Arthritis Care & Research最新文献

Objective: Pulmonary fibrosis (PF) is a severe extra-articular manifestation of rheumatoid arthritis (RA). This study aimed to externally validate a genetic risk score (GRS) and a combined risk score (CRS) for predicting the risk of RA-associated PF in an independent cohort of patients with early RA.

Methods: This study used an inception cohort of 1,118 patients diagnosed with RA from northern Sweden between 1996 and 2016. Clinical data were systematically collected, and genotyping was performed for 12 single-nucleotide polymorphisms (SNPs) associated with idiopathic PF. Statistical analyses, including logistic regression and area under the curve (AUC) assessments, were conducted to evaluate the performance of the GRS and in combination with clinical data as the CRS in predicting RA-PF development.

Results: Of the 1,115 patients with complete data, 60 (5.6%) were diagnosed with PF. PF was significantly associated with age, rheumatoid factor positivity, disease activity, and MUC5B (rs35705950) and FAM13A(rs2609255) SNPs. The GRS demonstrated a significant association with RA-PF (odds ratio 2.6, 95% confidence interval 1.6-4.5), whereas the CRS exhibited superior performance (AUC 0.75, P < 0.001) compared to the GRS alone (AUC 0.62). The combined risk score outperformed the GRS in discriminating RA-PF, indicating its potential utility in clinical practice.

Conclusion: This study provides external validation of the Veterans Affairs Rheumatoid Arthritis Registry interstitial lung disease GRS (VARA-ILD-GRS) and the VARA-ILD-CRS in an RA cohort, demonstrating their generalizability and effectiveness in identifying individuals at high risk for RA-ILD. The findings support the integration of genetic and clinical data in risk stratification models, which could significantly improve screening strategies for patients with RA at risk of developing PF.

Persistent pain remains a major challenge in inflammatory arthritis, even when joint inflammation is well controlled. Pain and associated symptoms such as fatigue cannot be explained by peripheral inflammation alone but reflect altered central pain processing. These changes may arise through “top-down” mechanisms, reflecting pre-existing dysfunction in pain perception, or “bottom-up” pathways, driven by peripheral inflammation acting on the brain. Neuroimaging has transformed understanding of these processes by providing in vivo markers of how brain function and structure are related to pain. Functional magnetic resonance imaging (MRI) demonstrates that both task-evoked and resting-state activity are altered in inflammatory arthritis. Connectivity changes involving the thalamus, insula, medial prefrontal cortex, and default mode and salience networks correlate with pain, fatigue, and affective symptoms. Notably, tumor necrosis factor α (TNF-α) inhibitors rapidly normalize pain-related activation, preceding improvements in joint swelling, strongly supporting a bottom-up role for peripheral inflammation. Recent randomized controlled trial data show that baseline central nervous system pain activation predicts analgesic response to TNF-α blockade, positioning neuroimaging as a potential tool for treatment stratification. Complementary modalities provide further insights. Proton electron tomography studies suggest altered pain responses, and novel tracers may clarify contributions of neuroinflammation. Magnetic resonance spectroscopy reveals neurochemical correlates such as increased choline and myo-inositol linked to fatigue, although group-level evidence for overt neuroinflammation remains limited. Structural MRI highlights gray matter changes in regions mediating sensory, cognitive, and affective processing. Together, this supports a dual top-down and bottom-up model of persistent pain in inflammatory arthritis, with important implications for mechanism-based therapies targeting both immune and brain pathways.

Objective: Relapsing polychondritis (RP) is a rare disease defined by recurrent cartilaginous inflammation. Anti-collagen II (Col2) antibodies have been proposed as a diagnostic biomarker for RP, but their performance characteristics are not well defined.

Methods: In an observational cohort, anti-Col2 antibody levels were measured in patients with RP compared to other inflammatory diseases that mimic RP. In parallel, a systematic review and meta-analysis was performed to assess anti-Col2 antibody prevalence across a broad spectrum of diseases. Individual study risk ratios (RRs) and pooled disease category RRs, study bias, and interstudy heterogeneity were assessed.

Results: In the observational cohort, anti-Col2 antibody prevalence did not differ between RP and comparators. The performance characteristics of anti-Col2 to diagnose RP were poor (sensitivity = 18%; specificity = 72%). Anti-Col2 antibody titers did not correlate with disease activity in RP (r = 0.08, P = 0.44). In the systematic review, 71 of 2,443 reviewed articles were included. Anti-Col2 antibodies were not associated with RP across five pooled studies (RR: 2.09; 95% confidence interval [CI]: 0.05-81.80; P = 0.69). Anti-Col2 antibodies were significantly associated with a composite group of inflammatory diseases with cartilaginous involvement (RR: 2.99; 95% CI: 1.29-6.91; P = 0.01). Studies using healthy controls reported increased effect sizes compared to studies that used disease controls (β-estimate = 1.14, I² = 17.08%; P = 0.0004).

