Arthritis Care & Research最新文献

Objective: The goal was to assess the diagnostic performance of three novel autoantibodies (NA) for Sjögren's disease (SjD) by comparing NA prevalence in patients with SjD, other autoimmune rheumatic diseases (ARDs), nonspecific chronic sialadenitis (CS), and controls.

Methods: We identified rheumatology outpatients with confirmed SjD, systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), systemic sclerosis (SSc), CS, and healthy controls. Subjects underwent serum testing for antibodies to salivary gland protein 1 (SP-1), parotid secretory protein (PSP) and carbonic anhydrase-6 (CA-6). Subjects with SjD, CS and controls also underwent testing of saliva. Receiver operating characteristic (ROC) curve C-statistics along with sensitivity, specificity, positive and negative likelihood ratios were calculated for each serum autoantibody for SjD vs. CS or controls.

Results: Among 468 patients screened, 444 were analyzed including cohorts with: SjD (n=149), SLE (n=70), SSc (n=56), RA (n=73), CS (n=31) and controls (n=65). There was no statistical difference (p=0.80) in the presence of one or more NA in the serum of SjD patients compared to subjects with other ARDs, CS, or controls. ROC curves demonstrated poor discriminative ability for SjD versus CS or controls for any positive NA (0.47) or any individual NA (range 0.44 to 0.53). The positive likelihood ratio for having any positive novel autoantibody was 1.04 and 0.83 for SjD vs. CS or controls, respectively.

Conclusion: Testing serum for NA demonstrated poor ability to distinguish patients with SjD from control patients or those with CS or other ARDs. This serum autoantibody panel is not likely to be useful as a diagnostic test for SjD.

Objective: Telehealth and shared decision-making (SDM) enhance the care of people with rheumatic diseases. Responding to calls for training on telehealth and SDM, we developed an educational intervention for rheumatology fellows-in-training (FITs).

Methods: FITs conducted two patient care telehealth encounters (pre- and post-intervention). Following the first encounter, FITs completed an online module highlighting the nuances of SDM during telehealth and a simulated patient encounter to practice telehealth skills, especially SDM. After each observation, FITs received feedback on their "webside" manner, SDM, and visit coordination skills via feedback forms (FF). Wilcoxon-signed rank tests compared quantitative FF measures, while qualitative methods analyzed written comments. FITs completed a survey and self-reported their confidence in SDM during telehealth visits.

Results: Nine and eleven FITs completed pre- and post-intervention encounters, respectively; Forty-seven FITs completed the simulation. Total points earned on the FF and points specific to the visit coordination subsection of the FF significantly increased from pre- to post-intervention (p=0.011 and p=0.049, respectively). "Webside" manner scores improved without reaching statistical significance (p=0.067). SDM scores remained unchanged, while confidence conducting SDM during telehealth improved significantly (p < 0.001). Qualitative analysis highlighted the apt use of technology as a skill FITs could further develop for enhancing SDM during telehealth.

Conclusions: Education dedicated to telehealth skills with an emphasis on SDM improves FITs' confidence in practicing SDM during telehealth and advances general telehealth skills implemented during patient care. Our materials and approach to instruction prepare FITs for delivering telehealth care and enriching patient-centeredness as new entrants into the rheumatology workforce.

Objective: Specialty care access remains a significant challenge, particularly for patients in rural and underserved areas. This study evaluates the implementation and impact of an electronic consultation (eConsult) program aimed at improving access to rheumatology care within the University of Colorado Hospital network.

Method: This mixed methods evaluation of a rheumatology eConsult program used electronic health record and Medicaid claims data to describe patient, provider, and referral characteristics, care process and utilization outcomes, and interviews to gain provider insights about the program.

Results: The analysis included 10,433 traditional referrals and 670 internal and external eConsults placed between April 2018 - June 2022. Most internal eConsults (445/595, 75%) were completed electronically without the need to convert to an in-person consultation, and 73% (325/445) were completed within 3 days. The eConsults that were converted to traditional face-to-face referrals had a higher 180-day completion rate (36%) compared to traditional referrals (19%, p< 0.001). Overall, eConsults and traditional referrals had comparable rates of pharmacotherapy initiation for referrals related to suspected rheumatoid arthritis (RA) (57.1% vs 31.4%, p=0.082). Most eConsults came from primary care providers internal to the network (596/670, 89%). Interviews with team members highlighted successes such as improved efficiency and reduced patient travel burdens, while also identifying challenges, notably the need for increased provider familiarity and usage of the eConsult platform.

