Cost-effectiveness of edoxaban for the treatment of venous thromboembolism based on the Hokusai-VTE study.

OBJECTIVE: Venous thromboembolism (VTE) is associated with almost 300,000 deaths per year in the United States. Novel oral anticoagulants (NOACs) offer an alternative to warfarin-based therapy without monitoring requirements and with fewer drug and food interactions. Edoxaban, a direct Xa inhibitor, is approved by the Food and Drug Administration (FDA), based upon results of the Hokusai-VTE Phase 3 trial. The trial demonstrated that edoxaban administered once daily after initial treatment with heparin was non-inferior in reducing the risk of VTE recurrence and caused significantly less major and clinically relevant non-major (CRNM) bleeding compared to warfarin. The objective of this study was to evaluate the cost-effectiveness of edoxaban versus warfarin for the treatment of adults with VTE. METHODS: A cost-effectiveness model was developed using patient-level data from the Hokusai-VTE trial, clinical event costs from real-world databases, and drug acquisition costs for warfarin of $0.36 and edoxaban of $9.24 per tablet. RESULTS: From a U.S. health-care delivery system perspective, the incremental cost-effectiveness ratio (ICER) was $22,057 per quality adjusted life year (QALY) gained. Probabilistic sensitivity analysis showed that edoxaban had an ICER <$50,000 per QALY gained relative to warfarin in 67% of model simulations. The result was robust to variation in key model parameters including the cost and disutility of warfarin monitoring. CONCLUSION: Despite its higher drug acquisition cost, edoxaban is a cost-effective alternative to warfarin for the treatment of VTE.

Cost-effectiveness analysis of tapentadol immediate release for the treatment of acute pain.

BACKGROUND: Tapentadol immediate-release (IR) tablets are indicated for the treatment of moderate to severe acute pain. In clinical trials, tapentadol IR effectively reduced moderate to severe pain with improved tolerability compared with oxycodone IR at doses providing comparable analgesia. OBJECTIVE: This analysis compared the cost-effectiveness of tapentadol IR with doses of oxycodone IR providing comparable analgesia in the outpatient treatment of acute postsurgical and nonsurgical pain. The perspective was that of a US managed care health plan as third-party payer. METHODS: A Markov model was developed to simulate clinical-economic outcomes for tapentadol IR 100 mg compared with oxycodone IR 15 mg in the treatment of acute postsurgical pain (3 days) and for tapentadol IR 50 mg compared with oxycodone IR 10 mg in the treatment of acute nonsurgical pain (10 days). The model simulated changes in pain relief; occurrence of opioid-related adverse events (AEs); opioid switching, discontinuation, and dose change; and number of quality-adjusted life-days (QALDs). Data inputs for the model were obtained from clinical trials, claims databases, surveys, Medicare fee schedules, and other published sources. Only direct costs were included. Drug costs were based on the wholesale acquisition cost. Prescription copayments were set at $5 for oxycodone IR and $25 for tapentadol IR. All costs were in 2008 US dollars. Sensitivity analyses were conducted on key model parameters. RESULTS: The cost of pain medication per patient was higher for tapentadol IR than for oxycodone IR in both the surgical pain setting ($15.23 vs $9.57, respectively) and the nonsurgical pain setting ($57.17 vs $21.31). However, this cost difference was offset by reductions in pharmacy and medical costs associated with the treatment of AEs and opioid switching/discontinuation, resulting in a lower mean treatment cost per patient for tapentadol IR 100 mg compared with oxycodone IR 15 mg in the treatment of acute surgical pain ($52.90 vs $55.99) and for tapentadol IR 50 mg compared with oxycodone IR 10 mg in the treatment of acute nonsurgical pain ($139.48 vs $144.79). Tapentadol IR also was associated with a greater mean number of treatment days with ≥30% improvement in pain intensity without opioid-related AEs compared with oxycodone IR and a greater mean number of QALDs (surgical pain: 1.73 vs 1.68; nonsurgical pain: 6.03 vs 4.92). Because both doses of tapentadol IR were dominant (ie, lower treatment costs and greater effectiveness) relative to the corresponding doses of oxycodone IR providing com- parable analgesia, incremental cost-effectiveness ratios were not calculated. CONCLUSION: The results of this model suggest that at doses providing comparable analgesia, tapentadol IR is a cost-effective alternative to oxycodone IR for the treatment of acute surgical and nonsurgical pain.

