INTRODUCTION/AIMS: Prospective, randomized, controlled trials of intravenous immunoglobulin (IVIG) maintenance therapy in myasthenia gravis (MG) are lacking. In this trial, we evaluated the safety and efficacy of caprylate/chromatography-purified IVIG; (IGIV-C) in patients with generalized MG undergoing standard care. METHODS: Sixty-two patients enrolled in this phase 2, multicenter, international, randomized trial (1:1 IGIV-C [2 g/kg loading dose; 1 g/kg every 3 weeks through week 21] or placebo). Efficacy was assessed by changes in Quantitative MG (QMG) score at week 24 versus baseline (primary endpoint) and percentage of patients with clinical improvement in QMG, MG Composite (MGC), and MG-Activities of Daily Living (MG-ADL) scores (secondary endpoints). Safety assessments reported all adverse events (AEs). RESULTS: The change in QMG at 24 weeks was -5.1 for IGIV-C and -3.1 for placebo (p = .187). Seventy percent of patients in the IGIV-C group had improvement in MG-ADL (≥2-point decrease) versus 40.6% in the placebo group (p = .025). Patients showing clinical improvement in QMG and MGC (≥3-point decrease) were 70.0% for IGIV-C versus 59.4% for placebo (p = .442) and 60.0% for IGIV-C versus 53.1% for placebo (p = .610). IGIV-C was well tolerated; serious AEs were similar between arms. Three of four MG exacerbations requiring hospitalizations occurred in the IGIV-C arm with one death. DISCUSSION: Several efficacy parameters showed numerical results greater than those seen in the placebo group. This was a small study and may have been underpowered to see significant differences. Additional studies may be warranted to fully determine the efficacy of IVIG maintenance therapy in MG.
- MeSH
- autoprotilátky krev MeSH
- činnosti denního života MeSH
- dospělí MeSH
- dvojitá slepá metoda MeSH
- imunologické faktory terapeutické užití škodlivé účinky aplikace a dávkování MeSH
- intravenózní imunoglobuliny * terapeutické užití škodlivé účinky aplikace a dávkování MeSH
- lidé středního věku MeSH
- lidé MeSH
- myasthenia gravis * farmakoterapie MeSH
- prospektivní studie MeSH
- receptory cholinergní * imunologie MeSH
- senioři MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze II MeSH
- multicentrická studie MeSH
- randomizované kontrolované studie MeSH
OBJECTIVE: To investigate the influence of statins on the survival outcomes of patients with non-muscle-invasive bladder cancer (NMIBC) treated with adjuvant intravesical bacille Calmette-Guérin (BCG) immunotherapy. PATIENTS AND METHODS: A retrospective cohort of consecutive patients with NMIBC who received intravesical BCG therapy from 2001 to 2020 and statins prescription were identified. Overall survival (OS), cancer-specific survival (CSS), recurrence-free survival (RFS), and progression-free survival (PFS) were analysed between the Statins Group vs No-Statins Group using Kaplan-Meier method and multivariable Cox regression. RESULTS: A total of 2602 patients with NMIBC who received intravesical BCG were identified. The median follow-up was 11.0 years. On Kaplan-Meier analysis, the Statins Group had significant better OS (P < 0.001), CSS (P < 0.001), and PFS (P < 0.001). Subgroup analysis indicated statins treatment started before BCG treatment had better CSS (P = 0.02) and PFS (P < 0.01). Upon multivariable Cox regression analysis, the 'statins before BCG' group was an independent protective factor for OS (hazard ratio [HR] 0.607, 95% confidence interval [CI] 0.514-0.716), and CSS (HR 0.571, 95% CI 0.376-0.868), but not RFS (HR 0.885, 95% CI 0.736-1.065), and PFS (HR 0.689, 95% CI 0.469-1.013). CONCLUSIONS: Statins treatment appears to offer protective effects on OS and CSS for patients with NMIBC receiving adjuvant intravesical BCG.
