Purpose The anti-CD19 chimeric antigen receptor T-cell therapy tisagenlecleucel was recently approved to treat relapsed or refractory pediatric acute lymphoblastic leukemia. With a one-time infusion cost of $475,000, tisagenlecleucel is currently the most expensive oncologic therapy. We aimed to determine whether tisagenlecleucel is cost effective compared with currently available treatments. Methods Markov modeling was used to evaluate tisagenlecleucel in pediatric relapsed or refractory acute lymphoblastic leukemia from a US health payer perspective over a lifetime horizon. The model was informed by recent multicenter, single-arm clinical trials. Tisagenlecleucel (under a range of plausible long-term effectiveness) was compared with blinatumomab, clofarabine combination therapy (clofarabine, etoposide, and cyclophosphamide), and clofarabine monotherapy. Scenario and probabilistic sensitivity analyses were used to explore uncertainty. Main outcomes were life-years, discounted lifetime costs, discounted quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (3% discount rate). Results With an assumption of a 40% 5-year relapse-free survival rate, tisagenlecleucel increased life expectancies by 12.1 years and cost $61,000/QALY gained. However, at a 20% 5-year relapse-free survival rate, life-expectancies were more modest (3.8 years) and expensive ($151,000/QALY gained). At a 0% 5-year relapse-free survival rate and with use as a bridge to transplant, tisagenlecleucel increased life expectancies by 5.7 years and cost $184,000/QALY gained. Reduction of the price of tisagenlecleucel to $200,000 or $350,000 would allow it to meet a $100,000/QALY or $150,000/QALY willingness-to-pay threshold in all scenarios. Conclusion The long-term effectiveness of tisagenlecleucel is a critical but uncertain determinant of its cost effectiveness. At its current price, tisagenlecleucel represents reasonable value if it can keep a substantial fraction of patients in remission without transplantation; however, if all patients ultimately require a transplantation to remain in remission, it will not be cost effective at generally accepted thresholds. Price reductions would favorably influence cost effectiveness even if long-term clinical outcomes are modest.

PURPOSE Two anti-CD19 chimeric antigen receptor T-cell (CAR-T) therapies are approved for diffuse large B-cell lymphoma, axicabtagene ciloleucel (axi-cel) and tisagenlecleucel; each costs $373,000. We evaluated their cost effectiveness. METHODS We used a decision analytic Markov model informed by recent multicenter, single-arm trials to evaluate axi-cel and tisagenlecleucel in multiply relapsed/refractory, adult, diffuse large B-cell lymphoma from a US health payer perspective over a lifetime horizon. Under a range of plausible long-term effectiveness assumptions, each therapy was compared with salvage chemoimmunotherapy regimens and stem-cell transplantation. Main outcomes were undiscounted life years, discounted lifetime costs, discounted quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (3% annual discount rate). Sensitivity analyses explored uncertainty. RESULTS In an optimistic scenario, assuming a 40% 5-year progression-free survival (PFS), axi-cel increased life expectancy by 8.2 years at $129,000/QALY gained (95% uncertainty interval, $90,000 to $219,000). At a 30% 5-year PFS, improvements in life expectancy were more modest (6.4 years) and expensive ($159,000/QALY gained [95% uncertainty interval, $105,000 to $284,000]). In an optimistic scenario, assuming a 35% 5-year PFS, tisagenlecleucel increased life expectancy by 4.6 years at $168,000/QALY gained (95% uncertainty interval, $105,000 to $414,000/QALY). At a 25% 5-year PFS, improvements in life expectancy were smaller (3.4 years) and more expensive ($223,000/QALY gained [95% uncertainty interval, $123,000 to $1,170,000/QALY]). Administering CAR-T to all indicated patients would increase US health care costs by approximately $10 billion over 5 years. Price reductions to $250,000 and $200,000, respectively, or payment only for initial complete response (at current prices) would allow axi-cel and tisagenlecleucel to cost less than $150,000/QALY, even at 25% PFS. CONCLUSION At 2018 prices, it is possible that both CAR-T therapies meet a less than $150,000/QALY threshold. This depends on long-term outcomes compared with chemoimmunotherapy and stem-cell transplantation, which are uncertain. Widespread adoption would substantially increase non-Hodgkin lymphoma health care costs. Price reductions or payment for initial response would improve cost effectiveness, even with modest long-term outcomes.

