National Drug Codes Research Articles

Hormonal Contraceptive Use and Association with Thromboembolism in Women with Sickle Cell Disease

Introduction Women with sickle cell disease (SCD) require broad access to highly effective contraceptive methods due to high rates of unplanned pregnancy and adverse maternal and fetal outcomes. Combined (estrogen-containing) hormonal contraception carries a known risk of thromboembolism (TE) in the general population, and women with SCD have higher baseline risk of TE, thus use of these agents in women with SCD may further increase that risk. The paucity of safety data on hormonal contraceptive use in women with SCD limits the ability of providers and patients to make informed decisions. Objectives This study aims to use population-level administrative claims data of publicly insured women with SCD in the United States (US) to assess patterns of hormonal contraception use and evaluate risk of TE during the first year of use. We hypothesized that TE rates are higher in women prescribed combined hormonal contraceptives (CHC) as compared to women prescribed progestin-only contraceptives (POC). Methods We obtained data using the Centers for Medicare and Medicaid Services Analytic eXtract (CMS MAX) from 2006-2018. Study population included females of reproductive age (12-44 years) with >3 ICD-9 or ICD-10 codes consistent with SCD. Women had to have ≥12 months of continuous enrollment with at least 6 months of data as 'washout period' prior to enrollment period. A new prescription for hormonal contraception was identified using national drug codes in pharmaceutical claims or ICD-9 or 10 procedure codes. CHC included the combined oral contraceptive pill (OCP), transdermal patch, and vaginal ring. POC included the progestin-only pill, depot medroxyprogesterone acetate (DMPA) injection, intrauterine device (IUD) and subdermal implant. TE was defined as the presence of ≥2 ICD-9 or ICD-10 codes for venous TE (deep vein thrombosis (DVT) or pulmonary embolism (PE)) or arterial TE (stroke or myocardial infarction (MI)). Arterial TE was also required to have an associated inpatient admission. Women were included in the analysis for 12 months after contraception initiation, or censored in the event of either contraceptive switch, pregnancy or abortion, or TE occurrence. Data were summarized descriptively and TE incidence rates were calculated as events per 1,000 person-years. Results We identified a total of 41,012 reproductive-aged women with SCD enrolled in CMS MAX, of whom 22.6% (n=9,261) had received ≥1 new prescription for hormonal contraception. Among women with new contraceptive use, 58.5% (n=5,420) initiated CHC and 41.5% (n=3,841) initiated POC. Median age at the start of contraception was 22.3 years (range: 12.0-43.9) and median age at the start of CHC and POC were 22.1 and 22.7 years respectively. Among CHC users, 84.6% (n=4,584) of women were prescribed the combined OCP, 7.7% (n=419) the transdermal patch, and 7.7% (n=417) the vaginal ring. For POC users, DMPA was prescribed to 72.3% (n=2,777), progestin-only pills to 21.2% (n=816), IUD to 4.2% (n=163) and subdermal implant to 2.2% (n=85) of women. A total of 141 (1.5%) new contraceptive users with SCD were identified to have a TE during the follow-up period. The median time from contraception initiation to TE diagnosis was 183 days (IQR: 82-244). The most common TE event was PE (46.1%) followed by DVT (41.8%), stroke (6.4%), and MI (2.1%); 3.5% of women had multiple TE events. TE rate was 16.4 events per 1,000 person-years in CHC users, and the TE event rate was 17.0 events per 1,000 person-years in POC users (p=0.84). Rates of TE did not differ between the two most commonly used methods in each group, the combined OCP (15.5 events per 1,000 person-years ) and DMPA (17.7 events per 1,000 person-years) (p=0.48). Conclusion Our work provides population-level data regarding contraceptive practices for women with SCD in the US. We found that CHC was more frequently prescribed than POC, and identified low rates of long-acting reversible contraception use. The most frequently prescribed agents were the combined OCP and the DMPA injection. TE rates after initiation of the combined OCP and DMPA did not differ. Although limited by the retrospective study design and use of administrative claims data, this study suggests a similar safety profile for CHC and POC in women with SCD with respect to risk of TE.

Characterization of Real-World Chronic Graft-Versus-Host-Disease Patients Receiving Belumosudil

