Cost-effectiveness and budget impact of dolutegravir/lamivudine for treatment of human immunodeficiency virus (HIV-1) infection in the United States.

BACKGROUND: Dolutegravir(DTG)/lamivudine(3TC) is the first 2-drug regimen recommended as an initial treatment for people living with HIV (PLHIV). OBJECTIVE: To assess the cost-effectiveness and potential budget impact of DTG/3TC in the US healthcare setting. METHODS: A previously published hybrid decision-tree and Markov cohort state transition model was adapted to estimate the incremental costs and health outcome benefits over a patients' lifetime. DTG/3TC was compared with current standard of care in treatment naive and treatment experienced virologically suppressed PLHIV. Health states included in the model were based upon virologic response and CD4 cell count, with death as an absorbing state. Clinical data was informed by the Phase III GEMINI 1 and 2 clinical trials, a published network meta-analysis (NMA) in treatment-naive patients and the Phase III TANGO clinical trial in treatment experienced patients. Costs and utilities were informed by published data and discounted annually at a rate of 3%. A separate 5-year budget impact analysis was conducted assuming 5%-15% uptake in eligible treatment naive and 10%-30% uptake in eligible treatment experienced patients. RESULTS: In the treatment naive analyses based on GEMINI 1 and 2, DTG/3TC dominated, i.e., was less costly and more effective, than all comparators. DTG/3TC resulted in 0.083 incremental quality-adjusted life-years (QALYs) at a cost saving of $199,166 compared with the DTG + tenofovir disoproxil(TDF)/emtricitabine(FTC) comparator arm. The incremental QALY and cost savings for DTG/3TC compared with DTG/abacavir(ABC)/3TC, cobicistat-boosted darunavir(DRV/c)/tenofovir alafenamide(TAF)/FTC, and bictegravir (BIC)/TAF/FTC, based on NMA results were 0.465, 0.142, and 0.698, and $42,948, $122,846, and $44,962, respectively. In the analyses of treatment-experienced virologically suppressed patients based on TANGO, DTG/3TC offered slightly lower QALYs (-0.037) with an estimated savings of $78,730 when compared with continuation of TAF-based regimen (TBR). Sensitivity analyses demonstrated that these conclusions were relatively insensitive to alternative parameter estimates. The budget impact analysis estimated that by 5th year a total of 70,240 treatment naive patients and 1,340,480 treatment experienced patients could be eligible to be prescribed DTG/3TC. The estimated budget savings over 5 years ranged from $1.12b to $3.35b (corresponding to 27,512 to 82,536 on DTG/3TC by year 5) in the lowest and highest uptake scenarios, respectively. CONCLUSION: In conclusion, DTG/3TC with its comparable efficacy and lower drug acquisition costs, has the potential to offer significant cost savings to US healthcare payers for the initial treatment of treatment naive patients and as a treatment switching option for virologically suppressed patients. DISCLOSURES: This study was funded in full by ViiV healthcare, Brentford, UK. Medical writing to support this study was also funded in full by ViiV Healthcare, Brentford, UK. Butler, Hayward, and Jacob are employees of HEOR Ltd, the company performing this study funded by ViiV Healthcare. Anderson is an employee of GlaxoSmithKline and owns shares in the company. Punekar, Evitt, and Oglesby are employees of ViiV Healthcare and own stocks in GlaxoSmithKline.

"It made me more confident that I have it under control": Patient and provider perspectives on moving to a two-drug ART regimen in the United States and Spain.

BACKGROUND: Two-drug regimens (2DR) to treat HIV infection have the potential to reduce long-term toxicity and increase therapeutic options for people living with HIV (PLHIV). Prior phase III trials, SWORD-1 and SWORD-2, as well as GEMINI-1 and GEMINI-2, have demonstrated that a dolutegravir-based 2DR is as effective as three- or four-drug regimens among virologically suppressed patients. Limited information exists, however, on patient and provider experiences with 2DR to inform roll-out and integration into routine clinical care. METHODS: We conducted 39 in-depth interviews with PLHIV currently on 2DR in the context of routine care and 8 of their clinical care providers in the United States (U.S.) and Spain. Participants included 33 male and 6 female PLHIV and 8 providers. Interview topics explored perceptions of and experiences with 2DR compared to prior anti-retroviral regimens (ARVs), side effects, patient satisfaction, and clinical performance. Interviews were audio-recorded, transcribed and analyzed using thematic content analysis. RESULTS: Participants viewed 2DR as a significant and positive advance, in terms of its ability to effectively treat HIV with reduced toxicity and essentially no reported side effects. Patients noted the central role providers played in the decision to switch to a 2DR regimen and, among U.S. participants, the importance of insurance coverage making this preferred option feasible. Patients and providers agreed that a 2DR regimen would be appropriate for any PLHIV regardless of whether they were treatment naïve or had significant experience with ARVs. CONCLUSIONS: Participants' experiences with a 2DR regimen were positive with no participants, reporting side effects and all reporting continued viral suppression. Providers valued the reduced toxicity offered by 2DR and served as the primary gateway to a transition to 2DR for patients in both settings. This study provides a foundation for further research on the transition to 2DR regimens in other populations and contexts including low- and middle-income settings.

