HPR4 ISPOR HEOR Trends Over Time: What Is the Influence of Macro HTA Changes?

Objectives: To better understand the constantly evolving global perspectives on health economics and outcomes research (HEOR), ISPOR conducts surveys among its members and global leaders to capture key methodological and policy HEOR trends expected to significantly impact on health care decision-making. To summarise these trends over time and capture the potential impact of health technology assessment (HTA) processes, we conducted a review of ISPOR's HEOR trends and where we are to-date. Method(s): We systematically searched for trends published by ISPOR between 2018 and 2022 and extracted key information to understand the consistency of trends over time and the evolution of themes. This search was supplemented by identifying key HTA developments and related methodological movements in decision-making in the same period that may have impacted the ranking of trends across years. Results were synthesized qualitatively using infographics. Result(s): Overall, across the last 5 years, 11 different trends were identified. Real-world evidence appeared as the third most influential trend in 2019 and became the number one trend since 2020, whereas drug and healthcare pricing dropped from a key trend in 2018 to 6th position in 2022. Some trends (e.g., biosimilars) only appeared once, due to potentially limited interest or lack of new related methods, whereas other topics (e.g., health equity) regained attention during recent years. Latest research initiatives such as the GetReal Initiative in Europe, HTA collaborations with real-world data organisations (Flatiron), the rise of advanced methodologies (e.g., value-based frameworks) and the recent COVID-19 pandemic may have influenced the appearance, upgrade, or disruption of some of these trends, reflecting changes occurring in HEOR landscape and decision-making. Conclusion(s): Capturing HEOR trends through a representative organisation such as ISPOR is key to understanding past and potential future developments in methods and processes of health policy, considering the wider interplay of contextual and methodological advances.Copyright © 2022

Real-world experience of rituximab biosimilar GP2013 in rheumatoid arthritis patients naïve to or switched from reference rituximab.

Randomized controlled trials showed high comparability of biosimilar rituximab (bs-RTX) GP2013 to biologic originator RTX (bo-RTX). Data on effectiveness of switching from bo-RTX to bs-RTX, starting therapy with bs-RTX, and bs-RTX drug survival in real-world setting are sparse. To explore long-term drug effectiveness and survival of bs-RTX GP2013 in rheumatoid arthritis (RA) patients both naïve to and mandatory switched from bo-RTX, and to clarify reasons for treatment cessation. Retrospective observational cohort study including RA outpatient clinic patients treated with bs-RTX between 2018 and 2021 in Norway. Patients were examined and monitored using recommended measures for disease activity and patient-reported outcomes (PROs). For description of population medians and interquartile range were used. Difference between observation times was assessed with Signed-Rank test, drug survival with Kaplan-Meier survival analysis. Reasons for discontinuation were ascertained. Among 110 patients, at baseline, 88 were mandatory switched from bo-RTX and 22 were RTX-naïve. During 2-year follow-up, disease activity and PROs measures remained stable in switchers subgroup and improved in subgroup starting bs-RTX for the first time. Overall drug survival was 80.0% after 1 year and 57.7% after 2 years and was significantly higher in bs-RTX-switched than in bs-RTX-naïve patients (p = 0.036). Two most frequently reported reasons for drug discontinuation were remission (38.6%) and doctor's decision (27.1%). RA patients treated with bs-RTX had satisfactory treatment response and drug retention rates which supports equivalence of bs-RTX GP2013 to bo-RTX, both in patients naïve to and mandatory switched from bo-RTX.

Multiple infliximab biosimilar switches appear to be safe and effective in a real-world inflammatory bowel disease cohort.

BACKGROUND: Switching from originator infliximab (IFX) to biosimilar IFX is effective and safe. However, data on multiple switching are scarce. The Edinburgh inflammatory bowel disease (IBD) unit has undertaken three switch programmes: (1) Remicade to CT-P13 (2016), (2) CT-P13 to SB2 (2020), and (3) SB2 to CT-P13 (2021). OBJECTIVE: The primary endpoint of this study was to assess CT-P13 persistence following switch from SB2. Secondary endpoints included persistence stratified by the number of biosimilar switches (single, double and triple), effectiveness and safety. METHODS: We performed a prospective, observational, cohort study. All adult IBD patients on IFX biosimilar SB2 underwent an elective switch to CT-P13. Patients were reviewed in a virtual biologic clinic with protocol driven collection of clinical disease activity, C-reactive protein (CRP), faecal calprotectin (FC), IFX trough/antibody levels, and drug survival. RESULTS: 297 patients (CD n = 196 [66%], ulcerative colitis/inflammatory bowel disease unclassified n = 101, [34%]) were switched (followed-up: 7.5 months [6.8-8.1]). This was the third, second and first IFX switch for 67/297 (22.5%), 138/297 (46.5%) and 92/297 (31%) of the cohort respectively. 90.6% of patients remained on IFX during follow-up. The number of switches was not independently associated with IFX persistence after adjusting for confounders. Clinical (p = 0.77), biochemical (CRP ≤5 mg/ml; p = 0.75) and faecal biomarker (FC<250 µg/g; p = 0.63) remission were comparable at baseline, week 12 and week 24. CONCLUSION: Multiple successive switches from IFX originator to biosimilars are effective and safe in patients with IBD, irrespective of the number of IFX switches.

