Relationships between Type 1 interferon signatures and clinical features of the new-onset lupus patients in Japan.

OBJECTIVES: The objective of the study is to investigate the relationships between Type 1 interferon (T1-IFN) signatures and clinical characteristics of lupus patients. METHODS: We examined 49 new-onset lupus patients who were diagnosed between 1999 and 2017. The patients treated with >10 mg of prednisolone or hydroxychloroquine were excluded from this study. Serum T1-IFN signatures were revealed by a functional reporter assay and standardized by recombinant IFN-α. Patient backgrounds, clinical findings, and treatments were retrospectively extracted from their electrical medical records. Clinical data were also available, including SLE Disease Activity Index of SLE patients on admission. RESULTS: T1-IFN signatures of lupus patients closely correlated with lupus disease activities, such as SLE Disease Activity Index-2K, white blood cell, C3 levels, and the titre of double-strand DNA antibody. We found fever and acute lupus dermatitis closely associated with T1-IFN signature. CONCLUSIONS: In lupus patients, fever and acute lupus dermatitis are good indicators of a strong T1-IFN signature.

Cluster analysis defines four groups of Japanese patients with adult-onset Still's disease.

OBJECTIVES: To define groups and characterize differences in the prognosis of patients with adult-onset Still's disease (AOSD). METHODS: We performed a retrospective cohort study. Patients with AOSD were grouped using hierarchical unsupervised cluster analysis according to age, sex, clinical features, and laboratory data. The primary endpoints were overall survival and drug-free remission rate. RESULTS: A total of 153 patients with AOSD were placed into four clusters. Those in Cluster 1 had a young onset, tended to be female, and had fewer complications and moderate ferritin concentrations. Those in Cluster 2 had a young onset and had more complications and higher ferritin concentrations. Those in Cluster 3 had a young onset, tended to be male, and had no lymphadenopathy and fewer complications. Those in Cluster 4 had an older onset, tended to be female, and had more complications and higher ferritin concentrations. Overall survival tended to be lower (P = .0539) in Cluster 4, and drug-free remission was higher in Clusters 1, 2, and 3 [hazard ratios (HRs) 2.19, 3.37, and 3.62 vs. Cluster 4, respectively]. CONCLUSIONS: Four groups of AOSD that have distinct clinical manifestations, ferritin concentrations, severity, and drug-free remission rate were identified, which were lowest in Cluster 4. Graphical Abstract.

Rituximab maintenance therapy for patients with antineutrophil cytoplasmic antibody-associated vasculitis in Japan.

OBJECTIVES: We examined the efficacy and safety of rituximab (RTX) maintenance therapy for patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in Japan. METHODS: We conducted a retrospective study using a multi-center cohort database of vasculitis patients. All maintenance treatment courses were divided into three groups: a RTX group, a group treated with other immunosuppressant drugs (IS) and a group receiving glucocorticoid monotherapy (GC). The primary endpoint was the comparison of relapse-free survival after 1 year. We also analyzed the occurrence of severe adverse events (SAEs) to assess safety. RESULTS: We included 123 courses of 107 patients (RTX n = 14, IS n = 64, GC n = 45). Twelve of 14 in the RTX group patients were diagnosed with granulomatosis with polyangiitis (GPA). The relapse-free survival of RTX maintenance therapy was comparable to that in the other groups (p = .122). After 1 year of treatment, the RTX group was administered lower steroid doses and one-third of them could withdraw corticosteroid. The overall incidence of SAE was 0.54/patient-year in the RTX group, 0.39/patient-year in the IS group and 0.34/patient-year in the GC group. CONCLUSION: RTX maintenance therapy could be effective and safe in Japanese GPA patients.

Still's Disease Onset in Older Adults: Clinical Features, Diagnosis, and Management.

Still's disease (SD) is a rare systemic inflammatory disease that is characterized by high fever, polyarthritis, and an evanescent rash as its main symptoms but that may also be complicated by pleuritis and macrophage activation syndrome (MAS). There has been a recent increase in studies on older-onset SD, which presents with less-typical clinical features, such as sore throat, skin lesions, and splenomegaly, but more complications including pleuritis and disseminated intravascular coagulation. Several reports have shown higher levels of inflammatory markers, including serum ferritin, and poorer outcomes in terms of survival and drug-free remission in older patients. In addition, caution is needed when diagnosing SD in older patients because of the increased incidence of differential diagnoses such as infectious diseases, malignancies, and inflammatory diseases. Prognosis is poor in older patients, and treatment-associated infections and severe complications such as MAS are the main cause of mortality. The use of biologics and treatment response may not differ greatly between older and younger patients. Although the data are limited, anti-IL-1 and anti-IL-6 agents may control SD in these patients with careful use and adequate infection prevention. Recent studies that classified adult-onset SD by cluster analysis or latent class analysis showed that older patients form a unique cluster of SD, indicating the need for clinicians to pay more attention to the diagnosis and management of SD in older patients.