scholarly journals Cost-effectiveness of the long-acting regimen cabotegravir plus rilpivirine for the treatment of HIV-1 and its potential impact on adherence and viral transmission: A modelling study

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0245955 ◽  
Author(s):  
Ben Parker ◽  
Tom Ward ◽  
Olivia Hayward ◽  
Ian Jacob ◽  
Erin Arthurs ◽  
...  

Introduction Combination antiretroviral therapy (cART) improves outcomes for people living with HIV (PLWH) but requires adherence to daily dosing. Suboptimal adherence results in reduced treatment effectiveness, increased costs, and greater risk of resistance and onwards transmission. Treatment with long-acting (LA), injection-based ART administered by healthcare professionals (directly observed therapy (DOT)) eliminates the need for adherence to daily dosing and may improve clinical outcomes. This study reports the cost-effectiveness of the cabotegravir plus rilpivirine LA regimen (CAB+RPV LA) and models the potential impact of LA DOT therapies. Methods Parameterisation was performed using pooled data from recent CAB+RPV LA Phase III trials. The analysis was conducted using a cohort-level hybrid decision-tree and state-transition model, with states defined by viral load and CD4 cell count. The efficacy of oral cART was adjusted to reflect adherence to daily regimens from published data. A Canadian health service perspective was adopted. Results CAB+RPV LA is predicted to be the dominant intervention when compared to oral cART, generating, per 1,000 patients treated, lifetime cost-savings of $1.5 million, QALY and life-year gains of 107 and 138 respectively with three new HIV cases averted. Conclusions Economic evaluations of LA DOTs need to account for the impact of adherence and HIV transmission. This study adds to the existing literature by incorporating transmission and using clinical data from the first LA DOT regimen. Providing PLWH and healthcare providers with novel modes of ART administration, enhancing individualisation of treatment, may facilitate the achievement of UNAIDS 95-95-95 objectives.

Author(s):  
Nadine T. Hillock ◽  
Tracy L. Merlin ◽  
Jonathan Karnon ◽  
John Turnidge ◽  
Jaklin Eliott

Abstract Background The frameworks used by Health Technology Assessment (HTA) agencies for value assessment of medicines aim to optimize healthcare resource allocation. However, they may not be effective at capturing the value of antimicrobial drugs. Objectives To analyze stakeholder perceptions regarding how antimicrobials are assessed for value for reimbursement purposes and how the Australian HTA framework accommodates the unique attributes of antimicrobials in cost-effectiveness evaluation. Methods Eighteen individuals representing the pharmaceutical industry or policy-makers were interviewed. Interviews were transcribed verbatim, coded, and thematically analyzed. Results Key emergent themes were that reimbursement decision-making should consider the antibiotic spectrum when assessing value, risk of shortages, the impact of procurement processes on low-priced comparators, and the need for methodological transparency when antimicrobials are incorporated into the economic evaluation of other treatments. Conclusions Participants agreed that the current HTA framework for antimicrobial value assessment is inadequate to properly inform funding decisions, as the contemporary definition of cost-effectiveness fails to explicitly incorporate the risk of future resistance. Policy-makers were uncertain about how to incorporate future resistance into economic evaluations without a systematic method to capture costs avoided due to good stewardship. Lacking financial reward for the benefits of narrower-spectrum antimicrobials, companies will likely focus on developing broad-spectrum agents with wider potential use. The perceived risks of shortages have influenced the funding of generic antimicrobials in Australia, with policy-makers suggesting a willingness to pay more for assured supply. Although antibiotics often underpin the effectiveness of other medicines, it is unclear how this is incorporated into economic models.


