804 research outputs found
Postępy w badaniach nad mechanizmem działania IVIg
Cząsteczka IgG stanowi główny składnik dożylnych preparatów
immunoglobulin (IVIg, intravenous immune globulin). Komercyjne
preparaty IVIg pochodzą od grupy dawców, w wyniku czego
zawierają również niewielkie ilości przeciwciał IgA, IgM, a także
cytokiny Th2 oraz antagonistów cytokin. Substancje te również
wpływają na efekt terapeutyczny. Podstawowe znaczenie dla działania
IVIg mają: komórki T, cytokiny, zjawisko przechodzenia komórek
odpornościowych przez błony biologiczne, komórki B, dopełniacz
oraz receptory Fc. Stwierdzono, że IVIg inaktywują autoreaktywne
komórki T poprzez współzawodniczenie i przerywanie
ich interakcji z komórkami prezentującymi antygen. Wydaje się,
że IVIg przywracają również równowagę w działaniu cytokin -
w badaniach wykazano, że IVIg zawierają przeciwciała i antagonistów
dla cytokin prozapalnych. Dodatkowo, uważa się, że IVIg
ingeruje i zapobiega przechodzeniu autoodpornościowych –komórek
T przez barierę krew-nerw. Badano efekty działania egzogennych
przeciwciał na komórki B. Uważa się, że IVIg zmniejszają
produkcję przeciwciał przez komórki B, zakłócają proliferację komórek
B poprzez blokadę receptorów powierzchniowych komórki
i zapobiegają aktywacji pewnych podtypów komórek B. Ponadto
IVIg mogą wpływać na odporność wrodzoną poprzez mechanizm
blokowania w kaskadzie aktywacji dopełniacza oraz blokowanie
aktywności, w której pośredniczy receptor Fc, co powoduje zmniejszenie aktywności makrofagów. Podsumowując, IVIg charakteryzują
się licznymi mechanizmami działania, których efekty kumulują
się w celu ograniczenia odpowiedzi immunologicznej. Może
to być istotne w leczeniu zaburzeń nerwowo-mięśniowych oraz
neuropatii immunologicznych.
Polski Przegląd Neurologiczny 2009; 5 (4): 208-21
The adenosinergic signaling in the pathogenesis and treatment of multiple sclerosis
Multiple sclerosis (MS) is a highly disabling, progressive neurodegenerative disease with no curative treatment available. Although significant progress has been made in understanding how MS develops, there remain aspects of disease pathogenesis that are yet to be fully elucidated. In this regard, studies have shown that dysfunctional adenosinergic signaling plays a pivotal role, as patients with MS have altered levels adenosine (ADO), adenosine receptors and proteins involved in the generation and termination of ADO signaling, such as CD39 and adenosine deaminase (ADA). We have therefore performed a literature review regarding the involvement of the adenosinergic system in the development of MS and propose mechanisms by which the modulation of this system can support drug development and repurposing
Multiple sclerosis: time for early treatment with high-efficacy drugs
This review addresses current changes in the approach to treating patients with multiple sclerosis (MS). The widely practiced approach of utilizing agents with lower treatment efficacy (LETA) at onset with subsequent escalation has been challenged by new data suggesting that MS patients derive greater benefit when therapy is initiated with high-efficacy treatment agents (HETA). Several recent studies compared treatment efficacy and safety of early administration of HETA versus LETA. The results of randomized, double blind, phase III studies with LETA as a control arm and population-based larger and longer studies using propensity scoring, marginal structural modeling and weighted cumulative exposure analysis support the benefit of early treatment with HETA. Patients initiating their treatment with HETA, regardless of prognostic factors and MRI burden at baseline, showed significantly lower annualized relapse rate (ARR) and reduced disability progression in follow-up periods of up to 10–15 years. Moreover, the safety profile of recently approved HETA ameliorates concerns about off-target effects associated with a number of earlier high-efficacy drugs. Patient perception has also changed with an increasing preference for medication profiles that both improve symptoms and prevent disease progression. Accumulating data from randomized studies and the results of large population-based studies demonstrating short-term and longer-term patient benefits support the view that HETA should be more widely used. The adoption of early treatment with HETA capitalizes on a window of opportunity for anti-inflammatory drugs to maximally impact disease pathology and heralds a sea change in clinical practice toward pro-active management and away from a philosophy routed in generating clinical benefit as a consequence of treatment failure
Safety and Tolerability of Intravenous Immunoglobulin in Chronic Inflammatory Demyelinating Polyneuropathy:Results of the ProCID Study
Background and Aims: The ProCID study evaluated the efficacy and safety of three doses of a 10% liquid intravenous immunoglobulin (IVIg) preparation (panzyga®) in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). This report describes the safety findings. Methods: Patients were randomised to receive a 2.0 g/kg induction dose followed by maintenance doses of either 0.5, 1.0 or 2.0 g/kg IVIg every 3 weeks over 24 weeks. Results:All 142 enrolled patients were included in the safety analyses. In total, 286 treatment-emergent adverse events (TEAEs) were reported in 89 patients, of which 173 (60.5%) were considered treatment-related. Most TEAEs were of mild severity. Eleven serious TEAEs were reported in 6 patients. Two serious TEAEs in one patient (headache and vomiting) were considered related to treatment, which resolved without study discontinuation. No treatment-related thrombotic events, haemolytic transfusion reactions or deaths occurred. One patient discontinued the study due to a TEAE (allergic dermatitis) probably related to IVIg. Headache was the only dose-dependent TEAE, with incidences ranging from 2.9 to 23.7%, the incidence of all other TEAEs was similar across treatment groups. Most TEAEs were associated with the induction dose infusion, and the rate of TEAEs decreased thereafter. The median (IQR) daily IVIg dose was 78 (64–90) g, and 94.4% of patients tolerated the maximal infusion rate of 0.12 ml/kg/min without pre-medication. Interpretation:Infusions of 10% IVIg at doses up to 2.0 g/kg with high infusion rates were safe and well tolerated in patients with CIDP. Clinical trial numbers: EudraCT 2015-005443-14, NCT02638207.</p
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