Impacts of Black Box Warning, National Coverage Determination, and Risk Evaluation and Mitigation Strategies on the Inpatient On-Label and Off-label Use of Erythropoiesis-Stimulating Agents

Background: FDA black box warning, Risk Evaluation and Mitigation Strategies (REMS), and CMS national coverage determination (NCD) aim to reduce inappropriate use of erythropoiesis-stimulating agents (ESAs) that are widely used in anemic patients. Previous studies have not linked specific safety interventions to changes in ESA utilization patterns in the inpatient settings nor assessed such interventions on off-label use of the drugs. Ineffectiveness of the intervention and lag time between such interventions and the observed change in clinical practice could lead to serious clinical outcomes. In addition, such interventions may unintentionally reduce on-label and some off-label use of ESAs considered “appropriate” in patients who could otherwise benefit. Objectives: The primary aim of the study is to quantify the impacts of the (1) addition of black box warning, (2) implementation of NCD, and (3) institution of REMS on ESA on-label and off-label utilization patterns of adult inpatients. Demographic, clinical condition, physician, and hospital characteristics of ESAs users by their use category are also described in detail. Methods: Electronic health records in Cerner Database from January 1, 2005 to June 30, 2011 were used. The use of the two erythropoietic drugs: epoetin alfa and darbepoetin alfa were categorized into three groups using ICD-9-CM diagnoses and procedures codes and patients’ medication information. The three categories were (1) on-label use (approved by the FDA); (2) off-label use supported (use for the indications not approved by the FDA, but there is strong clinical evidence to support its use); and (3) off-label use unsupported (use for the indications not approved by the FDA and lacking clinical evidence). The immediate and trend impacts of the interventions on the proportion of ESAs prescribed for each usage category between 2005 and 2011 were assessed using an interrupted time series technique. The likelihood of receiving ESAs among patients with on-label, off-label supported, off-label unsupported indications was assessed using a generalized estimating equation approach with binary logistic regression technique, clustering for hospitals and controlling for potential confounders such as patient characteristics, patient clinical conditions, physician specialty, and hospital characteristics. Results: During the study period, there were 111,363 encounters of ESA use. These encounters represented 86,763 patients admitted to Cerner health system between January 1, 2005 and June 30, 2011. Of these patients, 66,121 were prescribed epoetin alfa only (76.2%); 20,088 darbepoetin alfa only (23.2%); and 554 were prescribed both epoetin alfa and darbepoetin alfa (0.6%). Forty-nine percent of the patients used ESAs for the on-label indications, 8.6% for off-label supported indications, and 42.7% for the off-label unsupported indications. The main uses of ESAs in our sample were for CKD (ONS, 41.1%) and chronic anemia (OFU, 31.8%). From 2005 to 2010, the proportion of visits with ESA ONS and OFS use decreased 53.2% and 81.9%, while ESA OFU increased 112.6%. Results from binary logistic regression using GEE model showed overall decreasing trends in ESA use for the on-label and off-label supported indications, but not off-label unsupported indications. REMS had no impact on the odds of receiving ESAs among patients with on-label and off-label conditions. Black box warning reduced the odds of being prescribed with epoetin alfa in patients with off-label unsupported conditions by 40%. It was also associated with 4% and 15% per month reduction in the odds of using darbepoetin alfa in patients with off-label supported and unsupported conditions. Lastly, there was a significant decline in all categories of ESA use the month after Medicare national coverage determination was implemented. The impact of NCD ranged from a 20% reduction in the odds of off-label supported use to a 37% reduction in on-label use. Age, gender, race, source of payment, admission type, clinical complexity, discharge disposition, and hospital size were significant associated with ESA use on-label and off-label. Conclusion: This study was the first to determine the impact of safety interventions on ESA on-label and off-label utilization patterns in the inpatient settings using the Cerner database. We demonstrated lag between the interventions and observed change in clinical practice, and the relative impacts of three types of safety interventions on on-label and off-label ESA use in the hospital settings. The indirect impact of the reimbursement change was the potential unintended consequence of reducing the likelihood of receiving ESAs for a patient with indicated conditions who could have otherwise benefited from the drugs

Health care resource use and costs in patients with food allergies: A United States insurance claims database analysis

