Evaluation of Dabigatran for Appropriateness of Use and Bleeding Events in a Community Hospital Setting

Background

Warfarin has been the predominant anticoagulant for the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation (NVAF). Its disadvantages are well-known and include a narrow therapeutic index, drug interactions, and the need for frequent monitoring. Dabigatran etexilate, a direct thrombin inhibitor, presents less complexity in prescribing and has emerged as an alternate therapy to warfarin. Although dabigatran does not require routine monitoring, concerns associated with its use include the lack of a reversal agent, complex dose adjustments, and limited guidance to the management of drug interactions.

Objectives

The goals of this study are to describe and to evaluate the use of dabigatran at a community hospital to identify areas for improvement in its prescribing.

Methods

This retrospective chart review of patients at a community hospital in St Louis, MO, included patients who received at least 1 dose of dabigatran between December 2010 and June 2012. The appropriateness of dabigatran was evaluated based on recommendations approved by the US Food and Drug Administration for stroke prophylaxis in the setting of NVAF. The composite end point of bleeding included hospital readmission within 1 year of receiving at least 1 dose of dabigatran at the study institution secondary to bleeding, bleeding associated with a decrease in hemoglobin level by ≥2 g/dL or transfusion of ≥2 units of blood, or a notation of bleeding in the patient''s medical record.

Results

Of the 458 patients included in the evaluation, 76 (16.6%) patients receiving dabigatran were using an inappropriate regimen of this drug, based on dose and frequency on the first day of therapy of dabigatran or the presence of valvular disease. Many patients (42.3%) received at least 1 dose of a concomitant parenteral anticoagulant. The composite end point for bleeding was reported in 66 (14.4%) patients, including 23 (5%) with confirmed gastrointestinal bleeding.

Conclusions

High-risk medications such as dabigatran require monitoring of prescribing habits to improve patient safety and outcomes. Various initiatives, such as pharmacist interventions, therapeutic interchanges, and obtaining appropriate patient parameters, can be implemented in the practice setting to ensure the appropriate use of oral anticoagulants and improved patient outcomes.Oral anticoagulation has changed drastically in the past 4 years with the US Food and Drug Administration (FDA) approval of 3 new agents—dabigatran, rivaroxaban, and apixaban. Warfar-in has had a primary role in oral anticoagulation therapy for many decades. Although its efficacy and safety have been established, therapy with warfarin is associated with significant challenges, including the need for frequent monitoring, drug interactions, a delayed time to onset, and a narrow therapeutic index.1,2 The challenges associated with warfarin not only affect its efficacy, but they also impact patient satisfaction. These concerns have contributed to the development of novel oral anticoagulants, beginning with dabigatran etexilate.Dabigatran etexilate, a direct thrombin inhibitor, was approved by the FDA in October 2010 and is the first novel oral anticoagulant approved to reduce the risk for stroke in patients with nonvalvular atrial fibrillation (NVAF).3 Results from the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) study demonstrated the superiority of dabigatran 150 mg orally twice daily compared with warfarin for the prevention of stroke and systemic embolism in patients with NVAF.4 In that study, the rate of major bleeding was similar between the agents; however, dabigatran demonstrated a lower risk for intracranial hemorrhage, but with an increased risk for major gastrointestinal (GI) bleeding, compared with warfarin.4A recent analysis performed by the FDA confirmed these findings.5,6 In this analysis, compared with warfarin, dabigatran demonstrated lower rates of ischemic stroke, intracranial hemorrhage, and death; however, dabigatran was associated with a significant increase in major GI bleeding.5,6 In April 2014, dabigatran received new FDA indications for the treatment of patients with deep-vein thrombosis (DVT) and pulmonary embolism (PE) and for the risk reduction of recurrent DVT and PE in previously treated patients. Two studies, RE-COVER and RE-COVER II, compared dabigatran 150 mg twice daily with warfarin for the treatment of DVT and PE after 5 to 10 days of parenteral anticoagulation. Both studies demonstrated dabigatran''s noninferiority to warfarin.7,8 When the RE-COVER study was initiated, dabigatran was the only agent approved by the FDA for the risk reduction of recurrent venous thromboembolism (VTE).In November 2011, rivaroxaban, a factor Xa inhibitor, was the second novel oral anticoagulant to receive FDA approval to reduce the risk for stroke in patients with NVAF.9 Results from the ROCKET AF trial demonstrated the noninferiority of rivaroxaban to warfarin for the first occurrence of stroke or systemic embolism.10 In November 2012, rivaroxaban received an additional indication for the treatment of and reduction in the risk for recurrent VTE. Two studies, EINSTEIN-DVT and EINSTEIN-PE, compared rivaroxaban (at an initial dose of 15 mg twice daily for 3 weeks, followed by 20 mg once daily) with enoxaparin 1 mg/kg twice daily for at least 5 days with warfarin and then continued with warfarin after the target international normalized ratio (INR) of 2.0 to 3.0 was reached.11,12 Both studies demonstrated the noninferiority of rivaroxaban to warfarin in time to first recurrent DVT or PE event.11,12In December 2012, the factor Xa inhibitor apixaban was the newest novel oral anticoagulant to receive FDA approval to reduce the risk for stroke in patients with NVAF.13 The ARISTOTLE trial compared apixaban 5 mg twice daily (or 2.5 mg twice daily in select patients) with warfarin.14 Apixaban was superior to warfarin for the primary end point of reducing the risks for stroke and systemic embolism. Superiority to warfarin was primarily attributable to reductions in hemorrhagic stroke and ischemic stroke with hemorrhagic transformation compared with warfarin.14In AVERROES, patients with NVAF who were not candidates for therapy with warfarin were randomized to treatment with apixaban 5 mg twice daily (or 2.5 mg twice daily in select patients) or to aspirin 81 mg to 324 mg once daily.15 The primary objective of the study was to determine if apixaban was superior to aspirin for preventing the outcomes of stroke or systemic embolism. This trial was stopped early on the basis of a prespecified interim analysis that showed significant reductions in stroke and systemic embolism with apixaban compared with aspirin, but apixaban was associated with a modest increase in major bleeding.15

KEY POINTS

• ▸ Anticoagulation has changed drastically in the past 4 years in the United States with the FDA approval of novel oral anticoagulants, starting with dabigatran in 2010, rivaroxaban in 2011, and apixaban in 2012.
• ▸ These new anticoagulants present a safe alternative to warfarin for the prevention of stroke and systemic embolism in the setting of nonvalvular atrial fibrillation (NVAF).
• ▸ However, although anticoagulation has been simplified with the novel oral drugs, many safety issues must be considered when prescribing these agents.
• ▸ This retrospective chart review at a community hospital analyzed the appropriateness use of dabigatran, the first novel anticoagulant to receive FDA approval for the treatment of NVAF.
• ▸ Of the 458 patients included in this study, 76 patients were prescribed an inappropriate, mostly too high, dose of dabigatran.
• ▸ Although dabigatran is only approved for the treatment of NVAF, 13 patients had valvular disease.
• ▸ The majority of the patients were also receiving concomitant medications that are known to have drug interactions with dabigatran.
• ▸ These results indicate that high-risk medications require better monitoring of prescribing habits to improve patient safety and outcomes.

The current guidelines for the treatment of atrial fibrillation provide a class I recommendation for warfarin (level of evidence A) and dabigatran, rivaroxaban, and apixaban (level of evidence B) for the prevention of thromboembolism in patients with a CHA₂DS₂-VAS_c score of ≥2.16Dabigatran provides an effective alternative therapy to warfarin. It offers a predictable pharmacokinetic profile, which eliminates the need for routine monitoring of serum drug concentrations. Approximately 80% of dabigatran is excreted renally and requires dose reductions for patients with reduced creatinine clearance.17 Although dabigatran addresses some of the challenges associated with warfarin, there are remaining issues regarding the use of dabigatran.Warfarin interacts with numerous medications, disease states, and a variety of foods containing vitamin K; however, there is a great deal of clinical experience and resources available to effectively manage many of warfarin''s interactions.1 Unlike warfarin, dabigatran is not metabolized by cytochrome P450 enzymes and has fewer drug interactions. Although several drug interactions with dabigatran and P-glycoprotein inducers and inhibitors have been identified, little guidance has been provided on how to address them in practice.18Additional concerns surrounding dabigatran include the lack of a reversal agent and the lack of availability of laboratory testing to determine its degree of anticoagulation activity. Dabigatran prolongs markers of coagulation, such as the activated partial thromboplastin time (aPTT) and ecarin clotting time, and may potentially impact INR values. The aPTT can only provide an approximation of the anticoagulation effect of dabigatran, and the INR is relatively insensitive to the degree of anticoagulation. The ecarin clotting time is a more specific parameter to determine the effect of anticoagulation19; however, most laboratories are not adequately equipped to perform the laboratory test. Without laboratory parameters to guide dosing adjustments, it is unclear how to balance the drug interactions that have been identified to potentially increase or decrease dabigatran serum concentrations. The lack of monitoring also makes it difficult to manage special populations that typically require dosage adjustments (eg, the elderly, obese patients, underweight patients, and those with renal dysfunction).Since dabigatran became the first oral anticoagulant to be introduced to the US market, and the first to be included on hospital formularies, there has been a dramatic shift in the approach to anticoagulation. Laboratory markers of anticoagulation effect are no longer reliable, drug interactions require significantly less dose adjustments, and renal function continually needs to be addressed.20 The purpose of this study was to evaluate the use of dabigatran at a community hospital between December 2010 and June 2012 and to identify prescribing areas that can be improved to ensure appropriate use and patient outcomes.     

