Real-world safety of first-line immuno-oncology combination therapies for advanced non-small-cell lung cancer.

Aim: Real-world adverse event (AE) data are limited for first-line (1L) treatments in advanced non-small-cell lung cancer (NSCLC). Methods: Using Flatiron Health Spotlight data, information for a pre-specified list of AEs was abstracted and described among patients with advanced NSCLC receiving 1L nivolumab + ipilimumab (NIVO + IPI), NIVO + IPI + chemotherapy and other approved immuno-oncology (IO) therapy + chemotherapy combination therapies. Results: Fatigue, pain, dyspnea, weight loss, decreased appetite, diarrhea, nausea/vomiting, cough, constipation and rash were the most common AEs. Rates of AEs were generally numerically similar across the three cohorts. The majority of patients received treatment for AEs and approximately one fourth of the patients had hospitalization due to their AEs. Conclusion: The real-world safety experiences of patients treated with 1L NIVO + IPI-based regimens were in general similar to those treated with other approved IO + chemotherapy combination therapies.

Immuno-oncology (IO) therapies boost the immune system to fight cancer cells and have been approved to treat non-small-cell lung cancer (NSCLC). The IO combination of nivolumab + ipilimumab (NIVO + IPI) is approved to treat NSCLC that has spread to other parts of the body or come back and at least 1% of the tumor cells express a protein called PD-L1; NIVO + IPI is also approved in combination with a short course chemotherapy, independent of tumor PD-L1 expression. While NIVO + IPI-based regimens are generally safe, some patients experienced side effects during the clinical trial. However, there is limited information on the side effects of these treatments in a real-world setting. This study analyzed data on side effects from a de-identified database of patients with advanced NSCLC who were treated with NIVO + IPI, NIVO + IPI + chemotherapy, or other approved IO + chemotherapy combinations based on information obtained from physicians' notes in clinical practice settings. The most common side effects among patients in all groups were tiredness, pain, shortness of breath, weight loss, decreased appetite, diarrhea, nausea/vomiting, cough, constipation and rash. The rates at which the side effects occurred were numerically similar regardless of the specific treatment that patients received. Approximately one-quarter of patients in each treatment group were hospitalized because of a side effect. These results show that in a real-world setting, NIVO + IPI-based regimens have similar safety to other IO + chemotherapy combinations when used as a first treatment for NSCLC that has spread or come back.

Quality of life with Brain Symptom and Impact Questionnaire in patients with brain metastases.

BACKGROUND: To examine the baseline characteristics of patients who underwent different treatments for brain metastases. METHODS: Allocated into group A [whole brain radiation therapy (WBRT) alone], or group B [stereotactic radiosurgery (SRS) or neurosurgery with or without WBRT], brain metastases patients with assigned treatment completed the Brain Symptom and Impact Questionnaire (BASIQ). Items of BASIQ were arranged as a symptom score or function score. RESULTS: Lung, breast, melanoma and renal cancer were the most prevalent primary cancer site among the study population, with 91 (53%), 25 (15%), 17 (10%) and 15 (9%) patients, respectively. Baseline BASIQ results were obtained before patients were treated with WBRT, neurosurgery, or SRS. Seventy-six (44%) and 96 patients (56%) were grouped to A and B, respectively. Group A reported lower quality of life (QOL) in all function scores (P<0.0001) and all symptom scores (P values from <0.0001 to 0.005) with the exception of energy (P=0.1). CONCLUSIONS: Baseline QOL in patients assigned WBRT alone was statistically worse as compared to patients assigned SRS, neurosurgery with or without WBRT.

The Brain Symptom and Impact Questionnaire in brain metastases patients: a prospective long-term follow-up study.

AIMS: To assess the ability of the Brain Metastases Symptom and Impact Questionnaire (BASIQ) in evaluating symptoms and impact on daily life. PATIENTS & METHODS: Patients with brain metastases completed BASIQ, Functional Assessment of Cancer Therapy-General, FACT-Brain at baseline and at 1, 2 and 3 months follow-ups. RESULTS: Thirty-six patients completed all follow-ups. BASIQ correlated well (r ≥ 0.40) with FACT subscales, except for social/family and emotional wellbeing. Linear regression analysis found no significant changes in quality of life (QOL) over time in both the BASIQ and FACT scales. Therefore, the two questionnaires coincide as both detected nonchanges. CONCLUSION: The ability of the BASIQ in evaluating symptoms and impact on over longer assessment periods was supported by the FACT questionnaires.

