Ruxolitinib Re-Treatment in Patients with Myelofibrosis: Real-World Evidence on Patient Characteristics and Outcomes.

Ruxolitinib is an FDA-approved treatment of intermediate- and high-risk myelofibrosis. In the phase 3 COMFORT studies, ruxolitinib reduced spleen volume in patients with myelofibrosis, with a median time to response of 3 months. However, nearly 20% of patients discontinued by month 4 with few treatment options available following discontinuation of ruxolitinib treatment. In this study, 2 independent patient care data sources were queried (Cardinal Health Oncology Provider Extended Network [OPEN] and HealthCore Integrated Research Environment [HIRE®]), and a retrospective review of medical charts was conducted. Patients aged ≥18 years with a diagnosis of myelofibrosis (primary or secondary), use of ruxolitinib for myelofibrosis, and documented physician-directed ruxolitinib interruption were included. Among 26 included patients, pre-interruption median (interquartile range [IQR]) ruxolitinib treatment duration was 123 (57-391, OPEN) and 110 (37-148, HIRE) days. Half the patients interrupted treatment within 3 months, commonly for adverse events (42% and 71%, respectively). After restarting ruxolitinib, median (IQR) re-treatment duration was 196 (54-553) and 166 (108-262) days, respectively. Consistent with previous reports, symptoms and spleen size improved in (OPEN/HIRE) 45%/43% and 40%/33% of evaluable patients, respectively. Further studies investigating the management of dose modifications and interruptions are needed to optimize benefit from ruxolitinib therapy.

Real-World Effectiveness of Once-Weekly Semaglutide From a US Commercially Insured and Medicare Advantage Population.

PURPOSE: Patients managing type 2 diabetes mellitus (T2DM) often require combination therapy to meet their blood glucose control targets. With limited real-world evidence focused on the use of glucagon-like peptide 1 receptor agonist (GLP-1RA) therapies, the objective of this study was to describe the association between semaglutide once weekly (OW) initiation and changes in hemoglobin A1c (A1c) levels. METHODS: This retrospective, descriptive cohort study used the HealthCore Integrated Research Environment (HIRE) to examine commercially insured and Medicare Advantage patients who had T2DM while taking semaglutide OW from December 1, 2017, to April 30, 2019. The first semaglutide OW prescription fill was defined as the study index date. Changes in mean A1c levels and A1c target attainment were evaluated among an intention-to-treat (ITT) population (overall group). Furthermore, a persistent population (PP) analysis on the same outcomes was performed that was limited to ITT patients who were observed to continue to use semaglutide OW at the time of the postindex A1c measurement. In addition, these outcomes were explored in patients stratified based on prior use of GLP-1RA therapy (experienced vs naive) and baseline A1c values >9% (75 mmol/mol). FINDINGS: A total of 1888 patients were identified in the overall ITT group. The mean change in the overall ITT group between preindex and postindex A1c values was -0.9% percentage points (-9.8 mmol/mol) (mean preindex A1c, 8.2% [66.1 mmol/mol]) and -1.1 percentage points (-12.0 mmol/mol) (mean preindex A1c, 8.2% [66.1 mmol/mol]) in the PP subgroup (all P < 0.001). Among the subgroup of patients with a baseline A1c value >9% (75 mmol/mol), percentage point changes in A1c were -2.2 (-24.0 mmol/mol) and -2.4 (-26.2 mmol/mol) (all P < 0.001). When accounting for prior GLP-1RA use, the GLP-1RA-naive stratum had double the mean reduction in A1c compared with the GLP-1RA-experienced stratum (-1.2 [-13.1 mmol/mol] vs -0.6 [-6.6 mmol/mol] percentage points). IMPLICATIONS: Semaglutide OW is associated with clinically and statistically significant A1C reduction and increases in reaching A1 targets using real-world data, even in GLP-1RA-experienced patients, despite more frequent use of insulin or sodium glucose transport protein 2 inhibitors in this group. Target A1c attainment significantly increased overall and within all subgroups and strata, with approximately half of all patients attaining an A1c value <7% (53 mmol/mol) and three-quarters attaining an A1c value <8% (64 mmol/mol).

Rate of preventative vaccine use and vaccine beliefs among a commercially insured population.

