A clinical practice comparison of patients with chronic lymphocytic leukemia with and without deletion 17p receiving first-line treatment with ibrutinib.

Among patients with chronic lymphocytic leukemia (CLL) with deletion 17p (del[17p]), evidence from clinical trials for the effectiveness of single-agent ibrutinib as first-line therapy is limited. This retrospective analysis compared real-world clinical outcomes among patients with CLL, with and without del(17p), treated with first-line ibrutinib monotherapy. Overall survival, time to next treatment, time to treatment discontinuation, and reasons for ibrutinib discontinuation were evaluated. Using data from a real-world database, patients included were aged ≥18 years, had been diagnosed with CLL between January 1, 2011 and December 31, 2019, had undergone cytogenetic testing, and had received first-line ibrutinib monotherapy. A total of 1,069 patients were included in the analysis (62.7% male; median age 69 years); 23.8% (n=254) had del(17p). The median overall survival was significantly shorter in patients with del(17p) than in patients without (57.7 months vs. not reached; P=0.0006). Similar results were observed for median time to next treatment (49.4 months vs. not reached, P=0.0330). The median time to treatment discontinuation was non-significantly shorter in the group of patients with del(17p) (32.5 months vs. 42.9 months, P=0.3370). Results of an adjusted Cox proportional hazards model showed that the group with del(17p) was at significantly higher risk of death than was the group without del(17p) (hazard ratio=1.70, P=0.0031). Event rates for switching to new treatment and discontinuation were higher but not statistically significantly so. The most common reason for discontinuing ibrutinib treatment in both groups was toxicity, but discontinuation due to progression was significantly more frequent among patients with del(17p) (20% vs. 6%; P<0.0001). This study identifies an unmet need for more effective first-line therapeutic options in patients with CLL/small lymphocytic lymphoma and del(17p), despite the advent of ibrutinib.

Psychometric validation of the EORTC QLQ-HCC18 in patients with previously treated unresectable hepatocellular carcinoma.

To demonstrate the measurement properties of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Hepatocellular Carcinoma 18-question module (EORTC QLQ-HCC18) within a previously treated, unresectable hepatocellular carcinoma (HCC) clinical trial population that was distinct from the published QLQ-HCC18 validation population. Analyses were conducted using data from BGB-A317-208, an open label, international, clinical trial assessing efficacy and safety of the monoclonal antibody tislelizumab in adult HCC patients. The EORTC Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) and QLQ-HCC18 instruments were assessed at baseline and weeks 3 and 9 follow-up visits. Per US Food and Drug Administration guidance, psychometric validation of the QLQ-HCC18 included reliability (internal consistency and test-retest), construct validity (convergent and discriminant validity and known-groups validity), ability to detect change, and meaningful within-patient change (MWPC). Known-groups validity and MWPC analyses were also stratified on several pre-defined subgroups. A total of 248 patients were included. Only the QLQ-HCC18 fatigue, nutrition, and index domains demonstrated acceptable internal consistency; acceptable test-retest reliability was found for fatigue, body image, nutrition, pain, sexual interest, and index domains. The QLQ-HCC18 fatigue domain achieved the pre-specified criterion defining acceptable convergent and discriminant validity for 13 of 16 correlations, whereas the index domain achieved the pre-specified criterion for 14 of 16 correlations. Clear differentiation of the QLQ-HCC18 change scores between improvement and maintenance anchor groups were observed for body image, fatigue, pain, and index domains, whereas differentiation between deterioration and maintenance anchor groups were observed for fever and fatigue domains. MWPC point estimates defining improvement for the QLQ-HCC18 fatigue and index domains were -7.18 and -4.07, respectively; MWPC point estimates defining deterioration were 5.34 and 3.16, respectively. The EORTC QLQ-HCC18 fatigue and index domains consistently demonstrated robust psychometric properties, supporting the use of these domains as suitable patient-reported endpoints within a previously treated, unresectable HCC patient population.

Real-world experience of women using extended-cycle vs monthly-cycle combined oral contraception in the United States: the National Health and Wellness Survey.

