Validation of serostatus of rheumatoid arthritis using ICD-10 codes in administrative claims data.

PURPOSE: To determine the accuracy of International Classification of Diseases- Tenth Revision (ICD-10) diagnosis codes for rheumatoid arthritis (RA) serostatus using a U.S. claims database (Optum Clinformatics Data Mart, Optum) and to compare the results to a previous validation study performed in IBM Marketscan Research Database (sensitivity 73%, positive predictive value, PPV, 84%). METHODS: In Optum (01/01/2016-03/31/2020) linked with laboratory results, we selected RA patients based on ≥2 ICD-10 diagnosis codes for RA (M05 or M06) and at least one dispensing of RA treatments. We included individuals with at least one laboratory result for rheumatoid factor (RF) or anti-cyclic citrullinated peptide (CCP) performed 365 days prior to and including the cohort entry date. An individual was "seropositive" if at least one of the 2 diagnosis codes used to define RA status was M05. "Seronegative" patients were required to have only M06. Secondary analyses were performed using subsets of M05 and M06 diagnosis codes. We calculated the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and kappa of M05 and M06 against the prespecified reference standard laboratory data. RESULTS: We identified 14 490 adult RA patients who had at least 1 RF or anti-CCP result. The number of patients identified for each reference standard definition ranged from 3315 (reference standard definition: high + anti-CCP) to 13 636 (any + RF). PPV for seropositive RA, M05, was 77.1%. The PPV of M06 for seronegative RA was 61.6%. When we applied more restricted definitions of M05 and M06, the PPV for seropositive RA increased to 79.2%. The PPV for seronegative RA also notably increased to 89.5%. CONCLUSION: ICD-10 codes (M05 and M06) can help identify RA serostatus in claims data, but their limitations should be acknowledged. The PPVs for seropositive and seronegative RA found in the Optum database were lower than those found in MarketScan, perhaps related to database variability or differing patient characteristics and clinical practice. When more restricted definitions of M05 and M06 were used, the PPVs for seropositive and seronegative RA improved to 79.2% and 89.5%, respectively.

Secular Trends in the Pharmacologic Treatment of Osteoporosis and Malignancy-Related Bone Disease from 2009 to 2020.

BACKGROUND: New bone-directed therapies, including denosumab, abaloparatide, and romosozumab, emerged during the past decade, and recent trends in use of these therapies are unknown. OBJECTIVE: To examine temporal trends in bone-directed therapies. DESIGN: An open cohort study in a US commercial insurance database, January 2009 to March 2020. PARTICIPANTS/INTERVENTIONS: All-users of bone-directed therapies age >50 years, users with osteoporosis, users with malignancies, and patients with recent (within 180 days) fractures at key osteoporotic sites. MAIN MEASURES: The percentage of each cohort with prescription dispensing or medication administration claims for each bone-directed therapy during each quarter of the study period. KEY RESULTS: We analyzed 15.48 million prescription dispensings or medication administration claims from 1.46 million unique individuals (89% women, mean age 69 years). Among all users of bone-directed therapies, alendronate, and zoledronic acid use increased modestly (49 to 63% and 2 to 4%, respectively, during the study period). In contrast, denosumab use increased rapidly after approval in 2010, overtaking use of all other medications except alendronate by 2017 and reaching 16% of users by March 2020. Similar trends were seen in cohorts of osteoporosis, malignancy, and recent fractures. Importantly, use of any bone-directed therapy after fractures was low and declined from 15 to 8%. CONCLUSIONS: Rates of denosumab use outpaced growth of all other bone-directed therapies over the past decade. Treatment rates after osteoporotic fractures were low and declined over time, highlighting major failings in osteoporosis treatment in the US.

Development and Validation of a Pediatric Comorbidity Index.

Comorbidity scores are widely used to help address confounding bias in nonrandomized studies conducted within health-care databases, but existing scores were developed to predict all-cause mortality in adults and might not be appropriate for use in pediatric studies. We developed and validated a pediatric comorbidity index, using health-care utilization data from the tenth revision of the International Classification of Diseases. Within the MarketScan database of US commercial claims data, pediatric patients (aged ≤18 years) continuously enrolled between October 1, 2015, and September 30, 2017, were identified. Logistic regression was used to predict the 1-year risk of hospitalization based on 27 predefined conditions and empirically identified conditions derived from the most prevalent diagnoses among patients with the outcome. A single numerical index was created by assigning weights to each condition based on its ß coefficient. We conducted internal validation of the index and compared its performance with existing adult scores. The pediatric comorbidity index consisted of 24 conditions and achieved a C statistic of 0.718 (95% confidence interval (CI): 0.714, 0.723). The index outperformed existing adult scores in a pediatric population (C statistics ranging from 0.522 to 0.640). The pediatric comorbidity index provides a summary measure of disease burden and can be used for risk adjustment in epidemiologic studies of pediatric patients.