[Cerebrolysin in the treatment of cognitive impairment]. / Tserebrolizin v lechenii kognitivnykh narushenii.

Cognitive impairment is one of the most important problems of modern health care. Currently, according to WHO, more than 55 million people worldwide are living with dementia. Dementia is one of the leading causes of disability and addiction among older people worldwide. Even more significant is the number of patients with mild cognitive impairment who have an increased risk of progression to dementia compared to people of the same age without cognitive impairment. The number of patients with cognitive impairment has also increased due to the consequences of COVID-19. It is necessary to use drugs that not only improve cognitive functions, but also slow down their progression. One of these drugs is cerebrolysin, the effectiveness of which has been confirmed in various types of cognitive impairment. Cerebrolysin, being a preparation from the brain of a pig, belongs to the group of biological drugs. In the production of Cerebrolysin very strict measures are taken to comply with the technology, which ensures the quality and identity of the product from batch to batch. The experience of many years of clinical use of Cerebrolysin testifies not only to its high efficiency, but also to its safety. It should be taken into account that similar substances can be developed in relation to biological products - biosimilars or biosimilars, which can be considered comparable only in case of equivalent pharmacokinetic parameters, efficacy and safety.

Past, Present and (Foreseeable) Future of Biological Anti-TNF Alpha Therapy.

Due to the key role of tumor necrosis factor-alpha (TNF-α) in the pathogenesis of immunoinflammatory diseases, TNF-α inhibitors have been successfully developed and used in the clinical treatment of autoimmune disorders. Currently, five anti-TNF-α drugs have been approved: infliximab, adalimumab, golimumab, certolizumab pegol and etanercept. Anti-TNF-α biosimilars are also available for clinical use. Here, we will review the historical development as well as the present and potential future applications of anti-TNF-α therapies, which have led to major improvements for patients with several autoimmune diseases, such as rheumatoid arthritis (RA), ankylosing spondylitis (AS), Crohn's disease (CD), ulcerative colitis (UC), psoriasis (PS) and chronic endogenous uveitis. Other therapeutic areas are under evaluation, including viral infections, e.g., COVID-19, as well as chronic neuropsychiatric disorders and certain forms of cancer. The search for biomarkers able to predict responsiveness to anti-TNF-α drugs is also discussed.

Therapeutic delivery: industry update covering January 2022

This industry update covers the period from January 1 through January 31, 2022, and is based on information sourced from company press releases, scientific literature, patents and news websites. January 2022 saw Janssen and Midatech expand their collaboration on bioresorbable polymer microsphere technology for drug delivery. Takeda announced its plans to acquire UK-based Adaptate Biotherapeutics and Gandeeva raised further investment funds to support its drug discovery and development platform focused on the evaluation of protein-drug interactions. Biogen announced that it will sell its stake in a biosimilars joint venture and ABL Bio and Sanofi announced a collaboration around a novel treatment for Parkinson's disease. New regulatory announcements this month included US FDA approvals of a new insomnia treatment for Idorsia and a treatment for atopic dermatitis developed by Pfizer. Insulet gained FDA clearance for a closed-loop insulin pump and Ascendis Pharma followed up its United States approval last year for a once-weekly treatment for growth hormone deficiency with European approval. Pfizer and Ionis announced the discontinuation of the clinical development of a novel cardiovascular drug. In terms of collaborations, Novartis and Alnylam announced they will work together to explore targeted therapies to restore liver function;Scorpion Therapeutics partnered with AstraZeneca to develop novel cancer treatments and Nutriband Inc. and Kindeva Drug Delivery will work together to develop a transdermal fentanyl patch. Collaborations were also announced between Century Therapeutics and Bristol Myers Squibb and Lilly and Entos Pharmaceuticals in the areas of stem cell therapies for cancer treatment and neurology, respectively. A team from the Massachusetts Institute of Technology reported progress in developing oral mRNA treatments and West Pharmaceutical Services published a blog describing the development of a proof-of-principle system for a closed-loop feedback system targeting opioid overdose. A report on the BBC website highlighted the benefits of more sustainable inhalers.