BACKGROUND: The real-world experience of women receiving extended-cycle combined oral contraception (COC) versus monthly-cycle COC has not been reported. METHODS: Data were from the United States 2013 National Health and Wellness Survey. Eligible women (18-50 years old, premenopausal, without hysterectomy) currently using extended-cycle COC (3 months between periods) were compared with women using monthly-cycle COC. Treatment satisfaction (1 "extremely dissatisfied" to 7 "extremely satisfied"), adherence (8-item Morisky Medication Adherence Scale©), menstrual cycle-related symptoms, health-related quality of life (HRQOL) and health state utilities (Medical Outcomes Short Form Survey-36v2®), depression (9-item Patient Health Questionnaire), sleep difficulties, Work Productivity and Activity Impairment-General Health, and healthcare resource use were assessed using one-way analyses of variance, chi-square tests, and generalized linear models (adjusted for covariates). RESULTS: Participants included 260 (6.7%) women using extended-cycle and 3616 (93.3%) using monthly-cycle COC. Women using extended-cycle COC reported significantly higher treatment satisfaction (P = 0.001) and adherence (P = 0.04) and reduced heavy menstrual bleeding (P = 0.029). A non-significant tendency toward reduced menstrual pain (39.5% versus 47.3%) and menstrual cycle-related symptoms (40.0% versus 48.7%) was found in women using extended-cycle versus monthly-cycle COC. Significantly more women using extended-cycle COC reported health-related diagnoses, indicating preferential prescription for extended-cycle COC among women reporting more health problems. Consistent with this poorer health, more women using extended-cycle COC reported fatigue, headache, and activity impairment (P values < 0.05). There were no other significant differences between groups. CONCLUSIONS: This real-world observational study supports extended-cycle COC as a valuable treatment option with high satisfaction, high adherence, and reduced heavy menstrual bleeding.

Meta-analysis and indirect treatment comparison of lipegfilgrastim with pegfilgrastim and filgrastim for the reduction of chemotherapy-induced neutropenia-related events.

Background Granulocyte colony-stimulating factors are effective at reducing the risk and duration of neutropenia. The current meta-analysis compared the neutropenia-related efficacy and safety of lipegfilgrastim to those of pegfilgrastim and filgrastim. Methods Embase was searched for trials examining the efficacy/safety of lipegfilgrastim, pegfilgrastim, or filgrastim. Outcomes included febrile neutropenia, severe neutropenia, duration of severe neutropenia, time to recovery of absolute neutrophil count, and incidence of bone pain. Direct comparisons were made using random-effects models. No trials directly compared lipegfilgrastim and filgrastim. Indirect comparisons were made between lipegfilgrastim and filgrastim with pegfilgrastim as the common comparator. Results This meta-analysis included a total of 5769 patients from 24 studies. Over all cycles, lipegfilgrastim showed a lower, nonsignificant risk of febrile neutropenia compared with pegfilgrastim. Lipegfilgrastim has a lower risk of febrile neutropenia versus filgrastim but was also not statistically significant. The risk ratio for severe neutropenia in cycle 1 was 0.80, a 20% reduction in favor of lipegfilgrastim. For cycles 2-4, the risk ratio was 0.53 (0.35, 0.79) for lipegfilgrastim versus pegfilgrastim. The risk of severe neutropenia in cycles 2-4 was also significantly lower for lipegfilgrastim (risk ratio 0.45, 0.27, 0.75, respectively). No significant differences were found for febrile neutropenia and severe neutropenia in cycle 1. However, in cycles 2-4, lipegfilgrastim was associated with significant and clinically meaningful reductions in risk of severe neutropenia versus either pegfilgrastim or filgrastim. Conclusions Compared with pegfilgrastim or filgrastim, lipegfilgrastim has a statistically significantly lower absolute neutrophil count recovery time; however, differences in duration of severe neutropenia and bone pain were nonsignificant.

Trends in use of and complications from intrauterine contraceptive devices and tubal ligation or occlusion.

BACKGROUND: Long-acting reversible contraceptives such as intrauterine devices (IUDs) are highly effective in preventing pregnancy, cost effective, and increasing in popularity. It is unclear whether changes in IUD use are associated with changes in rates of irreversible tubal sterilization. In this analysis, we evaluate changes in rates of tubal sterilization, insertion of copper or levonorgestrel (LNG) IUDs, and related complications over time. METHODS: Data were obtained from a retrospective claims database (OptumTM ClinformaticsTM Data Mart) of women aged 15 to 45 years who underwent insertion of copper or LNG IUD or tubal sterilization between 1/1/2006 and 12/31/2011. Outcomes of interest included annual rates of insertion or sterilization and annual rates of potential complications and side effects. RESULTS: The number of women included in the analysis each year ranged from 1,870,675 to 2,016,916. Between 2006 and 2011, copper IUD insertion claim rates increased from 0.18 to 0.25% and LNG IUD insertion claim rates increased from 0.63 to 1.15%, while sterilization claims decreased from 0.78 to 0.66% (P < 0.0001 for all comparisons). Increases in IUD insertion were apparent in all age groups; decreases in tubal sterilization occurred in women aged 20 to 34 years. The most common side effects and complications were amenorrhea (7.36-11.59%), heavy menstrual bleeding (4.85-15.69%), and pelvic pain (11.12-14.27%). Significant increases in claims of certain complications associated with IUD insertion or sterilization were also observed. CONCLUSION: Between 2006 and 2011, a decrease in sterilization rates accompanied an increase in IUD insertion rates, suggesting that increasing numbers of women opted for reversible methods of long-term contraception over permanent sterilization.

