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MeSH: humanizované monoklonální protilátky-aplikace a dávkování

1 042 záznamů v Medvik Filtry

Článek

Ocrelizumab in Early-Stage Relapsing-Remitting Multiple Sclerosis: The Phase IIIb ENSEMBLE 4-Year, Single-Arm, Open-Label Trial

Hartung, Hans-Peter
Autor Autorita ORCID From the Department of Neurology (H.-P.H.), UKD, Centre of Neurology and Neuropsychiatry and LVR-Klinikum, Heinrich-Heine University Düsseldorf, Germany Brain and Mind Centre (H.-P.H.), University of Sydney, Australia Department of Neurology (H.-P.H.), Palacky University Olomouc, Czech Republic Department of Neurology (R.H.B.B.), Jacobs School of Medicine and Biomedical Sciences, University of Buffalo, NY Department of Neurology (T.B.), Medical University of Vienna, Comprehensive Center for Clinical Neurosciences and Mental Health, Austria Mellen Center for MS (R.A.B.), Cleveland Clinic, OH Neurocentre Magendie INSERM (B.B.), Université de Bordeaux, France Department of Neurology (W.M.C.), Sir Charles Gairdner Hospital, Perron Institute for Neurological and Translational Science, The University of Western Australia, Nedlands Department of Medicine and the Ottawa Hospital Research Institute (M.S.F.), University of Ottawa, Ontario, Canada Department of Neurology (T.H.), Akershus University Hospital, Lørenskog Institute of Clinical Medicine (T.H.), University of Oslo, Norway Department of Neurology (R.K.), Hacettepe University Faculty of Medicine, Ankara, Turkey Centre d'Esclerosi Mútiple de Catalunya (Cemcat) (C.N.), Vall d'Hebron Hospital Universitari, Barcelona, Spain Department of Medical and Surgical Sciences and Advanced Technologies (F.P.), GF Ingrassia, Neuroscience Section and Multiple Sclerosis Centre, University of Catania PO Policlinico G Rodolico, Italy Loyola University Chicago (A.P.R.), IL Department of Neurology (L.V.), AZ Sint-Jan Brugge-Oostende, Belgium Department of Neurology (T.V.), University of Colorado School of Medicine, Aurora Medical Image Analysis Center (MIAC AG) (J.W.), Department of Biomedical Engineering, University of Basel F. Hoffmann-La Roche Ltd (J.W., S.C., K.K., T.K., I.K., C.R., G.-A.T.), Basel, Switzerland and Department of Neurology (J.K.), VU University Medical Centre, Amsterdam, the Netherlands
Benedict, Ralph H B
Autor Benedict, Ralph H B From the Department of Neurology (H.-P.H.), UKD, Centre of Neurology and Neuropsychiatry and LVR-Klinikum, Heinrich-Heine University Düsseldorf, Germany Brain and Mind Centre (H.-P.H.), University of Sydney, Australia Department of Neurology (H.-P.H.), Palacky University Olomouc, Czech Republic Department of Neurology (R.H.B.B.), Jacobs School of Medicine and Biomedical Sciences, University of Buffalo, NY Department of Neurology (T.B.), Medical University of Vienna, Comprehensive Center for Clinical Neurosciences and Mental Health, Austria Mellen Center for MS (R.A.B.), Cleveland Clinic, OH Neurocentre Magendie INSERM (B.B.), Université de Bordeaux, France Department of Neurology (W.M.C.), Sir Charles Gairdner Hospital, Perron Institute for Neurological and Translational Science, The University of Western Australia, Nedlands Department of Medicine and the Ottawa Hospital Research Institute (M.S.F.), University of Ottawa, Ontario, Canada Department of Neurology (T.H.), Akershus University Hospital, Lørenskog Institute of Clinical Medicine (T.H.), University of Oslo, Norway Department of Neurology (R.K.), Hacettepe University Faculty of Medicine, Ankara, Turkey Centre d'Esclerosi Mútiple de Catalunya (Cemcat) (C.N.), Vall d'Hebron Hospital Universitari, Barcelona, Spain Department of Medical and Surgical Sciences and Advanced Technologies (F.P.), GF Ingrassia, Neuroscience Section and Multiple Sclerosis Centre, University of Catania PO Policlinico G Rodolico, Italy Loyola University Chicago (A.P.R.), IL Department of Neurology (L.V.), AZ Sint-Jan Brugge-Oostende, Belgium Department of Neurology (T.V.), University of Colorado School of Medicine, Aurora Medical Image Analysis Center (MIAC AG) (J.W.), Department of Biomedical Engineering, University of Basel F. Hoffmann-La Roche Ltd (J.W., S.C., K.K., T.K., I.K., C.R., G.-A.T.), Basel, Switzerland and Department of Neurology (J.K.), VU University Medical Centre, Amsterdam, the Netherlands
