Real-world treatment patterns, survival, health resource use and costs among Medicare beneficiaries with diffuse large B-cell lymphoma.

Aim: To examine real-world treatment patterns, survival, healthcare resource use and costs in elderly Medicare beneficiaries with diffuse large B-cell lymphoma (DLBCL). Methods: 11,880 Medicare patients aged ≥66 years with DLBCL between 1 October 2015 and 31 December 2018 were followed for ≥12 months after initiating front-line treatment. Results: Two-thirds (61.2%) of the patients received standard-of-care R-CHOP as first-line treatment. Hospitalization was common (57%) in the 12-months after initiation of 1L treatment; the mean DLCBL-related total costs were US$84,416 during the same period. Over a median follow-up of 2.1 years, 17.8% received at least 2L treatment. Overall survival was lower among later lines of treatment (median overall survival from initiation of 1L: not reached; 2L: 19.9 months; 3L: 9.8 months; 4L: 5.5 months). Conclusion: A large unmet need exists for more efficacious and well-tolerated therapies for older adults with DLBCL.

Diffuse large B-cell lymphoma (DLBCL) is the most common form of Non-Hodgkin lymphoma, and it becomes more common with age. While researchers continue to develop newer, more effective treatments for DLBCL, it is important to understand how patients use existing treatments and the associated costs, particularly among the elderly. In our real-world analysis of nearly 12,000 older patients with DLBCL, we found high rates of hospitalization and hospice use, short length of life in later lines of therapy and substantial healthcare costs. Our findings suggest a large current unmet need for more effective and well-tolerated therapies for older adults with DLBCL in both the front-line and relapse/refractory settings.

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

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

Real-World Characteristics, Treatment Patterns, Health Care Resource Use, and Costs of Patients with Diffuse Large B-Cell Lymphoma in the U.S.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) represents the most common subtype of non-Hodgkin lymphoma in the U.S., but current real-world data are limited. This study was conducted to describe real-world characteristics, treatment patterns, health care resource utilization (HRU), and health care costs of patients with treated DLBCL in the U.S. MATERIALS AND METHODS: A retrospective study was conducted using the Optum Clinformatics Data Mart database (January 2013 to March 2018). Patients with an International Classification of Diseases, Tenth Revision, Clinical Modification diagnosis for DLBCL after October 2015 and no prior International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis for unspecified DLBCL or primary mediastinal large B-cell lymphoma were classified as incident; those with such codes were classified as prevalent. An adapted algorithm identified lines of therapy (e.g., first line [1L]). All-cause HRU and costs were calculated per-patient-per-year (PPPY) among patients with a ≥1L. RESULTS: Among 1,877 incident and 651 prevalent patients with ≥1L, median age was 72 years and 46% were female. Among incident patients, 22.6% had at least two lines (2L), whereas 38.4% of prevalent patients had ≥2L. The most frequent 1L therapy was rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Incident patients had 1.3 inpatient and 42.0 outpatient (OP) visits PPPY, whereas prevalent patients had 0.8 and 31.3 visits PPPY, respectively. Total costs were $137,156 and $81,669 PPPY for incident and prevalent patients, respectively. OP costs were the main driver of total costs at $88,202 PPPY, which were higher within the first year. CONCLUSION: This study showed that a large portion of patients require additional therapy after 1L treatment to manage DLBCL and highlighted the substantial economic burden of patients with DLBCL, particularly within the first year following diagnosis. IMPLICATIONS FOR PRACTICE: Patients diagnosed with diffuse large B-cell lymphoma (DLBCL) carry a substantial clinical and economic burden. A large portion of these patients require additional therapy beyond first-line treatment. There is significant unmet need among patients with DLBCL who require additional therapy beyond first-line treatment. Patients who do not respond to first-line therapy and are not eligible for transplants have very high health care resource utilization and costs, especially in the first 12 months following initiation of treatment.

Quality of vitamin K antagonist control and outcomes in atrial fibrillation patients: a meta-analysis and meta-regression.

