Arthritis & Rheumatology最新文献

Objective: Rheumatologic disease-associated hemophagocytic lymphohistiocytosis (HLH), a rare, life-threatening, systemic hyperinflammatory syndrome, occurs as a complication of underlying rheumatologic disease. Real-world evidence is lacking on emapalumab, a fully human monoclonal antibody that neutralizes the proinflammatory cytokine interferon-gamma, approved for treating patients with primary HLH.

Methods: REAL-HLH, a retrospective medical chart review study conducted across 33 US hospitals, assessed real-world treatment patterns and outcomes in patients with HLH treated with ≥1 dose of emapalumab between November 20, 2018, and October 31, 2021. Data are presented for the subset of patients with rheumatologic disease-associated HLH.

Results: Fifteen of 105 patients (14.3%) had rheumatologic disease-associated HLH. Of these, 9 (60.0%) had systemic juvenile idiopathic arthritis, and 1 (6.7%) had adult-onset Still's disease. Median (range) age at HLH diagnosis was 5 (0.9-39) years. Most (9/15; 60.0%) patients initiated emapalumab in an intensive care unit. Emapalumab was most frequently initiated for treating refractory or recurrent (10/15; 66.7%) disease. Most patients received HLH-related therapies prior to (10/15; 66.7%) and concurrently (15/15; 100.0%) with emapalumab. Emapalumab-containing regimens stabilized or achieved physician-determined normalization of most laboratory parameters including fibrinogen (11/13; 84.6%), chemokine ligand 9 (7/8; 87.5%), and absolute neutrophil count (6/10; 60%), and reduced glucocorticoid dose by 80%. Overall survival and 12-month survival probability from emapalumab initiation were 86.7%.

Conclusion: Emapalumab-containing regimens stabilized or normalized most key laboratory parameters, reduced glucocorticoid dose, and were associated with low disease-related mortality, thereby demonstrating potential benefits in patients with rheumatologic disease-associated HLH.

Objective: In individuals without radiographic knee osteoarthritis (OA), we investigated whether magnetic resonance imaging (MRI)-defined knee OA at baseline was associated with incident radiographic and symptomatic disease during up to 11 years of follow-up.

Methods: Osteoarthritis Initiative participants without tibiofemoral radiographic knee OA at baseline were assessed for MRI-based tibiofemoral cartilage damage, osteophyte presence, bone marrow lesions, and meniscal damage/extrusion. We defined MRI knee OA using alternative, reported definitions (Def A and Def B). Kellgren-Lawrence (KL) grade, joint space narrowing (JSN), and frequent knee symptoms (Sx) were assessed at baseline, 1-, 2-, 3-, 4-, 6-, 8-, and 10/11-year follow-up visits. Incident tibiofemoral radiographic knee OA (outcome) was defined as (1) KL ≥2, (2) KL ≥2 and JSN, or (3) KL ≥2 and Sx. Adjusted Cox proportional hazards regression models examined associations of baseline MRI-defined knee OA (Def A and Def B) with incident outcomes during up to 11 years of follow-up.

Results: Among 1,621 participants (mean age ± SD 58.8 ± 9.0 years, mean body mass index ± SD 27.2 ± 4.5 kg/m², 59.5% women), 17% had MRI-defined knee OA by Def A and 24% by Def B. Baseline MRI-defined knee OA was associated with incident KL ≥2 (odds ratio 2.94 [95% confidence interval (95% CI) 2.34-3.68] for Def A and 2.44 [95% CI 1.97-3.03] for Def B). However, a substantial proportion of individuals with baseline MRI-defined knee OA did not develop incident KL ≥2 during follow-up (59% for Def A and 64% for Def B). Findings were similar for the other two outcomes.

Conclusion: Current MRI definitions of knee OA do not adequately identify knees that will develop radiographic and symptomatic disease.

Objective: Epitope spreading (ES), involving autoantibodies, plays a crucial role in the development and persistence of autoimmune reactions in various autoimmune diseases. This study aimed to investigate the relationship between ES of anti-RNA polymerase III (RNAP III) antibodies (ARAs) and the clinical manifestations of systemic sclerosis (SSc).

Methods: We investigated whether intermolecular ES occurs in the subunits of the RNAP III complex and whether intramolecular ES targets the major antigen, RNA polymerase III subunit A (RPC1), in patients with SSc. To achieve this, we synthesized 17 full-length subunit proteins of the RNAP III complex and 5 truncated forms of RPC1 in vitro using a wheat germ cell-free translation system. Subsequently, we prepared antigen-binding plates and measured autoantibodies in the serum of patients with SSc.

Results: Autoantibodies against different RNAP III complex subunits were found in patients who were ARA-positive with SSc. The intermolecular ES indicators significantly correlated with the modified Rodnan skin thickness score (mRSS) and surfactant protein-D, a biomarker of interstitial lung disease. However, the extent of disease on high-resolution computed tomography or pulmonary function tests did not show any significant correlation. Intramolecular ES indicator against RPC1 were significantly correlated with mRSS and renal crisis. Furthermore, longitudinal assessment of ES in RNAP III complex subunits correlated with mRSS and exhibited potential as a disease activity biomarker.

Conclusion: Our findings indicate a correlation between ES levels and the severity of skin sclerosis or the risk of other complications in SSc. This study suggests that measuring ES in SSc serves as a novel biomarker for disease activity.