Introduction Chronic graft-versus-host-disease (cGVHD) is a common complication of hematopoietic stem cell transplant (HSCT). cGVHD is characterized by inflammation and fibrosis that negatively impact multiple organ systems, resulting in substantial morbidity and mortality. While many systemic therapies are available to treat cGVHD, these therapies are associated with adverse events that may limit treatment adherence or lead to discontinuation. In July 2021, the Rho-associated coiled-coil kinase 2 (ROCK2) inhibitor belumosudil was approved by the United States Food and Drug Administration for the treatment of cGVHD for patients 12 years and older after failure of at least two prior lines of systemic therapy based on the efficacy observed in a randomized, open-label, multicenter trial (NCT03640481). Characteristics of patients being treated with belumosudil outside of a clinical trial have not been described previously. The objective of this study is to understand the real-world, non-clinical trial use of belumosudil for patients with cGVHD. Methods This retrospective study describes cGVHD patients recorded in the Komodo closed claims dataset between January 2016 and March 2022. The final cohort of interest included patients who were diagnosed with cGVHD (≥1 medical claim with the International Classifications of Disease Version 10 [ICD-10] diagnosis code D89.811), received belumosudil (≥1 claims with National Drug Code 79802020030), and were 12 years of age or older in the year of belumosudil initiation. Patients were required to have at least 36 months of continuous medical and pharmacy enrollment prior to their initial belumosudil prescription to ensure a complete medical diagnosis, treatment, and healthcare utilization history. Results A total of 151 patients were identified [median (interquartile range) age of 53 (40-62) years old; 54% female]. Sixty percent (92/151) of the patients had an HSCT within the 36-month observation period, and 73% (67/92) of the patients with an observable HSCT also had a diagnosis for a hematologic cancer in the 3 months prior to their HSCT. The median times from HSCT (in those with a recorded event) and cGVHD diagnoses (in all patients available) to belumosudil initiation were 3.2 (1.7-4.0) and 1.5 (0.5-3.1) years, respectively. During the 36 months pre-belumosudil treatment, common diagnoses included dyspnea (81%, 123/151), cytopenia (79%, 119/151; includes anemia, neutropenia, and thrombocytopenia), and "complications of stem cell transplant" (76%, 115/151; ICD-10 code T86.5). In the 12 months immediately prior to belumosudil initiation, the mean (standard deviation) Charlson Comorbidity Index score was 3.6 (2.2); a median of 9 (4-20) cGVHD-related healthcare encounters occurred; and nearly half of all patients had a hospitalization (all-cause 48%, 73/151; cGVHD-related, 27%, 41/151), with the most frequent primary diagnoses for admission attributed to respiratory illnesses and transplant complications. The majority of patients had received ≥3 lines of cGVHD treatment (85%, 128/151) in the 36 months pre-belumosudil, with a median of 5 (4-6) systemic therapies. Combination therapies containing either calcineurin inhibitors (17%; 25/151) or ruxolitinib (15% 23/151) were the most common lines of therapy immediately prior to belumosudil prescription. Use of strong Cytochrome P450 Family 3 Subfamily A (CYP3A) inducers was not observed during the observation period. In the 12 months prior to belumosudil initiation, 55% (83/151) patients were prescribed proton pump inhibitors. For the first belumosudil prescription that a patient received, 74% (111/151) of patients received once-daily dosing, and 26% (40/151) of patients received twice-daily dosing. Conclusions In this real-world data, prior to receiving belumosudil, patients received a median of 5 lines of systemic therapies at a median of 1.5 years from cGVHD diagnosis. Patients displayed multiple comorbidities and frequent hospitalizations that could complicate clinical management with existing cGVHD therapies. There is an unmet need for safe and effective treatment for cGVHD patients. Further research is needed to describe outcomes for patients being treated with belumosudil.

Incidence of Venous Thromboembolism After Hip Arthroscopy Is Low With or Without Prophylaxis but Risk Factors Include Oral Contraceptive Use, Obesity, and Malignancy

To determine the incidence of and risk factors for symptomatic venous thromboembolism (VTE) after hip arthroscopy (HA) and thromboprophylaxis prescription utilization for this procedure. The PearlDiver Mariner database was queried using Current Procedural Terminology codes to identify adult patients (aged ≥ 18 years) who underwent HA between 2010 and 2020. Patient demographic information, including age, oral contraceptive use, and medical comorbidities, as well as perioperative thromboprophylaxis utilization, was recorded using International Classification of Diseases codes and National Drug Codes. The incidence of postoperative VTE within 90 days was determined. Multivariate logistic regression was used to identify predictors of perioperative thromboprophylaxis utilization and risk factors for VTE. The queried records identified 60,181 patients who met the inclusion criteria. Of these patients, 367 (0.6%) experienced VTE, including deep venous thrombosis (0.5%) and/or pulmonary embolism (0.2%). Approximately 2.1% of patients used thromboprophylaxis, including aspirin (1.1%), low-molecular-weight heparin (0.9%), and oral factor Xa inhibitors (0.1%). Oral contraceptive pill use (adjusted odds ratio [aOR], 2.16; 95% confidence interval [CI], 1.34-3.46), obesity (aOR, 1.37; 95% CI, 1.05-1.79), and a history of malignancy (aOR, 1.69; 95% CI, 1.12-2.54) were associated with increased odds of experiencing VTE. Perioperative thromboprophylaxis (aOR, 0.52; 95% CI, 0.19-1.39) was not significantly associated with decreased odds of experiencing VTE. However, obesity (aOR, 1.17; 95% CI, 1.00-1.38) and hypertension (aOR, 1.17; 95% CI, 1.02-1.36) were associated with increased odds of thromboprophylaxis prescription utilization. Although the overall risk of symptomatic VTE after HA remains low, oral contraceptive use, obesity, and a history of malignancy are associated with increased odds of thromboembolic events within 90 days. Routine thromboprophylaxis after HA may not be indicated in all patients but can be considered based on patient-specific risk factors. Level III, retrospective prognostic comparative trial.

S477 A Real World Study of Cumulative Steroid Burden in Patients With Newly Diagnosed Eosinophilic Esophagitis