Immunization is an important component of preventive healthcare services. By recognizing and understanding factors associated with suboptimal vaccination compliance, healthcare providers can better approach at-risk populations and target efforts at reinforcing the vital importance of immunizations. The objective of this study was to understand the factors associated with adherence, beliefs and behaviors of influenza, pneumococcal, and herpes zoster vaccines receipt among commercially insured adults. A cross-sectional survey of patients with medical and pharmacy benefits for a 24-month period between August 1, 2014 and July 31, 2016 who were eligible to receive at least one of three adult vaccines (influenza, pneumococcal, and herpes zoster) was completed. Patients were identified as eligible to receive a vaccine based on current guidelines from the CDC ACIP. Health plan members were identified from administrative claims data in the HealthCore Integrated Research DatabaseSM (HIRD). Among the participants, 11% were eligible and up-to-date on all three vaccines; 52% on some and 37% were not up-to-date on any of the three vaccines. Participants with a healthcare provider were more likely to be up-to-date on eligible vaccines: 79.9% for none, 91.3% for some, and 97.8% for all eligible vaccines. The composite Vaccine Myth Belief score was significantly associated with being up to date on eligible vaccines: 45.0%/12.8% for none, 12/5%/30.8% for some, and 8.9%/33.3% for those up-to-date on all eligible vaccines. Despite numerous interventions designed to increase vaccination rates among adults, compliance remains suboptimal. It is evident that patient and provider education is necessary to fill knowledge gaps and misunderstandings; however knowledge by itself is not sufficient to improve immunization practices. Our results highlight a population that could benefit from a multidisciplinary approach, including interventions at the individual and health system levels.

Healthcare Costs of Diabetes and Microvascular and Macrovascular Disease in Individuals with Incident Type 2 Diabetes Mellitus: A Ten-Year Longitudinal Study.

OBJECTIVE: The objective of this study was to estimate the incremental long-term costs associated with T2DM attributable to vascular diseases. RESEARCH DESIGN AND METHODS: This retrospective cohort study identified newly diagnosed (incident) T2DM patients in 2007 (baseline to 01/01/2006) using the HealthCore Integrated Research Database, a repository of nationally representative claims data. Incident T2DM patients were 1:1 exact matched on age, gender and other factors of interest to non-DM patients, and followed until the earlier of 8 follow-up years or death. Patients with documented vascular disease diagnosis were identified during the study period. All-cause and T2DM/vascular disease-related annual healthcare costs were examined for each follow-up year. RESULTS: The study included 13,883 individuals with T2DM and matched non-DM controls. Among individuals with T2DM, 11,792 (85%) had vascular disease versus 9251 (66.6%) non-T2DM between 01/01/2006 and 12/31/2015. Among T2DM patients, mean all-cause annual costs were greater than in non-T2DM patients ($13,806 vs $7,243, baseline, $21,745 vs $8,524, post-index year 1, $12,756-$14,793 vs $8,349-$9,940 years 2-8, p< 0.001), respectively. A similar trend was observed for T2DM/vascular disease-related costs (p< 0. 001). T2DM/vascular disease-related costs were largest during post-index year 1, accounting for the majority of all-cause cost difference between T2DM patients and matched non-DM controls. Incident T2DM individuals without vascular disease at any time had significantly lower costs compared to non-DM controls (p< 0. 001) between years 2-8 of follow-up. CONCLUSION: Vascular disease increased the cost burden for individuals with T2DM. The cost impact of diabetes and vascular disease was highest in the year after diagnosis, and persisted for at least seven additional years, while the cost of T2DM patients without vascular disease trended lower than for matched non-DM patients. These data highlight potential costs that could be offset by earlier and more effective detection and management of T2DM aimed at reducing vascular disease burden.

Incidence and Prevalence of Microvascular and Macrovascular Diseases and All-cause Mortality in Type 2 Diabetes Mellitus: A 10-year Study in a US Commercially Insured and Medicare Advantage Population.

