A clinical and economic evaluation of protease-modulating matrix interventions for diabetic foot and leg ulcers: Towards the development of treatment guidelines in the United Kingdom

Background: Wounds such as Diabetic foot ulcers (DFU) and leg ulcers (LU) are burdensome, reduce a patient’s quality of life (QoL) and require a lot of time, money, and resources to heal. Patients have access to many types of dressing, but no guidance exists identifying a preferred dressing regimen, in part due to lack of data supporting clinical and cost-effectiveness. This research investigates treatment of DFU and LU with protease-modulating matrix interventions with the intent of creating treatment guidelines. Methods: A multi-method research protocol was designed to include; systematic literature reviews; Delphi methodology expert panel; patient reported outcomes study; retrospective real-world data analysis; and a collection of economic modelling. Economic models include budget impact modelling, cost-consequence analysis, cost-utility and cost-effectiveness analysis, supported by data collected in the four previous studies. Statistical and sensitivity analysis have been performed where necessary and external guidelines and best practice followed to assure high-quality research. Results: The studies showed the variance in care; the efficacy of the sucrose-octasulfate dressing and the burden of DFU and LU. Economic modelling found that the sucroseoctasulfate dressing was both a clinically and cost-effective option; improving time to healing and reducing the cost of care; whilst the incidence of adverse events such as infection or amputation was less. The results of this research have been included in guidance published by the National Institute for Health and Care Excellence (NICE). Discussion: The most cost-effective dressing is not the one with the lowest acquisition cost. Scenario analysis showed the sucrose-octasulfate dressing as cost-saving when a comparator was zero cost; demonstrating the impact of improved healing time on reducing overall costs. Patients, healthcare professionals and payers should be aware of the newly published NICE guidance; to accelerate healing, reduce cost and improve QoL for patients with DFU or LU

A Systematic Review of Clinical Efficacy Associated with use of Protease-Modulating Interventions with Diabetic Foot Ulcer or Venous Leg Ulcer

OBJECTIVES: Diabetic foot ulcers (DFUs) or leg ulcers (LUs) of venous, arterial or mixed origin can cause a considerable burden to a patient and healthcare provider, taking a long time to heal and requiring frequent interventions. Dressings are a mainstay of treatment with countless options for a Healthcare Provider. Protease-modulating matrix (PMM) interventions are an alternative to basic or other advanced dressings. A systematic review was undertaken to assess the clinical effectiveness of PMM interventions for DFUs and LUs. METHODS: A systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines. An online database search, and consultation with experts and manufacturers identified the literature. Databases searched included: Centre Reviews and Dissemination (CRD) York Database, Cochrane Library, Medline (PubMed), National Institute for Health and Clinical Excellence Evidence Search, Science Direct/Scopus. Two researchers performed data extraction with a third consulted in case of any discrepancies. A narrative synthesis of results and critical appraisal of included studies was performed. RESULTS: A total of 283 records were identified by literature searching. After initial screening of titles and abstracts, 215 full text articles were judged against pre-defined inclusion and exclusion criteria. Six randomised controlled trials and 2 observational studies were included in the review. A total of 1310 patients were included in this study. The three VLU RCTs included a total of 377 patients, and the DFU studies included 933 patients. Healing was the most frequently reported outcome, followed by wound area reduction. A meta-analysis was not possible given the heterogeneity of the included studies. CONCLUSIONS: This review provides some evidence that PMM interventions have a clinical benefit on wound healing outcomes; however, there were several methodological issues with the studies included. New evidence shows promising results for the treatment of DFUs involving protease modulation by sucrose octasulfate dressings

A retrospective observational study on characteristics, treatment patterns, and healthcare resource use of patients with myasthenia gravis in England

