Burden of chronic corticosteroid use among patients with ulcerative colitis initiated on targeted treatment or conventional therapy in the United States.

BACKGROUND: Chronic corticosteroid use is common in ulcerative colitis (UC); however, real-world evidence of its burden to the health care system is limited. OBJECTIVE: To quantify chronic corticosteroid use burden in UC. METHODS: Adults with UC initiated on targeted treatments (ie, biologics and advanced/small molecule therapies) or conventional therapy (index date) were selected from a deidentified US insurance claims database (January 1, 2004, to September 30, 2021). Targeted treatments and conventional therapy initiators were stratified into chronic (>90 days corticosteroid use 12 months post-index [landmark]) and nonchronic corticosteroid users. Patient characteristics 12 months pre-index were balanced with inverse probability of treatment weighting. Health care resource use, costs (US$ 2021), and corticosteroid-related complications were compared in the 12 months post-landmark. RESULTS: Targeted treatment initiators included 1,886 chronic and 1,911 nonchronic corticosteroid users; conventional therapy initiators included 4,980 chronic and 5,199 nonchronic users. Chronic vs nonchronic users had 94% more inpatient days and 16% more outpatient visits among targeted treatment initiators, and 135% more inpatient days and 30% more outpatient visits among conventional therapy initiators (all P < 0.01). Mean all-cause total costs per patient per year were $73,491 for chronic vs $58,884 for nonchronic users ($14,607 higher; P < 0.01) for targeted treatment initiators, and $39,335 for chronic vs $21,271 for nonchronic users ($18,065 higher; P < 0.01) for conventional therapy initiators. Odds of infection and bone loss were 14% and 113% higher, respectively, in chronic vs nonchronic users among targeted treatment initiators and 29% and 47% higher in chronic vs nonchronic users among conventional therapy initiators (all P < .01). CONCLUSIONS: The results of this study suggest that chronic corticosteroid use is associated with substantial clinical and economic burden and may indicate unmet needs in the management of UC progression.

Economic and clinical burden of chronic corticosteroid use in patients with Crohn[apos]s disease initiated on biologic or conventional therapies in the US: A retrospective claims study.

BACKGROUND: Chronic corticosteroid (CS) use is associated with complications, but estimates of the economic and clinical burden in patients with Crohn's disease (CD) are lacking. OBJECTIVE: To estimate the burden of chronic CS use in CD in the United States in terms of health care resource utilization (HRU), health care costs, and CS-related complications. METHODS: This was a retrospective study of adults with CD initiated on biologics or conventional therapies (index date). Patients from a deidentified insurance claims database (2004-2021) were classified as chronic CS users (>90 days of CS use) or nonchronic CS users based on a 12-month landmark period starting on the index date. Patient baseline characteristics were balanced, and outcomes (HRU, costs [2021 US dollars], and CS-related complications) 12 months after the landmark period were compared between CS groups using regressions with nonparametric bootstrap resampling to estimate confidence intervals and P values. RESULTS: Biologic initiators (mean age: 44 years, 55% female) included 3366 chronic and 3401 nonchronic CS users; conventional therapy initiators (mean age: 51 years, 59% female) included 3657 chronic and 3727 nonchronic CS users. Compared with nonchronic users, chronic users had significantly more inpatient days and outpatient visits (biologic initiators: 37% and 24% more, respectively; conventional therapy initiators: 36% and 17%, respectively; all P<0.05). Chronic users also had significantly higher mean all-cause total costs per-patient-per year (biologic: $72,967 vs. $63,100, mean cost difference [MCD] = $9867; conventional therapy: $40,144 vs. $26,426, MCD = $13,718; all P<0.001), as well as higher odds of infection (biologic: 14% higher; conventional therapy: 20% higher) and bone loss (63% and 41%, respectively) (all P<0.05). CONCLUSION: Chronic CS use in patients with CD is associated with a significant economic and clinical burden including higher HRU, health care costs, and prevalence of complications, suggesting unmet needs in the clinical management of this population.

Economic Burden of Delayed Diagnosis in Patients with Pulmonary Arterial Hypertension (PAH).

