Treatment patterns and clinical outcomes among patients with relapsed/refractory classical Hodgkin's lymphoma.

Aim: Limited real-world data exist on treatment patterns and clinical outcomes for patients with relapsed/refractory (R/R) classical Hodgkin's lymphoma (cHL). Methods: This study used the ConcertAI Oncology Dataset to assess treatment patterns, real-world progression-free survival (rwPFS), and real-world overall survival (rwOS) in adults with R/R cHL diagnosed from 2000 to 2019. Results: Among 226 (79%) treated patients, there was substantial treatment heterogeneity. Median rwPFS was 21.0 months in the second line (2L) of therapy. Median rwOS was 146.7 months in 2L and decreased to 40.6 months in the fifth line. Conclusion: Patients were exposed to a myriad of treatments in the R/R setting. These data support a relation between rwPFS and rwOS and highlight the need for effective therapeutic options.

A Pharmacoepidemiologic Approach to Evaluate Real-world Effectiveness of Hormonal Contraceptives in the Presence of Drug-drug Interactions.

BACKGROUND: Accurate estimation of conception is critical in the assessment of the effects of drugs used during pregnancy or to prevent pregnancy. In a novel application, we studied the effectiveness of oral contraceptives (OCs), where misclassification of conception relative to OC exposure may obscure effect estimates. METHODS: We studied OC failure, in a large claims database, among women who used antiepileptic drugs with metabolizing enzyme-inducing properties (carbamazepine or oxcarbazepine), which reduce OC's effectiveness or enzyme-neutral properties (lamotrigine or levetiracetam), with no expected impact on OC effectiveness. We compared conception rates in women 12-48 years of age concomitantly using OCs and enzyme-inducing drugs with rates in concomitant users of OCs and enzyme-neutral drugs. We measured conception with a validated algorithm that estimates gestational age based on pregnancy endpoints. We estimated relative and attributable risk using generalized estimating equation models after standardized mortality ratio weighting. RESULTS: We identified 89,777 concomitant use episodes with adjusted contraceptive failure rates of 1.6 (95% confidence interval (CI) = 1.4, 1.8) per 100 person-years among users of enzyme-neutral drugs and 18,964 episodes with a rate of 2.3 (1.9, 2.8) among users of enzyme-inducing drugs. The relative risk of conception for enzyme-inducing group was 1.4 (1.1, 1.8), and the rate difference was 0.7 (0.2, 1.2). CONCLUSIONS: OCs in combination with antiepileptic drugs that interact with metabolic enzymes were associated with increased contraceptive failure rates. Measurement of conception in claims data had adequate accuracy to uncover a strong drug-drug interaction, offering promise for broader application in comparative effectiveness studies on hormonal contraceptives to inform clinical and regulatory decisionmaking.

The association between acid-suppressive agent use and the risk of cancer: a systematic review and meta-analysis.

BACKGROUND: Acid-suppressive agents (ASAs) may be associated with cancer; previous studies reported that the risk of cancer with acid suppressants has differed depending on the site of cancer. Here, we conducted a systematic review and meta-analysis of the association between ASA use and the type of cancer risk. METHODS: MEDLINE, EMBASE, and Cochrane library databases were searched for publications up to the end of September 2019 for MeSH terms and text words related to cancer and ASAs. Studies on the association between ASAs and cancer risk, which included a control group and reported the relative risk of cancer, were included. The inverse-variance random effect model was used to estimate the pooled relative risk (RR) and 95% confidence interval (CI), and subgroup analysis for type of acid suppressants, drug uptake duration, and cumulative doses was performed. Heterogeneity was assessed using the I2 test and Q statistic. RESULTS: Thirty-nine cohort and case-control studies were included. ASA use was found to be significantly associated with a 46% higher risk of gastric cancer (RR, 1.46; 95% CI, 1.18-1.80) and a 53% higher risk of liver cancer (RR, 1.53; 95% CI, 1.31-1.78) compared with nonuse; however, there was no significant association for esophageal, colorectal, pancreatic, lung, breast, prostate, and kidney cancer; melanoma; and lymphoma. CONCLUSIONS: ASAs were significantly associated with an increased risk of gastric and liver cancer; therefore, special attention of ASA use considering the potential risk of gastric and liver cancer is needed.

Radiofrequency energy delivery to the lower esophageal sphincter improves gastroesophageal reflux patient-reported outcomes in failed laparoscopic Nissen fundoplication cohort.