Author(s):  
M Neyens ◽  
H M Crauwels ◽  
J J Perez-Ruixo ◽  
S Rossenu

Abstract Objectives To characterize the population pharmacokinetics of the rilpivirine long-acting (LA) formulation after intramuscular administration. Methods Rich and sparse rilpivirine plasma concentration data were obtained from seven clinical studies. In total, 18 261 rilpivirine samples were collected from 986 subjects (131 healthy subjects from Phase I studies and 855 people living with HIV from Phase IIb/III studies). Doses ranged from 300 to 1200 mg, as single-dose or multiple-dose regimens (every 4 or 8 weeks). In Phase III studies, an initiation injection of 900 mg followed by continuation injections of 600 mg every 4 weeks was used. Non-linear mixed-effects modelling was performed using NONMEM® software. Results A one-compartment model with linear elimination and two parallel absorption pathways (fast and slow) with sequential zero-first-order processes adequately captured rilpivirine flip-flop pharmacokinetics after intramuscular administration of the LA formulation. The estimated apparent elimination half-life of rilpivirine LA was 200 days. None of the evaluated covariates (age, body weight, BMI, sex, race, health status and needle length) had a clinically relevant impact on rilpivirine pharmacokinetics. Conclusions The population pharmacokinetic model suitably describes the time course and associated variability of rilpivirine plasma concentrations after rilpivirine LA intramuscular administration. The monthly regimen consists of an oral lead-in period (rilpivirine 25 mg tablets once daily for 4 weeks), followed by an initiation injection of 900 mg rilpivirine LA, then 600 mg rilpivirine LA continuation injections monthly. The absence of a clinically relevant effect of covariates on rilpivirine pharmacokinetics suggests that rilpivirine LA dose adjustments for specific subgroups are not warranted.


2021 ◽  
pp. 2004233
Author(s):  
Paola Rogliani ◽  
Beatrice Ludovica Ritondo ◽  
Luigino Calzetta

Conflicting evidence is currently available concerning the impact on asthma exacerbation of triple inhaled corticosteroid (ICS), long-acting β2-adrenoceptor agonist (LABA), and long-acting muscarinic receptor antagonist (LAMA) fixed-dose combination (FDC). Since meta-analyses allow settling controversies of apparently inconsistent results, we performed a network meta-analysis of Phase III randomised controlled trials including 9535 patients to assess the effect of ICS/LABA/LAMA combinations in uncontrolled asthma. Triple combination therapies with an ICS administered at high dose (HD) were more effective (p<0.05) than medium dose (MD) ICS/LABA/LAMA FDC and both MD and HD ICS/LABA FDCs against moderate to severe exacerbation (relative risk [RR] from 0.61 to 0.80) and increasing trough forced expiratory volume in the 1st second (mL from +33 to +114). Triple combination therapies including HD ICS were superior (p<0.05) than MD ICS/LABA/LAMA FDC in preventing severe exacerbation (RR from 0.46 to 0.65), but not with respect to moderate exacerbation (p>0.05). Triple combination therapies were equally effective on asthma control, with no safety concerns. This quantitative synthesis suggests that ICS/LABA/LAMA FDCs are effective and safe in uncontrolled asthma, and that the dose of ICS in the combination represents the discriminating factor to treat patients with a history of moderate or severe exacerbation.


2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S866-S866
Author(s):  
Andrea R Mantsios ◽  
Miranda Murray ◽  
Tahilin Sanchez Karver ◽  
Wendy Davis ◽  
David Margolis ◽  
...  

Abstract Background Adherence to antiretroviral therapy (ART) to treat HIV remains a critical global health challenge given its relationship with individual health outcomes and population-level transmission. Given barriers associated with oral ART adherence, and considerations of patients’ preferences, long-acting injectable (LA) ART (cabotegravir + rilpivirine) is under development and has been shown to be non-inferior to daily oral ART in Phase III trials. While most of the trial participants have been men, as LA ART gets closer to becoming available for routine clinical use, it is critical to understand how this option is perceived by women. Methods We conducted in-depth interviews with 67 individuals, 53 people living with HIV (PLHIV) and 14 healthcare providers, in 11 sites in the United States and Spain participating in Phase III LA ART trials (ATLAS, ATLAS 2-M and FLAIR). Twenty percent (10/53) of trial participants interviewed were women. Interviews explored patient and provider perspectives and experiences with LA ART, and appropriate candidates and recommendations to support use. Interviews were audio-recorded, transcribed and coded using thematic content analysis. Results Overall, several salient themes emerged regarding participant’s generally positive experiences transitioning from daily oral ART to injectable ART including: the importance of the clinical efficacy of LA ART, the ability to learn to manage injection side-effects over time, and the “freedom” reportedly afforded by LA ART logistically and psychosocially. Women interviewed shared many of the aforementioned positive perceptions of LA ART but also had some unique perspectives. Female participants discussed how LA ART was easier to integrate into their daily lives including managing their multiple roles and responsibilities, which often involved working full-time and taking care of themselves as well as their family and children. Conclusion Similar to all participants, female participants had generally positive views of LA ART. However, the gendered nature of their daily lives also led to some unique perspectives on why and how they were satisfied with LA ART that merits further exploration in future research. Disclosures All authors: No reported disclosures.