Benefits of Novel Oral Anticoagulant Agents for Thromboprophylaxis after Total Hip or Knee Arthroplasty

Background

The incidence of venous thromboembolism (VTE) after total hip arthroplasty (THA) or total knee arthroplasty (TKA) is reduced by the use of thromboprophylactics, such as vitamin K antagonists, low-molecular-weight heparin (LMWH), or fondaparinux. However, these agents have a number of limitations that constrain their use and increase the clinical and economic burden on patients, caregivers, and healthcare resources. Effective prophylaxis may also be complicated by poor adherence to guideline recommendations.

Objective

This article reviews the potential of newly developed oral anticoagulants to address many of the management challenges associated with vitamin K antagonists, LMWHs, and fondaparinux.

Discussion

The 3 oral anticoagulants rivaroxaban, apixaban, and dabigatran have been evaluated in large phase 3 trials, and all 3 represent promising alternatives to the current standard of care. Currently, rivaroxaban is the only new oral agent to have received US Food and Drug Administration approval in the United States for prophylaxis of deep-vein thrombosis, which may lead to pulmonary embolism in patients undergoing THA or TKA. The simplified management of the new oral agents may encourage adherence with published guidelines for VTE prophylaxis and help to reduce the economic burden of VTE. Pharmacoeconomic data suggest that rivaroxaban and dabigatran may result in cost-savings when compared with enoxaparin after THA or TKA.

Conclusions

The numbers of THA and TKA surgeries are expected to increase significantly in coming years, and safer and more effective thromboprophylaxis is essential to mitigate the morbidity and mortality associated with VTE. Newly developed oral anticoagulants have the potential to address many of the limitations of current thromboprophylaxis and may reduce the cost burden associated with the management of VTE after THA or TKA.Total hip arthroplasty (THA) and total knee arthroplasty (TKA) are among the most common orthopedic procedures performed in the United States, with almost 300,000 THA surgeries and more than 500,000 TKA surgeries performed annually.1 This number is projected to rise to approximately 572,000 annual THA surgeries and 3.5 million annual TKA surgeries by 2030.1THA and TKA procedures improve mobility and quality of life, but patients undergoing these surgeries are at a significantly increased risk for developing postoperative venous thromboembolism (VTE).2–4 VTE comprises both deep-vein thrombosis (DVT) and pulmonary embolism (PE). In the absence of thromboprophylaxis, proximal DVT occurs in approximately 5% to 36% of patients who have THA and TKA.5 PE occurs in 50% of patients with proximal DVT,4 and proves fatal in approximately 15% of these patients.6VTE is also associated with significant long-term complications, such as postthrombotic syndrome, chronic thromboembolic pulmonary hypertension, and an increased risk of recurrent events.7 Postthrombotic syndrome develops in 23% to 60% of patients, often in the 2 years after a DVT, and approximately 10% of cases are considered to be severe.8 Approximately 4% of patients with PE are diagnosed with chronic thromboembolic pulmonary hypertension within 2 years9; approximately 10% of patients who experience VTE after THA or TKA are readmitted to the hospital within 3 months after discharge.10

KEY POINTS

• ▸ THA and TKA are common orthopedic procedures that improve a patient''s quality of life but are associated with a significant risk for postoperative VTE and long-term complications.
• ▸ The incidence of VTE can be effectively reduced with thromboprophylactics, including vitamin K antagonists, LMWHs, or fondaparinux.
• ▸ However, these agents are associated with management challenges that limit their use and increase the clinical and economic burden on patients, caregivers, and the US healthcare overall.
• ▸ Currently, 3 new oral anticoagulants are in different stages of development—rivaroxaban, apixaban, and dabigatran—with the first agent recently receiving FDA approval in the United States.
• ▸ The new oral anticoagulants offer several benefits over current thromboprophylactics, including fixed dosing thanks to their predictable pharmacokinetics, no requirement for coagulation monitoring, few drug-drug and drug-food interactions, and once-daily or twice-daily oral administration.
• ▸ When considering the best thromboprophylactic agent, the associated costs related to anticoagulation need to be taken into account, including costs for drug acquisition, mode of administration, and routine coagulation monitoring.

The incidence of VTE can be effectively reduced with the use of thromboprophylactics, including vitamin K antagonists, low-molecular-weight heparins (LMWHs), or fondaparinux (Arixtra). Thromboprophylaxis reduces the cumulative incidence of symptomatic VTE to 1.7% within 3 months of THA and to 2.3% within 3 months of TKA.11 However, these agents pose a number of management challenges that limit their use and increase the clinical and economic burden on patients, caregivers, and healthcare resources.Effective prophylaxis may also be complicated by poor adherence to guideline recommendations, possibly resulting from physicians’ concern about the risk for bleeding or the difficulties of maintaining prophylaxis in an outpatient setting. Newly developed oral anticoagulants have the potential to address many of the limitations associated with vitamin K antagonists, LMWHs, and fondaparinux. They may also simplify treatment strategies for these patients, encourage compliance with therapy, and reduce the economic burden of VTE.     

Modeling the Frequency and Costs Associated with Postsurgical Gastrointestinal Adverse Events for Tapentadol IR versus Oxycodone IR

Background

Few studies have estimated the economic effect of using an opioid that is associated with lower rates of gastrointestinal (GI) adverse events (AEs) than another opioid for postsurgical pain.

Objective

To estimate the number of postsurgical GI events and incremental hospital costs, including potential savings, associated with lower GI AE rates, for tapentadol immediate release (IR) versus oxycodone IR, using a literature-based calculator.

Methods

An electronic spreadsheet–based cost calculator was developed to estimate the total number of GI AEs (ie, nausea, vomiting, or constipation) and incremental costs to a hospital when using tapentadol IR 100 mg versus oxycodone IR 15 mg, in a hypothetical cohort of 1500 hospitalized patients requiring short-acting opioids for postsurgical pain. Data inputs were chosen from recently published, well-designed studies, including GI AE rates from a previously published phase 3 clinical trial of postsurgical patients who received these 2 opioids; GI event–related incremental length of stay from a large US hospital database; drug costs using wholesale acquisition costs in 2011 US dollars; and average hospitalization cost from the 2009 Healthcare Cost and Utilization Project database. The base case assumed that 5% (chosen as a conservative estimate) of patients admitted to the hospital would shift from oxycodone IR to tapentadol IR.

Results

In this hypothetical cohort of 1500 hospitalized patients, replacing 5% of oxycodone IR 15-mg use with tapentadol IR 100-mg use predicted reductions in the total number of GI events from 1095 to 1085, and in the total cost of GI AEs from $2,978,400 to $2,949,840. This cost reduction translates to a net savings of $22,922 after factoring in drug cost. For individual GI events, the net savings were $26,491 for nausea; $12,212 for vomiting; and $7187 for constipation.

Conclusion

Using tapentadol IR in place of a traditional μ-opioid shows the potential for reduced GI events and subsequent cost-savings in the postsurgical hospital setting. In the absence of sufficient real-world data, this literature-based cost calculator may assist hospital Pharmacy & Therapeutics committees in their evaluation of the costs of opioid-related GI events.Pain is a global health problem that affects 1 of 5 adults in the community1 and occurs in 43% to 77%2–4 of the approximate 35.1 million patients who are hospitalized annually in the United States.5 Pain is ubiquitous among the nearly 30.2 million people who undergo inpatient surgery annually in the United States.5 Opioid analgesics are a mainstay of postsurgical pain management,6 but are often associated with treatment-limiting gastrointestinal (GI), central nervous system, and respiratory adverse events (AEs).7 Of these, opioid-related GI AEs are the most common,8–10 with an incidence rate of 10% to 32% for nausea and/or vomiting and 15% to 41% for constipation.7,11–14 These GI AEs are particularly troublesome after surgery, because they can exacerbate anesthesia-induced nausea and decreased GI motility, sometimes resulting in ileus.7 Furthermore, GI AEs are associated with increased healthcare resource utilization because of additional medications used to manage the GI AEs and an increase in hospital length of stay (LOS).7,10,15–17

KEY POINTS

• ▸ Opioid analgesics, a key to postsurgical pain management, are associated with lower gastrointestinal (GI) and other adverse event rates.
• ▸ Unlike traditional opioids, such as oxycodone IR, that exert analgesic activity by binding to μ-opioid receptors, tapentadol IR has a second mechanism involving norepinephrine reuptake inhibition, which may help to minimize GI events.
• ▸ Previous studies have shown that tapentadol IR causes fewer GI events than oxycodone IR in the postsurgical setting.
• ▸ This new study compared the total GI events and associated incremental costs for tapentadol IR versus oxycodone IR in the postsurgical setting from a hospital perspective, using a cost calculator and a hypothetical cohort of 1500 hospitalized patients requiring short-acting opioids.
• ▸ Replacing 5% of oxycodone IR 15-mg use with tapentadol IR 100 mg reduced the total number of postsurgical GI events from 1095 to 1085, which was associated with a cost reduction from $2,978,400 to $2,949,840.
• ▸ Individual GI event net savings for the 5% use of tapentadol IR instead of oxycodone IR were $26,491 for nausea, $12,212 for vomiting, and $7187 for constipation.
• ▸ The potential cost-savings associated with reduced GI events seen with tapentadol IR versus oxycodone IR in the postsurgical setting may suggest the need to look beyond drug-acquisition cost to consider the effect on net costs of care when making formulary decisions.