Estimating HIV Management and Comorbidity Costs Among Aging HIV Patients in the United States: A Systematic Review.

BACKGROUND: As life expectancy of patients infected with human immunodeficiency virus (HIV) approaches that of the general population, the composition of HIV management costs is likely to change. OBJECTIVES: To (a) review treatment and disease management costs in HIV, including costs of adverse events (AEs) related to antiretroviral therapy (ART) and long-term toxicities, and (b) explore the evolving cost drivers. METHODS: A targeted literature review between January 2012 and November 2017 was conducted using PubMed and major conferences. Articles reporting U.S. costs of HIV management, acquired immunodeficiency syndrome (AIDS)-defining events, end of life care, and ART-associated comorbidities such as cardiovascular disease (CVD), chronic kidney disease (CKD), and osteoporosis were included. All costs were inflated to 2017 U.S. dollars. A Markov model-based analysis was conducted to estimate the effect of increased life expectancy on costs associated with HIV treatment and management. RESULTS: 22 studies describing HIV costs in the United States were identified, comprising 16 cost-effectiveness analysis studies, 5 retrospective analyses of health care utilization, and 1 cost analysis in a resource-limited setting. Management costs per patient per month, including routine care costs (on/off ART), non-HIV medication, opportunistic infection prophylaxis, inpatient utilization, outpatient utilization, and emergency department utilization were reported as CD4+ cell-based health state costs ranging from $1,192 for patients with CD4 > 500 cells/mm3 to $2,873 for patients with CD4 < 50 cells/mm3. Event costs for AEs ranged from $0 for headache, pain, vomiting, and lipodystrophy to $31,545 for myocardial infarction. The mean monthly per-patient costs for CVD management, CKD management, and osteoporosis were $5,898, $6,108, and $4,365, respectively. Improvements in life expectancy, approaching that of the general population in 2018, are projected to increase ART-related and AE costs by 35.4% and comorbidity costs by 175.8% compared with estimated costs with HIV life expectancy observed in 1996. CONCLUSIONS: This study identified and summarized holistic cost estimates appropriate for use within U.S. HIV cost-effectiveness analyses and demonstrates an increasing contribution of comorbidity outcomes, primarily associated with aging in addition to long-term treatment with ART, not typically evaluated in contemporary HIV cost-effectiveness analyses. DISCLOSURES: This analysis was sponsored by ViiV Healthcare, which had no role in the analyses and interpretation of study results. Ward, Sugrue, Hayward, and McEwan are employees of HEOR Ltd, which received funding from ViiV Healthcare to conduct this study. Anderson is an employee of GlaxoSmithKline and holds shares in the company. Punekar and Oglesby are employees of ViiV Healthcare and hold shares in GlaxoSmithKline. Lopes was employed by ViiV Healthcare at the time of the study and holds shares in GlaxoSmithKline.

Improving access to antiretrovirals in China: economic analyses of dolutegravir in HIV-1 patients.

