P042 Early Versus Later Use of Vedolizumab In IBD: Patient Characteristics And Treatment Patterns In The Real World (RALEE).

BACKGROUND: Pivotal trials in inflammatory bowel disease (IBD) demonstrate that earlier use of biologics is associated with greater likelihood of response/remission, but multiple studies have identified that in the real world, biologic treatment is often delayed, thereby limiting optimal effectiveness and increasing likelihood of adverse outcomes. Further assessment of patient, provider, and payor factors that contribute to therapy choice is needed. We assessed utilization of vedolizumab (VDZ) and performed a real-world assessment using administrative datasets. Here, we describe the different treatment patterns and demographics of patients who received VDZ. METHODS: We identified VDZ-treated patients (aged ≥18 years) with Crohn's disease (CD) or ulcerative colitis (UC) in the MarketScan commercial and Medicare claims databases from 2017 to 2019 and included those who had continuous enrollment in the same health plan for ≥12 months prior to their initial IBD diagnostic claim, ≥1 VDZ claim after the initial IBD diagnosis, and continuous enrollment for ≥12 months prior to and after their initial UC or CD diagnosis. Patients exposed to VDZ, anti-TNF, or other biologic therapy in the 12-month pre-index period were excluded. We pre-defined 5 treatment pathways: (1) EARLY VDZ - VDZ within 30 days of first IBD diagnostic claim; (2) DELAYED VDZ 1 - immunomodulators and then switch to VDZ; (3) DELAYED VDZ 2 - corticosteroids with immunomodulators prior to VDZ; (4) DELAYED VDZ 3 - 5-ASA with corticosteroids prior to VDZ; or (5) DELAYED VDZ 4 - 5-ASA with corticosteroids and immunomodulators prior to VDZ. Differences in patient baseline characteristics among these treatment pathways were analyzed descriptively. RESULTS: We identified 136,315 patients with UC and 103,591 with CD, from which 1,342 patients with UC (median age 43 years; 51.0% male; 96.4% commercially insured; 86.4% diagnosed in 2017) and 964 with CD (median age 45 years; 43.6% male; 94.6% commercially insured; 88.6% diagnosed in 2017) received VDZ and met criteria. The proportions of patients by treatment pathway were (UC|CD): EARLY VDZ (6.6%|9.6%); DELAYED VDZ 1 (7.5%|19.0%); DELAYED VDZ 2 (14.8%|36.8%); DELAYED VDZ 3 (37.6%|19.0%); DELAYED VDZ 4 (33.4%|15.6%). Among patients with UC, EARLY VDZ vs DELAYED VDZ cohorts had median age of 40 vs 44 years and proportion of men of 46.1% vs 51.4%. Among patients with CD, EARLY VDZ vs DELAYED VDZ had median age of 43 vs 45 years and proportion of men of 39.8%% vs 43.9%. For both indications, no meaningful differences among treatment groups by geographic region, payor type (i.e., commercial vs Medicare), and year of diagnosis were observed. CONCLUSION: In this administrative real-world dataset, fewer than 10% of patients with IBD were treated with VDZ within 30 days of diagnosis, and these patients were more likely to be younger and women. These findings are distinct from guidelines suggesting VDZ may be used earlier, or due to its safety profile, preferentially in older patients at higher risk for infection. Further analyses of safety and effectiveness outcomes are underway.

Racial Disparities in the Arteriovenous Fistula Care Continuum in Hemodialysis Patients.

BACKGROUND AND OBJECTIVES: Arteriovenous fistulas are the optimal vascular access type for patients on hemodialysis. However, arteriovenous fistulas are used less frequently in Black than in White individuals. The arteriovenous fistula care continuum comprises a series of sequential steps. A better understanding is needed of where disparities exist along the continuum in order to mitigate racial differences in arteriovenous fistula use. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Using Medicare claims data from the United States Renal Data System, longitudinal analyses of patients ≥67 years initiating hemodialysis with a central venous catheter between July 1, 2010 and June 30, 2012 were performed. Three patient cohorts were identified: patients initiating hemodialysis with a catheter (n=41,814), patients with arteriovenous fistula placement within 6 months of dialysis initiation (n=14,077), and patients whose arteriovenous fistulas were successfully used within 6 months of placement (n=7068). Three arteriovenous fistula processes of care outcomes were compared between Blacks and Whites: (1) arteriovenous fistula creation, (2) successful arteriovenous fistula use, and (3) primary arteriovenous fistula patency after successful use. RESULTS: An arteriovenous fistula was placed within 6 months of dialysis initiation in 37% of patients initiating dialysis with a catheter. Among the patients with arteriovenous fistula placement, the arteriovenous fistula was successfully used for dialysis within 6 months in 48% of patients. Among patients with successful arteriovenous fistula use, 21% maintained primary arteriovenous fistula patency at 3 years. After adjusting for competing risks, Black patients on hemodialysis were 10% less likely to undergo arteriovenous fistula placement (adjusted subdistribution hazard ratio, 0.90; 95% confidence interval, 0.87 to 0.94); 12% less likely to have successful arteriovenous fistula use after placement (adjusted subdistribution hazard ratio, 0.88; 95% confidence interval, 0.83 to 0.93); and 22% less likely to maintain primary arteriovenous fistula patency after successful use (subdistribution hazard ratio, 0.78; 95% confidence interval, 0.74 to 0.84). CONCLUSIONS: Lower arteriovenous fistula use among Blacks older than 67 years of age treated with hemodialysis was attributable to each step along the continuum of arteriovenous fistula processes of care.