Aims: Food allergies impose a large clinical and financial burden on patients and the health care system. However, little is known about the factors associated with health care resource use and costs. The aim of this study was to investigate health care resource use and costs in individuals with food allergies utilizing health care in the United States. Methods: We conducted a retrospective analysis of insurance claims data from the Merative MarketScan Research Databases (indexed from 1 January 2015 to 30 June 2022). All-cause and food allergy-related health care resource use, direct medical, and out-of-pocket costs for medical services were estimated for 12 months post-index using International Classification of Diseases [ICD] codes. Results: Of 355,520 individuals with food allergies continuously enrolled in a health insurance plan for ≥12 months pre- and post-index, 17% had a food allergy-related emergency department visit and 0.9% were hospitalized. The top patient characteristic associated with all-cause and food allergy-related hospitalizations, all-cause costs, and food allergy-related outpatient visit costs was a Charlson Comorbidity Index score of ≥2. Food allergy-related direct medical and out-of-pocket costs were high among patients with a food allergy-related visit. Out-of-pocket cost per patient per year for outpatient visits, emergency department visits, and hospitalizations had an estimated mean of 1631 dollars for patients with food allergy-related visits, which is ∼11% of the total costs for these services (14,395 dollars per patient per year). Limitations: Study limitations are primarily related to the nature of claims databases, including generalizability and reliance on ICD codes. Nevertheless, MarketScan databases provide robust patient-level insights into health care resource use and costs from a large, commercially insured patient population. Conclusion: The health care resource use of patients with food allergies imposes a burden on both the health care system and on patients and their families, especially if patients had comorbidities.</p

Impact of list price changes on out-of-pocket costs and adherence in four high-rebate specialty drugs

Background Insurers manage the cost of specialty medicines via rebates, however it is unclear if the savings are passed on to patients, and whether reducing rebates may lead to changes in patient out-of-pocket (OOP) costs and medication adherence. This study examined two drug classes to understand the impact of reducing list prices to net prices, via lower-priced national drug codes (NDCs) or authorized generics, on patient OOP costs and adherence. Methods This retrospective analysis assessed IQVIA PharMetrics ® Plus adjudicated medical and pharmacy claims for commercially insured patients. Patient OOP costs per prescription and payer drug costs were assessed for evolocumab or alirocumab (proprotein convertase subtilisin/kexin type 9 inhibitors [PCSK9is]) or velpatasvir/sofosbuvir or ledipasvir/sofosbuvir (hepatitis C virus [HCV] medications). For PCSK9is and HCV medications, the original and lower-priced versions were compared. Adherence was estimated based on proportion of days covered (PDC) (PCSK9is) and receipt of full treatment regimen (HCV medications). Results In total, 10,640 patients were included (evolocumab, 5,042; alirocumab, 1,438; velpatasvir/sofosbuvir, 2,952; ledipasvir/sofosbuvir,1,208). After list price reductions, mean payer drug costs decreased by over 60%, while patient OOP cost reductions ranged from 14% to 55% (evolocumab: 55%, p 60% reductions). Six-month PDC for PCSK9is and proportion receiving full HCV treatment regimen were high with the original versions and did not substantially differ with the new, lower-priced versions. Conclusions Reducing list prices to approximate net prices (as a proxy for reducing rebates) resulted in lower patient OOP costs, particularly for those with coinsurance. Our findings suggest that future reduction of rebates may assist in patient affordability, although additional transparency is needed

Impact of list price changes on out-of-pocket costs and adherence in four high-rebate specialty drugs

Background Insurers manage the cost of specialty medicines via rebates, however it is unclear if the savings are passed on to patients, and whether reducing rebates may lead to changes in patient out-of-pocket (OOP) costs and medication adherence. This study examined two drug classes to understand the impact of reducing list prices to net prices, via lower-priced national drug codes (NDCs) or authorized generics, on patient OOP costs and adherence. Methods This retrospective analysis assessed IQVIA PharMetrics ® Plus adjudicated medical and pharmacy claims for commercially insured patients. Patient OOP costs per prescription and payer drug costs were assessed for evolocumab or alirocumab (proprotein convertase subtilisin/kexin type 9 inhibitors [PCSK9is]) or velpatasvir/sofosbuvir or ledipasvir/sofosbuvir (hepatitis C virus [HCV] medications). For PCSK9is and HCV medications, the original and lower-priced versions were compared. Adherence was estimated based on proportion of days covered (PDC) (PCSK9is) and receipt of full treatment regimen (HCV medications). Results In total, 10,640 patients were included (evolocumab, 5,042; alirocumab, 1,438; velpatasvir/sofosbuvir, 2,952; ledipasvir/sofosbuvir,1,208). After list price reductions, mean payer drug costs decreased by over 60%, while patient OOP cost reductions ranged from 14% to 55% (evolocumab: 55%, p &lt; 0.01; alirocumab: 51%, p &lt; 0.01; velpatasvir/sofosbuvir: 30%, p &lt; 0.01; ledipasvir/sofosbuvir: 14%, p = 0.03). Patients with coinsurance as the largest contributor to their OOP costs had the largest reductions in OOP costs, ranging from adjusted, mean values of US$135 to US$379 (&gt;60% reductions). Six-month PDC for PCSK9is and proportion receiving full HCV treatment regimen were high with the original versions and did not substantially differ with the new, lower-priced versions. Conclusions Reducing list prices to approximate net prices (as a proxy for reducing rebates) resulted in lower patient OOP costs, particularly for those with coinsurance. Our findings suggest that future reduction of rebates may assist in patient affordability, although additional transparency is needed. </jats:sec