Berger, Thomas
Autor Berger, Thomas ORCID From the Department of Neurology (H.-P.H.), UKD, Centre of Neurology and Neuropsychiatry and LVR-Klinikum, Heinrich-Heine University Düsseldorf, Germany Brain and Mind Centre (H.-P.H.), University of Sydney, Australia Department of Neurology (H.-P.H.), Palacky University Olomouc, Czech Republic Department of Neurology (R.H.B.B.), Jacobs School of Medicine and Biomedical Sciences, University of Buffalo, NY Department of Neurology (T.B.), Medical University of Vienna, Comprehensive Center for Clinical Neurosciences and Mental Health, Austria Mellen Center for MS (R.A.B.), Cleveland Clinic, OH Neurocentre Magendie INSERM (B.B.), Université de Bordeaux, France Department of Neurology (W.M.C.), Sir Charles Gairdner Hospital, Perron Institute for Neurological and Translational Science, The University of Western Australia, Nedlands Department of Medicine and the Ottawa Hospital Research Institute (M.S.F.), University of Ottawa, Ontario, Canada Department of Neurology (T.H.), Akershus University Hospital, Lørenskog Institute of Clinical Medicine (T.H.), University of Oslo, Norway Department of Neurology (R.K.), Hacettepe University Faculty of Medicine, Ankara, Turkey Centre d'Esclerosi Mútiple de Catalunya (Cemcat) (C.N.), Vall d'Hebron Hospital Universitari, Barcelona, Spain Department of Medical and Surgical Sciences and Advanced Technologies (F.P.), GF Ingrassia, Neuroscience Section and Multiple Sclerosis Centre, University of Catania PO Policlinico G Rodolico, Italy Loyola University Chicago (A.P.R.), IL Department of Neurology (L.V.), AZ Sint-Jan Brugge-Oostende, Belgium Department of Neurology (T.V.), University of Colorado School of Medicine, Aurora Medical Image Analysis Center (MIAC AG) (J.W.), Department of Biomedical Engineering, University of Basel F. Hoffmann-La Roche Ltd (J.W., S.C., K.K., T.K., I.K., C.R., G.-A.T.), Basel, Switzerland and Department of Neurology (J.K.), VU University Medical Centre, Amsterdam, the Netherlands
Bermel, Robert A
Autor Bermel, Robert A ORCID From the Department of Neurology (H.-P.H.), UKD, Centre of Neurology and Neuropsychiatry and LVR-Klinikum, Heinrich-Heine University Düsseldorf, Germany Brain and Mind Centre (H.-P.H.), University of Sydney, Australia Department of Neurology (H.-P.H.), Palacky University Olomouc, Czech Republic Department of Neurology (R.H.B.B.), Jacobs School of Medicine and Biomedical Sciences, University of Buffalo, NY Department of Neurology (T.B.), Medical University of Vienna, Comprehensive Center for Clinical Neurosciences and Mental Health, Austria Mellen Center for MS (R.A.B.), Cleveland Clinic, OH Neurocentre Magendie INSERM (B.B.), Université de Bordeaux, France Department of Neurology (W.M.C.), Sir Charles Gairdner Hospital, Perron Institute for Neurological and Translational Science, The University of Western Australia, Nedlands Department of Medicine and the Ottawa Hospital Research Institute (M.S.F.), University of Ottawa, Ontario, Canada Department of Neurology (T.H.), Akershus University Hospital, Lørenskog Institute of Clinical Medicine (T.H.), University of Oslo, Norway Department of Neurology (R.K.), Hacettepe University Faculty of Medicine, Ankara, Turkey Centre d'Esclerosi Mútiple de Catalunya (Cemcat) (C.N.), Vall d'Hebron Hospital Universitari, Barcelona, Spain Department of Medical and Surgical Sciences and Advanced Technologies (F.P.), GF Ingrassia, Neuroscience Section and Multiple Sclerosis Centre, University of Catania PO Policlinico G Rodolico, Italy Loyola University Chicago (A.P.R.), IL Department of Neurology (L.V.), AZ Sint-Jan Brugge-Oostende, Belgium Department of Neurology (T.V.), University of Colorado School of Medicine, Aurora Medical Image Analysis Center (MIAC AG) (J.W.), Department of Biomedical Engineering, University of Basel F. Hoffmann-La Roche Ltd (J.W., S.C., K.K., T.K., I.K., C.R., G.-A.T.), Basel, Switzerland and Department of Neurology (J.K.), VU University Medical Centre, Amsterdam, the Netherlands