Real-world treatment patterns and outcomes for patients with CLL using the Australian pharmaceutical benefits scheme (PBS) dataset.

This real-world retrospective cohort study using Australian Pharmaceutical Benefits Scheme (PBS) 10% investigated changes in chronic lymphocytic leukemia (CLL) treatment by line of therapy, time-to-next-treatment, treatment duration, and overall survival (OS). Overall, 803 patients received their first PBS-reimbursed CLL medication between 1 January 2011 to 31 July 2021 (median age: 70 years; 64.6% male), 289 post-1 August 2020. In 2011, most first-line (1 L) prescribing was fludarabine, cyclophosphamide, and rituximab (FCR). By 2021, common 1L were chlorambucil ± CD20 (26.1%), Bruton Tyrosine Kinase inhibitor (BTKi) (26.1%), and CD20 monotherapy (23.9%). In 2011, relapsed/refractory (R/R) CLL treatment was CD20 monotherapy or FCR. By 2021, BTKi (57.7%) and venetoclax ± CD20 (26.1%) were most common. Compared to FCR, 1 L treatment duration (Hazard Ratio) was shorter for CD20 monotherapy (1.7) or chlorambucil ± CD20 (2.5). In R/R CLL, median duration was 24 (ibrutinib) and 19 months (venetoclax). Median OS was 127 months. CLLtreatment pattern shave greatly changed in Australia since the introduction of novel therapies.

Costs and health care resource utilization among Medicare beneficiaries diagnosed with chronic lymphocytic leukemia.

BACKGROUND: Chronic lymphocytic leukemia (CLL) is the most common type of leukemia. However, published studies of CLL have either only focused on costs among individuals diagnosed with CLL without a non-CLL comparator group or focused on costs associated with specific CLL treatments. An examination of utilization and costs across different care settings provides a holistic view of utilization associated with CLL. OBJECTIVE: To quantify the health care costs and resource utilization types attributable to CLL among Medicare beneficiaries and identify predictors associated with each of the economic outcomes among beneficiaries diagnosed with CLL. METHODS: This retrospective study used a random 20% sample of the Medicare Chronic Conditions Data Warehouse (CCW) database covering the 2017-2019 period. The study population consisted of individuals with and without CLL. The CLL cohort and non-CLL cohort were matched using a 1:5 hard match based on baseline categorical variables. We characterized economic outcomes over 360 days across cost categories and places of services. We estimated average marginal effects using multivariable generalized linear regression models of total costs and across type of services. Total cost was compared between CLL and non-CLL cohorts using the matched sample. We used generalized linear models appropriate for the count or binary outcome to identify factors associated with various categories of health care resource utilization, such as inpatient admissions, emergency department (ED) visits, and oncologist/hematologist visits. RESULTS: A total of 2,736 beneficiaries in the CLL cohort and 13,571 beneficiaries in the non-CLL matched cohort were identified. Compared with the non-CLL cohort, the annual cost for the CLL cohort was higher (CLL vs non-CLL, mean [SD]: $22,781 [$37,592] vs $13,901 [$24,725]), mainly driven by health care provider costs ($6,535 vs $3,915) and Part D prescription drug costs ($5,916 vs $2,556). The main categories of health care resource utilization were physician evaluation/management visits, oncologist/hematologist visits, and laboratory services. Compared with beneficiaries aged 65-74 years, beneficiaries aged 85 years or older had lower use and cost in maintenance services (ie, oncologist visits, hospital outpatient costs, and prescription drug cost) but higher use and cost in acute services (ie, ED). Compared with residency in a metropolitan area, living in a nonmetropolitan area was associated with fewer physician visits but higher ED visits and hospitalizations. CONCLUSIONS: The cooccurrence of lower utilization of routine care services, along with higher utilization of acute care services among some individuals, has implications for patient burden and warrants further study.

Disparity in treatment patterns among Medicare beneficiaries diagnosed with chronic lymphocytic leukemia: an analysis of patient and contextual factors.

This study characterizes the patterns and timing of CLL treatment and, to our knowledge, is the first to identify social vulnerability factors associated with CLL treatment receipt in the Medicare population. A total of 3508 Medicare beneficiaries diagnosed with CLL from 2017 to 2019 were identified. We reported the proportion of individuals who received CLL treatment and the time until the first CLL treatment receipt after the first observed claim with a CLL diagnosis. Logistic regression and time-to-event models provided adjusted odds ratios and hazard ratios associated with baseline individual-level and county-level factors. Sixteen percent of individuals received CLL treatment, and the median follow-up time was 540 d. The median time to receipt of CLL treatment was 61 d. Older age and residence in a county ranked high in social vulnerability (as defined by minority status and language) were negatively associated with treatment receipt and time to treatment receipt.

