Tramadol utilization among patients with higher risk of adverse drug events: A claims analysis of commercially insured and Medicare Advantage members.

OBJECTIVE: To assess prescribing of tramadol among patients with contraindications and higher risks of adverse events in a large population of commercially insured and Medicare Advantage members. DESIGN: We performed a cross-sectional analysis evaluating tramadol utilization in patients with higher risk of adverse outcomes. SETTING: This study utilized 2016-2017 data from the Optum Clinformatics Data Mart. PATIENTS AND PARTICIPANTS: Patients with at least one tramadol prescription without a cancer or sickle cell diagnosis during the study period. MAIN OUTCOME MEASURES: We first determined if tramadol was prescribed among patients with contraindications or risk factors for adverse outcomes. We then determined if patient demographic or clinical factors were associated with the use of tramadol in these higher-risk scenarios using multivariable logistic regression models. RESULTS: Among patients with at least one prescription for tramadol, 19.66 percent (99 percent CI: 19.57-19.75) concurrently received an interacting cytochrome P450 isoenzyme medication, 19.24 percent (99 percent CI: 19.15-19.33) concurrently received a serotonergic medication, and 7.93 percent (99 percent CI: 7.88-8.00) concurrently received a benzodiazepine. Additionally, 1.59 percent (99 percent CI: 1.56-1.61) of patients who received tramadol also had a seizure disorder, while 0.55 percent (99 percent CI: 0.53-0.56) of patients were under the age of 18. Overall, nearly one in three patients (31.17 percent) received tramadol in the presence of at least one of these risks (99 percent CI: 31.06-31.27). CONCLUSION: Almost one in three patients prescribed tramadol had a clinically significant drug interaction or contraindication for use, suggesting that prescribers often disregard these concerns. Real-world studies are needed to better understand the likelihood of harms associated with the use of tramadol in these contexts.

Real-world utilization of top-down and step-up therapy and initial costs in Crohn disease.

BACKGROUND: Medication treatment strategies for Crohn disease (CD) include step-up (SU) therapy, beginning with oral anti-inflammatory agents, and top-down (TD) therapy, beginning with biologics or immunomodulators. The real-world utilization and short-term medical costs associated with these treatment strategies are not well described. OBJECTIVE: To examine the prevalence of TD therapy use over time and compare the first-year direct medical expenditures among patients initiating CD medication treatment with SU and TD therapy in a real-world setting. METHODS: We conducted a retrospective cohort study of Optum Clinformatics Data Mart examining adult patients with CD newly initiated on medication therapy from 2010 to 2018. Included patients had a CD-indicated medication dispensed within 60 days after their initial CD diagnosis, were continuously enrolled in the health plan throughout the study period, and did not have comorbidities treated with a biologic also indicated for CD. A generalized linear model was used to quantify the differences in adjusted mean first-year CD-specific, direct nonpharmacy medical costs between users of TD and SU therapy. RESULTS: We identified 3,157 patients newly initiating medication therapy for CD (2,392 [75.8%] patients treated with SU therapy and 765 [24.2%] treated with TD therapy). The use of TD therapy over the study period increased from 17% in 2011 to 31% in 2017. TD therapy was also associated with a 149.8% ($1,230) higher adjusted average per-patient first-year CD-direct nonpharmacy medical cost compared with SU therapy (adjusted ratio of cost for TD compared with SU [2.498, 95% CI = 2.12-2.95]). CONCLUSIONS: In patients newly initiating medication therapy for CD, TD therapy use increased between 2010 and 2017 and was associated with higher first-year nonpharmacy medical expenditure. These findings align with the strategy of initiating TD therapy in patients with a higher disease burden. Further research is needed to determine long-term overall health care costs and clinical outcomes associated with SU and TD strategies in a real-world setting. DISCLOSURES: Dr Caffrey received research funding from Gilead, Merck, Pfizer, and Shionogi and is a speaker for Merck. The views expressed are those of the author and do not necessarily reflect the position or policy of the US Department of Veterans Affairs. Material is based on work supported, in part, by the Office of Research and Development.

Initial Patterns of Prescription Opioid Supply and Risk of Mortality Among Insured Adults in the United States.

OBJECTIVE: To examine the association between initial patterns of prescription opioid supply (POS) and risk of all-cause mortality among an insured opioid-naïve patient population in the United States (US). METHODS: This retrospective observational cohort study used de-identified, administrative health care claims data from a large national insurer (Optum Clinformatics Data Mart) from 2010 to 2015. Participants included insured, cancer-free adults prescribed opioid analgesics. Prescription opioids received during the first 6 months of therapy were used to categorize initial patterns of POS as daily or nondaily. Cox regression was used to estimate the association of initial patterns of POS with all-cause mortality within one year of follow-up, adjusting for baseline covariates to control for confounding. RESULTS: A total of 4,054,417 patients were included, of which 2.75% had incident daily POS; 54.8% were female; median age was 50 years; mean Charlson comorbidity index (CCI) was 0.21 (standard deviation = 0.77); and mean daily morphine milligram equivalent was 34.61 (95% confidence intervals: 34.59, 34.63). There were 2068 more deaths per 100,000 person-years among patients who were prescribed opioids daily than nondaily. After adjusting for baseline covariates, the hazard of all-cause mortality among patients with incident daily POS was nearly twice that among those prescribed nondaily (hazard ratio [HR] = 1.94; 95% confidence intervals: 1.84, 2.04). CONCLUSIONS: Among insured adult patients with noncancer pain, incident chronic POS was associated with a significantly increased risk of all-cause mortality over at most 1 year of follow-up. Because these results may be susceptible to bias, more research is needed to establish causality.

