Publications by Year: 2021

Paik JM, Zhuo M, York C, Tsacogianis T, Kim SC, Desai RJ. Medication Burden and Prescribing Patterns in Patients on Hemodialysis in the USA, 2013-2017. Am J Nephrol 2021;52(12):919-928.Abstract
INTRODUCTION: The medication burden of patients with end-stage renal disease (ESRD) on hemodialysis, a patient population with a high comorbidity burden and complex care requirements, is among the highest of any of the chronic diseases. The goal of this study was to describe the medication burden and prescribing patterns in a contemporary cohort of patients with ESRD on hemodialysis in the USA. METHODS: We used the United States Renal Data System database from January 1, 2013, and December 31, 2017, to quantify the medication burden of patients with ESRD on hemodialysis aged ≥18 years. We calculated the average number of prescription medications per patient during each respective year (January-December), number of medications within classes, including potentially harmful medications, and trends in the number of medications and classes over the 5-year study period. RESULTS: We included a total of 163,228 to 176,133 patients from 2013 to 2017. The overall medication burden decreased slightly, from a mean of 7.4 (SD 3.8) medications in 2013 to 6.8 (SD 3.6) medications in 2017. Prescribing of potentially harmful medications decreased over time (74.0% with at least one harmful medication class in 2013-68.5% in 2017). In particular, the prescribing of non-benzodiazepine hypnotics, benzodiazepines, and opioids decreased from 2013 to 2017 (12.2%-6.3%, 23.4%-19.3%, and 60.0%-53.4%, respectively). This trend was consistent across subgroups of age, sex, race, and low-income subsidy status. CONCLUSIONS: Patients with ESRD on hemodialysis continued to have a high overall medication burden, with a slight reduction over time accompanied by a decrease in prescribing of several classes of harmful medications. Continued emphasis on assessment of appropriateness of high medication burden in patients with ESRD is needed to avoid exposure to potentially harmful or futile medications in this patient population.
Bateman BT, Hernandez-Diaz S, Straub L, Zhu Y, Gray KJ, Desai RJ, Mogun H, Gautam N, Huybrechts KF. Association of first trimester prescription opioid use with congenital malformations in the offspring: population based cohort study. BMJ 2021;372:n102.Abstract
OBJECTIVE: To evaluate the risk of first trimester exposure to prescription opioids for major congenital malformations, previously reported to be associated with such exposure. DESIGN: Population based cohort study. SETTING: Nationwide sample of publicly and commercially insured pregnant women linked to their liveborn infants, nested in the Medicaid Analytic eXtract (MAX, 2000-14) and the MarketScan Research Database (MarketScan, 2003-15). PARTICIPANTS: 1 602 580 publicly insured (MAX) and 1 177 676 commercially insured (MarketScan) pregnant women with eligibility from at least three months before pregnancy to one month after delivery; infants with eligibility for at least three months after birth. INTERVENTIONS: Use of prescription opioids was ascertained by requiring two or more dispensations of any opioid during the first trimester. MAIN OUTCOMES MEASURES: Major malformations overall, cardiac malformations overall, ventricular septal defect, secundum atrial septal defect/patent foramen ovale, neural tube defect, clubfoot, and oral cleft, defined based on validated algorithms. Propensity score stratification was used to adjust for potential confounders and/or proxies for confounders. Estimates from each database were combined using meta-analysis. RESULTS: 70 447 (4.4%) of 1 602 580 publicly insured and 12 454 (1.1%) of 1 177 676 commercially insured pregnant women had two or more dispensations of an opioid during the first trimester. Absolute risk of malformations overall was 41.0 (95% confidence interval 39.5 to 42.5) per 1000 pregnancies exposed to opioids versus 32.0 (31.7 to 32.3) per 1000 unexposed pregnancies in the MAX cohort, and 42.6 (39.0 to 46.1) and 37.3 (37.0 to 37.7) per 1000, respectively, in the MarketScan cohort. Pooled unadjusted relative risk estimates were raised for all outcomes but shifted substantially toward the null after adjustment; for malformations overall (relative risk 1.06, 95% confidence interval 1.02 to 1.10), cardiovascular malformations (1.09, 1.00 to 1.18), ventricular septal defect (1.07, 0.95 to 1.21), atrial septal defect/patent foramen ovale (1.04, 0.88 to 1.24), neural tube defect (0.82, 0.53 to 1.27), and clubfoot (1.06, 0.88 to 1.28). The relative risk for oral clefts remained raised after adjustment (1.21, 0.98 to 1.50), with a higher risk of cleft palate (1.62, 1.23 to 2.14). CONCLUSIONS: Prescription opioids used in early pregnancy are not associated with a substantial increase in risk for most of the malformation types considered, although a small increase in the risk of oral clefts associated with their use is possible.