Effect of Combination Therapy on Adherence Among US Patients Initiating Therapy for Hypertension: a Cohort Study.

BACKGROUND: New trial evidence suggests that many patients may require more aggressive pharmacologic management to achieve lower blood pressure goals. Especially when first initiating anti-hypertensive treatment, it is unknown whether starting patients on multiple medications may be better for long-term adherence and persistence compared with starting one medication. OBJECTIVE: To examine contemporary patterns of anti-hypertensive therapy initiation and compare long-term adherence and persistence among patients initiating fixed-dose combinations and single anti-hypertensive therapies. DESIGN: Retrospective cohort study. PATIENTS: Using claims from a large nationwide insurer, we identified all patients initiating oral hypertension treatment from 2009 to 2013. We categorized patients into three categories based on the number and type of anti-hypertensive medications they initiated: a fixed-dose combination, a multi-pill combination or a single therapy. MAIN MEASURES: The primary outcome was persistence to any anti-hypertensive medication, either the initiated medication or other anti-hypertensive, 12 months after initiation in administrative claims. We also measured adherence to at least one anti-hypertensive in the 12 months after initiation and refilling at least one anti-hypertensive medication as outcomes. Full adherence was defined as having ≥80% of potential days covered with medication. Multivariable modified Poisson regression models were used to examine the association between initiating a fixed-dose combination anti-hypertensive and medication outcomes. KEY RESULTS: Of the 484,493 patients who initiated oral anti-hypertensives, 78,958 patients initiated fixed-dose combinations, 383,269 initiated a single therapy, and 22,266 initiated multi-pill combinations. Patients initiating fixed-dose combinations were 9% more likely to be persistent (relative risk [RR]: 1.09, 95% CI: 1.08-1.10) and 13% more likely to be adherent (RR: 1.13 95% CI: 1.11-1.14) than those who started on a single anti-hypertensive therapy. Refill rates were also slightly higher among fixed-dose combination initiators. CONCLUSIONS: Fixed-dose combination pills appear to enhance adherence and persistence to anti-hypertensive medications among commercially insured patients starting treatment compared with single therapy.

Persistent opioid use following cesarean delivery: patterns and predictors among opioid-naïve women.

BACKGROUND: The incidence of opioid-related death in women has increased 5-fold over the past decade. For many women, their initial opioid exposure will occur in the setting of routine medical care. Approximately 1 in 3 deliveries in the United States is by cesarean, and opioids are commonly prescribed for postsurgical pain management. OBJECTIVE: The objective of this study was to determine the risk that opioid-naïve women prescribed opioids after cesarean delivery will subsequently become consistent prescription opioid users in the year following delivery and to identify predictors for this behavior. STUDY DESIGN: We identified women in a database of commercial insurance beneficiaries who underwent cesarean delivery and who were opioid naïve in the year prior to delivery. To identify persistent users of opioids, we used trajectory models, which group together patients with similar patterns of medication filling during follow-up, based on patterns of opioid dispensing in the year following cesarean delivery. We then constructed a multivariable logistic regression model to identify independent risk factors for membership in the persistent user group. RESULTS: A total of 285 of 80,127 (0.36%, 95% confidence interval, 0.32-0.40), opioid-naïve women became persistent opioid users (identified using trajectory models based on monthly patterns of opioid dispensing) following cesarean delivery. Demographics and baseline comorbidity predicted such use with moderate discrimination (c statistic = 0.73). Significant predictors included a history of cocaine abuse (risk, 7.41%; adjusted odds ratio, 6.11, 95% confidence interval, 1.03-36.31) and other illicit substance abuse (2.36%; adjusted odds ratio, 2.78, 95% confidence interval, 1.12-6.91), tobacco use (1.45%; adjusted odds ratio, 3.04, 95% confidence interval, 2.03-4.55), back pain (0.69%; adjusted odds ratio, 1.74, 95% confidence interval, 1.33-2.29), migraines (0.91%; adjusted odds ratio, 2.14, 95% confidence interval, 1.58-2.90), antidepressant use (1.34%; adjusted odds ratio, 3.19, 95% confidence interval, 2.41-4.23), and benzodiazepine use (1.99%; adjusted odds ratio, 3.72, 95% confidence interval, 2.64-5.26) in the year prior to the cesarean delivery. CONCLUSION: A very small proportion of opioid-naïve women (approximately 1 in 300) become persistent prescription opioid users following cesarean delivery. Preexisting psychiatric comorbidity, certain pain conditions, and substance use/abuse conditions identifiable at the time of initial opioid prescribing were predictors of persistent use.

Availability and utilization of cardiovascular fixed-dose combination drugs in the United States.

