Estimating prevalence of classical homocystinuria in the United States using Optum's de-identified market clarity data.

Background and objectives: Prevalence estimates for classical homocystinuria (HCU) are variable and likely underestimated due to underdiagnosis. Claims data represent a strong but seldom used resource to analyze prevalence of HCU. The aim of this study was to estimate a prevalence range of HCU in the US utilizing a combination of diagnosis codes, total homocysteine levels, and clinical presentations indicative of HCU. Methods: This was a non-interventional retrospective cohort study, using Optum's de-identified Market Clarity Data, with a patient identification period from January 01, 2016, through September 30, 2021. An algorithm was developed to identify 2 cohorts of patients using broad and strict definitions of HCU. The index date was the date within the identification period on which the first criterion was met for the inclusion criteria. Baseline demographics, clinical characteristics, and complications were assessed and summarized using descriptive statistics. Crude and standardized prevalence estimates were calculated. Results: There were 3880 and 633 patients that met the relevant inclusion criteria for the broad and strict cohorts, respectively. The projected US prevalence of HCU was calculated to be 17,631 and 3466 based on the broad and strict definitions, respectively. The average annual standardized prevalence across 2016-2020 was 5.29 and 1.04 per 100,000 people for the broad and strict cohorts, respectively. Conclusions: Prevalence estimates of HCU vary depending on databases or datasets used and identification criteria. Many patients with clinical presentations suggesting a diagnosis of HCU did not have an associated diagnosis, potentially indicating underdiagnosis or underreporting. Future research should study alternative methods, such as the identification algorithm in our analysis, to better diagnose and understand the true prevalence of HCU.

Cardiovascular Event Recurrence and Costs after First Myocardial Infarction, Ischemic Stroke, or Intracerebral Hemorrhage in Taiwan.

Background/Objectives: We aimed to assess the incidence of recurrent cardiovascular (CV) events after the first myocardial infarction (MI), ischemic stroke (IS), or intracerebral hemorrhage (ICH) and to estimate acute and follow-up medical costs. Methods: Using Taiwan's National Health Insurance Research Database, we identified patients with their first MI, IS, or ICH between 2011 and 2017. The cumulative incidence rates of second CV events (including events of the same type [recurrent] or of the other two types) were estimated. The costs for hospitalization and all-cause follow-up were calculated for the first and recurrent CV events and are presented as median (Q1~Q3) in 2017 US dollars. Results: We identified 70,428 patients with a first MI, 123,857 with a first IS, and 41,347 with a first ICH. The cumulative incidence rates of recurrence during the first year and after six years were 3.9% and 10.1% for MI, 5.3% and 13.8% for IS, and 3.9% and 8.9% for ICH, respectively. For first and recurrent nonfatal events, acute hospitalization costs were $4,729 (3,737~5,985) and $4,459 (2,887~6,026) for MI; $1,136 (756~2,183) and $1,224 (774~2,412) for IS; and $2,985 (1,264~8,831) and $2,170 (1,183~4,675) for ICH, respectively. Total annual costs for nonfatal first events in the first year and second year of follow-up were $2413 (1,393~6,120) and $1,293 (654~2,868) for MI, $2,174 (1,040~5,472) and $1,394 (602~3,265) for IS, and $2,963 (995~8,352) and $1,185 (405~3,937) for ICH, respectively. Conclusions: In patients with a first MI, IS, and ICH, recurrent CV events continue to substantially impact public health and escalate the economic burden.

Healthcare resource utilization and costs of cardiovascular events in patients with atherosclerotic cardiovascular disease in Germany - results of a claims database study.

