Opioid Prescribing and Outcomes in Patients With Sickle Cell Disease Post-2016 CDC Guideline.

Importance: Although the intention of the 2016 US Centers for Disease Control and Prevention (CDC) Guideline for Prescribing Opioids for Chronic Pain was not to limit pain treatment for patients with sickle cell disease (SCD), clinicians and patients have recognized the possibility that the guideline may have altered outcomes for this population. However, the outcomes of the 2016 guideline for this patient population are unknown. Objective: To examine changes in opioid prescribing patterns and health outcomes among patients with SCD before and after the release of the 2016 CDC guideline. Design, Setting, and Participants: This retrospective cohort study conducted interrupted time series analysis of claims data from the Merative MarketScan Commercial Database from January 1, 2011, to December 31, 2019. In this population-based study in the US, individuals with SCD who were at least 1 year of age, had no cancer diagnosis, and had pharmacy coverage for the month of measurement were included. The data were analyzed from January 2021 to November 2023. Exposure: The CDC Guideline for Prescribing Opioids for Chronic Pain released in March 2016. Main Outcomes and Measures: The main variables measured in this study included the practice of opioid prescribing among patients with SCD (ie, rate of opioid prescriptions dispensed, mean number of days supplied, mean total morphine milligram equivalents [MME] per patient, and mean daily MME per opioid prescription) and pain-related health outcomes (rates of emergency department visits related to vaso-occlusive crises [VOC] and hospitalizations related to VOC). Results: The cohort included 14 979 patients with SCD (mean [SD] age, 25.9 [16.9] years; 8520 [56.9%] female). Compared with the preguideline trends, the following changes were observed after the guideline was released: significant decreases in the coefficient for change in slope of the opioid dispensing rate (-0.29 [95% CI, -0.39 to -0.20] prescriptions per 100 person-month; P < .001), the number of days supplied per prescription (-0.05 [95% CI, -0.06 to -0.04] days per prescription-month; P < .001), and opioid dosage (-141.0 [95% CI, -219.5 to -62.5] MME per person-month; P = .001; -10.1 [95% CI, -14.6 to -5.6] MME/prescription-month; P < .001). Conversely, a significant increase in VOC-related hospitalizations occurred after the guideline release (0.16 [95% CI, 0.07-0.25] hospitalizations per 100 person-month; P = .001). These changes were observed to a greater extent among adult patients, but pediatric patients experienced similar changes in several measures, even though the guideline focused exclusively on adult patients. Conclusions and Relevance: This retrospective cohort study showed that the 2016 CDC guideline may have had unintended negative outcomes on the patient population living with SCD.

Impact of adherence to hydroxyurea on health outcomes among patients with sickle cell disease.

Although new pharmaceutical therapy options have recently become available, hydroxyurea is still the most commonly used and affordable treatment option for sickle cell disease (SCD). This study aimed to update the evidence on hydroxyurea adherence and its association with clinical and economic outcomes among individuals with SCD. This retrospective study used Texas Medicaid claims data from 09/2011-08/2016. Individuals were included if they had ≥1 inpatient or ≥2 outpatient SCD diagnoses, had ≥1 hydroxyurea prescription, were 2-63 years of age, and were continuously enrolled in Texas Medicaid between 6 months before and 1 year after the first hydroxyurea prescription fill date (index date). Hydroxyurea adherence (Medication Possession Ratio; MPR), vaso-occlusive crisis (VOC)-related outcomes, healthcare utilization and expenditures (SCD-related and all-cause) during the 1 year following the index date were measured. Bivariate and multivariable analyses were used to address the study objectives. Among 1035 included individuals (age: 18.8 ± 12.5 years, female: 52.1%), 20.9% were adherent to hydroxyurea (defined as MPR≥0.8). After adjustment for demographic and clinical characteristics, compared to being non-adherent, adhering to hydroxyurea was significantly associated with: a lower risk (Odds Ratio [OR] = 0.480, p = .0007) and hazard rate (Hazard Ratio [HR] = 0.748, p = .0005) of a VOC event, fewer VOC events (Incidence Rate Ratio [IRR] = 0.767, p = .0009), fewer VOC-related hospital days (IRR = 0.593, p = .0003), fewer all-cause and SCD-related hospitalizations (IRR = 0.712, p = .0008; IRR = 0.707, p = .0008, respectively) and emergency department visits (IRR = 0.768, p = .0037; IRR = 0.746, p = .0041, respectively), and lower SCD-related total healthcare expenditures (IRR = 0.796, p = .0266). Efforts to increase adherence to hydroxyurea could improve clinical and economic outcomes among individuals with SCD.