Effects of tislelizumab on health-related quality of life in patients with recurrent or metastatic nasopharyngeal cancer.

BACKGROUND: This study evaluated health-related quality of life (HRQoL) in the RATIONALE-309 (NCT03924986) intent-to-treat (ITT) population and in a subgroup of patients with liver metastases. METHODS: Patients were randomized 1:1 to tislelizumab + chemotherapy or placebo + chemotherapy. As the secondary endpoint, HRQoL was evaluated using seven selected scores from the EORTC QLQ-C30 and QLQ Head and Neck Cancer module (QLQ-H&N35). RESULTS: Of 263 randomized patients in the ITT population (tislelizumab + chemotherapy n = 131, placebo + chemotherapy n = 132), 43% had liver metastases (tislelizumab + chemotherapy n = 56; placebo + chemotherapy n = 57). No differences in change in selected scores on the QLQ-C30 from baseline to cycle 4 or cycle 8 were observed for the ITT or liver metastases subgroup. No differences in selected QLQ-H&N35 scores were observed between the arms from baseline to cycle 4. In the ITT population and the liver metastases subgroup, a greater reduction from baseline to cycle 8 was observed in the tislelizumab + chemotherapy arm than the placebo + chemotherapy arm in QLQ-H&N35 pain score. At cycle 8 in the liver metastases subgroup, the tislelizumab + chemotherapy arm experienced greater improvement in the QLQ-H&N35 senses problems score than the placebo + chemotherapy arm. Differences in time to deterioration between arms were not observed. CONCLUSIONS: The current findings, along with improved survival and favorable safety, suggests that tislelizumab + chemotherapy represents a potential first-line treatment for recurrent or metastatic nasopharyngeal cancer.

The effects of tislelizumab treatment on the health-related quality of life of patients with advanced non-small cell lung cancer.

This study examined the health-related quality of life (HRQoL) of patients with advanced non-small cell lung cancer (NSCLC) receiving tislelizumab versus docetaxel in the open-label, multicenter, Phase 3 trial called RATIONALE-303 (NCT03358875). HRQoL was assessed with the EORTC QLQ-C30, EORTC QLQ-LC13, and the EQ-5D-5L instruments. A longitudinal analysis of covariance assessed the change from baseline to Week 12 and from baseline to Week 18. A time to deterioration analysis was also performed using the Kaplan-Meier method. Eight hundred and five patients were randomized to either tislelizumab (n = 535) or docetaxel, respectively (535 and 270 to tislelizumab and docetaxel, respectively). The tislelizumab arm improved while the docetaxel arm worsened in the QLQ-C30 global health status/QoL scale score (difference LS mean change Week 18: 5.7 [95% CI: 2.38, 9.07, p = 0.0008]), fatigue (Week 12: -3.2 [95% CI: -5.95, -0.37, p < 0.0266]; Week 18: -4.9 [95% CI: -8.26, -1.61, p = 0.0037]), and QLQ-LC13 symptom index score (Week 12: -5.5 [95% CI: -6.93, -4.04, P < 0.0001]; Week 18: -6.6 [95% CI: -8.25, -4.95, p < 0.0001]). The tislelizumab arm had improvements in coughing versus the docetaxel arm (Week 12: -4.7 [95% CI: -8.57, -0.78, p = 0.0188]; Week 18: -8.3 [95% CI: -13.02, -3.51, p = 0.0007]). The patients who received tislelizumab were less at risk for clinically meaningful worsening in the overall lung cancer symptom index scale (hazard ratio (HR): 0.24 [95% CI: 0.162, 0.356], p < 0.0001), dyspnea (HR: 0.74 [95% CI: 0.567, 0.958], p = 0.0109), coughing (HR: 0.74 [95% CI: 0.534, 1.019], p = 0.0309), and peripheral neuropathy (HR: 0.55 [95% CI: 0.370, 0.810] p = 0.0011). In general, tislelizumab versus docetaxel was associated with improved HRQoL and symptoms of lung cancer in patients who previously failed treatment with platinum-containing chemotherapy.

Impact of atrial fibrillation in onco-hematological patients in Europe: a targeted literature review.