The guidelines for managing surgery-related pain advocate a multimodal, opioid-sparing approach to improve analgesic activity and to minimize the risk for opioid-related AEs.6,18 Most traditional opioids exert analgesic activity by binding to μ-opioid receptors in the brain; these receptors are also present in the GI tract. Tapentadol is a centrally acting analgesic with 2 mechanisms of action—μ-opioid receptor agonism and norepinephrine reuptake inhibition.19,20 These 2 mechanisms of action may account for the significant analgesia, along with the lower incidence and intensity of AEs that are normally associated with traditional μ-opioid receptor agonists, such as oxycodone.21In 2 phase 3 studies of patients with acute pain, including postoperative pain, the incidence of GI AEs was lower with tapentadol immediate release (IR) than with oxycodone IR at equianalgesic doses, including dose strengths other than tapentadol IR 100 mg.22,23We chose oxycodone IR as the traditional opioid because of its inclusion in guidelines for surgery-related pain,6 the availability of pivotal clinical studies comparing oxycodone IR with tapentadol IR,23,24 and its spectrum of AEs that is similar to that of tapentadol IR.23,24Although the clinical benefits of using opioids with different mechanisms of action are well documented, few studies have examined the potential economic effect of this strategy in postsurgical populations.The objective of this study was to estimate the number of potential reductions in postsurgical GI AEs and incremental hospital costs for GI event rates associated with tapentadol IR versus oxycodone IR, using a literature-based calculator. The analysis focused on data related to postsurgical GI AE rates, because of their availability in the published literature.     

Hematologic Complications,Healthcare Utilization,and Costs in Commercially Insured Patients with Myelodysplastic Syndrome Receiving Supportive Care

Background

Myelodysplastic syndrome (MDS) is rare in people aged <50 years. Most patients with this disorder experience progressive worsening of blood cytopenias, with an increasing need for transfusion. The more advanced and severe the disorder, the greater the risk that it will progress to acute myeloid leukemia. Therapy is typically based on the patient''s risk category, age, and performance status. Supportive care alone is a major option for lower-risk, older patients with MDS or those with comorbidities. The only potentially curative treatment option is hematopoietic stem-cell transplantation, which is typically used to treat high-risk, younger patients.

Objective

To describe and compare the hematologic complications, healthcare utilization, and costs of supportive care in patients with MDS aged <50 years and in older patients aged ≥50 years.

Methods

Using the i3/Ingenix LabRx claims database, this retrospective study included patients who were continuously enrolled (ie, 6 months preindex through 1 year postindex) in the study and who had an initial claim of MDS (index date) between February 1, 2007, and July 31, 2008. Patients treated with hypomethylating agents or thalidomide analogues were excluded. Claims included information on office visits, medical procedures, hospitalizations, drug use, and tests performed. The hematologic complications, costs, and utilization analyses were stratified by age into 2 age-groups—patients aged <50 years and those aged ≥50 years. The MDS-related diagnoses, utilization, and costs were analyzed postindex. The data used in this study spanned the period from August 1, 2006, to July 31, 2009.

Results

We identified 1133 newly diagnosed patients with MDS who received supportive care only during the study period; of these, 19.5% were younger than age 50 years. These younger patients included more females (62.0% vs 52.5%; P = .011) and had fewer comorbidities (mean Charlson comorbidy index, 1.2 vs 2.4; P <.001) and physician office visits than those aged ≥50 years. Postindex, compared with the older patients, the younger patients had less use of erythropoietin therapy and fewer transfusions, anemia diagnoses, and potential complications of neutropenia and pneumonia diagnoses; however, more diagnoses of neutropenia and of decreased white blood cell counts were seen in the younger patients than in the older patients (P ≤.034 for all comparisons). Furthermore, younger patients had fewer mean office visits in the postindex period than older patients (17.5 vs 24.2, respectively; P <.001) and fewer hospitalizations (32.1% vs 44.6%, respectively; P = .004), but they had a longer (although not statistically significant) mean length of hospital stay (21 vs 14 days, respectively; P = .131). Mean total healthcare charges were $96,277 (median, $21,287) in younger patients compared with $84,102 (median, $39,402) in older patients, although this difference, too, was not significant.

Conclusions

MDS is associated with frequent and prolonged hospitalizations, frequent outpatient visits, and high costs in younger and in older patients who are receiving supportive care. Although this study shows that younger patients aged <50 years do not have significantly higher costs overall, a small proportion may have a higher healthcare utilization and cost-related burden of MDS than patients aged ≥50 years.Myelodysplastic syndrome (MDS) encompasses a heterogeneous group of clonal disorders of hematopoiesis and is characterized by dysplastic morphology of marrow and blood cells, ineffective hematopoiesis, and peripheral blood cytopenias.1,2 Most patients with MDS experience progressive worsening of blood cytopenias, with an increasing need for transfusion.2 These patients also have an increasing number of potentially fatal infections and hemorrhagic complications.2 The more advanced and severe the MDS is, the greater the risk that the disease will progress to acute myeloid leukemia (AML).3 The disease may be classified into 1 of 5 subtypes—refractory anemia, refractory anemia with ringed sideroblasts (RARS), refractory anemia with excess of blasts (RAEB), RAEB in transformation (RAEB-T), or chronic myelomonocytic leukemia.3 Approximately 5% to 15% of the relatively lower-risk patients with refractory anemia/RARS transform to AML; by contrast, 40% to 50% of the high-risk patients with RAEB/RAEB-T transform to AML.3The therapeutic options that are tailored for specific MDS subgroups are typically based on factors such as the patient''s risk category, age, and performance status.3,4 The National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology recommend that all patients with MDS receive supportive care,3 which includes blood transfusions, erythropoietin with or without granulocyte colony-stimulating factor, iron chelation therapy, and prophylactic antibiotics.4,5 Other therapies indicated for the treatment of patients with MDS include the thalidomide analogue lenalidomide and the hypomethylating agents decitabine and 5-azacytidine.3,4 The only potentially curative treatment option is hematopoietic stem-cell transplantation, which is typically used to treat younger, high-risk patients.3,4 Supportive care alone remains a leading option for the treatment of lower-risk, older patients with MDS or those with comorbidities.3,4Data on the distribution of MDS in the general population are inconsistent, possibly because of misdiagnoses and/or underreporting of the disease.6,7 The most recent estimates of the annual incidence of MDS in the United States range from 3.3 to 5.0 per 100,000 persons.3,7,8 Some studies indicate that the median age of patients with MDS is approximately 65 years, whereas others note that more than 70% of cases occur in patients aged ≥70 years in the United States.3,6,9 The incidence of MDS in individuals aged ≥70 years is between 22 and 45 per 100,000 persons and increases with age.3,6,9–11Less than 10% of patients with MDS are aged <50 years; therefore, little is known about this disease in this younger age-group, particularly among patients who receive supportive care only.6,11,12 Some data suggest that younger patients with MDS have less aggressive disease.12,13 We compared hematologic complications, healthcare utilization, and costs in patients aged <50 years and in those aged ≥50 years who were newly diagnosed with MDS and received supportive care only.

KEY POINTS

• ▸ The more advanced and severe the myelodysplastic syndrome (MDS) is, the greater the risk of progression to acute myeloid leukemia. Therapy is currently based on risk category, age, and performance status.
• ▸ In the United States, the majority of newly diagnosed patients with MDS receive only supportive care, although for younger patients at high-risk, hematopoietic stem-cell transplantation is potentially the only curative option.
• ▸ This analysis compares the hematologic complications, healthcare utilization, and cost of care between patients with MDS aged <50 years and those aged ≥50 years who receive supportive care only.
• ▸ Although the younger patients had fewer office visits, they had longer mean length of hospital stay than the older group (21 vs 14 days, respectively).
• ▸ Mean total healthcare charges were $96,277 in younger patients compared with $84,102 in older patients.
• ▸ Based on this study, approximately 20% of patients with MDS are under age 50 years.
• ▸ The results of this study suggest that a small proportion of younger patients with MDS who receive supportive care only may have a higher healthcare utilization and cost-related burden of MDS than older patients with this condition.

     

Anticoagulation Bridging Therapy Patterns in Patients Undergoing Total Hip or Total Knee Replacement in a US Health Plan: Real-World Observations and Implications

Background

The necessity for anticoagulant bridging therapy after joint replacement surgery is widely understood, but treatment administration patterns in the prevention of venous thromboembolism (VTE) after total hip replacement (THR) or total knee replacement (TKR) surgery during the hospital stay have yet to be examined.

Objective

To investigate anticoagulation thromboprophylaxis patterns, especially the use of anticoagulant bridging therapy and/or nonbridged treatment strategies, in patients undergoing THR/TKR surgery.

Methods

This retrospective study was based on a large hospital database linked with outpatient claims from 2005 through 2007. The study population included 1770 patients who were admitted for either THR or TKR surgery and were aged ≥18 years on the date of the surgery, defined as the index date. Patients were required to have commercial insurance or Medicare coverage and be continuously enrolled in their health plan for at least 180 days before and 90 days after the index date. The data were analyzed retrospectively for risk-adjusted postsurgery VTE and major bleeding events among patients receiving anticoagulation thromboprophylaxis. Patterns of anticoagulant bridging therapy use were also assessed. A risk adjustment was performed using propensity score matching.

Results

Of 1770 eligible patients, 1551 (88%) received anticoagulant VTE prophylaxis; 264 (15%) received combination low-molecular-weight heparin and warfarin. Of these, 105 (40%) patients were switched between the 2 monotherapies, and 159 (60%) received bridged (overlapping) prophylaxis. The overall rates of VTE and bleeding events were significantly lower with bridged therapy than with nonbridged therapy (5.8% vs 18.4%, respectively, for VTE, P <.02; 2.3% vs 4.60% for major bleeding, P = .41; 1.15% vs 8.05% for minor bleeding, P <.03).