Treatment Patterns and Outcomes in Patients With Hepatocellular Carcinoma Stratified by Stage-Guided Treatment Categories.

PURPOSE: The purpose of this study was to assess the survival and treatment patterns of hepatocellular carcinoma (HCC) stratified by the NCCN stage-guided treatment categories in the absence of a universally accepted staging system for HCC. METHODS: Patients with HCC were identified using ICD-9 codes and inclusion in the Huntsman Cancer Institute tumor registry. Patients were stratified by the NCCN groupings around the time of diagnosis as potentially resectable or operable (RESECT), potentially transplantable (TRANSP), unresectable (UNRESECT), inoperable due to performance status (INOPER), or having metastatic (METAST) disease. Survival and treatment patterns were assessed by NCCN stage-guided treatment categories. RESULTS: A total of 221 patients (72.9% men) with HCC were identified. At the time of diagnosis, patients were categorized as RESECT (n=28, 12.7%), TRANSP (n=33, 14.9%), UNRESECT (n=77, 34.8%), INOPER (n=40, 18.1%), and METAST (n=38, 17.2%). Staging information was not specified for 5 patients (2.3%) even after chart review. Kaplan-Meier analysis demonstrated significant differences in survival between RESECT and UNRESECT categories, and between UNRESECT and METAST categories. The median survivals in RESECT, TRANSP, UNRESECT, INOPER, and METAST categories were 594, 562, 247, 167, and 44 days, respectively. Patients considered RESECT most frequently underwent resection (61%, n=17) and patients considered TRANSP had the highest use of liver transplants (33.3%, n=11). Use of any treatment was low in the METAST (31.6%, n=12) and INOPER (60.0%, n=24) groups. CONCLUSIONS: Treatment patterns in the NCCN groupings correlated with recommended treatment strategies. Overall, the NCCN groupings have a linear relationship in overall survival.

Psychometric validation of the Brain Symptom and Impact Questionnaire (BASIQ) version 1.0 to assess quality of life in patients with brain metastases.

OBJECTIVE: To test the reliability, clinical and psychometric validity of the Brain Symptom and Impact Questionnaire (BASIQ) in patients with brain metastases. METHODS: Brain metastases patients were interviewed using the BASIQ, Functional Assessment of Cancer-Brain (FACT-Br) and FACT-General (FACT-G) at baseline, with a follow-up assessment at 1 month. RESULTS: Forty patients had complete one data and the median age was 64 years. Patients with higher KPS, ECOG of 2, primary breast cancer, or >3 brain metastases, scored higher on the symptom scale of the BASIQ. All subscales showed no significant change in patient symptoms from baseline to follow-up. CONCLUSION: This study supports that the reliability, clinical and psychometric validity of BASIQ to be used in brain metastases patients.

Validation of the Brain Symptom and Impact Questionnaire (BASIQ) to assess symptom and quality of life in brain metastases.

OBJECTIVE: To validate the Brain Symptom and Impact Questionnaire (BASIQ) version 1.0 for brain metastases. METHODS: Patients with brain metastases and their healthcare professionals (HCPs) assessed the relevance of the BASIQ on a 0-10 scale with 10 as extremely relevant. RESULTS: A total of 52 patients and 20 HCPs participated in this study. In total, 95% of HCPs and 85% of patients found all items relevant. Balance and walking ability were rated relevant by 100% of patients and HCPs. Headache, nausea, energy, memory and ability to do housework were also rated relevant by 100% of HCPs. Over 95% of patients determined the items of ability to do housework, tiredness, energy, vision, memory and putting ideas into words as relevant. There were no items rated below 7 by patients or below 5 by HCPs. CONCLUSION: This study indicates that BASIQ version 1.0 has valid content items encompassing disease-related symptom and impact on daily living.

Treatment Patterns, Survival, and Healthcare Costs of Patients with Malignant Gliomas in a Large US Commercially Insured Population.

