ABSTRACT
Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 is a global pandemic and poses a major threat to human health worldwide. In addition to respiratory symptoms, COVID-19 is usually accompanied by systemic inflammation and liver damage in moderate and severe cases. Nuclear factor erythroid 2-related factor 2 (NRF2) is a transcription factor that regulates the expression of antioxidant proteins, participating in COVID-19-mediated inflammation and liver injury. Here, we show the novel reciprocal regulation between NRF2 and inflammatory mediators associated with COVID-19-related liver injury. Additionally, we describe some mechanisms and treatment strategies.
Subject(s)
COVID-19 , Inflammation Mediators , Liver Diseases/virology , NF-E2-Related Factor 2 , COVID-19/pathology , Humans , Inflammation Mediators/metabolism , Liver/metabolism , Liver/pathology , NF-E2-Related Factor 2/metabolism , Oxidative Stress , SARS-CoV-2 , Signal TransductionABSTRACT
BACKGROUND: Pembrolizumab (Pembro) in combination with chemotherapy has been approved for the treatment of pretreated advanced NSCLC in the United States and China for its significant efficacy. However, the cost-effectiveness is unknown considering Pembro's high price. The impact of programmed death ligand 1 (PD-L1) test on the cost-effectiveness is also unknown. The current study assessed the cost-effectiveness of combination therapy for nonsquamous NSCLC from the United States and China public payers' perspective. MATERIALS AND METHODS: A literature-based Markov model was conducted using KEYNOTE-189 trial data to compare cost and quality-adjusted life years (QALYs) of three treatment strategies for nonsquamous NSCLC: Pembro-chemotherapy combination and chemotherapy strategy without PD-L1 test, and treatment strategy according to their PD-L1 status. RESULTS: In base case analysis, the combination strategy generated an additional 0.78 QALYs and 0.59 QALYs over chemotherapy in the United States and China respectively, resulting in an ICER of $132 392/QALY in the United States and $92 533/QALY in China. In the PD-L1 ≥1% base case, the ICERs were $77 754/QALY and $56 768/QALY respectively in the United States and China for PD-L1 test strategy. In the PD-L1 ≥50% base case, the ICERs were $44 731/QALY and $34 388/QALY respectively in the United States and China for PD-L1 test strategy. Lowering Pembro price can also partly decrease the ICERs. CONCLUSION: Compared with chemotherapy, the combination strategy is not cost-effective for the treatment of NSCLC in the American and Chinese health care system at WTP threshold of $100 000/QALY for the United States and $27 351/QALY for China. Using PD-L1 test for patient selection and price reduction could improve the cost-effective probabilities of immunotherapy for nonsquamous NSCLC.
