Improvements in Health-related Quality of Life and Symptoms in Patients With Previously Untreated Chronic Lymphocytic Leukemia: Final Results From the Phase II GIBB Study of the Combination of Obinutuzumab and Bendamustine.

BACKGROUND: We evaluated health-related quality of life (HRQoL) in patients with chronic lymphocytic leukemia (CLL) receiving first-line chemoimmunotherapy in the GIBB single-arm, Phase II study of obinutuzumab plus bendamustine (BG). MATERIALS AND METHODS: Patients received six 28-day cycles of BG and were followed for up to 27 months. HRQoL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Core 30 (EORTC QLQ-C30) and EORTC QLQ Chronic Lymphocytic Leukemia 16 (QLQ-CLL16) questionnaires. Scores were linear-transformed to a 100-point scale, with clinically meaningful responses defined as a ≥ 10-point change from baseline. RESULTS: The patient-reported outcome (PRO) population comprised 98 patients (68.4% male; median age 61 years). EORTC QLQ-C30 global health status improvements were noted at all follow-up visits and were clinically meaningful 2 to 3 months after induction and at 3- and 27-months' follow-up. Clinically meaningful improvements were also observed for the EORTC QLQ-C30 role functioning, emotional functioning, fatigue and insomnia scales and the EORTC QLQ-CLL16 fatigue, disease symptoms and future health worries scales. Global health status was maintained throughout follow-up, and no clinically relevant deterioration in other HRQoL parameters was observed. CONCLUSION: PRO data from the GIBB study show improved overall HRQoL in patients with CLL who received first-line chemoimmunotherapy with BG.

US cost-effectiveness of polatuzumab vedotin, bendamustine and rituximab in diffuse large B-cell lymphoma.

Aim: To evaluate the cost-effectiveness of polatuzumab vedotin (pola) + bendamustine + rituximab (BR) in relapsed/refractory diffuse large B-cell lymphoma based on the GO29365 trial from a US payer's perspective. Materials & methods: A partitioned survival model used progression-free survival and overall survival data from the GO29365 trial. The base case analysis assumed overall survival was informed by progression-free survival; a mixture cure model estimated proportion of long-term survivors. Results: In the base case, pola + BR was cost-effective versus BR at US$35,864 per quality-adjusted life year gained. Probabilistic and one-way sensitivity analyses showed that the findings were robust. Conclusion: Pola + BR is cost-effective versus BR for the treatment of transplant-ineligible relapsed/refractory diffuse large B-cell lymphoma in the US.

Partial palivizumab prophylaxis and increased risk of hospitalization due to respiratory syncytial virus in a Medicaid population: a retrospective cohort analysis.

BACKGROUND: Infection with respiratory syncytial virus (RSV) is common among young children insured through Medicaid in the United States. Complete and timely dosing with palivizumab is associated with lower risk of RSV-related hospitalizations, but up to 60% of infants who receive palivizumab in Medicaid population do not receive full prophylaxis. The purpose of this study was to evaluate the association of partial palivizumab prophylaxis with the risk of RSV hospitalization among high-risk Medicaid-insured infants. METHODS: Claims data from 12 states during 6 RSV seasons (October 1st to April 30th in the first year of life in 2003-2009) were analyzed. Inclusion criteria were birth hospital discharge before October 1st, continuous insurance eligibility from birth through April 30th, ≥ one palivizumab administration from August 1st to end of season, and high-risk status (≤34 weeks gestational age or chronic lung disease of prematurity [CLDP] or hemodynamically significant congenital heart disease [CHD]). Fully prophylaxed infants received the first palivizumab dose by November 30th with no gaps >35 days up to the first RSV-related hospitalization or end of follow-up. All other infants were categorized as partially prophylaxed. RESULTS: Of the 8,443 high-risk infants evaluated, 67% (5,615) received partial prophylaxis. Partially prophylaxed infants were more likely to have RSV-related hospitalization than fully prophylaxed infants (11.7% versus 7.9%, p< 0.001). RSV-related hospitalization rates ranged from 8.5% to 24.8% in premature, CHD, and CLDP infants with partial prophylaxis. After adjusting for potential confounders, logistic regression showed that partially prophylaxed infants had a 21% greater odds of hospitalization compared with fully prophylaxed infants (odds ratio 1.21, 95% confidence interval 1.09-1.34). CONCLUSIONS: RSV-related hospitalization rates were significantly higher in high-risk Medicaid infants with partial palivizumab prophylaxis compared with fully prophylaxed infants. These findings suggest that reduced and/or delayed dosing is less effective.