BACKGROUND: Atrial fibrillation (AF) patients frequently require anticoagulation with vitamin K antagonists (VKAs) to prevent thromboembolic events, but their use increases the risk of hemorrhage. We evaluated time spent in therapeutic range (TTR), proportion of international normalized ratio (INR) measurements in range (PINRR), adverse events in relation to INR, and predictors of INR control in AF patients using VKAs. METHODS: We searched MEDLINE, CENTRAL and EMBASE (1990-June 2013) for studies of AF patients receiving adjusted-dose VKAs that reported INR control measures (TTR and PINRR) and/or reported an INR measurement coinciding with thromboembolic or hemorrhagic events. Random-effects meta-analyses and meta-regression were performed. RESULTS: Ninety-five articles were included. Sixty-eight VKA-treated study groups reported measures of INR control, while 43 studies reported an INR around the time of the adverse event. Patients spent 61% (95% CI, 59-62%), 25% (95% CI, 23-27%) and 14% (95% CI, 13-15%) of their time within, below or above the therapeutic range. PINRR assessments were within, below, and above range 56% (95% CI, 53-59%), 26% (95% CI, 23-29%) and 13% (95% CI, 11-17%) of the time. Patients receiving VKA management in the community spent less TTR than those managed by anticoagulation clinics or in randomized trials. Patients newly receiving VKAs spent less TTR than those with prior VKA use. Patients in Europe/United Kingdom spent more TTR than patients in North America. Fifty-seven percent (95% CI, 50-64%) of thromboembolic events and 42% (95% CI, 35 - 51%) of hemorrhagic events occurred at an INR <2.0 and >3.0, respectively; while 56% (95% CI, 48-64%) of ischemic strokes and 45% of intracranial hemorrhages (95% CI, 29-63%) occurred at INRs <2.0 and >3.0, respectively. CONCLUSIONS: Patients on VKAs for AF frequently have INRs outside the therapeutic range. While, thromboembolic and hemorrhagic events do occur patients with a therapeutic INR; patients with an INR <2.0 make up many of the cases of thromboembolism, while those >3.0 make up many of the cases of hemorrhage. Managing anticoagulation outside of a clinical trial or anticoagulation clinic is associated with poorer INR control, as is, the initiation of therapy in the VKA-naïve. Patients in Europe/UK have better INR control than those in North America.

Real-World Survival, Healthcare Resource Utilization, and Costs Among U.S. Elderly Patients With Diffuse Large B-Cell Lymphoma (DLBCL) Treated With R-GemOx in the Relapsed/Refractory Setting.

BACKGROUND: Little recent real-world evidence exists on overall survival, healthcare resource utilization (HCRU), and costs among R/R DLBCL patients treated with the combination of rituximab, gemcitabine, and oxaliplatin (R-GemOx), a widely-used regimen for patients ineligible for stem cell transplant due to age or comorbidities. PATIENTS AND METHODS: This retrospective analysis used 2014 to 2019 U.S. Medicare claims. Individuals aged ≥66 years with a new DLBCL diagnosis between October 1, 2015 and December 31, 2018 and continuous fee-for-service Medicare Part A, B, and D coverage in the 12 months pre- and postindex were followed to identify the sample of patients with evidence of R-GemOx treatment in the second-line (2L) or third-line (3L) setting. Outcomes included overall survival, all-cause and DLBCL-related HCRU, and costs after R-GemOx initiation. RESULTS: The final sample included 157 patients who received treatment with R-GemOx in the R/R settings (mean (SD) age 77.5 (6.0) years, 39.5% age>80 years; 66.9% male; 91.1% White). Of these, 126 received R-GemOx in the 2L setting and 31 received R-GemOx in the 3L setting. Median overall survival from R-GemOx initiation was 6.9 months and 6.8 months in the 2L and 3L setting, respectively. Rates of all-cause hospitalization (68.1% [2L] and >90% [3L]) and hospice use (42.9% [2L] and 51.7% [3L]) were high in the 12 months after R-GemOx initiation. All-cause total costs were substantial ($144,653 [2L] and $142,812 [3L]) and approximately 80% of costs were DLBCL-related within 12 months of R-GemOx initiation. CONCLUSION: Elderly U.S. Medicare beneficiaries diagnosed with DLBCL who initiated R-GemOx treatment in the R/R setting have poor overall survival, high rates of HCRU, and substantial costs.

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

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

Epidemiology and outcomes of complicated skin and soft tissue infections in hospitalized patients.