PURPOSE: The relationship between type 2 diabetes mellitus (T2DM) and increased microvascular and macrovascular disease and mortality is well established; however, data for the broad US T2DM population, especially by age, are limited. To help address this issue, we conducted a cohort study in a large national US commercially insured/Medicare Advantage population that incorporated a broad range of different age groups, including a large subset of younger individuals, during a 10-year study period. METHODS: This longitudinal study combined health plan claims and mortality data to identify incident T2DM patients and 1:1 directly matched non-DM controls. T2DM individuals (n = 13,883) were identified by a medical claim with a T2DM diagnosis or T2DM medication pharmacy claim in 2007; non-DM controls had no DM medical or pharmacy claims over the entire study period (January 1, 2006 to December 31, 2015). The outcomes assessed were incidence, prevalence, time to vascular disease and all-cause mortality, as well as age-stratified incidence and mortality based on Centers of Disease Control and Prevention-defined age strata. FINDINGS: Individuals with T2DM developed vascular disease at twice the rate as non-DM controls, 197 versus 98 per 1000 person-years, respectively. Vascular disease (composite) rates increased by age in T2DM/non-DM groups, 107.1/28.2 (18-44 years), 166.3/70.3 (45-64 years), and 391.0/199.7 (≥65 years) per 1000 person-years. The largest rate ratio was observed in younger individuals. All-cause mortality over follow-up was higher in T2DM individuals (27.5%) than in non-DM controls (19.6%). The largest increases in vascular disease prevalence and mortality among T2DM individuals were observed in the first year of follow-up. IMPLICATIONS: T2DM has a substantial effect on microvascular and macrovascular disease and all-cause mortality rates in all age groups. These outcomes appear to occur early after T2DM diagnosis, and have more pronounced, nearly fourfold, relative impact on younger individuals with T2DM compared to matched non-DM controls.

Impact of medical and/or pharmacy reimbursement on adult vaccination rates.

OBJECTIVES: To evaluate whether adults enrolled in commercial health insurance plans that provide reimbursement for herpes zoster vaccine (HZV) and pneumococcal vaccine (PV) through the medical and pharmacy benefits have higher vaccination rates compared with those whose health plans cover vaccines under the medical benefit alone. STUDY DESIGN: Retrospective claims analysis using medical and pharmacy claims data from January 1, 2012, through December 31, 2014. Separate but parallel analyses were conducted for HZV and PV. METHODS: Previously unvaccinated patients were divided into exposed (those in employer groups with both medical and pharmacy benefits for vaccinations) and unexposed (those in employer groups that covered vaccination under the medical benefit only) cohorts. RESULTS: For HZV, 32,506 and 1299 patients received vaccinations in the exposed and unexposed cohorts, respectively. The vaccination rate was significantly higher in the exposed (42 vaccinations per 1000 eligible person-years) than the unexposed cohort (15 vaccinations per 1000 eligible person-years; P <.001). For PV, 16,409 and 1386 received vaccinations in the exposed and unexposed cohorts, respectively. The vaccination rate was significantly higher in the exposed (22 vaccinations per 1000 eligible person-years) than the unexposed cohort (17 vaccinations per 1000 eligible person-years; P <.001). CONCLUSIONS: Among members with commercial health insurance, HZV and PV rates were significantly higher among those whose insurance covered vaccinations under both medical and pharmacy benefits, compared with members whose insurance covered vaccines under the medical benefit only. Pharmacy-based vaccination coverage from commercial health insurance plans may help improve adult vaccination rates.

Understanding the Patient's Journey in the Diagnosis and Treatment of Multiple Sclerosis in Clinical Practice.