Early treatment discontinuation and switching in first-line metastatic breast cancer: the role of patient-reported symptom burden.

Treatment options for metastatic breast cancer (MBC) are complex, and some patients experience early discontinuation or switching of treatment (ETDS). We examined the relationship between ETDS and patient-reported symptom burden among patients receiving first-line treatment of MBC in community oncology settings. This retrospective observational study used the ACORN Data Warehouse, a comprehensive community oncology repository of medical records and patient-reported outcomes. Patients with first-line treatment for MBC who had Patient Care Monitor (PCM) surveys were eligible. ETDS was defined as: record stating ETDS, treatment duration < planned, and planned therapy <6 weeks. Symptom burden was measured by two PCM composite scores [continuous (0-22) and categorical (absent, mild, moderate, and severe)] computed from 22 PCM items with varying cut points to assess symptom burden over time. Cox regression with time-varying covariates was used to assess risk for ETDS controlling for patient characteristics and treatment type: chemo (chemotherapy without targeted therapy (±hormone therapy); targeted (chemotherapy plus targeted therapy (±hormone therapy); and hormone (hormone therapy only). Overall, 197 (24.7 %) of a total sample of 797 patients had an ETDS event, of which 109 (55.3 %) were switches rather than early discontinuation. ETDS rate was nominally lower in the hormone group (11.1 %) versus chemo (27.6 %) or targeted (26.1 %). PCM continuous composite score predicted ETDS, controlling for other variables (HR = 1.132, p < 0.0001). ETDS was predicted by moderate and severe levels of PCM categorical composite score (HR = 4.135, and HR = 5.287 vs. absent, respectively, both p < 0.0001), with the pattern suggesting a threshold effect. Moderate or severe levels of a wide range of patient-reported symptoms and the accumulation of symptoms over time significantly predicted ETDS. Providers may better maintain patients on planned therapy if they attend to overall symptom burden patients experience over time.

Persistent recurring wheezing in the fifth year of life after laboratory-confirmed, medically attended respiratory syncytial virus infection in infancy.

BACKGROUND: Respiratory syncytial virus (RSV) infection in infancy is associated with subsequent recurrent wheezing. METHODS: A retrospective cohort study examined children born at ≥32 weeks gestation between 1996-2004. All children were enrolled in an integrated health care delivery system in Northern California and were followed through the fifth year of life. The primary endpoint was recurrent wheezing in the fifth year of life and its association with laboratory-confirmed, medically-attended RSV infection during the first year, prematurity, and supplemental oxygen during birth hospitalization. Other outcomes measured were recurrent wheezing quantified through outpatient visits, inpatient hospital stays, and asthma prescriptions. RESULTS: The study sample included 72,602 children. The rate of recurrent wheezing in the second year was 5.6% and fell to 4.7% by the fifth year. Recurrent wheezing rates varied by risk status: the rate was 12.5% among infants with RSV hospitalization, 8% among infants 32-33 weeks gestation, and 18% in infants with bronchopulmonary dysplasia. In multivariate analyses, increasing severity of respiratory syncytial virus infection was significantly associated with recurrent wheezing in year 5; compared with children without RSV infection in infancy, children who only had an outpatient RSV encounter had an adjusted odds ratio of 1.38 (95% CI,1.03-1.85), while children with a prolonged RSV hospitalization had an adjusted odds ratio of 2.59 (95% CI, 1.49-4.50). CONCLUSIONS: Laboratory-confirmed, medically attended RSV infection, prematurity, and neonatal exposure to supplemental oxygen have independent associations with development of recurrent wheezing in the fifth year of life.

Cost utility of palivizumab prophylaxis among pre-term infants in the United States: a national policy perspective.

