A novel etanercept biosimilar Anbainuo plus methotrexate exhibits increased cost-effectiveness compared to conventional disease-modifying anti-rheumatic drugs in treating rheumatoid arthritis patients.

The aim of this study was to evaluate the cost-effectiveness of Anbainuo (ABN) plus methotrexate (MTX) (ABN + MTX) versus conventional disease-modifying anti-rheumatic drugs (cDMARDs) in rheumatoid arthritis (RA) patients.Forty-eight moderate to severe RA patients underwent ABN + MTX or cDMARDs treatment were consecutively enrolled and assigned to ABN + MTX group (n = 26) and control group (n = 22). Patients were followed up and their disease activity and quality of life (QoL) were evaluated at 3rd month, 6th month and 12th month after initiation of treatment. Treatment costs of 2 groups were calculated, then pharmacoeconomic analysis was performed.ABN + MTX increased drug cost and total cost while decreased indirect cost compared with cDMARDs after 12-month treatment. ABN + MTX group gained additional 0.22 quality-adjusted life years (QALY) and yielded an incremental cost-effectiveness ratio (ICER) of ¥104,293.6 per QALY after treatment. Sensitivity analysis reveals that rising ABN price by 20% produced an ICER of ¥130,403.6 per QALY, which was still lower than 3 times of the mean gross domestic product (GDP) per capita during the same period in China (¥165,960). Besides, ABN + MTX was more cost-effective in severe RA patients compared to moderate RA patients.ABN + MTX is cost-effective in treating moderate to severe RA patients compared with cDMARDs, although the total cost of ABN + MTX is relatively higher.

BF02, a recombinant TNFR2 fusion protein, alleviates adjuvant arthritis by regulating T lymphocytes in rats.

AIM: To investigate the therapeutic effects of BF02 on adjuvant arthritis (AA) in rats and the regulatory effects of BF02 on T lymphocyte function. METHODS: SD rats received a single intradermal injection of Freund's complete adjuvant emulsion into the right hind metatarsal footpad. After the onset of AA, the rats were injected BF02 (1, 3, or 9 mg/kg, sc) every 3 d for a total of 15 d. Intragastric administration of methotrexate (MTX, 0.5 mg/kg, every 3 d for a total of 15 d) was taken as the positive control drug. Arthritis index, swollen joint count, ankle joint histopathology, spleen histopathology and the paw radiography were used for evaluating the drug effects on AA rats. T lymphocyte function was assessed by measuring T lymphocyte cytokine levels, IL17 and TNF-α mRNA expression levels, and percentage of T lymphocyte subsets. RESULTS: In the AA rats, remarkable secondary inflammatory responses exhibited, accompanied by significantly higher levels of IL-1, IL-6, TNF-α, IL-17, LTα, RANKL, and MMP-13. The expression of IL17 and TNF-α mRNAs was also substantially higher than in normal rats. The percentages of CD3(+)CD4(+) and CD4(+)CD25(+) T lymphocytes were increased, whereas the percentages of CD4(+)CD62L(+) and CD4(+)CD25(+)FoxP3(+) T lymphocytes were decreased. Treatment of the AA rats with BF02 (9 mg/kg) or MTX significantly decreased the arthritis index, swollen joint count and arthritis global assessment. Moreover, both BF02 (9 mg/kg) and MTX significantly inhibited T lymphocyte proliferation, and blocked the above mentioned aberrance in T lymphocyte cytokine levels, IL17 and TNF-α mRNA expression, and percentages of T lymphocyte subsets. CONCLUSION: BF02 exerts therapeutic effects on AA rats via the regulation of T lymphocytes.

Treatment of neuroinflammation by soluble tumor necrosis factor receptor Type II fused to a thermally responsive carrier.

OBJECT: Biochemical irritation of the dorsal root ganglion (DRG) after intervertebral disc herniation contributes to radiculopathy through tumor necrosis factor-alpha (TNFalpha)-mediated inflammation. Soluble TNF receptor Type II (sTNFRII) sequesters this cytokine, providing clinical benefit. Previous work involving conjugation of sTNFRII with thermally responsive elastin-like polypeptide (ELP) yielded a chimeric protein (ELP-sTNFRII) with in vitro anti-TNFalpha bioactivity. Furthermore, temperature-triggered ELP aggregation into a "depot" prolongs protein residence time following perineural injection. In this study the authors evaluated the inflammatory phenotype of DRG explants after TNFalpha stimulation, and assessed the abilities of sTNFRII or ELP-sTNFRII to attenuate these neuro-inflammatory changes. METHODS: Rat lumbar DRGs (35 animals) were treated in 6 groups, as follows: control; TNFalpha (25 ng/ml); TNFalpha with low-(0.2 microg/ml) or high-dose (1 microg/ml) sTNFRII; and TNFalpha with low-(52.5 microg/ml) or high-dose (262.5 microg/ml) ELP-sTNFRII. After 24 hours, supernatant was evaluated for inflammatory cytokines (interleukin [IL]-1, IL-6, and IL-10); prostaglandin E2; and metabolites (glutamate, lactate, and pyruvate). Single-factor analysis of variance with post hoc Dunn analysis (alpha = 0.05) was used to assess treatment differences. RESULTS: Incubation of explants with TNFalpha caused metabolic stress reflected by an increased lactate/pyruvate ratio (1.8 +/- 0.5-fold) and extracellular glutamate (79 +/- 8% increase). Inflammatory activation was observed with heightened IL-6 release (5.2 +/- 1.4-fold) and prostaglandin E2 production (14 +/- 3-fold). An autoregulatory response occurred with an 11.8 +/- 0.6-fold increase in sTNFRI shedding. Treatment with high doses of sTNFRII or ELP-sTNFRII reversed all changes. Values are expressed as the mean +/- standard deviation. CONCLUSIONS: These results demonstrate that TNFalpha stimulation of DRG explants yields a phenotype of neurotoxic metabolite release and inflammatory mediator expression. Coincubation with either sTNFRII or ELP-sTNFRII antagonizes TNFalpha activity to abrogate these changes, suggesting potential for therapeutic intervention to treat peripheral nerve inflammatory disease.