Introduction: Patients with eosinophilic esophagitis (EoE) are at risk for long-term corticosteroid (CS) exposure as swallowed topical CSs (STCs) are routinely prescribed as a treatment. Further, the prevalent type 2 comorbidities (such as asthma) in EoE patients may also be treated with CSs. However, real-world burden of long-term use of STCs in EoE patients is not well documented. The aim of this study is to describe the cumulative CS burden in newly diagnosed EoE patients compared to a general patient population. Methods: In this retrospective analysis of the US Optum Clinformatics Data Mart (2007–2019), eligible patients had ≥2 claims (≥30 to ≤365 days apart) with an EoE diagnosis and ≥1y of continuous enrollment (up to 31-day allowable gap) before the index date (first claim of EoE diagnosis). The matched (1:1 on age, sex, and history of asthma) patients without EoE met same enrollment and inclusion criteria on the EoE patient’s index date. Demographics were extracted in 1-y preindex period, and treatment history with systemic (SCS), oral (OCS), or inhaled CS (ICS) was identified by National Drug Codes. All-cause CSs use was measured at the follow-up starting at the index date and ending at disenrollment or the end of the study. Results: Overall, 17,777 patients with EoE (3095 1–17y old and 14,682 ≥18y old) were matched with 17,777 patients from a general population (3017 1–17y old and 14,760 ≥18y old) (Table). At baseline, patients with EoE across age groups had significantly (P< 0.01) higher exposure to CSs and a longer treatment duration than the matched patients (Table). In the follow-up, the exposure to SCS, OCS, and ICS was significantly (P< 0.01) higher in 1–17y old EoE patients (difference: 23.5%, 13.3%, and 51.6%, respectively) and ≥18y old EoE patients (difference: 13.8%, 10.2%, and 36.6%, respectively) than the matched patients (Figure). The mean annualized treatment duration with CSs was also significantly (P< 0.01) longer in EoE patients across all age groups versus matched patients (Figure). Conclusion: This study demonstrated that patients with EoE across all age groups had considerably more prescriptions, cumulative exposure, and treatment duration of SCS, OCS, and ICS than a matched general patient population. Prior and current exposure to CSs should be considered while prescribing CSs to EoE patients across all age groups, particularly pediatric patients, as they have increased likelihood of additional exposure throughout their lifespan.Figure 1.: (a) Cumulative Steroid Exposure and (b) Annualized Steroid Treatment Duration in Patients with EoE and Matched General Population During Follow-up. EoE, eosinophilic esophagitis; ICS, inhaled corticosteroid; OCS, oral corticosteroid; SCS, systemic corticosteroid; SD, standard deviation. *P<0.01. #The cumulative dose was calculated as the sum of the total dose for all dispensed prescriptions included in the drug class over the assessment period. $Oral and parenteral corticosteroids. Table 1. - Baseline Demographic and Clinical Characteristics of Patients with EoE and Matched General Population. Characteristics Aged 1–17y Aged ≥18y Patients with EoE Matched control patients Patients with EoE Matched control patients Number of patients 3095 3017 14682 14760 Age: mean years (SD) 10.01 (4.84) 10.18 (4.76) 45.02 (15.18) 45.25 (15.27) Female; n (%) 898 (29.0) 866 (28.7) 5567 (37.9) 5599 (37.9) Race/Ethnicity; n (%) Asian 110 (3.6) 173 (5.7) 264 (1.8) 842 (5.7) Black 167 (5.4) 263 (8.7) 726 (4.9) 1436 (9.7) White 2399 (77.5) 1976 (65.5) 12420 (84.6) 9977 (67.6) Hispanic 180 (5.8) 368 (12.2) 718 (4.9) 1821 (12.3) Unknown/Missing 239 (7.7) 237 (7.9) 554 (3.8) 684 (4.6) Type II comorbidities; n (%) Asthma 822 (26.6) 807 (26.7) 1666 (11.3) 1681 (11.4) Person years of follow-up; mean (SD) 2.91 (2.38) 2.73 (2.41) 2.61 (2.08) 2.42 (2.06) Cumulative# corticosteroid exposure; n (%) Systemic (SCS)$ 840 (27.1) 577 (19.1) 3983 (27.1) 3065 (20.8) Oral (OCS) 653 (21.1) 526 (17.4) 2719 (18.5) 2078 (14.1) Inhaled (ICS) 754 (24.4) 344 (11.4) 1309 (8.9) 343 (2.3) Annualized corticosteroid treatment duration; mean days, (SD) SCS$ 3.82 (20.07) 2.04 (12.45) 4.08 (23.01) 2.92 (19.14) OCS 3.82 (20.07) 2.03 (12.43) 4.02 (22.99) 2.88 (19.11) ICS 21.88 (56.36) 9.37 (35.66) 6.17 (30.12) 2.21 (19.89) EoE, eosinophilic esophagitis; ICS, inhaled corticosteroid; OCS, oral corticosteroid; SCS, systemic corticosteroid; SD, standard deviation.#The cumulative dose was calculated as the sum of the total dose for all dispensed prescriptions included in the drug class over the assessment period.$Oral and parenteral corticosteroids.

Should insulin billing procedure codes be considered for exposure ascertainment in pharmacoepidemiology studies?

Objectives: The purpose of the study was to examine whether Healthcare Common Procedure Coding System (HCPCS) billing codes should be used in conjunction with National Drug Codes (NDCs) to establish insulin exposure episodes. Materials and Methods: We identified insulin claims billed by NDCs or HCPCS codes in FDA’s Sentinel System from 2013 to 2018. We created insulin exposure episodes separately based on NDCs only, HCPCS only, and a combination of both NDC and HCPCS. We considered gaps of &lt;30 days between valid billing codes as continuous exposure. Patients were followed until the earliest of (1) episode end date, (2) death, (3) disenrollment, (4) query end date, and (5) evidence of the opposite exposure defining code type (for cohorts defined by only NDCs or only HCPCS). We examined the median duration of incident episodes, requiring no NDC or HCPCS codes in the 183 days (washout period) before the first billing code and prevalent episodes (no washout period required). For patients with more than 1 treatment episode, we calculated median gap length between episodes. Results: We identified 107,528,855 insulin claims using NDCs or HCPCS. Of these, 98.5% were billed using NDCs. HCPCS were largely billed during emergency and ambulatory visits (52.5% and 38%, respectively). We identified 6,350,872 incident and 12,922,593 prevalent NDC episodes; and 6,821,075 incident and 13,465,108 prevalent NDC-HCPCS episodes. The median length of the first incident NDC. NDC episodes was 110 days (IQR: 60; 212); 31 (IQR: 19; 31) days for HCPCS only and 90 (IQR: 19-31) for NDC-HCPCS episodes. The median gap between the first and second episodes was shorter for incident NDC episodes than HCPCS episodes (NDC: 49 [IQR: 17; 132]; HCPCS: 249 [IQR: 93; 550]). Prevalent episodes showed similar trends. Conclusion: HCPCS insulin codes appeared to indicate either 1 time or sporadic occurrences with long gaps between two codes. HCPCS codes in conjunction with NDC codes increased the number but reduced the median length of insulin episodes. Unless studies investigate the effects of insulin administered in specific settings to identify transient adverse reactions treated with insulin, we do not encourage the use of HCPCS to establish insulin exposure episodes.