Conclusion

Although existing guidelines recommend anticoagulant bridging therapy after THR or TKR surgery, the limited data regarding anticoagulant bridging practice patterns suggest that patients who undergo such surgery do not receive adequate anticoagulant thromboprophylaxis immediately after discharge. Our findings suggest that increased use of bridging therapy after THR or TKR surgery may help improve postsurgery patient outcomes by reducing VTE and bleeding rates.An estimated 350,000 to 600,000 American patients experience venous thromboembolism (VTE) annually, which includes deep-vein thrombosis and pulmonary embolism.1–5 Patients undergoing total hip replacement (THR) or total knee replacement (TKR) surgery are at high risk for VTE, because the large veins in the legs carrying blood back to the heart are significantly injured during these procedures.6,7 As a result of the aging and increasingly obese US population, an estimated 500,000 THR operations and 3.5 million TKR operations are expected to be performed by 2030.8Much is known about how to prevent and minimize the consequences of VTE. A number of established guidelines emphasize the need to provide appropriate thromboprophylaxis to patients at risk for VTE.9–12 However, the approach to the management and prevention of VTE varies, as is evident by the different clinical practice guidelines for VTE that have been developed by several organizations—most notably the American College of Chest Physicians (ACCP) and the American Academy of Orthopaedic Surgeons—according to their medical specialty and specific concerns and needs.9,13At the heart of this diversity are differing interpretations of evidence supporting anticoagulant therapy in a number of clinical settings, the contrasting opinions regarding the potential risk of bleeding that all anticoagulants carry, and the historical precedents that may unduly influence management decisions.13,14 As a result, many clinicians often find it difficult to know which VTE guidelines to follow and how to adhere to them in everyday practice.The ACCP''s evidence-based guidelines recommend that anticoagulation be used for at least 10 days and extended for up to 35 days after THR or TKR surgery.9 Bridging therapy is central to the recommendations for perioperative management for patients receiving long-term anticoagulant therapy. In general, bridging therapy may be defined as postoperative anticoagulant overlapping of at least 2 therapies that are administered together during the period of switching from an injectable anticoagulation agent (most often intravenous unfractionated heparin or subcutaneous low-molecular-weight heparin [LMWH]) to oral anticoagulation (most often a vitamin K antagonist, such as warfarin).Because warfarin requires a minimum of 3 to 4 days to reach therapeutic concentration,15 it is necessary to continue the use of injectable anticoagulants during the transitional (switching) period. When determining whether to use bridging therapy, the risk of bleeding should be balanced against the risk of thromboembolism. Although a consensus exists among the various guidelines on the need for bridging therapy, treatment patterns in clinical practice have yet to be examined.The aim of this retrospective study was to examine thromboprophylaxis patterns—particularly involving the use of anticoagulant bridging and/or nonbridged strategies—for patients undergoing either THR or TKR surgery. Because a main goal was to make the results of this analysis relevant to practicing clinicians, inpatient data from a large hospital database were linked to outpatient claims for accurate tracking of anticoagulant use.     

Fixed-Dose Combination Gel of Adapalene and Benzoyl Peroxide plus Doxycycline 100 mg versus Oral Isotretinoin for the Treatment of Severe Acne: Efficacy and Cost Analysis

Background

Acne vulgaris is a chronic skin disease with a high prevalence. Left untreated or inadequately treated, acne vulgaris can lead to psychological and physical scarring, as well as to unnecessary medical expenses. Oral isotretinoin is an effective treatment for severe resistant nodular and conglobate acne vulgaris. A regimen consisting of a fixed-dose combination of adapalene and benzoyl peroxide gel, 0.1%/2.5% (A-BPO) with oral doxycycline 100 mg (A-BPO/D) has been demonstrated to be efficacious and well tolerated in patients with severe acne and may be an alternative to oral isotretinoin for some patients with severe acne.

Objective

The objective of this analysis was to compare the relative efficacy and associated costs of A-BPO/D versus oral isotretinoin.

Methods

In this analysis, comparisons of relative efficacy were made using previously published studies involving similar patient populations with severe acne that warrant the use of oral isotretinoin. The pricing for oral doxycycline and oral isotretinoin was estimated based on the maximum allowable cost from 9 states, and the pricing for A-BPO was calculated as the range between the average wholesale price and the wholesale acquisition cost. For this analysis, 2 treatment models were generated to compare costs: (1) a basic treatment model that examined the costs of an initial regimen of either A-BPO/D or oral isotretinoin without considering probable outcomes, and (2) a long-term model that factored in likely treatment outcomes and subsequent treatments into associated costs. The basic treatment model assumed that patients would be prescribed a single regimen of A-BPO/D for 12 weeks or oral isotretinoin for 20 weeks. The long-term model considered the probability of each treatment successfully managing patients'' acne, as well as likely additional regimens of A-BPO monotherapy or an additional regimen of oral isotretinoin. As a result of different treatment durations, the costs for each treatment were normalized to weekly cost of treatment.

Results

Based on evidence from the published literature, patients treated with A-BPO/D would be expected to have an initial 72% reduction in inflammatory lesions, and patients treated with oral isotretinoin would have an 80% to 90% reduction of these lesions. The median weekly cost for the basic treatment model was $44 for A-BPO/D and $62 for oral isotretinoin. The weekly median costs for the long-term model were $44 for patients initially receiving a regimen of A-BPO/D followed by a maintenance regimen of A-BPO monotherapy and $50 for patients receiving an initial regimen of A-BPO/D who required a subsequent regimen of oral isotretinoin. The weekly cost for oral isotretinoin in the long-term model was $62.

Conclusions

The comparison of these 2 treatments demonstrated that they are both effective in treating severe acne, and that A-BPO/D was less expensive weekly than oral isotretinoin. These models show that A-BPO/D is safer than and is a more cost-effective alternative to oral isotretinoin for treating patients with severe acne vulgaris.Acne vulgaris is a chronic skin disease predominantly affecting the face, trunk, and back.1 The prevalence of acne vulgaris is high in many countries: acne afflicts up to 87% of adolescents and up to 54% of adults.2,3 Skin diseases, including acne, are often dismissed as being trivial or not as important as diseases of other organ systems.4 However, acne can negatively affect the patient''s quality of life (QOL).4 Responses to the 36-Item Short Form Survey, a generic QOL questionnaire, demonstrate that patients with acne report social, psychological, and emotional problems at levels as great as patients with epilepsy, diabetes, back pain, disabling asthma, or arthritis.4 Patients with acne also have fewer feelings of pride, lower self-esteem, lower body image satisfaction, more depressive symptoms, and more feelings of uselessness than people without acne.5 Adolescents with severe acne have suicidal thoughts more frequently than those with less severe acne.6 If left untreated, acne can result in significant psychosocial morbidity.7 Treatment improves the QOL of patients with acne and can prevent scarring.8–10

KEY POINTS

• ▸ Acne vulgaris is a chronic, prevalent skin disease that can affect a patient''s quality of life and lead to unnecessary medical expenses.
• ▸ Oral isotretinoin is indicated for the treatment of severe resistant nodular and conglobate acne vulgaris and is the only therapy that targets all 4 causitive factors.
• ▸ However, oral isotretinoin is a teratogenic drug that is associated with significant side effects and carries a REMS program; and although it is indicated for severe recalcitrant acne, it is often prescribed for mild or moderate acne.
• ▸ A fixed-dose combination of adapalene and benzoyl peroxide gel, 0.1%/2.5% (A-BPO) is efficacious and well tolerated in patients with severe acne.
• ▸ This new analysis of previously published data shows that although oral isotretinoin and A-BPO plus oral doxycycline 100 mg (A-BPO/D) are both effective for treating severe acne, A-BPO/D is less expensive per patient per week.
• ▸ Because the 2 treatment regimens are different in nature, a weekly cost analysis was used for comparison, showing that the median weekly cost for A-BPO/D is $44 compared with $62 for oral isotretinoin.
• ▸ In addition to being safer than oral isotretinoin for the management of patients with severe acne vulgaris, A-BPO/D is a cost-effective alternative to oral isotretinoin, which is associated with potential serious side effects that may further increase the indirect costs of treatment.

The pathophysiology of acne is multifactorial, involving 4 causative factors, including inflammation, hyperkeratinization, Propionibacterium acnes proliferation, and excess sebum production.11 Several topical and oral treatment options target the various causative mechanisms. The Global Alliance to Improve Outcomes in Acne has published recommended guidelines for the treatment of acne.12 Topical treatment is recommended for milder forms of acne. Oral isotretinoin is indicated for the most severe forms of nodular and conglobate acne and is the only available therapy that targets all 4 causative factors.Although indicated for severe recalcitrant acne, oral isotretinoin is frequently prescribed for the treatment of mild or moderate acne.13 However, oral isotretinoin is a pregnancy category × teratogen and is associated with significant side effects.14 The reported side effects associated with the use of oral isotretinoin include depression, attempted suicide, cheilitis, dermatitis, myalgia, dry eyes, nonspecific gastrointestinal symptoms, and arthralgia, among others.14 Patients who are prescribed oral isotretinoin must enroll in the Risk Evaluation and Mitigation Strategy (REMS) program iPLEDGE.15 Patients also require laboratory tests to monitor liver function and serum lipid levels.14For patients with severe acne with less nodular involvement, an oral antibiotic with a topical retinoid and benzoyl peroxide is recommended.12 Doxycycline 100 mg once daily is efficacious against acne and is relatively well tolerated.16 Adapalene, a third-generation retinoid with an established safety profile, has anticomedogenic and anti-inflammatory properties that are effective against acne.17–21 Benzoyl peroxide is an antimicrobial agent with demonstrated efficacy in treating acne.22 Benzoyl peroxide is more advantageous than other topical antibiotics, because it does not induce bacterial resistance and because it is effective against resistant P acnes strains.23A fixed-dose combination of adapalene and benzoyl peroxide gel, 0.1%/2.5% (A-BPO; Epiduo Gel) was approved by the US Food and Drug Administration in 2008. This is the only fixed-dose drug combination that is formulated with a topical retinoid and benzoyl peroxide. The safety and efficacy of A-BPO for the treatment of acne have been established in clinical trials.24,25Two related clinical trials investigated the use of A-BPO with oral doxycycline 100 mg once daily (A-BPO/D) for 12 weeks,26 followed by a maintenance therapy of A-BPO in patients with severe acne for an additional 24 weeks.27 Severe acne vulgaris in these studies was defined as up to 3 nodules or cysts, 30 to 120 noninflammatory lesions, and at least 20 inflammatory lesions.26,27 In the study by Gold and colleagues, patients who were treated with A-BPO/D had significantly better improvement in acne symptoms and in the acne symptom portion of the Acne-QOL questionnaire than patients given vehicle gel and doxycycline 100 mg.9,26 Patients with at least a “good” improvement in the first study, whether they were in the A-BPO/D group or in the vehicle gel plus doxycycline group, were eligible for the second study and were randomized to a maintenance regimen of A-BPO or to vehicle gel. Symptoms of acne and the QOL of patients using A-BPO continued to improve, whereas in patients using vehicle gel, QOL and acne symptoms worsened during the 24-week period.9,27 The majority of adverse events were mild and included erythema, scaling, dryness, and stinging and burning.26,27In addition to treating severe acne, A-BPO is also recommended for the treatment of mild and moderate acne, making it a versatile topical medication that can treat a spectrum of disease severity.12A model was developed to compare the efficacy and related costs of A-BPO/D versus oral isotretinoin in treating severe acne vulgaris.     

