Modern Rheumatology最新文献

Objective: To develop and validate algorithms for identifying patients with systemic lupus erythematosus (SLE) in Japanese administrative claims databases from tertiary care centers using statistical and machine learning methods.

Methods: This retrospective cross-sectional study included 13 538 patients from six hospitals. One-year claims data were linked to chart-confirmed SLE diagnoses. Patients were randomly assigned to training (n = 8 811) and test (n = 3 775) sets; an external validation set (n = 952) was drawn from another hospital. Feature selection used Least Absolute Shrinkage and Selection Operator (LASSO), Boruta, and Recursive Feature Elimination. Logistic regression, random forest, and decision tree models were trained with synthetic oversampling to address class imbalance. Model performance was evaluated using the Area Under the Receiver Operating Characteristic Curve (AUROC), and other standard performance metrics.

Results: The random forest model achieved the best performance (AUROC: 0.995; sensitivity: 0.971; specificity: 0.969). A simplified rule based on diagnosis code and anti-double-stranded DNA antibody testing showed high accuracy in both test and validation sets. Adding urine sediment examination modestly improved sensitivity but reduced specificity.

Conclusion: A claims-based algorithm incorporating diagnosis codes and standard laboratory tests accurately identified patients with SLE facilitating reliable use of administrative data in real-world research.

Objectives: This multicenter cohort study aimed to describe the clinical and demographic features of pediatric patients diagnosed with Chronic Non-Bacterial Osteomyelitis (CNO) in Turkey and to identify patient clusters based on bone involvement.

Methods: A total of 334 pediatric CNO patients from 21 pediatric rheumatology centers were included. Data on clinical presentation, imaging, and biopsy results were collected. A two-step cluster analysis was performed to classify patients by bone-site involvement, resulting in four distinct clusters.

Results: Axial-thoracic cluster, involving the vertebra, clavicle, and sternum, was more common in female patients and showed higher rates of skin involvement. Lower-extremity cluster, characterized by lower extremity bone involvement, included the largest number of patients. Unlike previous reports, the Turkish cohort had a higher proportion of male patients and a lower frequency of skin involvement. At a median follow-up of 42.4 months, 77.3% of patients achieved remission, while 22% experienced relapse. Mandibular involvement, additional rheumatologic diseases, and localized bone pain were associated with increased relapse risk.

Conclusions: This study highlights the clinical profile of pediatric CNO in Turkey, marked by male predominance and low skin involvement. The identified bone-site clusters may help guide prognosis and should be validated in other populations.

Objectives: To evaluate the clinical performance of three commercially available anti-dsDNA antibody immunoassays in Japan.

Methods: We compared the reactivity and diagnostic accuracy of three commercially available anti-dsDNA antibody immunoassays (radioimmunoassay [RIA], chemiluminescence enzyme immunoassay [CLEIA], and fluorescence enzyme immunoassay [FEIA]). We evaluated how well the three anti-dsDNA antibody immunoassays reflected disease activity and individual organ involvement in systemic lupus erythematosus (SLE).

Results: Three anti-dsDNA antibody immunoassays demonstrated moderate to substantial correlation and concordance, while some patients exhibited different reactivity because of assay principles and detection systems. The diagnostic accuracies of the three immunoassays were comparable based on the receiver operating characteristic analyses and optimal cutoff values. Among the three anti-dsDNA antibody immunoassays, a fully automated CLEIA-specific detection system demonstrated high sensitivity that reflects disease activity. The combined results of the titers and positivity rates of the three anti-dsDNA antibody immunoassays showed that nephritis was significantly associated with CLEIA and arthritis with RIA, and weak or no associations with other organ involvement were observed.

Conclusions: We confirmed that the clinical performances of the three dsDNA immunoassays are comparable. Our findings suggest that selecting an optimal anti-dsDNA immunoassay will be useful for clinical decision-making in SLE.

Objective: To clarify the diagnostic utility of serum calprotectin and gene expression in interferon (IFN)-α-activated neutrophils in macrophage activation syndrome (MAS) in patients with systemic lupus erythematosus (SLE).

Methods: This single-centre, cross-sectional study analysed serum calprotectin levels in 47 patients with SLE (including eight with MAS) and seven patients with adult-onset Still's disease (AOSD) complicated with MAS as a reference population. In neutrophil-based experiments, mRNA expression levels of S100A8 and S100A9 were measured following stimulation with IFN-α or interleukin (IL)-1β.