Complicated skin and soft tissue infections (cSSTIs) are among the most rapidly increasing reasons for hospitalization. To describe inpatients with regard to patient characteristics, cSSTI origin, appropriateness of initial antibiotics, and outcomes, we performed a retrospective cohort study in patients hospitalized for cSSTI. To identify independent predictors of outcomes, we performed multivariate analyses. Of 1,096 eligible patients, 48.7% had health care-associated (HCA) cSSTI and 51.3% had community-acquired (CA) cSSTI. After adjustment for baseline variables, hospital length of stay (LOS) was longer for HCA than for CA cSSTI (difference, 2.1 days; 95% confidence interval [CI], 0.8 to 3.5; P < 0.05). Other covariates associated with a longer LOS were need for dialysis (regression coefficient ± standard error, 4.5 ± 1.1) and diabetic wound diagnosis (2.6 ± 1.0) (all P < 0.05). In the subset with culture-positive cSSTI within 24 h of admission, the most common pathogen was Staphylococcus aureus (298/449 [66.4%]), of which 74.8% (223/298) were methicillin-resistant S. aureus (MRSA). Eighty-three patients (18.5%) received inappropriate initial antibiotics. After adjustment for other variables, the following were associated with inappropriate initial therapy: direct admission to hospital (not via emergency department), cSSTI caused by MRSA or mixed pathogens, and cSSTI caused by pathogens other than S. aureus or streptococci (all P < 0.05). We did not find an association between inappropriate therapy and outcomes, except in the subset with ulcers (adjusted odds ratio, 11.8; 95% CI, 1.3 to 111.1; P = 0.03). More studies are needed to examine the impact of HCA cSSTI and inappropriate initial therapy on outcomes.

A systematic literature review of the epidemiology, quality of life, and economic burden, including disease pathways and treatment patterns of relapsed/refractory classical Hodgkin lymphoma.

INTRODUCTION: A systematic literature review was conducted to understand disease burden in patients with relapsed/refractory classical Hodgkin lymphoma (R/R cHL). AREAS COVERED: Embase®, PubMed®, and Cochrane were searched for records from 2001 to 2020 in accordance with PRISMA guidelines. A total of 13,257 abstracts and 1731 papers were screened; 144 studies were identified. cHL accounted for 0.5% of all cancers, with 4‒66.7% of cases progressing to R/R disease (studies with >500 patients); this range varied across countries. Quality of life (QoL) was assessed via EORTC-QLQ-C30 (n = 7), EQ-5D (n = 5), SF-36 (n = 3), FACIT-F (n = 1), and MFI (n = 1) questionnaires. In general, pembrolizumab and other programmed cell death protein-1 inhibitors improved QoL scores. Brentuximab vedotin showed mixed outcomes, and high-dose therapy (HDT) and autologous stem-cell rescue (ASCR) showed worsening functionality/symptoms. Economic burden studies (n = 21) reported increased costs and health care resource in R/R cHL. Across clinical guidelines (n = 13) and treatment pattern studies (n = 46), HDT followed by ASCR was recommended as initial R/R cHL treatment. Pembrolizumab and nivolumab were frequently recommended for patients relapsing following HDT/ASCR. EXPERT OPINION: Despite recent treatment advances, patients with R/R cHL continue to report reduced quality of life. Unmet medical needs remain, particularly with respect to slowing disease progression and identifying the best treatment approaches for improving longer-term survival and quality of life. This systematic literature review provides an extensive overview of the current landscape in patients with R/R cHL, focusing on four key areas: epidemiology, QoL, economic burden, and disease management. These findings will be useful to those with an interest in managing patients with R/R cHL or in designing future studies.

Clinical outcomes of relapsed and refractory Hodgkin lymphoma patients after contemporary first-line treatment: a German Hodgkin Study Group analysis.

To evaluate patterns of rrHL after contemporary first-line treatment we studied 409 patients with first rrHL (HD13: n = 87, HD14: n = 118, HD15: n = 188, HDR3i: n = 51) at a median age of 37.4 years (18.4-76.8) from the GHSG database. Time to first relapse was ≤12 months in 49% and stage III/IV rrHL present in 52% of patients. In total, 291 patients received high-dose chemotherapy and autologous stem-cell transplantation (ASCT) and intended ASCT failed in 38 patients. ASCT was primarily not intended in 80 patients largely due to low risk disease or age/comorbidities. Overall, 10-year progression-free (PFS) and overall survival (OS) rates after first relapse were 48.2% (95% CI 41.9-54.2%) and 59.4% (95% CI 53.0-65.2%), respectively, with significant differences between subgroups. Inferior survival was observed with no ASCT due to advanced age/comorbidities (five-year PFS 36.2%, 95% CI 17.7-55.0%) or failure of salvage therapy (five-year PFS 36.3%, 95% CI 19.7-53.2%). Similarly, presence of primary refractory disease or stage IV at rrHL conferred inferior survival. In patients with low-risk disease, however, survival appeared favorable even without ASCT (10 y PFS 72.6%, 95% CI 53.7-84.8%). We herein confirm the curative potential of current rrHL treatments providing a robust benchmark to evaluate novel therapeutic strategies in rrHL. Approximately 50% of rrHL patients experienced a consecutive relapse.