OBJECTIVE: The cost-effectiveness of palivizumab has previously been reported among certain guideline-eligible, high-risk premature infants in Medicaid. Because guideline authorities base decisions on a national perspective, the economic model of palivizumab was adapted to include all infants, that is, public and privately insured patients (60% of palivizumab use is public, 40% is private). METHODS: This study examined four groups of premature infants without chronic lung disease of prematurity or congenital heart disease: (1) <32 weeks gestational age (wGA) and ≤ 6 months chronologic age (CA); (2) 32-34 wGA, ≤ 3 months CA, with 2009 American Academy of Pediatrics (AAP) risk factors (RFs); (3) 32-35 wGA, ≤ 6 months CA, with 2006 AAP RFs; and (4) 32-35 wGA, ≤ 6 months CA, with ≤ 1 RF. An average estimate was used between public and private payors for (1) background rates of respiratory syncytial virus hospitalization (RSV-H), (2) direct medical costs associated with RSV-H, and (3) cost of palivizumab. Incremental cost-effectiveness ratios (ICERs) are reported in cost per quality-adjusted life-year (QALY) gained. Sensitivity analyses were performed. RESULTS: Palivizumab saved costs and improved QALYs among infants <32 wGA. Palivizumab was cost-effective in infants 32-34 wGA with 2009 AAP RFs ($44,774 per QALY) and in infants 32-35 wGA with 2006 AAP RFs ($79,477 per QALY). The ICER for infants 32-35 wGA with ≤ 1 RF was $464,476 per QALY. Influential variables in the sensitivity analysis included background rate of RSV-H and cost and efficacy of palivizumab. LIMITATIONS: The results are not generalizable to populations outside of the US. The model did not examine all RFs. The wholesale acquisition cost was used as a payment benchmark; actual price paid by end providers varies. CONCLUSIONS: From a national policy perspective, palivizumab remained cost-effective for publically and commercially insured, guideline-eligible, high-risk premature infants. Palivizumab was not cost-effective in infants of 32-35 wGA with ≤ 1 RF.

Cost-effectiveness analysis of palivizumab among pre-term infant populations covered by Medicaid in the United States.

OBJECTIVE: Medicaid infants are at high risk of severe respiratory syncytial virus (RSV) disease. The study objective was to estimate the cost-effectiveness of palivizumab in a Medicaid population. METHODS: A societal cost-utility analysis was conducted of prophylaxis with palivizumab vs no prophylaxis among four groups of premature infants: (1) <32 weeks gestational age (wGA) and ≤ 6 months chronologic age (CA); (2) 32-34 wGA, ≤ 3 months CA with 2009 American Academy of Pediatrics (AAP) risk factors (RF); (3) 32-35 wGA, ≤ 6 months CA with 2006 AAP RF; and (4) 32-35 wGA, ≤ 6 months CA with ≤ 1 RF. Full dosing of palivizumab was assumed throughout the RSV season (consistent with the FDA-approved label). All costs were in 2010 US dollars. The societal public payer spend for palivizumab was estimated using Medicaid reimbursement methodologies for the top 10 palivizumab-using states in 2010 minus mandatory manufacturer rebates. This study reports the incremental cost-effectiveness ratios (ICERs) in cost per quality-adjusted life-year (QALY) gained. Sensitivity and probabilistic analyses were also conducted. RESULTS: Palivizumab saved costs and improved QALYs among infants <32 wGA. Palivizumab was cost-effective in infants 32-34 wGA with 2009 AAP RF ($16,037 per QALY) and in infants 32-35 wGA with 2006 AAP RF ($38,244 per QALY). The ICER for infants 32-35 wGA with ≤ 1 RF was $281,892 per QALY. Influential variables in the sensitivity analysis included the background rate of RSV hospitalization, the cost of palivizumab, and the efficacy of palivizumab. KEY LIMITATIONS: These results are not generalizable to commercially insured infants or infants outside of the US. CONCLUSIONS: This is the first cost-utility analysis of palivizumab in a Medicaid population. Palivizumab, when dosed consistent with the FDA-approved labeling, was either cost-saving or cost-effective among current guideline-eligible infants in the Medicaid population. Palivizumab did not demonstrate cost-effectiveness in 32-35 wGA infants with ≤ 1 RF.

Association of RSV lower respiratory tract infection and subsequent healthcare use and costs: a Medicaid claims analysis in early-preterm, late-preterm, and full-term infants.