Straub L, Huybrechts KF, Hernandez-Diaz S, Zhu Y, Vine S, Desai RJ, Gray KJ, Bateman BT. Chronic prescription opioid use in pregnancy in the United States. Pharmacoepidemiol Drug Saf 2021;30(4):504-513.Abstract
PURPOSE: To evaluate chronic opioid utilization patterns during pregnancy using nationwide data from publicly and commercially insured women. METHODS: Pregnancy cohorts were identified using data from the Medicaid Analytic eXtract 2008-2014 and the IBM Health MarketScan Research Database 2008-2015. Opioid dispensing was evaluated using claims from filled prescriptions. Two different definitions of chronic opioid use were employed: ≥90 days' supply and ≥180 days' supply of prescription opioids during pregnancy. Patient characteristics were assessed and variations in the prevalence of chronic opioid therapy were described by geographic region and over time. RESULTS: 1.50% of 975 169 Medicaid-insured and 0.32% of 1 037 599 commercially insured beneficiaries filled opioid prescriptions for ≥90 days' supply; 0.78% (Medicaid) and 0.17% (commercially insured) filled prescriptions for ≥180 days' supply. Prevalence approximately doubled in Medicaid beneficiaries during the study period, while it remained relatively stable for commercial insurance beneficiaries. The most commonly prescribed opioid for chronic therapy was hydrocodone, followed by oxycodone and tramadol. Indications commonly associated with chronic use were back/neck pain, abdominal/pelvic pain, musculoskeletal pain and migraine/headache. Substantial regional variation was observed, with several states reporting a frequency of ≥90 days' supply in excess of 3% in Medicaid-insured patients. CONCLUSIONS: Despite growing awareness of the risks associated with chronic opioid use and emphasis on improving opioid prescription patterns, prevalence of chronic use in pregnancy among publicly insured women nearly doubled from 2008-2014 and was 5-fold more common when compared to commercially insured women. Findings call for the development of guidelines on chronic pain management during pregnancy.
Pawar A, Desai RJ, He M, Bessette L, Kim SC. Comparative Risk of Nonvertebral Fractures Among Patients With Rheumatoid Arthritis Treated With Biologic or Targeted Synthetic Disease-Modifying Antirheumatic Drugs. ACR Open Rheumatol 2021;Abstract
OBJECTIVE: The objective of this study was to compare the incidence rate of nonvertebral osteoporotic fractures (NVFs) in patients with rheumatoid arthritis (RA) initiating one of the nine biologic or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs). METHODS: We analyzed claims data from Optum (2008 to March 2019), Medicare, and MarketScan (2008-2017) to identify adults with RA who newly initiated b/tsDMARDs. Adalimumab was the most frequently used and was thus selected as a reference. The primary outcome was a composite of incident NVFs, including hip, humerus, pelvis, and wrist fractures, based on validated algorithms. We adjusted for greater than 70 potential confounders in each database through propensity score-based inverse probability treatment weighting. Follow-up time started the day after cohort entry until the first occurrence of one of the following: outcome, treatment discontinuation, switching, nursing home admission, death, disenrollment, or end of study period. For each drug comparison, weighted Cox proportional hazards models estimated the hazard ratios (HRs) and 95% confidence intervals (CIs). Secondary analyses were conducted in patients switching from a tumor necrosis factor inhibitor to a different b/tsDMARD. RESULTS: A total of 134,693 b/tsDMARD initiators were identified across three databases. The adjusted HRs showed similar risk of composite NVFs in all b/tsDMARD exposures compared with adalimumab: abatacept, HR 1.03 (95% CI 0.82-1.30); certolizumab, HR 1.08 (95% CI 0.79-1.49); etanercept, HR 1.12 (95% CI 0.89-1.40); golimumab, HR 0.91 (95% CI 0.59-1.39); infliximab, HR 1.03 (95% CI 0.84-1.28); rituximab, HR 1.07 (95% CI 0.74-1.55); tocilizumab, HR 1.24 (95% CI 0.71-2.17); and tofacitinib, HR 1.07 (95% CI 0.69-1.64). Secondary analyses showed similar results. CONCLUSION: This multidatabase cohort study found no differences in the risk of NVFs across individual b/tsDMARDs for RA, which provides reassurance to physicians prescribing b/tsDMARDs, especially to patients at high risk of developing NVFs.