BACKGROUND: The aim of this study was to assess health care resource utilization (HRU) and costs associated with delayed pulmonary arterial hypertension (PAH) diagnosis in the United States. METHODS: Eligible adults with newly diagnosed PAH from Optum's de-identified Clinformatics® Data Mart Database (2016-2021) were assigned to mutually exclusive cohorts based on time between first PAH-related symptom and first PAH diagnosis (i.e., ≤12 months' delay, >12 to ≤24 months' delay, >24 months' delay). All-cause HRU and health care costs per patient per month (PPPM) were assessed during the first year following diagnosis and compared across cohorts using regression analysis adjusted for baseline covariates. Sensitivity analyses were conducted to assess outcomes during all available follow-up post-diagnosis. RESULTS: Among 538 patients (mean age: 65.6 years; 60.6% female), 60.8% had ≤12 months' delay, 23.4% had a delay of >12 to ≤24 months, and 15.8% had >24 months' delay. Compared with ≤12 months, delays of >12 to ≤24 months and >24 months were associated with increased hospitalizations (incidence rate ratio [95% confidence interval]: 1.40 [1.11-1.71] vs 1.71 [1.29-2.12]) and outpatient visits (1.17 [1.06-1.30] vs 1.26 [1.08-1.41]). Longer delays were also associated with more intensive care unit (ICU) stays and 30-day readmissions. Diagnosis delays translated into excess costs PPPM of US$3986 [1439-6436] for >12 to ≤24 months and US$5366 [2107-8524] for >24 months compared with ≤12 months' delay; increased hospitalization costs (US$3248 [1108-5135] and US$4048 [1401-6342], respectively) being the driver. Sensitivity analyses yielded similar trends. CONCLUSIONS: Delayed PAH diagnosis is associated with significant incremental economic burden post-diagnosis, driven by hospitalizations including ICU stays and 30-day readmissions, highlighting the need for increased awareness and a potential benefit of earlier screening.

Economic burden of illness among patients with pulmonary arterial hypertension (PAH) associated with connective tissue disorders (CTD).

Pulmonary arterial hypertension (PAH) is commonly associated with connective tissue disorders (CTDs). This study provides a contemporary assessment of the economic burden of CTD + PAH and PAH in the United States. Eligible adult patients identified from Optum's deidentified Clinformatics® Data Mart Database (10/01/2015-09/30/2021) were classified into mutually exclusive cohorts based on recorded diagnoses: (1) CTD + PAH, (2) PAH, (3) CTD, (4) control without CTD/PAH. The index date was a randomly selected diagnosis date for PAH (CTD + PAH, PAH cohorts) or CTD (CTD cohort), or a random date (control cohort). Entropy balancing was used to balance characteristics across cohorts. Healthcare costs and healthcare resource utilization (HRU) per patient per month (PPPM) were assessed for ≤12 months postindex and compared among balanced cohorts. A total of 552,900 patients were included (CTD + PAH: n = 1876; PAH: n = 8177; CTD: n = 209,156; control: n = 333,691). Average total all-cause costs were higher for CTD + PAH than PAH cohort ($16,854 vs. $15,686 PPPM; p = 0.02); both cohorts incurred higher costs than CTD and control cohorts ($4476 and $2170 PPPM; all p < 0.001). Average HRU PPPM was similar between CTD + PAH and PAH cohorts (inpatient stay: 0.15 vs. 0.15, outpatient visits: 4.23 vs. 4.11; all p > 0.05), while CTD and control cohorts incurred less HRU (inpatient stay: 0.07 and 0.03, outpatient visits: 2.67 and 1.69; all p < 0.001). CTD + PAH and PAH are associated with a substantial economic burden. The incremental burden attributable to PAH versus the general population and patients with CTD without PAH highlights significant unmet needs among PAH patients.

Indicators of Suboptimal Treatment and Associated Healthcare Costs Among Patients With Crohn's Disease Initiated on Biologic or Conventional Agents.