Conclusion: Anti-Col2 antibodies are neither sensitive nor specific for RP, are detected in the minority of patients with RP, and are detected at similar prevalences across a spectrum of inflammatory diseases with cartilage inflammation. Use of these antibodies to diagnose or monitor RP is not advisable.

Objective: Body mass index (BMI), glomerular filtration rate (GFR), and pretreatment urate levels have been reported to influence the urate-lowering response to allopurinol. We investigated whether the fractional excretion of uric acid (FEUA) also modulates this response and relates to oxypurinol concentrations. We further evaluated its potential influence on febuxostat, not as a direct comparison, but to determine whether the effect of FEUA was specific to allopurinol.

Methods: The data are from n = 1,547 and n = 296 patients starting allopurinol and febuxostat, respectively. The relationship between FEUA (≤5.5% or >5.5%) and the dose response to allopurinol or febuxostat was assessed by linear mixed-effects regression models on serum urate levels and adjusted for BMI, estimated GFR (eGFR), and treatment doses. Concentrations of oxypurinol were measured in a subgroup of patients (n = 181). A multiple linear regression model was used to assess the association between FEUA and oxypurinol concentrations, adjusted for BMI, eGFR, allopurinol dosage, and serum urate levels.

Results: The median FEUA in the whole population was 4.0% (quartile 1-3: 3%-5.1%). The changes in serum urate levels for each 150-mg increase in allopurinol in patients with FEUA ≤5.5% or >5.5% were -72.37 (confidence interval [CI] -74.81 to -69.94) μM and -65.96 (CI -71.29 to -60.62) μM, respectively (P = 0.032). We found higher oxypurinol concentrations in patients with the lowest FEUA (P = 0.032). However, we did not observe any interaction between the febuxostat response and FEUA (P = 0.13).

Conclusion: Allopurinol is more effective in patients with low FEUA, probably because of the reduced renal excretion of oxypurinol. These data highlight the similarity between the renal handling of oxypurinol and urate.

Objective: This investigation compared all-cause and cause-specific mortality in patients with and without rheumatoid arthritis (RA) in the Veterans Health Administration (VHA) following immune checkpoint inhibitor (ICI) cancer treatment.

Methods: Veterans with RA and a control set of Veterans without RA who were matched on age, sex, and year of Veterans Affairs enrollment and had received an ICI were identified. All-cause and cause-specific mortality were obtained. Survival from the time of ICI initiation was evaluated using Cox models, Kaplan-Meier curves, and log rank testing.

Results: There were 301 patients with RA and 2,114 controls without RA treated with an ICI. The majority of the participants were white, male, and current/former smokers. Lung cancer was the most common malignancy (51.2%), pembrolizumab was the most frequently used ICI (43.9%), and most patients received ICI monotherapy (97.1%). Cox proportional hazard ratio comparison of all-cause mortality in patients with RA to controls without RA was 1.08 (95% confidence interval [CI] 0.94-1.25) for the crude analysis and 1.09 (95% CI 0.94-1.25) for the adjusted analysis. Cause of death was similar in the two groups, most frequently neoplasm in 93.0% and 90.9% for RA and non-RA groups, respectively (P = 0.737). Deaths due to infection were rare in both groups (<1.0%).

Conclusion: Patients with RA who received ICIs for the treatment of malignancy did not experience increased mortality or differences in cause of death compared with patients without RA receiving ICIs. These preliminary data suggest ICI therapy may be considered as part of cancer treatment in RA patients based on individual patient circumstances.

Synovial fluid analysis remains to be a critical aspect of the diagnosis of crystal arthropathies. The gold standard, compensated polarized light microscopy (CPLM), has significant shortcomings due to poor reproducibility and improper training of specialists. Especially in cases of artifacts, low crystal counts, and combinations of crystals, errors are frequently made. There are several new techniques in development to improve the accuracy of crystal identifications. With modified CPLM, microscopes, often aided by machine-learning algorithms, enhance the image contrast, which significantly improves sensitivity. Examples are lens-free polarized light microscopy and polychromatic polarized light microscopy. These techniques have relatively low costs and are easy to use. Another approach is using Raman spectroscopy alone or as a second (verification) step for the objective identification of crystals. This improves objectivity and specificity of diagnosis. Examples include a point-of-care Raman spectroscope and integrated Raman-polarized light microscopy. Although these are more accurate than the microscopy-based platforms, they are often more expensive and require some additional training. Both Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM) have also been used for crystal identification in research. FTIR contributes specificity in a manner similar to Raman methods. SEM adds a higher resolution than optical methods and provides a clear view of morphology. In this narrative review, we provide an overview of the available literature comparing innovational techniques in synovial fluid analysis.