Adalimumab Biosimilar Efficacy and Safety in a 5-Year-Old Patient with Severe Plaque Psoriasis During SARS-CoV-2 Pandemic Outbreak

BACKGROUND: Psoriasis is a chronic inflammatory disease that affects 2% of population. About 0.5–2% of psoriatic cases develop during pediatric age. In most cases, the condition is responsive to topical treatment. However, a small percentage of children require systemic treatment with conventional systemic drugs or biological agents, such as anti-tumor necrosis factor (TNF)-α. Adalimumab (ADA) is an anti-TNF-α recently approved for pediatric psoriasis in the European Union (from 4 years of age, 2015). CASE PRESENTATION: We describe our experience treating a 5-year-old female patient affected by severe plaque psoriasis with ADA biosimilar during SARS-CoV-2 pandemic outbreak also using teledermatology. CONCLUSION: The case reported in this article highlights the safety and the effectiveness of ADA biosimilar MSB11022 (Idacio®) in the treatment of a 5-year-old female affected by plaque psoriasis and paves the way to bigger trials for a more extensive use of TNF-α inhibitor biosimilars for psoriasis in pediatric population.

Pegfilgrastim Biosimilars in US Supportive Oncology: A Narrative Review of Administration Options and Economic Considerations to Maximize Patient Benefit.

Granulocyte colony-stimulating factor (G-CSF) biologics, such as pegfilgrastim, are a standard of care in supportive cancer treatment that are administered once per chemotherapy cycle to reduce the incidence of febrile neutropenia. The high cost of these biologics in the United States can be a limiting factor to accessing care; however, lower-cost pegfilgrastim biosimilars have been available for several years for patients requiring prophylaxis of febrile neutropenia. Different options for pegfilgrastim administration are also now available to accommodate specific patient preferences. As patients may want to minimize the risk of both neutropenia and SARS-CoV-2 infection, same-day administration is a pertinent option during the present COVID-19 pandemic. Therefore, individualized, patient-centered approaches and risk-management strategies should be considered when selecting the treatment and administration method for prophylaxis of febrile neutropenia. Three methods of administration would minimize hospital or clinic visits while also providing the prophylactic effect of G-CSF: same-day administration after chemotherapy, use of the US Food and Drug Administration-approved on-body injector delivering pegfilgrastim approximately 27 h after chemotherapy, or self-administration by the patient or caregiver > 24 h after chemotherapy. Choice of the specific administration option should be based on the patient's specific needs, while also considering mitigating factors, such as the economic burden associated with biologic medications and the risk of COVID-19. Pegfilgrastim biosimilars can minimize the additional financial burden on patients and the health care system during this pandemic and beyond.

Txagorrapid: Ultrarapid infusion in 30 minutes of the biosimilar of rituximab truxima- A cohort study

Background: Rituximab (anti-CD20 Ab) is the cornerstone of the treatment of non-Hodgkin B lymphomas. Infusion-related reactions (IRR) are the most common adverse effects. To reduce them, intravenous premedication with antihistamine and acetaminophen is administered prior to rituximab. If no IRR after first infusion, subsequent infusions time takes 3-6 hours. Many centers use the rapid 90-minute infusion (off-label). Since 2017 subcutaneous rituximab formulation is available, that takes 5 minutes of administration. Nevertheless, in order to reduce cost, due to approval of biosimilars, some health providers continue using intravenous rituximab. On the other hand, with COVID pandemic, an effort to reduce visits and day-care hospitals stays has been made. In the current situation, it would be convenient to reduce day-care stay and the nursing care burden. We wanted to evaluate the safety of an ultrarapid infusion of biosimilar rituximab in a total time of 30 minutes by analyzing IRR and adverse events (AE). Methods: Since November 2021, 3 cohorts of ultrafast infusion have been studied as follows: One cohort (Cohort 1) with intravenous premedication with dexchlorpheniramine and acetaminophen, followed by rituximab infusion over 1 hour, and 2 cohorts with rituximab infusion over 30 minutes: Cohort 2: with intravenous premedication, and cohort 3 with oral premedication. IRR and adverse events have been independently reviewed and graded using Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 (November 27, 2017). Results: 34 patients have been included receiving 48 rituximab infusions (16 infusions in each cohort). Median age was 64 years old (range: 51-91). Diagnostic of NHL were as follows: large b cell: 10;follicular: 13;marginal: 7;mantle cell: 1, Waldeström: 1;Ritcher transformation: 2. Rituximab infusion was in monotherapy (21), and in combination (27) with: bendamustine: 9, CHOP: 17, GEMOX: 1. Considering safety, no IRR has been observed in cohort 1 (1 hour infusion), and 1 IRR grade II in cohort 3 (30 minutes, oral premedication). Other AE were: hypertension grade I and hypotension grade I, both in cohort 2. Conclusions: Ultrarapid rituximab infusion is safe. Oral premedication is feasibly allowing a total infusion time of 30 minutes. This infusion rate alleviates day-care burden saving between 75-90% of time in each rituximab infusion, reduce day-care stay and is comfortable for the patients.