BACKGROUND: The World Health Organisation recommended dolutegravir (DTG)-based antiretroviral therapy (ART) regimens are available but not reimbursed through the public reimbursement system in China. The objective of this analysis was to evaluate the cost-effectiveness of DTG (DTG + TDF/3TC) compared to efavirenz (EFV + TDF/3TC) in treatment-naive and ritonavir-boosted lopinavir (LPV/r + TDF/3TC) in first-line ART failure HIV-1-infected patients in China. METHODS: A dynamic Markov model comprising of 5 response states and 6 CD4+ count-based health states was used. Efficacy, estimated as probability of virologic suppression (HIV RNA < 50 copies/mL) at 48 weeks, was obtained from a published network meta-analysis for ART-naive patients and from the DAWNING study for patients failing first-line ART. Baseline cohort characteristics were informed using DTG phase 3 studies and the DAWNING study data, respectively. Health state utilities were derived from DTG phase 3 studies. A 5-year cost-effectiveness analyses was conducted using the societal perspective. Outcomes were quality-adjusted-life-years (QALYs), life-years (LYs), incremental cost per QALYs (ICER). RESULTS: The viral suppression rates for DTG + TDF/3TC were higher than EFV + TDF/3TC (75.3% vs 64.0%) in treatment-naive and LPV/r + TDF/3TC (74.8% vs 58.4%) in first-line ART failure patients. This resulted in higher QALYs for DTG + TDF/3TC in treatment-naive (4.232 vs 4.227) and first-line failure settings (4.224 vs 4.221). Total discounted cost for DTG + TDF/3TC patients (RMB 219.259 in treatment-naive and RMB 238,746 in first-line failures) were lower than comparators (EFV + TDF/3TC:RMB 221,605; LPV/r + TDF/3TC:RMB 244,364), thereby DTG dominated in both settings. Probabilistic sensitivity analyses indicated the probability of DTG + TDF/3TC being cost effective was 98.2% in treatment-naive setting and 100% in first-line failure setting at a willingness to pay threshold of RMB 100,000/QALY. CONCLUSIONS: With lower costs, higher response rates and higher QALYs, DTG + TDF/3TC can be considered as a cost-effective alternative for treatment naive and first-line failure patients in China.

Cost-Effectiveness of Dolutegravir as a First-Line Treatment Option in the HIV-1-Infected Treatment-Naive Patients in Russia.

OBJECTIVES: To evaluate the cost effectiveness of dolutegravir + abacavir/lamivudine (DTG + ABC/3TC) compared with raltegravir + abacavir/lamivudine (RAL + ABC/3TC) and ritonavir-boosted darunavir + abacavir/lamivudine (DRV/r + ABC/3TC) in HIV-1-infected treatment-naive patients in Russia. METHODS: A dynamic Markov model was developed with five response states and six CD4+-based health states. Efficacy estimated as probability of viral suppression (HIV RNA <50 copies/ml) at 48 weeks was obtained from a published network meta-analysis. Baseline cohort characteristics and health state utilities were informed using DTG phase 3 clinical trials. Health care resource use was obtained from literature and costed using published unit costs. Costs (presented in Russian rubles) included antiretroviral drug costs; HIV management costs such as routine care; costs of treating cardiovascular conditions, opportunistic infections, and drug-related adverse effects; and mortality costs. A patient lifetime analysis was conducted using the societal perspective. Outcomes were quality-adjusted life-years (QALYs), life-years, incremental cost per QALY ratio, and incremental cost per responder. RESULTS: The viral suppression rate among patients receiving DTG + ABC/3TC was 71.7% compared with 65.2% for RAL + ABC/3TC and 59.6% for DRV/r + ABC/3TC. The mean duration of response per patient was 116.6 months for DTG + ABC/3TC, 108.6 months for RAL + ABC/3TC, and 98.9 months for DRV/r + ABC/3TC. Total discounted costs for treatment over patient lifetime were RUB 2.89, 5.32, and 4.38 million for DTG + ABC/3TC, RAL + ABC/3TC, and DRV/r + ABC/3TC, respectively. Lifetime discounted QALYs were 12.73 for patients on DTG + ABC/3TC and 12.72 each for patients on RAL + ABC/3TC and DRV/r + ABC/3TC. DTG + ABC/3TC thus dominated the other two alternatives. CONCLUSIONS: With lower costs, higher response rates, and comparable QALYs, DTG + ABC/3TC can be considered as a cost-effective alternative.

Bronchodilator reliever use and its association with the economic and humanistic burden of COPD: a propensity-matched study.

BACKGROUND AND AIMS: Short-acting bronchodilators are normally used as supplemental relief medication for breakthrough symptoms in COPD patients. The objective of this cross-sectional study was to assess if more frequent vs infrequent use of relief medication in maintenance-treated COPD patients, split by the severity dyspnea, was associated with an increase in the overall disease burden. METHODS: A population-based cross-sectional survey (Adelphi DSP) was conducted among patients with COPD in five European countries. Information was collected on demographic and clinical characteristics, reliever inhaler use, dyspnea (mMRC), health status (CAT, EQ-5D), sleep quality (JSEQ) and healthcare resource use including moderate-severe COPD exacerbations, physician visits, COPD medications and other COPD related resources. The humanistic and economic burden was compared between patients with infrequent reliever use (<1 occasion/week) and more frequent use (≥ 1 occasion/week). The association between increased reliever use and economic burden was also examined after matching patients based on propensity-scores balancing demographic and disease burden characteristics. RESULTS: Among the 1373 COPD patients prescribed a reliever inhaler, 29% reported using reliever medication ≥1 occasion/week. In the unmatched cohort, more frequent reliever use (n = 377) compared to infrequent use (n = 996) was linked to poorer health status (CAT: 25.7 vs 20.0; p < .0001; EQ-5D-3L: 0.63 vs 0.82; p < .0001) and poorer sleep quality (JSEQ: 8.6 vs 4.6 units; p < .0001). More frequent reliever use was also associated with higher annual rates of moderate/severe exacerbations (1.6 vs 1.0 events/year; p < .0001) and respiratory specialist visits (2.8 vs 2.2 events/year; p = .0001). In the propensity-score matched population, more frequent reliever use was also associated with significantly higher annual costs for COPD management (€5,034 vs €3,705, p = .0327) compared to patients with infrequent reliever use. CONCLUSION: In moderate-to-severe COPD, more frequent reliever use is associated with increased exacerbation risk and increased management costs.

