MATERIALS AND METHODS: A Markov model was used to evaluate the economic and treatment outcomes of warfarin care bundles and NOACs compared with usual warfarin care. Cost-effectiveness was assessed from a societal perspective over a lifetime horizon with 3% discount rate in a hypothetical cohort of 65-year-old atrial fibrillation patients. Input parameters were derived from published literature, meta-analysis and local data when available. The outcome measure was incremental cost per quality-adjusted life years (QALY) gained (ICER).
RESULTS: Using USD5104 as the threshold of willingness-to-pay per QALY, patient's self-management of warfarin was cost-effective when compared to usual warfarin care, with an ICER of USD1395/QALY from societal perspective. All NOACs were not cost-effective in Thailand, with ICER ranging from USD8678 to USD14,247/QALY. When compared to the next most effective intervention, patient's self-testing and genotype-guided warfarin dosing were dominated. In the cost-effectiveness acceptability curve, patient's self-management had the highest probability of being cost-effective in Thailand, approximately 78%. Results were robust over a range of inputs in sensitivity analyses.
CONCLUSIONS: In Thailand, NOACs were unlikely to be cost-effective at current prices. Conversely, patient's self-management is a highly cost-effective intervention and may be considered for adoption in developing regions with resource-limited healthcare systems.
METHODS: In two phase 3 trials, we assessed iptacopan monotherapy over a 24-week period in patients with hemoglobin levels of less than 10 g per deciliter. In the first, anti-C5-treated patients were randomly assigned to switch to iptacopan or to continue anti-C5 therapy. In the second, single-group trial, patients who had not received complement inhibitors and who had lactate dehydrogenase (LDH) levels more than 1.5 times the upper limit of the normal range received iptacopan. The two primary end points in the first trial were an increase in the hemoglobin level of at least 2 g per deciliter from baseline and a hemoglobin level of at least 12 g per deciliter, each without red-cell transfusion; the primary end point for the second trial was an increase in hemoglobin level of at least 2 g per deciliter from baseline without red-cell transfusion.
RESULTS: In the first trial, 51 of the 60 patients who received iptacopan had an increase in the hemoglobin level of at least 2 g per deciliter from baseline, and 42 had a hemoglobin level of at least 12 g per deciliter, each without transfusion; none of the 35 anti-C5-treated patients attained the end-point levels. In the second trial, 31 of 33 patients had an increase in the hemoglobin level of at least 2 g per deciliter from baseline without red-cell transfusion. In the first trial, 59 of the 62 patients who received iptacopan and 14 of the 35 anti-C5-treated patients did not require or receive transfusion; in the second trial, no patients required or received transfusion. Treatment with iptacopan increased hemoglobin levels, reduced fatigue, reduced reticulocyte and bilirubin levels, and resulted in mean LDH levels that were less than 1.5 times the upper limit of the normal range. Headache was the most frequent adverse event with iptacopan.
CONCLUSIONS: Iptacopan treatment improved hematologic and clinical outcomes in anti-C5-treated patients with persistent anemia - in whom iptacopan showed superiority to anti-C5 therapy - and in patients who had not received complement inhibitors. (Funded by Novartis; APPLY-PNH ClinicalTrials.gov number, NCT04558918; APPOINT-PNH ClinicalTrials.gov number, NCT04820530.).