COVID‐19 and Anticoagulation for Atrial Fibrillation: An Analysis of US Nationwide Pharmacy Claims Data

Background Adherence to oral anticoagulation (OAC) is critical for stroke prevention in atrial fibrillation. However, the COVID‐19 pandemic may have disrupted access to such therapy. We hypothesized that our analysis of a US nationally representative pharmacy claims database would identify increased incidence of lapses in OAC refills during the COVID‐19 pandemic. Methods and Results We identified individuals with atrial fibrillation prescribed OAC in 2018. We used pharmacy dispensing records to determine the incidence of 7‐day OAC gaps and 15‐day excess supply for each 30‐day interval from January 1, 2019 to July 8, 2020. We constructed interrupted time series analyses to test changes in gaps and supply around the pandemic declaration by the World Health Organization (March 11, 2020), and whether such changes differed by medication (warfarin or direct OAC), prescription payment type, or prescriber specialty. We identified 1 301 074 individuals (47.5% women; 54% age ≥75 years). Immediately following the COVID‐19 pandemic declaration, we observed a 14% decrease in 7‐day OAC gaps and 56% increase in 15‐day excess supply (both P <0.001). The increase in 15‐day excess supply was more marked for direct OAC (69% increase) than warfarin users (35%; P <0.001); Medicare beneficiaries (62%) than those with commercial insurance (43%; P <0.001); and those prescribed OAC by a cardiologist (64%) rather than a primary care provider (48%; P <0.001). Conclusions Our analysis of nationwide claims data demonstrated increased OAC possession after the onset of the COVID‐19 pandemic. Our findings may have been driven by waivers of early refill limits and patients’ tendency to stockpile medications in the first weeks of the pandemic.

Retrospective Database Analysis: Dose Escalation and Adherence in Patients Initiating Biologics for Ulcerative Colitis

Background: Biologic therapies are often used in patients with ulcerative colitis who are non-responsive to conventional treatments. However, non-response or loss of response to biologics often occurs, leading to dose escalation, combination therapy, and/or treatment switching. We investigated real-world treatment patterns of biologic therapies among patients with ulcerative colitis in the USA. Methods: This study analyzed data from the IBM® MarketScan® Commercial and Medicare Supplemental Databases (medical/pharmacy claims for >250 million patients in the USA) to identify patients with ulcerative colitis initiating a biologic therapy (adalimumab, infliximab, golimumab, or vedolizumab) with 12 months of follow-up post-initiation. Key measures were patient baseline characteristics, dose escalation (average maintenance dose >20% higher than label), adherence (proportion of days covered), and ulcerative colitis-related healthcare costs in the 12 months following biologic therapy initiation. Results: Of 2,331 patients included in the study (adalimumab [N=1,291], infliximab [N=810], golimumab [N=127], vedolizumab [N=103]), 28.1% used concomitant immunosuppressant therapy within 12 months post-initiation. Overall, 23.6% (adalimumab), 34.8% (infliximab), 9.9% (golimumab), and 39.2% (vedolizumab) of patients dose escalated within 12 months. Patients who dose escalated incurred $20,106 higher total ulcerative colitis-related healthcare costs over 12 months than those who did not. Adherence (covariate-adjusted proportion of days covered) ranged from 0.63 to 0.73, and 39.3% of patients discontinued within 12 months (median treatment duration=112 days). Conclusion: Dose escalation was common, and incurred higher costs, in patients with ulcerative colitis initiating biologic therapies. Sub-optimal adherence and/or discontinuation within 12 months of initiation occurred frequently, highlighting the challenges in managing these patients.

Unmanaged Pharmacogenomic and Drug Interaction Risk Associations with Hospital Length of Stay among Medicare Advantage Members with COVID-19: A Retrospective Cohort Study

