Prescribing Patterns and Impact of Factors Associated with Time to Initial Biologic Therapy among Children with Non-systemic Juvenile Idiopathic Arthritis.

OBJECTIVE: The aim of this study was to examine patterns of initial prescriptions, investigate time to initiation of biologic disease-modifying anti-rheumatic drugs (bDMARDs), and evaluate the impact of clinical and other baseline factors associated with the time to first bDMARD in treating children with newly diagnosed non-systemic juvenile idiopathic arthritis (JIA). METHODS: Using longitudinal patient-level data extracted from electronic medical records (EMR) in a large Midwestern pediatric hospital from 2009 to 2018, the initial prescriptions and prescribing patterns of bDMARDs, conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), non-steroidal anti-inflammatory drugs (NSAIDs) and glucocorticoids within 3 months of JIA diagnosis were examined. Kaplan-Meier analyses were performed to assess time to initiation of bDMARDs. Cox proportional hazard models were used to identify factors associated with time to first bDMARD. RESULTS: Of 821 children, the proportion of patients with initial csDMARDs increased from 45.3% in 2009 to 60.3% in 2018. Around 57.5% of polyarthritis rheumatoid factor-positive (Poly RF+) patients and 43.2% of polyarthritis rheumatoid factor-negative (Poly RF-) patients received a bDMARD therapy within 3 months of diagnosis, 14.4% as monotherapy and 28.3% in combination with a csDMARD. Among patients who received combination therapy, combination of methotrexate with adalimumab increased from 16.7% in 2009 to 40% in 2018. The proportion of patients treated with adalimumab gradually increased and passed etanercept in 2016. The predictors of earlier initiation of biologic therapy were JIA category enthesitis-related arthritis (ERA) [hazard ratio (HR) vs persistent oligoarthritis 4.82; p < 0.0001], psoriatic arthritis (PsA) (HR 2.46; p = 0.0002), or Poly RF- (HR 2.43; p = 0.0002); the number of joints with limited range of motion (HR 1.02; p = 0.0222), and erythrocyte sedimentation rate (ESR, HR 1.01; p = 0.0033). CONCLUSIONS: There was a substantial increase in the proportion of patients receiving the combination of methotrexate and adalimumab among patients receiving combination therapy. Adalimumab overtook etanercept as the most frequently prescribed bDMARD. Multiple factors affect the time to biologic initiation, including the number of joints with limited range of motion, ESR, and JIA category.

Akebia trifoliata pericarp extract ameliorates inflammation through NF-κB/MAPK signaling pathways and modifies gut microbiota.

Akebia trifoliata fruits, a kind of popular edible berry in Asia, are widely consumed as daily fruits or functional foods. Our previous study found several bioactives from Akebia trifoliata pericarp extract (APE), and preliminarily investigated their anti-inflammatory activity. However, the underlying mechanism of APE for the observed anti-inflammatory effects is still unknown. Thus, the bioactive profiles and anti-inflammatory mechanism of APE were investigated by a combination of chemical assays: UPLC-LTQ-Orbitrap/MS technique, lipopolysaccharide (LPS)-induced RAW264.7 cells and DSS-induced mouse model. The results indicated that the phenolic acids and terpenoids are major bioactives of APE, which could inhibit the production of nitric oxide (NO) and prostaglandin E2 (PGE2) by blocking the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in RAW264.7 cells as well as reduce the expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1ß (IL-1ß), and suppress the phosphorylation of p-65, IκBα and mitogen-activated protein kinase (MAPKs including p38, ERKs, JNKs) proteins both in vitro and in vivo. Furthermore, APE treatment could regulate gut microbiota by increasing the richness of Rikenellaceae and Lactobacillaceae and reducing that of Lachnospiraceae and Ruminococcaceae. In summary, these findings clearly demonstrated that APE mitigates inflammation by restraining the production of cytokines through nuclear factor-κB (NF-κB) and MAPK signaling pathways, and altering gut microbiota, and therefore, this could be a potential functional food for the treatment and prevention of inflammatory bowel diseases.

Prevention of acute GVHD in mice by treatment with Tripterygium hypoglaucum Hutch combined with cyclosporin A.

OBJECTIVE: To elucidate the protective roles and the underlying mechanism of Tripterygium hypoglaucum Hutch (THH) in mice graft-versus-host disease (GVHD). METHODS: BALB/c (H-2k(d)) mice were firstly treated with total body irradiation and infused with a mixture of bone marrow and spleen cells from C57BL/6. Then the severity of acute GVHD (aGVHD), chimeras of donor cells, inflammatory cytokines (IFN-γ, IL-4, and IL-10) of plasma, and regulatory T cells were evaluated to elucidate the different drug combinations and concentrations of cyclosporin A (CsA) and THH in preventing aGVHD. RESULTS: The control group treated with phosphate buffer solution displayed more obvious ruffled hair, hunched posture, diarrhea, reduced weight and more lymphocytes infiltration into the spleen and intestine than these treated with CsA, THH or low-dosed CsA combined with THH, especially those treated with low-dosed CsA combined with THH. No significant differences were observed in the chimeras of donor cells and survival rate among the CsA, THH, or CsA combined with THH-treated groups. Further studies implied that THH might reduce the aGVHD by increasing IL-10, decreasing IL-4, activating Treg cell, and maintaining a relatively high Foxp3 mRNA level. CONCLUSION: THH decreased the occurrence of mouse aGVHD and prolonged the survival time by increasing the levels of CD(4)(+)/CD(25)(+) T cells, regulating the cytokine secretion and promoting the expression of Foxp3.