Migraine: a better way to recognize and treat it.

Consider using the Headache Assessment Quiz, which 76% of providers in this study said enabled patients to adequately convey headache severity/symptoms, compared with just 20% of providers at baseline who thought patients communicated clearly. Use the quiz also to better understand the impact of migraine on a patient's life, and to help determine which patients need migraine-specific therapy.

The effect of early intervention with sumatriptan tablets on migraine-associated productivity loss.

OBJECTIVE: Impaired performance, which can considerably impact employee output, occurs when employees attempt to continue work with inadequate treatment while experiencing a migraine episode. This analysis examined productivity loss as a result of migraine after treatment with sumatriptan tablets and patients' usual non-triptan therapy when pain was mild (early intervention) versus when pain was moderate/severe. METHODS: The authors conducted a retrospective analysis of data on 6803 migraine days reported by 251 subjects who participated in a clinical trial. RESULTS: Although early intervention significantly reduced productivity loss compared with treatment when pain was moderate/severe for both sumatriptan and non-triptan therapy, productivity loss was consistently lower for sumatriptan than non-triptan therapy for all predose pain intensity levels. CONCLUSIONS: These findings suggest that the pharmaco-economic benefits of early intervention with sumatriptan tablets, like the clinical benefits, exceed those of delayed intervention.

Effects of a fast disintegrating/rapid release oral formulation of sumatriptan on functional ability in patients with migraine.

BACKGROUND: A new oral form of sumatriptan has been developed to facilitate tablet disintegration and drug dispersion and to mitigate the effects of gastric stasis that can accompany migraine. OBJECTIVE: To evaluate the effects on functional ability of the new fast disintegrating/rapid release formulation of sumatriptan. METHODS: Sumatriptan 50 mg (n = 137), 100 mg (n = 142), or placebo (n = 153) was administered early when pain was mild for the acute treatment of a single migraine attack in a randomized, double-blind, parallel-group, placebo-controlled clinical trial. For this report, main health-outcomes endpoints (which were secondary endpoints for this clinical trial that was primarily designed to assess pain-free efficacy) included functional ability measured through 2 h postdose on a 5-point scale and lost time equivalents, a composite measure of migraine-associated time missed from activities, and reduced effectiveness at activities through 24 h postdose. RESULTS: Normal functional ability was restored in a significantly (p < 0.05) greater percentage of patients treated with sumatriptan than placebo beginning 45 min postdose for sumatriptan 100 mg and 1 h postdose for sumatriptan 50 mg. During the 24 h after initial dosing, the median (range) lost time equivalents for the combination of paid work activities and activities outside of paid work were significantly lower in the groups treated with sumatriptan (1.1 [0-10] sumatriptan 100 mg; 0.8 [0-36] sumatriptan 50 mg) compared with placebo (2.9 [0-24]) (p < or = 0.01 each sumatriptan group versus placebo). The corresponding mean +/- SD values for lost time equivalents were 1.9 +/- 2.3 and 2.5 +/- 4.7 for sumatriptan 100 mg and 50 mg, respectively, compared with 3.5 +/- 4.3 for placebo. CONCLUSION: A new oral sumatriptan formulation confers rapid, sustained restoration of functional ability in the acute treatment of migraine so that patients can return rapidly to normal functioning at work and outside of work.

Costs and outcomes of early versus delayed migraine treatment with sumatriptan.