Trends in Biologic Therapies for Rheumatoid Arthritis: Results from a Survey of Payers and Providers

Background

Advances in therapies for rheumatoid arthritis (RA), particularly biologics, have transformed the treatment paradigm for RA. However, the associated costs of these therapies result in a significant economic burden on the healthcare system. As a chronic disease requiring lifelong treatment, most health plans now position RA drugs as a high-priority therapeutic category.

Objective

To identify provider and payer practices and perceptions regarding coverage of RA biologics in the current marketplace, as well as emerging trends in reimbursement practices.

Method

In November 2011, Reimbursement Intelligence, a healthcare research company, collected and analyzed quantitative and qualitative data via parallel-structure online surveys of 100 rheumatologists and 50 health plan payers (medical and pharmacy directors) who represent more than 80 million covered lives. The surveys included approximately 150 questions, and the surveys were designed to force a response for each question.

Results

Payers reported using tier placement, prior authorization, and contracting in determining coverage strategies for RA biologics. Among providers, experience with older RA agents remains the key driver for the choice of a biologic agent. A majority of payers and providers (68% and 54%, respectively) reported that they did not anticipate a change in the way their plans would manage biologics over the next 2 to 4 years. Payers’ responses indicated uncertainty about how therapeutic positioning of newer, small-molecule drugs at price parity to biologics would affect the current reimbursement landscape. Survey responses show that approval of an indication for early treatment of RA is not likely to change the prescribing and reimbursement landscape for RA biologics. This survey further shows that payers and providers are generally aligned in terms of perceptions of current and future treatments for RA.

Conclusion

Advances in RA therapies allow patients increasing options for effective disease management. However, the high cost of biologic therapies and the need for lifelong treatment raise economic concerns. Payer satisfaction with current therapies and uncertainty about added value of new therapies will create challenges for new medications coming to market.Rheumatoid arthritis (RA) is a chronic systemic autoimmune disorder and the most common form of inflammatory arthritis.1 RA affects 1% of the population, most often adults aged 40 to 70 years.2 Recent epidemiologic data indicate that the incidence of RA in women has risen in the past 10 years.3Because RA affects many individuals who are of working age and remains a major cause of disability, the economic burden of RA adds a significant cost not only to patients and their families, but also to society as a whole.1,4 In addition, reduced quality of life, loss of work productivity, and substantial healthcare utilization are factors that must be considered in RA management.4,5Because complications of RA may begin to develop within months of disease onset, early and aggressive treatment is considered clinically necessary to manage immediate symptoms of pain associated with inflammation, but also to slow disease progression to prevent long-term disability.1,6,7 Historically, estimates of work disability rates for RA have been high, with higher rates associated with longer disease duration; work disability estimates have been shown to reach 30% within 2 to 3 years of diagnosis.4,5 Recent estimates suggest that RA-related work disability rates remain high, although potentially lower than in earlier estimates.8 This 2008 longitudinal analysis showed estimates of 23% work disability at 1 to 3 years of disease onset and of 35% within 10 years.8

KEY POINTS

• ▸ Advances in RA medications, particularly biologics, have transformed the treatment paradigm for RA; however, the associated costs of these therapies result in a significant economic burden on the healthcare system.
• ▸ With a chronic disease requiring lifelong treatment, most health plans are positioning RA drugs as a high-priority therapeutic category.
• ▸ This survey of 100 rheumatologists and 50 payers representing >80 million lives revealed that provider experience and satisfaction with older RA agents remains the underlying driver for choice of biologics.
• ▸ Payers and providers alike reported that they did not anticipate a change in the way their plans would manage biologics over the next 2 to 4 years.
• ▸ Payers were uncertain about the therapeutic positioning for newer, small-molecule drugs at price parity to biologics.
• ▸ Survey responses also suggest that an indication for a biologic to treat early RA will likely not change current prescribing and reimbursement patterns.

Clinical studies have shown better clinical outcomes when aggressive treatment is initiated early, including treatment with a wide range of disease-modifying antirheumatic drugs (DMARDs) and non-DMARD combination therapies.7–9 A recent joint collaboration of the American College of Rheumatology (ACR) and the European League Against Rheumatism has led to the development of an updated classification system of RA, to shift the focus from late-stage disease features—such as structural changes and joint damage that can be determined from various imaging techniques—to early-stage disease features that are associated with persistent disease.6 Given the advances in treatment for RA, including nonbiologic and biologic options, along with the associated improved outcomes, this classification system update to include early-disease features marked a major shift in the RA disease construct.6The ACR guidelines outline clinical treatment pathways by first defining disease duration and activity.7 Disease duration is divided into 3 major categories: <6 months (equivalent to early disease), 6 to 24 months (equivalent to intermediate disease duration), and >24 months (equivalent to longer disease duration).7 Disease activity measurements are often qualitative in early-stage disease, and measures are subject to clinical judgment.7Pharmacotherapy for RA often includes a non-steroidal antiinflammatory drug, selected use of glucocorticoids, and initiation of a DMARD early in the disease course.1,7 Biologic therapies may be added when adequate disease control has not been met by previously initiated drug therapies, which may occur within the first year of diagnosis.1,7 With regard to biologic therapies, the ACR further subdivides “early disease” by disease duration of <3 months or 3 to 6 months, to accommodate the needs for early advancement of the patient to biologic therapies when disease activity is high.7Despite positive clinical outcomes from treatment advances, healthcare costs associated with the treatment of a prevalent and lifelong disease such as RA are a considerable issue for health plans. The ACR estimates that per-patient treatment with biologic therapies is typically in excess of $12,000 annually.10 The Agency for Healthcare Research and Quality estimates the annual costs for RA medications from as low as a few hundred dollars for oral, nonbiologic DMARDs to a high of more than $16,000 for injectable biologic DMARDs.11 As new therapeutic options for RA become available, provider practices and payer strategies to support evidence-based care within the confines of cost management demand close examination.This study was conducted to identify provider and payer practices and perceptions regarding therapeutic options and reimbursement for RA. To this end, Reimbursement Intelligence, a healthcare research company, conducted parallel online surveys with health plan payers and rheumatologists. Payers were asked to also consider market trends and potential for formulary coverage of RA therapies currently in development.     

Outcomes Associated with 5-HT3-RA Therapy Selection in Patients with Chemotherapy-Induced Nausea and Vomiting: A Retrospective Claims Analysis

Background

Chemotherapy-induced nausea and vomiting (CINV) is a common side effect of chemotherapy, and may present during the administration of chemotherapy (ie, acute CINV) or within 25 to 120 hours of chemotherapy (ie, delayed CINV). Preventing CINV with the initiation of chemotherapy is important, because the risk for CINV in future chemotherapy cycles increases if CINV occurs in the first or previous treatment cycle. Inadequately controlled CINV is associated with increased resource utilization and costs, particularly for patients receiving highly or moderately emetogenic chemotherapy.

Objective

To evaluate the clinical and economic impacts of delayed CINV events in patients who receive initial and maintenance therapy with the newer-generation 5-hydroxytryptamine₃ receptor antagonist (5-HT₃-RA) palonosetron compared with patients who receive initial and maintenance therapy with an older 5-HT₃-RA agent.

Methods

A retrospective database analysis was conducted using the OptumInsight database covering the years 2005–2011 (96% commercially insured members, 4% Medicaid members). Patients with cancer who received initial therapy with an emetogenic single-day chemotherapy regimen and a 5-HT₃-RA agent (ie, dolasetron, granisetron, ondansetron, or palonosetron) were included in the analysis. The outcomes measured included the overall rates of delayed CINV for cycles 1 to 6, by 5-HT₃-RA cohort. For cycles 2 to 6, calculations were based on patients who experienced CINV in the previous cycle, maintained the same 5-HT₃-RA for all cycles, and had chemotherapy with a similar level of emetic potential. The economic outcomes (ie, cost and utilization) were also collected and calculated.

