Cost-effectiveness of first-line vs third-line ibrutinib in patients with untreated chronic lymphocytic leukemia.

The ALLIANCE A041202 trial found that continuously administered ibrutinib in the first-line setting significantly prolonged progression-free survival compared with a fixed-duration treatment of rituximab and bendamustine in older adults with chronic lymphocytic leukemia (CLL). In this study, we created a Markov model to assess the cost-effectiveness of ibrutinib in the first-line setting, compared with a strategy of using ibrutinib in the third-line after failure of time-limited bendamustine and venetoclax-based regimens. We estimated transition probabilities from randomized trials using parametric survival modeling. Lifetime direct health care costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs) were calculated from a US payer perspective. First-line ibrutinib was associated with an improvement of 0.26 QALYs and 0.40 life-years compared with using ibrutinib in the third-line setting. However, using ibrutinib in the first-line led to significantly higher health care costs (incremental cost of $612 700), resulting in an ICER of $2 350 041 per QALY. The monthly cost of ibrutinib would need to be decreased by 72% for first-line ibrutinib therapy to be cost-effective at a willingness-to-pay threshold of $150 000 per QALY. In a scenario analysis where ibrutinib was used in the second-line in the delayed ibrutinib arm, first-line ibrutinib had an incremental cost of $478 823, an incremental effectiveness of 0.05 QALYs, and an ICER of $9 810 360 per QALY when compared with second-line use. These data suggest that first-line ibrutinib for unselected older adults with CLL is unlikely to be cost-effective under current pricing. Delaying ibrutinib for most patients with CLL until later lines of therapy may be a reasonable strategy to limit health care costs without compromising clinical outcomes.

The cost utility of pitolisant as narcolepsy treatment.

OBJECTIVES: The cost-effectiveness of available pharmacological treatments for narcolepsy is largely unknown. Available pharmacological treatments are associated with tolerability, abuse, and adherence issues. Pitolisant is the first inverse agonist of the histamine H3 receptor to be prescribed for the treatment of narcolepsy with and without cataplexy. Studies suggest that pitolisant is both as effective as previously introduced drugs and is associated with fewer adverse effects. The objective in this study was to estimate the cost-effectiveness of pitolisant as monotherapy, and pitolisant as an adjunctive treatment to modafinil, compared with standard treatment. MATERIALS & METHODS: Calculations were performed using a Markov model with a 50-year time horizon. Healthcare utilization and quality-adjusted life years (QALYs) for each treatment alternative were calculated assuming no treatment effect on survival. Probabilistic sensitivity analyses were performed for treatment effectiveness and healthcare cost parameters. RESULTS: The cost per additional quality-adjusted life year was estimated at SEK 356 337 (10 SEK ≈ 1 Euro) for pitolisant monotherapy, and at SEK 491 128 for pitolisant as an adjunctive treatment, as compared to standard treatment. The cost-effectiveness measure was demonstrated to be particularly sensitive to the assumptions made concerning indirect effects on total healthcare utilization and the pitolisant treatment cost. CONCLUSIONS: The incremental cost-effectiveness ratios were below the unofficial willingness-to-pay threshold at SEK 500 000. The estimated costs per additional QALY obtained here are likely to overestimate the true cost-effectiveness ratio since significant potential indirect effects-pertaining both to labor-market and household-related productivity-of treatment are not taken into account.

Modelling the cost-effectiveness of tofacitinib for the treatment of rheumatoid arthritis in the United States.