OBJECTIVE: Healthcare use and costs within 1 year of a respiratory syncytial virus lower respiratory tract infection (RSV-LRI) among Medicaid early-preterm and late-preterm infants compared with full-term infants were evaluated. METHODS: Infants born during 2003-2005 were identified from the Thomson Reuters MarketScan Multi-State Medicaid Database. Infants <1 year of age were grouped based on RSV-LRI and unspecified bronchiolitis/pneumonia (UBP) diagnosis codes and stratified by inpatient or outpatient setting. Infants without RSV-LRI/UBP were selected for comparison. Economic and clinical outcomes were analyzed descriptively; the relationship between RSV-LRI/UBP and costs incurred within 1 year of infection were analyzed using logged ordinary least squares models. Results were stratified by gestational age. RESULTS: Most infants were diagnosed with RSV-LRI/UBP after 90 days of chronologic age. Early-preterm infants had the greatest mean number of inpatient, outpatient, and emergency department visits after an RSV-LRI/UBP episode. The marginal costs among infants with RSV-LRI compared with controls were $34,132 (p < 0.001) and $3869 (p = 0.115) among inpatients and outpatients, respectively. Among late-preterm infants, the marginal costs were $17,465 (p < 0.001) and $2158 (p < 0.001) among inpatients and outpatients, respectively. Full-term infants had the lowest marginal costs (inpatients, $9151 [p < 0.001]; outpatients, $1428 [p < 0.001]). Overall, inpatient infants with RSV-LRI/UBP had higher costs than outpatients, suggesting that increased downstream costs are associated with severity of RSV-LRI/UBP disease. LIMITATIONS: Infants with unknown etiology for bronchiolitis were assigned to the UBP group, which may underestimate the costs of the comparison group. CONCLUSIONS: The burden of RSV-LRI was substantial among early-preterm Medicaid infants. Costs were also higher among late-preterm relative to full-term infants.

Respiratory outcomes, utilization and costs 12 months following a respiratory syncytial virus diagnosis among commercially insured late-preterm infants.

OBJECTIVES: To determine, among a commercially-insured population of late-preterm infants, utilization of healthcare resources and costs during the 1 year following a diagnosis of respiratory syncytial virus lower respiratory infection (RSV LRI). METHODS: Administrative claims for non-capitated, commercially-insured infants <1 year old were used to identify infants diagnosed with RSV LRI and unspecified bronchiolitis/pneumonia (UBP). Infants were stratified by the setting of diagnosis. Infants without evidence of RSV LRI or UBP were selected as a comparison group. Economic and clinical outcomes were analyzed descriptively using propensity score weighting and logged ordinary least squares models were used to examine the relationship between RSV and costs (adjusted to 2006 USD) incurred within 1 year of RSV LRI. RESULTS: The majority of infants were 3 months or older at the time of RSV LRI or UBP diagnosis. The rate of wheezing was significantly greater for infants in the RSV LRI and UBP cohorts relative to the comparison group (p < 0.001). Infantile asthma rates were 6-9 times higher among RSV LRI and UBP infants than the comparison group. RSV LRI and UBP infants also had significantly more emergency department visits and outpatient visits than the comparison group. The marginal healthcare costs were significantly higher for RSV LRI inpatients ($24,027) and outpatients ($2703) infants than for the comparison group (all p < 0.001). CONCLUSION: Commercially insured late-preterm infants with RSV infection are at high risk for recurrent wheezing and infantile asthma during the 1-year period after the initial episode and impose a significant economic burden to the healthcare system.

Recurrent wheezing in the third year of life among children born at 32 weeks' gestation or later: relationship to laboratory-confirmed, medically attended infection with respiratory syncytial virus during the first year of life.