Background: There are limited data on the real-world healthcare resource use (HCRU) and management costs of myasthenia gravis (MG) in England. Objective: This study aims to assess the burden of disease for patients with MG in England. Design: A retrospective, observational cohort study of adult patients diagnosed with MG, using data from the Hospital Episode Statistics data warehouse. Methods: Patients with a first-ever recorded diagnosis of MG between 30 June 2015 and 30 June 2020 were followed up until 30 June 2021 or death, whichever occurred first. Post-diagnosis patient characteristics, treatment patterns, HCRU, and costs were described. Costs were evaluated using National Health Service reference costs. Results: A total of 9087 patients with a median follow-up time of 2.9 years (range, 1.7–4.3 years) were included. The mean age at diagnosis was 66.5 years and 53% of the patients were male. A large proportion of patients (72.8%) were admitted as inpatients during follow-up with a mean number of 1.3 admissions. Patients hospitalized for MG-related complications spent a mean of 9.7 days per patient-year in the hospital. During follow-up, 599 (6.6% of the total cohort) and 163 (1.8%) patients had a record of rescue therapy with intravenous immunoglobulin (IVIg) and plasma exchange (PLEX), respectively. Rituximab was administered to 81 (0.9%) patients and 268 (2.9%) patients underwent thymectomy. In those patients receiving rescue therapy or rituximab, >10% received at least three cycles of the same treatment. The average annual cost of hospital admissions across all patients treated with IVIg, PLEX, and rituximab were £907,072, £689,979, and £146,726, respectively. Conclusion: A majority of MG patients required hospitalization or accident and emergency attendance, resulting in high HCRU and costs. A subset of patients required rescue therapy (including IVIg and PLEX), rituximab administration, ventilation, or thymectomy

A Systematic Review of Economic Outcomes Associated with use of Topical Interventions for Treatment of Chronic Wounds

OBJECTIVES: A combination of interventions may be appropriate for a patient with a chronic wound. However, standard care varies by aetiology, geographical location and clinician discipline. A systematic review was undertaken to examine the economic impact of topical interventions for chronic wounds and variance associated with standard care. METHODS: A systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Searches of: Science Direct, National Institute for Health and Clinical Excellence Evidence search, Medline (PubMed), Centre of Reviews and Dissemination (University of York), Cochrane Database and discussion with experts and manufacturers identified the literature. Two researchers performed data extraction, with a third consulted where there were disagreements. Economic endpoints including: incremental cost-effectiveness ratio, cost-per Quality Adjusted Life Year and disease related resource use were extracted. A narrative synthesis of results and critical appraisal using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement were performed. RESULTS: 3422 records identified. After screening, 817 full text articles were judged versus inclusion and exclusion criteria. 15 studies were included: 6 economic analysis along clinical trials, and 9 modelling studies.10 studies focused on VLUs, 3 studies on DFUs and 1 on Pressure Ulcers and 1 on Chronic Wounds. Data tables for methods, results and appraisal using the CHEERS statement were completed. Quality scores ranged from 10 – 15 with a mean of 12.9. CONCLUSIONS: This review provides some evidence that topical interventions can offer cost-effective solutions for treating chronic wounds compared with standard care. Current evidence predominantly uses the endpoint of wound area reduction; evaluations using complete wound closure as primary endpoint could be more useful. This review informs decision makers and clinicians that more expensive wound care products can be cost-effective in the management of chronic wounds; in opposition to current NICE guidance to use the ‘least costly’ dressing

Long-Term Benefit-Risk Profiles of Treatments for Moderate-to-Severe Plaque Psoriasis : A Network Meta-Analysis