Rome BN, Feldman WB, Desai RJ, Kesselheim AS. Correlation Between Changes in Brand-Name Drug Prices and Patient Out-of-Pocket Costs. JAMA Netw Open 2021;4(5):e218816.Abstract
Importance: List prices set by manufacturers for brand-name prescription drugs in the US have been increasing faster than inflation, although confidential manufacturer rebates offset some of these increases. Most commercially insured patients pay at least some out-of-pocket costs for prescription drugs, and higher patient spending is associated with lower adherence and worse health outcomes. Objective: To examine whether price changes for brand-name drugs are correlated with changes in patient out-of-pocket spending and whether this association varies by insurance benefit design. Design, Setting, and Participants: A cohort study of 79 brand-name drugs with available pricing data from January 2015 to December 2017 was conducted, with data obtained from a national commercial insurance claims database. Exposures: Change in the list prices set by manufacturers and estimated net prices after rebates among non-Medicaid payers. Main Outcomes and Measures: Change in median out-of-pocket spending among all patients and stratified by insurance pharmacy benefit design, including high-deductible insurance plans and plans with any amount of deductibles or coinsurance. Results: Among 79 drugs, median increases were 16.7% (interquartile range [IQR], 13.6%-21.1%) for list prices, 5.4% (IQR, -3.9% to 11.7%) for net prices, and 3.5% (IQR, 1.4%-9.1%) for out-of-pocket spending from 2015 to 2017. Changes in list prices were correlated with changes in net prices (r = 0.34; P = .002). Overall, changes in out-of-pocket spending were not correlated with changes in list prices (r = 0.14; P = .22) or net prices (r = 0.04; P = .71). Among 53.7% of patients who paid any drug deductible or coinsurance, median out-of-pocket spending increased by 15.0%, and changes were moderately correlated with changes in list prices (r = 0.38; P = .001) but not net prices (r = 0.06; P = .62). Conclusions and Relevance: Some commercially insured patients who pay only prescription drug copayments appear to be insulated from increases in drug prices. However, more than half of patients pay deductibles or coinsurance and may experience substantial increases in out-of-pocket spending when drug prices increase. Among these patients, there was no evidence that manufacturer rebates to insurers are associated with patients' out-of-pocket spending. Policies to rein in unregulated annual increases in list prices for brand-name drugs may have important consequences for patient out-of-pocket spending.
Gopalakrishnan C, Desai RJ, Franklin JM, Jin Y, Lii J, Solomon DH, Katz JN, Lee YC, Franklin PD, Kim SC. Development of a Medicare Claims-Based Model to Predict Persistent High-Dose Opioid Use After Total Knee Replacement. Arthritis Care Res (Hoboken) 2021;Abstract
OBJECTIVE: To develop a claims-based model to predict persistent high-dose opioid use amongst patients undergoing total knee replacement (TKR). METHODS: Using Medicare claims (2010-2014), we identified patients ≥65 years who underwent TKR with no history of high-dose opioid use (>25 mean morphine equivalents (MME)/day) in the year prior. We used group-based trajectory modeling to identify distinct opioid use patterns. The primary outcome was persistent high-dose opioid use in the year after TKR. We split the data into training (2010-2013) and test (2014) sets and used logistic regression with least absolute shrinkage and selection operator (LASSO) regularization utilizing a total of 83 pre-operative patient characteristics as candidate predictors. A reduced model with ten pre-specified variables which included demographics, opioid use and medication history was also considered. RESULTS: The final study cohort included 142,089 patients who underwent TKR. The group-based trajectory model identified 4 distinct trajectories of opioid use (Group 1- short-term, low-dose, Group 2- moderate-duration, low-dose, Group 3- moderate-duration, high-dose, and Group 4-persistent high-dose). The model predicting persistent high-dose opioid use achieved high discrimination (area under the receiver operating characteristic curve (AUC) of 0.85; 95% CI, 0.84-0.86)) in the test set. The reduced model with ten predictors performed equally well (AUC=0.84; 95% CI, 0.84-0.85). CONCLUSIONS: In this cohort of older patients, 10.6% became persistent high dose (mean=22.4 MME/day) opioid users after TKR. Our model with 10 readily available clinical factors may help identify patients at high risk of future adverse outcomes from persistent opioid use after TKR.