Results

A total of 26,974 patients were included in the analysis. The overall rate for delayed CINV at cycle 1 was 15.6%, and the lowest rate was for palonosetron at 15%. The patients who initiated palonosetron had lower CINV rates throughout all cycles. The regression analysis compared individual agents to palonosetron and demonstrated higher odds of CINV in the second cycle for the older agents (ondansetron: odds ratio [OR], 1.41; 95% confidence interval [CI], 1.14–1.74; P <.002; granisetron: OR, 1.70; 95% CI, 1.39–2.08; P <.001; dolasetron: OR, 1.65; 95% CI, 1.27–2.15; P = .002). This trend continued through cycle 6, and not all ORs were significant. Over 6 cycles, ondansetron cost an additional $126,775 compared with palonosetron; granisetron an additional $169,838 versus palonosetron; and dolasetron an additional $148,960.

Conclusions

Current guidelines support the use of 5-HT₃-RA agents for the prevention of CINV. As shown in this analysis, the selection of a specific 5-HT₃-RA agent has a clinical and subsequent economic impact on patients with cancer experiencing delayed CINV. Specifically, patients receiving therapy with palonosetron had a lower incidence of delayed CINV and incurred lower overall costs.Chemotherapy-induced nausea and vomiting (CINV) is a common side effect of chemotherapy, and may present during or soon after (0–24 hours) chemotherapy administration (ie, acute CINV) or between 25 to 120 hours after chemotherapy administration (ie, delayed CINV).1,2 In the absence of antiemetic prophylaxis, many emetogenic agents will cause emesis in more than 90% of patients within 24 hours of the administration of chemotherapy.1–3 Preventing CINV during the initiation of chemotherapy is important, because the risk for CINV in future chemotherapy cycles increases if CINV occurs in the first or previous treatment cycle.4–8 The 5-hydroxytryptamine₃ receptor antagonists (5-HT₃-RAs) have proved to be very effective in the prevention of CINV, with current guidelines supporting the use of the 5-HT₃-RA agents for CINV prophylaxis.9–11Despite the effectiveness of the 5-HT₃-RAs, uncontrolled CINV still occurs in more than 25% of patients receiving chemotherapy.4 Antiemesis guidelines from the American Society of Clinical Oncology, National Comprehensive Cancer Network (NCCN), and Multinational Association of Supportive Care in Cancer/European Society for Medical Oncology (MASCC/ESMO) recommend palonosetron as a preferred treatment among the 5-HT₃-RAs for CINV prophylaxis before moderately emetogenic chemotherapy (MEC).9–11 In addition, the NCCN''s antiemesis guidelines have granted palonosetron preferred status for the prevention of CINV with strongly emetogenic chemotherapy (HEC) regimens.10 The MASCC/ESMO guidelines consider palonosetron as the preferred 5-HT₃-RA for anthracycline plus cyclo-phosphamide chemotherapy regimens when a neurokinin 1 receptor antagonist is not available.11The effectiveness of palonosetron has also been supported by studies conducted in solid tumors, as well as in blood cancers, demonstrating that patients receiving palonosetron had significantly lower CINV event rates than patients receiving other 5-HT₃-RAs, and that palonosetron can be safely and effectively administered to patients receiving chemotherapy regimens administered over multiple days per cycle.12–15Although the effectiveness of the older 5-HT₃-RA agents (ie, ondansetron, dolasetron, and granisetron) in preventing emesis in the acute phase (0–24 hours after chemotherapy administration) has been well documented, delayed CINV (2–5 days after chemotherapy administration), particularly nausea, continues to pose clinical (ie, including negative impact on quality of life)16 and economic burdens for patients with cancer.Uncontrolled delayed CINV has been defined as nausea and/or vomiting or a diagnosis of dehydration made during an office visit, emergency department visit, or hospitalization.4,14 The rates of uncontrolled CINV have been estimated to be as high as 28%,4 and uncontrolled CINV has been associated with 25% to 50% of patients delaying or refusing chemotherapy.17 Up to 82% of women receiving MEC or HEC can experience delayed nausea.18 Even if patients do not experience CINV in the first 24 hours of chemotherapy administration, delayed CINV affects activities of daily life in 23% of patients.18–20 Uncontrolled CINV has been shown to be associated with increased resource utilization and costs, particularly for patients receiving MEC or HEC.21,22 In a study assessing CINV costs for the first cycle of a MEC or HEC regimen, 64% of CINV-associated visits included an inpatient visit and 26% included an outpatient visit, with the mean cost of a CINV visit calculated to be $5299 (standard deviation [SD], $6639).21 Another study has estimated the average daily cost of CINV to be approximately $1850.22 These costs further show the need to establish control of CINV at the first chemotherapy cycle.

KEY POINTS

• ▸ Without antiemetic prophylaxis, emesis occurs in more than 90% of patients within 24 hours of receiving emetogenic chemotherapy.
• ▸ Uncontrolled CINV is associated with increased costs and resource utilization, as well as poorer quality of life.
• ▸ The risk for CINV in future chemotherapy cycles increases if it occurs early in the treatment cycle.
• ▸ Based on the current analysis, patients receiving 5-HT₃-RA agents, especially palonosetron, have fewer delayed CINV events and incur lower costs than other agents.
• ▸ Overall, palonosetron was found to reduce all CINV events compared with the older 5-HT₃-RA agents.
• ▸ Delayed CINV was 15% with palonosetron, followed by 16.9% with ondansetron, 17% with granisetron, and 17.3% with dolasetron.
• ▸ Over 6 cycles of chemotherapy, ondansetron cost an additional $126,775 compared with palonosetron, granisetron an additional $169,838, and dolasetron an additional $148,960.
• ▸ In addition, when CINV is not controlled early, palonosetron can still exhibit benefits in subsequent cycles compared with the older 5-HT₃-RA agents.
• ▸ This analysis also shows that choosing the most effective 5-HT₃-RA agent for the first chemotherapy cycle can help to reduce CINV rates in subsequent cycles, and therefore reduce costs.
• ▸ For patients receiving chemotherapy, considering the efficacy and associated costs of the 5-HT₃-RA agent used for CINV prevention can improve the patient''s quality of life and reduce overall costs.

Because CINV in the delayed phase is still a problem for patients receiving chemotherapy, the evidence for the effectiveness of palonosetron, and the increasing pressure to contain healthcare costs, we conducted this study to evaluate the clinical and economic impacts of delayed CINV in patients who initiated therapy with palonosetron and maintained therapy with palonosetron versus patients who initiated therapy with an older 5-HT₃-RA and received maintenance therapy with that older agent throughout their chemotherapy cycles.     

Evolving Trends in Insulin Delivery In Pursuit of Improvements in Diabetes Management

Diabetes mellitus affects 23.6 million Americans and its incidence is rapidly increasing, particularly in older, overweight patients. Large-scale studies conclusively show that elevated blood glucose levels are associated with an increased risk for microvascular complications, such as retinopathy and nephropathy. The high rates of morbidity and mortality associated with this disease, and the costs associated with it, underscore the importance of effective glycemic control. Conventional syringe/vial insulin delivery is associated with many barriers for patients with diabetes mellitus and for their healthcare providers. Substantial developments in insulin delivery show promise in overcoming these barriers. New technologies in insulin delivery focus on increasing patient convenience, reducing the frequency of daily injections, and improving glycemic control. This article outlines the challenges associated with conventional insulin delivery and describes recent developments that may help to overcome these barriers and, ultimately, could enhance glycemic control.Diabetes mellitus affects 23.6 million Americans, or about 8% of the US population.1 This includes nearly 18 million persons with diagnosed disease and about 5.7 million undiagnosed cases. The incidence of type 2 diabetes is rapidly increasing, particularly among older, overweight persons who have concomitant cardiovascular (CV) risks.2 The coexistence of diabetes mellitus and hypertension works synergistically to increase morbidity and mortality, especially renal and CV injury.3 Well-known, large-scale studies, such as the Diabetes Control and Complications Trial and the UK Prospective Diabetes Study, conclusively show that elevated levels of blood glucose are associated with an increased risk of microvascular complications, such as retinopathy and nephropathy.4–6 The high rates of morbidity and mortality associated with diabetes, coupled with the costs of treating these sequelae, underscore the importance of effective glycemic control.Maintaining optimal glucose control—defined by the American Diabetes Association as a glycosylated hemoglobin level of <7%7—may require multiple daily insulin injections. However, conventional insulin injection techniques are a major cause of reduced patient adherence to treatment.8 Patient medication adherence and satisfaction with treatment regimens are more likely to occur with fewer medication side effects, as well as with reduced patient burden and inconvenience.9,10 Typical side effects of insulin therapy may include weight gain or hypoglycemic events.2,11Significant advances in insulin delivery have been aimed at improving patient convenience and enhancing glycemic control.12 Alternatives to syringe/vial insulin delivery include:

• Insulin pens
• Injection ports
• Insulin infusion pumps
• Transdermal insulin patches
• Inhaled insulin.

Some of these methods, however, have not met with great success. Inhalable insulin was available in the United States from September 2006 through October 2007 but was subsequently withdrawn from the market because of poor utilization rates. Other advances currently in development include oral insulin and buccal insulin spray. An international phase 3 clinical trial is ongoing for both types of insulin delivery.This article reviews the barriers to adherence to conventional therapy and evaluates developments in the management of insulin-requiring diabetes that may help to overcome some of these barriers, as well as improve glycemic control and quality of life for patients with diabetes.

KEY POINTS

• ▸ Nearly 18 million Americans are diagnosed with diabetes, and about 5.7 million have the disease but have not been diagnosed.
• ▸ The high rates of morbidity and mortality associated with diabetes, and the costs associated with its treatment, underscore the importance of effective glycemic control.
• ▸ Conventional syringe/vial insulin delivery is associated with patient and physician barriers, such as psychological insulin resistance, patients'' fear of insulin side effects and complications, and required lifestyle changes/restrictions.
• ▸ Despite evidence that many patients with type 2 diabetes do not achieve glycemic control with oral therapy alone, some physicians are still reluctant to initiate insulin therapy.
• ▸ Developments in insulin delivery during the past 20 years have focused on increasing patient convenience and improved glycemic control.
• ▸ The newer insulin delivery modes include insulin pens, insulin injection ports, continuous subcutaneous insulin infusion pumps, transdermal patches, and inhalable devices.