Brochet, Bruno
Autor Brochet, Bruno ORCID From the Department of Neurology (H.-P.H.), UKD, Centre of Neurology and Neuropsychiatry and LVR-Klinikum, Heinrich-Heine University Düsseldorf, Germany Brain and Mind Centre (H.-P.H.), University of Sydney, Australia Department of Neurology (H.-P.H.), Palacky University Olomouc, Czech Republic Department of Neurology (R.H.B.B.), Jacobs School of Medicine and Biomedical Sciences, University of Buffalo, NY Department of Neurology (T.B.), Medical University of Vienna, Comprehensive Center for Clinical Neurosciences and Mental Health, Austria Mellen Center for MS (R.A.B.), Cleveland Clinic, OH Neurocentre Magendie INSERM (B.B.), Université de Bordeaux, France Department of Neurology (W.M.C.), Sir Charles Gairdner Hospital, Perron Institute for Neurological and Translational Science, The University of Western Australia, Nedlands Department of Medicine and the Ottawa Hospital Research Institute (M.S.F.), University of Ottawa, Ontario, Canada Department of Neurology (T.H.), Akershus University Hospital, Lørenskog Institute of Clinical Medicine (T.H.), University of Oslo, Norway Department of Neurology (R.K.), Hacettepe University Faculty of Medicine, Ankara, Turkey Centre d'Esclerosi Mútiple de Catalunya (Cemcat) (C.N.), Vall d'Hebron Hospital Universitari, Barcelona, Spain Department of Medical and Surgical Sciences and Advanced Technologies (F.P.), GF Ingrassia, Neuroscience Section and Multiple Sclerosis Centre, University of Catania PO Policlinico G Rodolico, Italy Loyola University Chicago (A.P.R.), IL Department of Neurology (L.V.), AZ Sint-Jan Brugge-Oostende, Belgium Department of Neurology (T.V.), University of Colorado School of Medicine, Aurora Medical Image Analysis Center (MIAC AG) (J.W.), Department of Biomedical Engineering, University of Basel F. Hoffmann-La Roche Ltd (J.W., S.C., K.K., T.K., I.K., C.R., G.-A.T.), Basel, Switzerland and Department of Neurology (J.K.), VU University Medical Centre, Amsterdam, the Netherlands
Carroll, William M
Autor Carroll, William M ORCID From the Department of Neurology (H.-P.H.), UKD, Centre of Neurology and Neuropsychiatry and LVR-Klinikum, Heinrich-Heine University Düsseldorf, Germany Brain and Mind Centre (H.-P.H.), University of Sydney, Australia Department of Neurology (H.-P.H.), Palacky University Olomouc, Czech Republic Department of Neurology (R.H.B.B.), Jacobs School of Medicine and Biomedical Sciences, University of Buffalo, NY Department of Neurology (T.B.), Medical University of Vienna, Comprehensive Center for Clinical Neurosciences and Mental Health, Austria Mellen Center for MS (R.A.B.), Cleveland Clinic, OH Neurocentre Magendie INSERM (B.B.), Université de Bordeaux, France Department of Neurology (W.M.C.), Sir Charles Gairdner Hospital, Perron Institute for Neurological and Translational Science, The University of Western Australia, Nedlands Department of Medicine and the Ottawa Hospital Research Institute (M.S.F.), University of Ottawa, Ontario, Canada Department of Neurology (T.H.), Akershus University Hospital, Lørenskog Institute of Clinical Medicine (T.H.), University of Oslo, Norway Department of Neurology (R.K.), Hacettepe University Faculty of Medicine, Ankara, Turkey Centre d'Esclerosi Mútiple de Catalunya (Cemcat) (C.N.), Vall d'Hebron Hospital Universitari, Barcelona, Spain Department of Medical and Surgical Sciences and Advanced Technologies (F.P.), GF Ingrassia, Neuroscience Section and Multiple Sclerosis Centre, University of Catania PO Policlinico G Rodolico, Italy Loyola University Chicago (A.P.R.), IL Department of Neurology (L.V.), AZ Sint-Jan Brugge-Oostende, Belgium Department of Neurology (T.V.), University of Colorado School of Medicine, Aurora Medical Image Analysis Center (MIAC AG) (J.W.), Department of Biomedical Engineering, University of Basel F. Hoffmann-La Roche Ltd (J.W., S.C., K.K., T.K., I.K., C.R., G.-A.T.), Basel, Switzerland and Department of Neurology (J.K.), VU University Medical Centre, Amsterdam, the Netherlands