Association of Proton Pump Inhibitor/Histamine-2 Blocker Use and Ocular Toxoplasmosis: Findings from a Large US National Database

To test the hypothesis that the use of proton pump inhibitors (PPIs) is associated with an increased risk of being diagnosed with toxoplasmic retinochoroiditis. Retrospective, matched case-control study using data from 2000 to2020. Patients with ocular toxoplasmosis and controls were matched 5:1 for age, sex, and race, with the eligibility date ± 3 months from the index date of exposed match. Patients aged < 18 years with congenital toxoplasmosis, having < 2 years in the insurance plan before the index date, and without ≥ 1 visit to an eyecare provider before the index date were excluded from the study. Patients with ocular toxoplasmosis were identified using the International Classification of Diseases, Ninth Revision and International Classification of Diseases, Tenth Revision codes, and PPI use or diseases highly associated with PPIs were identified using national drug codes from an administrative medical claims database. The primary outcome was defined as having a prescription for a PPI or histamine-2 (H2) blocker. Multivariable logistic regression analyses were performed, controlling for demographic and systemic health variables. A total of 4069 cases and 19 177 controls met the eligibility criteria. Of the 4069 patients with ocular toxoplasmosis, 989 (24.3%) were on PPI/H2 blockers compared with 3763 of 19 177 (19.2%) controls. The adjusted logistic regression model demonstrated 1.28 greater odds of PPI/H2 blocker use in cases of ocular toxoplasmosis than matched controls (95% confidence interval, 1.17-1.40; P < 0.001). Proton pump inhibitor/H2 blocker exposure was associated with an increased risk of being diagnosed with ocular toxoplasmosis, corroborating findings from a prior case series. Proprietary or commercial disclosure may be found after the references.

Ancillary Data Record Linkage to characterize the completeness of data for the All of Us Research Program.

ObjectiveThe All of Us Research Program (AoURP) is an ambitious effort to gather health data from one million Americans to accelerate research. We linked Electronic Health Records (EHR) and insurance claims data to characterize the degree to which ancillary datasets can improve data completeness for care received by AoURP participants. ApproachWe sought to link EHR data for 400,000 consented AoURP participants with insurance claims data provided by IPM.AI (Swoop Analytics), a commercial analytics company who have insurance claims data for 300M (over 90% of) Americans. We utilized a HIPAA-compliant privacy-preserving record linkage method (tokenization, provided by Datavant) to match patients between datasets. We evaluated match fidelity and the degree of overlap between AoURP EHRs and IPM.AI claims data. We characterized the association of patient and organizational level factors (demographics, healthcare provider organization, reporting site) with match performance. ResultsAs of submission of this abstract, 41% of AoURP EHRs matched with IPM.AI claims. We compared patient healthcare encounters, diagnosis codes (DX), procedure codes (PX), and national drug codes (NDC) for matched patients by month. The union of AoU and IPM.AI data greatly increased data completeness in matched patients. Only 20% of healthcare encounters were seen by AoURP and IPM.AI concurrently while 25% were unique to AoU EHRs and 55% to IPM.AI claims on a monthly level. The number of diagnosis events compared between AoURP and IPM.AI is roughly equal (AoU +6%) while procedure events are elevated in claims data (23%) and drug counts are greatly elevated in AoURP EHR data (71%). We found that matched patients had more healthcare encounters compared to unmatched patients. ConclusionTo our knowledge this is the first effort to address challenges in AoURP data completeness through complementary data linkage. Our results suggest that supplementary data linkage can improve data completeness in a large national research initiative. We identified several patient factors that require further investigation in improving match fidelity.

Treatment of Hepatitis C Virus Prior to Posterior Lumbar Fusion: No Difference in Medical Outcomes or Reoperation.

Retrospective cohort. To analyze and confirm the rates of postoperative complications of patients with hepatitis C virus (HCV) undergoing primary posterior lumbar fusion (PLF) and assess whether treatment of HCV before surgery reduces complications. HCV causes chronic disease, leading to increased risk of cirrhosis and chronic illness. Currently, there is a lack of research regarding whether the patient's HCV is a modifiable risk factor for postoperative complications after spinal procedures. The Mariner database was utilized to find patients from 2010 to 2018 undergoing PLF with active follow-up for a year. Cases involving same-day revision procedures and patients with a history of spine, infection, trauma, human immunodeficiency virus, hepatitis B, or neoplasm were excluded. Patients with a history of HCV diagnosis were identified and further stratified whether they had prior treatment using the national drug codes for antiviral, interferons, or ribavirin. Patients with HCV were matched with those without respect to age, sex, and comorbidity of burden. Outcome measured included 90-day medical complications, infection, readmission, and 1-year reoperation. There were 2,129 patients with HCV and 10,544 patients in the matched control group who underwent primary PLF. Out of the 2,129 patients, 469 (22.0.%) were treated with HCV medications before surgery. Patients with prior history of HCV had a significantly increased risk of wound complications (4.4% vs. 3.2%, odds ratio 1.56, 95% confidence interval 1.24-1.96, P =0.009), and infection (7.7% vs. 5.7%, odds ratio 1.26, 95% confidence interval 1.07-1.53, P =0.009) within 90 days of surgery. Patients treated before surgery did not have a difference in major ( P =0.205) or minor medical complications ( P =0.681) after surgery. Patients with prior history of HCV are at increased risk for many complications after surgery; however, this risk factor does not seem to be modifiable as the treatment group did not experience any improvement in postoperative outcomes. Level III.

