Assessing the value of mepolizumab for severe eosinophilic asthma: a cost-effectiveness analysis.

BACKGROUND: Adding mepolizumab to standard treatment with inhaled corticosteroids and controller medications could decrease asthma exacerbations and use of long-term oral steroids in patients with severe disease and increased eosinophils; however, mepolizumab is costly and its cost effectiveness is unknown. OBJECTIVE: To estimate the cost effectiveness of mepolizumab. METHODS: A Markov model was used to determine the incremental cost per quality-adjusted life year (QALY) gained for mepolizumab plus standard of care (SoC) and for SoC alone. The population, adults with severe eosinophilic asthma, was modeled for a lifetime time horizon. A responder scenario analysis was conducted to determine the cost effectiveness for a cohort able to achieve and maintain asthma control. RESULTS: Over a lifetime treatment horizon, 23.96 exacerbations were averted per patient receiving mepolizumab plus SoC. Avoidance of exacerbations and decrease in long-term oral steroid use resulted in more than $18,000 in cost offsets among those receiving mepolizumab, but treatment costs increased by more than $600,000. Treatment with mepolizumab plus SoC vs SoC alone resulted in a cost-effectiveness estimate of $386,000 per QALY. To achieve cost effectiveness of approximately $150,000 per QALY, mepolizumab would require a more than 60% price discount. At current pricing, treating a responder cohort yielded cost-effectiveness estimates near $160,000 per QALY. CONCLUSION: The estimated cost effectiveness of mepolizumab exceeds value thresholds. Achieving these thresholds would require significant discounts from the current list price. Alternatively, treatment limited to responders improves the cost effectiveness toward, but remains still slightly above, these thresholds. Payers interested in improving the efficiency of health care resources should consider negotiations of the mepolizumab price and ways to predict and assess the response to mepolizumab.

An internet-based randomized, placebo-controlled trial of kava and valerian for anxiety and insomnia.

The herbal extracts kava and valerian are the leading dietary supplements used in the self-management of anxiety and insomnia, respectively. There is limited evidence to support their effectiveness for these common symptoms. The Internet has been used to a limited extent for research, but it is not known whether randomized controlled trials can be conducted entirely using Internet technology. We performed a randomized, double-blind, placebo-controlled trial using a novel Internet-based design to determine if kava is effective for reducing anxiety and if valerian is effective for improving sleep quality. E-mail recruitment letters and banner advertisements on websites were used to recruit a large pool of interested participants (1551) from 45 states over an 8-week period. Participants were first asked to read study information, complete an online informed consent process, and undergo electronic identity verification. In order to be eligible for the study, participants were required to have 1) anxiety as documented by scores of at least 0.5 standard deviations above the mean on the State-Trait Anxiety Inventory State subtest (STAI-State) on 2 separate occasions, and 2) insomnia, defined as a "problem getting to sleep or staying asleep over the past 2 weeks." We randomly assigned 391 eligible participants to 1 of the following 3 groups, and mailed 28 days' supply: kava with valerian placebo (n = 121), valerian with kava placebo (n = 135), or double placebo (n = 135). The primary outcome measures were changes from baseline in anxiety (STAI-State questionnaire) and insomnia (Insomnia Severity Index [ISI]) compared with placebo. Participants receiving placebo had a 14.4 point decrease in anxiety symptoms on the STAI-State score and an 8.3 point decrease in insomnia symptoms on the ISI. Those receiving kava had similar reductions in STAI-State score (2.7 point greater reduction in placebo compared with kava; 95% confidence interval [CI], -0.8 to +6.2). Those receiving valerian and placebo had similar improvements in sleep (0.4 point greater reduction in the placebo than the valerian group; 95% CI, -1.3 to +2.1). Results were similar when limited to the 83% of participants who adhered to study compounds for all 4 weeks. Neither kava nor valerian relieved anxiety or insomnia more than placebo. This trial demonstrates the feasibility of conducting randomized, blinded trials entirely via the Internet.