Background: As the treatment landscape for Crohn's disease (CD) evolves, an up-to-date understanding of the burden associated with indicators of suboptimal treatment is needed. The aim of this study was to describe suboptimal treatment indicators and associated healthcare costs among CD patients initiated on a biologic or conventional agent. Methods: Adults with CD were identified in a US healthcare claims database (Optum's Clinformatics Data Mart; 01/2004-03/2019). The first biologic or conventional agent claim within 12 months of a CD diagnosis was the index date/agent. Indicators of suboptimal treatment (nonadherence, dose escalation, chronic corticosteroid use, augmentation, ≥1 CD surgery, ≥2 CD emergency department visits, ≥1 CD inpatient (IP) stay, switch, cycling, restart, inadequate induction) were identified in the 12-month postindex landmark period. The mean per-patient-per-year (PPPY) healthcare costs (2019 USD) were evaluated in the year postlandmark. Results: There were 5107 patients (mean age ~44 years, 56% female) in the biologic and 6072 patients (~51 years; 59% female) in the conventional cohort. In the biologic cohort, 79.4% of patients had ≥1 suboptimal treatment indicator. Mean PPPY healthcare costs increased with the number of suboptimal treatment indicators, from $46 100 (no indicator) to $68 572 (≥4 indicators). The conventional cohort had similar patterns: 72.5% of patients presented ≥1 suboptimal treatment indicator, and mean PPPY healthcare costs increased from $17 329 (no indicator) to $67 568 (≥4 indicators). In both cohorts, IP and outpatient medical costs (excluding biologics) contributed a major portion of the increase. Conclusions: Among CD patients, suboptimal treatment indicators were common and were associated with an increased burden to the healthcare system.

Real-world treatment sequencing and healthcare costs among CLL/SLL patients treated with venetoclax.

OBJECTIVE: This study aimed to describe treatment sequencing and healthcare costs among chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) patients treated with venetoclax in a US managed care population. METHODS: CLL/SLL patients initiating venetoclax between 04/11/2016 and 06/30/2019 were selected from Optum's de-identified Clinformatics Data Mart Database. Costs per-patient-per-month were described during the first 60 days of venetoclax-based treatment (initiation phase) and subsequent post-initiation phase. Based on venetoclax prescribing information, clinical event-related costs were identified through claims for tumor lysis syndrome (TLS) diagnosis, monitoring, prophylaxis, immunoglobulin treatment, neutropenia, thrombocytopenia, infection, renal impairment, hypertension, or cardiac arrhythmia. Statistical testing was not conducted due to small sample size. RESULTS: Twenty-five, 30, and 66 patients initiated venetoclax as their first observed regimen (1L), second observed regimen (2L), and third or later observed regimen (3L+), respectively. Most 2L (56.7%) and 3L+ (74.2%) venetoclax recipients previously received ibrutinib. Mean monthly all-cause costs during the initiation phase were $26,429 (1L cohort), $19,580 (2L cohort), and $23,918 (3L + cohort). Among the 2L cohort, mean monthly all-cause [clinical event-related] (including TLS) costs during initiation and post-initiation phases of venetoclax treatment were $15,506 [$6368] (initiation phase) and $14,318 [$5273] (post-initiation phase; median duration: 3.7 months) for patients receiving 1L ibrutinib, and $24,908 [$12,198] (initiation phase) and $16,905 [$7066] (post-initiation phase; median duration: 3.0 months) for patients not receiving 1L ibrutinib. CONCLUSIONS: In this descriptive study, highest mean costs were observed during venetoclax initiation phase. Venetoclax patients previously receiving ibrutinib had lower mean total all-cause and clinical event-related (including TLS) costs during their venetoclax line of therapy than those previously receiving non-ibrutinib therapy.

Burden of Crohn's disease in the United States: long-term healthcare and work-loss related costs.

AIMS: To quantify the long-term direct and indirect costs among patients with Crohn's disease (CD) and specific subgroups of these patients in the United States from the private payer's perspective. MATERIALS AND METHODS: This retrospective study used the OptumHealth Care Solutions, Inc database (01 January 1999-31 March 2017) to match (1:5) adult patients with ≥2 claims for CD to patients without inflammatory bowel disease (IBD). Patterns observed during follow-up (i.e. biologics, opioids, or steroids; CD-related surgery; moderate-to-severe disease; and comorbidities) were used to identify CD subgroups. Comparisons of healthcare resource utilization, work loss days, and direct and indirect work loss-related costs were made between matched cohorts. Descriptive analyses of costs were conducted within each CD subgroup. RESULTS: There were 6,715 and 33,575 patients in the CD and non-IBD cohorts, respectively. The direct burden was significantly higher in the CD cohort compared to the non-IBD cohort, with 0.34 inpatient admissions per patient per year (PPPY) versus 0.12 (217% increase; p < .001), and $24,500 direct healthcare costs PPPY versus $7,037 ($17,463 increase; p < .001). The trend was similar for the indirect burden, with work loss-related costs PPPY of $5,490 in the CD cohort versus $3,322 in the non-IBD cohort ($2,168 increase; p < .001). The burden was numerically higher in the CD subgroups, with direct healthcare costs reaching $101,013 PPPY in the surgery subgroup. LIMITATIONS: Severity of CD was determined based on claims-based algorithms due to the lack of access to medical files. Absenteeism was imputed based on claims data, and presenteeism was not assessed. CONCLUSIONS: The direct healthcare and indirect work loss-related costs of patients with CD was significantly higher compared to patients without IBD over an average follow-up of 5 years.

