Relation between hydroxychloroquine dose and continuation rate in patients with systemic lupus erythematosus.

OBJECTIVES: Hydroxychloroquine (HCQ) is recommended at a target dose of 5 mg/kg per actual body weight to reduce the risk of retinopathy in systemic lupus erythematosus (SLE). However, the efficacy of HCQ has been established at doses of 6.5 mg/kg per ideal body weight. This study aimed to clarify the effects of the HCQ dose on the continuation rate in Japanese patients, who generally have a lower body mass index than Western patients. METHODS: This retrospective single-centre observational study enrolled patients with SLE on HCQ therapy. Patients were divided into two groups with a dose per actual body weight [the low-dose (<5 mg/kg) group and the high-dose (≥5 mg/kg) group], and continuation rates were compared. The efficacy of 1-year HCQ therapy was assessed in patients without additional immunosuppressive agents and biologics. RESULTS: Of the 231 patients enrolled, 48 (20.8%) discontinued HCQ. The HCQ dose per actual body weight was identified as an independent risk factor for discontinuation. The low-dose group showed a significantly higher 1-year HCQ continuation rate than the high-dose group (83.2% vs. 72.8%, respectively). Both groups showed reductions in glucocorticoid requirement and serological activity after 1-year HCQ therapy. CONCLUSIONS: HCQ <5 mg/kg per actual body weight may facilitate greater continuation.

The muscle tissue transcriptome of idiopathic inflammatory myopathy reflects the muscle damage process by monocytes and presence of skin lesions.

OBJECTIVE: To investigate transcriptomic and immunophenotypic features of muscle specimens from patients with idiopathic inflammatory myopathy (IIM). METHODS: Bulk RNA-sequencing was performed on muscle biopsy samples from 16 patients with dermatomyositis (DM) and 9 patients with polymyositis (PM). Seven tested positive for anti-aminoacyl t-RNA synthetase antibodies in the DM patients (ARS-DM). We conducted weighted gene coexpression network analysis (WGCNA), differentially expressed gene (DEG) analysis, and gene set variation analysis (GSVA) to assess contributions of specific pathways. Cell proportions in muscle specimens were estimated using a deconvolution approach. RESULTS: WGCNA revealed significant positive correlations between serum creatine kinase (CK) levels and gene modules involved in cellular respiration, phagocytosis, and oxidative phosphorylation (OXPHOS). Significant positive correlations were also observed between CK levels and proportions of CD16-positive and -negative monocytes and myeloid dendritic cells. Notably, DM patients demonstrated enrichment of complement and interferon-α and -γ pathway genes compared to those with PM. Furthermore, ARS-DM demonstrated a higher proportion of Th1 cells and DEGs related to OXPHOS. Additionally, serum Krebs von den Lungen-6 levels correlated with gene modules associated with extracellular matrix and transforming growth factor-ß signaling pathway. CONCLUSION: Our study highlights a significant involvement of monocytes in muscle damage and delineates pathological differences among IIM subtypes. DM was characterized by complement, interferon-α and -γ signaling, whilst ARS-DM was associated with OXPHOS. Distinctive gene expression variations in muscle specimens suggest that different pathologic mechanisms underlie muscle damage in each IIM phenotype.