Author(s):  
Jennifer A Smith ◽  
Geoffrey P Garnett ◽  
Timothy B Hallett

Abstract Background Although effective, some oral pre-exposure prophylaxis (PrEP) users face barriers to adherence using daily pills, which could be reduced by long-acting formulations. Long-acting cabotegravir (CAB LA) is a potential new injectable formulation for human immunodeficiency virus (HIV) PrEP being tested in phase III trials. Methods We use a mathematical model of the HIV epidemic in South Africa to simulate CAB LA uptake by population groups with different levels of HIV risk. We compare the trajectory of the HIV epidemic until 2050 with and without CAB LA to estimate the impact of the intervention. Results Delivering CAB LA to 10% of the adult population could avert more than 15% of new infections from 2023 to 2050. The impact would be lower but more efficient if delivered to populations at higher HIV risk: 127 person-years of CAB LA use would be required to avert one HIV infection within 5 years if used by all adults and 47 person-years if used only by the highest risk women. Conclusions If efficacious, a CAB LA intervention could have a substantial impact on the course of the HIV epidemic in South Africa. Uptake by those at the highest risk of infection, particularly young women, could improve the efficiency of any intervention.


Author(s):  
Thitima Kongnakorn ◽  
Christian Eckmann ◽  
Matteo Bassetti ◽  
Eszter Tichy ◽  
Roberto Di Virgilio ◽  
...  

Abstract Background The rising incidence of resistance to currently available antibiotics among pathogens, particularly Gram-negative pathogens, in complicated intra-abdominal infections (cIAIs) has become a challenge for clinicians. Ceftazidime/avibactam (CAZ-AVI) is a fixed-dose antibiotic approved in Europe and the United States for treating (in combination with metronidazole) cIAI in adult hospitalised patients who have limited or no alternative treatment options. The approval was based on the results of RECLAIM, a Phase III, parallel-group, comparative study (RECLAIM 1 [NCT01499290] and RECLAIM 2 [NCT01500239]). The objective of our study was to assess the cost-effectiveness of CAZ-AVI plus metronidazole compared with 1) ceftolozane/tazobactam plus metronidazole and 2) meropenem, as an empiric treatment for the management of cIAI in Italy. Methods A sequential, patient-level simulation model, with a 5-year time horizon and 3% annual discount rate (applied to both costs and health benefits), was developed using Microsoft Excel® to demonstrate the clinical course of the disease. The impact of resistant pathogens was included as an additional factor. Results In the base-case analysis, the CAZ-AVI sequence (CAZ-AVI plus metronidazole followed by a colistin + tigecycline + high-dose meropenem combination after treatment failure), when compared to sequences for ceftolozane/tazobactam (ceftolozane/tazobactam plus metronidazole followed by colistin + tigecycline + high-dose meropenem after treatment failure) and meropenem (meropenem followed by colistin + tigecycline + high-dose meropenem after treatment failure), had better clinical outcomes with higher cure rates (93.04% vs. 91.52%; 92.98% vs. 90.24%, respectively), shorter hospital stays (∆ = − 0.38 and ∆ = − 1.24 days per patient, respectively), and higher quality-adjusted life years (QALYs) gained per patient (4.021 vs. 3.982; 4.019 vs. 3.960, respectively). The incremental cost effectiveness ratio in the CAZ-AVI sequence was €4099 and €15,574 per QALY gained versus each comparator sequence, respectively, well below the willingness-to-pay threshold of €30,000 per QALY accepted in Italy. Conclusions The model results demonstrated that CAZ-AVI plus metronidazole could be a cost-effective alternative when compared with other antibiotic treatment options, as it is expected to provide better clinical benefits in hospitalised patients with cIAI in Italy.