The association between hydroxyurea adherence and opioid utilization among Texas Medicaid enrollees with sickle cell disease.

BACKGROUND: Individuals with sickle cell disease (SCD) suffer from recurrent catastrophic pain crises that are often managed by opioid analgesics. Being adherent to hydroxyurea has been associated with decreased health care resource use for pain; however, evidence of its association with opioid use is limited. OBJECTIVE: To determine if adherence to hydroxyurea is associated with opioid use among patients with SCD. METHODS: This retrospective study used Texas Medicaid data from September 1, 2011, to August 31, 2016 (study period). The index date was the date of hydroxyurea initiation. Patients who were aged 2-63 years at the index date, had ≥ 1 inpatient or ≥ 2 outpatient SCD diagnoses during the study period, had ≥ 1 hydroxyurea prescription during the identification period (September 1, 2011-August 31, 2015), had no diagnosis of other indications for hydroxyurea during the study period, and were continuously enrolled for at least 12 months after the index date were included. Hydroxyurea adherence was measured using medication possession ratio (MPR). The study outcomes (measured 1-year post-index) were (a) opioid use; (b) number of opioid prescriptions; (c) strong opioid use (morphine, hydromorphone, fentanyl, and methadone); (d) number of strong opioid prescriptions; (e) high-dose opioid use (≥ 50 mg morphine milligram equivalent [MME]); and (f) days supply for opioid prescriptions. Covariates included demographic (age and gender) and clinical (vaso-occlusive crisis [VOC], avascular necrosis, iron overload, acute chest syndrome, and blood transfusion) characteristics. Descriptive, bivariate (chi-square and Wilcoxon-Mann-Whitney tests), multiple logistic regression, and negative binomial regression analyses were performed. RESULTS: 1,146 patients (18.3 [12.3] years) met the inclusion criteria. Of these, 19.6% were adherent to hydroxyurea (defined as MPR ≥ 80%) and mean (SD) MPR was 48.3% (29.7%). In the 1 year following hydroxyurea initiation, 923 (80.5%) patients had ≥ 1 opioid prescription with 7.6 (9.4) opioid prescriptions per patient, while 259 (22.6%) patients had ≥ 1 strong opioid prescription with 1.5 (4.4) strong opioid prescriptions per patient. Average (SD) opioid dose was 41.7 (74.3) mg MME, and 27.1% had high daily MME doses (≥ 50 mg MME). Average (SD) opioid days supply was 83.1 (112.2) days. After adjusting for covariates, compared with being nonadherent, being adherent to hydroxyurea was associated with a 50.5% decreased risk of having strong opioids (OR = 0.495, 95% CI = 0.278-0.879, P = 0.0165). Additionally, SCD-related complications (VOC, avascular necrosis, and iron overload) and older age were significant factors associated with opioid use and higher MME. Post hoc analyses showed that being adherent to hydroxyurea was significantly associated with lower probabilities of experiencing SCD-related complications. CONCLUSIONS: Results showed that patients with SCD are moderately adherent to hydroxyurea. Being adherent to hydroxyurea was found to be associated with a lower risk of receiving a prescription for strong opioids. Findings suggest that close monitoring and interventions to improve adherence may help mitigate strong opioid use among these patients. DISCLOSURES: This research did not receive any specific funding. Barner and Kang report grants from Novartis Pharmaceuticals, unrelated to this work. A part of this study was presented as a poster at the American Pharmacists Association (APhA) 2019 Annual Meeting and Exposition (March 22-25, 2019, Seattle, WA) and received the 2019 APhA-APRS Presentation Award in the APhA-APRS Contributed Research Paper, Graduate Student/Fellow/Postdoctoral Scholar category.