     

Patient Preferences and Treatment Adherence Among Women Diagnosed with Metastatic Breast Cancer

Background

Given the various profiles (eg, oral vs intravenous administration, risk of hot flashes vs fatigue) of treatment options (eg, endocrine therapy, chemotherapy) for metastatic breast cancer (mBC), how patients value these attributes of their medications has implications on making treatment decisions and on adherence.

Objectives

To understand how patients trade off medication side effects with improved effectiveness and/or quality of life, to provide estimates of nonadherence among women with mBC, and to quantify the association of medication nonadherence with health outcomes.

Methods

The study was a cross-sectional, Internet-based survey of 181 women diagnosed with mBC who were recruited from cancer-specific online panels (response rate, 7%). Treatment information, demographics, nonadherent behaviors, and quality of life assessed by the Functional Assessment of Cancer Therapy-Breast (FACT-B) were collected in the survey, and each respondent completed a choice-based conjoint exercise to assess patient preferences. The patients'' preferences were analyzed using hierarchical Bayesian logistic regression models, and the association between the number of nonadherent behaviors and the health outcomes was analyzed using general linear models.

Results

The mean age of the patient sample was 52.2 years (standard deviation, ±9.1), with 93.9% of participants being non-Hispanic white. Results from the conjoint model indicated that effectiveness (overall survival) was of primary importance to patients, followed by side effects—notably alopecia, fatigue, neutropenia, motor neuropathy, and nausea/vomiting—and finally, dosing regimen. In all, 34.8% of survey respondents either discontinued their treatment or were nonadherent to their treatment regimen. Among those who have ever used oral chemotherapy (N = 95; 52.5%) and those currently using oral chemotherapy (N = 44; 24.3%), the number of nonadherent behaviors was significantly associated with a decrease in functional well-being (b [unstandardized regression coefficient] = −2.01 for patients who had ever used a targeted therapy and b = −3.14 for current users of a targeted therapy), FACT-General total score (b = −4.30 and b = −7.37, respectively), FACT-B total score (b = −3.93 and b = −6.11, respectively), and FACT trial outcome index (b = −5.22 and b = −8.63, respectively; all P <.05).

Conclusions

Patients were willing to accept substantial additional risks from side effects for gains in overall survival. Approximately 33% of women with mBC reported engaging in nonadherent behaviors. Because forgetfulness and adverse events were among the most frequent reasons for nonadherence, these results suggest that less complex treatment regimens, as well as regimens with less toxic profiles, may be associated with improvements in adherence and, subsequently, could correspond to perceptible patient benefits.Breast cancer is the most common cancer diagnosed among women in the United States, with an estimated 232,000 new cases diagnosed annually.1 It is also the second most deadly cancer, accounting for nearly 40,000 deaths annually.1 The 5-year survival rates for early-stage breast cancer is between 84% for regional disease (ie, contained within the breast and lymph nodes) and 99% for localized disease (ie, contained within the breast); the survival rate drops to 24% in more advanced stages of the disease.2 Metastatic breast cancer (mBC) is defined as breast cancer that has spread to other parts of the body. Whereas less than 10% of women are initially diagnosed with mBC, approximately 33% of women who are treated for early-stage disease will progress to mBC.2,3 The majority of breast cancer metastases affect the lymph nodes, followed by bone, liver, and lung.4,5At present, mBC is incurable, and treatment is focused on arresting the disease and extending patient survival, as well as promoting quality of life (QOL) and ensuring adequate symptom management.3,4 Treatment strategies may include endocrine therapy (eg, exemestane); targeted therapies, such as anti-HER2 agents (eg, trastuzumab); and chemotherapy (eg, capecitabine).6 As a result of the currently incurable nature of mBC and the side-effect profile associated with various forms of therapy, investigators have explored the potential role of patient preferences in decision-making regarding their treatment goals and desired outcomes.7–11 For example, aggressive treatment may maximize the duration of survival but may also be associated with significant and burdensome side effects that impair QOL.3,4Using the responses of 102 patients with breast cancer, Beusterien and colleagues recently revealed distinct preferences across side-effect profiles and a willingness to undergo more difficult treatment regimens to reduce the risk of more severe symptoms.7 Moreover, another study of 121 patients with breast cancer demonstrated the importance of a relatively minor survival benefit (as little as 3 months) for the perceived value of chemotherapy among patients with breast cancer, despite an increased risk for treatment toxicities.8 Further studies have shown a willingness of patients to trade a minor increase in disease recurrence risk for more convenient treatment regimens,9 as well as examining patient preferences for follow-up care10 and the ability for preferences to predict the eventual use of chemotherapy.11To our knowledge, no study to date has examined patient preferences using a conjoint method in women with mBC. In part, this may be because it is difficult to recruit this patient population for research survey purposes. Several studies have been conducted that have focused on patients diagnosed with early-stage breast cancer.12,13 McQuellon and colleagues surveyed women diagnosed with early-stage disease to assess their preferences for the hypothetical treatment of mBC.14 Although there was a wide range of preference profiles among the women who were surveyed, they were once again consistently willing to trade the risk of major side effects and toxicities for a modest survival benefit.14 However, because that study was initiated nearly 20 years ago, treatment advances since the time of that study were not included in that analysis.The primary objective of the current study is to provide an examination of contemporary treatments and to provide data on the treatment preferences of women with mBC to understand how these patients trade off side effects with increases in effectiveness and/or QOL.Patient preferences may have implications not only for treatment decision-making but also potentially for treatment adherence and follow-up care.15 If patient preferences and prescribed treatment regimens are misaligned, women diagnosed with breast cancer may become nonadherent, which could have implications for symptom management and for survival.15 To date, much of the research in this domain has focused on adherence to adjuvant therapy in patients with early-stage disease.16–18 A secondary objective of this study is to provide real-world evidence of nonadherence among women with mBC and to quantify the association with nonadherent behavior and health outcomes. We focused on adherence among patients receiving oral chemotherapy, because these agents are increasing in availability, and they represent a frequently self-administered treatment (as opposed to intravenous treatment, which is often not self-administered), and are thus more susceptible to nonadherent behaviors.

KEY POINTS

• ▸ Metastatic breast cancer (mBC) involves various drug regimens with different efficacy and side-effect profiles that may affect medication adherence.
• ▸ This is the first study to examine patient preferences in women with mBC.
• ▸ Of the 181 women with mBC surveyed, approximately 33% were nonadherent to their treatment regimen.
• ▸ Patients receiving hormone therapy reported the greatest nonadherence, followed by patients receiving an oral chemotherapeutic agent.
• ▸ Across all treatment modalities, forgetfulness (41.3%) and intolerance of side effects (36.5%) were the most common reasons for nonadherence.
• ▸ Although it is more convenient, women receiving oral chemotherapy were more likely to have significant declines in their health status.
• ▸ Patients are willing to trade substantial side-effect risks for gains in overall survival.
• ▸ The most important attributes of treatments were effectiveness and side effects; cost-related concerns were listed as the least important.
• ▸ The survey suggests that less complex and less toxic regimens may improve medication adherence and, ultimately, health outcomes.

     

Estimates of Commercial Population at High Risk for Cardiovascular Events: Impact of Aggressive Cholesterol Reduction

Objectives

To model the financial and health outcomes impact of intensive statin therapy compared with usual care in a high-risk working-age population (actively employed, commercially insured health plan members and their adult dependents). The target population consists of working-age people who are considered high-risk for cardiovascular disease events because of a history of coronary heart disease.

Study Design

Three-year event forecast for a sample population generated from the National Health and Nutrition Examination Survey data.

Methods

Using Framingham risk scoring system, the probability of myocardial infarction or stroke events was calculated for a representative sample population, ages 35 to 69 years, of people at high risk for cardiovascular disease, with a history of coronary heart disease. The probability of events for each individual was used to project the number of events expected to be generated for this population. Reductions in cardiovascular and stroke events reported in clinical trials with aggressive statin therapy were applied to these cohorts. We used medical claims data to model the cohorts'' event costs. All results are adjusted to reflect the demographics of a typical working-age population.

Results

The high-risk cohort (those with coronary heart disease) comprises 4% of the 35- to 69-year-old commercially insured population but generates 22% of the risk for coronary heart disease and stroke. Reduced event rates associated with intensive statin therapy yielded a $58 mean medical cost reduction per treated person per month; a typical payer cost for a 30-day supply of intensive statin therapy is approximately $57.