OBJECTIVE: To quantify the relationship between recurrent wheezing (RW) in the third year of life and respiratory syncytial virus (RSV) infection, prematurity, and neonatal oxygen exposure. DESIGN: Retrospective cohort study linking inpatient, outpatient, and laboratory databases for cohort assembly and logistic regression analysis. SETTING: Integrated health care delivery system in Northern California. PARTICIPANTS: A total of 71,102 children born from 1996 to 2002 at 32 weeks' gestational age or later who were health plan members for 9 or more months in their first and third years. MAIN EXPOSURES: Laboratory-confirmed, medically attended RSV infection during first year and supplemental oxygen during birth hospitalization. OUTCOME MEASURES: Recurrent wheezing, quantified through outpatient visits, inpatient hospital stays, and asthma prescriptions. RESULTS: The rate of RW in the third year of life was 16.23% among premature infants with RSV and 6.22% among those without RSV. The risk of RW increased among infants who had an RSV outpatient encounter (adjusted odds ratio [AOR], 2.07; 95% CI, 1.61-2.67), uncomplicated RSV hospitalization (AOR, 4.66; 95% CI, 3.55-6.12), or prolonged RSV hospitalization (AOR, 3.42; 95% CI, 2.01-5.82) compared with infants without RSV encounters. Gestational age of 34 to 36 weeks was associated with increased risk of RW (AOR, 1.23; 95% CI 1.07-1.41) compared with 38 to 40 weeks, while a gestational age of 41 weeks or more was protective (AOR, 0.90; 95% CI, 0.81-0.99). Supplemental oxygen exposure was associated with increased risk at all levels. CONCLUSION: Laboratory-confirmed, medically attended RSV infection, prematurity, and exposure to supplemental oxygen during the neonatal period have independent associations with the development of RW in the third year of life.

Healthcare costs within a year of respiratory syncytial virus among Medicaid infants.

Limited research exists on the economic impact of respiratory syncytial virus lower respiratory infection (RSV LRI) among vulnerable infant populations. This study evaluated healthcare costs of full-term and late-preterm Medicaid infants with RSV LRI within 1 year of infection. Medicaid administrative claims were used to conduct a retrospective study of infants born 2003-2005. Full-term and late-preterm infants <1 year old were assigned to groups based on RSV LRI and unspecified bronchiolitis/pneumonia (UBP) diagnosis codes and stratified by setting of diagnosis. Infants without evidence of RSV LRI/UBP were selected as a comparison group. Economic and clinical outcomes were analyzed descriptively using propensity score weighting, and logged ordinary least squares models were used to examine relationship between RSV and costs incurred within 1 year of infection. RSV LRI and UBP infants, regardless of gestational age or healthcare setting, were more likely to experience respiratory diagnoses of wheezing and infantile asthma versus comparisons. Adjusted and weighted healthcare costs were significantly higher for all groups of RSV LRI and UBP infants relative to comparison infants (P < 0.001). Among late-preterm infants with inpatient and outpatient RSV, marginal costs compared with controls were $17,465 and $2,158, respectively. Costs for RSV LRI and UBP Medicaid infants are substantial. While much of the costs result from initial RSV episodes, higher post-episode costs and rates of respiratory events, procedures, and medications in RSV and UBP infants versus comparisons indicate long-term economic impact from infection and the impact is greater among late-preterm compared to full-term infants.

Comparative costs of hospitalisation among infants at high risk for respiratory syncytial virus lower respiratory tract infection during the first year of life.

OBJECTIVE: This retrospective cohort study compared the total cost of hospitalisation due to respiratory syncytial virus (RSV) lower respiratory tract infection (LRI) during the first year of life between late-preterm (33-36 weeks gestational age [wGA]) and term (≥ 37 wGA) infants. RESEARCH DESIGN AND METHODS: A large national claims database of commercially insured members was examined to identify hospital admissions associated with RSV between January 2003 and June 2007 among infants at high risk for RSV LRI, including late-preterm infants. Hospital use and costs were compared with those of a reference cohort of term infants with RSV. RESULTS: The cost of hospitalisation for RSV among late-preterm infants with at least one hospital admission associated with RSV (n=173) was twice that of term infants (n=1,983; $20,269 vs. 9,635; p< 0.001). The mean length of stay was also higher (5.3 vs. 3.4 days; p< 0.001). Approximately 21.9% of hospitalisations for late-preterm infants included an intensive care unit admission compared with 9.6% among term infants (p< 0.001). LIMITATIONS: Reliance on ICD-9 codes to identify potential cohort members may result in misclassification and underreporting the cohort size for conditions of interest. CONCLUSIONS: Hospitalisation costs and length of stay due to RSV LRI were significantly greater among late-preterm infants compared with term infants and higher than general estimates previously reported in the broader paediatric population.