BACKGROUND AND OBJECTIVES: Rheumatoid arthritis (RA) is a chronic, debilitating disease affecting an estimated 1.5 million patients in the US. The condition is associated with a substantial health and economic burden. An economic model was developed to evaluate the cost-effectiveness of tofacitinib (a novel oral Janus kinase inhibitor) versus biologic therapies commonly prescribed in the US for the treatment of RA. METHODS: A cost-utility model was developed whereby sequences of treatments were evaluated. Response to treatment was modeled by HAQ change, and informed by a network meta-analysis. Mortality, resource use and quality of life were captured in the model using published regression analyses based on HAQ score. Treatment discontinuation was linked to response to treatment and to adverse events. Patients were modeled as having had an inadequate response to methotrexate (MTX-IR), or to a first biologic therapy (TNFi-IR). RESULTS: The tofacitinib strategy was associated with cost savings compared with alternative treatment sequences across all modeled scenarios (i.e. in both the MTX-IR and TNFi-IR scenarios), with lifetime cost savings per patient ranging from $65,205 to $93,959 (2015 costs). Cost savings arose due to improved functioning and the resulting savings in healthcare expenditure, and lower drug and administration costs. The tofacitinib strategies all resulted in an increase in quality-adjusted life years (QALYs), with additional QALYs per patient ranging from 0.01 to 0.22. CONCLUSIONS: Tofacitinib as a second-line therapy following methotrexate failure and as a third-line therapy following a biologic failure produces lower costs and improved quality of life compared with the current pathway of care.

Fast-track pathway for minimally invasive colorectal surgery with and without alvimopan (Entereg)™: which is more cost-effective?

Multimodal fast-track (FT) pathways for both open and laparoscopic colorectal surgery have been shown to improve gastrointestinal recovery, shorten length of stay, and decrease morbidity. The aim of our study was to determine if using alvimopan (Entereg)™ in the setting of a FT minimally invasive colorectal pathway is beneficial and cost-effective. All minimally invasive colorectal surgeries performed by one surgeon using a multimodal FT pathway with and without alvimopan were reviewed. Ninety total patients were identified, 64 patients treated without and 26 with alvimopan. Main outcomes included postoperative day tolerating a soft diet, return of gastrointestinal function, length of stay, 30-day readmission rate, and patient care, anesthesia, pharmacy, and combined cost. Tolerance of a soft diet, return of gastrointestinal function, and length of stay were all shorter and showed significance in the alvimopan group (mean 2.1 vs 2.8 days, mean 1.5 vs 2.4 days, and mean 3.5 vs 4.5 days, respectively) (P = 0.0197, P = 0.0029, and 0.0158, respectively). Patient care and combined hospital costs were both increased in the nonalvimopan group; however, combined hospital costs was not significant (P = 0.0216 and P = 0.0875, respectively). The 30-day readmission rate of 6.3 per cent was also not significant in this group (P = 0.0941). Patients undergoing minimally invasive colorectal surgery treated with a multimodal FT pathway tolerated a soft diet sooner, had earlier return of bowel function, a shorter length of stay, and lower patient care and combined costs when alvimopan was used.

What is the clinical effectiveness and cost-effectiveness of using drugs in treating obese patients in primary care? A systematic review.