Health Resource Utilization and Costs Associated with the Use of Obinutuzumab-Based Regimens Are Similar to Rituximab-Based Regimens for the First-Line Treatment of Follicular Lymphoma

Introduction: Obinutuzumab (GA101; G), a fully humanized, glycoengineered, type II anti-CD20 monoclonal antibody, is approved in the US for the first-line (1L) treatment of follicular lymphoma (FL). Despite the superior efficacy of G plus chemotherapy (G-chemo) versus rituximab (R) plus chemotherapy (R-chemo) in patients with previously untreated FL demonstrated in the Phase III, randomized GALLIUM study (NCT01332968; Marcus et al. N Engl J Med 2017), information on healthcare resource use (HRU) and real-world costs with G in previously untreated FL patients is limited. The aim of this retrospective cohort study was to examine HRU and costs for G-based and R-based therapies for the 1L treatment of FL using a US claims database. Methods: The data source for this study was the PharMetrics Plus Commercial Claims database. Adult patients (≥18 years) diagnosed with FL between February 1, 2015 and September 30, 2018 and who began any treatment for FL between February 1, 2016 and September 30, 2018 were included. The first FL treatment date within this selection window was denoted the index date. Patients were required to have ≥12 months of pre-index and ≥3 months of post-index continuous study enrolment, and to have at least one FL diagnosis on or during the 12-month pre-index period. Patients with FL treatment during the 12-month pre-index period were excluded in order to select only previously untreated patients. HRU and cost data during the 1L treatment period were descriptive and categorized by HRU category. Costs are in 2018 US dollars ($) and standardized as per patient per month (PPPM) costs. FL treatment determination was based on National Comprehensive Cancer Network guidelines. Results: A total of 1584 FL patients with ≥3 months follow up were analyzed. Overall, 26 patients received G-chemo (any combination) as their 1L treatment, 208 patients received R-CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone), 391 patients received R-Benda (bendamustine) and 17 patients received R-CVP (cyclophosphamide, vincristine, prednisone); the remaining 942 patients received other regimens (predominantly other R combinations). Data are reported for those patients who received G-chemo, R-CHOP, R-Benda or R-CVP as 1L therapy (n=642; 281 females, 361 males). Baseline patient characteristics were similar for most variables across treatment groups. Mean (standard deviation [SD]) age was 56.9 (9.7) years and all patients had a Charlson Comorbidity Index (CCI) of ≥2 (mean [SD]: 2.9 [1.9]). Mean (SD) patient follow-up was 14.1 (8.0) months and mean (SD) duration of 1L treatment was 7.0 (5.1) months. A summary of all-cause HRU in patients receiving 1L treatment is provided by treatment category (Figure 1A). The proportion of patients with at least one hospitalization was highest with R-CHOP (23.6$17,874 [$13,465]). Medical costs (mean [SD]) were highest for R-Benda ($27,716 [$19,610] PPPM) and lowest for R-CVP ($17,373 [$12,908] PPPM). G-chemo was associated with the lowest pharmacy costs ($76 [$107] PPPM) (Figure 1B). Mean (SD) total cost of FL drug treatment PPPM was$16,028 ($9,942) for G-chemo,$11,684 ($6,122) for R-CHOP and$12,108 ($8,794) for R-CVP. Mean (SD) total cost of FL drug treatment PPPM was highest with R-Benda ($21,263 [$15,328]). G-specific drug costs PPPM ($9,643 [$6,071]) were similar to R-specific drug costs ($9,992 [$5,234] R-CHOP;$9,083 [$5,859] R-Benda; and$10,702 [$7,717] R-CVP). Conclusions: Our results depict real-world HRU and costs associated with G and commonly used 1L regimens for FL. In this setting, HRU and costs associated with G-chemo were comparable with R-chemo, supporting the use of G-chemo as a treatment option for patients with previously untreated FL. The study findings are limited by the small sample size of the G-chemo patient cohort (n=26) and short follow-up; to address this, an updated analysis incorporating a larger number of patients is planned. Disclosures To: Genentech, Inc.: Employment, Equity Ownership. Dawson:Roche/Genentech: Equity Ownership; Genentech: Employment. Masaquel:Genentech: Employment; Roche: Equity Ownership. Seetasith:Genentech: Employment, Equity Ownership. </jats:sec