- MeSH
- adjuvancia imunologická terapeutické užití MeSH
- aplikace intravezikální MeSH
- BCG vakcína * terapeutické užití MeSH
- invazivní růst nádoru MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory močového měchýře neinvadující svalovinu MeSH
- nádory močového měchýře * farmakoterapie patologie mortalita MeSH
- retrospektivní studie MeSH
- senioři MeSH
- statiny * terapeutické užití MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
AIM: To evaluate the real-world comparative effectiveness and the cost-effectiveness, from a UK National Health Service perspective, of natalizumab versus fingolimod in patients with rapidly evolving severe relapsing-remitting multiple sclerosis (RES-RRMS). METHODS: Real-world data from the MSBase Registry were obtained for patients with RES-RRMS who were previously either naive to disease-modifying therapies or had been treated with interferon-based therapies, glatiramer acetate, dimethyl fumarate, or teriflunomide (collectively known as BRACETD). Matched cohorts were selected by 3-way multinomial propensity score matching, and the annualized relapse rate (ARR) and 6-month-confirmed disability worsening (CDW6M) and improvement (CDI6M) were compared between treatment groups. Comparative effectiveness results were used in a cost-effectiveness model comparing natalizumab and fingolimod, using an established Markov structure over a lifetime horizon with health states based on the Expanded Disability Status Scale. Additional model data sources included the UK MS Survey 2015, published literature, and publicly available sources. RESULTS: In the comparative effectiveness analysis, we found a significantly lower ARR for patients starting natalizumab compared with fingolimod (rate ratio [RR] = 0.65; 95% confidence interval [CI], 0.57-0.73) or BRACETD (RR = 0.46; 95% CI, 0.42-0.53). Similarly, CDI6M was higher for patients starting natalizumab compared with fingolimod (hazard ratio [HR] = 1.25; 95% CI, 1.01-1.55) and BRACETD (HR = 1.46; 95% CI, 1.16-1.85). In patients starting fingolimod, we found a lower ARR (RR = 0.72; 95% CI, 0.65-0.80) compared with starting BRACETD, but no difference in CDI6M (HR = 1.17; 95% CI, 0.91-1.50). Differences in CDW6M were not found between the treatment groups. In the base-case cost-effectiveness analysis, natalizumab dominated fingolimod (0.302 higher quality-adjusted life-years [QALYs] and £17,141 lower predicted lifetime costs). Similar cost-effectiveness results were observed across sensitivity analyses. CONCLUSIONS: This MSBase Registry analysis suggests that natalizumab improves clinical outcomes when compared with fingolimod, which translates to higher QALYs and lower costs in UK patients with RES-RRMS.
- MeSH
- analýza nákladové efektivity MeSH
- analýza nákladů a výnosů MeSH
- fingolimod hydrochlorid terapeutické užití MeSH
- imunosupresiva terapeutické užití MeSH
- lidé MeSH
- natalizumab terapeutické užití MeSH
- relabující-remitující roztroušená skleróza * farmakoterapie MeSH
- roztroušená skleróza * farmakoterapie MeSH
- státní lékařství MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Spojené království MeSH
The use of nanoparticles as a delivery system for a specific antigen could solve many limitations of mucosal vaccine applications, such as low immunogenicity, or antigen protection and stabilization. In this study, we tested the ability of nasally administered chitosan nanoparticles loaded with glycoprotein B of murine cytomegalovirus to induce an immune response in an animal model. The choice of chitosan nanoparticle type was made by in vitro evaluation of sorption efficiency and antigen release. Three types of chitosan nanoparticles were prepared: crosslinked with tripolyphosphate, coated with hyaluronic acid, and in complex with polycaprolactone. The hydrodynamic size of the nanoparticles by dynamic light scattering, zeta potential, Fourier transform infrared spectroscopy, scanning electron microscopy, stability, loading efficiency, and release kinetics with ovalbumin were evaluated. Balb/c mice were immunized intranasally using the three-dose protocol with nanoparticles, gB, and adjuvants Poly(I:C) and CpG ODN. Subsequently, the humoral and cell-mediated antigen-specific immune response was determined. On the basis of the properties of the tested nanoparticles, the cross-linked nanoparticles were considered optimal for further investigation. The results show that nanoparticles with Poly(I:C) and with gB alone raised IgG antibody levels above the negative control. In the case of mucosal IgA, only gB alone weakly induced the production of IgA antibodies compared to saline-immunized mice. The number of activated cells increased slightly in mice immunized with nanoparticles and gB compared to those immunized with gB alone or to negative control. The results demonstrated that chitosan nanoparticles could have potential in the development of mucosal vaccines.
- MeSH
- adjuvancia imunologická MeSH
- aplikace intranazální MeSH
- chitosan * chemie MeSH
- glykoproteiny MeSH
- imunizace MeSH
- imunoglobulin A MeSH
- Muromegalovirus * MeSH
- myši inbrední BALB C MeSH
- myši MeSH
- nanočástice * chemie MeSH
- slizniční imunita MeSH
- vakcíny * MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Jessenius Moderní farmakoterapie
3. aktualizované a doplněné vydání 614 stran : ilustrace ; 24 cm
Publikace se zaměřuje na možnosti farmakoterapie autoimunitních nemocí. Určeno odborné veřejnosti.