Quality-of-life analysis of pembrolizumab vs brentuximab vedotin for relapsed/refractory classical Hodgkin lymphoma.

KEYNOTE-204 (NCT02684292) demonstrated a progression-free survival advantage for pembrolizumab over brentuximab vedotin (BV) in patients who had relapsed or refractory classical Hodgkin lymphoma (R/R cHL) following, or who were ineligible for, autologous stem cell transplantation (ASCT). Health-related quality of life (HRQoL), measured by patient-reported outcomes (PROs) from KEYNOTE-204, are reported from patients who received ≥1 dose of study treatment and completed ≥1 PRO assessment. The EORTC QoL Questionnaire Core 30 (QLQ-C30) and EuroQoL EQ-5D were administered at baseline, every 6 weeks until week 24, and every 12 weeks thereafter. Prespecified end points included least squares mean (LSM) changes from baseline to week 24 and time to true deterioration (TTD; ≥10-point decline from baseline). Comparisons were evaluated using 2-sided P values uncontrolled for multiplicity. High compliance at baseline (>90%) and through week 24 (>80%) was demonstrated across treatment groups (PRO analysis set: pembrolizumab, n = 146; BV, n = 150). The EORTC QLQ-C30 global health status (GHS)/quality of life (QoL) score improved from baseline to week 24 on pembrolizumab and worsened on BV and demonstrated significant LSM differences at 24 weeks (GHS/QoL: 8.60 [95% confidence interval, 3.89-13.31]; P = .0004). Significant improvements were observed in each QLQ-C30 domain except emotional and cognitive functioning. Compared with BV, pembrolizumab prolonged TTD for GHS/QoL (hazard ratio, 0.40 [95% CI, 0.22-0.74]; P = .003) and each QLQ-C30 domain except cognitive functioning. In conclusion, pembrolizumab demonstrated overall improvements in PROs of HRQoL measures over BV in the KEYNOTE-204 study. These data and previously reported efficacy results support pembrolizumab as the preferred treatment option for patients with R/R cHL who are ineligible for or experience relapse after ASCT.

A clinical pathway for community-acquired pneumonia: an observational cohort study.

BACKGROUND: Six hospitals instituted a voluntary, system-wide, pathway for community acquired pneumonia (CAP). We proposed this study to determine the impact of pathway antibiotics on patient survival, hospital length of stay (LOS), and total hospital cost. METHODS: Data were collected for adults from six U.S. hospitals with a principal CAP discharge diagnosis code, a chest infiltrate, and medical notes indicative of CAP from 2005-2007. Pathway and non-pathway cohorts were assigned according to antibiotics received within 48 hours of admission. Pathway antibiotics included levofloxacin 750 mg monotherapy or ceftriaxone 1000 mg plus azithromycin 500 mg daily. Multivariable regression models assessed 90-day mortality, hospital LOS, total hospital cost, and total pharmacy cost. RESULTS: Overall, 792 patients met study criteria. Of these, 505 (64%) received pathway antibiotics and 287 (36%) received non-pathway antibiotics. Adjusted means and p-values were derived from Least Squares regression models that included Pneumonia Severity Index risk class, patient age, heart failure, chronic obstructive pulmonary disease, and admitting hospital as covariates. After adjustment, patients who received pathway antibiotics experienced lower adjusted 90-day mortality (p = 0.02), shorter mean hospital LOS (3.9 vs. 5.0 days, p < 0.01), lower mean hospital costs ($2,485 vs. $3,281, p = 0.02), and similar mean pharmacy costs ($356 vs. $442, p = 0.11). CONCLUSIONS: Pathway antibiotics were associated with improved patient survival, hospital LOS, and total hospital cost for patients admitted to the hospital with CAP.