BACKGROUND: Patients with uncontrollable gastroesophageal reflux disease (GERD) often undergo laparoscopic Nissen fundoplication (LNF); however, long-term there are often recurring symptoms and need for continuous medication use. Refractory LNF patients may receive radiofrequency energy delivery to the lower esophageal sphincter (Stretta) to ameliorate symptoms and medication requirements. The aim was to assess and compare long-term patient-reported outcomes of Stretta in refractory patients with and without previous LNF. METHODS: We prospectively assessed and compared patient-reported outcomes in 18 refractory LNF patients and 81 standard refractory GERD patients that all underwent Stretta during 10-year follow-up. Patient-reported outcomes measured were GERD-HRQL (health-related quality of life), patient satisfaction scores, and daily medication requirements. RESULTS: The refractory LNF subset demonstrated median improvements in GERD-HRQL, satisfaction, and medication use at all follow-up time points ≥6 months to 10 years, which was significant from a baseline of both on- and off-medications (p < 0.05). Specifically at 10 years, median GERD-HRQL decreased from 36 to 7 (p < 0.001), satisfaction increased from 1 to 4 (p < 0.001), and medication score decreased from 7 to 6 (p = 0.040). Nine patients decreased medication use by half at 10 years. No significant differences existed between refractory LNF and standard refractory GERD subsets at any follow-up time point ≥6 months to 10 years (p > 0.05) after Stretta. At 10 years, no significant differences were noted between refractory LNF and standard Stretta subsets regarding medication use (p = 0.088), patient satisfaction (p = 0.573), and GERD-HRQL (p = 0.075). Stretta procedures were completed without difficulty or significant intraoperative or long-term adverse events. CONCLUSION: Within a small cohort of refractory LNF patients, Stretta resulted in sustained improvement over 10 years with equivalent outcomes to non-LNF standard Stretta patients. Refractory LNF patients are a subpopulation that may be safely, effectively, and robustly aided by Stretta with fewer complications compared to redo of Nissen or chronic medication use.

Long-term maintenance effect of radiofrequency energy delivery for refractory GERD: a decade later.

BACKGROUND: Patients with gastroesophageal reflux disease (GERD) often seek alternative therapy for inadequate symptom control, with over 40% not responding to medical treatment. We evaluated the long-term safety, efficacy, and durability of response to radiofrequency treatment of the lower esophageal sphincter (Stretta). METHODS: Using an intent-to-treat analysis, we prospectively assessed 217 patients with medically refractory GERD before and after Stretta. There was no concurrent control group in the study. Primary outcome measure was normalization of GERD-health-related quality of life (GERD-HRQL) in 70% or greater of patients at 10 years. Secondary outcomes were 50% reduction or elimination of proton pump inhibitors (PPIs) and 60% or greater improvement in satisfaction at 10 years. Successful treatment was defined as achievement of secondary outcomes in a minimum of 50% of patients. Complications and effect on existing comorbidities were evaluated. The results of a 10-year study are reported. RESULTS: The primary outcome was achieved in 72% of patients (95% confidence interval 65-79). For secondary outcomes, a 50% or greater reduction in PPI use occurred in 64% of patients, (41% eliminating PPIs entirely), and a 60% or greater increase in satisfaction occurred in 54% of patients. Both secondary endpoints were achieved. The most common side effect was short-term chest pain (50%). Pre-existing Barrett's metaplasia regressed in 85% of biopsied patients. No cases of esophageal cancer occurred. CONCLUSIONS: In this single-group evaluation of 217 patients before and after Stretta, GERD-HRQL scores, satisfaction, and PPI use significantly improved and results were immediate and durable at 10 years.

Assessing unmet need among elderly Medicare Beneficiaries with Mantle cell lymphoma: an analysis of treatment patterns, survival, healthcare resource utilization, and costs.

Studies evaluating real-world outcomes and health care utilization for mantle cell lymphoma are limited. We utilized national Medicare claims (2009-2019) to examine treatment patterns, healthcare resource utilization, costs, and survival in 3664 elderly patients receiving 1 L treatment for MCL. Over a median follow-up of 2.8 years, 40.3% received at least 2 L treatment. The most common 1 L regimen was bendamustine-rituximab (50.1%), with increased use of BTKi-based regimens observed in 2 L (39.4%). Half (51.8%) of patients had an all-cause hospitalization within 12 months of initiating 1 L; hospitalization rates were higher in later lines. Healthcare costs were substantial and most costs (>80%) were MCL-related. Overall survival was poorer among later lines of treatment (median OS from initiation of 1 L: 53.5 months; 2 L: 22.0 months; 3 L: 11.8 months; 4 L: 7.8 months). These results suggest a large unmet need and future work should evaluate whether novel therapies have improved outcomes among elderly patients with MCL.