Unmanaged pharmacogenomic and drug interaction risk can lengthen hospitalization and may have influenced the severe health outcomes seen in some COVID-19 patients. To determine if unmanaged pharmacogenomic and drug interaction risks were associated with longer lengths of stay (LOS) among patients hospitalized with COVID-19, we retrospectively reviewed medical and pharmacy claims from 6025 Medicare Advantage members hospitalized with COVID-19. Patients with a moderate or high pharmacogenetic interaction probability (PIP), which indicates the likelihood that testing would identify one or more clinically actionable gene–drug or gene–drug–drug interactions, were hospitalized for 9% (CI: 4–15%; p < 0.001) and 16% longer (CI: 8–24%; p < 0.001), respectively, compared to those with low PIP. Risk adjustment factor (RAF) score, a commonly used measure of disease burden, was not associated with LOS. High PIP was significantly associated with 12–22% longer LOS compared to low PIP in patients with hypertension, hyperlipidemia, diabetes, or chronic obstructive pulmonary disease (COPD). A greater drug–drug interaction risk was associated with 10% longer LOS among patients with two or three chronic conditions. Thus, unmanaged pharmacogenomic risk was associated with longer LOS in these patients and managing this risk has the potential to reduce LOS in severely ill patients, especially those with chronic conditions.

Profile of Pain Medication Use in Hemophilia and Hemarthrosis: An Analysis of a Pharmacy Claims Database

Introduction: Chronic joint pain associated with bleeding disorders (particularly Hemophilia A and Hemophilia B) is well characterized. The most common treatments reported by patients with bleeding disorders include acetaminophen, traditional nonsteroidal anti-inflammatory drugs (tNSAIDs; cyclooxygenase 1/2 inhibitors, COX-1/2), COX-2 selective NSAIDs, and opioids (Witkop, et al. Haemophilia . 2017;23:556). Up to 50% of patients have reported opioid use to manage both acute and chronic pain(Witkop, et al. Haemophilia . 2017;23:556). The aim of this study was to compare and analyze different types of prescription pain medications in patients with a diagnosis of hemophilia A, B, and hemarthrosis using a pharmacy claims database. Methods: A cross-sectional analysis was conducted on a retrospective cohort of patients with bleeding disorders receiving pain medications in the Truven Health MarketScan Commercial Claims and Encounters database, for which IRB approval was not required. Index encounters were reported from April 1, 2017 to March 30, 2018, with one year of follow up. Patients were outpatients, inpatients, or both. Patient-level demographics were not collected. Results: Unique patients totaling 876 received 5,702 prescriptions. Patient diagnosis codes included Hemophilia A (D66), Hemophilia B (D67), and hemarthrosis (M362), each of which contributed 79.2%, 11.9%, and 8.8%, respectively, to the total prescriptions. Outpatient prescriptions comprised 81.0% of total prescriptions. Scheduled prescriptions comprised 70.8% of all prescriptions, 81.7% of inpatient prescriptions, and 68.2% of outpatient prescriptions (see Table). Schedule II drugs comprised 82.6% and 77.3% of all scheduled inpatient and outpatient prescriptions, respectively (see Table). Schedule IV prescriptions were the next most common, followed by schedule III. Prescription NSAIDs were more common in the outpatient than in the inpatient setting (see Table). Among NSAIDs, celecoxib comprised approximately half of the outpatient NSAID prescriptions and 15.1% of all outpatient prescriptions. Discussion: Regardless of setting, schedule II drugs are the most common form of pain management prescription in patients with hemophilia or hemarthrosis. Prescriptions for scheduled medications appear similar to what might be inferred in previous studies of patient reported use (Witkop, et al. Haemophilia . 2017;23:556). Consistent with self-reports (Witkop, et al. Haemophilia . 2017;23:556), hydrocodone or oxycodone with acetaminophen were confirmed to be the most frequently prescribed schedule II opioids. tNSAIDs, such as those reported in this analysis share gastrointestinal (GI) bleeding risk which may be heightened in persons with hemophilia compared with those who have no bleeding disorders. Celecoxib represents approximately 50% of outpatient NSAID prescriptions in this analysis despite data showing its clinically significant GI event risk is similar to both ibuprofen and naproxen (Nissen, et al. N Engl J Med. 2016:2519). Over-the counter acetaminophen is commonly used to treat chronic joint pain in hemophilia (Witkop, et al. Haemophilia. 2017;23:556) presumably to avoid GI bleeding, yet is reported to be less efficacious than celecoxib (Rodriguez-Merchan, et al. Blood Rev. 2018: 116). The broad use of opioids with their attendant risk of misuse, addiction, and diversion; as well as tNSAIDs, with their attendant GI risks, underscores the limited pain management options available for persons with hemophilia. This cross-sectional prescription claims data analysis highlights the need to identify and develop alternate forms of chronic pain medications for this population who have unique unmet needs (Humphries, et al. Haemophilia. 2015:41). Figure 1 Figure 1. Disclosures Helm: Tremeau Pharmaceuticals Inc.: Current Employment, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. Buckner: Genetech: Honoraria; Spark: Honoraria; Sanofi: Honoraria; Bayer: Honoraria; Pfizer: Honoraria; Takeda: Honoraria; American Thrombosis: Membership on an entity's Board of Directors or advisory committees; Hemostasis Network: Membership on an entity's Board of Directors or advisory committees; Novo Nordisk: Honoraria; CSL Behring: Honoraria; Tremeau Pharmaceuticals: Consultancy, Honoraria; uniQure: Consultancy, Honoraria; BioMarin: Consultancy, Honoraria. Macgregor: Tremeau Pharmaceuticals Inc.: Current Employment, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. Boice: Tremeau Pharmaceuticals Inc.: Current Employment, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. Cerasoli: RX Medical Dynamics LLC: Consultancy, Current Employment, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. Khan: Rx Medical Dynamics, LLC: Current Employment. Argoff: Tremeau Pharmaceuticals,Inc: Consultancy.