Long-term direct and indirect costs of ulcerative colitis in a privately-insured United States population.

Objective: Prior evaluations of ulcerative colitis (UC)-related costs are dated or encompassed limited follow-up. This study assessed the incremental direct and indirect work loss-related costs of privately-insured patients with UC in the United States, overall and in specific subgroups.Methods: In this retrospective matched cohort study, the OptumHealth Care Solutions, Inc (formerly Optum Health Reporting and Insights employer) database (01 January 1999-31 March 2017) was used to identify adult patients with ≥2 claims for UC, who were matched 1:5 to patients with no claims for inflammatory bowel disease (IBD). UC subgroups were identified based on indicators during the observation period (i.e. use of biologics, opioids, or corticosteroids; UC-related surgery; moderate-to-severe disease; UC-related comorbidities). Healthcare resource utilization (HRU), work loss days, and direct and work loss-related costs were compared between matched cohorts. Descriptive analyses of direct and work loss-related costs were conducted within each UC subgroup.Results: Compared to the non-IBD cohort (n = 46,765), the UC cohort (n = 9353) incurred higher HRU, including 128% more inpatients visits, resulting in $11,029 higher direct costs per patient per year (PPPY; $7170 vs. $18,198; p < .001). Patients in the UC cohort also incurred more work loss days, resulting in $2142 higher work loss-related costs PPPY ($3165 vs. $5307; p < .001). Direct and work loss-related costs were particularly high in the UC subgroups, with patients undergoing UC-related surgery incurring the highest costs.Conclusions: Over ∼5 years follow-up, patients with UC had significantly higher all-cause direct healthcare and indirect work loss-related costs compared to matched patients without IBD.

The societal economic burden of autosomal dominant polycystic kidney disease in the United States.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common inherited kidney diseases characterized by progressive development of renal cysts and numerous extra-renal manifestations, eventually leading to kidney failure. Given its chronic and progressive nature, ADPKD is expected to carry a substantial economic burden over the course of the disease. However, there is a paucity of evidence on the impact of ADPKD from a societal perspective. This study aimed to estimate the direct and indirect costs associated with ADPKD in the United States (US). METHODS: A prevalence-based approach using data from scientific literature, and governmental and non-governmental organizations was employed to estimate direct healthcare costs (i.e., medical services, prescription drugs), direct non-healthcare costs (i.e., research and advocacy, donors/recipients matching for kidney transplants, transportation to/from dialysis centers), and indirect costs (i.e., patient productivity loss from unemployment, reduced work productivity, and premature mortality, caregivers' productivity loss and healthcare costs). The incremental costs associated with ADPKD were calculated as the difference between costs incurred over a one-year period by individuals with ADPKD and the US population. Sensitivity analyses using different sources and assumptions were performed to assess robustness of estimates and account for variability in published estimates. RESULTS: The estimated total annual costs attributed to ADPKD in 2018 ranged from $7.3 to $9.6 billion in sensitivity analyses, equivalent to $51,970 to $68,091 per individual with ADPKD. In the base scenario, direct healthcare costs accounted for $5.7 billion (78.6%) of the total $7.3 billion costs, mostly driven by patients requiring renal replacement therapy ($3.2 billion; 43.3%). Indirect costs accounted for $1.4 billion (19.7%), mostly driven by productivity loss due to unemployment ($784 million; 10.7%) and reduced productivity at work ($390 million; 5.3%). Total excess direct non-healthcare costs were estimated at $125 million (1.7%). CONCLUSIONS: ADPKD carries a considerable economic burden, predominantly attributed to direct healthcare costs, the majority of which are incurred by public and private healthcare payers. Effective and timely interventions to slow down the progression of ADPKD could substantially reduce the economic burden of ADPKD.

Costs associated with renal and cardiovascular events among patients with type 2 diabetes mellitus and nephropathy: a cost model based on the CREDENCE clinical trial.