Desai RJ, Patorno E, Vaduganathan M, Mahesri M, Chin K, Levin R, Solomon SD, Schneeweiss S. Effectiveness of angiotensin-neprilysin inhibitor treatment versus renin-angiotensin system blockade in older adults with heart failure in clinical care. Heart 2021;Abstract
OBJECTIVE: To evaluate the effectiveness of angiotensin receptor-neprilysin inhibitor (ARNI) versus renin-angiotensin system (RAS) blockade alone in older adults with heart failure with reduced ejection fraction (HFrEF). METHODS: We conducted a cohort study using US Medicare fee-for-service claims data (2014-2017). Patients with HFrEF ≥65 years were identified in two cohorts: (1) initiators of ARNI or RAS blockade alone (ACE inhibitor, ACEI; or angiotensin receptor blocker, ARB) and (2) switchers from an ACEI to either ARNI or ARB. HR with 95% CI from Cox proportional hazard regression and 1-year restricted mean survival time (RMST) difference with 95% CI were calculated for a composite outcome of time to first worsening heart failure event or all-cause mortality after adjustment for 71 pre-exposure characteristics through propensity score fine-stratification weighting. All analyses of initiator and switcher cohorts were conducted separately and then combined using fixed effects. RESULTS: 51 208 patients with a mean age of 76 years were included, with 16 193 in the ARNI group. Adjusted HRs comparing ARNI with RAS blockade alone were 0.92 (95% CI 0.84 to 1.00) among initiators and 0.79 (95% CI 0.74 to 0.85) among switchers, with a combined estimate of 0.84 (95% CI 0.80 to 0.89). Adjusted 1-year RMST difference (95% CI) was 4 days in the initiator cohort (-1 to 9) and 12 days (8 to 17) in the switcher cohort, resulting in a pooled estimate of 9 days (6 to 12) favouring ARNI. CONCLUSION: ARNI treatment was associated with lower risk of a composite effectiveness endpoint compared with RAS blockade alone in older adults with HFrEF.
Mahesri M, Chin K, Kumar A, Barve A, Studer R, Lahoz R, Desai RJ. External validation of a claims-based model to predict left ventricular ejection fraction class in patients with heart failure. PLoS One 2021;16(6):e0252903.Abstract
BACKGROUND: Ejection fraction (EF) is an important prognostic factor in heart failure (HF), but administrative claims databases lack information on EF. We previously developed a model to predict EF class from Medicare claims. Here, we evaluated the performance of this model in an external validation sample of commercial insurance enrollees. METHODS: Truven MarketScan claims linked to electronic medical records (EMR) data (IBM Explorys) containing EF measurements were used to identify a cohort of US patients with HF between 01-01-2012 and 10-31-2019. By applying the previously developed model, patients were classified into HF with reduced EF (HFrEF) or preserved EF (HFpEF). EF values recorded in EMR data were used to define gold-standard HFpEF (LVEF ≥45%) and HFrEF (LVEF<45%). Model performance was reported in terms of overall accuracy, positive predicted values (PPV), and sensitivity for HFrEF and HFpEF. RESULTS: A total of 7,001 HF patients with an average age of 71 years were identified, 1,700 (24.3%) of whom had HFrEF. An overall accuracy of 0.81 (95% CI: 0.80-0.82) was seen in this external validation sample. For HFpEF, the model had sensitivity of 0.96 (95%CI, 0.95-0.97) and PPV of 0.81 (95% CI, 0.81-0.82); while for HFrEF, the sensitivity was 0.32 (95%CI, 0.30-0.34) and PPV was 0.73 (95%CI, 0.69-0.76). These results were consistent with what was previously published in US Medicare claims data. CONCLUSIONS: The successful validation of the Medicare claims-based model provides evidence that this model may be used to identify patient subgroups with specific EF class in commercial claims databases as well.