Results: Serum calprotectin levels were significantly elevated in patients with SLE-MAS compared to those with SLE without MAS and comparable to those in patients with AOSD-MAS. Calprotectin levels correlated with serum ferritin levels (rs = 0.49, p = 0.004), but not with anti-dsDNA antibodies, or complement levels. At a cut-off value of 9184.4 ng/mL, serum calprotectin demonstrated sensitivity of 62.5% and specificity of 94.9% for identifying MAS. Recombinant IFN-α2a induced a dose-dependent increase in S100A8 and S100A9 expression in neutrophils, whereas recombinant IL-1β had no effect. Pre-treatment with an anti-IFN-α2 neutralizing antibody effectively suppressed the IFN-α2a-induced expression of S100A8 and S100A9.

Conclusion: Serum calprotectin, upregulated by IFN-α, may serve as a useful biomarker for diagnosing MAS in SLE.

Objective: Evaluation of bone erosion is important in assessing the progression in rheumatoid arthritis (RA). It is known that cortical bone defects also exist in healthy individuals. We examined erosions occurring in the metacarpophalangeal (MCP) and wrist joints of healthy subjects using high-resolution peripheral quantitative computed tomography (HR-pQCT).

Methods: Twenty healthy female subjects were included. The second and third MCP and wrist joints were scanned using HR-pQCT. The number, volume, and anatomical distribution of erosions were measured, and the correlation between erosions number and age was analyzed.

Results: An average of 4.0 erosions were found in the MCP joints, 30.8 in the carpal bones, and 7.9 in the distal radius and ulna. Most erosions (69.3%) were smaller than 0.5 mm3. Larger erosions (>0.5 mm3) were mainly seen in the carpal bones, with an average of 12.1 in total, especially the capitate and lunate (3.9 and 2.2, respectively). The number of carpal erosions correlated with age, especially for erosions smaller than 0.5 mm3 (R = 0.48).

Conclusions: Numerous bone erosions were identified in the MCP and wrist joints of healthy individuals. Relatively well-defined erosions measuring ≥0.5 mm3 were frequently observed in specific carpal bones, particularly the capitate and lunate. Additionally, erosions smaller than 0.5 mm3 showed a positive correlation with age, suggesting that numerous small cortical bone defects may represent age-related physiological changes. These findings provide important context when interpreting erosive changes associated with joint diseases in clinical practice.

Background: This study evaluated the efficacy, safety, and drug retention of anakinra and canakinumab in pediatric patients with colchicine-resistant familial Mediterranean fever (cr-FMF) within a real-world cohort.

Methods: This retrospective cohort study was conducted from June 2016 to April 2024, including 86 patients diagnosed with cr-FMF. Clinical and laboratory parameters, including attack frequency, C-reactive protein (CRP), serum amyloid A (SAA), and autoinflammatory disease activity index (AIDAI) scores, were recorded at baseline and during follow-up.

Results: A total of 86 patients (50 females, 36 males) were included in the study. All carried exon 10 MEFV mutations, with 69 patients (80.2%) having the M694V/M694V genotype. Anakinra was initiated in36 patients (41.9%), and canakinumab in 50 patients (58.1%). The median treatment duration was significantly longer for canakinumab (48 months) compared to anakinra (7 months) (p<0.001). Both treatments significantly reduced attack frequency, AIDAI scores, CRP, and SAA levels compared to baseline (p<0.001). While the reduction in attack frequency was comparable between the groups, patients treated with canakinumab achieved significantly lower mean AIDAI scores at 12 months compared to the anakinra group (p = 0.021). Anakinra provided a more rapid onset of symptom control but was commonly discontinued due to injection site reactions (44.4%). Canakinumab was associated with sustained long-term disease control with fewer local side effects. However, rare serious events, including acute myeloid leukemia and inflammatory bowel disease, were observed, though causality with treatment could not be established.

Conclusion: In this pediatric cohort of cr-FMF patients, both anakinra and canakinumab were effective in reducing disease activity and inflammation. Anakinra offered rapid symptom relief but had frequent injection site reactions. Canakinumab provided sustained control with fewer local side effects but required monitoring for rare complications.

Objectives: To clarify the clinical characteristics of patients with ocular involvement in giant cell arteritis (GCA).

Methods: This was an observational, single-centre, retrospective study of patients with GCA treated at Juntendo University Hospital between January 2012 and July 2023. The study involved 71 patients, including 21 with ocular involvement: 10 had fundus findings such as anterior ischemic optic neuropathy or central retinal artery occlusion (6 with permanent vision loss), and 11 without fundus findings. The demographic and clinical features of GCA were compared between patients with and without ocular involvement.