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 6607-6607 ◽  
Author(s):  
E. Remák ◽  
C. D. Mullins ◽  
E. Akobundu ◽  
C. Charbonneau ◽  
K. Woodruff

6607 Background: A randomized phase III trial of sunitinib vs. IFN-a as first-line therapy for patients with mRCC is ongoing. An interim analysis of this study demonstrated superiority for the primary endpoint, progression-free survival (PFS), in the sunitinib arm vs. the IFN-a arm (median PFS = 11 months [95% CI: 10–12] vs. 4 months [95% CI: 4–6]; P<0.000001). Because of the clinical significance of these results, the objective of this study was to demonstrate the economic value of sunitinib vs. IFN-a in this setting from a US third-party payer perspective. Methods: Two Markov models with a 5- and 10-year time horizon were developed to evaluate the cost- effectiveness of sunitinib vs. IFN-a. The models projected survival and costs in 6-week cycles based on extrapolation of the trial survival data. Model 1 looked at first-line treatment followed by palliative care only, while Model 2 incorporated second-line treatment. Effectiveness was measured in terms of progression-free months (PFM) in Model 1, and life-years (LY) gained and quality adjusted life-years (QALY) gained in Model 2. Resource utilization included drugs, tests, scans, monitoring, physician visits, hospitalizations and treatment of adverse events. Costs and survival benefits were discounted annually at 3% and 5% in Model 1 and 2, respectively. All costs were adjusted to 2006 US dollars. Scenario and probabilistic sensitivity analyses were conducted. Results: Projected PFS and overall survival were longer for sunitinib than for IFN-a. The incremental cost-effectiveness ratios of sunitinib vs. IFN-a over 5- and 10-years were $7,769 and $7,782/PFM, respectively, in Model 1. Model 2 results at 10 years were $67,215/LY and $52,593/QALY gained. The key drivers of the model results were survival and sunitinib drug costs. Both models were robust in the tested scenarios. Conclusions: Both analyses found that sunitinib is a cost-effective alternative to IFN-a as first-line treatment in mRCC, with cost-effectiveness ratios within the established threshold that society is willing to pay for health benefits (i.e. $50,000–100,000/LY or QALY). No significant financial relationships to disclose.


2021 ◽  
Author(s):  
Elizabeth Mutubuki ◽  
Mohamed El Alili ◽  
Judith Bosmans ◽  
Teddy Oosterhuis ◽  
Frank Snoek ◽  
...  

Abstract Background: Baseline imbalances, skewed costs, the correlation between costs and effects, and missing data are statistical challenges that are often not adequately accounted for in the analysis of cost-effectiveness data. This study aims to illustrate the impact of accounting for these statistical challenges in trial-based economic evaluations. Methods: Data from two trial-based economic evaluations, the REALISE and HypoAware studies, were used. In total, 14 full cost-effectiveness analyses were performed per study, in which the four statistical challenges in trial-based economic evaluations were taken into account step-by-step. Statistical approaches were compared in terms of the resulting cost and effect differences, ICERs, and probabilities of cost-effectiveness. Results: In the REALISE study and HypoAware study, the ICER ranged from 636,744€/QALY and 90,989€/QALY when ignoring all statistical challenges to -7,502€/QALY and 46,592€/QALY when accounting for all statistical challenges, respectively. The probabilities of the intervention being cost-effective at 0€/ QALY gained were 0.67 and 0.59 when ignoring all statistical challenges, and 0.54 and 0.27 when all of the statistical challenges were taken into account for the REALISE study and HypoAware study, respectively.Conclusions: Not accounting for baseline imbalances, skewed costs, correlated costs and effects, and missing data in trial-based economic evaluations may notably impact results. Therefore, when conducting trial-based economic evaluations, it is important to align the statistical approach with the identified statistical challenges in cost-effectiveness data. To facilitate researchers in handling statistical challenges in trial-based economic evaluations, software code is provided.


Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 601-601
Author(s):  
Miriam Yunhee Kim ◽  
Richard Sposto ◽  
Asher Chanan-Khan ◽  
Sikander Ailawadhi