Objective: To estimate the avoided costs associated with reductions in end-stage kidney disease (ESKD), certain CV events (non-fatal myocardial infarction [MI], non-fatal stroke, hospitalization for heart failure [HHF]), and renal and CV death for patients treated with canagliflozin versus placebo, based on CREDENCE trial results.Methods: Renal (including ESKD) and CV events averted, based on the differences in adjusted rates of events between the canagliflozin and placebo arms in CREDENCE, were projected to the proportion of the members of a managed care organization (MCO) fitting the inclusion criteria in CREDENCE (i.e. diabetic nephropathy, at least 30 years old). The number of events averted for the population was multiplied by the unit-cost of the event, extracted from a targeted literature review, to obtain costs avoided per member per year (PMPY). One-way sensitivity analysis provided a range for the cost avoided PMPY, based on variations in the events averted, unit cost and size of the projected population.Results: Costs avoided PMPY were $2.92 for ESKD with a range of $1.28-$4.20. Costs avoided PMPY were $0.54 (-$0.28-$1.16) for non-fatal MI, $0.30 (-$0.22-$0.65) for non-fatal stroke, $1.56 ($0.80-$2.11) for HHF, $0.06 ($0.05-$0.07) for renal death, and $0.51 ($0.00-$0.91) for CV death. For non-fatal MI and non-fatal stroke, the lower bound of the range is interpreted as an incremental cost.Conclusions: Positive costs avoided for each of the outcomes considered were predicted in the main analysis, with ESKD as the outcome predicted to have the greatest costs avoided at $2.92 PMPY.

Development of risk models for major adverse chronic renal outcomes among patients with type 2 diabetes mellitus using insurance claims: a retrospective observational study.

Objective: To develop and validate models allowing the prediction of major adverse chronic renal outcomes (MACRO) in patients with type 2 diabetes mellitus (T2DM) using insurance claims data.Methods: The Optum Integrated Real World Evidence Electronic Health Records and Claims de-identified database (10/01/2006-09/30/2016) was used to identify T2DM patients ≥50 years old. Risk factors were assessed over a 12-month baseline period, and MACRO were subsequently assessed until the end of data availability, continuous enrollment, or death. Separate models were built for moderate-to-severe diabetic kidney disease (DKD), end-stage renal disease (ESRD), and renal death. A random split-sample approach was employed, where 70% of the sample served for model development (training set) and the remaining 30% served for validation (testing set). C-statistics were used to assess model performance.Results: A total of 160,031 patients were included. Risk factors associated with MACRO for all models included adapted diabetes complications severity index, heart failure, anemia, diabetic nephropathy, and CKD. C-statistics ranged between 0.70 (moderate-to-severe DKD) and 0.84 (renal death) in the testing set. A substantial proportion (e.g. 88.7% for moderate-to-severe DKD) of patients predicted to be at high-risk of MACRO did not have diabetic nephropathy, proteinuria, or CKD at baseline.Conclusions: The models developed using insurance claims data could reliably predict the risk of MACRO in patients with T2DM and enabled patients at higher-risk of DKD to be identified in the absence of baseline diabetic nephropathy, CKD, or proteinuria. These models could help establish strategies to reduce the risk of MACRO in T2DM patients.

Are Medicaid Coverage Gaps Associated with Higher Health Care Resource Utilization and Costs in Patients with Schizophrenia?

The objective was to assess the association of Medicaid coverage gaps with health care resource utilization (HRU) and costs of patients with schizophrenia. Patients with schizophrenia were identified from the Medicaid database. The beginning of the first eligible gap was defined as the index date. Per-patient per-month (PPPM) HRU and costs before versus after a gap were assessed, and the association between gap duration and PPPM HRU and costs was examined up to 12 months post index. Together with 95% confidence intervals, HRU differences were reported in rate ratios (RRs), and cost differences were reported in 2016 US dollars. A subgroup of males with substance use disorder (SUD; risk factors for incarceration) also was analyzed. Total PPPM health care costs increased significantly by $711.04 following a coverage gap (P < 0.001). Gaps of 180-365 days were associated with a significant increase in inpatient visits (RR = 1.27; P < 0.001) relative to gaps of <90 days. Gaps of 90-179 days were associated with significantly more PPPM inpatient visits (RR = 1.14; P = 0.024) relative to a gap of <90 days. Inpatient costs were particularly increased for gaps of 180-365 days versus those of <90 days (cost difference = $101.81 PPPM; P = 0.0008). Similar results were found in male patients with SUD, in whom HRU and cost differences appeared larger. In patients with schizophrenia, longer Medicaid coverage gaps were associated with increases in inpatient admissions, emergency room visits, and inpatient costs, particularly among patients with risk factors for incarceration. These results support policies that aim to facilitate Medicaid reinstatement for patients with schizophrenia.