Altres ajuts: AbbVie Inc.Introduction: The long-term benefit-risk profiles of licensed and investigational treatments for moderate-to-severe plaque psoriasis have not been fully characterized. Methods: Randomized controlled trials (RCTs) of licensed and investigational treatments for moderate-to-severe plaque psoriasis were identified through a systematic literature review through 2 May 2021. Bayesian network meta-analyses (NMAs) were conducted to compare the efficacy (Psoriasis Area and Severity Index [PASI] 75/90/100 [at least a 75/90/100% reduction in PASI score from baseline] response) and safety outcomes (any adverse event [AE], any serious AE [SAE], and AEs leading to treatment discontinuation) of each treatment evaluated between weeks 48 and 56 after baseline. Surfaces under the cumulative ranking curves (SUCRAs) were calculated to evaluate the relative ranking of treatments. The benefit-risk profiles of treatments were assessed by bidimensional plots of the NMA-estimated efficacy and safety outcomes. Results: In the efficacy NMA (N = 14 RCTs), the relative rankings for PASI 75/90/100 responses by weeks 48-56 were the highest for risankizumab (SUCRA: 98.5%) and bimekizumab (83.8% for dosing every 4 weeks [Q4W], 72.7% for dosing Q4W then every 8 weeks). The PASI response rates did not differ significantly between risankizumab and the two bimekizumab regimens. Additionally, risankizumab was associated with significantly higher PASI response rates than brodalumab, guselkumab, ixekizumab, secukinumab, ustekinumab, adalimumab, and etanercept. In the safety NMAs (N = 8 RCTs), risankizumab had the highest relative rankings for all three outcomes (SUCRA: 92.1%, 82.0%, and 91.0% for any AE, any SAE, and AEs leading to treatment discontinuation, respectively). Risankizumab had a significantly lower rate of any AE than bimekizumab, ustekinumab, and secukinumab. Conclusions: Risankizumab was associated with the most favorable long-term benefit-risk profile for the treatment of moderate-to-severe plaque psoriasis. Although ixekizumab and bimekizumab had favorable efficacy profiles, both treatments had lower rankings for safety outcomes

Real Life use of Dressings in the Treatment of Leg Ulcers and Diabetic Foot Ulcers

OBJECTIVES: Leg ulcers (LUs) and diabetic foot ulcers (DFUs) can take a long time to heal, with dressings requiring frequent changes. Establishing current treatment pathways and reasoning for changing a care plan, will provide real life understanding regarding the use of dressings and areas providing opportunity to improve patient outcomes and reduce the economic burden of these conditions. The study aimed to establish treatment pathways, incidence of treatment switching, patient outcomes and resource use of patients with a LU or DFU. METHODS: A multi-centre, retrospective, chart examination performed in multiple care settings. The data extracted included wound characteristics, each visit by the patient, and every intervention. Reasons for a change of treatment plan, and infection and healing rates were captured. Reasons for changing treatment were coded and analysed. RESULTS: 7 UK centres provided data from 97 patients, totalling 107 wounds and 1050 visits. 90 (9%) wounds were observed for the first time and 42 (4%) healed wounds not requiring dressings were observed, 189 (18%) changes used the same dressing as previously recorded. This left 729 (69%) instances of treatment switching. Reasons for changes to treatment plan were either Clinical (28%), Patient (5%), External (5%) or No reason (62%). External reasons included available stock and guidance from other clinicians. CONCLUSIONS: 69% of visits resulted in a different type of dressing being applied, with 62% of these changes being made without a reason. The data also suggests superior clinical outcomes are achieved in Randomised Clinical Trials compared to real life. Patients in RCTs receive the same intervention for the trial duration; yet this study finds a switch in nearly 80% of eligible visits. It is theorised therefore that without mandated guidance regarding dressings, current treatment switching practices may continue as observed, with potential adverse outcomes on patient health and quality of life

Comparative Efficacy and Relative Ranking of Biologics and Oral Therapies for Moderate-to-Severe Plaque Psoriasis : A Network Meta-analysis