Treatment patterns, healthcare resource utilization, and costs of patients diagnosed with primary mediastinal B-cell lymphoma in the United States.

AIMS: With the advent of ICD-10-CM codes for PMBCL on 10/01/2015, assessment of treatment patterns and healthcare burden among US patients is possible. This study sought to describe the real-world treatment patterns and economic outcomes of patients with PMBCL. METHODS: Data from the Optum Clinformatics DataMart database was used (January 2013-March 2018). Patients with a first PMBCL ICD-10-CM diagnosis (with or without an antecedent ICD-10-CM diagnosis of DLBCL/other lymphoma, which may have been assigned before PMBCL confirmation) after 10/01/2015 (index date) and no ICD-9-CM diagnosis code for unspecified PMBCL/DLBCL were identified as incident patients. Those with PMBCL ICD-10-CM and unspecified ICD-9-CM diagnosis for PMBCL/DLBCL before 10/01/2015 (index date) were identified as prevalent patients. Patients were observed from the index date up to the earliest among death, end of data availability, or end of continuous health plan enrollment. An adapted algorithm was used to identify lines of therapy (LOT). RESULTS: Among 118 incident and 30 prevalent PMBCL patients, 14% and 20% of patients received ≥2 LOTs, respectively. In incident patients, 48% received ≥1 LOT, 14% ≥2, and 4% ≥3 LOTs. Among prevalent patients, 63% received ≥1 LOT and 20% ≥2 LOTs. The most frequently recorded 1 L therapy was R-CHOP both among incident and prevalent patients. Mean total healthcare costs for incident and prevalent patients were $149,340 and $92,799 per patient per year, respectively, with higher costs ≤12 months ($187,241 and $167,553). Outpatient costs were the main driver (accounting for 60.5% and 64.6% for incident and prevalent patients, respectively). LIMITATIONS: Potential underuse of ICD-10-CM codes shortly after discontinuation of ICD-9-CM codes in 01/2015; regimens identified for each LOT using the claims-based algorithm may not reflect the regimen administered. CONCLUSION: The multiple LOTs necessary for a sizeable minority of patients and the high costs of care highlight the significant unmet needs of PMBCL patients.

Real-World Healthcare Resource Utilization in Patients with Classical Hodgkin Lymphoma Treated with Pembrolizumab and Nivolumab in the USA.

BACKGROUND: Patients with classical Hodgkin lymphoma (cHL) relapsed or refractory (R/R) disease who relapse after or are ineligible for autologous stem cell transplantation have a poor prognosis. Recently, the anti-PD1 monoclonal antibodies nivolumab and pembrolizumab were approved by the US Food and Drug Administration (FDA; May 2016 and March 2017, respectively) as treatment options for R/R cHL patients. OBJECTIVE: In the absence of comparative clinical trials between these agents, this observational study was conducted to evaluate the healthcare resource utilization (HRU) of patients with cHL initiated on pembrolizumab compared to nivolumab in the USA. PATIENTS AND METHOD: Healthcare insurance claims from Symphony Health's IDV® (Integrated Dataverse) (July 2014-June 2018) were used in this retrospective study. The study population included adult patients with cHL initiated on pembrolizumab or nivolumab (index date). Inverse probability of treatment weighting was used to adjust for differences in patient characteristics between cohorts. All-cause and cHL-related hospitalizations and outpatient visits were measured during the observation (post-index) period and reported per patient-year (PPY). Rates of HRU were compared between cohorts using rate ratios (RRs). RESULTS: A total of 92 and 218 patients initiated on pembrolizumab and nivolumab, respectively, were included in the study population. After weighting, the mean age was similar at 55 years in both cohorts, while the proportion of females was lower in the pembrolizumab cohort (35.3%) compared to the nivolumab cohort (44.1%). Mean Quan-Charlson Comorbidity Index score was well balanced after weighting in the pembrolizumab and nivolumab cohorts (4.2 and 4.3, respectively). During the observation period, patients in the pembrolizumab cohort had significantly lower rates of all-cause hospitalizations (RR [95% CI] 0.33 [0.09-0.80]) and cHL-related hospitalizations (RR [95% CI] 0.14 [0.02-0.37]) than those in the nivolumab cohort. Rates of all-cause and cHL-related outpatient visits were not statistically different between patients in the pembrolizumab and nivolumab cohorts. CONCLUSIONS: In this real-world study, adult cHL patients initiated on pembrolizumab had significantly lower rates of all-cause and cHL-related hospitalizations compared to patients initiated on nivolumab.