BACKGROUND: Glioblastoma multiforme is the most common malignant primary brain tumor in adults and is associated with poor survival rates. Symptoms often include headaches; nausea and vomiting; and progressive memory, personality, or neurologic deficits. The treatment remains a challenge, and despite the approval of multiple new therapies in the past decade, survival has not improved. OBJECTIVE: To describe treatment patterns, survival, and healthcare costs of patients with incident glioblastoma in a large US population. METHODS: For this population-based study, adult patients (aged ≥18 years) with incident malignant brain neoplasm who had undergone brain surgery between January 1, 2006, and December 31, 2010, were identified in the Truven Health Analytics MarketScan Research Databases. The patients were stratified into 4 cohorts based on the use of temozolomide and/or external beam radiation therapy within 90 days after brain surgery (ie, the index event). Treatment patterns, survival, and healthcare costs were assessed until patient death, disenrollment, or the end-of-study period. RESULTS: A total of 2272 patients met the inclusion criteria; of these, 37% received temozolomide and radiation therapy, 13.8% received radiation alone, 3.9% received temozolomide alone, and 45.3% of patients received neither. The average patient age ranged from 55.3 years to 59.8 years across the study cohorts; between 29.8% and 44% of patients in each cohort were female. The duration of temozolomide use was similar between the temozolomide-only cohort and patients receiving temozolomide with external beam radiation; approximately 76% of patients received temozolomide at least 60 days, dropping to 48.1% and 23% at 180 days and 360 days of follow-up, respectively. The median survival was 456 days, ranging from 331 days in the temozolomide-only cohort to 529 days in the cohort that received neither temozolomide nor external beam radiation. The average total costs in the 6 months postindex were $106,896, from $79,099 for patients who received neither temozolomide nor radiation to $138,767 for those who received both therapies. CONCLUSION: The survival patterns of patients with glioblastoma seen in this real-world study of current treatments in a clinical setting is similar to the survival rate reported in clinical trials. However, further cost-effectiveness and quality-of-life analyses will be critical to better understand the role of temozolomide therapy in this patient population, considering its considerable cost burden and potential negative impact on survival seen in this study.

Patterns of treatment, healthcare utilization and costs by lines of therapy in metastatic breast cancer in a large insured US population.

AIM: Metastatic breast cancer guidelines contain multiple lines of treatment and regimens; however, little data on therapeutic patterns and costs is available from real-world clinical practice. This descriptive study reports chemotherapy and biologic use, healthcare utilization and costs by line of therapy in a large insured US population. MATERIALS & METHODS: Adult women with newly diagnosed metastatic breast cancer (between 2005 and 2009) were identified from MarketScan® databases containing medical and pharmacy claims of >40 million enrollees insured with >100 US health plans. Descriptive statistics were reported for use, duration and mean per patient per month costs across four lines of therapy. RESULTS: Out of 7767 patients identified (mean [standard deviation] age = 58.2 [12] years), ≥50% received a subsequent line of therapy across the four lines (line 2: n = 4077; line 3: n = 2033; line four: n = 1059). The top two chemotherapies were paclitaxel and capecitabine in lines one and two, and paclitaxel and gemcitabine in lines three and four. The top two biologics were trastuzumab and bevacizumab across the multiple lines of treatments. Duration (mean, standard deviation and median days) varied across multiple lines of treatments: 162.7, 176.9 and 108.0 in line one; 147.5, 146.7 and 99.0 in line two; 139.9, 131.1 and 99.0 in line three; and 130.9, 123.4 and 94.0 in line four, respectively. Mean per patient per month costs decreased with increasing follow-up from US$13,147 (<6 months) to US$11,610 (7-12 months) to US$10,219 (12-24 months) to US$9,192 (24-36 months) to US$7,384 (>36 months). Cumulative costs increased with follow-up, from US$78,882 (<6 months) to US$443,062 (>36 months). CONCLUSION: Longer follow-up, regardless of number of lines of therapy, was associated with higher cumulative, but lower monthly, costs. Delaying progression and improving survival with more individualized treatment regimens may help slow the rate of increasing long-term costs of metastatic breast cancer treatment and care.

