Cost-effectiveness of an insertable cardiac monitor in a high-risk population in the US.

BACKGROUND: Insertable cardiac monitors (ICMs) are a clinically effective means of detecting atrial fibrillation (AF) in high-risk patients, and guiding the initiation of non-vitamin K oral anticoagulants (NOACs). Their cost-effectiveness from a US clinical payer perspective is not yet known. The objective of this study was to evaluate the cost-effectiveness of ICMs compared to standard of care (SoC) for detecting AF in patients at high risk of stroke (CHADS2 ≥ 2), in the US. METHODS: Using patient data from the REVEAL AF trial (n = 393, average CHADS2 score = 2.9), a Markov model estimated the lifetime costs and benefits of detecting AF with an ICM or with SoC (specifically intermittent use of electrocardiograms and 24-h Holter monitors). Ischemic and hemorrhagic strokes, intra- and extra-cranial hemorrhages, and minor bleeds were modelled. Diagnostic and device costs, costs of treating stroke and bleeding events and medical therapy-specifically costs of NOACs were included. Costs and health outcomes, measured as quality-adjusted life years (QALYs), were discounted at 3% per annum, in line with standard practice in the US setting. One-way deterministic and probabilistic sensitivity analyses (PSA) were undertaken. RESULTS: Lifetime per-patient cost for ICM was $31,116 versus $25,330 for SoC. ICMs generated a total of 7.75 QALYs versus 7.59 for SoC, with 34 fewer strokes projected per 1000 patients. The model estimates a number needed to treat of 29 per stroke avoided. The incremental cost-effectiveness ratio was $35,528 per QALY gained. ICMs were cost-effective in 75% of PSA simulations, using a $50,000 per QALY threshold, and a 100% probability of being cost-effective at a WTP threshold of $150,000 per QALY. CONCLUSIONS: The use of ICMs to identify AF in a high-risk population is likely to be cost-effective in the US healthcare setting.

Targeted systemic therapies for psoriatic arthritis: a systematic review and comparative synthesis of short-term articular, dermatological, enthesitis and dactylitis outcomes.

INTRODUCTION: Randomised controlled trials (RCTs) have compared biological and targeted systemic disease-modifying antirheumatic drugs (DMARDS) against placebo in psoriatic arthritis (PsA); few have compared them head to head. OBJECTIVES: To compare the efficacy and safety of all evaluated DMARDs for active PsA, with a special focus on biological DMARDs (bDMARDs) licensed for PsA or psoriasis. METHODS: A systematic review identified RCTs and Bayesian network meta-analysis (NMA) compared treatments on efficacy (American College of Rheumatology (ACR) response, Psoriasis Area and Severity Index (PASI) response, resolution of enthesitis and dactylitis) and safety (patients discontinuing due to adverse events (DAE)) outcomes. Subgroup analyses explored ACR response among patients with and without prior biological therapy exposure. RESULTS: The NMA included 46 studies. Results indicate that some tumour necrosis factor inhibitors (anti-TNFs) may perform numerically, but not significantly, better than interleukin (IL) inhibitors on ACR response but perform worse on PASI response. Few significant differences between bDMARDs on ACR response were observed after subgrouping for prior bDMARD exposure. Guselkumab and IL-17A or IL-17RA inhibitors-brodalumab, ixekizumab, secukinumab-were best on PASI response. These IL-inhibitors and adalimumab were similarly efficacious on resolution of enthesitis and dactylitis. Infliximab with and without methotrexate, certolizumab 400 mg every 4 weeks and tildrakizumab showed the highest rates of DAE; abatacept, golimumab and the IL-inhibitors, the lowest. CONCLUSIONS: Despite similar efficacy for ACR response, IL-17A and IL-17RA inhibitors and guselkumab offered preferential efficacy to anti-TNFs in skin manifestations, and for enthesitis and dactylitis, thereby supporting drug selection based on predominant clinical phenotype.