BACKGROUND: Solid clinical evidence supports the effectiveness and safety of multiple drugs in treating diabetes, dyslipidemia, and hypertension, and numerous fixed-dose combination products (FDCs) containing such drugs have been developed for patients with more severe forms of these diseases. We sought to evaluate the extent to which utilization of treatment combinations for these conditions corresponded to the availability of FDCs. METHODS: Using claims data from a large national commercial insurer, we identified 2 cohorts of patients: those who filled multiple single-agent drugs to treat diabetes, dyslipidemia, and hypertension in 2012, and those who used FDCs containing these products during the same period. We determined the fill rate of single-agent pairs and FDCs, availability of FDCs for the most frequently filled single-agent and drug class pairs, and the number of conditions treated by frequently filled single-agent pairs and FDCs. RESULTS: During our study period, 848,082 patients filled prescriptions for 3,248 unique single-agent pairs (mean 4.7 per patient, standard deviation [SD] 5.0); and 568,923 patients received prescriptions for 43 unique FDCs (mean 1.1 per patient, SD 0.3). Three (15%) of the 20 most frequently filled single-agent pairs were available as FDCs, whereas 9 (45%) of the 20 most frequently filled drug class pairs were available as FDCs. Nearly all of the frequently filled FDCs had lower fill rates than the most frequently filled single-agent pairs. CONCLUSIONS: Utilization of drug combinations to treat cardiovascular conditions does not correspond well with availability of FDCs containing these agents. A concerted set of strategies should be implemented to streamline the development of useful combination products, including expedited approval pathways and increased investment in formulation studies.

A cohort study of the risk of seizures in a pediatric population treated with atomoxetine or stimulant medications.

PURPOSE: Stimulant medications used for treating attention deficit hyperactivity disorder (ADHD) can be associated with an increased risk of seizures. Atomoxetine is a non-stimulant medication approved for treating ADHD. This retrospective cohort analysis evaluated risk of seizures among pediatric patients naïve to ADHD medication therapy, with exposure to atomoxetine relative to stimulant medications. METHODS: Among members of a large US health plan from 1/1/2003 to 12/31/2006, aged 6-17 years, we identified initiators of atomoxetine or stimulants with no evidence of prior study drug use. We created study cohorts using propensity score matching within 6-month calendar blocks. The outcome was a seizure event in the 6-month follow-up period verified through medical record review. Relative risks (RR) based on current use of each study drug adjusted for baseline covariates were calculated using Poisson regression. We estimated hazard ratios from Cox proportional hazards models for the comparison of atomoxetine to stimulants based on initial cohort assignment. RESULTS: We matched 13,398 initiators of atomoxetine to 13,322 initiators of stimulants. We identified 97 seizure events. After adjustment, current atomoxetine therapy was associated with a non-statistically significant 28% lower risk of seizure compared to current stimulant therapy (RR 0.72; 95%CI 0.37, 1.38). The adjusted RR of seizure with atomoxetine compared to stimulants based on initial cohort assignment was 0.90 (95%CI 0.54, 1.49). CONCLUSIONS: These results do not support an increase in the risk of seizure with atomoxetine therapy. The risk of seizure was not significantly different between pediatric patients taking atomoxetine compared with those taking stimulants.

Real-world patient characteristics and use of disease-modifying anti-rheumatic drugs in patients with rheumatoid arthritis: a cross-national study.