Comparative analysis of survival, treatment, cost and resource use among patients newly diagnosed with brain metastasis by initial primary cancer.

Brain metastases are a frequent complication of many systemic cancers and portend a poor prognosis. This retrospective analysis of health claims data compared survival, treatment and health care utilization and costs in patients with brain metastasis by primary tumor site. Adult commercial and Medicare Advantage enrollees newly diagnosed with brain metastasis in 01 Jan 2004 through 30 Apr 2010 were identified. Inclusion required at least 2 claims that identified the same primary cancer site prior to diagnosis of brain metastasis and no evidence of primary brain tumors. Health care utilization rates and costs were calculated at the patient level for each month of follow-up. Differences among primary cancer site cohorts were assessed by ANOVA (continuous variables), Chi square test (proportions) and the Poisson distribution (utilization rates). The primary cancer cohorts comprised 1,031 lung cancer, 93 melanoma and 395 female breast cancer patients. During the 6 months prior to brain metastasis diagnosis, 59 % of lung cancer patients had no evidence of lymph node involvement or other metastatic disease compared to 55 and 42 % of melanoma and breast cancer patients (P < 0.001). Survival after brain metastasis diagnosis was less than 3 months for 52, 43 and 39 % for lung cancer, breast cancer and melanoma, respectively (P < 0.001). Melanoma patients had the highest rate of inpatient stays and outpatient visits (P ≤ 0.003). Total monthly all-cause costs were: melanoma, $23,426; breast cancer $19,708; lung cancer, $17,007 (P = 0.003). Health care utilization and costs after brain metastasis diagnosis were substantial and differed by primary tumor site.

The impact of second-line agents on patients' health-related quality of life in the treatment for non-small cell lung cancer: a systematic review.

PURPOSE: In advanced non-small cell lung cancer (NSCLC), progressive disease burdens patients considerably. Second-line (2L) chemotherapy improves survival marginally but humanistic outcomes (i.e., quality of life, QOL) are underreported. The impact of 2L therapy remains an important consideration for patients and caregivers, and there have been QOL reviews for 1L, but not 2L, therapies. This review assessed QOL outcomes of approved, guideline-supported 2L chemotherapy with docetaxel, erlotinib, gefitinib, and pemetrexed in advanced NSCLC. METHODS: Clinical trial reports of approved, guideline-supported 2L or maintenance therapy for NSCLC published from 2000 to 2010 were identified from PubMed/Medline and clinical meetings. Outcomes were stratified by overall QOL impact, domain/symptom-specific effects, effect over time, and subgroup effects. RESULTS: Of 145 studies identified, 24 full-text articles were retained. Studies with docetaxel versus best supportive care (n = 1) and active comparators (n = 4) reported non-significant overall QOL improvements, as did studies of gefitinib versus placebo and active comparator (n = 7). Overall QOL improvements were seen for gefitinib versus docetaxel (n = 2) and gefitinib in a single-arm study (n = 1). At the symptom level, studies of docetaxel (n = 4/7), gefitinib (n = 7/9), and pemetrexed (n = 1) reported non-significant results. Subgroup analyses indicated improved QOL outcomes for gefitinib-treated responders versus non-responders, worse QOL for gefitinib-treated smokers versus placebo, worse QOL for gefitinib-treated Asian patients versus placebo, and longer time to symptom deterioration in erlotinib versus placebo-treated elderly patients. CONCLUSIONS: Significant improvements in overall QOL with 2L chemotherapy for advanced NSCLC were infrequent. Single-arm studies and those with less toxic regimens more commonly provided statistically significant improvements in QOL outcomes. Methodological heterogeneity impedes cross-study QOL comparisons.

Economic burden of dermatologic adverse drug reactions in the treatment of colorectal, non-small cell lung, and head and neck cancers with epidermal growth factor receptor inhibitors.