Targeted therapies for patients with moderate-to-severe psoriasis: a systematic review and network meta-analysis of PASI response at 1 year.

PURPOSE: To compare PASI outcomes of approved biologics and apremilast after 1 year of treatment. METHODS: A systematic review identified RCTs and long-term extensions reporting PASI 75, 90, and 100 responses in adults with moderate-to-severe psoriasis. Data for analysis were modeled using a Bayesian multinomial likelihood model with probit link. RESULTS: Twenty-eight studies reporting PASI responses were included in the network meta-analysis. Differences in study design led to a stepwise approach to synthesis, consisting of two analyses. The primary analysis included nine RCTs investigating comparative efficacy at 1 year. Results indicated risankizumab, brodalumab, and guselkumab were the most effective therapies, followed by ixekizumab and secukinumab; all demonstrated superiority to ustekinumab and etanercept. The secondary analysis extended the primary analysis with 19 further studies comparing active interventions to placebo outcomes extrapolated from induction. The interventions generating the highest PASI response were the same as the primary analysis. These therapies were more effective than apremilast, ustekinumab, adalimumab, certolizumab, etanercept, and infliximab. CONCLUSIONS: This NMA demonstrated that evaluated IL-17 and IL-23 inhibitors outperformed other biological therapies after 1 year. Risankizumab had a higher probability of achieving PASI outcomes than all other biologics, except brodalumab and guselkumab, where no significant difference could be concluded.

Assessing the Quality and Coherence of Network Meta-Analyses of Biologics in Plaque Psoriasis: What Does All This Evidence Synthesis Tell Us?

INTRODUCTION: A range of treatments are available for moderate-to-severe psoriasis; however, there remains a paucity of direct comparisons of these in head-to-head trials. Network meta-analyses (NMA) allow comparisons of these to support clinical decision making. This systematic literature review assesses the methodological quality of NMAs available for moderate-to-severe psoriasis and compares their methods and results. Their validity and applicability for current practice is also assessed. METHODS: A systematic review of published NMAs of at least two biologics for moderate-to-severe psoriasis was undertaken. Embase, MEDLINE, MEDLINE In-Process, and the Cochrane Library were last searched on 19 February 2020. The quality of NMAs was assessed using the International Society of Pharmacoeconomics and Outcomes Research (ISPOR) criteria. NMA methodology, funding, and results were compared and differences in results explored. RESULTS: Twenty-five analyses evaluating up to 19 different treatments at 8-24 weeks, and two analyses at 1 year, were included. Psoriasis Area Severity Index (PASI) response was assessed in 23, facilitating comparisons between NMAs. All NMAs met at least half of the ISPOR criteria. The major limitations were explaining the rationale for methodology, exploring effect modifiers, and consistency between direct and indirect estimates. The analyses differed in model type (Bayesian or frequentist), analysis of PASI response (binomial or multinomial), and analysis of different treatment doses (separate or pooled). PASI results were broadly similar, except for the Cochrane Collaboration NMA which provided lower estimates of treatment efficacy versus placebo. This analysis differed methodologically from others, including pooling data for different doses. CONCLUSIONS: Based on PASI 90 at induction, the majority of recent NMAs came to similar conclusions: interleukin (IL) 17 inhibitors (brodalumab, ixekizumab, secukinumab), IL-23 inhibitors (guselkumab and risankizumab) and infliximab were most efficacious, supporting the validity of NMAs in this clinical area. Decisions should be made using high-quality, up-to-date NMAs with assumptions relevant to clinical practice.

Cost-effectiveness of an insertable cardiac monitor to detect atrial fibrillation in patients with cryptogenic stroke.