INTRODUCTION: Rheumatoid arthritis (RA) is associated with significant morbidity and economic burden. This study aimed to compare baseline characteristics and patterns of anti-inflammatory drug use and disease-modifying anti-rheumatic drug (DMARD) use among patients with RA in Southern Italy versus the United States. METHOD: Using Caserta Local Health Unit (Italy) and Optum's de-identified Clinformatics® Data Mart (United States) claims databases, patients with ≥ 2 diagnosis codes for RA during the study period (Caserta: 2010-2018; Optum: 2010-2019) were identified. Baseline patient characteristics, as well as proportion of RA patients untreated/treated with NSAIDs/glucocorticoids/conventional DMARDs (csDMARDs)/biological/targeted synthetic DMARDs (b/tsDMARDs) during the first year of follow-up, and the proportion of RA patients with ≥ 1 switch/add-on between the first and the second year of follow-up, were calculated. These analyses were then stratified by age group (< 65; ≥ 65). RESULTS: A total of 9227 RA patients from Caserta and 195,951 from Optum databases were identified (two-thirds were females). During the first year of follow-up, 45.9% RA patients from Optum versus 79.9% from Caserta were exclusively treated with NSAIDs/glucocorticoids; 17.2% versus 11.3% from Optum and Caserta, respectively, were treated with csDMARDs, mostly methotrexate or hydroxychloroquine in both cohorts. Compared to 0.6% of RA patients from Caserta, 3.2% of the Optum cohort received ≥ 1 b/tsDMARD dispensing. Moreover, 61,655 (33.7%) patients from Optum cohort remained untreated compared to 748 (8.3%) patients from the Caserta cohort. The subgroup analyses stratified by age showed that 42,989 (39.8%) of elderly RA patients were untreated compared to 18,666 (24.9%) young adult RA patients in Optum during the first year of follow-up. Moreover, a higher proportion of young adult RA patients was treated with b/tsDMARDs, with and without csDMARDs, compared to elderly RA patients (Optum<65: 6.4%; Optum≥65: 1.0%; P-value < 0.001; Caserta<65: 0.8%; Caserta≥65: 0.1%; P-value < 0.001). Among RA patients untreated during the first year after ID, 41.2% and 48.4% RA patients from Caserta and Optum, respectively, received NSAIDs, glucocorticoids, and cs/b/tsDMARDs within the second year of follow-up. Stratifying the analysis by age groups, 50.6% of untreated young RA patients received study drug dispensing within the second year of follow-up, compared to only 36.7% of elderly RA patients in Optum. Interestingly, more young adult RA patients treated with csDMARDs during the first year after ID received a therapy escalation to b/tsDMARD within the second year after ID in both cohorts, compared to elderly RA patients (Optum<65: 7.8%; Optum≥65: 1.8%; Caserta<65: 3.2%; Caserta≥65: 0.6%). CONCLUSIONS: Most of RA patients, with heterogeneous baseline characteristics in Optum and Caserta cohorts, were treated with anti-inflammatory/csDMARDs rather than bDMARDs/tsDMARDs during the first year post-diagnosis, especially in elderly RA patients, suggesting a need for better understanding and dealing with barriers in the use of these agents for RA patients. Key Points • Substantial heterogeneity in baseline characteristics and access to bDMARD or tsDMARD drugs between RA patients from the United States and Italy exists. • Most of RA patients seem to be treated with anti-inflammatory/csDMARD drugs rather than bDMARD/tsDMARD drugs during the first year post-diagnosis. • RA treatment escalation is less frequent in old RA patients than in young adult RA patients. • An appropriate use of DMARDs should be considered to achieve RA disease remission or low disease activity.

Predictors of Treatment Change Among Patients with Rheumatoid Arthritis Treated with TNF Inhibitors as First-Line Biologic Agent in the USA: A Cohort Study from Longitudinal Electronic Health Records.

BACKGROUND: Previous observational studies utilizing administrative claims data have largely been unable to consider clinical factors that may be related to patterns of drug use among patients with rheumatoid arthritis (RA). OBJECTIVE: To understand predictors of treatment changes following initiation of a tumor necrosis factor inhibitor (TNFi) using nation-wide electronic health record (EHR) data in the USA. METHODS: The Optum Immunology Condition EHR data (01/01/2011-09/30/2019) was used to identify a population of adult patients with RA initiating a TNFi as the first line biologic disease-modifying anti-rheumatic drug (DMARD). The primary outcome was any treatment change during the 1-year post-index period defined as cycling to a different TNFi or switching to non-TNFi biologic or targeted synthetic DMARDs. Secondary outcomes were the individual components of TNFi cycling and switching, examined separately. To identify predictors of DMARD treatment changes, we used a least absolute shrinkage and selection operator (LASSO) regression model. Model c-statistics and odds ratios (ORs, 95% confidence intervals (CIs)) of predictors were reported. RESULTS: We identified 24,871 patients with RA who initiated a TNFi. The mean age was 55.5 (± 13.7) years and 77.2% were female. Among the TNFi initiators, 22.2% experienced TNFi cycling or switching during the 1-year follow-up time. Predictors that are associated with higher likelihood of TNFi cycling or switching included female gender (OR: 1.26, 95% CI: 1.16-1.36) and glucocorticoid use (OR: 1.30, 95% CI: 1.21-1.40). In contrast, inflammatory bowel disease (OR: 0.62, 95% CI: 0.48-0.78), psoriasis (OR: 0.82, 95% CI: 0.70-0.95), recent use of methotrexate (OR: 0.89, 95% CI: 0.81-0.97), and vitamin D intake (OR: 0.92, 95% CI: 0.85-0.99) were negatively associated with TNFi cycling or switch. CONCLUSIONS: Gender, glucocorticoid use, inflammatory bowel disease, psoriasis, and vitamin D intake were identified as significant predictors of TNFi cycling or switching for TNFi initiators in the RA population. Predicting treatment change remains challenging even with large detailed EHR data. This study aimed to identify key determinants of treatment changes among patients with rheumatoid arthritis (RA) initiating a tumor necrosis factor inhibitor (TNFi) as their first-line biologic disease-modifying antirheumatic drug (DMARD) in routine care settings using a US nation-wide longitudinal electronic health record (EHR). Among 24,871 patients with RA who initiated a TNFi, 22.2% experienced TNFi cycling or switching during the 1-year follow-up time. Female patients and those who used glucocorticoids were more likely to experience TNFi cycling or switching, whereas inflammatory bowel disease, psoriasis, recent methotrexate use, and vitamin D intake were negatively associated with the outcome. However, predicting treatment change remains challenging even with larger detailed EHR data potentially due to unmeasured factors such as prescriber's preference or patient's belief in the medication.