Can Assessment of Disease Burden Prior to Changes in Initial COPD Maintenance Treatment Provide Insight into Remaining Unmet Needs? A Retrospective Database Study in UK Primary Care.

This retrospective cohort study aimed to assess treatment patterns over 24 months amongst patients with chronic obstructive pulmonary disease (COPD), initiating a new COPD maintenance treatment, and to understand clinical indicators of treatment change. Patients included in the study initiated a long-acting ß2-agonist (LABA), a long-acting muscarinic antagonist (LAMA), or a combination of LABA and an inhaled corticosteroid (ICS/LABA) between January 1, 2009, and November 30, 2013, as recorded in the United Kingdom Clinical Practice Research Datalink (UK CPRD). Treatment modifications (switching or adding maintenance treatments) over 24 months were assessed, and patient characteristics, disease burden, medication and healthcare resource use during the 30 days before treatment modification were evaluated. The cohort comprised 17,258 patients [LABA (8%), LAMA (39%) and ICS/LABA (54%)] with similar age, body mass index and dyspnoea distribution. LABA users were more likely than LAMA users to add a maintenance therapy. Distinct patterns of treatment augmentations were noted, whereby LABA users typically received dual therapy before moving to triple therapy, while LAMA users moved to triple therapy by directly adding an ICS/LABA. Exacerbation events immediately prior to treatment change were not frequently recorded; however, the need for rescue short-acting medication and assessment of dyspnoea in the 30 days prior to the treatment change suggest that dyspnoea is a remaining unmet need driving therapy change.

Continuing to Confront COPD International Patient Survey: Economic Impact of COPD in 12 Countries.

BACKGROUND: The Continuing to Confront COPD International Patient Survey estimated the prevalence and burden of COPD across 12 countries. Using data from this survey we evaluated the economic impact of COPD. METHODS: This cross-sectional, population-based survey questioned 4,343 subjects aged 40 years and older, fulfilling a case definition of COPD based on self-reported physician diagnosis or symptomatology. Direct cost measures were based on exacerbations of COPD (treated and those requiring emergency department visits and/or hospitalisation), contacts with healthcare professionals, and COPD medications. Indirect costs were calculated from work loss values using the Work Productivity and Activity Impairment scale. Combined direct and indirect costs estimated the total societal costs per patient. RESULTS: The annual direct costs of COPD ranged from $504 (South Korea) to $9,981 (USA), with inpatient hospitalisations (5 countries) and home oxygen therapy (3 countries) being the key drivers of direct costs. The proportion of patients completely prevented from working due to their COPD ranged from 6% (Italy) to 52% (USA and UK) with 8 countries reporting this to be ≥20%. Total societal costs per patient varied widely from $1,721 (Russia) to $30,826 (USA) but a consistent pattern across countries showed greater costs among those with increased burden of COPD (symptoms, health status and more severe disease) and a greater number of comorbidities. CONCLUSIONS: The economic burden of COPD is considerable across countries, and requires targeted resources to optimise COPD management encompassing the control of symptoms, prevention of exacerbations and effective treatment of comorbidities. Strategies to allow COPD patients to remain in work are important for addressing the substantial wider societal costs.

Cost-effectiveness of umeclidinium/vilanterol combination therapy compared to tiotropium monotherapy among symptomatic patients with chronic obstructive pulmonary disease in the UK.