Arteriovenous Fistula Placement, Maturation, and Patency Loss in Older Patients Initiating Hemodialysis.

RATIONALE & OBJECTIVE: The current clinical guidelines for vascular access do not have specific recommendations for older hemodialysis patients. Our study aimed to determine the association of age with arteriovenous fistula (AVF) placement, maturation, and primary and secondary patency loss among older hemodialysis recipients. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: A US national cohort of incident hemodialysis patients 67 years or older (N = 43,851) assembled from the US Renal Data System. EXPOSURE: Age at dialysis initiation. OUTCOMES: AVF placement, maturation, primary patency loss, and abandonment. ANALYTICAL APPROACH: Cause-specific and subdistribution proportional hazards models were used to examine the association of age and AVF outcomes, with kidney transplantation, peritoneal dialysis, and death treated as competing events. Age cutoff was identified by restricted cubic splines. We compared crude and inverse probability-weighted cumulative incidence functions using Gray's test. RESULTS: As compared with those aged 67-<77 years, patients 77 years or older had significantly lower probabilities of AVF placement (adjusted cause-specific HR [cHR], 0.96 [95% CI, 0.92-0.99]; adjusted subdistribution HR [sHR], 0.92 [95% CI, 0.89-0.95]; Gray's test P < 0.001) and maturation (adjusted cHR, 0.95 [95% CI, 0.91-0.99]; adjusted sHR, 0.93 [95% CI, 0.90-0.97]; P < 0.001). However, age was not associated with AVF primary (adjusted cHR, 1.05 [95% CI, 1.00-1.11]; adjusted sHR, 1.04 [95% CI, 0.99-1.09]; P = 0.09) or secondary (adjusted cHR, 1.06 [95% CI, 0.94-1.20]; adjusted sHR, 1.05 [95% CI, 0.93-1.18]; P = 0.4) patency loss. LIMITATIONS: Reliance on administrative claims to ascertain AVF outcomes. CONCLUSIONS: The likelihood of AVF maturation is an important consideration for vascular access planning. Age alone should not be the basis for excluding older dialysis patients from AVF creation because maintenance of fistula patency was not reduced with older age despite a modest reduction in fistula maturation.

Selecting important predictors for arteriovenous fistula maturation in older hemodialysis patients by using random survival forests.

BACKGROUND: Placing an arteriovenous fistula (AVF) in older hemodialysis patients at great risk of primary failure leads to prolonged dependency on central venous catheter (CVC). A model which accurately predicts AVF maturation can facilitate better clinical determination for AVF placement. METHODS: We assembled a retrospective cohort of 14 892 patients aged 67 years and older who started hemodialysis with a CVC between 7/1/2010 and 6/30/2012 and had a subsequent, incident AVF placement from the United States Renal Data System (USRDS). We used random survival forests (RSF) with competing risks to identify important predictors for AVF maturation. RESULTS: Approximately 49.7% patients achieved AVF maturation and 13.6% had a competing event. The median time to maturation was 4 (IQR: 3-5) months. Patient's gender had the highest variable importance (VIMP, 0.0027), followed by race, being institutionalized, days on hemodialysis without an AVF, estimated glomerular filtration rate, and body mass index with borderline importance (VIMP ≥0.0005). The out-of-bag (OOB) error rate of the RSF was 45.3% and 45.8% for AVF maturation in the training and validation data sets, respectively. CONCLUSIONS: Predictors in USRDS data have limited ability to predict AVF maturation. Patient's gender might be considered as the most important predictor for AVF maturation.

Validation of a Risk Equation Predicting Hemodialysis Arteriovenous Fistula Primary Failure in Elderly.