INTRODUCTION: Atrial fibrillation (AF) is a common complication in cancer patients, and the increased risk associated with certain therapies poses a major challenge. The objective was to determine the clinical and economic burden of AF in onco-hematological patients in Europe. AREAS COVERED: A targeted literature review was completed for observational, retrospective and case studies, and reviews on AF in onco-hematology published between January 2010 and 2022 in PubMed, Science Direct, Medes and IBECS. The search was based on epidemiology, cost, health-related quality of life (HRQoL), disease burden and management, and patient journey. Thirty-one studies fulfilled eligibility criteria. Annual incidence of AF during treatment varies up to 25%, and increased with first-generation Bruton tyrosine kinase inhibitors (BTKi). Risk factors include age ≥65, prior AF or hypertension, hyperlipidemia and ibrutinib use. Complications are managed with anticoagulants and/or antiarrhythmics, and regular monitoring. When AF is no longer controllable, dose reduction or discontinuation is recommended. No data on costs, HRQoL and patient journey were identified. EXPERT OPINION: There is scarce and heterogeneous information on AF in onco-hematology in Europe. Available evidence reports a higher risk of AF associated with first-generation BTKi. Further studies are needed to understand the burden of AF in these patients.

A real-world study to assess the association of cardiovascular adverse events (CVAEs) with ibrutinib as first-line (1L) treatment for patients with chronic lymphocytic leukaemia (CLL) in the United States.

Ibrutinib, a Bruton's tyrosine kinase inhibitor, is often used as first-line (1L) treatment of chronic lymphocytic leukaemia (CLL); however, it is associated with an increased risk for cardiovascular adverse events (CVAEs). This real-world study adds to existing literature by simultaneously investigating the correlation between pre-existing CV risk factors and the relative cardiotoxicity of ibrutinib vs other therapies in CLL/small lymphocytic lymphoma (SLL). Using a real-world database, the risk of subsequent CVAEs (any CVAE, atrial fibrillation [AF], or hypertension) were compared among patients who received 1L ibrutinib monotherapy or another type of non-ibrutinib therapy, grouped as intensive (IT) or non-intensive therapy (NIT). Each patient's baseline CV risk was estimated using the Framingham risk score. Inverse probability treatment weighting was incorporated into a logistic regression model to reduce baseline imbalance. Results showed ibrutinib was significantly associated with higher risk of CVAEs regardless of baseline CV risk. Compared with IT, odds ratios of any CVAE, hypertension, or AF were 2.61, 3.66, and 3.02, respectively vs 1.88, 2.13, and 2.46, respectively, with NIT. Sensitivity analyses confirmed the findings were robust. These results suggest clinical caution should be taken when selecting ibrutinib for patients with CLL/SLL, especially in those with high baseline CV risk.

Examining the Impact of Tislelizumab Added to Chemotherapy on Health-Related Quality-of-Life Outcomes in Previously Untreated Patients With Nonsquamous Non-Small Cell Lung Cancer.

PURPOSE: This study assessed the effects of tislelizumab, a programmed cell death protein 1 inhibitor, in combination with chemotherapy versus chemotherapy alone as first-line treatment on health-related quality of life (HRQoL) in patients with advanced nonsquamous non-small cell lung cancer (nSQ-NSCLC). METHODS: Patients in this randomized, open-label, multicenter phase III study RATIONALE 304 (NCT03663205) with histologically confirmed stage IIIB/IV nSQ-NSCLC were randomized 2:1 to tislelizumab plus platinum-pemetrexed (arm T + PP) or platinum-pemetrexed alone (arm PP). Health-related QoL was measured using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 items and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Lung Cancer. Key patient-reported outcome endpoints include mean score change from baseline at weeks 12 (during chemotherapy) and 18 (following chemotherapy) in the 30-item Quality of Life Questionnaire Core's global health status/quality of life (GHS/QoL) and time to deterioration in GHS/QoL. RESULTS: Three hundred thirty-two patients received at least 1 dose of study drug and completed at least 1 HRQoL assessment. Global health status/QoL score improved in arm T + PP at week 18 (between-group least square mean difference, 5.7; 95% confidence interval [CI], 1.0-10.5; P = 0.018). Patients in arm T + PP experienced greater reduction in coughing (-5.9; 95% CI, -11.6 to -0.1; P = 0.044), dyspnea (-3.8; 95% CI, -7.8 to 0.1; P = 0.059), chest pain (-6.2; 95% CI, -10.8 to -1.6; P = 0.008), and peripheral neuropathy (-2.6; 95% CI, -5.5 to 0.2; P = 0.066). Median time to deterioration in GHS/QoL was not achieved for either arm. DISCUSSION: The addition of tislelizumab to platinum-based chemotherapy was associated with improvements in nSQ-NSCLC patients' HRQoL as well as the important disease-specific symptoms of coughing, chest pain, and dyspnea.ClinicalTrials.gov Identifier: NCT03663205.