BACKGROUND: Obesity [defined as a body mass index (BMI) ≥ 30 kg/m(2)] represents a considerable public health problem and is associated with a significant range of comorbidities and an increased mortality risk. The primary aim of the management of obesity is to achieve weight reduction in the interests of health. For obese patients who cannot achieve or maintain a healthy weight by non-pharmacological means, drug therapy is recommended in combination with non-pharmacological interventions such as dietary modifications and exercise. OBJECTIVE: To evaluate the clinical effectiveness and cost-effectiveness of three pharmacological interventions in obese patients. DATA SOURCES: Clinical effectiveness data used in the meta-analysis were sourced from articles identified in a systematic review of the literature. Data used to inform transitions to obesity-related comorbidities were derived from the General Practice Research Database (GPRD). The results of the meta-analysis and GPRD analyses informed the economic model supplemented by data from the Health Survey for England and other UK-specific data sourced from the literature. REVIEW METHODS: A systematic literature review was conducted of the clinical effectiveness and cost-effectiveness of orlistat, sibutramine and rimonabant within their licensed indications for the treatment of obese patients. Electronic bibliographic databases including MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, The Cochrane Library databases and Cumulative Index to Nursing and Allied Health Literature (CINAHL) were searched in January 2009, and the reference lists of relevant articles were checked. Studies were included if they compared orlistat, sibutramine or rimonabant with lifestyle and/or exercise advice (standard care), placebo or metformin. RESULTS: Overall, 94 studies involving 24,808 individuals were included in the clinical meta-analysis. Eighty-three trials included data on weight change, 41 included data on BMI change and 45 and 36 studies reported on 5% and 10% body weight loss, respectively. Overall, the results show that the active drug interventions are all effective at reducing weight and BMI compared with placebo. In the case of sibutramine, the higher dose (15 mg) resulted in a greater reduction than the lower dose (10 mg). Generally, the data quality of the trials included was low with poor reporting of standard errors and standard deviations. Results from the BMI risk models derived from the GPRD showed consistent increases in risk with increasing BMI. Adjustments for key confounders, such as age, sex and smoking status, were found to be statistically significant at the 5% level, in all risk models. Applying linear models to estimate BMI trajectories, for the diabetic cohort, an average increase in BMI of 0.040 per year for both men and women was observed. The non-diabetic cohort model showed an increase in BMI of 0.175 per year for women and 0.145 per year for men. The results of the cost-effectiveness analyses suggest that sibutramine 15 mg dominates the other three active interventions and the net benefit analyses show that sibutramine 15 mg is the most cost-effective alternative for thresholds > £2000 per quality-adjusted life-year (QALY). However, both sibutramine and rimonabant have been withdrawn because of safety concerns relating to potential treatment-induced fatal adverse events. If the proportion of patients who experienced a fatal adverse event was > 1.8% (1.5%, 1.0%) for sibutramine 15 mg (sibutramine 10 mg, rimonabant) the treatment would not be considered cost-effective when using a threshold of £20,000 per QALY. LIMITATIONS: The clinical review did not include all possible lifestyle comparators, with the inclusion limited to only those trials included one of the active drug interventions. We also excluded all studies not reported in English. Although the clinical review included data from 94 studies, the quality of data was generally low, particularly in terms of the reporting of standard deviation. There was also inconsistency between the results of the mixed-treatment comparison (MTC) and the pair-wise analyses. CONCLUSION: The MTC of anti-obesity treatments shows that all the active treatments are effective at reducing weight and BMI. The economic results show that, compared with placebo, the treatments are all cost-effective when using a threshold of £20,000 per QALY, and, within the limitations of the data available, sibutramine 15 mg dominates the other three interventions. This work has highlighted many areas of methodological research that could be explored, including assessing inconsistencies within a network to determine differences between the results of pair-wise and MTC analyses; the use of meta-regression methods to look for effect modifiers; exploring the effect of local publication bias; and the use of joint models to analyse the repeated measures of BMI and the time-to-event processes simultaneously. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

From evidence assessments to coverage decisions?: the case example of glinides in Germany.

In Germany, coverage decisions in the statutory health insurance (SHI) system are based on the principles of evidence-based medicine. Recently, an evidence assessment by the Institute for Quality and Efficiency in Health Care (IQWiG) of the oral antidiabetics of the glinide class showed that their long-term benefit is not proven. Accordingly, the responsible Federal Joint Committee (G-BA) decided to exclude glinides from prescription in the SHI system. This was, however, objected to by the Ministry of Health, which is charged with legal supervision. We use this case to illustrate the path from evidence assessments to coverage decisions in Germany against the background of the latest health reform, which has changed the legal requirements for evidence assessments and the ensuing coverage decisions.

Analysis of the cost-effectiveness of remifentanil-based general anesthesia: a survey of clinical economics under the Japanese health care system.