Conclusion: Overall, the eConsult program represents a promising strategy to enhance specialty care delivery, particularly for underserved and distant populations, though ongoing education and system integration efforts are crucial for maximizing its impact.

Objective: We aimed to validate the Pediatric Arthritis Ultrasound Scoring System (PAUSS) for upper extremity joints in children with juvenile idiopathic arthritis (JIA).

Methods: Children with JIA were evaluated for elbow, wrist, or finger arthritis by clinical examination (CE) and musculoskeletal ultrasound (MSUS) with images scored according to the joint-specific PAUSS. A subset of children received contrast-enhanced magnetic resonance imaging (ceMRI) of the affected joint(s). The performance of the PAUSS as a measure of arthritis activity was compared to CE and ceMRI, using ceMRI as the reference standard.

Results: Seventy-five children contributed 44 elbows, 55 wrists, and 106 fingers for MSUS and 15 elbows, 16 wrists, and 40 fingers for ceMRI. B-mode PAUSS scores for the finger joints demonstrated moderate correlations with CE findings of arthritis, and the PAUSS-elbow noted a strong correlation. PAUSS scores for all joints showed a sensitivity of 75% to 94% in detecting synovitis when compared to ceMRI and good to excellent diagnostic accuracy for elbow and finger arthritis. The addition of MSUS to CE markedly improved the sensitivity of CE to 92% to 100%. The PAUSS and ceMRI scores for assessment of disease severity had strong correlation for each specific joint (r = 0.65-0.84, P ≤ 0.005).

Conclusion: There is moderate to high sensitivity and diagnostic accuracy of the PAUSS in detecting synovitis in elbow, wrist, and finger joints, as well as a strong correlation of the PAUSS severity scores with the ceMRI severity scores, providing strong support that the PAUSS enhances the clinical assessment of disease activity in children with JIA.

Objective: We evaluated the role of 25-hydroxyvitamin D (25[OH]D), prednisone, and other risk factors for bone mineral density (BMD) loss and osteoporosis in systemic lupus erythematosus (SLE).

Methods: We calculated the association between 25(OH)D levels and other potential risk factors and BMD measures (spine T scores) and osteoporosis (defined as a T score ≤ -2.5) in a lupus cohort of 1,003 patients. Generalized estimating equations were used to assess the statistical significance of observed differences, accounting for patients with multiple BMD measures.

Results: Univariate analysis showed that older age, lower body mass index (BMI), mean past SLE activity (Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index > 2), mean daily prednisone dose at any level, and a history of low C3 or C4 were associated with osteoporosis. Older age, lower BMI, mean 25(OH)D levels, mean daily prednisone dose (again at any dose), and prior low C3 were associated with lower spine T scores. In the multivariate analysis for osteoporosis, older age, lower BMI, low mean 25(OH)D levels, and prednisone dose >5 mg/day remained predictors. Discontinuation of prednisone within one year before the next BMD measurement led to higher mean spine T scores.

Conclusion: Prednisone dose, even at 5 mg/day, and low mean 25(OH)D levels were found to be modifiable predictors of osteoporosis. Mean (reflecting supplementation), rather than initial, 25(OH)D levels were significantly associated with BMD. Some of the bone loss from prior prednisone use appears to be reversible.

Objective: Low preoperative cardiorespiratory fitness is associated with poorer functional and subjective recovery following hip or knee arthroplasty. The objective of this study was to evaluate the ability of simple, indirect assessment tools (the Duke Activity Status Index, daily step count, and timed up and go test) to estimate directly measured cardiorespiratory fitness and identify patients with low preoperative fitness (<15 mL/kg/min) among those with severe hip or knee osteoarthritis.

Methods: Ninety-one patients with severe hip or knee osteoarthritis who were scheduled for total joint arthroplasty were recruited. Within 1 week before surgery, participants performed symptom-limited maximal cardiopulmonary exercise testing, the Duke Activity Status Index questionnaire, accelerometry to determine daily step count, and the timed up and go test.