BACKGROUND: The cost-effectiveness of umeclidinium bromide-vilanterol (UMEC/VI) versus tiotropium monotherapy in the UK was assessed using a UMEC/VI treatment-specific economic model based on a chronic obstructive pulmonary disease (COPD) disease-progression model. METHODS: The model was implemented as a linked-equation model to estimate COPD progression and associated health service costs, and its impact on quality-adjusted life years (QALYs) and survival. Statistical risk equations for clinical endpoints and resource use were derived from the ECLIPSE and TORCH studies, respectively. For the selected timeframe (1-40 years) and probabilistic analysis, model outputs included disaggregated costs, total costs, exacerbations, life-years and QALYs gained, and incremental cost-effectiveness ratios (ICERs). RESULTS: Random-effects meta-analysis of tiotropium comparator trials estimated treatment effect of UMEC/VI as 92.17 mL (95 % confidence interval: 61.52, 122.82) in forced expiratory volume in 1 s. With this benefit, UMEC/VI resulted in an estimated annual exacerbation reduction of 0.04 exacerbations/patient and 0.36 life years gained compared to tiotropium over patient lifetime. With an additional 0.18 QALYs/patient and an additional lifetime cost of £372/patient at price parity, the incremental cost effectiveness ratio (ICER) of UMEC/VI compared to tiotropium was £2088/QALY. This ICER increased to £17,541/QALY when price of UMEC/VI was increased to that of indacaterol plus tiotropium in separate inhalers. The ICER improved when model duration was reduced from patient lifetime to 1 or 5 years, or when treatment effect was assumed to last for 12 months following treatment initiation. CONCLUSION: UMEC/VI can be considered a cost-effective alternative to tiotropium at a certain price.

Characteristics, disease burden and costs of COPD patients in the two years following initiation of long-acting bronchodilators in UK primary care.

BACKGROUND: To assess the symptomatic and cost burden among patients initiating long-acting bronchodilator (LABD) therapy and impact of adherence on healthcare resource use and costs. METHODS: This retrospective cohort study identified patients with COPD who were newly prescribed a LABD (long-acting muscarinic antagonist [LAMA], long-acting beta2-agonist [LABA], a combination of LABA+LAMA or combination of LABA with inhaled corticosteroid [ICS]/LABA) between January 1, 2009 and November 30, 2013 from the UK Clinical Practice Research Datalink. Health care resource use, costs and symptom burden up to 24 months after treatment initiation were estimated. Adherence in the follow-up period was assessed using the medication possession ratio (MPR ≥ 80%). RESULTS: The cohort comprised 8283 LABD initiators (16% LABA, 81% LAMA and 3% LABA+LAMA) and 9246 LABA+ICS initiators with generally similar baseline characteristics; prior exacerbation rate was higher in the LABA+ICS cohort. Less than half the patients (LAMA:42%; LABA:34% and LABA+ICS:34%) were adherent to their index medication. Among adherent patients, the total annual per patient cost of COPD was £3008 for LAMA initiators, £2783 for LABA initiators and £3376 for LABA+ICS initiators; primarily due to general practitioner interactions. Among patients with a Medical Research Council dyspnea score recorded during 24 months follow-up, a substantial proportion of adherent patients (LAMA: 41%; LABA: 45%; LABA+ICS 44%) had clinically significant dyspnoea (MRC ≥ 3). CONCLUSION: Cost and symptomatic burden of COPD was high among patients initiating maintenance treatment, including patients adherent with their initial treatment. General practitioner interactions were the primary driver of costs. Further, real world studies are required to address unmet needs and optimize treatment pathways to improve COPD symptom burden and outcomes.

Systematic review of humanistic and economic burden of symptomatic chronic obstructive pulmonary disease.

BACKGROUND: An understanding of the humanistic and economic burden of individuals with symptomatic chronic obstructive pulmonary disease (COPD) is required to inform payers and healthcare professionals about the disease burden. OBJECTIVES: The aim of this systematic review was to identify and present humanistic [health-related quality of life (HRQoL)] and economic burdens of symptomatic COPD. METHODS: A comprehensive search of online databases (reimbursement or claims databases/other databases), abstracts from conference proceedings, published literature, clinical trials, medical records, health ministries, financial reports, registries, and other sources was conducted. Adult patients of any race or gender with symptomatic COPD were included. Humanistic and economic burdens included studies evaluating HRQoL and cost and resource use, respectively, associated with symptomatic COPD. RESULTS: Thirty-two studies reporting humanistic burden and 74 economic studies were identified. Symptomatic COPD led to impairment in the health state of patients, as assessed by HRQoL instruments. It was also associated with high economic burden across all countries. The overall, direct, and indirect costs per patient increased with an increase in symptoms, dyspnoea severity, and duration of disease. Across countries, the annual societal costs associated with symptomatic COPD were higher among patients with comorbidities. CONCLUSIONS: Symptomatic COPD is associated with a substantial economic burden. The HRQoL of patients with symptomatic COPD is, in general, low and influenced by dyspnoea.