BACKGROUND: Choice of vascular access for older hemodialysis patients presents a special challenge since the rate of arteriovenous fistula (AVF) primary failure is high. The Lok's risk equation predicting AVF primary failure has achieved good prediction accuracy and holds great potential for clinical use, but it has not been validated in the United States older hemodialysis patients. METHODS: We assembled a validation data set of 14,892 patients aged 67 years and older who initiated hemodialysis with a central venous catheter between July 1, 2010, and June 30, 2012, and had a subsequent, incident AVF placement from the United States Renal Data System. We examined the external validity of Lok's model by applying it to this validation data set. The discriminatory accuracy and calibration were evaluated by the concordance index (C-statistics) and calibration plot, respectively. RESULTS: The observed frequency of AVF primary failure varied from 0.45 to 0.53 in hemodialysis patients in the validation data set. The predicted probabilities of AVF primary failure calculated by using the Lok's risk equation ranged from 0.08 to 0.61, and 77.8, 40.5, and 51.7% of patients were categorized as having high, intermediate, and low risk of AVF primary failure, respectively. The C-statistics of the Lok's risk equation in the validation data set was 0.53 (95% CI 0.52-0.54). The predicted probabilities of AVF primary failure corresponded poorly with the observed proportions in the calibration plot. CONCLUSIONS: When externally applied to a cohort of U.S. older hemodialysis patients, the Lok's risk equation exhibited poor discrimination and calibration accuracy. It is invalid to use it to predict AVF primary failure. A more complex model with strong predictors is expected to better serve clinical determination for AVF placement in this population.

Long-Term Outcomes of Arteriovenous Fistulas with Unassisted versus Assisted Maturation: A Retrospective National Hemodialysis Cohort Study.

BACKGROUND: About half of arteriovenous fistulas (AVFs) require one or more interventions before successful dialysis use, a process called assisted maturation. Previous research suggested that AVF abandonment and interventions to maintain patency after maturation may be more frequent with assisted maturation versus unassisted maturation. METHODS: Using the US Renal Data System, we retrospectively compared patients with assisted versus unassisted AVF maturation for postmaturation AVF outcomes, including functional primary patency loss (requiring intervention after achieving AVF maturation), AVF abandonment, and frequency of interventions. RESULTS: We included 7301 patients ≥67 years who initiated hemodialysis from July 2010 to June 2012 with a catheter and no prior AVF; all had an AVF created within 6 months of starting hemodialysis and used for dialysis (matured) within 6 months of creation, with 2-year postmaturation follow-up. AVFs matured without prior intervention for 56% of the patients. Assisted AVF maturation with one, two, three, or four or more prematuration interventions occurred in 23%, 12%, 5%, and 4% of patients, respectively. Patients with prematuration interventions had significantly increased risk of functional primary patency loss compared with patients who had unassisted AVF maturation, and the risk increased with the number of interventions. Although the likelihood of AVF abandonment was not higher among patients with up to three prematuration interventions compared with patients with unassisted AVF maturation, it was significantly higher among those with four or more interventions. CONCLUSIONS: For this cohort of patients undergoing assisted AVF maturation, we observed a positive association between the number of prematuration AVF interventions and the likelihood of functional primary patency loss and frequency of postmaturation interventions.

Gender Disparities in Vascular Access Surgical Outcomes in Elderly Hemodialysis Patients.

BACKGROUND: Despite national vascular access guidelines promoting the use of arteriovenous fistulas (AVF) over arteriovenous grafts (AVGs) for dialysis, AVF use is substantially lower in females. We assessed clinically relevant AVF and AVG surgical outcomes in elderly male and female patients initiating hemodialysis with a central venous catheter (CVC). METHODS: Using the United States Renal Data System standard analytic files linked with Medicare claims, we assessed incident hemodialysis patients in the United States, 9,458 elderly patients (≥67 years; 4,927 males and 4,531 females) initiating hemodialysis from July 2010 to June 2011 with a catheter and had an AVF or AVG placed within 6 months. We evaluated vascular access placement, successful use for dialysis, assisted use (requiring an intervention before successful use), abandonment after successful use, and rate of interventions after successful use. RESULTS: Females were less likely than males to receive an AVF (adjusted likelihood 0.57, 95% CI 0.52-0.63). Among patients receiving an AVF, females had higher adjusted likelihoods of unsuccessful AVF use (hazard ratio [HR] 1.46, 95% CI 1.36-1.56), assisted AVF use (OR 1.34, 95% CI 1.17-1.54), and AVF abandonment (HR 1.28, 95% CI 1.10-1.50), but similar relative rate of AVF interventions after successful use (relative risk [RR] 1.01, 95% CI 0.94-1.08). Among patients receiving an AVG, females had a lower likelihood of unsuccessful AVG use (HR 0.83, 95% CI 0.73-0.94), similar rates of assisted AVG use (OR 1.05, 95% CI 0.78-1.40) and AVG abandonment, and greater relative rate of interventions after successful AVG use (RR 1.16, 95% CI 1.01-1.33). CONCLUSIONS: While AVFs should be considered the preferred vascular access in most circumstances, clinical AVF surgical outcomes are uniformly worse in females. Clinicians should also consider AVGs as a viable alternative in elderly female patients initiating hemodialysis with a CVC to avoid extended CVC dependence.