The Impact of Allergy Specialty Care on Health Care Utilization Among Peanut Allergy Children in the United States

The influence of allergist management on peanut allergy (PA)-related health care utilization is unknown. To determine whether allergist care lowers PA costs. IBM MarketScan Commercial Claims and Encounters Database was analyzed for PA diagnosis/reaction-related codes (January 2010-June 2019) in patients 64 years or younger, with demographically matched non-PA food allergy controls (NPAFACs). Outcomes were measured and compared 12 months before/after first claim date. Among 72,854 persons with PA (39,068 with ≥1 allergist visit, 53.6%), and 166,825 NPAFACs, the number of National Drug Codes and International Classification of Diseases, 10th Revision codes was higher for persons with PA with versus without an allergist visit during both baseline and follow-up (all P < .001). Persons with PA with versus without an allergist visit were prescribed epinephrine at significantly higher rates (RR, 1.67; P < .001). Rates of epinephrine claims, mean epinephrine costs, and proportion with peanut anaphylaxis were higher among the PA group with versus without an allergist visit (69.9% vs 63.3%; $676 vs $493, 48.9% vs 20.7%; all P < .001). The proportion with anaphylaxis episodes was higher in the PA group versus the NPAFAC group (53.1% vs 31.6%; P < .001). Total health care costs were higher in the NPAFAC group versus the PA group ($7863 vs $7261; P < .001) and lower for persons with PA with versus without an allergist visit ($6347 vs $8270; P < .001), with no significant differences in PA reaction-related costs between PA groups. Higher rates of anaphylaxis were seen among the PA group with versus without an allergist visit during the follow-up period (53.6% of overall PA group). Allergist care was associated with a reduction in total health care costs and higher rates of epinephrine prescription.

Perioperative Thromboprophylaxis Is Associated With Lower Risk of Venous Thromboembolism After Knee Arthroscopy

To determine the rate of symptomatic venous thromboembolism (VTE) among patients undergoing arthroscopic knee procedures, risk factors associated with postoperative VTE, and current perioperative thromboprophylaxis prescription patterns associated with this population in the United States. Medical records for patients ≥18 years of age were queried from the Mariner database using Current Procedural Terminology codes for knee arthroscopy performed in the United States from 2010 to 2020 in this cross-sectional study. Patients who received thromboprophylaxis and those diagnosed with VTE, including deep-vein thrombosis or pulmonary embolism, within 90 days of surgery were identified using International Classification of Diseases and National Drug Codes. Two multivariable logistic regression models were used to identify VTE risk factors and likelihood of perioperative thromboprophylaxis. Covariates included procedure type, age, oral contraceptive pill (OCP) use, and medical comorbidities. A total of 718,289 patients met inclusion criteria and 7,618 patients (1.06%) experienced VTE, including deep-vein thrombosis (n= 6,394, 0.9%) and/or pulmonary embolism (n= 2,211, 0.3%). A total of 10,769 patients (1.5%) filled perioperative thromboprophylaxis, including aspirin (n= 5,353, 0.7%), low-molecular-weight heparin (n= 4,563, 0.6%), and oral factor Xa inhibitors (n= 947, 0.1%). Perioperative thromboprophylaxis was associated with decreased odds of experiencing VTE (adjusted odds ratio [aOR] 0.65, 95% confidence interval [CI] 0.51-0.80). Procedure types categorized as moderate-to-greater risk were associated with increased odds of VTE (aOR 1.42, 95% CI 1.34-1.50). OCP use (aOR 1.63, 95% CI 1.38-1.91), obesity (aOR 1.17, 95% CI 1.11-1.24), renal disease (aOR 1.33, 95% CI 1.18-1.50) and congestive heart failure (aOR 1.30, 95% CI 1.13-1.50) were associated with increased odds of VTE. While the overall rate of symptomatic VTE following knee arthroscopy remains low, procedure types that are more complex and generally require restrictive rehabilitation protocols, OCP use, obesity, renal disease, and congestive heart failure are associated with increased odds of postoperative VTE. Conversely, the use of perioperative thromboprophylaxis is associated with significantly lower VTE risk. III, retrospective comparative prognostic trial.

Comparing the variability of ingredient, strength, and dose form information from electronic prescriptions with RxNorm drug product descriptions.

To determine the variability of ingredient, strength, and dose form information from drug product descriptions in real-world electronic prescription (e-prescription) data. A sample of 10399324 e-prescriptions from 2019 to 2021 were obtained. Drug product descriptions were analyzed with a named entity extraction model and National Drug Codes (NDCs) were used to get RxNorm Concept Unique Identifiers (RxCUI) via RxNorm. The number of drug product description variants for each RxCUI was determined. Variants identified were compared to RxNorm to determine the extent of matching terminology used. A total of 353002 unique pairs of drug product descriptions and NDCs were analyzed. The median (1st-3rd quartile) number of variants extracted for each standardized expression in RxNorm, was 3 (2-7) for ingredients, 4 (2-8) for strength, and 41 (11-122) for dosage forms. Of the pairs, 42.35% of ingredients (n = 328032), 51.23% of strengths (n = 321706), and 10.60% of dose forms (n = 326653) used matching terminology, while 16.31%, 24.85%, and 13.05% contained nonmatching terminology, respectively. A wide variety of drug product descriptions makes it difficult to determine whether 2 drug product descriptions describe the same drug product (eg, using abbreviations to describe an active ingredient or using different units to represent a concentration). This results in patient safety risks that lead to incorrect drug products being ordered, dispensed, and used by patients. Implementation and use of standardized terminology may reduce these risks. Drug product descriptions on real-world e-prescriptions exhibit large variation resulting in unnecessary ambiguity and potential patient safety risks.

