Effectiveness and safety of vedolizumab for treatment of Crohn's disease : a systematic review and meta-analysis

Introduction: The aim of this systematic review (SR) and meta-analysis was to assess the efficacy and safety of vedolizumab in the treatment of Crohn’s disease (CD). Material and methods: A systematic literature search was conducted in Medline/PubMed, Embase and Cochrane Library until 25 January, 2015. Included studies were critically appraised according to the PRISMA protocol. Assessment in specified subgroups of CD patients and meta-analysis with Revman software were performed. Results: Two randomized controlled trial (RCTs) were included in a meta-analysis for the induction phase of therapy: GEMINI II and GEMINI III. The clinical response was significantly higher for patients who received vedolizumab compared to placebo in the general population (risk benefit (RB) = 1.48; p = 0.0006) and in both analyzed subgroups: patients with previous failure of anti-TNFs treatment (RB = 1.51; p = 0.006) and patients naive to earlier anti-TNFs (RB = 1.41; p = 0.001). The clinical remission in the general population and subpopulation of TNF-antagonist naive patients was significantly higher for patients who received vedolizumab compared to placebo (RB = 1.77; p = 0.003; RB = 2.29; p = 0.0004; respectively). Meta-analysis for adverse events, serious adverse events (SAEs) and serious infections, revealed that vedolizumab was as safe as placebo in the induction phase of therapy. Conclusions: The clinical response was significantly higher for patients who received vedolizumab in the general population and in both analyzed subgroups of patients. The clinical remission in the general population and subpopulation of TNF-antagonist naive patients was significantly higher for vedolizumab, but no significant differences were revealed in the subgroup of patients with previous TNF antagonist failure

Capturing the value of vaccination within health technology assessment and health economics:Literature review and novel conceptual framework

Background: Vaccination provides significant health gains to individuals and society and can potentially improve health equity, healthcare systems and national economies. Policy decisions, however, are rarely informed by comprehensive economic evaluations (EE) including vaccination's wide-ranging value. The objective of this analysis was to focus on health technology assessment systems to identify relevant value concepts in order to improve current EE of non-pandemic vaccines. Methods: Following a literature review, a novel Value of Vaccination (VoV) framework was developed with experts in vaccine EE from developed countries with established health technology assessment systems. Results: Forty-four studies presenting value frameworks or concepts applicable to vaccination were included. Eighteen unique value concepts relevant to EE were identified and defined. These were categorised within the VoV framework using three dimensions, moving from a narrow payer perspective to a more expansive and societal perspective. The dimensions were: (I) conventional payer perspective concepts (e.g., health gains in vaccinees, direct medical costs); (II) conventional societal perspective concepts (e.g., indirect health/economic gains to caregivers/households, productivity in vaccinees); and (III) novel societal concepts (e.g., financial risk protection, peace of mind, societal health gains, healthcare systems security, political stability, social equity and macroeconomic gains). While good quality evidence and methods are available to support concepts in Dimensions I and II, further work is needed to generate the required evidence for vaccination impact on Dimension III concepts. Conclusions: The devastating effect on nations of the COVID-19 pandemic has helped to highlight the potential far-reaching benefits that many vaccination programmes can offer. This VoV framework is particularly relevant to policy decisions considering EE, and the potential future expansion of non-pandemic vaccination value considerations. The framework helps to understand and compare current value considerations across countries and payer versus societal perspectives. It provides decision-makers with a transparent and logical path to broaden consideration of VoV in EE. (C) 2022 GlaxoSmithKline Biologicals S.A. Published by Elsevier Ltd

Chemoimmunotherapy of neuroblastoma – application of anti-GD2 ganglioside antibody 14G2a and focal adhesion kinase inhibitor TAE226 in experiments on human neuroblastoma cell lines in vitro.