Association between Vaso-occlusive Crises and Opioid Prescriptions among Patients with Sickle Cell Disease: A Retrospective Claims-based Study.

BACKGROUND/OBJECTIVES: Among sickle cell disease (SCD) patients, vaso-occlusive crises (VOCs) are recurrent and unpredictable attacks of acute pain. These pain crises are often treated with analgesics, including opioids, which have been associated with misuse and overdose. The aim of this study was to examine the association between VOC events and opioid use and assess the association between opioid prescriptions and health care resource utilization among SCD patients. METHODS: This was a retrospective cohort study using Texas Medicaid medical and prescription claims between September 2011 and August 2016. The index date was the first SCD diagnosis. Patients (2-63 years) with at least one inpatient or two outpatient SCD diagnoses, who were continuously enrolled during 12 months postindex, were included in the study. The primary outcome was number of opioid prescriptions, while the independent variable was number of VOC events. Covariates included age, gender, nonopioid medication use, nonstudy SCD-related medication (penicillin and folic acid) use, evidence of blood transfusions, number of SCD-related complications, number of SCD-related comorbid conditions, and Charlson Comorbidity Index score. Negative binomial regression analysis was used to address study objectives. RESULTS: Of 3368 included patients, 1978 (58.7%) had at least one opioid prescription with a mean of 4.2 (SD=7.2). Overall, 2071 (61.5%) had at least one VOC event with an average of 2.9 (SD=4.4). The results from the negative binomial regression showed that for every increase in VOC events, the number of opioid prescriptions increased by 9.5% (Incidence rate ratio=1.095, 95% CI: 1.078-1.111; P ≤ 0.0001). Other significant covariates associated with higher opioid use included age (13 and older compared to 2-12) and increase in the number of nonopioid pain medications, nonstudy SCD-related medications, and SCD-related complications. CONCLUSIONS: The majority of SCD patients had at least one VOC event and were prescribed opioids during the 12-month study period. We found that each VOC event was associated with a 9.5% increase in the use of opioids. SCD guidelines recommend opioids for the treatment of VOC-related pain. Payers and providers should be aware of opioid use in this population, consider appropriate VOC prevention measures, and provide SCD patients with access to appropriate pain management.

Association Between Vaso-Occlusive Crises and Opioid Prescriptions Among Patients with Sickle Cell Disease: A Retrospective Claims-Based Study.

Background/Objectives: Among sickle cell disease (SCD) patients, vaso-occlusive crises (VOCs) are recurrent and unpredictable attacks of acute pain. These pain crises are often treated with analgesics, including opioids, which have been associated with misuse and overdose. The aim of this study was to examine the association between VOC events and opioid use and assess the association between opioid prescriptions and health care resource utilization among SCD patients. Methods: This was a retrospective cohort study using Texas Medicaid medical and prescription claims between September 2011 and August 2016. The index date was the first SCD diagnosis. Patients (2-63 years) with at least one inpatient or two outpatient SCD diagnoses, who were continuously enrolled during 12 months postindex, were included in the study. The primary outcome was number of opioid prescriptions, while the independent variable was number of VOC events. Covariates included age, gender, nonopioid medication use, nonstudy SCD-related medication (penicillin and folic acid) use, evidence of blood transfusions, number of SCD-related complications, number of SCD-related comorbid conditions, and Charlson Comorbidity Index score. Negative binomial regression analysis was used to address study objectives. Results: Of 3368 included patients, 1978 (58.7%) had at least one opioid prescription with a mean of 4.2 (SD=7.2). Overall, 2071 (61.5%) had at least one VOC event with an average of 2.9 (SD=4.4). The results from the negative binomial regression showed that for every increase in VOC events, the number of opioid prescriptions increased by 9.5% (Incidence rate ratio=1.095, 95% CI: 1.078-1.111; P ≤ 0.0001). Other significant covariates associated with higher opioid use included age (13 and older compared to 2-12) and increase in the number of nonopioid pain medications, nonstudy SCD-related medications, and SCD-related complications. Conclusions: The majority of SCD patients had at least one VOC event and were prescribed opioids during the 12-month study period. We found that each VOC event was associated with a 9.5% increase in the use of opioids. SCD guidelines recommend opioids for the treatment of VOC-related pain. Payers and providers should be aware of opioid use in this population, consider appropriate VOC prevention measures, and provide SCD patients with access to appropriate pain management.