RWD51 Comparing the Food and Drug Administration National Drug Code Directory and Redbook to Identify Prescription Records

The National Drug Code (NDC) Directory by the Food and Drug Administration (FDA) is a publicly available, and frequently used in pharmacoepidemiologic to identify prescription drug usage. The current study compared the FDA NDC Directory data and Micromedex Redbook® in identifying frequently prescribed medication records in nationally representative utilization data using the NDC generic name mapping tables.

904-P: Trends in Out-of-Pocket Cost for Glucagon 2010–2020

The ADA Standards of Care recommend that all patients with diabetes at risk of hypoglycemia have glucagon available for emergency use. However, glucagon prescriptions are filled by only a small minority of patients with type 1 and type 2 diabetes in the United States each year. While there are multiple barriers to glucagon use, the extent to which out-of-pocket medication costs contributes to low uptake is not clear. Using administrative claims from Optum’s de-identified Clinformatics® Data Mart Database (2007-2019) for adults with commercial or Medicaid insurance from 2010-2020, we sought to describe the trends in out-of-pocket costs for glucagon over time. Analyzed claims included all fills of glucagon, based on National Drug Codes, from 20through 9/30/2020. Our primary outcome was total out-of-pocket costs defined as the sum of copays and deductibles. Costs were adjusted for inflation based on 2020 dollars and scaled per single-use kit. Insurance type was based on the primary payor at the time of the glucagon fill. The median (IQR) out-of-pocket cost of unmixed glucagon was $27.42 (15.09-37.98) in 2010, $33.58 (5.60-41.97) in 2015, and $30.42 (15.21-40.56) in 2020 for commercially insured beneficiaries. For Medicare beneficiaries, cost for unmixed glucagon was $0 (0-25.35) in 2010, $0 (0-33.58) in 2015, and $0 (0-40.56) in 2020. After introduction in 2019, the 2020 out-of-pocket cost of intranasal glucagon was $15.21 (7.60-35.49) for commercially insured beneficiaries and $10.14 (0.99-23.83) for Medicare beneficiaries. Out-of-pocket costs for unmixed glucagon was stable for most commercially insured patients, and $0 for most Medicare beneficiaries from 20through 2020; therefore, cost should not serve as the primary barrier to accessing glucagon for most patients. However, for the subset of patients (4th quartile) with the highest out-of-pocket costs in both insurance groups, the cost of unmixed glucagon has increased over time. Novel intranasal glucagon had lower out-of-pocket cost compared to unmixed glucagon for most commercially insured patients immediately after introduction. Disclosure M.Zupa: None. R.Feldman: None. J.Luo: None. Funding NCATS KL2 (TR001856)

Real-world treatment patterns in patients with Sézary syndrome in the United States and the impact of Covid-19.

e19578 Background: Sézary syndrome (SS) is an aggressive type of cutaneous T-cell lymphomas (CTCL). Due to its low prevalence, there are limited data on real-world treatment patterns of currently available SS therapies. Furthermore, recent approvals of new agents for patients with CTCL as well as COVID-19 likely impacted real-world treatment patterns. Objective: To examine real-world treatment patterns and the impact of COVID-19 among SS patients treated in 2018-2020 in the US. Methods: Patients with public or private insurance in the 2018-2020 Symphony Health Solutions database were classified into 3 groups: ≥1 diagnosis of SS (ICD-10-CM code: C84.1x) in 2018, 2019, and 2020, respectively. Patient characteristics and treatment patterns for all therapies recommended by the National Comprehensive Cancer Network guidelines version 2.2021 were examined: systemic therapy (e.g., extracorporeal photopheresis (ECP), parenteral, or oral agents), skin-directed therapy (SDT, e.g., topical, local radiation, total skin electron beam therapy, or phototherapy) and bone marrow transplant. The impact of COVID-19 was assessed via quarterly analysis. National drug codes, current procedural terminology and healthcare common procedure coding system codes were used to identify all treatments. Results: The analyses included 869, 882, and 853 SS patients in 2018, 2019, and 2020, respectively (mean age: 66.3, 66.9 and 67.3 years; male: 54.4%, 54.8%, and 55.6%). Overall, systemic therapy increased from 2018 to 2020 (41.8% to 46.5%), with increased parenteral (20.7% to 28.7%) but decreased ECP (17.0% to 13.5%) usage. SDT increased from 2018 to 2020 (48.9% to 52.9%), with increased topical (42.3% to 48.3%) but decreased phototherapy (6.3% to 4.1%) usage. ECP, mogamulizumab, and bexarotene were the most prescribed systemic therapies in 2019-2020, with mogamulizumab being the only one with increased usage over time. Quarterly analysis showed a decreasing ECP from Q1 to Q4 within each year, with a notable drop in Q2 2020. For parental systemics, there was an increasing trend in 2019 and 2020, but utilization in Q4 2020 was lower than that of Q3 2020. For oral systemic, there was a notable drop in Q2 2020 but an increased trend in Q3-Q4 2020. Conclusions: This claims analysis indicated increased use in systemic and SDT among SS patients in 2018-2020. The quarterly analysis indicated that the drop in ECP and oral systemic usage in Q2 2020 coincided with the onset of the pandemic, but there was a stable use of parenteral systemic during 2020.