Resource Use and Costs up to Two Years Post Diagnosis Among Newly Diagnosed COPD Patients in the UK Primary Care Setting: A Retrospective Cohort Study.

The objective of this study was to estimate the annual resource use and costs before and after COPD diagnosis and compare it across stages of airflow obstruction and levels of dyspnoea in the UK primary care setting. A retrospective cohort of newly diagnosed COPD patients (1/1/2008-31/12/2009) was identified in the UK Clinical Practice Research Datalink (CPRD). Resource use did not include medication costs and comprised of exacerbations, all cause GP interactions, and non-COPD hospitalisations, which were estimated for up to 12 months before and 24 months after COPD diagnosis. It was further stratified using baseline characteristics, Medical Research Council (MRC) dyspnoea score, and stages of airflow limitation. COPD costs were estimated using NHS reference costs. The analysis included 7881 newly diagnosed COPD patients (mean age, 67.2 years; 45% females). In the 2 years follow-up, the cohort experienced moderate and severe exacerbations, non-COPD hospitalisations, and GP surgery visits at an annual rate of 0.51, 0.13, 0.47, and 12.85, respectively. All resource components showed an upward trend with increase airflow limitation and dyspnoea. GP interactions accounted for 58.5% of annual per patient COPD management costs, estimated to be £ 2047 during the observation period. The annual costs doubled from patients with low levels of dyspnoea (MRC = 1; £ 1473) to those with high levels of dyspnoea (MRC = 5; £ 3243). COPD management costs in the primary care setting continued to remain high up to 2 years following initial diagnosis. The cost burden increased with high levels of dyspnoea and airflow obstruction, suggesting that both measures can identify patients requiring increased monitoring.

Treatment evolution after COPD diagnosis in the UK primary care setting.

RATIONALE: To assess the treatment progression during the 24 months following a formal diagnosis of chronic obstructive pulmonary disease (COPD) in the UK primary care setting. METHODS: A retrospective cohort of newly diagnosed COPD patients was identified in the Clinical Practice Research Datalink (CPRD) from 1/1/2008 until 31/12/2009. Maintenance therapy prescribed within the first 3 months of diagnosis and in the subsequent 3-month intervals for 24 months were analyzed. Treatment classes included long-acting ß2-agonists (LABAs), long-acting muscarinic antagonists (LAMAs), inhaled corticosteroids (ICSs), and respective combinations. At each 3-month interval, discontinuation, switching, addition, and stepping down patterns were analyzed cumulatively for the first 12 months and over the 24-month of follow-up. RESULTS: A total of 3199 patients with at least one prescription of a maintenance therapy at baseline and during 4th-6th month interval were included in the analysis. At diagnosis (0-3 months), the most frequently prescribed maintenance therapy was LABA+ICS (43%), followed by LAMA (24%) and LABA+LAMA+ICS (23%). Nearly half the patients (LABA-50%, LAMA-43%) starting on a monobronchodilator had additions to their treatment in 24 months. Compared to other medications, patients starting on a LAMA were most likely to escalate to triple therapy in 24 months. Nearly one-fourth of the patients prescribed triple therapy at baseline stepped down to LABA+ICS (25%) or LAMA (31%) within 24 months. CONCLUSION: Disease progression is evident over the 24 months after COPD diagnosis, as more patients were prescribed additional maintenance therapy in the 24-month period compared to baseline. The changes in therapy suggest that it is difficult to achieve a consistently improved COPD disease state.

COPD management costs according to the frequency of COPD exacerbations in UK primary care.

BACKGROUND: The economic burden of chronic obstructive pulmonary disease (COPD) exacerbations is significant, but the impact of other sources on the overall cost of COPD management is largely unknown. We aimed to estimate overall costs for patients experiencing none, one, or two or more exacerbations per year in the UK. METHODS: A retrospective cohort of prevalent COPD patients was identified in the Clinical Practice Research Datalink UK database. Patients with information recorded for at least 12 months before and after cohort entry date were included (first prevalent COPD diagnosis confirmed by spirometry on/after April 1, 2009). Patients were categorized as having none, one, or two or more moderate-to-severe COPD exacerbations in the 12 months after cohort entry and further classified by the Global initiative for chronic Obstructive Lung Disease (GOLD) category of airflow obstruction and the Medical Research Council dyspnea scale. Study outcomes included counts of general practitioner interactions, moderate-severe COPD exacerbations, and non-COPD hospitalizations. Estimated resource use costs were calculated using National Health Service reference costs for 2010-2011. RESULTS: The cohort comprised 58,589 patients (mean age 69.5 years, mean dyspnea grade 2.5, females 46.6%, current smokers 33.1%). The average total annual per patient cost of COPD management, excluding medications, was £2,108 for all patients and £1,523, £2,405, and £3,396 for patients experiencing no, one, or two or more moderate-to-severe exacerbations, respectively. General practitioner interactions contributed most to these annual costs, accounting for £1,062 (69.7%), £1,313 (54.6%), and £1,592 (46.9%) in patients with no, one, or two or more moderate-to-severe exacerbations, respectively. CONCLUSION: Disease management strategies focused on reducing costs in primary care may help reduce total COPD costs significantly.