OBJECTIVES: We assessed healthcare resource utilization (HCRU) and costs of cardiovascular (CV) events in patients with a history of atherosclerotic cardiovascular disease (ASCVD) in Germany. METHODS: We conducted a retrospective matched case-control study based on German claims data from 1 January 2012 to 31 December 2017 using the "Institute for Applied Health Research Berlin" (InGef) Research Database. Cases who had a myocardial infarction (MI), stroke and angina pectoris identified by ICD-10-GM codes between 1 January 2014 and 31 December 2016 were matched to event-free controls by an exact matching approach without replacement at a ratio of 1:2. Costs and HCRU were assessed in individual 1-year follow-up periods after the index event for the overall cohort and subgroups of MI cases and stroke cases. RESULTS: The overall cohort consisted of a total of 14,169 cases with a CV index event matched to 28,338 controls. The mean age of the overall cohort was 73.3 years, 34.1% of the patients were female, 3,717 (26.2%) had an MI, and 3,752 (26.5%) had stroke. Following the index events, 12.2% of cases in the overall cohort, 12.6% of MI cases, and 8.7% of stroke cases experienced a recurrent CV event. CV cases had on average 1.7 more all-cause hospitalizations (p <0.001) and 6.1 more outpatient visits (p <0.001) during the 1-year follow-up period than did controls. In the MI and stroke subgroups, cases had on average 1.8 and 1.6 more all-cause hospitalizations and 7.0 and 4.0 more outpatient visits, respectively (differences were statistically significant). Compared to controls, cases incurred on average higher total healthcare costs: by €11,898 for overall cases, by €16,349 for MI, and by €14,360 in stroke cases (overall: p <0.001; MI: p <0.001; stroke: p <0.001). CONCLUSION: CV events in ASCVD patients pose a considerable clinical burden on patients and cause significant costs for the German statutory healthcare system.

Lipid lowering therapy patterns and the risk of cardiovascular events in the 1-year after acute myocardial infarction in United Arab Emirates.

AIM: In United Arab Emirates, cardiovascular disease (CVD) is a leading cause of mortality and 22% of CVD deaths are attributable to acute myocardial infarction (MI). Adherence to guidelines for lipid management is incompletely described in the Middle East. This study aimed to characterize lipid lowering therapy (LLT) patterns and the risk of subsequent cardiovascular events (CVEs) in the first year after MI. METHODS: This was a retrospective cohort study using the Dubai Real-World Claims Database, including all patients discharged with MI between January 01, 2015 and December 31, 2018, followed-up until December 31, 2019. RESULTS: In the first year after MI, 8.42% of 4,595 patients included experienced at least one recurrent MI (rate 6.77 events/100 person-years [PYs]), 2.94% had one revascularization (cumulative rate 0.55 events/100 PYs) and 2.66% had one hospitalization due to unstable angina (cumulative rate 5.16 new events/100 PYs). The majority (60.40%) of the patients presented with LDL-C levels ≥ 70 mg/dL after MI. In the first year after MI, 93.45% of the patients received LLT, mainly high-intensity statin (67.79%); with a minority of patients receiving statin + ezetimibe (4.55%), PCSK9i (0.20%) or ezetimibe alone (0.07%). CONCLUSION: Patients hospitalized with MI in Dubai present an increased risk of CVEs in their first-year post-discharge. Majority of the patients presented with LDL-C levels above 70 mg/dL, which indicates suboptimal lipid control with existing LLT, particularly in high-risk patients.

Prevalence of atherosclerotic cardiovascular disease and subsequent major adverse cardiovascular events in Alberta, Canada: A real-world evidence study.

BACKGROUND: Atherosclerotic cardiovascular disease (ASCVD) is a leading cause of morbidity and mortality worldwide. Data from Canadian populations regarding the burden of ASCVD are limited. Therefore, we describe the 5-year period prevalence of ASCVD and subsequent major adverse cardiovascular event (MACE) outcomes among patients with ASCVD in Alberta, Canada. METHODS: A retrospective, observational study was conducted by linking provincial health services data, vital statistics, and pharmaceutical dispenses data. Five-year period prevalence of clinical ASCVD was captured between 2011 and 2016, and a cohort of adult patients with an initial clinical ASCVD event were identified between 2012 and 2016. One-year incidence rates (IRs) of subsequent MACE outcomes were calculated as composite and individual measures. A subgroup of patients with acute myocardial infarction (AMI) as their index event was examined. RESULTS: There were 198 573 patients (mean [standard deviation] age: 63.9 [15.6] years; 56.6% males) identified with clinical ASCVD between 2012 and 2016. Overall, the 5-year period prevalence of ASCVD in Alberta was 89.9 per 1000 persons and the 1-year IR for a primary MACE outcome was 6.15 (95% confidence interval [CI]: 6.03-6.26) per 100 person-years. Among the ASCVD cohort, 9465 had an AMI as their index event and the IR for a primary MACE outcome was 14.30 (95% CI: 13.45-15.20) per 100 person-years. CONCLUSIONS: This study found that the prevalence of ASCVD and the rate of subsequent MACE outcomes 1 year following the initial ASCVD event are substantial, particularly among patients with an AMI. Secondary prevention strategies aimed at lowering this risk are needed for patients with ASCVD.