Freedman, Mark S
Autor Freedman, Mark S ORCID From the Department of Neurology (H.-P.H.), UKD, Centre of Neurology and Neuropsychiatry and LVR-Klinikum, Heinrich-Heine University Düsseldorf, Germany Brain and Mind Centre (H.-P.H.), University of Sydney, Australia Department of Neurology (H.-P.H.), Palacky University Olomouc, Czech Republic Department of Neurology (R.H.B.B.), Jacobs School of Medicine and Biomedical Sciences, University of Buffalo, NY Department of Neurology (T.B.), Medical University of Vienna, Comprehensive Center for Clinical Neurosciences and Mental Health, Austria Mellen Center for MS (R.A.B.), Cleveland Clinic, OH Neurocentre Magendie INSERM (B.B.), Université de Bordeaux, France Department of Neurology (W.M.C.), Sir Charles Gairdner Hospital, Perron Institute for Neurological and Translational Science, The University of Western Australia, Nedlands Department of Medicine and the Ottawa Hospital Research Institute (M.S.F.), University of Ottawa, Ontario, Canada Department of Neurology (T.H.), Akershus University Hospital, Lørenskog Institute of Clinical Medicine (T.H.), University of Oslo, Norway Department of Neurology (R.K.), Hacettepe University Faculty of Medicine, Ankara, Turkey Centre d'Esclerosi Mútiple de Catalunya (Cemcat) (C.N.), Vall d'Hebron Hospital Universitari, Barcelona, Spain Department of Medical and Surgical Sciences and Advanced Technologies (F.P.), GF Ingrassia, Neuroscience Section and Multiple Sclerosis Centre, University of Catania PO Policlinico G Rodolico, Italy Loyola University Chicago (A.P.R.), IL Department of Neurology (L.V.), AZ Sint-Jan Brugge-Oostende, Belgium Department of Neurology (T.V.), University of Colorado School of Medicine, Aurora Medical Image Analysis Center (MIAC AG) (J.W.), Department of Biomedical Engineering, University of Basel F. Hoffmann-La Roche Ltd (J.W., S.C., K.K., T.K., I.K., C.R., G.-A.T.), Basel, Switzerland and Department of Neurology (J.K.), VU University Medical Centre, Amsterdam, the Netherlands
Holmøy, Trygve
Autor Holmøy, Trygve ORCID From the Department of Neurology (H.-P.H.), UKD, Centre of Neurology and Neuropsychiatry and LVR-Klinikum, Heinrich-Heine University Düsseldorf, Germany Brain and Mind Centre (H.-P.H.), University of Sydney, Australia Department of Neurology (H.-P.H.), Palacky University Olomouc, Czech Republic Department of Neurology (R.H.B.B.), Jacobs School of Medicine and Biomedical Sciences, University of Buffalo, NY Department of Neurology (T.B.), Medical University of Vienna, Comprehensive Center for Clinical Neurosciences and Mental Health, Austria Mellen Center for MS (R.A.B.), Cleveland Clinic, OH Neurocentre Magendie INSERM (B.B.), Université de Bordeaux, France Department of Neurology (W.M.C.), Sir Charles Gairdner Hospital, Perron Institute for Neurological and Translational Science, The University of Western Australia, Nedlands Department of Medicine and the Ottawa Hospital Research Institute (M.S.F.), University of Ottawa, Ontario, Canada Department of Neurology (T.H.), Akershus University Hospital, Lørenskog Institute of Clinical Medicine (T.H.), University of Oslo, Norway Department of Neurology (R.K.), Hacettepe University Faculty of Medicine, Ankara, Turkey Centre d'Esclerosi Mútiple de Catalunya (Cemcat) (C.N.), Vall d'Hebron Hospital Universitari, Barcelona, Spain Department of Medical and Surgical Sciences and Advanced Technologies (F.P.), GF Ingrassia, Neuroscience Section and Multiple Sclerosis Centre, University of Catania PO Policlinico G Rodolico, Italy Loyola University Chicago (A.P.R.), IL Department of Neurology (L.V.), AZ Sint-Jan Brugge-Oostende, Belgium Department of Neurology (T.V.), University of Colorado School of Medicine, Aurora Medical Image Analysis Center (MIAC AG) (J.W.), Department of Biomedical Engineering, University of Basel F. Hoffmann-La Roche Ltd (J.W., S.C., K.K., T.K., I.K., C.R., G.-A.T.), Basel, Switzerland and Department of Neurology (J.K.), VU University Medical Centre, Amsterdam, the Netherlands