- Konspekt
- Farmacie. Farmakologie
- NLK Obory
- farmakoterapie
- alergologie a imunologie
- NLK Publikační typ
- kolektivní monografie
BACKGROUND AND OBJECTIVES: Early treatment of multiple sclerosis (MS) reduces disease activity and the risk of long-term disease progression. Effectiveness of ocrelizumab is established in relapsing MS (RMS); however, data in early RMS are lacking. We evaluated the 4-year effectiveness and safety of ocrelizumab as a first-line therapy in treatment-naive patients with recently diagnosed relapsing-remitting MS (RRMS). METHODS: ENSEMBLE was a prospective, 4-year, international, multicenter, single-arm, open-label, phase IIIb study. Patients were treatment naive, aged 18-55 years, had early-stage RRMS with a disease duration ≤3 years, Expanded Disability Status Scale (EDSS) score ≤3.5, and ≥1 clinically reported relapse(s) or ≥1 signs of brain inflammatory activity on MRI in the prior 12 months. Patients received IV ocrelizumab 600 mg every 24 weeks. Effectiveness endpoints over 192 weeks were proportion of patients with no evidence of disease activity (NEDA-3; defined as absence of relapses, 24-week confirmed disability progression [CDP], and MRI measures, with prespecified MRI rebaselining at week 8), 24-week/48-week CDP and 24-week confirmed disability improvement, annualized relapse rate (ARR), mean change in EDSS score from baseline, and safety. Cognitive status, patient-reported outcomes, and serum neurofilament light chain (NfL) were assessed. Descriptive analysis was performed on the intention-to-treat population. RESULTS: Baseline characteristics (N = 678) were consistent with early-stage RRMS (n = 539 patients, 64.6% female, age 40 years and younger; median age: 31.0 years; duration since: MS symptom onset 0.78 years, RRMS diagnosis 0.24 years; mean baseline EDSS score [SD] 1.71 [0.95]). At week 192, most of the patients had NEDA-3 (n = 394/593, 66.4%), 85.0% had no MRI activity, 90.9% had no relapses, and 81.8% had no 24-week CDP over the study duration. Adjusted ARR at week 192 was low (0.020, 95% CI 0.015-0.027). NfL levels were reduced to and remained within the healthy donor range, by week 48 and week 192, respectively. No new or unexpected safety signals were observed. DISCUSSION: Disease activity based on clinical and MRI measures was absent in most of the patients treated with ocrelizumab over 4 years in the ENSEMBLE study. Safety was consistent with the known profile of ocrelizumab. Although this single-arm study was limited by lack of a parallel group for comparison of outcome measures, the positive benefit-risk profile observed may provide confidence to adopt ocrelizumab as a first-line treatment in newly diagnosed patients with early RMS. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that adult patients with early-stage MS who were treatment naive maintained low disease activity (NEDA-3) over 4 years with ocrelizumab treatment; no new safety signals were detected. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov Identifier NCT03085810; first submitted March 16, 2017; first patient enrolled: March 27, 2017; available at clinicaltrials.gov/ct2/show/NCT03085810.
- MeSH
- dospělí MeSH
- humanizované monoklonální protilátky * terapeutické užití škodlivé účinky aplikace a dávkování MeSH
- imunologické faktory * terapeutické užití škodlivé účinky aplikace a dávkování MeSH
- lidé středního věku MeSH
- lidé MeSH
- magnetická rezonanční tomografie MeSH
- mladiství MeSH
- mladý dospělý MeSH
- posuzování pracovní neschopnosti MeSH
- progrese nemoci MeSH
- prospektivní studie MeSH
- relabující-remitující roztroušená skleróza * farmakoterapie diagnostické zobrazování MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze III MeSH
- multicentrická studie MeSH
Bakteriální lyzáty nespecificky stimulují celkovou imunitu organismu. Působí na nespecifické obranné mechanismy, což vede ke zvýšení IgA na sliznicích, fagocytární aktivitě a produkci interferonu gama. Mohou také stimulovat tvorbu specifických protilátek proti bakteriálním antigenům, které tvoří přípravek. V mnoha klinických studiích bylo prokázáno, že perorální bakteriální lyzáty snižují četnost opakovaných respiračních infekcí u dětí i dospělých a snižují potřebu podávání antibiotik.
Bacterial lysates stimulate the general immunity of the body in a non-specific way. They act on non-specific defense mechanisms, leading to an increase IgA in mucous membranes, phagocytic activity and interferon gamma production. They can also stimulate the production of specific antibodies against the bacterial antigens that make up the preparation. In many clinical trials, oral bacterial lysates have been shown to decrease the risk of recurrent respiratory infections in children and adults and reduce the need for antibiotics.