Concurrent Utilization of Prescription Opioids and Non-opioid Controlled Substances: Rhode Island Prescription Drug Monitoring Program, 2018.

OBJECTIVE: To estimate the prevalence of concurrent prescription opioid and non-opioid controlled substance use in Rhode Island (RI). METHODS: We conducted a cross sectional observational study using data from the RI Prescription Drug Monitoring Program on controlled substance prescriptions dispensed in 2018. We estimated the prevalence of concurrent use of other prescribed controlled substances among adults who received at least one opioid prescription. RESULTS: In 2018, 142,692 RI adult residents received at least one opioid prescription, of whom 25.1% (99% confidence interval [CI]: 24.8-25.4) were concurrently prescribed at least one other controlled substance, including benzodiazepines (17.0%, 99% CI: 16.8-17.3), medications for insomnia (4.0%, 99% CI: 3.9-4.2), and stimulants (3.8%, 99% CI: 3.6-3.9). CONCLUSION: The concurrent use of prescription opioids and other prescribed controlled substances is common. Our findings suggest an urgent need to implement focused initiatives to address controlled substance polypharmacy to reduce the risk of overdose.

Association between polypharmacy and health-related quality of life among cancer survivors in the United States.

PURPOSE: Polypharmacy (PP) is present in many cancer survivors and may lead to lower health-related quality of life (HRQoL). The study's objective was to evaluate the association between PP and HRQoL among cancer survivors in the US. METHODS: A cross-sectional analysis of the Medical Expenditure Panel Survey (MEPS) was conducted. Our analytic sample included all adult patients with cancer, during even years 2008-2014. PP was defined as reported use of five or more unique therapeutic classes of prescription medications. The MEPS measured HRQoL using the Short Form 12-Item Health Survey Version 2 (SF-12v2) physical component summary (PCS) and mental component summary (MCS) scores. Ordinary least squares regressions were used to assess associations between PP and HRQoL controlling for demographic, socioeconomic, and clinical factors. RESULTS: PP was prevalent among 44.4% of 10.1 million cancer survivors per calendar year (on average) for years 2008, 2010, 2012, and 2014. The mean adjusted PCS score for cancer survivors with PP was 35.8 points, which was significantly lower compared with cancer survivors without PP (39.5) by 3.7 points (p value < .0001). Conversely, the mean adjusted MCS scores were not significantly lower in cancer survivors with PP compared with cancer survivors without PP (44.9 versus 45.4, p value = 0.3145). CONCLUSIONS: PP was prevalent in 44.4% of cancer survivors and was associated with significantly poorer physical HRQoL than reported in their counterparts without PP. IMPLICATIONS FOR CANCER SURVIVORS: PP should be examined closely among cancer survivors because of increased association with poorer physical HRQoL.

Real-World Direct Health Care Costs Associated with Psychotropic Polypharmacy Among Adults with Common Cancer Types in the United States.

BACKGROUND: Psychotropic polypharmacy is not uncommon among cancer patients and may contribute to the increased direct health care cost burden in this population. OBJECTIVE: To estimate average direct health care costs in the year following cancer diagnosis among cancer patients receiving psychotropic polypharmacy compared with those without psychotropic polypharmacy, using a multivariable analysis framework. METHODS: A retrospective cross-sectional study was conducted among patients aged 18 years and older diagnosed with the most commonly occurring cancers (breast, prostate, lung, and colorectal) in the United States during 2011-2012 using the deidentified Optum Clinformatics Data Mart commercial claims database. Psychotropic polypharmacy was defined as concurrent use of 2 or more psychotropic medications for at least 90 days. Direct health care costs in the year following cancer diagnosis were estimated as total medical payments made by the health plans and were derived from claims files. A generalized linear regression model with log-link function and gamma distribution was used to model average direct health care costs, controlling for baseline patient demographic and clinical covariates. RESULTS: Average annual direct health care costs for cancer patients with psychotropic polypharmacy ($53,497; SD $72,590) were higher than those without psychotropic polypharmacy ($38,255; SD $59,844), with an unadjusted average cost difference of $15,242 (P < 0.0001). In the adjusted regression model, the average difference in costs shrunk to $5,888 but remained notable. When examined by type of cancer, average direct health care costs for all cancer patients with psychotropic polypharmacy were significantly higher than those for patients without psychotropic polypharmacy, except for colorectal cancer patients. CONCLUSIONS: Overall health care costs were higher among cancer patients with psychotropic polypharmacy compared with those without psychotropic polypharmacy. Our findings support the need for future research to better understand the benefits and risks of psychotropic polypharmacy, given its potential to cause adverse health outcomes and avoidable health care utilization and costs for this vulnerable patient population. DISCLOSURES: This study was funded by the American Association of Colleges of Pharmacy (AACP) New Investigator Award mechanism, which was received by Vyas. Aroke was partially supported by the AACP grant for conducting data analysis of the study. Kogut is partially supported by Institutional Development Award Number U54GM115677 from the National Institute of General Medical Sciences of the National Institutes of Health, which funds Advance Clinical and Translational Research (Advance-CTR). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health and the AACP. The authors report no conflicts of interest. An abstract of this study was presented as a poster at the American Association of Colleges of Pharmacy Annual Meeting on July 22, 2018, in Boston, MA.