Real-World longitudinal practice patterns in the use of PD-1 and PD-L1 inhibitors as First-Line therapy in patients with Non-Small cell lung cancer in the United States.

BACKGROUND: Immune checkpoint inhibitors targeting the programmed cell death protein-1 (PD-1) and programmed death ligand-1 (PD-L1) axis (collectively referred to as PD[L]1i) have demonstrated clinical benefits in non-small cell lung cancer (NSCLC) patients. The purpose of this United States-based real-world study is to examine changes in the landscape of first-line therapies for NSCLC since the introduction of PD(L)1i. METHODS: Patients with NSCLC initiating first-line treatment between May 1, 2017, and October 31, 2020, were identified in the IBM MarketScan® database. Patients were assigned groups based on first-line therapy: PD(L)1i monotherapy, chemotherapy alone, PD(L)1i with chemotherapy, or targeted therapy for patients with actionable driver mutations. RESULTS: A total of 5431 patients with NSCLC starting first-line treatment were identified: chemotherapy alone 2568 (47%), PD(L)1i with chemotherapy 1364 (25%), PD(L)1i monotherapy 790 (15%), and targeted therapy 709 (13%). The use of PD(L)1i monotherapy and targeted therapy remained consistent, while the percentage of patients receiving PD(L)1i with chemotherapy more than doubled. Over a third of patients in 2019 and 2020 received chemotherapy alone. Patients aged ≥65 years (odds ratio [OR]: 0.80; 95% confidence interval [CI]: 0.68-0.95), females (OR: 0.86; 95% CI: 0.74-0.98), and those with respiratory (OR: 0.82; 95% CI: 0.71-0.94) or kidney (OR: 0.56; 95% CI: 0.40-0.77) disease were less likely to have received PD(L)1i with chemotherapy than patients that received chemotherapy alone. CONCLUSIONS: Since the approval of PD(L)1i for NSCLC, their use has significantly increased for first-line treatment, especially when used in combination with chemotherapy. A significant proportion of patients received chemotherapy alone.

Patient-Administered Biologic and Biosimilar Filgrastim May Offer More Affordable Options for Patients with Nonmyeloid Malignancies Receiving Chemotherapy in the United States: A Budget Impact Analysis from the Payer Perspective.

BACKGROUND: Granulocyte colony-stimulating factors (G-CSFs) are often administered to reduce the incidence, severity, and duration of febrile neutropenia (FN) in chemotherapy patients. Tbo-filgrastim and filgrastim-sndz represent a follow-on biologic and a biosimilar version, respectively, of the short-acting G-CSF filgrastim with comparable efficacy and safety. OBJECTIVE: To estimate the budget impact of increasing use of patient-(home-) administered tbo-filgrastim and filgrastim-sndz from a U.S. payer perspective. METHODS: An interactive budget impact model was developed to estimate the changes in drug cost associated with projected increases in the market share of tbo-filgrastim from 5% to 10% and of filgrastim-sndz from 10% to 12% (with a corresponding decrease in filgrastim market share from 85% to 78%) for a 1 million-member health plan among patients with nonmyeloid malignancies receiving chemotherapy with a high risk of FN. Patient self-administration at home was assumed for 20% of patients receiving short-acting G-CSF treatment; all products were purchased through the patient's pharmacy benefit and were assumed to have tier 3 formulary status with a patient copay of $54 per prescription. Base-case data were derived from publicly available resources. The total plan budget impact was calculated using a 1-year time horizon, along with the differences in per member per month and per member per year (PMPY) costs between the current and future scenarios. RESULTS: The effective annual per-patient drug cost to the plan totaled between $16,961 and $27,199, depending on dosage and packaging, for tbo-filgrastim; between $16,216 and $26,015 for filgrastim-sndz; and between $19,134 and $30,663 for filgrastim. The estimated total annual plan cost associated with patient-administered short-acting G-CSFs was $53,298,217 (PMPY = $53.30) in the current scenario and $52,828,832 (PMPY = $52.82) in the future scenario. Cost savings totaled $469,385 (PMPY = $0.48). The model was most sensitive to changes in the percentage of patients self-administering G-CSF at home and to the wholesale acquisition cost for filgrastim. CONCLUSIONS: The effective annual plan per-patient drug costs for tbo-filgrastim and filgrastim-sndz were 11% and 15% lower than filgrastim, respectively. The present analysis estimated an annual U.S. health plan cost savings approaching $0.5 million following increases in market shares of approximately 5% for tbo-filgrastim and 2% for filgrastim-sndz. DISCLOSURES: This study was sponsored by Teva Branded Pharmaceutical Products R & D, which participated in the study design, data interpretation and analysis, the writing of the report, and the decision to submit. Aventine Consulting received consulting fees from Teva Pharmaceuticals and developed the cost model and provided data analysis support. Trautman and James are employed by Aventine Consulting. Szabo and Tang are employed by Teva Pharmaceuticals.