Relapsed/refractory primary mediastinal large B-cell lymphoma: a structured review of epidemiology, treatment guidelines and real-world treatment practices.

Background: Primary mediastinal (thymic) large B-cell lymphoma (PMBCL) is an uncommon subtype of diffuse large B-cell lymphoma. Approximately 10-30% of patients experience refractory or relapsed PMBCL (rrPMBCL) after first-line therapy. Data and treatment guidelines for rrPMBCL are scarce, and management is based on clinical experience.Methods: Two structured literature reviews were undertaken to determine the incidence, prevalence, and mortality rates associated with rrPMBCL, and to identify clinical practice guidelines and real-world patterns of care.Results: Epidemiology studies included reported lymphomas (n = 1), non-Hodgkin lymphoma (n = 1), lymphoid neoplasm (n = 1), PMBCL (n = 6), and rrPMBCL (n = 1). Of 12 published treatment guidelines, only four provided recommendations for rrPMBCL. Sixteen studies provided data on real-world treatment patterns, but most were single-center studies with small patient numbers. Chemotherapy/immunochemotherapy, followed by high-dose treatment (HDT) and stem cell transplantation, was a mainstay of salvage therapy in most studies; real-world care generally followed treatment guidelines.Conclusions: Salvage chemotherapy (often with rituximab and radiotherapy), followed by HDT and stem cell transplantation, appears to be the standard real-world treatment for rrPMBCL. However, large prospective and retrospective studies are warranted to improve our knowledge of real-world treatment patterns.

Treatment patterns, health care resource utilization, and costs in patients with relapsed/refractory Hodgkin lymphoma treated with brentuximab vedotin.

Data are limited on the real-world utilization and costs of brentuximab vedotin (BV) among patients with relapsed/refractory Hodgkin lymphoma (rrHL) in the United States. A total of 219 BV patients identified from the Truven MarketScan® databases were followed up for a median of 2.9 years before and 1.0 year after initiation of BV. Of these patients, 109 (50.6%) received systemic therapy after BV (post-BV ST). Median duration of treatment was short for BV (2.1 months) and post-BV ST treatment (1.3 months); time to next treatment was 6.2 and 9.1 months, respectively. Average total US dollar 2014 costs/person for BV and post-BV ST line of therapy were $167,152 and $132,115, respectively; mean per-patient-per-month costs for BV and post-BV ST were $30,434 and $29,138, respectively. Findings underscore the unmet medical need and substantial economic burden in BV-treated patients with rrHL.

Patient-reported outcomes in KEYNOTE-087, a phase 2 study of pembrolizumab in patients with classical Hodgkin lymphoma.

In KEYNOTE-087, pembrolizumab had a 69% overall response rate and acceptable safety in patients with relapsed/refractory classical Hodgkin lymphoma (rrHL). We assessed health-related quality of life (HRQoL) in KEYNOTE-087. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (QLQ-C30) and the EuroQoL Five Dimensions Questionnaire 3-level version (EQ-5D) were administered to 206 patients across three cohorts defined by lymphoma progression after: (1) autologous stem cell transplantation (ASCT) and subsequent brentuximab vedotin (BV) (n = 69); (2) salvage chemotherapy and BV (n = 79); and (3) ASCT without post-transplantation BV (n = 58). Compliance/completion rates were ≥90% at week 12 and ≥70% at week 24. QLQ-C30 global health status/QoL and EQ-5D visual analog scale scores showed mean increases from baseline in overall health at all assessed timepoints. With few exceptions, mean improvements from baseline to weeks 12 and 24 in QLQ-C30 functional and symptom scores occurred in all cohorts.Clinicaltrials.gov identifier: NCT02453594.

Current management of anemia in critically ill patients: analysis of a database of 139 hospitals.