Low-density lipoprotein cholesterol lowering in real-world patients treated with evolocumab.

BACKGROUND: Low-density lipoprotein cholesterol (LDL-C) is a risk factor for atherosclerotic cardiovascular disease (ASCVD). There are limited real-world data on LDL-C lowering with evolocumab in United States clinical practice. HYPOTHESIS: We assessed LDL-C lowering during 1 year of evolocumab therapy. METHODS: This retrospective cohort study used linked laboratory (Prognos) and medical claims (IQVIA Dx/LRx and PharMetrics Plus® ) data. Patients with a first fill for evolocumab between 7/1/2015 and 10/31/2019 (index event) and LDL-C ≥ 70 mg/dL were included (overall cohort; N = 5897). Additionally, a patient subgroup with a recent myocardial infarction (MI) within 12 months (median 130 days) before the first evolocumab fill was identified (N = 152). Reduction from baseline LDL-C was calculated based on the lowest LDL-C value recorded during a 12-month follow-up period. RESULTS: The mean (SD) age was 65 (10) years; 61.9% of patients had ASCVD diagnoses and 70.7% of patients were in receipt of lipid-lowering therapy. Following evolocumab treatment, changes in LDL-C from baseline were -60% in the overall cohort (median [interquartile range (IQR)] 146 [115-180] mg/dL to 58 [36-84] mg/dL) and -65% in the recent MI subgroup (median [IQR] 137 [109-165] mg/dL to 48 [30-78] mg/dL). In the overall cohort and recent MI subgroup, 62.1% and 69.7% of patients achieved LDL-C < 70 mg/dL, respectively. CONCLUSIONS: In this real-world analysis, evolocumab was associated with significant reductions in LDL-C comparable to that seen in the FOURIER clinical trial, which were durable over 1 year of treatment.

Developing a preference-based utility scoring algorithm for the Psoriasis Area Severity Index (PASI).

Introduction: It is challenging to identify health state utilities associated with psoriasis because generic preference-based measures may not capture the impact of dermatological symptoms. The Psoriasis Area Severity Index (PASI) is one of the most commonly used psoriasis rating scales in clinical trials. The purpose of this study was to develop a utility scoring algorithm for the PASI. Methods: Forty health states were developed based on PASI scores of 40 clinical trial patients. Health states were valued in time trade-off interviews with UK general population participants. Regression models were conducted to crosswalk from PASI scores to utilities (e.g. OLS linear, random effects, mean, robust, spline, quadratic). Results: A total of 245 participants completed utility interviews (51.4% female; mean age = 45.3 years). Models predicting utility based on the four PASI location scores (head, upper limbs, trunk, lower limbs) had better fit/accuracy (e.g. R2, mean absolute error [MAE]) than models using the PASI total score. Head/upper limb scores were more strongly associated with utility than trunk/lower limb. The recommended model is the OLS linear model based on the four PASI location scores (R2 = 0.13; MAE = 0.03). An alternative is recommended for situations when it is necessary to estimate utility based on the PASI total score. Conclusions: The derived scoring algorithm may be used to estimate utilities based on PASI scores of any treatment group with psoriasis. Because the PASI is commonly used in psoriasis clinical trials, this scoring algorithm greatly expands options for quantifying treatment outcomes in cost-effectiveness analyses of psoriasis therapies. Results indicate that psoriasis of the head/upper limbs could be more important than trunk/lower limbs, suggesting reconsideration of the standard PASI scoring approach.

Correction to: Treatment patterns in patients with osteoporosis at high risk of fracture in Japan: retrospective chart review.

In this article it was mistakenly stated that Akimitsu Miyauchi is affiliated with both Miyauchi Medical Center, Osaka and Amgen Astellas BioPharma K.K., Tokyo. In fact he is affiliated only with Miyauchi Medical Center; he has no connection with Amgen Astellas.

Treatment patterns in patients with osteoporosis at high risk of fracture in Japan: retrospective chart review.