Jin Y, Lee H, Lee MP, Landon JE, Merola JF, Desai RJ, Kim SC. Risk of Hospitalized Serious Infection After Initiating Ustekinumab or Other Biologics for Psoriasis or Psoriatic Arthritis. Arthritis Care Res (Hoboken) 2021;Abstract
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 adalimumab, apremilast, certolizumab, etanercept, golimumab, ixekizumab, secukinumab, or ustekinumab between 2009 and 2018. The primary outcome was hospitalized serious infections including bacterial, viral, or opportunistic infections. We estimated hazard ratios (HR) comparing each study drugs with 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 HR (95% confidence interval) for serious infections was 1.66 (1.34-2.06) for adalimumab, 1.42 (1.02-1.96) for apremilast, 1.09 (0.68-1.75) for certolizumab, 1.39 (1.01-1.90) for etanercept, 1.74 (1.00-3.03) for golimumab, 2.92 (1.80-4.72) for infliximab, 2.98 (1.20-7.41) for ixekizumab, and 1.84 (1.24-2.72) for secukinumab. CONCLUSIONS: Other biologics and apremilast were associated with 1.4- to 3-times higher risk of hospitalized serious infections in PsO/PsA patients when compared with ustekinumab; such safety profile should be considered when selecting appropriate treatment regimens in patients with PsO/PsA.
Desai RJ, Pawar A, Khosrow-Khavar F, Weinblatt ME, Kim SC. Risk of venous thromboembolism associated with tofacitinib in patients with rheumatoid arthritis: a population-based cohort study. Rheumatology (Oxford) 2021;61(1):121-130.Abstract
OBJECTIVE: To evaluate the risk of venous thromboembolism (VTE) with tofacitinib compared with TNFis in patients with RA. METHODS: RA patients initiating tofacitinib or a TNFi without use of any biologic or tofacitinib any time prior were identified from IBM 'MarketScan' (2012-18), Medicare (parts A, B and D, 2012-17) or 'Optum' Clinformatics (2012-19) and followed until treatment discontinuation, treatment switch, insurance disenrollment or administrative censoring. The primary outcome, VTE, was identified using inpatient claims for pulmonary embolism or deep vein thrombosis. A Cox proportional hazards model provided hazard ratio (HR) and 95% CIs after accounting for confounding through propensity score fine-stratification weighting. HRs were pooled across databases with inverse variance meta-analytic method. RESULTS: A total of 42 201, 25 078 and 20 374 RA patients were identified from MarketScan, Medicare and Optum, respectively, of whom 7.1, 7.1 and 9.7% were tofacitinib initiators. The crude incidence rates per 100 person-years (95% CI) were 0.42 (0.20-0.77) and 0.35 (0.29-0.42) in MarketScan, 1.18 (0.68-1.92) and 0.83 (0.71-0.97) in Medicare, and 0.19 (0.04-0.57) and 0.34 (0.26-0.44) in Optum for tofacitinib and TNFis, respectively. Propensity score-weighted HRs showed no significant differences in the risk of VTE between tofacitinib and TNFis in any database with a pooled HR (95% CI) of 1.13 (0.77-1.65). CONCLUSION: Overall, VTE occurred infrequently (<1 per 100) in a total of 87 653 RA patients initiating tofacitinib or a TNFi. We observed no evidence for an increased risk of VTE for tofacitinib vs TNFis in RA patients.
Pawar A, Desai RJ, Liu J, Kim E, Kim SC. Updated Assessment of Cardiovascular Risk in Older Patients With Gout Initiating Febuxostat Versus Allopurinol. J Am Heart Assoc 2021;10(7):e020045.