The clinical benefits of biologic and oral treatments for moderate-to-severe plaque psoriasis are well-established, but efficacy outcomes can vary across therapies. Comparative efficacy analysis can be highly informative in clinical settings with multiple therapeutic options. This study assessed the short-term and long-term comparative efficacy of biologic and oral treatments for moderate-to-severe psoriasis. A systematic literature review identified phase 2/3/4 randomized controlled trials (RCTs) through to 1 July 2020 for Food and Drug Administration- or European Medicines Agency-licensed treatments for moderate-to-severe psoriasis. Psoriasis Area and Severity Index (PASI) 75/90/100 response rates at the end of the primary response (short-term: 10-16 weeks from baseline) and maintenance periods (long-term: 48-52 weeks from baseline) were estimated using Bayesian network meta-analysis. Surfaces under the cumulative ranking curves (SUCRA) were estimated to present the relative ranking of treatments. In the short term (N = 71 RCTs), the PASI 90 response rates were highest for ixekizumab (72.9%, SUCRA 0.951), risankizumab (72.5%, 0.940), and brodalumab (72.0%, 0.930), which were significantly higher than those for guselkumab (65.0%, 0.795), secukinumab (65.0%, 0.794), infliximab (56.8%, 0.702), certolizumab (400 mg: 49.6%, 0.607; 200 mg: 42.2%, 0.389), ustekinumab (90 mg: 47.9%, 0.568; weight-based: 45.7%, 0.505; 45 mg: 44.6%, 0.460), adalimumab (43.0%, 0.410), tildrakizumab (200 mg: 39.7%, 0.327; 100 mg: 37.2%, 0.268), etanercept (18.0%, 0.171), apremilast (12.4%, 0.090), and dimethyl fumarate (12.2%, 0.092). The PASI 100 response rates were highest for ixekizumab (41.4%), risankizumab (40.8%), and brodalumab (40.3%). In the long term (N = 11 RCTs), the PASI 90 rate was highest for risankizumab (85.3%, SUCRA: 0.998), which were significantly higher than those for brodalumab (78.8%, 0.786), guselkumab (78.1%, 0.760), ixekizumab (72.1%, 0.577), secukinumab (67.0%, 0.450), ustekinumab (weight-based: 55.0%, 0.252), adalimumab (51.6%, 0.176), and etanercept (37.9%, 0.001). Risankizumab had the highest PASI 100 response rate (65.4%), followed by brodalumab (55.7%) and guselkumab (54.8%). Ixekizumab, risankizumab, and brodalumab had the highest short-term efficacy, and risankizumab had the highest long-term efficacy. The online version contains supplementary material available at 10.1007/s13555-021-00511-1

Comparative safety and benefit-risk profile of biologics and oral treatment for moderate-to-severe plaque psoriasis: A network meta-analysis of clinical trial data

Background The comparative safety and benefit-risk profiles of moderate-to-severe psoriasis treatment have not been well studied. Objective To compare the short-term (12-16 weeks) and long-term (48-56 weeks) safety and benefit-risk profiles of moderate-to-severe psoriasis treatments. Methods A systematic literature review of phase II-IV randomized controlled trials of moderate-to-severe psoriasis treatments was conducted (cutoff: July 1, 2020). Any adverse events (AEs), any serious AEs, and AEs leading to treatment discontinuation were compared using Bayesian network meta-analyses (NMAs). Results Fifty-two and 7, respectively, randomized controlled trials were included in the short- and long-term NMAs, respectively. In the short-term NMA, the rates of any AEs were the lowest for tildrakizumab (posterior median: 46.0%), certolizumab (46.2%), and etanercept (49.1%). The rates of any serious AE were the lowest for certolizumab (0.8%), risankizumab (1.2%), and etanercept (1.6%). The rates of AEs leading to treatment discontinuation were the lowest for risankizumab (0.5%), tildrakizumab (1.0%), and guselkumab (1.5%). In the long-term NMA, risankizumab had the lowest rates of all 3 outcomes (67.5%, 4.4%, and 1.0%, respectively) and the most favorable benefit-risk profile. Limitations The results may not be generalizable to real-world populations. Conclusions Anti–interleukin 23 agents were associated with low rates of safety events. Risankizumab had the most favorable benefit-risk profile in the long term