PURPOSE: This analysis focused on three objectives: 1) to measure packed red blood cell (pRBC) use across different critical care settings; 2) to characterize transfused and nontransfused critically ill patients; and (3) to identify potential predictors of transfusion use. METHODS: A retrospective analysis of critically ill patients from 139 hospitals across the United States was conducted. Hospital administrative and laboratory data were collected for patients 18 years of age and older admitted to the intensive care unit (ICU) (including coronary care unit and intermediate care units) from January 1, 2004, to May 31, 2005. Multivariate analyses controlling for patient and hospital heterogeneity evaluated the association between pRBC transfusions and patients' ICU or hospital length of stay. RESULTS: A total of 180,221 patients met all inclusion criteria, with 29,331 (16.3%) receiving pRBCs during their ICU stay. There was differential use of pRBCs by ICU/coronary care unit setting (ie, 23% of general ICU patients versus 7% of intermediate coronary care unit patients). Increasing age [odds ratio (OR), 1.007; 95% confidence interval (CI), 1.006-1.008], declining hemoglobin concentrations (OR, 2.315; 95% CI, 2.288-2.342), mechanical ventilation (OR, 1.338; 95% CI, 1.287-1.392), dialysis (OR, 2.071; 95% CI, 1.913-2.242), and presence of acute renal failure (OR, 1.259; 95% CI, 1.193-1.329), congestive heart failure (OR, 1.156; 95% CI, 1.106-1.208), or septicemia (OR, 1.143; 95% CI, 1.071-1.221) were associated with a higher likelihood of pRBC use. Each pRBC transfusion significantly increased hospital length of stay (1.6, 0.5, and 2.7 additional days for patients with 1, 2, and 3 or more transfusions, respectively, P < 0.0001) as compared with nontransfused patients. CONCLUSIONS: Multiple factors increased the likelihood of pRBC use in ICU patients. In addition, pRBC transfusion was associated with increased length of stay. Clinicians should evaluate the risk-benefit ratio and consider interventions to limit any unnecessary pRBC use in the critically ill.

Red blood cell transfusions and the risk of acute respiratory distress syndrome among the critically ill: a cohort study.

INTRODUCTION: Recent data indicate that transfusion of packed red blood cells (pRBCs) may increase the risk for the development of acute respiratory distress syndrome (ARDS) in critically ill patients. Uncertainty remains regarding the strength of this relationship. METHODS: To quantify the association between transfusions and intensive care unit (ICU)-onset ARDS, we performed a cohort study within Crit, a multicenter, prospective, observational study of transfusion practice in the ICU which enrolled 4,892 critically ill patients in 284 ICUs in the United States. Diagnostic criteria for ARDS were prospectively defined, and we focused on subjects without ARDS at admission. The development of ARDS in the ICU served as the primary endpoint. RESULTS: Among the 4,730 patients without ARDS at admission, 246 (5.2%) developed ARDS in the ICU. At baseline, ARDS cases were younger, more likely to be in a surgical ICU, and more likely to be admitted with pneumonia or sepsis than controls without ARDS. Cases also were more likely to have a serum creatinine of greater than 2.0 mg/dl (23% versus 18%) and a serum albumin of less than or equal to 2.3 g/dl (54% versus 30%) and were more severely ill upon ICU admission as measured by either the APACHE II (Acute Physiology and Chronic Health Evaluation II) or SOFA (Sequential Organ Failure Assessment) score (p < 0.05 for all). Sixty-seven percent and 42% of cases and controls, respectively, had exposure to pRBC transfusions (p < 0.05), and the unadjusted odds ratio (OR) of developing ARDS in transfused patients was 2.74 (95% confidence interval [CI], 2.09 to 3.59; p < 0.0001) compared to those never transfused. After age, baseline severity of illness, admitting diagnosis, and process-of-care factors were adjusted for, the independent relationship between pRBC transfusions and ICU-onset ARDS remained significant (adjusted OR, 2.80; 95% CI, 1.90 to 4.12; p < 0.0001). CONCLUSION: Development of ARDS after ICU admission is common, occurring in approximately 5% of critically ill patients. Transfusion of pRBCs is independently associated with the development of ARDS in the ICU.

The impact of aggressive debridement used as an adjunct therapy with terbinafine on perceptions of patients undergoing treatment for toenail onychomycosis.