Tradeoffs in Vascular Access Selection in Elderly Patients Initiating Hemodialysis With a Catheter.

RATIONALE & OBJECTIVE: National vascular access guidelines recommend placement of arteriovenous fistulas (AVFs) over grafts (AVGs) in hemodialysis patients, but have not been comprehensively assessed in the elderly. We evaluated clinically relevant vascular access outcomes in elderly patients receiving an AVF or AVG after hemodialysis therapy initiation. STUDY DESIGN: Retrospective cohort study using national administrative data. SETTINGS & PARTCIPANTS: Claims data from the US Renal Data System of 9,458 US patients 67 years and older who initiated hemodialysis therapy from July 1, 2010, to June 30, 2011, with a catheter and received an AVF (n=7,433) or AVG (n=2,025) within the ensuing 6 months. PREDICTOR: Arteriovenous access subtype, AVF or AVG. OUTCOMES: Successful use of vascular access, interventions to make vascular access functional, duration of catheter dependence before successful use of vascular access, frequency of interventions, and abandonment after successful use of vascular access. ANALYTICAL APPROACH: Multivariable logistic regression analysis was used to compare the need for intervention before successful use of AVFs and AVGs, and negative bionomial regression was used to calculate the frequency of intervention after successful use of vascular access. RESULTS: Unsuccessful use of vascular access within 6 months of creation was higher for AVFs versus AVGs (51% vs 45%; adjusted HR, 1.86; 95% CI, 1.73-1.99). Interventions to make vascular access functional were greater in AVFs versus AVGs (42% vs 23%; OR, 2.66; 95% CI, 2.26-3.12). AVFs had a lower 1-year abandonment rate after successful use compared with AVGs (OR, 0.71; 95% CI, 0.62-0.83) and required one-fourth fewer interventions after successful use (relative risk, 0.75; 95% CI, 0.69-0.81). Patients receiving an AVF had substantially longer catheter dependence before successful use than those receiving an AVG (median time, 3 vs 1 month; P<0.001). LIMITATIONS: Residual confounding due to vascular access choice, restriction to an elderly population, and 1-year follow-up period. CONCLUSIONS: In elderly hemodialysis patients initiating hemodialysis therapy with a catheter, the optimal vascular access selection depends on tradeoffs between shorter catheter dependence and less frequent interventions to make the vascular access (AVG) functional versus longer access patency and fewer interventions after successful use of the vascular access (AVF).

Medicare Costs Associated With Arteriovenous Fistulas Among US Hemodialysis Patients.

BACKGROUND: An arteriovenous fistula (AVF) is the recommended vascular access for hemodialysis (HD). Previous studies have not examined the resources and costs associated with creating and maintaining AVFs. STUDY DESIGN: Retrospective observational study. SETTING & PARTICIPANTS: Elderly US Medicare patients initiating hemodialysis therapy during 2010 to 2011. PREDICTOR: AVF primary and secondary patency and nonuse in the first year following AVF creation. OUTCOMES: Annualized vascular access costs per patient per year. RESULTS: Among patients with only a catheter at HD therapy initiation, only 54% of AVFs were successfully used for HD, 10% were used but experienced secondary patency loss within 1 year of creation, and 83% experienced primary patency loss within 1 year of creation. Mean vascular access costs per patient per year in the 2.5 years after AVF creation were $7,871 for AVFs that maintained primary patency in year 1, $13,282 for AVFs that experienced primary patency loss in year 1, $17,808 for AVFs that experienced secondary patency loss in year 1, and $31,630 for AVFs that were not used. Similar patterns were seen among patients with a mature AVF at HD therapy initiation and patients with a catheter and maturing AVF at HD therapy initiation. Overall, in 2013, fee-for-service Medicare paid $2.8 billion for dialysis vascular access-related services, ∼12% of all end-stage renal disease payments. LIMITATIONS: Lack of granularity with certain billing codes. CONCLUSIONS: AVF failure in the first year after creation is common and results in substantially higher health care costs. Compared with patients whose AVFs maintained primary patency, vascular access costs were 2 to 3 times higher for patients whose AVFs experienced primary or secondary patency loss and 4 times higher for patients who never used their AVFs. There is a need to improve AVF outcomes and reduce costs after AVF creation.