Abstract Abstract 601 Background: Despite therapeutic advances and availability of novel agents, multiple myeloma (MM) remains an incurable malignant disorder and strategies to improve survival are being actively sought. One such approach is the use of maintenance therapy with lenalidomide (Revlimid®; R), which has shown PFS benefit, without conclusive evidence of OS benefit except in a selected population (CALGB100104). Shrinking resources with rising healthcare costs warrant careful assessment of the financial impact of expensive anticancer therapeutics in context with the true benefit to patients. Methods: This analysis was not supported or solicited by any pharmaceutical industry. For our pharmacoeconomic study we selected the MM-015 trial; a large (n=459) double-blind, randomized, placebo-controlled phase III study that investigated the efficacy of continuous R maintenance after initial therapy with melphalan/prednisone/lenalidomide (MPR) in a uniform cohort of patients (≥65 years, newly diagnosed MM, transplant ineligible). The three study arms were MP, MPR and MPR followed by R maintenance (MPR-R). The cost-effectiveness model included medical costs (drugs, office visits, laboratory tests) and costs of treatment-related adverse events (AEs) for an individual patient. Drug costs were calculated from the average wholesale price, using average US adult weight of 80kg. Office visit and laboratory test costs were obtained using Medicare reimbursement fees. Costs of AEs were obtained from peer-reviewed publications. Incidence of AEs was obtained from the published MM-015 trial. Costs were valued in 2011 US dollars. Cost calculations included: (1) computing distribution of the numbers of induction and maintenance courses completed by patients treated with each of these regimens; (2) computing the per-course probabilities of the occurrence of individual AEs during induction and maintenance for each of these toxicities; (3) combining these data with the treatment costs and costs of individual AEs to compute cumulative cost of treatment through 40 maintenance cycles and cumulative cost of treatment per progression-free survivor. Summary measures computed for each treatment: (1) average cumulative cost per patient (ACCP) treated; (2) average cumulative cost per progression free survivor (ACCPFS), representing the average cumulated cost/patient who is progression free at that time. The distribution of courses received was obtained from the MM-015 publication. Data on subsequent therapy at the time of disease progression was not available. Results: Median follow up reported in the published study was 30 months. Median PFS was 13 months (MP), 14 months (MPR) and 31 months (MPR-R) in the three arms. Table 1 summarizes the calculated ACCP and the ACCPFS of each regimen for induction and maintenance treatment. MPR-R was the most expensive of the three arms in terms of total cumulative costs, with an ACCP of $231,314, compared to $166,211 for MPR and $17,972 for MP. However, taking the efficacy of each regimen into account (ACCPFS), MPR greatly exceeds both MPR-R and MP ($1,540,139 vs. $516,322 vs. $309,346), while the difference between MPR-R and MP was less distinct. Figure 1 illustrates the exponential increase in ACCPFS of MPR, compared to MPR-R and MP. Conclusions: From a cost-effectiveness perspective, if MPR is used as the induction regimen, maintenance with R should be strongly considered, as MPR without maintenance does not confer any significant benefit over MP, while incurring a much higher cost. However, the overall cost of MPR-R is substantial with no reported OS benefit at present. In the absence of clear survival benefit the financial burden of prolonged treatment becomes an important factor to consider prior to adopting this therapeutic strategy in MM. As part of a global strategy for addressing healthcare costs, it is important to consider this in appropriate medical decision making for patients, and to include cost-effectiveness analyses as a part of large prospective clinical trial efforts. Disclosures: No relevant conflicts of interest to declare.


2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Vanessa Shih ◽  
Renske M. ten Ham ◽  
Christine T. Bui ◽  
Dan N. Tran ◽  
Jie Ting ◽  
...  

Purpose. Two BRAFV600Etargeted therapies, dabrafenib and vemurafenib, have received US approval for treatment of metastatic melanoma in BRAFV600Epatients, a mutation that affects ~50% of patients. We evaluated the cost-effectiveness of BRAF inhibitors and traditional chemotherapy for treatment of metastatic melanoma.Methods. A Markov model was developed using a societal perspective. Transition probabilities were derived from two Phase III registration trials comparing each BRAF inhibitor against dacarbazine. Costs were obtained from literature, national databases, and Medicare fee schedules. Utilities were obtained from published literature. Deterministic and probabilistic sensitivity analyses were run to test the impact of uncertainties.Results. The incremental cost-effectiveness ratio of dabrafenib was $149,035/QALY compared to dacarbazine. Vemurafenib was dominated by dabrafenib. Probabilistic sensitivity analysis showed that, at a willingness-to-pay (WTP) threshold of ≤$100,000/QALY, dacarbazine was the optimal treatment in ~85% of simulations. At a WTP threshold of ≥$150,000/QALY, dabrafenib was the optimal treatment.Conclusion. Compared with dacarbazine, dabrafenib and vemurafenib were not cost-effective at a willingness-to-pay threshold of $100,000/QALY. Dabrafenib is more efficient compared to vemurafenib. With few treatment options, dabrafenib is an option for qualifying patients if the overall cost of dabrafenib is reduced to $30,000–$31,000 or a WTP threshold of ≥$150,000/QALY is considered. More comparative data is needed.


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