Budget Impact Analysis of Circulating Tumor DNA Testing for Colon Cancer in Commercial Health and Medicare Advantage Plans.

Importance: In a randomized clinical trial, treatment guided by tumor-informed circulating tumor (ct)DNA testing reduced adjuvant chemotherapy use without compromising recurrence-free survival in patients with stage II colon cancer. The potential effects of adopting ctDNA testing into routine patient care is unknown. Objective: To compare the total cost of patient care scenarios with and without the adoption of ctDNA testing. Design, Setting, and Participants: This budget impact analysis was conducted from the perspectives of US commercial health and Medicare Advantage payers. A decision-analytical model was populated with age-specific incidence of colon cancer, use of adjuvant chemotherapy, and use of single-agent or multiagent regimens. Total cost was estimated with the costs of ctDNA testing, drug acquisition, administration, surveillance, and adverse events. The analysis was conducted from September 2023 to January 2024. Exposures: The adoption of ctDNA testing. Main Outcomes and Measures: The incremental cost in the first year following the adoption of ctDNA testing, where testing will affect patient treatment and costs. Results: In hypothetical plans with 1 million individuals covered, 35 commercial health plan members and 102 Medicare Advantage members aged 75 years and younger were eligible for ctDNA testing. In the base case with a 50% adoption rate, total cost savings were $221 684 (equivalent to $0.02 per member per month [PMPM]) for a commercial payer and $116 720 (equivalent to $0.01 PMPM) for a Medicare Advantage payer. Cost savings were robust to variations in assumptions of all parameters in the commercial population but sensitive to variations in assumptions of adjuvant chemotherapy use rates in the Medicare Advantage population. The number needed to test to avoid 1 patient receiving adjuvant chemotherapy was 4 in the commercial population and 10 in the Medicare Advantage population. The budget-neutral cost for ctDNA testing was $16 202 for a commercial payer and $5793 for a Medicare Advantage payer. Conclusions and Relevance: Use of tumor-informed ctDNA testing to guide adjuvant chemotherapy in postsurgery patients with stage II colon cancer was projected to result in cost savings for both commercial and Medicare Advantage payers. Adoption of ctDNA testing is therefore advantageous from a budgetary perspective.

Evaluation of the Economic Benefit of Earlier Systemic Lupus Erythematosus (SLE) Diagnosis Using a Multivariate Assay Panel (MAP).

OBJECTIVE: Diagnosis of systemic lupus erythematosus (SLE) made by standard diagnostic laboratory tests (SDLTs) has sensitivity and specificity of 83% and 76%, respectively. A multivariate assay panel (MAP) combining complement C4d activation products on erythrocytes and B cells with SDLTs yields a sensitivity and specificity of 80% and 86%, respectively, presumably enabling earlier SLE diagnosis at lower severity, with associated lower health care costs compared with SDLT diagnoses. We compared the payer budget impact of diagnosing SLE using MAP (incremental cost of $108) versus SDLTs. METHODS: We modeled a health plan of 1 million enrollees. SLE diagnosis among suspected patients was 9.2%. The MAP arm assumed 80%/20% of patients were tested with MAP/SDLTs, versus 100% tested with SDLTs in the SDLT arm. Prediagnosis direct costs were estimated from claims data, and postdiagnosis costs were obtained from the literature. Based on improved MAP performance, the assumed hazard ratio for diagnosis rate compared with SDLTs was 1.74 (71%, 87%, 90%, and 91% of patients who develop SLE are diagnosed in years 1 to 4 compared with 53%, 75%, 84%, and 88% of patients diagnosed with SDLTs). RESULTS: Total 4-year pre- and postdiagnosis direct costs for patients with suspected SLE tested with MAP were $59 183 666 compared with $61 174 818 tested by SDLTs, with lower costs in the MAP arm due primarily to prediagnosis savings related to reduced hospital admissions. CONCLUSION: Incorporating MAP into SLE diagnosis results in estimated 4-year direct cost savings of $1 991 152 ($0.04 per member per month). By facilitating earlier diagnosis of SLE, MAP may enhance patient outcomes.

Human IFN-γ immunity to mycobacteria is governed by both IL-12 and IL-23.

Hundreds of patients with autosomal recessive, complete IL-12p40 or IL-12Rß1 deficiency have been diagnosed over the last 20 years. They typically suffer from invasive mycobacteriosis and, occasionally, from mucocutaneous candidiasis. Susceptibility to these infections is thought to be due to impairments of IL-12-dependent IFN-γ immunity and IL-23-dependent IL-17A/IL-17F immunity, respectively. We report here patients with autosomal recessive, complete IL-12Rß2 or IL-23R deficiency, lacking responses to IL-12 or IL-23 only, all of whom, unexpectedly, display mycobacteriosis without candidiasis. We show that αß T, γδ T, B, NK, ILC1, and ILC2 cells from healthy donors preferentially produce IFN-γ in response to IL-12, whereas NKT cells and MAIT cells preferentially produce IFN-γ in response to IL-23. We also show that the development of IFN-γ-producing CD4+ T cells, including, in particular, mycobacterium-specific TH1* cells (CD45RA-CCR6+), is dependent on both IL-12 and IL-23. Last, we show that IL12RB1, IL12RB2, and IL23R have similar frequencies of deleterious variants in the general population. The comparative rarity of symptomatic patients with IL-12Rß2 or IL-23R deficiency, relative to IL-12Rß1 deficiency, is, therefore, due to lower clinical penetrance. There are fewer symptomatic IL-23R- and IL-12Rß2-deficient than IL-12Rß1-deficient patients, not because these genetic disorders are rarer, but because the isolated absence of IL-12 or IL-23 is, in part, compensated by the other cytokine for the production of IFN-γ, thereby providing some protection against mycobacteria. These experiments of nature show that human IL-12 and IL-23 are both required for optimal IFN-γ-dependent immunity to mycobacteria, both individually and much more so cooperatively.