Objective: A patient-centered approach for chronic disease management, including systemic lupus erythematosus (SLE), aligns treatment with patients' values and preferences, leading to improved outcomes. This paper summarizes how patient experiences, perspectives, and priorities informed the American College of Rheumatology (ACR) 2024 Lupus Nephritis (LN) and 2025 SLE screening, treatment guidelines.

Methods: We completed a cross-sectional qualitative study using content analysis of two Patient Panel meetings for the ACR LN and SLE guidelines. Key themes were presented by Patient Panel representatives during Voting Panel Meetings along with evidence for each recommendation, to ensure comprehensive discussions and align treatment recommendations with patients' priorities and values.

Results: Nineteen people (90% women) with diagnoses of SLE and/or LN participated in the Patient Panels and 17 consented to use their feedback for analysis. Thematic analysis of their discussions revealed nine patient-reported key themes in three domains: (1) treatment and monitoring of LN and SLE: medication side effects, daily function, treatment goals, and monitoring and screening; (2) clinical communication: strategies to optimize communication and provider and structural impediments to effective communication; and (3) improving transparency and information sharing: clinical trial participation, and medical costs and insurance coverage. These themes were actively incorporated into discussions during the Voting Panels for the ACR LN and SLE guidelines.

Conclusion: This work supported the integration of patient experiences in the clinical practice guideline development process and aligned recommendations with real-world patient experiences and priorities, thereby enhancing the clinical applicability of the ACR LN and SLE guidelines.

Objective: To provide evidence-based and expert guidance for the treatment and management of non-renal systemic lupus erythematosus (SLE); treatment and management of lupus nephritis are addressed in a separate guideline.

Methods: Clinical questions for treatment and management of SLE were developed in the PICO format (population, intervention, comparator, and outcome). Systematic literature reviews were developed for each PICO question, and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology was used to assess evidence quality and formulate recommendations. The Voting Panel achieved a consensus of ≥70% agreement on the direction (for or against) and strength (strong or conditional) of each recommendation.

Results: We present recommendations and ungraded, consensus-based good practice statements for the treatment and management of SLE that are applicable to pediatric and adult patients. Recommendations emphasize uniform treatment with hydroxychloroquine, limiting duration of glucocorticoid use, and early introduction of conventional and/or biologic immunosuppressive therapies to achieve and maintain control of SLE inflammation (remission or a low level of disease activity), reduce SLE-related morbidity and mortality, and minimize medication-related toxicities.

Conclusion: This guideline presents direction regarding treatment and management of SLE and provides a foundation for well-informed, shared clinician-patient decision-making. These recommendations should not be used to limit or deny access to therapies, as treatment decisions may vary due to the unique clinical situation and personal preferences of each person with SLE.

Objective: Cognitive impairment is prevalent in rheumatoid arthritis (RA), yet risk factors are not well understood. We explored associations between clinical characteristics and cognitive impairment in an RA cohort.

Methods: Data were from a longitudinal RA cohort at Veterans Affairs Puget Sound Health Care System. Cognition was evaluated using the Saint Louis University Mental Status (SLUMS) examination. Demographics and health factors, objectively measured physical function, participant-reported symptoms, RA disease characteristics, and comorbidities were evaluated. Univariable linear regressions explored the association between clinical factors and SLUMS scores. Those with P < 0.1 in the univariable models were evaluated in separate multivariable linear regressions controlling for age, sex, and years of education.

Results: A total of 145 participants with RA were included, with a mean age of 64.5 (SD 11.6) years, and were predominantly male (74%). Using SLUMS, 42 participants (29%) had normal cognition, 83 (57%) had mild cognitive impairment, and 20 (14%) had dementia. Physical performance (aβ: 0.35, confidence interval [CI] 0.11 to 0.59), self-reported exhaustion (aβ: -2.22, CI -3.44 to -0.99), pain (aβ: -0.25, CI -0.50 to -0.00), disability (aβ: -1.79, CI -3.16 to -0.42), and trouble falling asleep (aβ: -2.57, CI -4.00 to -1.14) were all independently associated with a lower SLUMS score (all P < 0.05).

Conclusion: Cognitive impairment was prevalent in our cohort of veterans with RA and was associated with several modifiable clinical factors. Future longitudinal studies are needed to determine the directionality of these associations and evaluate interventions for modifiable risk factors that may mitigate cognitive dysfunction.