How to select a best-value biological medicine? A practical model to support hospital pharmacists.

PURPOSE: With the growing availability of biosimilars on the global market, clinicians and pharmacists have multiple off-patent biological products to choose from. Besides the competitiveness of the product's price, other criteria should be considered when selecting a best-value biological. This article aims to provide a model to facilitate transparent best-value biological selection in the off-patent biological medicines segment. SUMMARY: The presented model was developed on the basis of established multicriteria decision analysis tools for rational and transparent medicine selection, ie, the System of Objectified Judgement Analysis and InforMatrix. Criteria for the model were informed by earlier research, a literature search, and evaluation by the authors. The developed model includes up-to-date guidance on criteria that can be considered in selection and provides background on the allocation of weights that may aid hospital pharmacists and clinicians with decision-making in practice. Three main categories of criteria besides price were identified and included in the model: (1) product-driven criteria, (2) service-driven criteria, and (3) patient-driven criteria. Product-driven criteria include technical product features and licensed therapeutic indications. Service-driven criteria consist of supply conditions, value-added services, and environment and sustainability criteria. Patient-driven criteria contain product administration elements such as ease of use and service elements such as patient support programs. Relative weighting of the criteria is largely context dependent and should in a given setting be determined at the beginning of the process. CONCLUSION: The practical model described here may support hospital pharmacists and clinicians with transparent and evidence-based best-value biological selection in clinical practice.

Efficacy and Safety of Anti-TNF Biosimilars for Psoriasis in Pediatric and Geriatric Populations: A 72-Week Real-Life Study.

Purpose: To determine the efficacy and safety of adalimumab (ADA) and etanercept (ETA) biosimilars in elderly and children with psoriasis. Methods: A real-life retrospective observational study was conducted on pediatric (<18 years) and geriatric (≥65 years) psoriasis patients treated with anti-TNF biosimilar agents referring to the Psoriasis Unit of the University of Naples Federico II, Italy, from January 2018 to January 2022. At baseline, demographic characteristics (age and sex), data on psoriasis duration and severity (measured by Psoriasis Area Severity Index [PASI] and body surface area [BSA]), presence of psoriatic arthritis if applicable, comorbidities, and previous psoriasis treatments were recorded. Patients were monitored by regular follow-ups (week 12, 24, 48 and 72) through clinical and haematological assessments and adverse events (AEs) were registered. Results: A total of 11 children and 23 elderly psoriasis patients were enrolled. Concerning children, 6 (54.5%) were under ADA biosimilar and 5 (45.5%) under ETA biosimilar. ETA and ADA biosimilars were equally effective and safe for up to 72 weeks (mean PASI and BSA < 3). No significant AEs were reported, and none discontinued treatment. In the elderly, 15 (65.2%) were treated with ADA biosimilar and 8 (34.8%) with ETA biosimilar. ETA and ADA biosimilars were equally effective up to 72 weeks (mean PASI < 4 and mean BSA < 5%). AEs (mainly mild) were registered in 9 subjects (39.1%). Also, 4 (17.4%) patients discontinued biologicals for secondary lack of efficacy (3, 75%) or AEs (1, 25%). Conclusion: Our study found that ADA and ETA biosimilars are effective and safe for the treatment of moderate-to-severe psoriasis in children and the elderly. No statistically significant efficacy and safety differences were found between ADA and ETA biosimilars in both children and the elderly. Geriatric patients displayed a higher discontinuation rate and side effects than the pediatric counterpart even if without approaching statistical significance.

The second decade of anti-TNF-a therapy in clinical practice: new lessons and future directions in the COVID-19 era.