Economic modelling of costs associated with outcomes reported for type 2 diabetes mellitus (T2DM) patients in the CANVAS and EMPA-REG cardiovascular outcomes trials.

AIMS: To model direct medical costs associated with reductions in cardiovascular disease (CVD) events in T2DM patients reported in the CANVAS and EMPA-REG trials, which assessed the cardiovascular safety of canagliflozin and empagliflozin, respectively. MATERIALS AND METHODS: Costs were modeled from a US managed care organization (MCO) perspective for the CVD outcomes included in both trials: three-point major adverse cardiovascular event (MACE) and its components (cardiovascular-related death, nonfatal myocardial infarction, nonfatal stroke), as well as heart failure requiring hospitalization. The rate of CVD events averted (difference between study drug and placebo) was projected to the portion of an MCO T2DM population matching the respective trial's inclusion criteria. A targeted literature search for paid amounts directly associated with each CVD event provided the unit costs, which were applied to the projected number of events averted, to calculate costs avoided per member per year (PMPY). One-way sensitivity analyses were performed on events averted, unit costs, and percentages of trial-applicable patients. RESULTS: Based on three-point MACE events averted, costs avoided PMPY of $6.17 (range: $1.27-$10.94) for CANVAS and $2.75 ($0.19-$4.83) for EMPA-REG were estimated. Costs avoided for individual components of MACE ranged from $0.77 to $3.84 PMPY for CANVAS and from -$0.97 (additional costs) to $1.54 for EMPA-REG. PMPY costs avoided for heart failure were $2.72 for CANVAS and $1.32 for EMPA-REG. LIMITATIONS AND CONCLUSIONS: Models assumed independent, non-recurrent outcomes and were restricted to medical costs directly associated with the trial-reported events. The reductions in CVD events in T2DM patients reported for both CANVAS and EMPA-REG project to a positive cost avoidance for these events in an MCO population. The analysis did not include an assessment of the impact on total cost, as the costs associated with adverse events, drug utilization or other clinical outcomes were not examined.

Postsurgical treatment landscape and economic burden of locoregional and distant recurrence in patients with operable nonmetastatic melanoma.

Surgery is the mainstay treatment for operable nonmetastatic melanoma, but recurrences are common and limit patients' survival. This study aimed to describe real-world patterns of treatment and recurrence in patients with melanoma and to quantify healthcare resource utilization (HRU) and costs associated with episodes of locoregional/distant recurrences. Adults with nonmetastatic melanoma who underwent melanoma lymph node surgery were identified from the Truven Health MarketScan database (1 January 2008 to 31 July 2017). Locoregional and distant recurrence(s) were identified on the basis of postsurgery recurrence indicators (i.e. initiation of new melanoma pharmacotherapy, new radiotherapy, or new surgery; secondary malignancy diagnoses). Of 6400 eligible patients, 219 (3.4%) initiated adjuvant therapy within 3 months of surgery, mostly with interferon α-2b (n=206/219, 94.1%). A total of 1191/6400 (18.6%) patients developed recurrence(s) over a median follow-up of 23.1 months (102/6400, 1.6% distant recurrences). Among the 219 patients initiated on adjuvant therapy, 73 (33.3%) experienced recurrences (distant recurrences: 13/219, 5.9%). The mean total all-cause healthcare cost was $2645 per patient per month (PPPM) during locoregional recurrence episodes and $12 940 PPPM during distant recurrence episodes. In the year after recurrence, HRU was particularly higher in patients with distant recurrence versus recurrence-free matched controls: by 9.2 inpatient admissions, 54.4 inpatient days, 8.8 emergency department admissions, and 185.9 outpatient visits (per 100 person-months), whereas all-cause healthcare costs were higher by $14 953 PPPM. It remains to be determined whether the new generation of adjuvant therapies, such as immune checkpoint inhibitors and targeted agents, will increase the use of adjuvant therapies, and reduce the risk of recurrences and associated HRU/cost.