Karabudak, Rana
Autor Karabudak, Rana ORCID From the Department of Neurology (H.-P.H.), UKD, Centre of Neurology and Neuropsychiatry and LVR-Klinikum, Heinrich-Heine University Düsseldorf, Germany Brain and Mind Centre (H.-P.H.), University of Sydney, Australia Department of Neurology (H.-P.H.), Palacky University Olomouc, Czech Republic Department of Neurology (R.H.B.B.), Jacobs School of Medicine and Biomedical Sciences, University of Buffalo, NY Department of Neurology (T.B.), Medical University of Vienna, Comprehensive Center for Clinical Neurosciences and Mental Health, Austria Mellen Center for MS (R.A.B.), Cleveland Clinic, OH Neurocentre Magendie INSERM (B.B.), Université de Bordeaux, France Department of Neurology (W.M.C.), Sir Charles Gairdner Hospital, Perron Institute for Neurological and Translational Science, The University of Western Australia, Nedlands Department of Medicine and the Ottawa Hospital Research Institute (M.S.F.), University of Ottawa, Ontario, Canada Department of Neurology (T.H.), Akershus University Hospital, Lørenskog Institute of Clinical Medicine (T.H.), University of Oslo, Norway Department of Neurology (R.K.), Hacettepe University Faculty of Medicine, Ankara, Turkey Centre d'Esclerosi Mútiple de Catalunya (Cemcat) (C.N.), Vall d'Hebron Hospital Universitari, Barcelona, Spain Department of Medical and Surgical Sciences and Advanced Technologies (F.P.), GF Ingrassia, Neuroscience Section and Multiple Sclerosis Centre, University of Catania PO Policlinico G Rodolico, Italy Loyola University Chicago (A.P.R.), IL Department of Neurology (L.V.), AZ Sint-Jan Brugge-Oostende, Belgium Department of Neurology (T.V.), University of Colorado School of Medicine, Aurora Medical Image Analysis Center (MIAC AG) (J.W.), Department of Biomedical Engineering, University of Basel F. Hoffmann-La Roche Ltd (J.W., S.C., K.K., T.K., I.K., C.R., G.-A.T.), Basel, Switzerland and Department of Neurology (J.K.), VU University Medical Centre, Amsterdam, the Netherlands
Nos, Carlos
Autor Nos, Carlos From the Department of Neurology (H.-P.H.), UKD, Centre of Neurology and Neuropsychiatry and LVR-Klinikum, Heinrich-Heine University Düsseldorf, Germany Brain and Mind Centre (H.-P.H.), University of Sydney, Australia Department of Neurology (H.-P.H.), Palacky University Olomouc, Czech Republic Department of Neurology (R.H.B.B.), Jacobs School of Medicine and Biomedical Sciences, University of Buffalo, NY Department of Neurology (T.B.), Medical University of Vienna, Comprehensive Center for Clinical Neurosciences and Mental Health, Austria Mellen Center for MS (R.A.B.), Cleveland Clinic, OH Neurocentre Magendie INSERM (B.B.), Université de Bordeaux, France Department of Neurology (W.M.C.), Sir Charles Gairdner Hospital, Perron Institute for Neurological and Translational Science, The University of Western Australia, Nedlands Department of Medicine and the Ottawa Hospital Research Institute (M.S.F.), University of Ottawa, Ontario, Canada Department of Neurology (T.H.), Akershus University Hospital, Lørenskog Institute of Clinical Medicine (T.H.), University of Oslo, Norway Department of Neurology (R.K.), Hacettepe University Faculty of Medicine, Ankara, Turkey Centre d'Esclerosi Mútiple de Catalunya (Cemcat) (C.N.), Vall d'Hebron Hospital Universitari, Barcelona, Spain Department of Medical and Surgical Sciences and Advanced Technologies (F.P.), GF Ingrassia, Neuroscience Section and Multiple Sclerosis Centre, University of Catania PO Policlinico G Rodolico, Italy Loyola University Chicago (A.P.R.), IL Department of Neurology (L.V.), AZ Sint-Jan Brugge-Oostende, Belgium Department of Neurology (T.V.), University of Colorado School of Medicine, Aurora Medical Image Analysis Center (MIAC AG) (J.W.), Department of Biomedical Engineering, University of Basel F. Hoffmann-La Roche Ltd (J.W., S.C., K.K., T.K., I.K., C.R., G.-A.T.), Basel, Switzerland and Department of Neurology (J.K.), VU University Medical Centre, Amsterdam, the Netherlands