Risk of Hospitalization for Serious Infection After Initiation of Ustekinumab or Other Biologics in Patients With Psoriasis or Psoriatic Arthritis.

OBJECTIVE: To compare the risk of serious infections requiring hospitalization in patients with psoriasis (PsO) or psoriatic arthritis (PsA) initiating ustekinumab versus other biologics or apremilast. METHODS: In this multi-database cohort study, we identified patients with PsO/PsA who initiated therapy with adalimumab, apremilast, certolizumab, etanercept, golimumab, ixekizumab, secukinumab, or ustekinumab between 2009 and 2018. The primary outcome measure was hospitalizations due to serious infections, which included bacterial, viral, or opportunistic infections. We estimated hazard ratios (HRs) comparing each study drug to ustekinumab after applying propensity score fine stratification weights for confounding control in each database. Database-specific weighted HRs were combined by meta-analysis. RESULTS: We identified 123,383 patients with PsO/PsA who initiated one of the study drugs. During a total of 117,744 person-years of follow-up, 1,514 serious infections occurred with a crude incidence of 1.29 per 100 person-years. After propensity score fine stratification and weighting, the incidence rates of serious infection among ustekinumab initiators ranged from 0.59 to 0.95 per 100 person-years. Compared with ustekinumab, the combined weighted HRs (95% confidence interval [95% CI]) for serious infections were 1.66 (95% CI 1.34-2.06) for adalimumab, 1.42 (95% CI 1.02-1.96) for apremilast, 1.09 (95% CI 0.68-1.75) for certolizumab, 1.39 (95% CI 1.01-1.90) for etanercept, 1.74 (95% CI 1.00-3.03) for golimumab, 2.92 (95% CI 1.80-4.72) for infliximab, 2.98 (95% CI 1.20-7.41) for ixekizumab, and 1.84 (95% CI 1.24-2.72) for secukinumab. CONCLUSION: Other biologics and apremilast were associated with a 1.4- to 3-times higher risk of hospitalization for serious infections in PsO/PsA patients when compared to ustekinumab; this finding should be considered in the safety profile of these therapies when selecting appropriate treatment regimens in patients with PsO/PsA.

Aprotinin during coronary-artery bypass grafting and risk of death.

BACKGROUND: Aprotinin (Trasylol) is used to mitigate bleeding during coronary-artery bypass grafting (CABG). Accumulating evidence suggests that this practice increases mortality. METHODS: Using electronic administrative records of the Premier Perspective Comparative Database, we studied hospitalized patients with operating-room charges for the use of aprotinin (33,517 patients) or aminocaproic acid (44,682 patients) on the day CABG was performed. We tabulated the numbers of patients with a hospital-discharge status of death and performed three types of analyses: a multivariable logistic-regression analysis (primary analysis); propensity-score matching in the highly selected subcohort of patients who received full amounts of the study drug, who underwent CABG by surgeons who performed 50 or more CABG surgeries during the study period, and for whom information on 10 additional covariates was available because the surgery occurred on hospital day 3 or later; and an instrumental-variable analysis of data from patients whose surgeons showed a strong preference for one of the two study drugs. RESULTS: In all, 1512 of the 33,517 aprotinin recipients (4.5%) and 1101 of the 44,682 aminocaproic acid recipients (2.5%) died. After adjustment for 41 characteristics of patients and hospitals, the estimated risk of death was 64% higher in the aprotinin group than in the aminocaproic acid group (relative risk, 1.64; 95% confidence interval [CI], 1.50 to 1.78). In the first 7 days after surgery, the adjusted relative risk of in-hospital death in the aprotinin group was 1.78 (95% CI, 1.56 to 2.02). The relative risk in a propensity-score-matched analysis was 1.32 (95% CI, 1.08 to 1.63). In the instrumental-variable analysis, the use of aprotinin was found to be associated with an excess risk of death of 1.59 per 100 patients (95% CI, 0.14 to 3.04). Postoperative revascularization and dialysis were more frequent among recipients of aprotinin than among recipients of aminocaproic acid. CONCLUSIONS: Patients who received aprotinin alone on the day of CABG surgery had a higher mortality than patients who received aminocaproic acid alone. Characteristics of neither the patients nor the surgeons explain the difference, which persisted through several approaches to control confounding.

Incidence of hospitalized rhabdomyolysis with statin and fibrate use in an insured US population.