7561 Background: Two anti-CD19 chimeric antigen receptor T-cell therapies are approved for large B-cell lymphoma (DLBCL): axicabtagene ciloleucel (axi-cel) and tisagenlecleucel. Each costs $373,000 (wholesale acquisition). We evaluated each therapy’s cost-effectiveness. Methods: A decision analytic Markov model evaluated axi-cel and tisagenlecleucel in multiply relapsed/refractory adult DLBCL from a US health-payer perspective over a lifetime horizon. The model was informed by recent multi-center, single-arm clinical trials. Under a range of plausible long-term effectiveness assumptions, axi-cel and tisagenlecleucel were each compared with salvage chemoimmunotherapy regimens and stem-cell transplantation. Main outcomes were un-discounted life-years, discounted lifetime costs, discounted quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (3% discount rate). Sensitivity analyses explored uncertainty. Results: In an optimistic scenario, assuming 40% five-year progression-free survival (PFS), axi-cel increased life-expectancy by 8.15 years at $129,000/QALY (95% UI: $90,000-215,000/QALY) gained. At 30% five-year PFS, improvements in life-expectancy were more modest (6.4 years) and expensive ($159,000/QALY [$107,000-281,000/QALY] gained). In an optimistic scenario, assuming 35% five-year PFS, tisagenlecleucel increased life-expectancy by 4.6 years at $168,000/QALY ($104,000-453,000/QALY) gained. At 25% five-year PFS, improvements in life-expectancies were more modest (3.4 years) and expensive ($224,000/QALY [$124,000-1,190,000/QALY] gained). Administering CAR-T to all indicated patients would increase US healthcare costs by $10 billion over 5 years. Price reductions to $250,000 or payment only for initial CR or 90-day CR/PR (at current prices) would allow both therapies to cost < $150,000/QALY down to 25% PFS. Conclusions: At current prices, it is possible that each CAR-T therapy may meet a < $150,000/QALY threshold; this is dependent on long-term benefit compared with chemoimmunotherapy and SCT, which is uncertain. Widespread adoption would increase non-Hodgkin lymphoma healthcare costs substantially. Price reductions or payment for initial CR or 90-day CR/PR would favorably influence cost-effectiveness even if long-term outcomes are modest.

Ibrutinib is a novel oral therapy that has shown significant efficacy as initial treatment of chronic lymphocytic leukemia (CLL). It is a high-cost continuous therapy differing from other regimens that are given for much shorter courses. Our objective was to evaluate the cost-effectiveness of ibrutinib for first-line treatment of CLL in patients older than age 65 years without a 17p deletion. We developed a semi-Markov model to analyze the cost-effectiveness of ibrutinib vs a comparator therapy from a US Medicare perspective. No direct comparison between ibrutinib and the best available treatment alternative, obinutuzumab plus chlorambucil (chemoimmunotherapy), exists. Therefore, we compared ibrutinib to a theoretical treatment alternative, which was modeled to confer the effectiveness of an inferior treatment (chlorambucil alone) and the costs and adverse events of chemoimmunotherapy, which would provide ibrutinib with the best chance of being cost-effective. Even so, the incremental cost-effectiveness ratio of ibrutinib vs the modeled comparator was $189 000 per quality-adjusted life-year (QALY) gained. To reach a willingness-to-pay threshold (WTP) of $150 000 per QALY, the monthly cost of ibrutinib would have to be at most $6800, $1700 less than the modeled cost of $8500 per month (a reduction of $20 400 per year). When the comparator efficacy is increased to more closely match that seen in trials evaluating chemoimmunotherapy, ibrutinib costs more than $262 000 per QALY gained, and the monthly cost of ibrutinib would need to be lowered to less than $5000 per month to be cost-effective. Ibrutinib is not cost-effective as initial therapy at a WTP threshold of $150 000 per QALY gained.

Background: Carpal tunnel syndrome is the most common upper-extremity nerve compression syndrome. Over 500,000 carpal tunnel release (CTR) procedures are performed in the U.S. yearly. We estimated the cost-effectiveness of endoscopic CTR (ECTR) versus open CTR (OCTR) using data from published meta-analyses comparing outcomes for ECTR and OCTR. Methods: We developed a Markov model to examine the cost-effectiveness of OCTR versus ECTR for patients undergoing unilateral CTR in an office setting under local anesthesia and in an operating-room (OR) setting under monitored anesthesia care. The main outcomes were costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs). We modeled societal (modeled with a 50-year-old patient) and Medicare payer (modeled with a 65-year-old patient) perspectives, adopting a lifetime time horizon. We performed deterministic and probabilistic sensitivity analyses (PSAs). Results: ECTR resulted in 0.00141 additional QALY compared with OCTR. From a societal perspective, assuming 8.21 fewer days of work missed after ECTR than after OCTR, ECTR cost less across all procedure settings. The results are sensitive to the number of days of work missed following surgery. From a payer perspective, ECTR in the OR (ECTROR) cost $1,872 more than OCTR in the office (OCTRoffice), for an ICER of approximately $1,332,000/QALY. The ECTROR cost $654 more than the OCTROR, for an ICER of $464,000/QALY. The ECTRoffice cost $107 more than the OCTRoffice, for an ICER of $76,000/QALY. From a payer perspective, for a willingness-to-pay threshold of $100,000/QALY, OCTRoffice was preferred over ECTROR in 77% of the PSA iterations. From a societal perspective, ECTROR was preferred over OCTRoffice in 61% of the PSA iterations. Conclusions: From a societal perspective, ECTR is associated with lower costs as a result of an earlier return to work and leads to higher QALYs. Additional research on return to work is needed to confirm these findings on the basis of contemporary return-to-work practices. From a payer perspective, ECTR is more expensive and is cost-effective only if performed in an office setting under local anesthesia. Level of Evidence: Economic and Decision Analysis Level I. See Instructions for Authors for a complete description of levels of evidence.