Mahesri M, Schneeweiss S, Globe D, Mutebi A, Bohn R, Achebe M, Levin R, Desai RJ. Clinical outcomes following bone marrow transplantation in patients with sickle cell disease: A cohort study of US Medicaid enrollees. Eur J Haematol 2021;106(2):273-280.Abstract
OBJECTIVES: Bone marrow transplantation (BMT) is currently the only curative therapy available for patients with sickle cell disease (SCD), but clinical outcomes in routine care are not well understood. We describe the rates of vaso-occlusive crises (VOCs), transplant complications, and mortality in SCD patients after BMT. METHODS: A cohort study of SCD patients who underwent BMT was designed using US Medicaid claims data (2000-2013). RESULTS: A total of 204 SCD patients undergoing BMT were identified with a mean (SD) age of 10.6 (7.3) years, with 52.9% male and 67.6% African American. The overall VOC rate was 0.99 per person-year (95% CI: 0.91-1.07) over a median follow-up time of 2.1 years (IQR: 0.8-4.3 years). A total of 138 (67.6%) remained free of VOCs. The mortality rate was 1.7 (95% CI: 0.9-3.1) per 100 person-years, transplant-related complications occurred among 113 (55.4%) patients with an incidence rate of 38.2 (95% CI: 31.7-45.9) per 100 person-years, while 47 (23%) patients had GvHD with an incidence rate of 8.0 (95% CI: 6.0-10.7) per 100 person-years. CONCLUSION: Two thirds of the BMT recipients remained VOC-free over 2 years of follow-up, but transplant-related complications, including GvHD occurred with high frequency. This highlights a continuing unmet need for alternative curative interventions in SCD.
Franklin JM, Patorno E, Desai RJ, Glynn RJ, Martin D, Quinto K, Pawar A, Bessette LG, Lee H, Garry EM, Gautam N, Schneeweiss S. Emulating Randomized Clinical Trials With Nonrandomized Real-World Evidence Studies: First Results From the RCT DUPLICATE Initiative. Circulation 2021;143(10):1002-1013.Abstract
BACKGROUND: Regulators are evaluating the use of noninterventional real-world evidence (RWE) studies to assess the effectiveness of medical products. The RCT DUPLICATE initiative (Randomized, Controlled Trials Duplicated Using Prospective Longitudinal Insurance Claims: Applying Techniques of Epidemiology) uses a structured process to design RWE studies emulating randomized, controlled trials (RCTs) and compare results. We report findings of the first 10 trial emulations, evaluating cardiovascular outcomes of antidiabetic or antiplatelet medications. METHODS: We selected 3 active-controlled and 7 placebo-controlled RCTs for replication. Using patient-level claims data from US commercial and Medicare payers, we implemented inclusion and exclusion criteria, selected primary end points, and comparator populations to emulate those of each corresponding RCT. Within the trial-mimicking populations, we conducted propensity score matching to control for >120 preexposure confounders. All study measures were prospectively defined and protocols registered before hazard ratios and 95% CIs were computed. Success criteria for the primary analysis were prespecified for each replication. RESULTS: Despite attempts to emulate RCT design as closely as possible, differences between the RCT and corresponding RWE study populations remained. The regulatory conclusions were equivalent in 6 of 10. The RWE emulations achieved a hazard ratio estimate that was within the 95% CI from the corresponding RCT in 8 of 10 studies. In 9 of 10, either the regulatory or estimate agreement success criteria were fulfilled. The largest differences in effect estimates were found for RCTs where second-generation sulfonylureas were used as a proxy for placebo regarding cardiovascular effects. Nine of 10 replications had a standardized difference between effect estimates of <2, which suggests differences within expected random variation. CONCLUSIONS: Agreement between RCT and RWE findings varies depending on which agreement metric is used. Interim findings indicate that selection of active comparator therapies with similar indications and use patterns enhances the validity of RWE. Even in the context of active comparators, concordance between RCT and RWE findings is not guaranteed, partially because trials are not emulated exactly. More trial emulations are needed to understand how often and in what contexts RWE findings match RCTs. Registration: URL:; Unique identifiers: NCT03936049, NCT04215523, NCT04215536, NCT03936010, NCT03936036, NCT03936062, NCT03936023, NCT03648424, NCT04237935, NCT04237922.