Results: The temporal artery was found to be affected more frequently in cases with ocular involvement than in those without on positron emission tomography/computed tomography (P=0.013) and vascular ultrasound (P=0.02). The average number of signs and symptoms observed before diagnosis was higher in patients with ocular involvement than in those without (P<0.001). The period from the appearance of ocular involvement to therapy initiation was shorter in patients with fundus findings than in those without (8.2 vs. 73.8 days; P=0.032).

Conclusions: Early imaging and early consultation with an ophthalmologist are important, as ocular involvement with fundus findings tended to occur earlier in GCA patients than without fundus findings.

Objectives: To evaluate the induction of antidrug antibodies (ADA) and the expression of neutralising antibodies (NAb) during ozoralizumab treatment, a trivalent anti-TNFα NANOBODY® compound for rheumatoid arthritis, and their impact on safety and efficacy.

Methods: Data from a phase II/III trial of ozoralizumab co-administered with methotrexate (OHZORA) and a phase III trial without methotrexate (NATSUZORA) were analysed. Participants were stratified by ADA and NAb status. Safety and efficacy outcomes were compared across subgroups.

Results: ADA induction was observed in 29.2% (OHZORA) and 44.3% (NATSUZORA) of participants; NAb expression was observed in 7.5% and 19.3%, respectively. ADA induction was not associated with treatment continuation or safety. In NATSUZORA, reduced efficacy was observed in the NAb-positive participants, although approximately half of those participants maintained low disease activity through Week 52. In OHZORA, NAb expression showed no significant impact on efficacy. Several NAb-positive participants in either trial showed sustained disease control in the long-term extension (HOSHIZORA).

Conclusions: ADA induction had no apparent impact on safety. The effect of NAb expression on efficacy was limited particularly in OHZORA, suggesting that methotrexate co-administration may reduce NAb development and contribute to the optimal preservation of efficacy and safety in clinical practice.

Objectives: Rituximab (RTX) is a standard maintenance therapy for ANCA-associated vasculitis. Its efficacy in Japan remains unclear, where microscopic polyangiitis (MPA) predominates and clinical characteristics differ from Western-dominated RCT populations.

Methods: Japanese patients with MPA or granulomatosis with polyangiitis (GPA) enrolled in a nationwide registry were included. Exposure was RTX use during maintenance therapy. The primary endpoint was major relapse-free survival at 104 weeks. The secondary endpoint was any relapse-free survival (major or minor) at 104 weeks. Baseline differences were adjusted using inverse probability of treatment weighting (IPTW) based on key demographic and disease-related covariates.

Results: A total of 389 patients were analyzed, with 85 in the RTX group. The RTX group included a higher proportion of GPA cases (37/85 vs. 74/304), resulting in baseline imbalance. After IPTW, no major relapses were observed in the RTX group, whereas the major relapse-free survival at 104 weeks was 94.8% in the non-RTX group. The RTX group showed significantly higher any relapse-free survival at 104 weeks (95.4% vs. 83.3%; HR for any relapse, 0.27; 95% CI, 0.09-0.74; p = 0.02).

Conclusions: Our findings suggest that RTX may be an effective option for remission maintenance in Japanese patients with MPA or GPA.

Objective: To evaluate the long-term safety and exploratory efficacy of filgotinib, a JAK1-preferential inhibitor, in patients with idiopathic multicentric Castleman disease (iMCD) over 52 weeks in a small, single-arm extension study.

Methods: This Phase Ib single-arm extension study enrolled five patients with iMCD who completed an initial 8 weeks' treatment with filgotinib. Patients received filgotinib 200 mg once daily for an additional 44 weeks (total 52 weeks). The primary endpoints assessed the comprehensive safety parameters. The secondary endpoints were efficacy.

Results: All five patients completed the full 52-week treatment period without permanent discontinuation. No serious adverse events or deaths were observed. All adverse events were mild-to-moderate (Grade 1-2), with upper respiratory infections in 4 patients and headache in 3 of 5 patients. Herpes zoster occurred in one patient. At week 52, three of five patients had ≥1-point CHAP score reduction (one additional patient compared with week 8). Median changes from baseline included: CRP -1.85 mg/dL, hemoglobin +0.50 g/dL, albumin +0.30 g/dL, and ECOG-PS 0 points.

Conclusion: Filgotinib was well-tolerated over 52 weeks with no serious adverse events reported. Numerical changes in disease activity markers were observed over time, providing preliminary support for the therapeutic concept of JAK inhibition in iMCD.