BACKGROUND: The incidence of hospitalized rhabdomyolysis is not well characterized among patients taking statin-fibrate combination therapies. OBJECTIVE: To estimate and compare the rates of hospitalized rhabdomyolysis during periods of exposure to different statins and fibrates. METHODS: We retrospectively identified a cohort of patients who initiated a statin or fibrate between January 1, 1998, and December 31, 2007, using a database of a large US health insurer. Patients were followed for the occurrence of hospitalized rhabdomyolysis, determined by clinical review of medical records. Exposure status during the study period was determined by electronic records of statin and fibrate dispensing. Incidence rates (IRs) and incidence rate ratios (IRRs) for various combinations of fibrate and statin exposure were modeled, using Poisson regression. RESULTS: There were 1,116,805 patients who initiated statin and/or fibrate therapy, with 2.4 million person-years of observation. Seventy cases of hospitalized rhabdomyolysis were confirmed. Adjusted analyses showed a persistent increased risk of rhabdomyolysis with combination therapy, while statin and fibrate therapy alone showed similar, nonsignificant increases in risk. The adjusted IRR for a statin and fenofibrate was 3.26 (95% CI 1.21 to 8.80), while the adjusted IRR for a statin and gemfibrozil was 11.93 (95% CI 3.96 to 35.93) versus statin therapy alone. The individual IRs for statin monotherapy ranged from 0.00 to 3.34 per 100,000 person-years. The number needed to harm was lower for combination statin-gemfibrozil therapy (2753) compared with that for statin therapy alone (454,545). CONCLUSIONS: The incidence of hospitalized rhabdomyolysis is rare, but higher in patients with concomitant statin-fibrate treatment than in patients on statin therapy alone. The rate found in this study is consistent with the known profile of the statin-fibrate treatment option for mixed dyslipidemia.

Patient characteristics associated with use of TNF vs interleukin inhibitors as first-line biologic treatment for psoriatic arthritis.

BACKGROUND: Previous studies have examined treatment patterns among patients who use tumor necrosis factor (TNF) inhibitors for psoriatic arthritis (PsA). However, little data exist for a comparison between the TNF inhibitor treatment pattern and that of newly available biologics such as interleukin (IL)-12/23 or 17 inhibitors in the United States. OBJECTIVES: To (a) examine patient characteristics and their association with initiation of TNF inhibitors vs IL-12/23 or 17 inhibitors among PsA patients and (2) compare treatment persistence of PsA patients who initiated TNF inhibitors vs IL-12/23 or 17 inhibitors as first-line biologic treatment in a real-world setting in the United States. METHODS: Using claims data from MarketScan (2013-2017), we identified a cohort of PsA patients who initiated TNF inhibitors or IL-12/23 or 17 inhibitors. The primary outcome was treatment persistence, defined as continuous use of the index drug at 1 year, regardless of refill gaps. The secondary outcome was treatment persistence with high adherence at 1 year (ie, refill gaps ≤ 30 days). Multivariable logistic regression was used to assess the association between patient characteristics and treatment initiation and persistent use of TNF inhibitors vs IL-12/23 or 17 inhibitors. RESULTS: We identified 3,180 TNF inhibitor initiators and 214 IL-12/23 or 17 inhibitor initiators. Initiators of IL-12/23 or 17 inhibitors had more comorbidities than TNF inhibitor initiators. The proportion of patients with treatment persistence was 53.0% in TNF inhibitor initiators and 53.7% in IL-12/23 or 17 inhibitor initiators; 37.1% of TNF inhibitor users and 24.8% of IL-12/23 or 17 inhibitor users were treatment persistent with high adherence. There was no difference in 1-year treatment persistence between the 2 groups after adjusting for baseline characteristics (adjusted odds ratio [aOR] for TNF inhibitors vs IL-12/23 or 17 inhibitors: 0.86, 95% CI = 0.63-1.15). However, use of TNF inhibitors was associated with a greater treatment persistence with high adherence compared with use of IL-12/23 or 17 inhibitors (aOR = 1.61, 95% CI = 1.15-2.26). CONCLUSIONS: PsA patients who initiated an IL 12/23 or 17 inhibitor had a greater comorbidity burden compared with those who initiated TNF inhibitors. Treatment persistence was similar between the 2 groups, whereas medication adherence was higher with TNF inhibitors than with IL 12/23 or 17 inhibitors during the first year of treatment. DISCLOSURES: This study was funded by an investigator-initiated research grant from Pfizer, Inc (grant number: WI235988). The content is solely the responsibility of the authors. The sponsor was given the opportunity to make nonbinding comments on a draft of the manuscript. Publication of the manuscript was not contingent on approval by the sponsor. Kim has received research grants to the Brigham and Women's Hospital from Roche, AbbVie, and Bristol-Myers Squibb for unrelated topics. Merola is a consultant and/or investigator for BMS, AbbVie, Dermavant, Lilly, Novartis, Janssen, UCB, Sun Pharma, and Pfizer. Jin, Chen, Lee, and Landon have nothing to disclose.