BACKGROUND: Patients treated with epidermal growth factor receptor inhibitors (EGFRIs) may develop dermatologic adverse drug reactions (ADRs) that may affect patients' quality-of-life, require medical care, and may lead to substantial costs. This study assessed the economic burden of dermatologic ADRs in colorectal cancer (CRC), head and neck cancer (HNC), and non-small cell lung cancer (NSCLC) patients. METHODS: Adult patients with ≥1 diagnosis for the study cancer initiated on EGFRIs indicated for CRC, HNC, and NSCLC were selected from a large commercial database (MarketScan Commercial Database [2000-2010]; Thomas Reuters, New York, NY). For each cancer type, patients were classified into two mutually exclusive cohorts: 'ADR' (patients with ≥1 ADR following EGFRI initiation) and 'ADR-free' (patients without any ADR). Patients were observed from the index date up to the end of continuous healthcare plan enrollment or 90 days after EGFRI discontinuation, whichever occurred first. For each cancer group, the proportion of patients and the incidence rate (IR) of experiencing ≥1 dermatologic ADR were reported. Incidence rate ratios for healthcare resource utilization and monthly incremental costs (2010 USD) were estimated using Poisson regression and generalized linear or two-part models, respectively. RESULTS: Overall, the proportion of patients with ≥1 ADR ranged between 20.5-36.4% across cancer groups (IR ranged between 44.2-57.4 per 100 patient-years). After adjusting for confounders, in each cancer group, ADR patients had higher incidence of healthcare resource utilization, generally driven by higher incidence of emergency room visits and incurred incremental total monthly healthcare costs that ranged between $2284-$3210 across cancer groups. LIMITATIONS: There was no clinical measure of cancer staging and ADR severity in the database. CONCLUSIONS: Results suggest that patients with CRC, NSCLC, and HNC, who may benefit from EGFRI therapies, may also incur a substantial economic burden that is associated with dermatologic ADRs.

Comparison of FACT- and EQ-5D-based utility scores in cancer.

OBJECTIVE: Although utility-based algorithms have been developed for the Functional Assessment of Cancer Therapy (FACT), their properties are not well known compared with those of generic utility measures such as the EQ-5D. Our objective was to compare EQ-5D and FACT preference-based scores in cancer patients. METHODS: A retrospective analysis was conducted on cross-sectional data collected from 472 cancer patients who completed both FACT-General and the EQ-5D. Preference-based scores were calculated by using published scoring functions for the EQ-5D (Dolan P. Modeling valuations for EuroQol health states. Med Care 1997;35:1095-108; Shaw JW, Johnson JA, Coons SJ. US valuation of the EQ-5D health states: development and testing of the D1 valuation model. Med Care 2005;43:203-20) and FACT (Dobrez D, Cella D, Pickard AS, et al. Estimation of patient preference-based utility weights from the Functional Assessment of Cancer Therapy-General. Value Health 2007;10:266-72; Kind P, Macran S. Eliciting social preference weights for Functional Assessment of Cancer Therapy-Lung health states. Pharmacoeconomics 2005;23:1143-53; Cheung YB, Thumboo J, Gao F, et al. Mapping the English and Chinese versions of the Functional Assessment of Cancer Therapy-General to the EQ-5D utility index. Value Health 2009;12:371-6). Scores were compared on the basis of clinical severity by using Eastern Cooperative Oncology Group performance status ratings by physicians and patients. Relative efficiency of each scoring function was examined by using ratios of F statistics. RESULTS: Mean scores for the overall cohort were lowest when using Kind and Macran's FACT UK societal algorithm (0.55, SD 0.09) and highest when using Dobrez et al.'s FACT US patient algorithm (0.83, SD 0.08). Mean difference scores associated with clinical severity, when extrapolated to quality-adjusted life-years (QALYs), had a range of 0.18 QALYs gained using FACT (Kind and Macran) to 0.45 QALYs gained using the EQ-5D (Dolan). However, relative efficiencies suggested that FACT (Kind and Macran) scores may provide greater statistical power to detect significant differences based on clinical severity. CONCLUSIONS: We found important differences in utilities scores estimated by each algorithm, with FACT-based algorithms tending to underestimate the QALY benefit compared with algorithms based on the EQ-5D. These differences highlight some of the challenges in using disease-specific preference-based measures for decision making despite potentially more relevant disease-specific content.

Medical care costs and survival associated with hepatocellular carcinoma among the elderly.