Prevalence of multiple sclerosis and treatment utilization in a large, highly diverse population

BackgroundDespite advances in algorithms for identifying people with MS (PwMS) in large data sets, limited data exists on regional prevalence, or prevalence and care in minority populations. ObjectivesTo report the 7-year (01/01/2012–12/31/2018) prevalence and demographics of MS and disease-modifying therapy (DMT) utilization in a large, diverse population. MethodsThis retrospective analysis used the OneFlorida Data Trust, which captures health data from >15 million Floridians across 10 constituent organizations. A validated algorithm identified subjects with MS. DMTs were identified using RxNorm concept unique identifiers and National Drug Codes. Results were stratified across age, sex, race-ethnicity, and location. ResultsOf 6,638,649 adults in the database, the algorithm identified 9681 PwMS. Overall prevalence per 100,000 was 145.83. MS prevalence was considerable in women of all races and ethnicities ranging from 138.86 to 253.76 per 100,000. 52.6% of PwMS had one or more DMT prescription. DMT prescription was more likely in Hispanic PwMS. ConclusionPrevalence analysis of the OneFlorida Data Trust revealed a substantial burden of disease in women of all races and ethnicities. Variation in treatment utilization among demographic subgroups underscores the need for additional studies to assess health care disparities in MS at the population level.

Understanding treatment patterns and patient-reported outcomes associated with the use of authorized generics and corresponding independent generics across multiple therapeutic areas

Objectives To assess patient characteristics, treatment patterns, and patient-reported outcomes (PROs) associated with authorized generics (AGs) and independent generics (IGs) use. Methods Prescription claims and National Health and Wellness Survey (NHWS) data were linked. Adults with billable national drug code (AG or IG), NHWS completion from June 2015 to July 2019, AG or IG on-hand at NHWS completion, and continuous insurance eligibility in 12 months pre- and post-NHWS completion were included. To be included, all unique medication formulations had to have at least one AG and one IG observation. PRO index date was NHWS completion; claims index date was defined as the first prescription claim identified during the 180-day period prior to NHWS completion for the same active ingredient and formulation type that was on-hand at NHWS completion. Results Patients (N = 20,229; 17.2% AG users) in six therapeutic areas (attention deficit-hyperactivity disorder [ADHD], antidepressants, beta blockers [BBs], calcium channel blockers [CCBs], statins, and thyroid) were included. Generally, AG (vs. IG) users were younger and differed in regional access and insurance type (all, p < .05). In multivariable analysis, significant differences were observed for presenteeism and overall work impairment (BBs), healthcare provider visits (BBs), and indirect costs (thyroid) (all, p < .05). AG and IG users differed in persistence (ADHD and statins; both, p < .05) and switch (BBs and CCBs; both, p < .01) rates. Conclusions PRO differences were often small in magnitude and varied by therapeutic area. The impact of switching should consider observed PRO differences, patient preferences, and market availability of AG and IG alternatives.

Countries Manufacturing Pharmaceuticals for the US Market: A 10-Year Analysis of Public Data

Concerns about strategic supplies and quality have increased the scrutiny of the countries where US pharmaceuticals are made. To examine the locations of manufacturers of brand name, biological, and generic drugs over 10 years. This longitudinal descriptive study used publicly available data from US government Web sites, including the Food and Drug Administration (FDA) Drug Establishments list, FDA National Drug Code Directory, FDA Orange Book, FDA Purple Book, and the National Institutes of Health DailyMed Drug Labels. These data were collected from 2011 to 2020. Brand name drug manufacturing in the United States and Europe decreased from 89% in 2011 to 79% in 2020. Biological manufacturing in the United States decreased, while that in Western European countries increased; 100% of biological manufacturing was done in the United States or Europe in 2011 and decreased to 93% by 2020. Generic manufacturing in India increased from 21% to 51%, while US manufacturing decreased from 52% to 35% from 2011 to 2020. These analyses were limited to publicly available data, and the results could be affected by the accuracy and completeness of the data. Brand name drugs and biologicals are primarily made in the United States and Europe. Generic drugs are increasingly made in India, but the United States remains a major supplier. If the country of origin for pharmaceuticals is important, these findings support supply chain concerns for generic drugs. We recommend that product containers and official labeling prominently include the manufacturer and location for active pharmaceutical ingredients and finished dosage forms.

Postoperative Oral Antibiotic Use and Infection-Related Complications After Spinal Cord Stimulator Surgery

ObjectivesSpinal cord stimulation (SCS) is considered a minimally invasive and reversible neuromodulation therapy for various chronic pain disorders. The rates of infection following SCS surgery reported in the literature range from 2.8% to 10%. Several studies indicated no potential benefit of postoperative antibiotics (beyond 24 hours) on subsequent device infection. This study aimed to understand the characteristics of postoperative antibiotic prescriptions and subsequent infections following SCS surgery. Materials and MethodsThe study was a retrospective cohort using the IBM® MarketScan® Commercial and Medicare Supplemental Databases from 2013 to 2018. Adult patients undergoing SCS surgical procedures with at least 90 days of follow-up were identified using Current Procedural Terminology (CPT®) codes. Postprocedural oral antibiotics within 14 days and preprocedural corticosteroid use within seven days were identified using National Drug Codes (NDC). Administrative claims were analyzed to understand the characteristics of prescribed postoperative antibiotics. Infection-related complications within 90 days were identified using administrative codes. ResultsA total of 18,105 patients (age 55.5 ± 13.1 years, 40.2% male) underwent SCS surgery during the study period. Postprocedural oral antibiotics and preprocedural steroids were prescribed for 35.3% and 2.6%, respectively, for SCS surgery patients. The most commonly used postprocedural antibiotics were cephalexin (55.4%) and sulfamethoxazole-trimethoprim (10.6%). The most common duration of antibiotic prescriptions was seven, ten, and five days in our study, from most to least common duration. Superficial surgical site infection (SSI), deep SSI, device infection, or any infection within 90 days occurred in 2.9%, 1.0%, 1.8%, and 4%, respectively, of the patients undergoing SCS surgery. ConclusionsProspective studies are needed to understand the reasons for noncompliance with expert consensus recommendations on postoperative antibiotic use beyond 24 hours of SCS surgery. Neuromodulation team members should play an important role in antibiotic stewardship.