Osteoporosis (OP) causes reduced bone strength and increases risk of fractures. Medical records from specialist clinics in Japan of postmenopausal women with OP and high risk of fracture were analysed. Majority of patients were treated for OP as recommended and were prescribed OP medications soon after high-risk OP diagnosis. PURPOSE: The incidence of osteoporosis (OP) in Japan is predicted to increase significantly in coming decades. Resultant osteoporotic fractures are a significant contributor of economic and social burden among elderly osteoporosis patients. This retrospective chart review was conducted as a response to the current evidence gap in the treatment patterns for OP patients with high risk of fracture in Japan. METHODS: This was a multi-centre retrospective chart review that analysed data extracted from the medical records of postmenopausal OP patients at high risk for fracture who received care at 11 specialist clinics and medical centers in Japan for at least 18 to 24 months. Main outcome was OP treatment patterns. RESULTS: The study included 709 eligible patients of whom 623 (87.9%) were prescribed OP medication during the study period. The most common reason for not taking OP medication was patient unwillingness to take medication. The most common OP medications prescribed initially were minodronic acid (20.1%), alendronate (19.9%), raloxifene (14.1%), weekly teriparatide acetate (12.4%) and eldecalcitol (11.4%). Majority of patients (62.1%) were still taking their initial medication at the end of the 18-24 month follow-up. CONCLUSIONS: A high percentage of patients (87.9%) in Japan received OP medications soon after their high-risk diagnosis, with bisphosphonates, selective estrogen receptor modulators and teriparatide being the predominant treatment options.

Two-year persistence and compliance with osteoporosis therapies among postmenopausal women in a commercially insured population in the United States.

This retrospective, observational study assessed 2-year persistence and compliance by treatment, route of administration, and dosing frequency in postmenopausal women initiating a new osteoporosis therapy. Two-year persistence and compliance rates were higher in women receiving injectables compared with oral agents. PURPOSE: This study extends previous studies limited to 1-year follow-up by examining persistence with osteoporosis therapies over a 2-year period and compares short- and long-term trends in persistence and compliance among postmenopausal women with commercial or Medicare supplemental insurance in the USA. METHODS: This retrospective, observational cohort study enrolled women ≥50 years newly initiating osteoporosis therapy between January 1 and December 31, 2012 (i.e., the index date), with continuous enrollment ≥14 months before and ≥24 months after their index date. Persistence (continuous therapy without a >60-day gap) and compliance with the index therapy were evaluated at 2 years of follow-up. Multivariable logistic regression was used to compare the odds of persistence and compliance across treatment and dosing regimens. RESULTS: This study included 43,543 patients with mean (standard deviation) age 65 (10) years. At 2 years of follow-up, persistence and compliance were higher for patients treated with injectable agents (ranging from 34 to 41%, excluding an every-3-month injection) than those treated with oral agents (ranging from 20 to 31%). Additionally, patients initiating oral bisphosphonates (except risedronate once daily), raloxifene (daily), or zoledronic acid (annually) had significantly lower odds of persistence compared with denosumab (every 6 months). CONCLUSIONS: Patients initiating injectable therapies had greater persistence and compliance at 2 years than those initiating oral therapies. Patients initiating an every-6-month injection had significantly higher persistence compared with those initiating more frequently dosed (e.g., daily and weekly) oral or injectable agents.

Clinical meaningfulness of complete skin clearance in psoriasis.

BACKGROUND: New psoriasis therapies have increased the ability to achieve skin clearance. However, insufficient evidence exists on the impact of total skin clearance from the patient perspective. OBJECTIVE: We sought to determine if complete skin clearance is clinically meaningful compared with treatment responses without clearance. METHODS: Pooled data from 3 phase-III trials were used to compare results for patients with complete skin clearance (Psoriasis Area and Severity Index [PASI] 100 or static Physician Global Assessment score 0) with patients without complete skin clearance (PASI 75 to <100 or static Physician Global Assessment score 1) based on Psoriasis Symptom Inventory and Dermatology Life Quality Index. RESULTS: Percentages of patients with Psoriasis Symptom Inventory score 0 were 45% for those achieving PASI 100 and 8% for PASI 75 to <100 (P < .001). Respective percentages with Dermatology Life Quality Index score 0/1 were 80% and 55% (P < .001). PASI 100 resulted in incremental improvement over PASI 90 to <100 (incremental differences of 28% for Psoriasis Symptom Inventory score 0 and 18% for Dermatology Life Quality Index score 0). Similar results were observed for static Physician Global Assessment scores 0 versus 1. CONCLUSIONS: Complete skin clearance represents a clinically meaningful end point and outcome for patients, reflected in experiences of no psoriasis symptoms and no impairment on health-related quality of life.

Biologic therapy adherence, discontinuation, switching, and restarting among patients with psoriasis in the US Medicare population.