BACKGROUND & AIMS: We assessed the burden of hepatocellular carcinoma (HCC), in terms of mortality and medical care costs, based on analysis of the Surveillance, Epidemiology and End Results (SEER)-Medicare database. METHODS: We analyzed data from the SEER-Medicare database on patients 66 years or older who were diagnosed with primary HCC from 1991 to 2007, entitled for Medicare Parts A and B, and not enrolled in health maintenance organizations (n = 5712). Controls were individuals without HCC, identified from a 5% sample of Medicare beneficiaries residing in SEER areas; they were matched 1:1 with individuals with HCC (cases) for age, sex, race, and geographic region (average age, 75 y; 34.7% female). Kaplan-Meier analysis was used to estimate survival distributions. Costs were reported in 2009 dollars; per-patient-per-month (PPPM) costs were compared between cases and controls using the Wilcoxon rank sum test. RESULTS: The largest proportion of cases had localized disease (38.2%), followed by regional (24.0%), unstaged (20.4%), and distant (17.3%) disease. The median survival times were 5 months for cases and 60 months for controls; they were 3 months for patients with distant disease, 4 months for patients with regional disease, and 9 months for those with localized disease. The mean PPPM costs were $7863 for cases and $1243 for controls (P < .001). These costs were primarily driven by inpatient (mean, $5439 vs $682 without HCC; P < .001) and hospice (mean $554 vs $42 without HCC; P < .001) care. Mean PPPM costs by stage were $7265 for localized disease, $8072 for regional disease, and $9585 for distant disease (P < .001 for trend). CONCLUSIONS: Based on analysis of the SEER-Medicare database, costs for patients with HCC are approximately 6- to 8-fold higher than for those without this cancer. Patients with distant HCC had the greatest costs. These findings highlight that HCC is a substantial medical cost burden for elderly patients.

Treatment pattern by hormone receptors and HER2 status in patients with metastatic breast cancer in the UK, Germany, France, Spain and Italy (EU-5): results from a physician survey.

BACKGROUND: The differences in country-specific treatment patterns across Europe for metastatic breast cancer (mBC) patients have not been extensively studied. This study compared the treatment choices in aggregate, as well as by biomarker status, between various lines of therapy in clinical practice in the EU-5 countries among newly diagnosed mBC patients. MATERIALS & METHODS: The IMS LifeLink™ Oncology Analyzer database, based on surveys of practicing oncologists, was used to identify mBC patients aged ≥21 years. In this database, sample-level data are projected to national-level estimates for each country using a sample projection technique. RESULTS: The prevalence of hormone receptors (71-74%) is quite similar across different countries, while HER2 overexpression varies from 22 (France) to 34% (Italy); chemotherapy combined with HER2-targeted medicine was the mainstay of treatment for HER2(+) patients. The use of HER2-targeted medicine and bevacizumab greatly varied: while they were most frequently used in France, they were least frequently used in the UK. Fewer treatment options existed for triple-negative patients and patients with HER2(+) disease following trastuzumab treatment. Chemotherapy was the treatment choice for triple-negative patients, as these patients do not respond to hormonal therapy and HER2-targeted medicine. CONCLUSION: This study found that, while a trastuzumab-based regimen is the preferred option for treating HER2(+) mBC patients in the EU-5, variations in this personalized medicine approach exist between different EU-5 countries. However, fewer treatment options exist for triple-negative and HER2(+) patients after trastuzumab treatment, highlighting the unmet need for these patient subgroups.

Improvement in work place and household productivity for patients with early rheumatoid arthritis treated with adalimumab plus methotrexate: work outcomes and their correlations with clinical and radiographic measures from a randomized controlled trial companion study.