Neurology. 2024 ; 103 (12) : e210049. [pub] 20241203

ISSN 1526-632X
Medvik
Zdroj

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.

Článek

PARP inhibitory v terapii pokročilého, metastatického nebo recidivujícího karcinomu endometria
[Current status of PARP inhibition in advanced, metastatic and recurent endometrial cancer]

Onkologie. 2024 ; 18 (5) : 305-310. [pub] 20241128

ISSN 1802-4475
Medvik
Zdroj

Poznatky o molekulárních subtypech karcinomu endometria (EC) vedly v posledních několika letech k velkým změnám v klasifikačním systému, v prognostických skupinách a ve svém důsledku v terapeutických postupech u pacientek s pokročilým, metastatickým a recidivujícím karcinomem endometria. Nejvýznamnějším posunem v obtížně léčitelné kohortě pacientek s pokročilým, metastatickým a recidivujícím EC od dob konvenční chemoterapie je jednoznačně kombinace checkpoint inhibitoru pembrolizumabu s antiangiogenním preparátem lenvatinibem, nezávislá na přítomnosti mikrosatelitové nestability (MSI) nádorových buněk. Ve skupině MSI-high karcinomů se jako velmi úspěšné jeví podání dostarlimabu v monoterapii. iPARP byly vyšetřovány v mnoha terapeutických designech a je evidentní, že jejich léčebné využití bude u pacientek s EC s deficitem v homologní rekombinaci, bez ohledu na BRCA status. Mechanizmus účinku iPARP je u pacientek s EC založený na frekventní přítomnosti PTEN mutace a mutace TP53, jež souvisí právě s deficitem v homologní rekombinaci. iPARP mají jednak vlastní cytotoxický účinek a jednak senzitizují buňky EC k účinkům checkpoint inhibitorů. Ve sdělení je sumarizována současná evidence o preklinickém výzkumu a klinickém využití iPARP u pacientek s pokročilým, metastatickým a rekurentním EC. Nově je v České republice olaparib schválen k podávání v udržovací léčbě v kombinaci s durvalumabem u pacientek s primárně pokročilým nebo rekurentním EC (mismatch repair proficientním - pMMR), které neprogredovaly na I. linii systémové terapie v kombinaci paclitaxel, karboplatina a durvalumab.