BACKGROUND: Studies indicate adherence to biologics among patients with psoriasis is low, yet little is known about their use in the Medicare population. OBJECTIVE: We sought to investigate real-world utilization patterns in a national sample of Medicare beneficiaries with psoriasis initiating infliximab, etanercept, adalimumab, or ustekinumab. METHODS: We conducted a retrospective claims analysis using 2009 through 2012 100% Medicare Chronic Condition Data Warehouse Part A, B, and D files, with 12-month follow-up after index prescription. Descriptive and multivariate analyses were used to examine rates of and factors associated with biologic adherence, discontinuation, switching, and restarting. RESULTS: We examined 2707 patients initiating adalimumab (40.0%), etanercept (37.9%), infliximab (11.7%), and ustekinumab (10.3%); during 12-month follow-up, 38% were adherent and 46% discontinued treatment, with 8% switching to another biologic and 9% later restarting biologic treatment. Being female and being ineligible for low-income subsidies were associated with increased odds of decreased adherence. Outcomes varied by index biologic. LIMITATIONS: Patient-reported reasons for nonadherence or gaps in treatment are unavailable in claims data. CONCLUSION: Medicare patients initiating biologics for psoriasis had low adherence and high discontinuation rates. Further investigation into reasons for inconsistent utilization, including exploration of patient and provider decision-making and barriers to more consistent treatment, is needed.

Differences in psoriasis signs and symptom severity between patients with clear and almost clear skin in clinical practice.

INTRODUCTION: In psoriasis clinical trials, treatment success is often defined as achieving a static Physician Global Assessment (sPGA) score of 0 (clear) or 1 (almost clear). Patients with clear versus almost clear skin may experience psoriasis differently. This study assessed whether aggregating these patients underestimates subjective improvements associated with total skin clearance. METHODS: Patients with plaque psoriasis with stable sPGA 0 or 1 currently treated with adalimumab, etanercept, infliximab, or ustekinumab reported Psoriasis Symptom Inventory (PSI) scores for seven days and Dermatology Life Quality Index (DLQI) scores on day 8. The PSI measures psoriasis signs and symptom severity; the DLQI measures the impact of skin disease on quality of life. This analysis compared PSI and DLQI outcomes between patients with sPGA 0 and 1. RESULTS: This study assessed 230 patients: 79 sPGA 0 and 151 sPGA 1. A greater percentage with sPGA 0 than sPGA 1 achieved a total PSI score of 0 ("best"; 61% vs. 5%, p < 0.0001) and DLQI 0 ("no effect"; 79% vs. 24%, p < 0.001). Patients with sPGA 0 reported better scores than sPGA 1 on all other PSI and DLQI assessments. CONCLUSIONS: Achieving total skin clearance, compared with almost clear skin, provides clinically meaningful improvements in psoriasis.

Psoriasis in the US Medicare Population: Prevalence, Treatment, and Factors Associated with Biologic Use.

Psoriasis is a common chronic inflammatory disorder, primarily of the skin. Despite an aging population, knowledge of the epidemiology of psoriasis and its treatments among the elderly is limited. We examined the prevalence of psoriasis and its treatments, with a focus on biologics and identification of factors associated with biologic use, using a nationally representative sample of Medicare beneficiaries in 2011. On the basis of several psoriasis identification algorithms, the claims-based prevalence for psoriasis in the United States ranged from 0.51 to 1.23%. Treatments used for moderate-to-severe psoriasis (phototherapy, oral systemic, or biologic therapies) were received by 27.3% of the total psoriasis sample, of whom 37.2% used biologics. Patients without a Medicare Part D low-income subsidy (LIS) had 70% lower odds of having received biologics than those with LIS (odds ratio 0.30; 95% confidence interval, 0.19-0.46). Similarly, the odds of having received biologics were 69% lower among black patients compared with white patients (0.31; 0.16-0.60). This analysis identified potential financial and racial barriers to receipt of biologic therapies and underscores the need for additional studies to further define the epidemiology and treatment of psoriasis among the elderly.

The experience of pain and redness in patients with moderate to severe plaque psoriasis.