Background: We assessed cost-effectiveness of insertable cardiac monitors (ICMs) in a US cryptogenic stroke population. Materials & methods: We modelled lifetime costs and quality-adjusted life years for three monitoring strategies post cryptogenic stroke: ICM starting immediately, ICM starting after Holter monitoring (delayed ICM) and standard of care involving intermittent ECG and Holter monitoring. Patient characteristics and detection efficacy were based on the CRYSTAL-AF trial. AF detection altered the modelled anticoagulation therapy and subsequent stroke and bleed risks. Results & conclusion: Immediate ICM was found to be cost-effective versus standard of care and cost-saving versus delayed ICM. Results were robust to sensitivity analyses. ICMs are a cost-effective diagnostic tool for the prevention of recurrent stroke in a US cryptogenic stroke population.

Cost per PASI-75 responder of calcipotriol plus betamethasone dipropionate cutaneous foam versus nonbiologic systemic therapies for the treatment of plaque psoriasis in seven European countries.

PURPOSE: To compare the short-term cost and effectiveness of calcipotriol/betamethasone dipropionate (Cal/BD) cutaneous foam against nonbiologic systemics in psoriasis patients for whom oral systemic or topical therapy is considered appropriate in seven European countries. METHODS: Matching-adjusted indirect comparisons of four-week PASI-75 responses of Cal/BD foam were performed versus 12-week responses of methotrexate, acitretin, fumaric acid esters (FAE) and 16-week responses of apremilast. Analyses took a payer perspective and included drug, physician visit and monitoring costs. RESULTS: In all countries, Cal/BD foam generated the lowest cost per responder (CPR). Against methotrexate, apremilast and acitretin, Cal/BD foam generated response for less than €190 in Italy, €195 in Portugal, €216 in Greece, £218 in the United Kingdom, €250 in Belgium, €319 in Spain, and €359 in the Netherlands. Relative to treatment with FAE, Cal/BD foam resulted in response for less than €298, €430, €382 and £262 in Belgium, the Netherlands, Spain and the United Kingdom, respectively. For Cal/BD foam, apremilast and FAE, total costs were driven by drug costs; for methotrexate and acitretin, by monitoring. CONCLUSIONS: Driven by its lower costs and high response rates, Cal/BD foam is likely to be a cost-effective option over the short-term in the investigated psoriasis population.

Assessing the relative efficacy of interleukin-17 and interleukin-23 targeted treatments for moderate-to-severe plaque psoriasis: A systematic review and network meta-analysis of PASI response.

INTRODUCTION: New generation biologics, including interleukin (IL)-17 and IL-23 inhibitors, have delivered higher rates of skin clearance than older treatments in head-to-head studies. However, studies comparing these new biologics directly to one another are limited. OBJECTIVES: To compare the short-term efficacy of available (or imminently available) biologic and non-biologic systemic therapies for treating patients with moderate-to-severe plaque psoriasis. METHODS: A systematic review was undertaken to identify randomised controlled trials evaluating biologic treatments, apremilast and dimethyl fumarate. MEDLINE, MEDLINE In-Process, Embase and the Cochrane Library were searched from the 1st January 2000 to 22nd November 2018. A Bayesian network meta-analysis (NMA) using a random-effects multinomial likelihood model with probit link and meta-regression to adjust for cross-trial variation in placebo responses compared the efficacy of interventions at inducing different levels of Psoriasis Area and Severity Index (PASI) response during the induction period. A range of sensitivity analyses was undertaken. RESULTS: Seventy-seven trials (34,816 patients) were included in the NMA. The base-case analysis showed that all active treatments were superior to placebo. IL-17 inhibitors, guselkumab and risankizumab were found to be more efficacious than tildrakizumab, ustekinumab, all TNF inhibitors and non-biologic systemic treatments at inducing all levels of PASI response. In addition, brodalumab, ixekizumab and risankizumab were significantly more efficacious than secukinumab; no significant difference was found in the comparison with guselkumab. The greatest benefit of brodalumab, ixekizumab, guselkumab, and risankizumab was seen for PASI 90 and PASI 100 response. Results were consistent across all analyses. CONCLUSIONS: In the NMA brodalumab, ixekizumab, risankizumab and guselkumab showed the highest levels of short-term efficacy. There were differences in efficacy between treatments within the same class. Longer-term analyses are needed to understand differences between these drugs beyond induction in what is a life-long condition.