OBJECTIVE: To evaluate household and work place outcomes for patients with rheumatoid arthritis (RA) who were homemakers or employed workers, respectively, and who were treated with adalimumab plus methotrexate versus methotrexate monotherapy. We also determined baseline predictors of household and work place outcomes. METHODS: Data were from a health economic companion study to PREMIER, a 2-year, randomized controlled trial of methotrexate-naive patients with early RA (<3 years) who received treatment with adalimumab plus methotrexate, adalimumab, or methotrexate. Absenteeism (number of days missed or unfit to work), presenteeism (self-judgment of the effects of RA on job or household performance), and employment status were collected from self-reports at baseline and varying time points during the study. RESULTS: Household and work place outcomes were generally similar for homemakers and employed workers. Over 2 years, patients who received combination therapy missed approximately half as many days as patients who received methotrexate (17.4 versus 36.9 days for employed workers; 7.9 versus 18.6 days for homemakers). Presenteeism was lower (reflecting better productivity) for combination therapy than methotrexate monotherapy. The likelihood of gaining/retaining employment over 2 years was greater for combination therapy than methotrexate monotherapy (odds ratio 1.530, 95% confidence interval 1.038-2.255; P = 0.0318). Baseline radiographic progression was an independent predictor for retaining/gaining employment at 2 years. CONCLUSION: Compared with methotrexate monotherapy, combination therapy was associated with more positive work outcomes: less absenteeism, less presenteeism, and greater likelihood of gaining/retaining employment. Radiographic progression at baseline was predictive of the ability to retain or gain employment.

Differences in annual medication costs and rates of dosage increase between tumor necrosis factor-antagonist therapies for rheumatoid arthritis in a managed care population.

BACKGROUND: Tumor necrosis factor (TNF) antagonists are commonly used to treat rheumatoid arthritis (RA). Differences in the dosage and mode of administration of these agents may result in differential rates of dosage adjustment and costs of care. OBJECTIVE: This study compared dosing patterns and annual costs associated with the use of the subcutaneous TNF antagonists adalimumab and etanercept, and the intravenous TNF antagonist infliximab. METHODS: A large managed care database (PharMetrics) was used to identify patients with RA who newly initiated TNF-antagonist therapy with adalimumab, etanercept, or infliximab on or after January 1, 2003, and had at least 6 months of continuous health plan enrollment before initiation of therapy and 12 months of continuous enrollment after initiation. The patients were followed over 12 months of enrollment. Annual pharmacy, inpatient, and outpatient costs were estimated based on plan reimbursements and were compared between cohorts. The average daily dosage (ADD) between prescription refills was used to compare the percentages of patients with greater-than-expected dosing (GTED), defined as 2 consecutive increases in ADD relative to the patient's established maintenance dosage. RESULTS: A total of 2382 patients (568 adalimumab, 1181 etanercept, 633 infliximab) were included in the analysis. Significantly more patients had GTED with infliximab compared with adalimumab and etanercept (32.1%, 8.5%, and 4.7%, respectively; both comparisons, P < 0.05). For patients with a dosage increase, the mean time to the first GTED was significantly shorter for infliximab compared with adalimu-mab and etanercept (154.5, 173.3, and 167.9 days; both, P < 0.05). The mean annual costs of anti-TNF therapy, adjusted for baseline differences, were significantly greater for infliximab compared with adalimumab and etanercept ($15,617, $12,200, and $12,146; both, P < 0.05). There were also significant differences between infliximab relative to adalimumab and etanercept in total RA-related medication costs ($16,280, $12,989, and $12,794; P < 0.05) and total pharmacy costs ($17,854, $14,805, and $14,398; P < 0.05). CONCLUSION: Patients initiating TNF-antagonist treatment for RA with infliximab incurred annual medication costs that were nearly 30% greater than costs in those initiating therapy with adalimumab or etanercept, in part because of the significantly greater rate of GTED in infliximab recipients.

Inhaled corticosteroids or long-acting beta-agonists alone or in fixed-dose combinations in asthma treatment: a systematic review of fluticasone/budesonide and formoterol/salmeterol.