Fetal fibronectin testing and pregnancy outcomes among Texas Medicaid patients at risk for preterm birth.

OBJECTIVES: Fetal fibronectin (fFN) testing between the 24th and 34th weeks of pregnancy in patients with symptomatic preterm labor (PTL) helps assess the risk of spontaneous preterm birth (sPTB), yet the extent of its use is unknown. We assessed use of fFN testing among Texas Medicaid enrollees with symptomatic PTL and evaluated time to infant delivery and healthcare utilization/costs. STUDY DESIGN: Retrospective cohort study using medical and pharmacy claims for Texas Medicaid enrollees. METHODS: We identified pregnant women triaged through the emergency department (ED) and hospital labor-and-delivery units with symptomatic PTL between January 1, 2012, and May 31, 2015. Patients with fFN testing prior to delivery were propensity score matched 1:1 to patients without fFN testing. Primary outcomes included time to delivery from initial PTL encounter and all-cause maternal healthcare utilization and costs. RESULTS: A total of 29,553 women met the criteria for analysis, of whom 14% had a record of receiving fFN testing. Each matched cohort included 4098 patients. Compared with those who did not, patients who underwent fFN testing had significantly more clinical risk factors (mean [SD]: 1.7 [1.1] vs 1.1 [1.0]; P <.0001) and were less likely to deliver during the initial hospital stay (odds ratio [OR], 0.539; 95% CI, 0.489-0.594), deliver ≤3 days following the hospital/ED encounter (OR, 0.499; 95% CI, 0.452-0.551); and receive their first PTL diagnosis during the initial hospital/ED encounter (OR, 0.598; 95% CI, 0.539-0.665). Patients who had an fFN test, compared with those who did not, had 17.5% higher total costs (P <.0001) during the 5 months prior to delivery, but had gestation lengths 9.4 days longer (24.6 vs 15.2 days) than those without testing. CONCLUSIONS: Frequency of fFN testing was low in Texas Medicaid enrollees with symptomatic PTL. Patients with fFN testing had longer gestation periods and were less likely to deliver within ≤3 days of a hospital/ED encounter for PTL. These results support the role of fFN in screening for risk for sPTB among women with symptomatic PTL.

Prevalence and predictors of non-steroidal anti-inflammatory drug/analgesic therapeutic duplication in the South Korean ambulatory care setting.

PURPOSE: Therapeutic duplication (TD) in prescriptions is a common cause of inappropriate drug use. This study aimed to determine the prevalence of TD in the Korean ambulatory setting and to determine the patient and prescriber characteristics that were associated with TD of non-steroidal anti-inflammatory drugs (NSAIDs) and analgesics. METHODS: Ambulatory care cases with NSAID/analgesic prescriptions were extracted from the National Health Insurance database for January­March 2011. The Korean TD classification (64 ingredients) was used to define cases of TD. Multivariate logistic regression was used to determine the predictors of TD. The independent variables in the regression model included patient characteristics (sex, age, insurance type, comorbidity, diagnosis, and number of prescribed drugs) and prescriber characteristics (type of medical institution and specialty). RESULTS: Among 21 million patients, we identified 59,636,222 ambulatory care visits with NSAID/analgesic prescriptions; 13.3 % of these cases involved TD. The most frequent duplications were diclofenac/aceclofenac (12.4 % of TDs), diclofenac/talniflumate (11.2 %), and diclofenac/loxoprofen sodium (10.7 %). Male sex, older age, and a Charlson comorbidity index of ≥1 were associated with an increased likelihood of TD. Arthritis, injection administration (OR 3.676, 95 % CI 3.670­3.683), and the number of drugs per prescription were associated with an increased likelihood of TD. Orthopedic and pediatric specialties were associated with an increased likelihood of TD. CONCLUSIONS: This study is the first to determine the prevalence of NSAID TD and the factors that were associated with its occurrence in South Korea. These results may help prevent TD and improve appropriate medication use.