Decline in prenatal buprenorphine/naloxone fills during the COVID-19 pandemic in the United States

Background and Aims: Pregnancy provides a critical opportunity to engage women with substance use disorder in care. Buprenorphine/naloxone treatment is associated with improved pregnancy and fetal outcomes, but prior to the COVID-19 pandemic, there were multiple barriers to accessing buprenorphine/naloxone during pregnancy. Care disruptions during the pandemic may have further exacerbated these already existing barriers. To quantify these changes, we examined trends in the number of individuals filling prescriptions for prenatal buprenorphine/naloxone prescriptions during the COVID-19 pandemic. Methods: We estimated an interrupted time series model using linked national pharmacy claims and medical claims data from May 2019 to December 2020. We estimated changes in the level and trend in the monthly number of individuals filling prescriptions for prenatal buprenorphine/naloxone during the COVID-19 pandemic. We then stratified our analyses by payer. Results: We identified 2,947 pregnant patients filling buprenorphine/naloxone prescriptions. Before the pandemic, there was positive growth in the monthly number of individuals filling prescriptions for prenatal buprenorphine/naloxone (4.83% (95% confidence interval (CI): 3.40% to 6.26%). During the pandemic, the monthly growth rate in individuals filling prescriptions for prenatal buprenorphine/naloxone declined for both patients on commercial insurance and patients on Medicaid (all payers: -5.53% (95% CI: -7.28% to -3.78%); Medicaid: -7.66% (95% CI: -10.42% to -4.90%); Commercial: -3.59% (95% CI: -5.53% to -1.66%)). Conclusion: The number of pregnant individuals filling buprenorphine/naloxone prescriptions was increasing prior to the pandemic, but this growth has been lost during the pandemic.

Trends in drug poisoning deaths, by sex, in Ireland: a repeated cross-sectional study from 2004 to 2017

ObjectiveTo examine sex differences in age-standardised rates (ASR) of overall and drug-specific drug poisoning deaths in Ireland between 2004 and 2017.DesignRepeated cross-sectional study.SettingDrug poisoning deaths in Ireland.ParticipantsNational Drug-Related Deaths Index and pharmacy claims database (Primary Care Reimbursement Service-General Medical Services) data from 2004 to 2017.Outcome measuresThe primary outcome was trends in drug poisoning death rates by sex. The secondary outcomes were trends in drug poisoning death rates involving (1) any CNS (Central Nervous System) depressants, (2) ≥2 CNS depressants and (3) specific drugs/drug classes (eg, prescription opioids, benzodiazepines, antidepressants, alcohol, cocaine and heroin) by sex. Joinpoint regression was used to examine trends, stratified by sex, in the ASR of drug poisoning deaths (2004–2017), change points over time and average annual percentage changes (AAPCs) with 95% CI.ResultsIncreased ASR for all drug poisoning deaths from 6.86 (95% CI 6.01 to 7.72) per 100 000 in 2004 to 8.08 (95% CI 7.25 to 8.91) per 100 000 in 2017 was mainly driven by increasing deaths among men (AAPC 2.6%, 95% CI 0.2 to 5.1), with no significant change observed among women. Deaths involving ≥2 CNS depressants increased for both men (AAPC 5.6%, 95% CI 2.4 to 8.8) and women (AAPC 4.0%, 95% CI 1.1 to 6.9). Drugs with the highest significant AAPC increases for men were cocaine (7.7%, 95% CI 2.2 to 13.6), benzodiazepines (7.2%, 95% CI 2.9 to 11.6), antidepressants (6.1%, 95% CI 2.4 to 10.0) and prescription opioids (3.5%, 95% CI 1.6 to 5.5). For women, the highest AAPC was for antidepressants (4.2%, 95% CI 0.2 to 8.3), benzodiazepines (3.3%, 95% CI 0.1 to 6.5) and prescription opioids (3.0%, 95% CI 0.7 to 5.3).ConclusionDrugs implicated in drug poisoning deaths vary by sex. Policy response should include prescription monitoring programmes and practical harm reduction information on polydrug use, especially CNS depressant drugs.