Desai RJ, Mahesri M, Chin K, Levin R, Lahoz R, Studer R, Vaduganathan M, Patorno E. Epidemiologic Characterization of Heart Failure with Reduced or Preserved Ejection Fraction Populations Identified Using Medicare Claims. Am J Med 2021;134(4):e241-e251.Abstract
BACKGROUND: Administrative claims do not contain ejection fraction information for heart failure patients. We recently developed and validated a claims-based model to predict ejection fraction subtype. METHODS: Heart failure patients aged 65 years or above from US Medicare fee-for-service claims were identified using diagnoses recorded after a 6-month baseline period of continuous enrollment, which was used to identify predictors and to apply the claims-based model to distinguish heart failure with reduced or preserved ejection fraction (HFrEF or HFpEF). Patients were followed for the composite outcome of time to first worsening heart failure event (heart failure hospitalization or outpatient intravenous diuretic treatment) or all-cause mortality. RESULTS: A total of 3,134,414 heart failure patients with an average age of 79 years were identified, of which 200,950 (6.4%) were classified as HFrEF. Among those classified as HFrEF, men comprised a larger proportion (68% vs 41%) and the average age was lower (76 vs 79 years) compared with HFpEF. History of myocardial infarction was more common in HFrEF (32% vs 13%), while hypertension was more common in HFpEF (71% vs 77%). One-year cumulative incidence of the composite endpoint was 42.6% for HFrEF and 36.9% for HFpEF. One-year all-cause mortality incidence was similar between the groups (27.4% for HFrEF and 26.4% for HFpEF), however, cardiovascular mortality was higher for HFrEF (15.6% vs 11.3%), whereas noncardiovascular mortality was higher for HFpEF (11.8% vs 15.1%). CONCLUSION: We replicated well-documented differences in key patient characteristics and cause-specific outcomes between HFrEF and HFpEF in populations identified based on the application of a claims-based model.
Huybrechts KF, Bateman BT, Zhu Y, Straub L, Mogun H, Kim SC, Desai RJ, Hernandez-Diaz S. Hydroxychloroquine early in pregnancy and risk of birth defects. Am J Obstet Gynecol 2021;224(3):290.e1-290.e22.Abstract
BACKGROUND: Hydroxychloroquine is generally considered safe in pregnancy for the treatment of rheumatic conditions, but studies have been too small to evaluate teratogenicity. Quantifying the risk of congenital malformations associated with early pregnancy exposure to hydroxychloroquine is important in both the context of its ongoing use for rheumatological disorders and its potential future use for coronavirus disease 2019 prophylaxis, for which a number of clinical trials are ongoing despite initial trials for coronavirus disease 2019 treatment having been negative. OBJECTIVE: The study objective was to evaluate the risk of major congenital malformations associated with exposure to hydroxychloroquine during the first trimester of pregnancy, the period of organogenesis. STUDY DESIGN: We performed a population-based cohort study nested in the Medicaid Analytic eXtract (MAX, 2000-2014) and IBM MarketScan Research Database (MarketScan, 2003-2015). The source cohort included 2045 hydroxychloroquine-exposed pregnancies and 3,198,589 pregnancies not exposed to hydroxychloroquine continuously enrolled in their respective insurance program for 3 months before the last menstrual period through at least 1 month after delivery; infants were enrolled for at least 3 months after birth. We compared the risk of congenital malformations in women using hydroxychloroquine during the first trimester of pregnancy with that of those not using hydroxychloroquine, restricting the cohort to women with rheumatic disorders and using propensity score matching to control for indication, demographics, medical comorbidities, and concomitant medications (1867 hydroxychloroquine-exposed pregnancies and 19,080 pregnancies not exposed to hydroxychloroquine). The outcomes considered included major congenital malformations diagnosed during the first 90 days after delivery and specific malformation types for which there were at least 5 exposed events: oral cleft, cardiac, respiratory, gastrointestinal, genital, urinary, musculoskeletal, and limb defects. RESULTS: Overall, 54.8 per 1000 infants exposed to hydroxychloroquine were born with a major congenital malformation versus 35.3 per 1000 unexposed infants, corresponding to an unadjusted relative risk of 1.51 (95% confidence interval, 1.27-1.81). Patient characteristics were balanced in the restricted, propensity score-matched cohort. The adjusted relative risk was 1.26 (95% confidence interval, 1.04-1.54); it was 1.33 (95% confidence interval, 1.08-1.65) for a daily dose of ≥400 mg and 0.95 (95% confidence interval, 0.60-1.50) for a daily dose of <400 mg. Among the different malformation groups considered, more substantial increases in the risk of oral clefts, respiratory anomalies, and urinary defects were observed, although estimates were imprecise. No pattern of malformation was identified. CONCLUSION: Our findings suggest a small increase in the risk of malformations associated with first-trimester hydroxychloroquine use. For most patients with autoimmune rheumatic disorders, the benefits of treatment during pregnancy will likely outweigh this risk. If hydroxychloroquine were shown to be effective for coronavirus disease 2019 prophylaxis in ongoing trials, the risk of malformations would need to be balanced against such benefits.