Conclusions

Aggressive low-density lipoprotein cholesterol–lowering therapy for working-age people at high risk for cardiovascular events and with a history of heart disease appears to have a significant potential to reduce the rate of clinical events and is cost-neutral for payers.Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the United States. The estimated direct and indirect cost of CVD for 2008 is $448.5 billion.1 CVD ranked highest among all disease categories for hospital discharges and was the most frequent primary diagnosis coded for physician, outpatient, and emergency department visits.1 Hypercholesterolemia, particularly elevated low-density lipoprotein cholesterol (LDL-C), is strongly associated with an increased risk of CVD, including coronary heart disease (CHD) events (ie, myocardial infarction [MI], angina, coronary revascularization) and stroke.2–4 Landmark statin studies targeting LDL-C lowering have shown dramatic reductions in heart attacks, stroke, and cardiac death.5–14 More recent studies have shown that intensive reduction of LDL-C levels in high-risk individuals with a history of CHD is associated with an even greater reduction in CVD events than conventional LDL-C lowering.7–9Although aggressive LDL-C therapy resulting in positive patient outcomes has been well documented, reports continue to find inadequate LDL-C therapy and poor compliance with statin therapy.15–17 Employers and commercial insurers bear significant medical cost and productivity burdens associated with undertreatment of hypercholesterolemia and poor compliance with statins, particularly for the high-risk population. Although studies have reported cost-effectiveness associated with statin therapy,18–23 none has reported the cost burden in terms relevant to an employer or a health plan, such as per member per month costs.Specifically, reports lack outcomes adjusted to a working-age population. Many studies report cost-effectiveness utilizing quality-adjusted life-years, which provides information of limited utility for employers and payers. A more meaningful approach may be to provide cost-effectiveness in terms that would allow employers and payers to project short-term impact on medical utilization and costs for budgetary purposes. Other studies report cost-effectiveness using LDL-C reduction and unit drug costs across statins, without considering the impact of CVD event reduction cost offsets.Our analysis models the cost impact of aggressive statin therapy for a commercially insured cohort of members at high risk for secondary events from CVD as a result of a history of CHD. This group represents an important subset of working-age health plan members for a commercial insurer. Using this newly developed model, we compare the CVD event and cost burden under conventional current therapy to represent the results of intensive statin therapy, which is the current standard of care for high-risk patients.Disease management efforts by employers and other payers that are focused on commercial members with CHD can represent a substantial financial investment. Such efforts seek to identify and provide early clinical intervention to improve outcomes in populations at risk for adverse events. Therefore, individuals with a history of CHD are targeted for disease management programs, because payers believe that such interventions can avoid various complications, including stroke and secondary events (eg, acute MI). However, the claims of improved outcomes of disease management vendors have received significant criticism.24,25 In particular, the range of improved outcomes demonstrated by applying the results of intensive statin therapy to this population can suggest plausible maximum improvements from disease management programs.In addition, employers and insurers are experimenting with benefit designs, such as lower copayments or other financial incentives to maximize drug compliance for those with chronic diseases. Studies consistently report decreased statin compliance with higher copayments.26–29 The present article offers guidance to such experiments on the potential health and cost improvements possible through various initiatives.

KEY POINTS

• ▸ This actuarial study highlights the potential cost-savings for employers and payers with the use of intensive cholesterol-lowering therapy in people with coronary heart disease.
• ▸ This study calculates cost-effectiveness in terms that facilitate projections of short-term impact on medical utilization and costs.
• ▸ The target population is commercially insured people aged 35 to 69 years who have a high risk for cardiovascular/cerebrovascular events.
• ▸ Results suggest that in these high-risk patients, intensive lipid-lowering therapy, would result in a 33% overall reduction in events.
• ▸ This risk reduction would result in incremental average cost reductions of $58 per target patient per month, a $696 annual reduction per target patient.

Using the National Health and Nutrition Survey (NHANES) 2003–2004 and 2005–2006 survey data, we identified the target population of people at high risk for CVD who had a history of CHD. NHANES is a survey of healthcare information for US residents readily available from the National Center for Health Statistics and the Centers for Disease Control and Prevention. It is designed to provide reliable estimates of the health and nutritional status of the US civilian noninstitutionalized population.30     

The Impact of 5-HT3RA Use on Cost and Utilization in Patients with Chemotherapy-Induced Nausea and Vomiting: Systematic Review of the Literature

Background

Individual studies have assessed the impact of standard prophylactic therapy with 5-hydroxytryptamine receptor antagonists (5-HT₃RAs) for chemotherapy-induced nausea and vomiting (CINV) on cost and utilization, but no synthesis of the findings exists.

Objective

To systematically review published literature on costs and utilization associated with CINV prophylaxis with palonosetron and other 5-HT₃RAs.

Methods

PubMed and the National Institute for Health Research Centre for Reviews and Dissemination databases, conferences of 4 organizations (ie, Academy of Managed Care Pharmacy, American Society of Clinical Oncology, International Society for Pharmacoeconomics and Outcomes Research, and Multinational Association of Supportive Care in Cancer), and the bibliographies of relevant articles were queried for the medical subject headings and key terms of “ondansetron,” “granisetron,” “palonosetron,” “dolasetron mesylate,” “costs,” “cost analysis,” and “economics.” We included records published (full-length articles after 1997 and conference presentations after 2010) in English and with human patients, reporting data on cost and utilization (rescue medication, outpatient and inpatient services) associated with the use of 5-HT₃RAs for the treatment or prevention of CINV.

Results

Of the 434 identified studies, 32 are included in the current analysis: 7 studies report costs, 18 report utilization, and 7 studies report both. The costs are reported in US dollars (7 studies), in Euros (5 studies), and in Canadian dollars (2 studies). The studies vary in designs, patients, 5-HT₃RA regimens, and the definition of outcomes. The US studies report higher drug costs for CINV prophylaxis with palonosetron compared with ondansetron, lower medical outpatient and inpatient costs for palonosetron versus other 5-HT₃RAs, and higher acquisition costs for palonosetron versus ondansetron or other 5-HT₃RAs. Fewer patients receiving palonosetron versus with ondansetron or other 5-HT₃RAs required rescue medication or used outpatient or inpatient care. In Europe and in Canada, the total pharmacy costs and use of rescue medications reported are lower for patients receiving prophylaxis with palonosetron.

Conclusions

This analysis shows that prophylaxis with palonosetron for the treatment of CINV is associated with higher acquisition treatment costs, but also with lower use of rescue medications and outpatient and inpatient services compared with ondansetron or other 5-HT₃RAs in the United States. Therefore, the use of palonosetron as a standard treatment may lead to reduced service utilization for CINV.Chemotherapy-induced nausea and vomiting (CINV) is an adverse effect of cancer treatment. It may occur within a few minutes of or up to 24 hours after the administration of chemotherapy (ie, acute CINV), or it may occur more than 24 hours after treatment (ie, delayed CINV). CINV may last up to 7 days.1–7Although there are several patient-specific factors that place patients at an increased risk for developing CINV (eg, female sex, low consumption of alcohol, history of motion or morning sickness, age under 50 years, previous CINV), the most contributory risk factor is the emetogenic potential of the chemotherapy regimen itself.8

KEY POINTS

• ▸ Poorly controlled CINV may lead to nutrient depletion, reduced functional ability, diminished quality of life, or the premature discontinuation of chemotherapy.
• ▸ Previous studies have examined the impact of CINV prophylaxis with palonosetron and other 5-HT₃RAs on cost and utilization, but this is the first systematic review of the published literature on this topic.
• ▸ A total of 32 studies were included in this systematic literature review, of which 14 studies report costs and 25 reported utilization.
• ▸ This review indicates that palonosetron is associated with higher treatment costs but also with lower rescue medication use and outpatient and inpatient services use compared with other 5-HT₃RAs.
• ▸ Based on this analysis, the use of palonosetron as a standard treatment may lead to reduced service utilization for CINV.

More than 90% of patients undergoing highly emetogenic chemotherapy (HEC) will experience emesis without antiemetic prophylaxis, and 30% to 90% of those undergoing moderately emetogenic chemotherapy (MEC) will vomit without the prophylactic administration of antiemetics.8 From 10% to 30% of the patients receiving low emetogenic risk chemotherapy (LEC), and <10% of patients receiving minimal emetogenic risk chemotherapy (MinEC), will experience emesis without the administration of antiemetics.3,6,7,9 The dose, frequency, and length of administration, as well as the combination of agents may impact the emetogenicity of the chemotherapy.7Poorly controlled CINV may lead to nutrient depletion, reduced functional ability, diminished quality of life, or the premature discontinuation of chemotherapy.1-4,6,7,9 The use of prophylactic antiemetic medications in patients undergoing HEC may reduce the incidence of CINV to as low as 30%.7 A multidrug regimen containing a 5-hydroxytryptamine receptor antagonist (5-HT₃RA) is the standard approach for CINV prophylaxis.7 Drugs in this category include dolasetron mesylate, granisetron, ondansetron, palonosetron, and tropisetron, with palonosetron recommended as the preferred 5-HT₃RA for CINV prophylaxis with MEC by the guidelines of the National Comprehensive Cancer Network (NCCN), the Multinational Association of Supportive Care in Cancer/Economic Society for Medical Oncology (MASCC/ESMO), and the American Society of Clinical Oncology (ASCO).5,7,10Secondary rescue medications are used to treat breakthrough CINV among patients who have received prophylaxis.7 These medications may include metoclopramide, lorazepam, diphenhydramine, olanzapine, prochlorperazine, or dexamethasone.CINV increases direct costs (eg, medication, office visits, or hospitalizations) and indirect costs (eg, missed work).3,4,9 The effective prevention of CINV may reduce these costs. The clinical and economic impact of CINV underscore the importance of achieving CINV prophylaxis.3,4,9 Palonosetron—which has greater binding affinity and a longer half-life than the other 5-HT₃RAs, binds allosterically, stimulates receptor internalization, demonstrates positive cooperativity, and cross talks with the neurokinin (NK)-1 signaling pathway—prevents both acute and delayed CINV more effectively than the other 5-HT₃RAs.7,11-14The extent to which the clinical benefit of 5-HT₃RAs translates into reduced costs or utilization of healthcare services among patients with CINV has been shown in individual studies for subsets of outcomes,3,15 but no summary of the literature exists. We conducted a systematic literature review of published research on the healthcare costs and utilization associated with the use of 5-HT₃RAs for the prevention of CINV in patients receiving chemotherapy, with the goal of comparing palonosetron with the other 5-HT₃RAs.