Analysis of patient and nurse preferences for self-administered FSH injection devices in select European markets.

PURPOSE: The purpose of this study was to assess product-specific features for a variety of self-administered injection devices and identify key factors that patients and nurses in select European markets find most important when selecting injection devices for self-administration of recombinant human follicle-stimulating hormone and urinary human follicle-stimulating hormone for fertility/reproductive therapy. PATIENTS AND METHODS: Patients (N=402) in France, Italy, Spain, Germany, the UK, the Netherlands, and Belgium, as well as reproductive/fertility nurses (N=40) in Germany, Italy, France, Spain, and the Czech Republic were surveyed. All patients were previously prescribed a follicle-stimulating hormone (FSH) treatment for either in vitro fertilization or ovulation induction. Patient and nurse preferences for attributes across all injection devices in the market were obtained via an online questionnaire and evaluated using the maximum differential scaling (MaxDiff) and conjoint analyses, which captured the relative importance of the selected FSH injection device attributes to determine specific qualities in overall product preference. RESULTS: Both the MaxDiff and conjoint analyses indicated that, for patients and nurses, the ideal FSH injection device would be a highly accurate, multi-use reusable pen injector with a dial-back function that would be easy for both use and education/instruction. Patients and nurses each selected attributes pertinent to their own experiences with the FSH injection device. Categorically, patients valued factors that resulted in minimal impact on daily life, including reduced injection volume to minimize injection-site pain, as well as a reusable device that would be easy to use; nurses placed greater value on a device that would be easy to teach in order to instruct the greatest number of patients while minimizing risk. CONCLUSION: Patient and nurse preferences were aligned on certain selected attributes of the FSH products. Although this study was an unbranded examination of attributes across all injection devices currently in the market, results demonstrated that the preferred product attributes were all characteristics of the Ovaleap® Pen.

Real-world Adherence and Persistence with Bisphosphonate Therapy in Postmenopausal Women: A Systematic Review.

PURPOSE: Bisphosphonate therapy is a well-established and effective treatment for postmenopausal osteoporosis and the prevention of osteoporotic fracture. However, poor adherence to and poor persistence with bisphosphonate therapy may reduce its benefits. Previous studies have documented the poor rates of adherence and persistence among postmenopausal women with osteoporosis. The objective of this systematic literature review was to evaluate adherence, persistence, and the impact of adherence and persistence on fracture risk in postmenopausal women with diagnosed osteoporosis. METHODS: Articles eligible for review included observational studies of the real-world use of bisphosphonates in 23 countries and were identified by using MEDLINE, EMBASE, IMSEAR (Index Medicus for South-East Asia Region), and LILACS (Latin American and Caribbean Health Sciences Database). FINDINGS: We identified and evaluated 10 studies that assessed bisphosphonate adherence by measuring medication possession ratio (MPR), persistence, and/or the impact of adherence and persistence on fracture risk. Mean MPR at 1 year ranged from 54% to 71% in the 3 studies that reported this assessment of adherence, and 40%-85% of patients at 1 year were adherent, defined as an MPR ≥80%, in the 8 studies that reported this end point. At 1 year, rates of persistence ranged from 28% to 74%. Rates of adherence and persistence were highest with agents requiring less frequent administration and typically declined over time. Fracture rates were significantly lower among adherent women with MPRs ≥80% compared with women with MPRs <80%. IMPLICATIONS: Our results show that suboptimal adherence to and persistence with bisphosphonate therapy in postmenopausal women are common and increase the risk of fracture. Additional research is needed to identify and incorporate effective strategies for improving adherence to bisphosphonates in postmenopausal women.

Treatment persistence with adalimumab, etanercept, or infliximab in combination with methotrexate and the effects on health care costs in patients with rheumatoid arthritis.