PURPOSE: The aim of this study was to describe the treatment journey of patients with multiple sclerosis (MS). METHODS: This study was conducted in 2 phases. The first consisted of a claims-based analysis of data from patients diagnosed with MS between October 1, 2010, and May 31, 2014. Study patients were aged ≥18 years, had ≥12 months of continuous eligibility before and after the earliest MS diagnosis (index date), ≥1 disease-modifying therapy (DMT) claim postindex, and no claims with a code for DMT or MS during the 12-month preindex period. The second phase consisted of medical record reviews in a subset of patients in the claims study who had ≥1 neurologist visit within 90 days of the index MS diagnosis. FINDINGS: A total of 1639 patients were selected for claims-based analysis, and medical record analysis was conducted in a subset of 327 of those patients. The mean age in both samples was 42 years; females constituted about 70% of each group. Medical records showed that within a year of the first neurologist visit, 97.6% patients had a confirmed MS diagnosis; however, in 58.0%, MS type was not specified. MS symptoms were documented in less than half of all patients at the index neurologist visit. Early management consisted of magnetic resonance imaging (98.5% of patients), and the management of flares (annualized relapse rate, 0.3 [0.6] per patient). Use of spinal tap (21.7%), Expanded Disability Status Scale score (4.6%), and timed 25-foot walk score (8.6%) to evaluate disease progression was infrequent. The percentages of patients discontinuing the first DMT over time were high (43.1% among patients with 12-24 months of postindex follow-up, to 65.7% among patients with >36 months of postindex follow-up). Neurologists noted that about 10% of patients had difficulty adhering to an MS medication regimen, and documented several reasons for discontinuation, including adverse drug events and lack of desired effectiveness. IMPLICATIONS: In clinical practice, early MS treatment in DMT users is focused on symptom management, irrespective of MS type. Patients may benefit from initiating optimal treatment earlier. First-line therapy was often a transient option.

Impact of a gene expression classifier on the long-term management of patients with cytologically indeterminate thyroid nodules.

OBJECTIVES: The gene expression classifier (GEC, Afirma ) reclassifies as molecularly benign approximately one half of thyroid nodule fine-needle aspiration (FNA) biopsies with an initial indeterminate cytopathology diagnosis, facilitating clinical monitoring in lieu of diagnostic thyroid surgery. This study evaluated the long-term management patterns and thyroid surgery rates of GEC benign patients compared to a control group of cytopathology benign patients and also described the costs of thyroid surgery. METHODS: This retrospective cohort study used laboratory test results linked to payer medical claims data. Patients who underwent FNA biopsy between 1 January 2011 and 31 July 2013 were selected. GEC benign patients were matched 1:3 to cytopathology benign patients on biopsy year, gender, nodule size and age. Outcomes measured included thyroid-related follow-up clinic visits, ultrasound examinations and surgeries. RESULTS: Out of 2059 patients, matched groups consisting of 201 GEC benign patients and 603 cytopathology benign patients were evaluated over an average follow-up of 20 months. The proportions of GEC benign and cytopathology benign patients that underwent thyroid surgery (11.4% versus 10.1%, p = 0.594), and received a follow-up ultrasound exam (60.2% versus 61.7%, p = 0.706), respectively, were not significantly different. Average thyroid-related medical cost for the surgical episode and during 6 months following surgery were $10,432.00 (SD $8301) and $10,939.00 (SD $9656) respectively. LIMITATIONS: The study cohort included only patients whose diagnostic laboratory test results and administrative claims data were uniquely identifiable and could be linked on multiple identifiers; the rigorous matching and patient selection algorithms utilized improved the robustness and internal validity of the study. Claims were used as a proxy for clinical utilization without chart review confirmation. CONCLUSION: Patients with GEC and cytopathology benign diagnoses were managed similarly. The majority of patients in both groups did not undergo surgery and were managed with usual care, consisting of clinical follow-up and ultrasound exams.

Impact of specialty pharmacy on telaprevir-containing 3-drug hepatitis C regimen persistence.