Since the late 1990s, tumor necrosis factor alpha (TNF-α) inhibitors (anti-TNFs) have revolutionized the therapy of immune-mediated inflammatory diseases (IMIDs) affecting the gut, joints, skin and eyes. Although the therapeutic armamentarium in IMIDs is being constantly expanded, anti-TNFs remain the cornerstone of their treatment. During the second decade of their application in clinical practice, a large body of additional knowledge has accumulated regarding various aspects of anti-TNF-α therapy, whereas new indications have been added. Recent experimental studies have shown that anti-TNFs exert their beneficial effects not only by restoring aberrant TNF-mediated immune mechanisms, but also by de-activating pathogenic fibroblast-like mesenchymal cells. Real-world data on millions of patients further confirmed the remarkable efficacy of anti-TNFs. It is now clear that anti-TNFs alter the physical course of inflammatory arthritis and inflammatory bowel disease, leading to inhibition of local and systemic bone loss and to a decline in the number of surgeries for disease-related complications, while anti-TNFs improve morbidity and mortality, acting beneficially also on cardiovascular comorbidities. On the other hand, no new safety signals emerged, whereas anti-TNF-α safety in pregnancy and amid the COVID-19 pandemic was confirmed. The use of biosimilars was associated with cost reductions making anti-TNFs more widely available. Moreover, the current implementation of the "treat-to-target" approach and treatment de-escalation strategies of IMIDs were based on anti-TNFs. An intensive search to discover biomarkers to optimize response to anti-TNF-α treatment is currently ongoing. Finally, selective targeting of TNF-α receptors, new forms of anti-TNFs and combinations with other agents, are being tested in clinical trials and will probably expand the spectrum of TNF-α inhibition as a therapeutic strategy for IMIDs.

AUDIT ON THE UPTAKE OF COVID-19 VACCINATION IN BIOLOGIC PATIENTS WITH AUTOIMMUNE CONDITIONS

Background/Aims Coronavirus-2 (SARS-CoV-2) has become a disastrous pandemic since its first outbreak in December 2019. Until 8th of October, 2021, more than 239 million people were infected by COVID-19 leading to over 4.8 million deaths. While vaccines and drugs are two arms in controlling the pandemic, safe and effective vaccines are one of the most reliable interventions to suppress viral transmission. Patients with specific immunological deficits, such as patients with autoimmune diseases or those receiving immunosuppressive need special attention. Besides, vaccination in these patients is problematic due to the probable suppression or over-activation of the immune system. However, there still remain questions about the efficacy and safety of vaccination in immunocompromised patients. Studies are ongoing into the safety and immunogenicity of approved of SARS-CoV-2 vaccines, with regards to immuno-deficient individuals. The aim of this audit was to check the uptake and side effects of the BNT162b2 and ChAdOx1 vaccines. Methods We collected data on 352 patients from routine clinics which included diagnosis, type of vaccine, number of doses, side effects of the vaccines and flare up of arthritis or underlying autoimmune condition. Descriptive statistics were used to analyse the data. Results Of the 352,174 (49%) were Males and 178 (51%) Females. Most common diagnosis was Rheumatoid Arthritis 181 (51%), Axial spondyloarthropathy, 80(23%), Psoriatic Arthritis 65 (18%), GCA 10 (3%), Non-Radiographic Axial Spondyloarthropathy 5 (1.4%), JIA 3 (0.9%), Sarcoidosis 1 (0.3%), and overlap 6 (2%). Medications: 227(65%) patients were on Biosimilars, 26 (7%) on Biologics, 28 (8%) Certolizumab pegol, 21 (6%) Secukinumab, 2 (0.6%) Baricitinib, 3 (0.8%) Abatacept, 29 (8%) Tocilizumab and 16 (4.5%) on Tofacitinib. Vaccination uptake: 329 patients received double dose and 8 received single dose. 15 (4.3%) patients didn't take vaccine. Reasons for not taking vaccine were severe reactions to Arthritis medication and biologics, concerned they may have severe reaction with the vaccine. Some were worried that vaccine may trigger flares, COVID-19 vaccine potentially has tracking chips, didn't trust the vaccine as not gone through enough clinical trialling, lack of any statistics on side effects of the vaccines in immunocompromised patients. Side effects: 146 patients experienced mild side effects based on CTAE5 criteria. Only 3 (2.1%) had severe side effects Grade 3 or above, this included Pulmonary embolism, Stroke, and symptomatic pleural effusion. 15(10%) reported Arthritis flare. Most common side effects were Headache 50(34%), Fatigue 32(22%, Myalgia 32(22%), Fever 30(21%), Chills 30(21%), Injection site pain 28(19%), Rhinorrhoea 11(7.5%), Lethargy 11(7.5%) and maculopapular rash 5(3.4%). Conclusion This audit highlights both the ChAdOx1 and BNT162b2 are safe for use in immune-deficient patients. Immunocompromised patients should be encouraged to take vaccines as benefits of the COVID-19 vaccination outweigh the risks and might reduce the risk of developing severe complications due to COVID-19.