OBJECTIVE: To evaluate the impact on costs and outcomes of early migraine treatment with sumatriptan while pain is mild versus sumatriptan treatment of moderate to severe pain. BACKGROUND: Migraines result in substantial pain, impairment, and costs. Recent clinical studies have shown that early treatment with sumatriptan when migraine pain is mild is more effective than sumatriptan treatment when pain is moderate to severe. DESIGN/METHODS: We developed a decision analytical model to assess the costs and outcomes per treated migraine attack, comparing early treatment while pain is mild versus delayed treatment when pain may become moderate/severe using 50 and 100 mg of sumatriptan. Parameters for the model were derived from published literature and analysis of migraine patient diary data. For each patient group the model determined the duration of mild and moderate/severe migraine pain, the proportion of patients pain free at 4 hours after initial therapy with no recurrence, medical care costs, and work loss costs (from migraine-related absenteeism and decreased productivity) during a 24-hour period. Total costs were calculated as the sum of medical care costs plus work loss costs. RESULTS: Early treatment with sumatriptan when migraine pain is mild resulted in substantially decreased total costs per treated attack as compared with treatment when pain is moderate/severe. Early treatment also resulted in decreased time with headache pain, an increased proportion of patients pain free at 4 hours without recurrence, and decreased physician and emergency department visits. Treatment with 100 mg sumatriptan resulted in better outcomes than did treatment with 50 mg sumatriptan, but outcomes with either dose for early treatment of mild pain were superior to those for either dose in delayed treatment when pain may be moderate/severe. CONCLUSIONS: Model-based results indicate that on a treated attack basis, early treatment of migraine with sumatriptan while pain is mild leads to decreased costs and improved outcomes compared to delayed sumatriptan treatment.

Antidepressant-induced sexual dysfunction.

OBJECTIVE: To review the evidence regarding antidepressant-induced sexual dysfunction and address implications for treatment strategy and health plan coverage policies for antidepressant medications. DATA SOURCES: Primary articles were identified by a MEDLINE and HealthSTAR search to identify English-language studies published between January 1986 and July 2000. Search terms included sexual dysfunction or sexual function and antidepressants, fluoxetine, sertraline, paroxetine, fluvoxamine, citalopram, venlafaxine, nefazodone, bupropion, and mirtazapine. A cross-check of references cited in 10 published reviews yielded additional in-scope articles. STUDY SELECTION AND DATA EXTRACTION: Approximately 200 articles were identified, including 8 randomized controlled trials and numerous open-label studies, case series, and case reports. Of the randomized controlled trials, only 5 were designed to evaluate the incidence of sexual dysfunction associated with antidepressant treatment. Three additional randomized controlled trials included a structured assessment of sexual dysfunction within an efficacy trial. Data extraction excluded case reports, letters, and other limited study designs. A panel survey augmented published reports. DATA SYNTHESIS: Sexual dysfunction is a relatively common adverse effect of many of the antidepressants in common use today. Rates of sexual dysfunction observed in clinical practice may be higher than those reported in the product information for several agents. Selective serotonin-reuptake inhibitors (SSRIs) appear to be the class of antidepressants most likely to cause sexual dysfunction. Published studies suggest that between 30% and 60% of SSRI-treated patients may experience some form of treatment-induced sexual dysfunction. Bupropion and nefazodone appear to be much less likely to cause sexual dysfunction (

Improved Health-Related Quality of Life and Reduced Productivity Loss After Treatment With Bupropion Sustained Release: A Study in Patients With Major Depression.

BACKGROUND: This open-label portion of a 2-phase study assessed the effects of the antidepressant bupropion sustained release (SR) on health-related quality of life (QOL) and workplace productivity in patients with major depression. METHOD: Patients (N = 816) with DSM-IV major depression were treated with bupropion SR, 300 mg/day, for 8 weeks. The Clinical Global Impressions scale for Improvement of Illness (CGI-I) was completed at weekly clinic visits. At baseline and week 8, QOL and productivity were assessed. QOL was assessed using the Quality of Life in Depression Scale (QLDS). RESULTS: QOL and productivity were significantly improved from baseline after 8 weeks of treatment with bupropion SR. Mean QLDS scores were 18.98 and 10.36 at baseline and week 8, respectively (mean change = 8.62; p <.001). At week 8 compared with baseline, patients working at a paid job reported missing 1.58 fewer hours of work because of depression during the past 7 days, being 14.6% more effective on the job, working at reduced effectiveness less often, and incurring 6.37 fewer hours of overall lost productivity (p <.001 each variable). Improvements in QOL and productivity were significantly (p <.001) greater in bupropion SR responders (i.e., those with CGI-I scores of "very much improved" or "much improved" during the last 3 weeks of open-label therapy) than in nonresponders. CONCLUSION: Effective treatment of major depression with bupropion SR for 8 weeks is associated with improvements in QOL and reductions in lost workplace productivity. Patients who responded clinically to bupropion SR showed significantly greater improvements in these variables than those who did not respond.