Cost-effectiveness of an insertable cardiac monitor in a high-risk population in the UK.

Objective: To evaluate the cost-effectiveness of insertable cardiac monitors (ICMs) compared with standard of care (SoC) for detecting atrial fibrillation (AF) in patients at high risk of stroke (CHADS2 >2), using a UK National Health Service (NHS) perspective. Methods: Using patient characteristics and clinical data from the REVEAL AF trial, a Markov model assessed the cost-effectiveness of detecting AF with an ICM compared with SoC. Costs and benefits were extrapolated across modelled patient lifetime. Ischaemic and haemorrhagic strokes, intracranial and extracranial haemorrhages and minor bleeds were modelled. Diagnostic and device costs were included, plus costs of treating stroke and bleeding events and costs of oral anticoagulants (OACs). Costs and health outcomes, measured as quality-adjusted life years (QALYs), were discounted at 3.5% per annum. One-way deterministic and probabilistic sensitivity analyses (PSA) were undertaken. Results: The total per-patient cost for ICM was £13 360 versus £11 936 for SoC (namely, annual 24 hours Holter monitoring). ICMs generated a total of 6.50 QALYs versus 6.30 for SoC. The incremental cost-effectiveness ratio (ICER) was £7140/QALY gained, below the £20 000/QALY acceptability threshold. ICMs were cost-effective in 77.4% of PSA simulations. The number of ICMs needed to prevent one stroke was 21 and to cause a major bleed was 37. ICERs were sensitive to assumed proportions of patients initiating or discontinuing OAC after AF diagnosis, type of OAC used and how intense the traditional monitoring was assumed to be under SoC. Conclusions: The use of ICMs to identify AF in a high-risk population is cost-effective for the UK NHS.

Cost-effectiveness of an insertable cardiac monitor to detect atrial fibrillation in patients with cryptogenic stroke.

BACKGROUND AND AIMS: Documentation of atrial fibrillation is required to initiate oral anticoagulation therapy for recurrent stroke prevention. Atrial fibrillation often goes undetected with traditional electrocardiogram monitoring techniques. We evaluated whether atrial fibrillation detection using continuous long-term monitoring with an insertable cardiac monitor is cost-effective for preventing recurrent stroke in patients with cryptogenic stroke, in comparison to the standard of care. METHODS: A lifetime Markov model was developed to estimate the cost-effectiveness of insertable cardiac monitors from a UK National Health Service perspective using data from the randomized CRYSTAL-AF trial and other published literature. We also conducted scenario analyses (CHADS2 score) and probabilistic sensitivity analyses. All costs and benefits were discounted at 3.5%. RESULTS: Monitoring cryptogenic stroke patients with an insertable cardiac monitor was associated with fewer recurrent strokes and increased quality-adjusted life years compared to the standard of care (7.37 vs 7.22). Stroke-related costs were reduced in insertable cardiac monitor patients, but overall costs remained higher than the standard of care (£19,631 vs £17,045). The incremental cost-effectiveness ratio was £17,175 per quality-adjusted life years gained, compared to standard of care in the base-case scenario, which is below established quality-adjusted life years willingness-to-pay thresholds. When warfarin replaced non-vitamin-K oral anticoagulants as the main anticoagulation therapy, the incremental cost-effectiveness ratio was £13,296 per quality-adjusted life years gained. CONCLUSION: Insertable cardiac monitors are a cost-effective diagnostic tool for the prevention of recurrent stroke in patients with cryptogenic stroke. The cost-effectiveness results have relevance for the UK and across value-based healthcare systems that assess costs relative to outcomes.

Cost-Effectiveness Analysis of Alternative Antiviral Strategies for the Treatment of HBeAg-Positive and HBeAg-Negative Chronic Hepatitis B in the United Kingdom.