BACKGROUND: Anti-tumor necrosis factor (TNF) biologic agents are effective in treating rheumatoid arthritis (RA). Information on patient persistence with biologic anti-TNF therapies is limited, and the effects of persistence on the costs of therapy are unknown. OBJECTIVES: The aims of this study were to compare treatment persistence with adalimumab, etanercept, or infliximab in combination withmethotrexate (MTX) and evaluate the effects of persistence on overall health care costs. METHODS: This retrospective study used data from the PharMetrics managed care administrative claims database. Data from patients with RA who received combination treatment with an anti-TNF agent plus MTX and had > or = 24 months of continuous plan eligibility were collected. The 3 anti-TNF cohorts were adalimumab + MTX (adalimumab group), etanercept + MTX (etanercept group), and infliximab + MTX (infliximab group). Treatment persistence was defined as the number of days between the first and last anti-TNF treatment and was reported as a percentage of the 1-year period after treatment initiation. Costs were compared between patients with treatment persistence rates > or = 80% or <80%. Demographics, comorbidities, disease severity, and RA-related costs were assessed using descriptive statistics. Univariate and multivariate analyses were applied to identify differences in mean persistence between the 3 cohorts. RESULTS: Data from 1242 patients were included (77.7% female; mean age, 50.0 years). The mean persistence rate in the overall population was 74.6%, and the mean treatment time was 272.3 days. The infliximab group had a higher persistence rate compared with the etanercept and adalimumab groups (78.0% vs 72.8% and 70.8%, respectively; P < 0.005). In all patients combined, those with treatment persistence > or = 80% had higher mean total health care costs compared with those with treatment persistence <80% ($19,271.52 vs $15,598.46; P < 0.001), largely due to higher pharmacy costs. However, nonpharmacy costs were lower in the > or = 80% persistence cohort ($3091 vs $4601; P = 0.015). CONCLUSIONS: In this population of patients with RA, overall treatment persistence was high, with patients treated with infliximab + MTX having significantly higher persistence compared with those treated with adalimumab + MTX or etanercept + MTX. While pharmacy costs were higher in patients with > or = 80% persistence, nonpharmacy costs were lower.

Administrative claims analysis of all-cause annual costs of care and resource utilization by age category for ulcerative colitis patients.

BACKGROUND: Ulcerative colitis (UC) is a chronic inflammatory disease with peak incidence in the third decade of life and a second peak in the sixth or seventh decade. While drug therapy can be used to control the inflammation and reduce symptoms, patients with UC may be treated surgically. There is little information in the published literature evaluating the all-cause health care costs of patients with UC according to age. OBJECTIVE: To assess from administrative claims the direct all-cause (not disease-related) costs of care and resource utilization for patients with UC compared with members without UC by 3 age categories. METHODS: A retrospective analysis was conducted using the PharMetrics database of patients with a diagnosis of UC (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] code 556.x) from January 1, 2000, through June 30, 2005. This database contains enrollment data and pharmacy and medical claims from more than 85 different managed care organizations and more than 55 million patients in the United States. Patients had to be continuously enrolled for 6 months before and 12 months after the initial UC diagnosis and have at least 2 distinct claims with a diagnosis code for UC. The mean per-patient health care resource utilization and costs were calculated for patients in the year following their initial UC diagnosis and compared with the same measures for a group of age- and gender-matched members (without UC claims) at a ratio of 4:1. Three age groups were analyzed: pediatric-adolescent (aged < 18 years), adults (aged 18 to 64 years), and older adults (aged e 65 years). Differences in the measures of all-cause health care resource utilization (claims and costs) between the UC and non-UC groups were tested for statistical significance using the Wilcoxon signed-rank test, a non-parametric alternative to the paired t test. Differences between the 3 age cohorts were tested using the Mann-Whitney U test. RESULTS: Data were collected for 15,105 patients with UC and for 59,159 members in the comparator cohort without UC matched by age and gender. The average age for both cohorts was 44 years, and 54% were female. Mean ([SD], median) annual all-cause total health care costs in 2005 dollars for patients with UC were $13,233 ([$40,715], $5,190) versus $3,214 ([$12,741], $753) for the comparator group (P < 0.001). For all UC patients, all-cause inpatient hospitalization costs constituted the largest component ($5,771, 43.6%) of the mean annual total costs, followed by prescription medications ($2,423, 18.3%); miscellaneous services, such as hospice, psychiatric facility, and nursing home care ($2,092, 15.8%); outpatient hospital visits ($1,310, 9.9%); physician office visits ($899, 6.8%); laboratory procedures ($470, 3.6%); and emergency department visits ($268, 2.0%). Resource utilization (e.g., physician visits, laboratory claims, pharmacy claims) was highest for older adults aged e 65 years, followed by pediatricadolescent patients and adults aged 18 to 64 years (all comparisons P < 0.01). The mean ([SD], median) all-cause total health care costs were highest for pediatric-adolescent patients with UC (n = 589, 3.9%) at $23,113 ([$70,999], $6,214), followed by older adults (n = 650, 4.3%) at $15,811 ([$23,882], $6,886, P < 0.001), while adults aged 18 to 64 years (n = 13,866, 91.8%) incurred the lowest cost at $12,693 ([$39,505], $5,108, P < 0.001). CONCLUSION: Patients with UC identified from medical claims incurred significantly higher all-cause health care costs for all 3 age categories than did the comparator group of health plan members without diagnosis for UC.