FDA Approves First Dietary Supplement under New Drug Application with the Indication of Serious or Life-Threatening Illnesses

Background: Research began on botanical/herbal organisms to study plant cells. The idea behind this was that plant cells have basic similar actions as do animal cells (i.e., both are Eukaryotic cells). These cells can show what activity is produced from the Technology/Innovation behind ImunStem, without risk to animals or humans, and still retrieve data to verify the theory. By using plants and studying plant cell activity, then later comparing plant cell, animal cells, and human cell responses, it thus shows activity for all cell structures. The activity was also studied from patients taking ImunStem for the indication of Serious or Life-threatening conditions or diseases. Patient medical report results showed an overall improvement in bodily function as blood report results were compared. Patients that were administered ImunStem showed improvement in their overall health and patients with chronic disease had reduced pain as ImunStem was administered over time. The pain was reduced because the body was in the healing process and a reduction in inflammation would occur during healing and the patient’s health would improve. ImunStem was produced based on the theory that the product could rejuvenate the cell and bring the cell back to a homeostasis balance. This balance to the cell (through nutrition) can give the surrounding cells a homeostasis balance that may heal cells and tissues in the body. It is believed that the function of a Quantum Wave effect is explained through the discipline of Quantum Mechanics. The Quantum Wave may disrupt the subatomic particles that provide adhesion to allow the product through the cell wall and move to its target location. In Quantum Mechanics, particles have wavelike properties. The Schrödinger equation, for example, governs how these waves behave. Methods: Administration of ImunStem was given to patients in a life-threatening situation where no standard acceptable treatment was available and in which there was not sufficient time to obtain approval from the Institutional Review Board. Results: ImunStem showed positive medical results for patients with Serious or Life-threatening conditions or diseases, which prompted the US Food and Drug Administration (FDA) to move forward so patients could be provided treatment that was not otherwise available to them from their physicians/doctors. ImunStem was applied for and received its New Drug Application (NDA) No.: 204701 with the indication of Serious or Life-threatening conditions or diseases and National Drug Code (NDC) No.: 70642-001-01 on July 02, 2018. Golden Sunrise submitted an NDA application on January 07, 2013, November 05, 2018, and April 03, 2020 with a request for FDA Fast Track designation, Breakthrough Therapy designation, Accelerated Approval designation, and Priority Review program process are the pathway allowing the ImunStem product to receive acceptance by the FDA.

71. Increasing Trends in Multimorbidity and Polypharmacy Over a 5-Year Period in People Living with HIV in the United States

BackgroundAdvances in antiretroviral therapies (ART) have resulted in people living with HIV (PLWH) living longer with higher risk for age-related comorbid conditions and polypharmacy. The aim of this study was to describe trends in comorbidity and comedication burden in PLWH over a 5-year time period. MethodsA retrospective analysis of commercial and Medicare Advantage enrollees from the Optum Research Database was conducted. Annual cohorts of PLWH were constructed for each calendar year from 2014-2018 and included adults (≥ 18 years) with ≥ 1 pharmacy claim for an ART or medical claim with an HIV/AIDS diagnosis code (index date=earliest claim date in each calendar year). Continuous health plan enrollment of 12 months prior to (baseline), and 30 days after index date was required for each annual cohort. Comorbidities were identified using ICD-9/10 diagnosis codes from medical claims during baseline period and comedications from pharmacy/medical claims in the 90-days prior to index using National Drug Codes. Charlson Comorbidity Index (CCI) was computed excluding HIV/AIDS. P-for-trend values accounting for clustering by patients across calendar years were assessed.ResultsOverall, 14,222 - 20,249 PLWH who were enrolled in commercial (80.7%-65.4%) or Medicare Advantage (19.3%-34.6%) plans were identified in 2014 - 2018 calendar years. Notable trends in demographics of PLWH were observed across years, including increases in mean age (48.9 to 52.4 years), proportion of females (17.2% to 20.3%) and Black race (25.9% to 29.0%), all p-trend< 0.001. Mean CCI scores increased across years (0.72 to 0.93), p-trend< 0.001. Multimorbidity (≥2 non-HIV conditions) and polypharmacy (≥ 5 non-ART medications) prevalence increased over 5 years (Figure 1). Hypertension, hyperlipidemia, neuropsychiatric conditions and Type 2 diabetes mellitus were the most prevalent comorbid conditions with statistically significant upward trends in prevalence across years (Figure 1). ConclusionMultimorbidity and polypharmacy are common in PLWH and have been increasing in prevalence over the past 5 years. Study findings highlight the importance of an individualized approach to care for a diverse PLWH population, in order to minimize drug-drug interactions and adverse events and thereby improve patient outcomes. Figure 1. Comorbidity and Comedication Trends by Index Year among People Living with HIV Disclosures Misti Paudel, PhD, Merck (Other Financial or Material Support, This study was funded by Merck & Co.) Girish Prajapati, M.B.B.S., MPH , Merck & Co., Inc. (Employee, Shareholder) Erin K. Buysman, MS, Merck & Co., Inc. (Other Financial or Material Support, I am an employee of Optum, which was contracted by Merck to complete the research described in this abstract) Jianbin Mao, PhD, Merck & Co. (Employee, Shareholder) Kimberly McNiff, MPH, Merck (Other Financial or Material Support, Merck funded the research project) Princy N. Kumar, MD, Amgen (Consultant)Eli Lilly (Grant/Research Support)Gilead (Consultant, Grant/Research Support, Shareholder)GSK (Consultant, Grant/Research Support, Shareholder)Merck (Consultant, Grant/Research Support, Shareholder, Honoraria)