Montefiore Medical Center

Fast-acting subperception therapy in spinal cord stimulation (FAST-SCS) uses low-frequency, subthreshold stimulation to engage the dorsal column-mediated surround inhibition mechanism and thereby relieve pain. Our study was performed to better characterize the multidimensional long-term clinical outcomes of FAST-SCS therapy in patients with chronic low back and/or leg pain. Our prospective, multicenter, single-arm, open-label trial, conducted at 12 pain management centers across the USA, included male and female patients with chronic low back pain with/without leg pain refractory to conservative therapy. All eligible patients received an SCS implant. Outcomes evaluated included pain relief, disability, mobility, health-related quality of life, sleep quality, depression, pain catastrophizing, and global impression of change. Fifty-six patients received a permanent SCS implant and 55 were activated with FAST-SCS therapy. At 12months, 89% and 59% of patients achieved ≥ 50% and ≥ 80% pain relief, respectively (p < 0.0001), and pain intensity (verbal numerical rating scale) decreased by 4.9 ± 2.2 points (p < 0.0001). Significant improvements were observed in disability (Oswestry Disability Index - 24 ± 16 points, p < 0.0001) and endurance (6-Minute Walk Test + 73 ± 96m, p < 0.0001), while mobility and balance improved without reaching statistical significance (Timed Up-and-Go test - 7.5 ± 37.5s, p = 0.17). All psychosocial measures improved significantly at 12months compared to baseline, with an increase in the EQ5D-5L index (+ 0.200 ± 0.182, p < 0.0001) and decreases in the Pittsburgh Sleep Quality index (- 3.96 ± 4.31, p < 0.0001), Pain Catastrophizing Score (- 13.3 ± 11.4, p < 0.0001), and Beck Depression Index (- 7.9 ± 10.0, p < 0.0001). At 12months, 87% of patients reported being "much" or "very much" improved. Responses to FAST-SCS were at or above the minimal clinically important differences across all measured clinical dimensions. This prospective study demonstrated that FAST-SCS provided statistically significant, multidimensional benefits across pain, disability, mobility, and psychosocial outcomes over 12months in patients with chronic low back and/or leg pain. These findings support the use of FAST-SCS in this patient population. ClinicalTrials.gov (NCT04618471). https://www. gov/study/NCT04618471 .

Semaglutide, a glucagon-like peptide-1 receptor agonist, and resmetirom, a thyroid hormone receptor-β agonist, are approved therapies for noncirrhotic metabolic dysfunction–associated steatohepatitis (MASH) with moderate to advanced fibrosis. Their comparative economic value has not been established. To evaluate the cost-effectiveness of semaglutide and resmetirom compared with standard of care (SOC) in patients with noncirrhotic MASH and F2–F3 fibrosis. A state-transition model simulated disease progression in a hypothetical cohort with F2–F3 fibrosis over 5- and 10-year horizons from a U.S. healthcare payer perspective. Clinical efficacy inputs were derived from phase 3 trials (ESSENCE and MAESTRO-NASH), with costs and utilities obtained from published sources. Scenario analyses incorporated semaglutide’s cardiovascular mortality benefit. Deterministic and probabilistic sensitivity analyses assessed uncertainty. Semaglutide was cost-effective versus SOC at 5 years (ICER, $42,200/QALY) and 10 years (ICER, $44,138/QALY). Resmetirom produced higher ICERs ($95,981/QALY at 5 years; $107,002/QALY at 10 years) but remained below a $150,000/QALY threshold. Inclusion of cardiovascular mortality benefits improved semaglutide’s ICER to $38,324/QALY. Probabilistic analyses showed semaglutide had the highest probability of cost-effectiveness across willingness-to-pay thresholds. Over a 10-year horizon, treatment of 100,000 patients with F2–F3 MASH was projected to prevent 270 cases of decompensated cirrhosis, 10 cases of hepatocellular carcinoma, and 1,040 liver-related deaths with semaglutide, compared with 310 cases of decompensated cirrhosis, 10 cases of hepatocellular carcinoma, and 1,180 liver-related deaths with Resmetirom. Semaglutide demonstrated superior cost-effectiveness compared with SOC and resmetirom, with cardiovascular benefits further strengthening its economic value. Not applicable.