INTRODUCTION: The Psoriasis Symptom Inventory is a patient-reported outcome instrument that assesses severity of psoriasis signs and symptoms. In early qualitative research, patients reported pain related to psoriasis skin lesions and redness of affected areas of skin as key symptoms. METHODS: Individual concept elicitation interviews and cognitive interviews were conducted in adults with moderate to severe plaque psoriasis. Interviews were audio-recorded and transcribed. Concepts were identified, coded and grouped by similar content using Atlas.ti software. Results were evaluated using qualitative research methods. RESULTS: Of 30 patients recruited, 20 patients participated in concept elicitation interviews and 10 participated in cognitive interviews. Concept codes for skin pain and descriptions of color comprised 11% and 15%, respectively, of all symptom-related expressions. Of 90 pain-related expressions, 22 were about pain related to unconscious scratching and 68 were about pain from the psoriasis lesions. Of 199 color-related expressions, 72 were about red or reddish lesion color. Patients with darker skin tones were found to interpret redness consistently. DISCUSSION: These results provide further support to content validity of pain and redness concepts in the Psoriasis Symptom Inventory. CONCLUSIONS: Symptoms of skin pain and redness are highly relevant to patients with psoriasis.

Cost effectiveness of contraceptives in the United States.

BACKGROUND: The study was conducted to estimate the relative cost effectiveness of contraceptives in the United States from a payer's perspective. METHODS: A Markov model was constructed to simulate costs for 16 contraceptive methods and no method over a 5-year period. Failure rates, adverse event rates and resource utilization were derived from the literature. Sensitivity analyses were performed on costs and failure rates. RESULTS: Any contraceptive method is superior to "no method". The three least expensive methods were the copper-T intrauterine device (IUD) (US$647), vasectomy (US$713) and levonorgestrel (LNG)-20 intrauterine system (IUS) (US$930). Results were sensitive to the cost of contraceptive methods, the cost of an unintended pregnancy and plan disenrollment rates. CONCLUSION: The copper-T IUD, vasectomy and the LNG-20 IUS are the most cost-effective contraceptive methods available in the United States. Differences in method costs, the cost of an unintended pregnancy and time horizon are influential factors that determine the overall value of a contraceptive method.

Impact of systemic hypertension on the cardiovascular benefits of statin therapy--a meta-analysis.

The ASCOT-LLA and ALLHAT-LLT trials provide conflicting evidence of the efficacy of statins in decreasing cardiovascular (CV) morbidity and mortality in hypertensive patients. We performed a meta-analysis to compare the overall efficacy of statins in hypertensive and nonhypertensive patients enrolled in major randomized clinical trials. We systematically reviewed PubMed publications from 1985 onward for placebo-controlled randomized trials that examined the effect of statins on cardiac morbidity and mortality. Only trials that followed >or=1,000 patients for >or=2 years were included in the meta-analysis. Outcomes included cardiac or CV death, major coronary events, or major CV events. Pooled estimates of relative risk (RR) were calculated separately for hypertensive and nonhypertensive patients. The moderating effect of the percentage of hypertensive patients at baseline was tested using meta-regression. Besides the ASCOT-LLA and ALLHAT-LLT, 12 trials enrolling 69,984 patients met inclusion criteria. Overall, in these 12 trials, statin therapy decreased cardiac death by 24% (RR 0.76, 95% confidence interval [CI] 0.71 to 0.82). There was no evidence of difference in RR estimates for hypertensive (RR 0.78, 95% CI 0.72 to 0.84) and nonhypertensive (RR 0.76, 95% CI 0.72 to 0.80) patients. Similarly, meta-regression showed that the efficacy of statins was not moderated by the percentage of hypertensive patients at baseline (Q estimate 1.51, p=0.22). In conclusion, statin therapy effectively decreases CV morbidity and mortality to the same extent in hypertensive and nonhypertensive patients.

Comparison of pegfilgrastim with filgrastim on febrile neutropenia, grade IV neutropenia and bone pain: a meta-analysis of randomized controlled trials.