Effect of isoflavones on lipids and bone turnover markers in menopausal women.

OBJECTIVES: The purpose of this analysis was to compare the effects of two dietary supplements derived from red clover to placebo on lipids and bone turnover markers in symptomatic menopausal women. METHODS: The study was a 12-week randomized, double-blind, placebo-controlled trial. Two hundred and fifty-two menopausal women ages 45-60 years experiencing > or =35 hot flashes per week were randomly assigned to Promensil (82 mg total isoflavones), Rimostil (57.2 mg total isoflavones), or placebo. Primary outcome measures were mean absolute changes for HDL-cholesterol, serum osteocalcin, and urinary N-telopeptide. Secondary outcome measures were mean changes of total cholesterol, LDL-cholesterol, the ratio of HDL- to LDL-cholesterol, and triglycerides. RESULTS: Ninety-eight percent of participants completed the 12-week protocol. Women taking Rimostil or Promensil compared to those taking placebo had greater mean increases in HDL-cholesterol; however, this change was small in magnitude (<2 mg/dl) and did not reach significance. There was a significant decrease in triglyceride levels among women taking Rimostil (14.4 mg/dl, P = 0.02) or Promensil (10.9 mg/dl, P = 0.05) compared to those taking placebo. The decrease was primarily among women with elevated baseline triglyceride levels (P for interaction = 0.009). There were no differences in mean changes of total cholesterol, LDL-cholesterol, or the ratio of HDL- to LDL-cholesterol among treatment groups. There were no statistically significant differences among treatment groups for bone turnover markers. CONCLUSIONS: Compared with placebo, both of the supplements containing isoflavones decrease levels of triglycerides in symptomatic menopausal women; however, this effect is small in magnitude.

Phytoestrogen supplements for the treatment of hot flashes: the Isoflavone Clover Extract (ICE) Study: a randomized controlled trial.

CONTEXT: Clinical trials demonstrating increased risk of cardiovascular disease and breast cancer among women randomized to hormone replacement therapy have increased interest in other therapies for menopausal symptoms. Dietary supplements containing isoflavones are widely used as alternatives to hormonal therapies for hot flashes, but there is a paucity of data supporting their efficacy. OBJECTIVE: To compare the efficacy and safety of 2 dietary supplements derived from red clover with placebo in symptomatic menopausal women. DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind, placebo-controlled trial of menopausal women, aged 45 to 60 years, who were experiencing at least 35 hot flashes per week. The study was conducted between November 1999 and March 2001 at 3 US medical centers and included women who were recently postmenopausal (mean [SD], 3.3 [4.5] years since menopause) experiencing 8.1 hot flashes per day. Women were excluded if they were vegetarians, consumed soy products more than once per week, or took medications affecting isoflavone absorption. INTERVENTION: After a 2-week placebo run-in, 252 participants were randomly assigned to Promensil (82 mg of total isoflavones per day), Rimostil (57 mg of total isoflavones per day), or an identical placebo, and followed-up for 12 weeks. MAIN OUTCOME MEASURE: The primary outcome measure was the change in frequency of hot flashes measured by participant daily diaries. Secondary outcome measures included changes in quality of life and adverse events. RESULTS: Of 252 participants, 246 (98%) completed the 12-week protocol. The reductions in mean daily hot flash count at 12 weeks were similar for the Promensil (5.1), Rimostil (5.4), and placebo (5.0) groups. In comparison with the placebo group, participants in the Promensil group (41%; 95% confidence interval [CI], 29%-51%; P =.03), but not in the Rimostil group (34%; 95% CI, 22%-46%; P =.74) reduced hot flashes more rapidly. Quality-of-life improvements and adverse events were comparable in the 3 groups. CONCLUSION: Although the study provides some evidence for a biological effect of Promensil, neither supplement had a clinically important effect on hot flashes or other symptoms of menopause.