Knowledge of molecular subtypes of endometrial cancer (EC) has led to major changes in the classification system, prognostic groups and, as a result, in therapeutic procedures in patients with advanced, metastatic and recurrent endometrial cancer (EC) in the last few years. The most significant shift in the difficult-to-treat cohort of patients with advanced, metastatic and recurrent EC since conventional chemotherapy is clearly the combination of the checkpoint inhibitor pembrolizumab with the antiangiogenic agent lenvatinib, independent of the presence of microsatellite instability (MSI) of tumor cells. In the MSI-high group of carcinomas, the administration of dostarlimab monotherapy appears to be very successful. iPARPs have been investigated in many therapeutic designs and it is evident that their therapeutic use will be in EC patients with homologous recombination deficiency, regardless of BRCA status. The mechanism of action of iPARP in EC patients is based on the frequent presence of PTEN mutation and TP53 mutation, which is related to the deficit in homologous recombination. iPARPs have both their own cytotoxic effect and sensitize EC cells to the effects of checkpoint inhibitors. The article summarizes the current evidence on preclinical research and clinical use of iPARP in patients with advanced, metastatic and recurrent EC. In the Czech Republic, olaparib is newly approved for administration in maintenance therapy in combination with durvalumab in patients with primarily advanced or recurrent EC (mismatch repair proficient - pMMR) who have not progressed on first-line systemic therapy in combination with paclitaxel, carboplatin and durvalumab.

Článek

Imunoterapie v léčbě pokročilých a recidivujících stadií karcinomu děložního hrdla
[Current status of immunotherapy for the pacients with advanced, metastatic and recurent cervical cancer]

Onkologie. 2024 ; 18 (5) : 315-317. [pub] 20241128

ISSN 1802-4475
Medvik
Zdroj

I přes rozpoznanou etiopatogenezi, primární prevenci a národní screeningový program zůstává pokročilý a metastatický cervikální karcinom (CC) významným klinickým problémem s limitovanými možnostmi léčebného ovlivnění. Imunoterapeutika - checkpoint inhibitory vstupují do léčebného portfolia u pacientek s inoperabilními lokálně pokročilými stadii a u pacientek s progredujícím, metastatickým a rekurentním cervikálním karcinomem. Přinášejí potřebnou naději v kohortě křehkých obtížně léčitelných pacientek. Včlenění imunoterapie v kombinaci s chemoterapií s nebo bez bevacizumabu do první linie systémové léčby a v monoterapii v druhé linii léčby navazující na chemoterapii založené na platině vedlo k signifikantnímu prodloužení celkového přežítí pacientek s CC.

Despite the identified etiopathogenesis, primary prevention and national screening program, advanced and metastatic cervical cancer remains a significant clinical problem with limited treatment options. Immunotherapeutics - checkpoint inhibitors enter the treatment portfolio in patients with inoperable locally advanced stages and bring the necessary hope in patients with progressive, metastatic and recurrent cervical cancer in the cohort of fragile, difficult-to-treat patients. The inclusion of immunotherapy in combination with chemotherapy with or without bevacizumab in first-line systemic therapy and in second-line therapy monotherapy following platinum-based chemotherapy resulted in a significant prolongation of overall survival of patients with CC.