Zhu Y, Huybrechts KF, Desai RJ, Franklin JM, Hernandez-Diaz S, Krumme A, Straub L, Neuman M, Wunsch H, Levin R, Mogun H, Bateman BT. Prescription opioid use after vaginal delivery and subsequent persistent opioid use and misuse. Am J Obstet Gynecol MFM 2021;3(2):100304.Abstract
BACKGROUND: Vaginal delivery is the most common reason for hospitalization in the United States, and approximately 30% of women fill an opioid prescription after vaginal delivery, making this a common source of opioid exposure in women of reproductive age. OBJECTIVE: This study aimed to evaluate the effect of receiving an opioid prescription after vaginal delivery on the risk of subsequent persistent opioid use, opioid use disorders, and overdose. STUDY DESIGN: We assembled a nationwide cohort of Medicaid beneficiaries in the United States using the Medicaid Analytic eXtract 2009-2014. The study population included pregnant women who delivered vaginally between 2009 and 2013 and were continuously enrolled in Medicaid from 90 days before to 365 days after delivery. We identified patients with prescription opioids dispensed within 7 days of the date of vaginal delivery. Persistent opioid use was defined as ≥10 opioid fills or >120 days' supply dispensed from 30 to 365 days after delivery. Incident diagnoses of opioid use disorder and overdose were ascertained during the same interval. Propensity score matching was used to control for potential confounding factors. RESULTS: Among 459,829 pregnancies ending in vaginal deliveries, 140,807 (30.62%) had an opioid dispensed within 7 days of delivery. Overall, 5770 of 140,807 (4.10%) women who filled an opioid prescription vs 2668 of 319,022 (0.84%) unexposed women had subsequent persistent opioid use, with an unadjusted relative risk of 4.90 (95% confidence interval, 4.68-5.13) and a risk difference of 3.26% (95% confidence interval, 3.15-3.37). After propensity score matching, the risk remained higher among pregnancies with an opioid prescription dispensed, with a relative risk of 2.57 (95% confidence interval, 2.43-2.72) and a risk difference of 2.21% (95% confidence interval, 2.08-2.33), which was confirmed by the instrumental variable analysis with a risk difference of 1.31% (95% confidence interval, 1.06-1.56) by using the rate of opioid prescribing at the delivery facility in a given geographic region as the instrument. The adjusted relative risk of newly diagnosed opioid use disorder and overdose was 1.48 (95% confidence interval, 1.40-1.57) and 1.92 (95% confidence interval, 1.20-3.09), respectively. CONCLUSION: Opioid dispensing following vaginal delivery is associated with future persistent opioid use and misuse, independent of confounding factors. Opioid prescriptions to women after vaginal delivery should be avoided, except in rare circumstances.
Kim SC, Neogi T, Kim E, Lii J, Desai RJ. Trends in Utilization of Urate-Lowering Therapies Following the US Food and Drug Administration's Boxed Warning on Febuxostat. Arthritis Rheumatol 2021;73(3):542-543.