BACKGROUND: Although the recommended treatment of hepatitis C continues to evolve as newer and more effective medications are made available, hepatitis C drug regimens consisting of a 3-drug combination of a protease inhibitor, pegylated interferon, and ribavirin were recommended by the American Association for the Study of Liver Diseases for the HCV genotype I beginning in 2011. Although more effective than the earlier standard of care, these regimens have complex dosing schedules, prolonged duration, and deleterious side effects. It has been shown that patients tend to discontinue these regimens prematurely. Specialty pharmacies offer specialized care management programs to hepatitis C patients, consisting of such services as regularly scheduled patient counseling, assessing regimen appropriateness, monitoring treatment progress, scheduling refill reminders, and coordinating patient care with prescribers. The use of specialty pharmacies by hepatitis C patients may improve persistence on the 3-drug hepatitis C regimens. OBJECTIVE: To examine the association of pharmacy dispensing channel (specialty pharmacy or retail pharmacy) and hepatitis C regimen persistence among patients on a 3-drug hepatitis C regimen containing telaprevir, a widely used hepatitis C protease inhibitor.  METHODS: A retrospective, observational study was conducted using pharmacy claims data from a national pharmacy benefits manager for the period July 2011 to June 2013. Continuously eligible patients who started a new 3-drug regimen containing telaprevir were included in the study and followed for up to 12 months after the index hepatitis C claim. The study outcome was persistence to the 3-drug regimen at treatment week 24 (day 168), representing the completion of an important milestone in the regimen. Patients were defined as persistent if they filled 84 days' supply of telaprevir and 168 days' supply of pegylated interferon and ribavirin each, as required by the regimen protocol. Multivariate logistic regression was used to evaluate the association between dispensing channel and persistence, controlling for differences in demographics, medication burden, out-of-pocket spend per 30-day adjusted hepatitis C prescription, and average days' supply per unadjusted hepatitis C prescription. RESULTS: The final study sample consisted of 1,475 patients-1,182 in the specialty pharmacy group and 293 in the retail pharmacy group. A significantly greater proportion of patients were persistent to the 3-drug hepatitis C regimen containing telaprevir in specialty pharmacy, compared with retail pharmacy (56.0% vs. 39.9%, P less than 0.001). After multivariate adjustment, patients in the specialty pharmacy group had 1.89 times greater odds of being persistent to 3-drug hepatitis C regimens containing telaprevir compared with patients in the retail group (95% CI=1.44-2.48). CONCLUSIONS: Patients who used a specialty pharmacy offering refill reminders, care management, and care coordination with prescribers were significantly more likely to be persistent to 3-drug hepatitis C regimens, compared with patients using a retail pharmacy.

Dispensing channel and medication adherence: evidence across 3 therapy classes.

OBJECTIVES: To examine the association of mail order versus retail pharmacy dispensing channels with medication adherence for patients on diabetes, hypertension, or high blood cholesterol medications, controlling for prior adherence behavior (PAB) and days of supply. STUDY DESIGN: Retrospective analysis using de-identified pharmacy claims data from a large national pharmacy benefits manager between April 2009 and December 2011. METHODS: Continuously eligible patients with an antidiabetic, antihypertensive, or antihyperlipidemic prescription claim between October and December 2009 were identified and followed over a 2-year period. Multivariate logistic regression was used to evaluate the impact of dispensing channel on medication adherence, controlling for differences in demographics, disease burden, and drug use pattern. Patients with a medication possession ratio of 80% or greater were considered adherent. The analysis controlled for PAB by using patients' adherence status in 2010. RESULTS: Overall, patients using the mail order channel had higher adherence rates than their retail counterparts across all 3 therapeutic classes. In 2011, the likelihood of a mail order patient being adherent was approximately 1.15 times higher than that of a retail patient for antidiabetics, 1.11 times higher for antihypertensives, and 1.19 times higher for antihyperlipidemics. PAB was the strongest contributor to the odds of a patient being adherent across all 3 therapy classes: odds ratios ranged from 5.87 to 9.49. CONCLUSIONS: After adjusting for PAB, differential days of supply, and differences in demographics and disease burden, patients who use mail order have a greater likelihood of being adherent than patients who use a retail pharmacy.

Comparing the cost of community pharmacy and mail-order pharmacy in a US retirement system.

Although community pharmacies have been the mainstay for drug distribution in the USA, plan members are encouraged to use mail-order pharmacies as a cost-containment strategy. Both channels differ with respect to reimbursement rates, utilization, and costs. We evaluated the differences in reimbursement rates and in ingredient costs between the two dispensing channels. We used pharmacy claims from a large Midwestern retirement system for the period 2000-2005. A representative sample of drug products was selected. We estimated the aggregated gross reimbursement, the ingredient cost, dispensing fee, pharmacy incentives for drug substitution, professional fee for other services, sales tax, and reimbursement per payer. The sample contained 1964 observations-four million claims. There were 58.5% observations for single source brands and 39.0% for generics. Observations with lower unit gross reimbursement rate in community pharmacy increased from 10.3% to 16.5%. Unit ingredient cost and dispensing fees were higher in community pharmacy than in mail-order pharmacy. Community pharmacy had a lower reimbursement rate per unit of medication (33.5-44.6% observations) compared with mail-order pharmacy. There were 87.3-98.1% observations with a higher patient co-financing per unit of medication in community pharmacy. Gross pharmaceutical reimbursement rates and unit ingredient costs were higher in community pharmacy than in mail-order pharmacy; but in more than 10% of the observations, the costs were higher in mail-order pharmacy than in community pharmacy.