Cost effectiveness of golimumab for the treatment of active psoriatic arthritis.

BACKGROUND: Golimumab is a novel TNF-α inhibitor licensed to treat patients with active PsA. Although its clinical efficacy has been proven in clinical trials, its cost effectiveness is yet to be established. OBJECTIVES: To estimate the cost effectiveness of golimumab among patients with active PsA from the UK NHS perspective. METHODS: A decision analytic model was used to simulate progression of a hypothetical cohort of active PsA patients on golimumab and other TNF-α inhibitors as well as palliative care. The clinical evidence was derived from clinical trials of TNF-α inhibitors and compared using mixed treatment models. The primary outcome measure was quality-adjusted life years (QALYs) estimated based on change in Health Assessment Questionnaire (HAQ) and Psoriasis Area Severity Index (PASI) from baseline. The annual acquisition cost of golimumab was assumed to be identical to annual cost of other subcutaneous TNF-α inhibitors. The resource use costs and outcomes were discounted at 3.5% over a period of 40 years. The uncertainty surrounding important variables was further explored using probabilistic sensitivity analyses (PSA). RESULTS: TNF-α inhibitors were significantly superior to palliative care but comparable to each other on Psoriatic Arthritis Response Criteria (PsARC), HAQ and PASI response. The incremental cost effectiveness ratio (ICERs) for golimumab compared to palliative care was £16,811 for PsA patients and £16,245 for a subgroup of PsA patients with significant psoriasis. At an acceptability threshold of £30,000 per QALY, the probability of golimumab being cost effective is 89%. CONCLUSION: Once monthly, golimumab is a cost-effective treatment alternative for patients with active PsA. With its patient-focussed attributes, golimumab is likely to offer additional choice in PsA treatment.

Cost-effectiveness of infliximab for the treatment of active and progressive psoriatic arthritis.

BACKGROUND: Despite its proven efficacy, infliximab is often considered to be an expensive treatment for patients with psoriatic arthritis. OBJECTIVES: To estimate the cost-effectiveness of infliximab among patients with active and progressive psoriatic arthritis. METHODS: A decision analytic model was constructed to simulate disease progression in hypothetical cohorts of patients with psoriatic arthritis receiving infliximab maintenance treatment. The primary response measure was change in Health Assessment Questionnaire score from a baseline estimated from mixed treatment models drawn from published clinical trials. Palliative care, comprising nonbiologic disease-modifying antirheumatic drugs, was used as a comparator. The primary outcome was quality-adjusted life years. The dose of infliximab was estimated for a range of 60 to 80 kg per patient body weight. The costs and outcomes were discounted at 3.5% for a period of 40 years. Uncertainty around the results was explored with probabilistic sensitivity analysis. RESULTS: The mixed treatment comparison showed a significant reduction in Health Assessment Questionnaire score across all patients. The tumor necrosis factor α inhibitors were significantly superior to palliative care but comparable with one another. The incremental cost-effectiveness ratios for etanercept, adalimumab, and infliximab relative to palliative care were £17,327; £19,246; and £16,942 to £23,022, respectively, across all patients with psoriatic arthritis and £16,613; £18,170; and £15,788 to £21,736, respectively, in the subgroup with significant psoriasis. CONCLUSION: Infliximab represents a cost-effective treatment option well within the National Institute for Health and Clinical Excellence threshold relative to palliative care. In light of equivalent outcomes with other tumor necrosis factor α inhibitors, its position in the treatment pathway is likely to be governed by treatment costs.

Cost-effectiveness of scheduled maintenance treatment with infliximab for pediatric Crohn's disease.

