mild (0-3), moderate (4-6), or severe (7-10) via the Numerical Rating Scale. HRQoL was assessed using four domains: self-rated health, physical/mental unhealthy days, and activity limitation. Multivariable logistic regression examined the association between joint pain severity and loss of HRQoL in overall and across demographic subgroups.

Results: Compared to no/mild pain, moderate pain was associated with higher odds of poor self-rated health (OR = 2.18, 95%CI = 2.08-2.27), physical unhealthiness (2.46, 2.35-2.58), mental unhealthiness (2.05, 1.93-2.17), and activity limitation (2.33, 2.20-2.47). Severe pain showed stronger associations (e.g., poor self-rated health: OR = 4.61, 4.40-4.83; physical unhealthiness: 6.74, 6.41-7.09). Subgroup analyses revealed stronger associations in women, Non-Hispanic Whites, and adults aged 45-64 years. Joint pain severity was associated with worse HRQoL, with heterogeneous effects by demographic subgroups.

Conclusions: Moderate-to-severe joint pain is associated with poorer HRQoL across all domains, with severity-correlated HRQoL decline and subgroup variations. Targeted pain management strategies, particularly for severe pain and vulnerable populations, are critical to improving outcomes in arthritis.