Safety and Effectiveness of Dabigatran and Other Direct Oral Anticoagulants Compared With Warfarin in Patients With Atrial Fibrillation.

The study objective was to evaluate the safety and effectiveness of dabigatran and other direct oral anticoagulants (DOACs) compared with warfarin among patients with nonvalvular atrial fibrillation using a prospective monitoring program. We implemented a cohort design with propensity score matching to compare initiators of DOACs and warfarin between 2010 and 2015 in two US healthcare databases. Proportional hazards regression was used to estimate hazard ratios (HRs) for stroke and major bleeding. The final analyses included 29,448 dabigatran, 35,520 rivaroxaban, and 19,588 apixaban initiators, matched to warfarin initiators. The pooled HR for stroke was 0.75 (95% confidence interval (CI) 0.58-0.98) for dabigatran, 0.77 (95% CI 0.61-0.98) for rivaroxaban, and 0.69 (95% CI 0.50-0.96) for apixaban, consistent with findings from randomized trials. For major hemorrhage, the HRs were 0.72 (95% CI 0.65-0.80), 1.02 (95% CI 0.94-1.12), and 0.56 (95% CI 0.49-0.64), respectively, showing a decreased risk of major bleeding for both dabigatran and apixaban, as compared with trial evidence.

Association of Opioid Overdose With Opioid Prescriptions to Family Members.

IMPORTANCE: Prescription opioid misuse is a public health problem that leads to overdose. Although existing interventions focus on limiting prescribing to patients at high risk, individuals may still access prescription opioids dispensed to family members. OBJECTIVE: To determine whether opioid prescriptions to family members were associated with overdose for individuals who themselves did not have an opioid prescription. DESIGN, SETTING, AND PARTICIPANTS: We conducted a 1:4 matched case-control study using health care utilization data from 2004 through 2015 from a large US commercial insurance company. Eligible individuals were required to have at least 12 months of continuous enrollment and 1 or more family members in the database. Individuals who experienced overdose were identified by their first opioid overdose after the baseline period and matched to control participants by time in the database, calendar time, age, sex, and number of individuals in the family unit. Both groups were restricted to individuals with no prior opioid dispensing of their own. Data analysis was conducted from January 2018 to August 2018. EXPOSURES: Any prior opioid dispensing to a family member, total morphine milligram equivalents dispensed to family members, and the type of opioid product dispensed. MAIN OUTCOMES AND MEASURES: Individual odds of opioid overdose resulting in an emergency department visit or hospitalization were the primary end point. The primary analysis evaluated the odds of overdose among individuals whose family members had been dispensed an opioid. Sensitivity analyses examined the odds stratified by age and timing relative to the dispensing of opioids to family members. RESULTS: A total of 2303 individuals who experienced opioid overdose and 9212 matched control individuals were identified. The mean (SD) age was 23.2 (18.1) years; 1158 affected individuals and 4632 control individuals (50.3%) were female. The mean (SD) time in the database before an overdose case was 3.2 (3.3) years. Prior opioid dispensing to family members was associated with individual overdose (odds ratio [OR], 2.89 [95% CI, 2.59-3.23]). There was a significant dose-response association between increasing amounts of opioids dispensed to family members and odds of overdose (>0-<50 morphine milligram equivalents per day: OR, 2.71 [95% CI, 2.42-3.03]; 50-<90 morphine milligram equivalents per day: OR, 7.80 [95% CI, 3.63-16.78]; ≥90 morphine milligram equivalents per day: OR, 15.08 [95% CI, 8.66-26.27]). CONCLUSIONS AND RELEVANCE: In this analysis, opioid prescriptions to family members were associated with overdose among individuals who do not receive opioid prescriptions. Interventions may focus on expanding access to opioid antagonists, locking prescription opioids in the home, and providing greater patient education to limit fatal overdose among family members.

Claims Data Studies of Direct Oral Anticoagulants Can Achieve Balance in Important Clinical Parameters Only Observable in Electronic Health Records.

Claims databases provide information on the effects of direct oral anticoagulants (DOACs) as used in routine care but may not contain important data on clinical characteristics, which may be captured in electronic health records (EHRs). Within a US claims database, we identified patients initiating a DOAC or warfarin between October 2010 and December 2014. Propensity score (PS) matching, 1:1, was used to balance 78 claims-defined baseline characteristics. We evaluated whether balance was achieved in patient characteristics immeasurable in the claims data study by evaluating the balance in clinical information (using absolute standardized differences (aSDs)) from linked EHR data. From a claims data cohort study of 140,187 patients, 5,935 (4.2%) were linked to EHR data. After PS matching, almost all EHR-defined patient characteristics were well balanced (aSD < 0.1). A new user active comparator design with 1:1 PS matching on many patient characteristics improved balance on clinical risk factors observed in EHRs but not in claims data.

Coronary heart disease outcomes in patients receiving antidiabetic agents in the PharMetrics database 2000-2007.