BACKGROUND: Inhaled corticosteroids (ICSs) and long-acting inhaled beta(2)-agonists (LABAs) are recommended treatment options for asthma. OBJECTIVE: This review compares the clinical effectiveness and tolerability of the ICSs fluticasone propionate and budesonide and the LABAs formoterol fumarate and salmeterol xinafoate administered alone or in combination. METHODS: A systematic review of the clinical studies available on MEDLINE (database period, 1950-September 2009) was conducted to assess English-language randomized controlled trials in children and adults with asthma. Treatment outcomes included lung function, symptom-free days (SFDs), use of rescue/reliever medications, asthma exacerbations, and tolerability profile. RESULTS: Use of fluticasone was associated with significantly greater improvement in lung function and better asthma symptom control than budesonide. Similarly, formoterol was associated with significantly greater improvement in lung function and better asthma symptom control (as measured by less rescue medication use and more SFDs) compared with salmeterol. Single inhaler combination regimens (budesonide/ formoterol and fluticasone/salmeterol) were frequently more effective in improving all treatment outcomes than either monotherapy alone. Across all comparisons, a review of studies in adults and children did not find statistically significant differences in outcomes between the ICS and LABA therapies considered in this research. In general, no differences in tolerability profiles were reported between the ICS and LABA options, although the risk for growth retardation was lower with fluticasone than budesonide and with budesonide/formoterol than with budesonide monotherapy. CONCLUSIONS: In this systematic review, fluticasone and formoterol appear to provide improved therapeutic benefits versus budesonide and salmeterol, respectively. Both fluticasone/salmeterol and budesonide/ formoterol combination therapies appeared to be associated with greater improvements in outcomes measures than the corresponding ICS and LABA monotherapies.

Validation of the Investigator's Assessment Questionnaire, a new clinical tool for relative assessment of response to antipsychotics in patients with schizophrenia and schizoaffective disorder.

The success of long-term therapy in schizophrenia is contingent upon real-world effectiveness or improvements in several domains, including efficacy, safety and tolerability. This report describes the Investigator's Assessment Questionnaire (IAQ), a new 10-item instrument designed to assess relative effectiveness (efficacy, safety and tolerability) of antipsychotic medications in patients with schizophrenia or schizoaffective disorder. To measure content validity, 300 psychiatrists rated the importance of the IAQ items. Efficacy (i.e., positive and negative symptoms) was considered most important, but importance scores relative to the mean ranged only from 0.87 to 1.18, suggesting similar importance of the items. Cronbach's coefficient alpha values showed that the items were internally consistent. Factor analyses indicated that all IAQ items belong to a single domain. Data from the US Broad Effectiveness Trial of Aripiprazole were used for construct validation. Total IAQ score correlated significantly with time to treatment discontinuation (r=-0.50), Clinical Global Impressions-Improvement (CGI-I) score (r=0.76) and medication preference of patients (r=0.71) or caregivers (r=0.70). A one-unit decrease in IAQ score corresponded to an additional 1.35 days in the study and a decrease in CGI-I of 0.21 units. These results provide initial validation of the IAQ as a tool for evaluating antipsychotic response in patients with schizophrenia or schizoaffective disorder.

Comparative analysis of individuals with and without chiropractic coverage: patient characteristics, utilization, and costs.

BACKGROUND: Back pain accounts for more than $100 billion in annual US health care costs and is the second leading cause of physician visits and hospitalizations. This study ascertains the effect of systematic access to chiropractic care on the overall and neuromusculoskeletal-specific consumption of health care resources within a large managed-care system. METHODS: A 4-year retrospective claims data analysis comparing more than 700 000 health plan members with an additional chiropractic coverage benefit and 1 million members of the same health plan without the chiropractic benefit. RESULTS: Members with chiropractic insurance coverage, compared with those without coverage, had lower annual total health care expenditures ($1463 vs $1671 per member per year, P<.001). Having chiropractic coverage was associated with a 1.6% decrease (P = .001) in total annual health care costs at the health plan level. Back pain patients with chiropractic coverage, compared with those without coverage, had lower utilization (per 1000 episodes) of plain radiographs (17.5 vs 22.7, P<.001), low back surgery (3.3 vs 4.8, P<.001), hospitalizations (9.3 vs 15.6, P<.001), and magnetic resonance imaging (43.2 vs 68.9, P<.001). Patients with chiropractic coverage, compared with those without coverage, also had lower average back pain episode-related costs ($289 vs $399, P<.001). CONCLUSIONS: Access to managed chiropractic care may reduce overall health care expenditures through several effects, including (1) positive risk selection; (2) substitution of chiropractic for traditional medical care, particularly for spine conditions; (3) more conservative, less invasive treatment profiles; and (4) lower health service costs associated with managed chiropractic care. Systematic access to managed chiropractic care not only may prove to be clinically beneficial but also may reduce overall health care costs.