Analysis of the impact of the Uruguay Round Agreements Act on pharmaceutical patents.

The Uruguay Round Agreements Act (URAA) was enacted by the United States Congress in 1994. The URAA provided substantial modifications to the framework for U.S. patent law that came into effect January 1, 1953. Changes in patent regulation are especially important in the pharmaceutical sector because the patent system determines, in large part, the reward that an inventor can derive from discovery of a new drug. Most pharmaceutical patents are classified as utility patents. Pharmaceutical patents may include claims for the active ingredient per se, for the formulation of the active ingredient for use as a pharmaceutical, for therapeutic indications and uses, and for methods of manufacturing the drug. The U.S. has a First-to-Invent system to establishing the right of priority of an invention, but most countries have a First-to-File priority system. The First-to-Invent system allows for public disclosure of inventions prior to patent filing. In contrast, the First-to-File system encourages early filing of patent applications. In both systems, filing an application for a patent as soon as the drug is discovered allows inventors to obtain an earlier date of invention relative to potential competitors and establish the right of priority over the invention.

Incentives for orphan drug research and development in the United States.

BACKGROUND: The Orphan Drug Act (1983) established several incentives to encourage the development of orphan drugs (ODs) to treat rare diseases and conditions. This study analyzed the characteristics of OD designations, approvals, sponsors, and evaluated the effective patent and market exclusivity life of orphan new molecular entities (NMEs) approved in the US between 1983 and 2007. METHODS: Primary data sources were the FDA Orange Book, the FDA Office of Orphan Drugs Development, and the US Patent and Trademark Office. Data included all orphan designations and approvals listed by the FDA and all NMEs approved by the FDA during the study period. RESULTS: The FDA listed 1,793 orphan designations and 322 approvals between 1983 and 2007. Cancer was the main group of diseases targeted for orphan approvals. Eighty-three companies concentrated 67.7% of the total orphan NMEs approvals. The average time from orphan designation to FDA approval was 4.0 +/- 3.3 years (mean +/- standard deviation). The average maximum effective patent and market exclusivity life was 11.7 +/- 5.0 years for orphan NME. OD market exclusivity increased the average maximum effective patent and market exclusivity life of ODs by 0.8 years. CONCLUSION: Public programs, federal regulations, and policies support orphan drugs R&D. Grants, research design support, FDA fee waivers, tax incentives, and orphan drug market exclusivity are the main incentives for orphan drug R&D. Although the 7-year orphan drug market exclusivity provision had a positive yet relatively modest overall effect on effective patent and market exclusivity life, economic incentives and public support mechanisms provide a platform for continued orphan drug development for a highly specialized market.

Exogenous endoscopy-related infections, pseudo-infections, and toxic reactions: clinical and economic burden.

OBJECTIVES: The objective of this study was to analyze the characteristics and costs of exogenous endoscopy-related infections, pseudo-infections, and toxic reactions in the US. METHODS: A systematic review of the scientific literature published between 1966 and 2005 was conducted in Medline. Data collection was based on a prospective protocol developed by the authors. RESULTS: The literature review included 70 outbreaks described in 64 scientific articles. Bronchoscopy accounted for half of all reported outbreaks. Inadequate decontamination practices were the leading cause of contamination; equipment malfunction became the second leading cause of contamination during the period 1990-2004. More than 91% of the infections identified could be prevented by health care providers if quality control systems are improved and implemented. The available economic information concerning exogenous endoscope related events is very limited. A model for the analysis of the economic burden of exogenous endoscopy-related events is proposed. CONCLUSIONS: Proper decontamination practices, the use of protective sheaths, and the improvement of surveillance systems could reduce the clinical and economic burdens associated with exogenous endoscopy-related events.