BACKGROUND: Infliximab recently became the only biologic approved for use in pediatric patients with severe active Crohn's disease (CD). OBJECTIVES: To estimate the cost-effectiveness of scheduled maintenance treatment with infliximab compared with standard care in children suffering from severe active CD over 5 years from the UK National Health Service perspective. METHODS: A Markov model was constructed to simulate the progression of a hypothetical cohort of CD children through predefined health states on scheduled maintenance treatment with infliximab (5 mg/kg). The data to populate the model came from infliximab trials from Targan et al., ACCENT I, and REACH. The health states included in the model were remission, responding active disease, nonresponding active disease, surgery, postsurgery remission, postsurgery complications, and death. Standard care, comprising immunomodulators, and/or corticosteroids were used as a comparator. The primary outcome was quality-adjusted life-years (QALY) estimated using the EuroQol (EQ-5D) from a European CD population. To account for the weight-based dosing of infliximab, a baseline patient weight of 40 kg that increased by 5 kg/year up to 60 kg was used. The costs and outcomes were discounted at 3.5% over a period of 5 years. Probabilistic sensitivity analyses were performed by varying the infliximab efficacy estimates, costs, and utilities. RESULTS: The incremental cost-effectiveness ratio (ICER) for infliximab treatment was pound14,607 compared with standard care. The sensitivity analyses revealed the treatment effect of infliximab to be the most influential parameter with ICERs ranging from pound10,480 to pound37,017. Assuming a willingness to pay of pound30,000 per QALY, the probability of infliximab being cost-effective is 78.6%. CONCLUSION: Scheduled maintenance treatment with infliximab (5 mg/kg) is likely to be a cost-effective treatment in children suffering from severe active CD under an 8-week maintenance program.

Cost-effectiveness of infliximab for the treatment of acute exacerbations of ulcerative colitis.

BACKGROUND: Infliximab has been shown to be efficacious in acute exacerbations of ulcerative colitis (UC). AIM: To evaluate the cost-effectiveness of infliximab treatment in patients hospitalised with acute exacerbations of UC. METHODS: A decision analysis model was constructed to simulate the progression of acute UC patients treated with infliximab induction regimen over 1 year. Infliximab treatment was compared with standard care, ciclosporin and surgery using transitions derived from infliximab and ciclosporin randomised trials. Costs and outcomes were discounted at 3.5%. Intermediate outcomes of colectomy and post-surgery complications were translated into the primary effectiveness measurement, which was quality-adjusted life years (QALYs) estimated using EQ-5D. One-way and probabilistic sensitivity analyses were performed to estimate the uncertainty around the results. RESULTS: The incremental cost effectiveness ratio (ICER) for infliximab was pound19,545 per QALY compared to ciclosporin, which in turn dominated standard care. Sensitivity analysis indicated patient body weight, utility estimates and treatment effect of alternative treatment strategies to be the most important factors affecting cost-effectiveness. CONCLUSION: Infliximab induction regimen appears to be a cost-effective treatment option for UC patients hospitalised with an acute exacerbation.

Survey of pharmacist collaborative drug therapy management in hospitals.

PURPOSE: The extent and scope of collaborative drug therapy management (CDTM) in U.S. hospitals and pharmacy directors' perceptions regarding CDTM were studied. METHODS: A survey was developed after reviewing the literature on CDTM. The sample for the study was obtained from the 2001 American Hospital Association Guide. The mail survey was pretested in January 2002 with 30 hospital pharmacy directors in Illinois, Indiana, and Michigan. A national random sample of 1000 hospital pharmacy directors stratified by state were mailed surveys in March 2003. Two follow-up surveys were mailed at approximately four-week intervals. RESULTS: Responses were received from 327 hospitals, a 32.7% response rate. A total of 158 respondents (49.7%) indicated that some pharmacists in their hospital were engaged in CDTM. Most hospitals with CDTM authorized pharmacists to adjust a drug's strength (86.7%), order laboratory or related tests (84.2%), and change a drug's frequency of administration (81.6%). The CDTM-related activities pharmacists performed varied with disease and treatment area. Payment or reimbursement for some CDTM was received by 12.7% of hospitals with CDTM. Respondents from hospitals with CDTM perceived significantly greater support for CDTM and greater strategic impact of CDTM than those from hospitals without CDTM. Respondents perceived positive support for CDTM but believed that CDTM had little or no financial impact on pharmacy departments. CONCLUSION: Approximately 50% of respondent hospitals had some pharmacists engaged in CDTM. Although CDTM was perceived as not having a positive financial impact on pharmacy departments, it was perceived as having a positive strategic impact by improving the views of upper administration regarding the value of pharmacists and facilitating implementation of other pharmacy services.