The effects of oral anticancer parity laws on out-of-pocket spending and adherence among commercially insured patients with chronic myeloid leukemia.

BACKGROUND: Over the past 12 years, 43 states and Washington DC have implemented oral anticancer medication parity laws in response to the burden of pharmacy cost sharing. Parity laws are designed to provide equal coverage and cost sharing between orally and parenterally administered anticancer medications for patients in commercial, fully insured health plans (FIHPs). However, there is considerable state-level variation in the requirements to achieve compliance with parity laws, and the clinical and economic effectiveness of parity is not fully known. OBJECTIVES: To (a) understand the impact of parity laws on out-of-pocket (OOP) spending and adherence to tyrosine kinase inhibitors (TKI) among commercially insured patients with chronic myeloid leukemia (CML) and (b) compare these effects across states with and without per prescription or per 30-day OOP spending limits as part of their parity laws. METHODS: Patients aged 18-64 years with CML, at least 1 pharmacy claim for a TKI, and residence in a state that implemented oral anticancer parity legislation between January 1, 2007, and January 1, 2017, were identified from the IBM MarketScan Commercial Claims and Encounters database. A propensity score-weighted difference-in-difference approach was used to measure the impact of parity on OOP spending and adherence in the 6 months after the first pharmacy claim for a TKI (index date) for patients enrolled in FIHPs (subject to parity) and self-funded health plans (SFHPs; exempt from parity). OOP spending was standardized to a 30-day equivalent amount and adjusted to 2017 US dollars. Adherence was assessed using the proportion of days covered (PDC), and patients were categorized as adherent with PDC ≥ 0.80. RESULTS: Of 1,887 patients initiating a TKI before or after their state's parity law, 678 (35.9%) were enrolled in FIHPs (480 before vs 198 after parity), and 1,209 (64.1%) were enrolled in SFHPs (688 before vs 521 after parity). Implementation of parity laws was not associated with any changes in mean OOP spending; however, it was associated with a reduced likelihood of paying $0 per 30 days across all states (adjusted difference-in-difference [aDD] OR = 0.662; 95% CI = 0.535-0.820) and states without OOP spending limits (aDD OR = 0.654; 95% CI = 0.508-0.848), but not in states with limits. Nonsignificant but directionally opposite changes at each end of the OOP spending distribution were observed for states with and without OOP spending limits, with increased spending observed at the 75th, 90th, and 95th percentiles in states without limits. Mean PDC and adherence showed a nonsignificant increase among FIHP and SFHP patients across all states, states with limits, and states without limits. CONCLUSIONS: Oral anticancer parity laws are not associated with reduced OOP spending or improved adherence in a commercially insured sample of patients with CML. These findings were consistent for states that included OOP spending limits as a component of their parity laws. DISCLOSURES: This study did not receive any external funding. Spargo, Yost, Raju, and Schroader are or were employees of Xcenda, which receives contracts from various industry partners unrelated to this work. There are no other conflicts of interest to disclose.

Optimizing Identification of People Living with HIV from Electronic Medical Records: Computable Phenotype Development and Validation.

BACKGROUND: Electronic health record (EHR)-based computable phenotype algorithms allow researchers to efficiently identify a large virtual cohort of Human Immunodeficiency Virus (HIV) patients. Built upon existing algorithms, we refined, improved, and validated an HIV phenotype algorithm using data from the OneFlorida Data Trust, a repository of linked claims data and EHRs from its clinical partners, which provide care to over 15 million patients across all 67 counties in Florida. METHODS: Our computable phenotype examined information from multiple EHR domains, including clinical encounters with diagnoses, prescription medications, and laboratory tests. To identify an HIV case, the algorithm requires the patient to have at least one diagnostic code for HIV and meet one of the following criteria: have 1+ positive HIV laboratory, have been prescribed with HIV medications, or have 3+ visits with HIV diagnostic codes. The computable phenotype was validated against a subset of clinical notes. RESULTS: Among the 15+ million patients from OneFlorida, we identified 61,313 patients with confirmed HIV diagnosis. Among them, 8.05% met all four inclusion criteria, 69.7% met the 3+ HIV encounters criteria in addition to having HIV diagnostic code, and 8.1% met all criteria except for having positive laboratories. Our algorithm achieved higher sensitivity (98.9%) and comparable specificity (97.6%) relative to existing algorithms (77-83% sensitivity, 86-100% specificity). The mean age of the sample was 42.7 years, 58% male, and about half were Black African American. Patients' average follow-up period (the time between the first and last encounter in the EHRs) was approximately 4.6 years. The median number of all encounters and HIV-related encounters were 79 and 21, respectively. CONCLUSION: By leveraging EHR data from multiple clinical partners and domains, with a considerably diverse population, our algorithm allows more flexible criteria for identifying patients with incomplete laboratory test results and medication prescribing history compared with prior studies.