Prevalence of Psychotropic Polypharmacy and Associated Healthcare Resource Utilization during Initial Phase of Care among Adults with Cancer in USA.

BACKGROUND: The use of psychotropic medications is not uncommon among patients with newly diagnosed cancer. However, the impact of psychotropic polypharmacy on healthcare utilization during the initial phase of cancer care is largely unknown. METHODS: We used a claims database to identify adults with incident breast, prostate, lung, and colorectal cancers diagnosed during 2011-12. Psychotropic polypharmacy was defined as concurrent use of two or more psychotropic medication classes for at least 90 days. A multivariable logistic regression was performed to identify significant predictors of psychotropic polypharmacy. Multivariable Poisson and negative binomial regressions were used to assess the associations between psychotropic polypharmacy and healthcare utilization. RESULTS: Among 5604 patients included in the study, 52.6% had breast cancer, 30.6% had prostate cancer, 11.4% had colorectal cancer, and 5.5% had lung cancer. During the year following incident cancer diagnosis, psychotropic polypharmacy was reported in 7.4% of patients, with the highest prevalence among patients with lung cancer (14.4%). Compared with patients without psychotropic polypharmacy during the initial phase of care, patients with newly diagnosed cancer with psychotropic polypharmacy had a 30% higher rate of physician office visits, an 18% higher rate of hospitalization, and a 30% higher rate of outpatient visits. The rate of emergency room visits was similar between the two groups. CONCLUSION: Psychotropic polypharmacy during the initial phase of cancer care was associated with significantly increased healthcare resource utilization, and the proportion of patients receiving psychotropic polypharmacy differed by type of cancer. IMPACT: Findings emphasize the importance of evidence-based psychotropic prescribing and close surveillance of events causing increased healthcare utilization among patients with cancer receiving psychotropic polypharmacy.

Decreased persistence to cholinesterase inhibitor therapy with concomitant use of drugs that can impair cognition.

STUDY OBJECTIVES: To assess persistence with cholinesterase inhibitor therapy 6 months after the start of treatment, and to determine whether the likelihood of persistence is associated with the coprescription of drugs that can impair cognition. DESIGN: Retrospective cohort study. SETTING: Community (home residence) or long-term care facility. PATIENTS: A total of 1183 patients enrolled in the Rhode Island Medicaid program, aged 45 years or older, who were dispensed a cholinesterase inhibitor from January 1, 2000-June 30, 2002. MEASUREMENTS AND MAIN RESULTS: Patients were considered persistent with treatment if they filled at least five prescriptions for a 1-month supply of the same cholinesterase inhibitor, without an extended gap in days between refills. We compared rates of persistence among patients receiving and those not receiving drugs that can impair cognition. Covariates assessed were patient age, sex, race, and care setting. Approximately one in four patients discontinued cholinesterase inhibitor therapy within 6 months. Patients aged 85 years or older were more persistent than younger patients (77% vs 71%, p<0.05). Caucasian patients were more likely to be persistent than non-Caucasian patients (74% vs 52%, p<0.001). Patients living in the community were less likely to persist than those residing in long-term care facilities (58% vs 76%, p<0.001). After adjusting for race and care setting, patients who were prescribed drugs that can impair cognition were more likely not to have persisted with cholinesterase inhibitor therapy at 6 months than those who did not receive such drugs (odds ratio 1.56, 95% confidence interval 1.13-2.16). CONCLUSION: A substantial percentage of patients who began receiving cholinesterase inhibitor therapy had discontinued the therapy within 6 months. Many patients also received prescriptions for agents that can impair cognition. Our findings indicated a modest but statistically significant increase in likelihood of treatment discontinuation among patients who also received prescriptions for drugs that can impair cognition. Iatrogenic causes of dementia are important to recognize and address so that therapies for enhancing cognition can be fully effective.