Results: All three indirect tools provided strong estimates of peak oxygen consumption ( $\dot{V}$ O₂) (r² ≥ 0.61). The Duke Activity Status Index slightly underestimated peak $\dot{V}$ O₂ by 0.9 mL/kg/min. All three metrics performed strongly in their ability to accurately identify patients without a peak $\dot{V}$ O₂ < 15 mL/kg/min; however, their accuracy to positively predict peak $\dot{V}$ O₂ > 15 mL/kg/min was only fair.

Conclusion: These simple, practical, cost-effective tools have utility for estimating preoperative fitness to rule out low fitness. These tools could be used by perioperative clinicians for identifying patients who may not require preoperative cardiopulmonary exercise testing, thereby optimizing resource allocation.

Objective: This study aimed to characterize the pharmacokinetics, pharmacodynamics, safety, and exploratory efficacy of subcutaneous belimumab in pediatric patients with active systemic lupus erythematosus (SLE) receiving standard therapy.

Methods: This single-arm, multicenter, open-label trial (GSK study 200908; ClinicalTrials.gov identifier: NCT04179032) used three-weight-band subcutaneous dosing of belimumab 200 mg every week (qw) for pediatric patients weighing ≥50 kg, every 10 days for pediatric patients weighing 30 to <50 kg, and every 2 weeks (q2w) for pediatric patients weighing 15 to <30 kg. The pharmacokinetic profile was characterized by observed concentration at week 12 and population pharmacokinetics (popPK) estimates derived from concentrations over 52 weeks. Pharmacodynamics, safety, and exploratory efficacy (≥4-point reduction from the baseline Safety of Estrogens in Lupus Erythematosus National Assessment - Systemic Lupus Erythematosus Disease Activity Index [SELENA-SLEDAI] score) were descriptively evaluated. Alternative two-weight-band subcutaneous dosing (≥40 kg: 200 mg qw; 15 to <40 kg: 200 mg q2w) was simulated to predict pharmacokinetics for this regimen.

Results: Patients weighing 30 to <50 kg had lower observed belimumab concentrations than those weighing ≥50 kg (week 12 geometric mean 82.8 vs 134 μg/mL), but popPK analyses predicted the three weight bands to be generally consistent and in alignment with established adult subcutaneous and pediatric intravenous exposures. The pharmacodynamic and safety profile was consistent with known belimumab effects. By week 52, 18 of 22 patients (81.8%) had a ≥4-point reduction from baseline SELENA-SLEDAI scores. Hypothetical two-weight-band dosing simulations predicted consistent exposure across weight bands and in line with established exposures in SLE.

Conclusion: Exposure following subcutaneous belimumab administration in pediatric patients is consistent with approved usage; these findings, along with consistent safety and efficacy data, support subcutaneous belimumab use for pediatric patients with SLE.

Objective: This study assessed sarilumab in treating patients with polyarticular-course juvenile idiopathic arthritis (pcJIA).

Methods: This phase 2b, open-label study (NCT02776735) consisted of three sequential parts (each with a core-treatment and extension-phase). During part 1, three doses were assessed in two weight groups (Group A/B: ≥30-60 kg/≥10-<30 kg) to select the optimal dose with regards to pharmacokinetics, safety and efficacy to evaluate in latter parts. During the extension-phase of part 1, patients initially assigned to the selected optimal dose continued on this dose; the remaining patients were switched to this selected dose. Patients in parts 2 and 3 received the selected dose from baseline. The primary endpoint was pharmacokinetic exposure (AUC_{0- Շ}, C_max, C_trough). Safety and efficacy were assessed.

Results: Mean age of treated patients (n=101; 76.2% female) was 9.4 years. Of the evaluated doses in part 1, dose 2 (Group A/B: 3.0/4.0 mg/kg every 2 weeks [q2w]) was selected. In patients receiving selected dose from baseline (n=73), C_max, AUC_0-14days and C_trough at steady-state in Group A/B were 27.1/40.4 mg/L, 276/395 day*mg/L, and 9.57/14.4 mg/L respectively. At Week 48, JIA-ACR 30/50/70/90 rates were 100%/100%/93.8%/76.6%. Adverse events were reported in 70/73 (95.9%) patients. Twenty-seven (37%) patients experienced grade 3/4 neutropenia; with no associated infections. No death occurred.

Conclusion: In pcJIA patients receiving the selected dose from baseline, pharmacokinetic exposure was comparable to a dose of 200mg q2w for adults with rheumatoid arthritis. Clinically relevant improvements were observed in disease activity, with safety being consistent with the known profile of sarilumab.

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.