BACKGROUND: The risk of coronary heart disease (CHD) in users of antidiabetic agents must be quantified to permit reasoned therapeutic choices. OBJECTIVES: To assess the risk of myocardial infarction (MI) and coronary revascularization (CR), in diabetic patients who began rosiglitazone, pioglitazone, metformin, or sulfonylureas. METHODS: We conducted a retrospective cohort study of MI and CR in the PharMetrics database. We performed head-to-head comparisons using propensity-score-stratified Cox proportional hazards models, examining risks both on-treatment and during total follow-up before regimen switches. RESULTS: For the combined outcome (MI and CR), the crude rates per 1000 person years were 9 on monotherapy, 13 on dual therapy, and 21 on therapies combined with insulin. In the absence of insulin, regimens containing thiazolidinediones (TZDs) tended toward lower risk than comparable regimens containing sulfonylureas and higher risk than those containing metformin. The summary hazard ratio for rosiglitazone versus pioglitazone was 1.04 (95%CI: 0.94-1.14) for total follow-up and 1.05 (0.92-1.19) for on-treatment time. For MI, the hazard ratios were 1.07 (0.89-1.27) for total follow-up and 1.21 (0.95-1.54) for on-treatment time. CONCLUSIONS: The present data indicate that the risk of CHD in patients using TZDs appears to lie between the risks associated with sulfonylureas and metformin. Neither the risk of MI and CR together nor the risk of MI alone was significantly different between rosiglitazone and pioglitazone. A nonsignificant observed excess risk of 21% for MI during on-treatment time will require combination with the results of other studies to provide a reliable assessment.

Changes in Outpatient Use of Antibiotics by Adults in the United States, 2006-2015.

INTRODUCTION: Numerous initiatives over the past decade have targeted the problem of antibiotic overuse in the US; however, the cumulative impact of such initiatives upon recent patterns of use is not known. OBJECTIVES: The aims of this study were to (1) describe general trends in outpatient antibiotic use among adults over the period 2006-2015; and (2) identify rapid shifts in use during this time period as potential indicators for key events. METHODS: This was an observational study set in the ambulatory setting. Patients ≥ 18 years of age were selected from the Optum Clinformatics Datamart™, a commercial insurance claims database. The outcome measures of interest were prescriptions filled/1000 enrolled individuals, by year or quarter. We used linear regression to identify trends in use over multiple years, and change-point regression to identify rapid shifts in use within individual years. RESULTS: From 2006 to 2015, antibiotic use declined significantly, decreasing by 12% for adults younger than 65 years of age (913-807 prescriptions/1000 individuals, p = 0.0001) and by 5% for adults ≥ 65 years of age (991-943 prescriptions/1000 individuals, p = 0.018). With change-point regression, we identified a number of rapid shifts in the use of specific antibiotic classes, such as downward shifts in the use of quinolones and macrolides during the second quarter of 2008 and 2013, respectively. CONCLUSIONS: Over the period 2006-2015 outpatient use of antibiotics decreased substantially among adults. Rapid shifts in use occurring in 2008 and 2013 may reflect the presence of key drivers of change, such as abrupt changes in access to care or perceived antibiotic safety.

Comparative effectiveness and safety of thalidomide and lenalidomide in patients with multiple myeloma in the United States of America: A population-based cohort study.

BACKGROUND: The comparative effectiveness of thalidomide and lenalidomide in the treatment of multiple myeloma has not been established. We conducted an observational cohort study of multiple myeloma patients receiving either thalidomide or lenalidomide in routine care in the United States of America to assess their comparative survival and rates of peripheral neuropathy. METHODS: Myeloma patients were identified and followed using administrative claims data from a large national health insurance provider (UnitedHealth). Patients were eligible if they initiated treatment with either lenalidomide or thalidomide between 2004 and 2013. Propensity score stratified Cox proportional hazards regression was used to estimate the hazard ratios (HR) and 95% confidence intervals (CI) for death and new-onset peripheral neuropathy (defined by International Classification of Disease, Ninth Revision codes or a new prescription intended to treat neuropathic pain). FINDINGS: Our cohort included 1264 myeloma patients who initiated either thalidomide or lenalidomide. Among 406 new users of thalidomide, 142 (35%) developed peripheral neuropathy during a mean 499 person-days of follow-up. Among 858 new users of lenalidomide, 244 (29%) developed neuropathy during 587 person-days. Compared with thalidomide initiators, lenalidomide initiators had a reduced risk of peripheral neuropathy (HR 0.71, 95% CI: 0.56-0.92). We found no difference in rates of death (HR 1.00, 95% CI: 0.71-1.41). INTERPRETATION: Our results agree with the findings of recently published trials suggesting that thalidomide and lenalidomide are equivalent with respect to survival outcomes but different with respect to neurotoxicity in clinical practice settings.