OBJECTIVE: To determine whether adding aggressive debridement to oral terbinafine for treating toenail onychomycosis impacts patient-reported outcomes (PROs). MATERIALS AND METHODS: A total of 504 patients were randomized to receive 12 weeks of terbinafine 250 mg/day with or without debridement, with an additional 36-week follow-up. The OnyCOE-t, a validated disease-specific PRO questionnaire, was completed at baseline and weeks 6, 12, 24, and 48. It included six multi-item scales (symptom frequency, appearance problems, physical activities problems, stigma, and treatment satisfaction), and one single-item scale: overall problem. Longitudinal analysis of change was conducted to assess treatment effect. Repeated-measures models adjusted for visit, age, sex, baseline scores, severity and duration of infection; treatment interactions were also tested. RESULTS: Symptom frequency and treatment satisfaction significantly improved in the terbinafine + debridement group compared with terbinafine alone (p = 0.0395 and p = 0.0077, respectively). Age and sex were often significant explanatory variables, and further analysis of change scores at 12 weeks revealed that females treated with terbinafine + debridement reported significantly less improvement in the physical activities problems (p = 0.0021) and overall problem (p = 0.0112) scores. CONCLUSIONS: Aggressive debridement, when used as an adjunct therapy with oral terbinafine, improved treatment satisfaction and reduced symptom frequency. The observed sex differences warrant further investigation.

Economic burden of atopic manifestations in patients with atopic dermatitis--analysis of administrative claims.

BACKGROUND: Atopic dermatitis (AD) has been associated with atopic manifestations (AMs), such as food allergies, asthma, allergic rhinitis, and allergic conjunctivitis. OBJECTIVES: To (1) compare the risk of developing AMs in patients with AD versus those without AD, (2) estimate the incremental costs attributable to AMs in patients with AD, and (3) examine the factors associated with incremental costs. METHODS: In this retrospective cohort study, the authors used MarketScan research databases containing medical and pharmacy claims with dates of service from January 1, 1999, to December 31, 2004. Patients were considered to have AD if they had at least 1 medical claim with a primary or secondary diagnosis of AD (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] codes 691.8x) or contact dermatitis or other eczema of unspecified cause (ICD-9-CM codes 692.9x). To create comparable study cohorts, patients with AD were matched with non-AD patients using propensity scores that represented the likelihood of developing AD as predicted by logistic regression. After propensity score matching, the AD and non-AD cohorts did not statistically differ with respect to age, gender, geographic region, type of health insurance, Charlson Comorbidity Index, or baseline measures of medical and prescription drug utilization. The relative risks of developing AMs in the AD and non-AD cohorts were estimated using competing risk-survival analysis. AM was defined by ICD-9-CM codes for asthma (493.xx), allergic rhinitis (477.xx), allergic conjunctivitis (372.05 or 372.14), and food allergy (693.1x, 692.5x, 995.60). The annual incremental cost attributable to AMs in these AD patients was calculated from medical claims with AM and AD diagnosis codes and from pharmacy claims for prescription drugs used to treat asthma, allergic rhinitis, allergic conjunctivitis, or food allergy, and 95% confidence intervals (CIs) were calculated using the bootstrap method. RESULTS: Patients with AD were significantly more likely to develop AMs than patients without AD (21.8% versus 16.9%, adjusted relative risk [RR] = 1.33, 95% CI, 1.28-1.38). Among AD patients who developed AMs, allergic rhinitis was the most frequent manifestation (66.3%), followed by asthma (24.8%), allergic conjunctivitis (7.6%), and food allergy (1.8%). The incidence and adjusted RRs of developing AM for AD patients versus comparison patients were 5.3% versus 4.5% for asthma (RR = 1.20, 95% CI, 1.12-1.29), 14.6% versus 11.2% for allergic rhinitis (RR = 1.35, 95% CI, 1.29-1.41), 1.6% versus 1.1% for allergic conjunctivitis (RR = 1.50, 95% CI, 1.31-1.72), and 0.3% versus 0.1% for food allergy (RR = 2.35, 95% CI, 1.66-3.32). The annual AD + AM treatment costs for patients with AD increased substantially after they developed AMs. The additional financial burden attributable to AMs was estimated to be $482 per year, an almost 1.5-fold increase compared with AD cost alone (from $338 before AM development to $820 afterward, P < 0.001), with approximately equal distribution of costs between medical services ($243) and prescription drugs ($239). The largest incremental costs were observed in asthma ($973), followed by allergic rhinitis ($341). CONCLUSIONS: Patients with AD are significantly more likely to develop AM compared with patients without AD. The total treatment costs for AD patients who developed AMs were nearly 2.5 times the total treatment costs for patients with AD alone.