- Klíčová slova
- bakteriální lyzáty,
- MeSH
- adaptivní imunita účinky léků MeSH
- adjuvancia imunologická * aplikace a dávkování farmakologie terapeutické užití MeSH
- infekce dýchací soustavy imunologie patologie prevence a kontrola MeSH
- infekce močového ústrojí imunologie prevence a kontrola MeSH
- infekce reprodukčního traktu imunologie MeSH
- lidé MeSH
- přirozená imunita účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
Background: We report a successful wound treatment of a chronic ulcer with bone exposure using a somehow forgotten technique of creating burr holes into the bone. Most clinics would promote flap surgery to cover wounds with bone exposure, however, in some cases invasive surgery is not mandatory. We bring up an alternative treatment for such cases. Case: We report a case of chronic ulcers on both lower extremities in a 43-year-old Caucasian male. He suffers from a leukocytoclastic vasculitis and sarcoidosis which is medicated by immunosuppressive medication. The patient‘s wounds were initially treated with mechanical debridement and split-thickness skin grafts, however, his wounds tended to worsen the more they were manipulated and finally resulted in tibial bone exposure. After levelling up his immune suppressive drugs, the wounds finally stabilized but didn’t heal after several weeks of follow-up. The wound was ultimately treated by placing burr holes in the underlying cortical bone. Conclusion: Chronic ulcers with bone exposure at the lower leg are challenging to treat. They often require local or free flap surgery. In some cases, because of underlying systemic disease, it is mandatory to stay away from invasive flap surgery. With this case, we like to put under attention an old technique of decorticating the exposed bone to promote secondary wound healing. It has been described mainly for scalp injuries, however, we have proven the viability of this technique for pretibial wounds as well.
- MeSH
- bércové vředy chirurgie etiologie patologie terapie MeSH
- dospělí MeSH
- imunosupresiva škodlivé účinky MeSH
- komorbidita MeSH
- lidé MeSH
- poranění dolní končetiny chirurgie komplikace patologie terapie MeSH
- terapie neúspěšná MeSH
- tibie * chirurgie patologie zranění MeSH
- záchrana končetiny metody MeSH
- zákroky plastické chirurgie * metody MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
Ofatumumab představuje první plně humánní anti-CD20 monoklonální protilátku, vyvinutou pro subkutánní autoaplikaci v měsíčních intervalech. Je určen k terapii aktivní relabující-remitující RS (RR-RS) a u pacientů se známkami nepříznivé prognózy nemoci ho lze uplatnit v první linii léčby. V registračních klinických studiích prokázal jasnou superioritu oproti teriflunomidu a data z extenzí klinických hodnocení potvrzují jeho setrvalou účinnost, příznivý bezpečnostní profil i vysokou míru adherence pacientů k léčbě. Z pohledu pacienta se jedná o atraktivní možnost terapie vysoce účinným lékem s jednoduchou podkožní aplikací v domácím prostředí, bez nutnosti premedikace. Ofatumumab splňuje předpoklady moderní farmakoterapie a je jedním z průlomových přípravků, který může významně zlepšit prognózu pacientů s RR-RS.
Ofatumumab represents the first fully human anti-CD20 monoclonal antibody, developed for subcutaneous self-administration once a month. It is indicated for the treatment of active relapsing-remitting multiple sclerosis (RR-MS) and can be used as a first-line therapy in patients with negative prognostic factors suggestive of an unfavorable disease course. Ofatumumab demonstrated clear superiority over teriflunomide in registration clinical trials and long-term data from open-label extension studies which confirmed its sustained efficacy, favorable safety profile, and also a high level of patient compliance. From the patient‘s point of view, it is an attractive treatment option with a high-efficacy drug that is easy to administer via subcutaneous injection at home, requiring no premedication. Ofatumumab meets the requirements of modern pharmacotherapy and is one of the breakthrough drugs that can significantly improve the prognosis of patients with RR-MS.
- Klíčová slova
- ofatumumab,
- MeSH
- adherence k farmakoterapii MeSH
- antigeny CD20 škodlivé účinky terapeutické užití MeSH
- humanizované monoklonální protilátky * škodlivé účinky terapeutické užití MeSH
- imunosupresiva terapeutické užití MeSH
- injekce subkutánní MeSH
- klinická studie jako téma MeSH
- lidé MeSH
- relabující-remitující roztroušená skleróza farmakoterapie MeSH
- Check Tag
- lidé MeSH