PURPOSE: Remifentanil has been available in Japan for 3 years. The use of this new opioid is considered a useful adjuvant to general anesthesia. Knowing the exact cost-effectiveness of remifentanil should lead to improved anesthetic outcomes with a reasonable cost. METHODS: This single-blinded, prospective, randomized study compared the cost of remifentanil-based general anesthesia combined with isoflurane, sevoflurane, or propofol with fentanyl-based conventional techniques in 210 women who underwent breast surgeries. RESULTS: Remifentanil-based general anesthesia was no more expensive than fentanyl-based conventional anesthesia. Postoperative nausea and vomiting was significantly less frequent after remifentanil-based than fentanyl-based anesthesia. CONCLUSION: This study shows that remifentanil-based general anesthesia is no more expensive than conventional fentanyl-based anesthesia under the Japanese health care system because of the small difference in price between remifentanil and fentanyl.

How do we treat people with dementia in Croatia.

The current clinical view on pharmacological treatment and the Croatian reality regarding approved antidementia drugs is presented. Dementia is a syndrome of high incidence and Alzheimer's disease is the most common cause of dementia. New data show that dementia prevalence will nearly double every 20 years, and we believe that current estimated number of persons with dementia (PWD) for Croatia is more than 80,000. The standard treatment with antidementia drugs is unavailable in Croatia, for the majority of PWD, because antidementia drugs are not on the reimbursement list, although Croatian algorithm for psychopharmacological treatment and Alzheimer Disease Societies Croatia recommend early and adequate treatment. Alzheimer's dementia is becoming a world's health priority in 21st century, so we strongly believe that antidementia drugs should be reimbursed in Croatia.

Cost-utility analysis of rimonabant in the treatment of obesity.

OBJECTIVE: To estimate the incremental cost-utility ratio (ICUR) of rimonabant 20 mg/day in the treatment of obesity from a third-party payer's perspective. METHODS: Pooled data from three randomized clinical trials were used to develop a decision tree with five treatment alternatives: 1- and 2-year treatment with rimonabant, 2-year placebo, 1-year rimonabant followed by 1-year placebo, and no treatment. All alternatives, except no treatment, were accompanied by lifestyle interventions. Treatment benefits included gains in quality-adjusted life-years (QALYs) and reduced incidence of type-2 diabetes mellitus and coronary heart disease (CHD). Drug acquisition cost was based on the average wholesale price of a comparator drug minus 15%. One-way and probabilistic sensitivity analyses were conducted to assess the stability of the base-case results. RESULTS: One-year rimonabant and 1-year rimonabant followed by placebo were extensively dominated. Rimonabant for 2 years showed an average weight reduction of 8.49 kg, a body mass index reduction of 2.98 kg/m(2) and reduced waist circumference by 8.24 cm (placebo: 3.55 kg, 1.22 kg/m(2), 4.18 cm). Two-year rimonabant was associated with a relative reduction in the 5-year incidence of CHD by 7.15% and of diabetes by 9.28%. Incremental benefits (costs) were 0.0984 QALYs ($5209) compared to no treatment and 0.0581 QALYs ($4182) compared to placebo, producing ICURs of $52,936/QALY (95% confidence interval $39K-$69K) and $71,973/QALY ($51K-$98K), respectively. CONCLUSIONS: Rimonabant combined with lifestyle interventions has the potential to decrease the rate of obesity-related comorbidities and improve health-related quality of life, albeit at considerable cost.

Iloperidone: a new benzisoxazole atypical antipsychotic drug. Is it novel enough to impact the crowded atypical antipsychotic market?

Iloperidone is a new-generation atypical antipsychotic agent, acting as a serotonin/dopamine (5-HT(2A)/D(2)) antagonist, under development by Vanda Pharmaceuticals for the treatment of schizophrenia, bipolar disorder and other psychiatric conditions. Chemically, iloperidone is a benzisoxazole, like risperidone, and shows a multiple receptor binding profile, sharing this feature with the other atypical antipsychotic agents. Administered orally, the drug is highly bound to plasma proteins and extensively metabolised. Several clinical trials have been carried out, to check efficacy, safety and side effects. In order to introduce iloperidone as an agent for the treatment of schizophrenia, a short overview of the disease and of the most important antipsychotic drugs available or under development will be reported. Iloperidone pharmacokinetics and pharmacodynamics are presented herein, together with an evaluation of clinical safety and efficacy results.