Comparison of Two Different Analgesic Prescription Strategies and Healthcare Systems: Slovenia vs. the Netherlands

Background: Prescribing practice of pain medication is changing in the Netherlands; opioids are used more often instead of nonsteroidal anti-inflammatory drugs (NSAIDs), therefore we aimed to compare the use of pain medication with Slovenia which has stringent prescribing rules for strong opioids.Methods: We conducted a cohort study into national prescription databases of the Netherlands and Slovenia covering pharmacy claims between January 1, 2013 and December 31, 2019. In the analysis about 17 million Dutch and 2 million Slovenian residents were included.Findings: The use of opioids and NSAIDs was higher in Slovenia than in the Netherlands. More frequent use of opioids in Slovenia could be almost entirely explained by weak opioids (about 6% of the population), whereas they were prescribed 50% less frequently in the Netherlands. The opioid use has increased by about 20% in the Netherlands (4.85 and 6.00% of the population in 2013 and 2018, respectively), and the majority of this increase could be explained by strong opioids (4.05% in 2018), specifically, by oxycodone whose use increased by more than 2-fold between 2013 and 2019. In comparison, oxycodone was seldomly used in Slovenia (about 0.3% of the population received a prescription in a year).Interpretation: When medication use is controlled by stringent prescribing rules, like for strong opioids in Slovenia, the use is lower as compared to when such rules do not exist.

Adherence to self-administered biologic disease-modifying antirheumatic drugs across health-system specialty pharmacies

Disclaimer In an effort to expedite the publication of articles related to the COVID-19 pandemic, AJHP is posting these manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Purpose Adherence to self-administered biologic disease-modifying antirheumatic drugs (bDMARDs) is necessary for therapeutic benefit. Health-system specialty pharmacies (HSSPs) have reported high adherence rates across several disease states; however, adherence outcomes in rheumatoid arthritis (RA) populations have not yet been established. Methods We performed a multisite retrospective cohort study including patients with RA and 3 or more documented dispenses of bDMARDs from January through December 2018. Pharmacy claims were used to calculate proportion of days covered (PDC). Electronic health records of patients with a PDC of &lt;0.8 were reviewed to identify reasons for gaps in pharmacy claims (true nonadherence or appropriate treatment holds). Outcomes included median PDC across sites, reasons for treatment gaps in patients with a PDC of &lt;0.8, and the impact of adjusting PDC when accounting for appropriate therapy gaps. Results There were 29,994 prescriptions for 3,530 patients across 20 sites. The patient cohort was mostly female (75%), with a median age of 55 years (interquartile range [IQR], 42-63 years). The original(ie, prereview) median PDC was 0.94 (IQR, 0.83-0.99). Upon review, 327 patients had no appropriate treatment gaps identified, 6 patients were excluded due to multiple unquantifiable appropriate gaps, and 420 patients had an adjustment in the PDC denominator due to appropriate treatment gaps (43 instances of days’ supply adjusted based on discordant days’ supply information between prescriptions and physician administration instructions, 11 instances of missing fills added, and 421 instances of clinically appropriate treatment gaps). The final median PDC after accounting for appropriate gaps in therapy was 0.95 (IQR, 0.87-0.99). Conclusion This large, multisite retrospective cohort study was the first to demonstrate adherence rates across several HSSPs and provided novel insights into rates and reasons for appropriate gaps in therapy.