Neuroblastoma (NB) to jeden z najczęściej występujących guzów litych u dzieci. Rokowania u dzieci będących w grupie najwyższego ryzyka, która stanowi aż ponad 50% przypadków chorych, są bardzo słabe, ponieważ mniej niż 30% pacjentów z tej grupy uzyskuje długie przeżycia. Z powodu stosowania coraz bardziej agresywnych terapii i jednoczesnego - wciąż niepomyślnego - rokowania u dzieci zakwalifikowanych do grupy wysokiego ryzyka, wciąż poszukuje się nowych strategii terapeutycznych. Zaliczyć można do nich między innymi immunoterapię. Przykładem immunoterapii jest stosowanie przeciwciał monoklonalnych (mAb) przeciwko gangliozydowi GD2 ulegającemu wysokiej ekspresji na komórkach neuroblastoma. Prowadzi się też badania mające na celu hamowanie aktywności kinazy kontaktów zogniskowanych, której nadekspresja występuje między innymi w neuroblastoma, a która jest zaangażowana w wiele procesów komórek nowotworowych, np.: w przerzutowanie. Coraz częściej bada się też skuteczność terapii łączonych, które mogą dawać lepsze rezultaty, a jednocześnie mogą stwarzać możliwość używania mniejszych stężeń czynników terapeutycznych.Uzyskane w tej pracy wyniki wykazały, że przeciwciało 14G2a wiążące gangliozyd GD2 zmniejsza żywotność i zmienia morfologię komórek ludzkiej linii neuroblastoma IMR-32 oraz CHP-134, a ponadto hamuje przyczepność komórek wyżej wymienionych linii oraz linii BE(2)-C do wybranych białek macierzy zewnątrzkomórkowej: lamininy, kolagenu IV, fibronektyny. Ponadto wykazano hamowanie żywotności komórek IMR-32 oraz CHP-134 po traktowaniu ich inhibitorem białka FAK: TAE226 oraz zmierzono zwiększony efekt hamowania żywotności komórek przez inhibitor po połączeniu go z przeciwciałem 14G2a. Wykazano także zmiany w poziomie białka FAK oraz jego ufosforylowanej na tyrozynie 397 formy po zastosowaniu TAE226 w stężeniu 0,3 µM, 14G2a w stężeniu 40 µg/ml oraz ich kombinacji.Uzyskane wyniki przyczyniły się do poszerzenia wiedzy dotyczącej oddziaływania przeciwciała 14G2a oraz inhibitora TAE226 na komórki neuroblastoma. Jednocześnie zachęcają one do dalszych badań zmierzających do lepszego poznania mechanizmów procesów zachodzących w tych komórkach.Neuroblastoma (NB) is the most frequent solid tumor of childhood. It originates from sympathetic nervous system. Prognosis for patients in the most advanced stage, which represents more than 50% of cases, is still poor, as less then 30% of children from this group achive improvement for long time. Despite the use of aggressive therapies, patients with high risk neuroblastoma have poor prognosis. Therefore scientists and doctors are looking for new therapeutic strategies, including immunotherapy. Passive immunotherapy with monoclonal anti-GD2 ganglioside is an important field of current research. The GD2 ganglioside is highly expressed on neuroblastoma cells. There is some research in which inhibition of focal adhesion kinase is investigated. FAK protein is upregulated in neuroblastoma cells and is involved in many processes associated with carcinogenesis, for example metastasis. Also, new strategies with combined drugs are tested to improve the efficacy of therapy, and simultaneously to create the opportunity of lowering the concentration of agents used.The results of my work have shown that the 14G2a antibody decreases viability and changes morphology of IMR-32 and CHP-134 human neuroblastoma cells, and it inhibits adhesion of IMR-32, CHP-134 and BE(2)-C cells to extracellular matrix proteins. Furthermore, the results have shown decrease of viability of IMR-32 and CHP-134 cells after treatment with TAE226. Even greater effect was shown after combined treatment with TAE226 and the 14G2a antibody. Moreover, changes in the expression level of FAK protein and its phosphorylation on tyrosine 397 were observed after treatment with TAE226 (in concentration of 0,3 µM), 14G2a (in concentration of 40µg/ml) and their combination.Taken together, these results contribute to our knowledge about the influence of the 14G2a mAb and TAE226 inhibitor on neuroblastoma cells. They encourage further studies to better understand mechanisms of processes in these cells

Efficacy and Safety of Avatrombopag in Patients with Chronic Immune Thrombocytopenia : A Systematic Literature Review and Network Meta-Analysis

INTRODUCTION: A network meta-analysis (NMA) was performed to assess the efficacy and safety of avatrombopag, relative to eltrombopag, romiplostim, and fostamatinib, for patients with chronic immune thrombocytopenia (ITP) not responding adequately to corticosteroids. METHODS: A systematic search of publication and clinical trial databases was conducted to identify relevant randomized controlled trials (RCTs) and observational studies. Data from eligible studies were extracted and analyzed in a Bayesian framework using relative effect sizes vs placebo. Outcomes included durable platelet response; need for rescue therapy; reduction in use of concomitant ITP medication; incidence of any or World Health Organization (WHO) grade 2–4 bleeding events, and any adverse events. Results were reported as odds ratios or incidence rate ratios (IRR) with 95% credible intervals (CrIs). RESULTS: The NMA included seven phase 3 RCTs. Compared with placebo, avatrombopag was associated with statistically significant improvements in durable platelet response, reduction in use of concomitant ITP medication, and incidence of any bleeding events. Statistically significant differences vs placebo were also observed for durable platelet response and need for rescue therapy (eltrombopag, romiplostim, and fostamatinib); reduction in use of concomitant ITP medication (eltrombopag and romiplostim); incidence of any bleeding events (fostamatinib); and incidence of WHO grade 2–4 bleeding events (romiplostim and fostamatinib). No statistically significant differences were observed for any adverse events. Avatrombopag was associated with a statistically significant lower incidence of any bleeding events vs eltrombopag (IRR 0.38 [95% CrI 0.19, 0.75]) and romiplostim (IRR 0.38 [95% Crl 0.17, 0.86]); no other between-treatment differences were observed. CONCLUSION: In this NMA, avatrombopag significantly increased the chance of achieving durable platelet response and reducing the use of concomitant ITP medication vs placebo, and significantly reduced the incidence of any bleeding events compared with placebo, eltrombopag, and romiplostim. The study aims to help guide clinicians managing patients with chronic ITP and insufficient response to previous treatment. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12325-021-01752-4