Impact of Anticholinergic Medication Burden on Mobility and Falls in the Lifestyle Interventions for Elders (LIFE) Study.

Anticholinergic cognitive burden (ACB) may be associated with detrimental effects on mobility and physical independence in older adults. We evaluated the incidence of major mobility disability (MMD), persistent major mobility disability (PMMD), and injurious falls among participants within the Lifestyle Interventions for Elders (LIFE) trial according to varied anticholinergic burden levels. Participants aged 70-89 years were randomized to a physical activity (PA) or successful aging (SA) intervention and evaluated by ACB medication use as a summed score of a previously developed ACB scale. Confounders included demographic characteristics, physical function, cognitive function, and fall history. Average participant follow-up was 2.6 years and included outcome assessment for MMD, PMMD, and injurious falls every six months. Adjusted proportional hazards models evaluated the independent effects of ACB scores as well as interaction effects with the intervention. Of the 1635 participants, 986 (60%) used ≥1 anticholinergic medication. Compared to those with no burden, participants with an ACB score of 1 demonstrated increased MMD (HR = 1.42 [1.13-1.78]), PMMD (HR = 1.53 [1.12-2.09]), and injurious falls (HR = 1.60 [1.10-2.32]). Results similar in magnitude were observed for all other ACB levels versus the no burden group. Stepwise dose-response comparisons between ACB groupings did not demonstrate significant differences in outcomes. Stratification by PA or SA interventions demonstrated few differences from the combined overall trial results. Compared to those not taking anticholinergic medications, participants taking anticholinergic medications generally demonstrated increased risk of MMD, PMMD, and injurious falls. Total anticholinergic burden was not associated with a stepwise dose-response relationship in mobility disability and may lack sensitivity to capture varied responses.

Effect of Gastric Acid Suppressants on Response to a Physical Activity Intervention and Major Mobility Disability in Older Adults: Results from the Lifestyle Interventions for Elders (LIFE) Study.

OBJECTIVES: Proton pump inhibitors (PPIs) and histamine2 receptor antagonists (H2 RAs) are associated with pharmacologic effects that may be detrimental to mobility and response to physical activity. Mobility disability and injurious fall outcomes in PPI and H2 RA users were compared with nonusers in this secondary analysis of data from the Lifestyle Interventions for Elders (LIFE) study. METHODS: Participants ages 70-89 years were randomized to a physical activity (PA) or successful aging intervention and evaluated by medication use. Confounders included baseline demographic characteristics, physical function, cognitive function, sleep quality, and acid reflux symptoms that were adjusted via propensity score weighting. Outcomes were incident and persistent major mobility disability (MMD and pMMD) and injurious falls. Weighted proportional hazard models evaluated independent and interaction effects of PPIs and H2 RAs. RESULTS: No interaction was found between PPIs and H2 RAs and the PA intervention. Drug use associations were significant for H2 RAs (hazard ratio [HR] 1.74 [95% confidence interval [CI] 1.12-2.68]) and PPIs (HR 1.32 [95% CI 1.02-1.70]) compared with nonusers for pMMD. PPIs were associated with increased injurious falls compared with nonusers (HR 1.44 [95% CI 1.06-1.96]). Pooling of data from the H2 RA and PPI exposure groups showed a 26% increase in MMD (HR 1.26 [95% CI 1.07-1.48]), a 44% increase in pMMD (HR 1.44 [95% CI 1.16-1.77]), and a 48% increase in injurious falls (HR 1.48 [95% CI 1.15-1.91]) compared with nonusers. All direct comparisons between PPIs and H2 RAs were nonsignificant. CONCLUSIONS: Compared with nonusers, participants using either PPIs or H2 RAs had an increased risk of MMD, pMMD, and injurious falls. It is not known if these effects are related to the individual pharmacology of each medication, reduced acid secretion, or the underlying disease state. Further study is required to determine causality.