BACKGROUND AND OBJECTIVE: While head-to-head clinical trials demonstrate pegfilgrastim to be as efficacious as filgrastim in reducing chemotherapy-induced neutropenia, these studies lacked the statistical power to demonstrate better outcomes with one therapy compared to the other. Our objective was to obtain a pooled estimate of the effect of pegfilgrastim compared with filgrastim on incidence of febrile neutropenia (FN), and related outcomes among patients with solid tumors and malignant lymphomas receiving myelosuppressive chemotherapy. RESEARCH DESIGN AND METHODS: We searched PubMed and EMBASE for articles published from January 1, 1990 to August 31, 2006 reporting on randomized controlled trials (RCTs) that compared the efficacy and safety of pegfilgrastim versus filgrastim. We only accepted studies in which filgrastim (5 microg/kg/day) and pegfilgrastim (100 microg/kg or a fixed dose of 6 mg) were administered at approved doses indicated on the package insert. Pooled relative risk (RR) was estimated using the conservative random effects, empirical Bayesian method of Hedges and Olkin. MAIN OUTCOME MEASURES: Rates of grade IV neutropenia and of FN, time to absolute neutrophil count (ANC) recovery, and bone pain. RESULTS: We identified five RCTs, with a total of 617 patients, evaluating the efficacy of a single dose of pegfilgrastim per cycle versus daily filgrastim injections. Although only one study had a statistically significant difference in FN reductions favoring pegfilgrastim over filgrastim (relative risk reduction of 50%; p = 0.027), the pooled RR showed a statistically significant favorable result for pegfilgrastim (RR = 0.64; 95% CI, 0.43-0.97). Grade IV neutropenia rates (for cycle 1: RR = 0.99; 95% CI, 0.91-1.08; cycle 2: RR = 0.88; 95% CI, 0.70-1.11; cycle 3: RR = 0.80; 95% CI, 0.47-1.36; cycle 4: RR = 0.90; 95% CI, 0.71-1.13), time to ANC (SMD = 0.11, 95% CI, -0.34-0.56), and incidence of bone pain (RR = 0.95; 95% CI, 0.76-1.19) were similar between the two G-CSFs. The included trials varied in the type of cancer, chemotherapy regimen and type of trial. CONCLUSION: A single dose of pegfilgrastim performed better than a median of 10-14 days of filgrastim in reducing FN rates for patients undergoing myelosuppressive chemotherapy.

Benefits of GM-CSF Versus Placebo or G-CSF in Reducing Chemotherapy-Induced Complications: A Systematic Review of the Literature.

Unlike granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF) is not approved for reducing the incidence or duration of chemotherapy-induced febrile neutropenia. However, some studies have been conducted in this setting. A systematic review assessing the efficacy of GM-CSF versus placebo or G-CSF in reducing chemotherapy-induced febrile neutropenia and related complications was performed. Medline was reviewed for articles published between January 1987 and March 2003 that contained specific search terms. Explicit inclusion/exclusion criteria were developed for titles, abstracts, and articles. Two researchers reviewed (kappa>/= 0.7) and divided studies according to their evaluation of GM-CSF versus placebo or versus G-CSF. Nine studies were accepted: 6 randomized controlled trials compared GM-CSF versus placebo and 3 studies compared GM-CSF versus GCSF. Three placebo-controlled trials showed that GM-CSF was ineffective in reducing the risk of chemotherapy-induced febrile neutropenia. The remaining 3 trials reported incidence of fever and not febrile neutropenia: 2 reported a significantly increased incidence of fever in the GM-CSF group, and 1 reported that more patients receiving placebo experienced fever compared with patients in the GMCSF group (P > 0.05). The 3 studies comparing GM-CSF versus G-CSF reported fever as a primary outcome also. All 3 reported higher incidence of fever in the GM-CSF group (P < 0.05). Head-to-head trials of G-CSF and GM-CSF in reducing chemotherapy-induced complications are lacking. Identified GM-CSF studies did not show significant reduction in febrile neutropenia and fever.

The risk of hospitalization in patients with asthma switched from an inhaled corticosteroid to a leukotriene receptor antagonist.

Asthma-related hospitalization rates were compared over a 2-year period between a cohort of patients with asthma who switched from an inhaled corticosteroid in year 1 to a leukotriene modifier in year 2 (n = 285) and a matched cohort continuously treated with an inhaled corticosteroid (n = 570). During year 1, patients were well maintained, with a hospitalization rate of 1.1% to 1.4%. During year 2, 2.5% of the patients switched to a leukotriene modifier had one or more asthma-related hospitalizations compared with 0.6% of the patients continuously receiving an inhaled corticosteroid. Patients treated with a leukotriene modifier were at 7 times greater risk for an asthma-related hospitalization compared with patients who continued to receive an inhaled corticosteroid (risk-adjusted odds ratio, 7.1; 95% CI, 2.79-17.95). These data are consistent with the results of well-controlled clinical trials showing that leukotriene modifiers may be associated with deterioration of asthma control relative to inhaled corticosteroids. Considered in aggregate, the data support the conclusion that leukotriene modifiers should not be substituted for inhaled corticosteroids as a single-controller therapy for asthma.