Background: The Controlled Study of Lanreotide Antiproliferative Response in Neuroendocrine Tumors (CLARINET) trial showed prolonged progression-free survival in patients initially treated with lanreotide versus placebo. We evaluated the cost-effectiveness of upfront lanreotide versus active surveillance with lanreotide administered after progression in patients with metastatic enteropancreatic neuroendocrine tumors (NETs), both of which are treatment options recommended in NCCN Clinical Practice Guidelines in Oncology for Neuroendocrine and Adrenal Tumors. Methods: We developed a Markov model calibrated to the CLARINET trial and its extension. We based the active surveillance strategy on the CLARINET placebo arm. We calculated incremental cost-effectiveness ratios (ICERs) in dollars per quality-adjusted life-year (QALY). We modeled lanreotide’s cost at $7,638 per 120 mg (average sales price plus 6%), used published utilities (stable disease, 0.77; progressed disease, 0.61), adopted a healthcare sector perspective and lifetime time horizon, and discounted costs and benefits at 3% annually. We examined sensitivity to survival extrapolation and modeled octreotide long-acting release (LAR) ($6,183 per 30 mg). We conducted one-way, multiway, and probabilistic sensitivity analyses. Results: Upfront lanreotide led to 5.21 QALYs and a cost of $804,600. Active surveillance followed by lanreotide after progression led to 4.84 QALYs and a cost of $590,200, giving an ICER of $578,500/QALY gained. Reducing lanreotide’s price by 95% (to $370) or 85% (to $1,128) per 120 mg would allow upfront lanreotide to reach ICERs of $100,000/QALY or $150,000/QALY. Across a range of survival curve extrapolation scenarios, pricing lanreotide at $370 to $4,000 or $1,130 to $5,600 per 120 mg would reach ICERs of $100,000/QALY or $150,000/QALY, respectively. Our findings were robust to extensive sensitivity analyses. The ICER modeling octreotide LAR is $482,700/QALY gained. Conclusions: At its current price, lanreotide is not cost-effective as initial therapy for patients with metastatic enteropancreatic NETs and should be reserved for postprogression treatment. To be cost-effective as initial therapy, the price of lanreotide would need to be lowered by 48% to 95% or 27% to 86% to reach ICERs of $100,000/QALY or $150,00/QALY, respectively.

Key PointsQuestionAmong patients with newly diagnosed diabetes, are preexisting mental health (MH) or substance use (SU) disorders and primary care utilization before a new diabetes diagnosis associated with the long-term severity of diabetes complications?FindingsIn this cohort study of 122 992 patients in the US Department of Veterans Affairs health system, more than 90% of patients with MH or SU disorders had primary care visits before diabetes was newly diagnosed, compared with approximately 58% of patients without MH or SU disorders. Patients with MH or SU disorders experienced significantly lower severity of diabetes complications for 7 years thereafter, compared with patients without preexisting MH or SU disorders, even after controlling for sociodemographic characteristics and medical comorbidities.MeaningAmong patients with MH or SU disorders, receiving more medical and mental health care from an integrated health care system before the onset of diabetes is associated with modest, albeit impermanent, health benefits after the onset of diabetes.

Background Complex regional pain syndrome (CRPS) occurs in 2 to 8% of patients that receive open or endoscopic carpal tunnel release (CTR). Because CRPS is difficult to treat after onset, identifying risk factors can inform prevention. We determined the incidence of CRPS following open and endoscopic CTR using a national claims database. We also examined whether psychosocial conditions were associated with CRPS after CTR. Methods We accessed insurance claims using diagnostic and procedural codes. We calculated the incidence of CRPS following open carpal tunnel release and endoscopic carpal tunnel release within 1 year. The response variable was the presence of CRPS after CTR. Explanatory variables included procedure type, age, gender, and preoperative diagnosis of anxiety or depression. Results The number of open CTRs (85% of total) outweighs the number of endoscopic procedures. In younger patients, the percentage of endoscopic CTRs is increasing. Rates of CRPS are nearly identical between surgery types for both privately insured (0.3%) and Medicare patients (0.1%). Middle aged (range: 40–64 years) and female patients had significantly higher rates of CRPS than did the general population. Preoperative psychosocial conditions did not correlate with the presence of CRPS in surgical patients. Clinical Relevance The decision between endoscopic and open CTR should not be made out of concern for development of CRPS postsurgery, as rates are low and similar for both procedures. Rates of CRPS found in this study are much lower than rates found in previous studies, indicating inconsistency in diagnosis and reporting or generalizability of prior work. Preoperative psychosocial disorders and CRPS are unrelated.