BACKGROUND: Seven drugs are licensed for the treatment of chronic hepatitis B (CHB) in the United Kingdom. Which initial treatment, secondary therapy, and whether antivirals should be given alone or in combination are questions of considerable uncertainty. OBJECTIVE: The aim of this model was to undertake a comprehensive economic evaluation of all antiviral treatments for CHB to recommend the most cost-effective therapeutic sequence. METHODS: We developed a probabilistic Markov model to compare the cost-effectiveness of all clinically relevant antiviral treatment sequences for nucleos(t)ide-naive adults with hepatitis B e-antigen (HBeAg)-positive or HBeAg-negative CHB. Relative rates of HBeAg seroconversion and viral suppression were obtained from a network meta-analysis. Data on mortality, antiviral drug resistance, durability of response, adverse events, and costs were obtained from published literature. Results are reported in terms of lifetime costs, quality-adjusted life-years (QALYs), and expected net benefit. RESULTS: In the base-case analysis, pegylated interferon alpha-2a (peg-IFN α-2a) followed by tenofovir disoproxil fumarate was most effective and cost-effective in HBeAg-positive patients, with a cost of £7488 per QALY gained compared with no treatment. In HBeAg-negative patients, peg-IFN α-2a followed by entecavir was most effective and cost-effective, with a cost of £6981 per QALY gained. The model was robust to a wide range of sensitivity analyses. CONCLUSIONS: Peg-IFN α-2a followed by tenofovir disoproxil fumarate or entecavir is the most effective antiviral treatment strategy for people with both variants of CHB. At a cost of less than £10,000 per QALY gained, these sequences are considered cost-effective in England and Wales. The results of this analysis were used to inform 2013 National Institute for Health and Care Excellence guideline recommendations.

Biological therapies for the treatment of severe psoriasis in patients with previous exposure to biological therapy: a cost-effectiveness analysis.

BACKGROUND: Biologic therapies have revolutionised the care of patients with psoriasis, although they come at significant extra cost. Guidance on their use in the UK National Health Service (NHS) has so far focused on patients who are "biologic naive", yet a minority of patients have poor response and require further treatment. OBJECTIVES: To assess the potential cost effectiveness of sequential biologic therapies in patients with psoriasis who have been exposed to previous biologic therapy. METHODS: A two-part model with a 10-year time horizon was built to model an initial 13.5-week "trial" phase and a longer-term "treatment" period with annual Markov cycles. Psoriasis Area and Severity Index (PASI) response rates from subgroup analyses of three randomised placebo-controlled trials evaluating biologic agents were considered. A meta-analysis of these data provided probabilities of achieving PASI response (50/75/90) in the short term, and published evidence and assumptions were used to predict outcomes over the longer term. Benefits were measured in quality-adjusted life years (QALYs), and costs (2013-14) to the UK NHS included drugs, administration, monitoring, and hospitalisation. Costs and benefits were discounted 3.5 % per annum. Cost effectiveness of sequential biologic therapy was measured using an incremental cost-effectiveness ratio (ICER) compared to best supportive care (BSC). Extensive sensitivity analyses were performed to assess the impact of alternative assumptions on the results. RESULTS: Results indicate that over 10 years, switching to a second biologic following intolerance to or failure of a first is likely to generate more QALYs than BSC, but at a higher cost. Base case results suggest the ICER of the second biologic compared to BSC is £17,681 per QALY; however, sensitivity analyses indicate that changes in the efficacy of BSC, drug costs, dropout rates, and rates of hospitalisation have a significant impact, causing the ICER to range from less than £10,000 to over £50,000 per QALY. CONCLUSIONS: Further biologic therapy for patients with psoriasis who have previously been treated with biologic therapy may be cost effective, although there is considerable uncertainty in the results. Future studies should be designed to evaluate the clinical efficacy of biologic therapies in this subgroup with particular attention given to short-term and longer-term responses.