Článek

Současná role lipoproteinové aferézy v kontextu nových doporučení hypolipidemické farmakoterapie
[Current role of lipoprotein apheresis in the context of new recommendations for hypolipidemic pharmacotherapy]

Athero Review. 2024 ; 9 (2) : 81-91.

ISSN 2464-6563
Medvik
Zdroj

Východisko: Lipoproteinová aferéza (LA) je velmi účinná, časově náročná a nákladná metoda snižování hladin LDL-cholesterolu (Low Denzity Lipoprotein Cholesterol – LDL-C), lipoproteinu(a) – Lp(a) a dalších apoB obsahujících lipoproteinů, včetně na triglyceridy bohatých lipoproteinů. Tato metoda byla poprvé použita téměř před 50 lety a dlouho byla terapií „poslední možnosti“ pro dyslipidemie, které jinak nelze řešit. V posledních letech jsou vyvíjena nová, velmi účinná hypolipidemika a účelem tohoto přehledu je definovat roli lipoproteinové aferézy v současném kontextu. Rozbor problematiky: Lipoproteinová aferéza stále hraje důležitou roli v léčbě pacientů s homozygotní familiární hypercholesterolemií (HoFH) a některých pacientů s dalšími formami hypercholesterolemie a aterosklerotickými kardiovaskulárními chorobami (ASKVO). Zejména pacienti, kteří nedosahují léčebných cílů navzdory moderní hypolipidemické farmakoterapii, ať už proto, že ji netolerují nebo je terapeutická odpověď nedostatečná. Lp(a) je vedle LDL-C další důležitý kardiovaskulární rizikový faktor a lipoproteinová aferéza je taktéž využívána ke snížení koncentrací lipoproteinu(a) u pacientů s významným zvýšením Lp(a) a kardiovaskulárním onemocněním. Existuje však značná heterogenita v doporučeních vědeckých autorit ohledně toho, které skupiny pacientů by měly být léčeny lipoproteinovou aferézou. Závěr: Doporučení odborných společností indikují léčbu klasickými i moderními hypolipidemiky před zahájením léčby lipoproteinovou aferézou a současně také s aferézou s cílem snížení a dosažení cílových hladin LDL-C. LA nemusí předcházet farmakoterapii, naopak klinické studie ukázaly možnost weaningu z LA při použití testovaných nových léčiv. Kombinované použití lipoproteinové aferézy a nových hypolipidemik (inhibitorů PCSK9, lomitapidu a evinakumabu) nabízí cenný terapeutický přístup u pacientů s obtížně kontrolovatelnými hladinami LDL-C. Lipoproteinová aferéza zůstává důležitým nástrojem pro terapii pacientů se závažnými dyslipidemiemi rezistentními na léčbu, zejména pacientů s homozygotní FH.

Background: Lipoprotein apheresis (LA) is a very effective, time-consuming and costly method of lowering low-density lipoprotein cholesterol (LDL-C), lipoprotein(a) – Lp(a) and other apoB-containing lipoproteins, including triglyceride-rich lipoproteins. This method was first used almost 50 years ago and has long been a “last resort” therapy for dyslipidemias that cannot otherwise be addressed. In recent years, new, highly effective hypolipidemic agents have been developed and the purpose of this review is to define the role of lipoprotein apheresis in the current context. Discussion of the problem: Lipoprotein apheresis still plays an important role in the treatment of patients with homozygous familial hypercholesterolemia (HoFH) and some patients with other forms of hypercholesterolemia and atherosclerotic cardiovascular disease (ASCVD). In particular, patients who fail to achieve therapeutic goals despite modern hypolipidemic drug therapy, either because they are intolerant or the therapeutic response is inadequate. Lp(a) is another important cardiovascular risk factor besides LDL-C, and lipoprotein apheresis is also used to reduce lipoprotein(a) concentrations in patients with significant elevations of Lp(a) and cardiovascular disease. However, there is considerable heterogeneity in the recommendations of scientific authorities regarding which groups of patients should be treated with lipoprotein apheresis. Conclusion. Recommendations of professional societies indicate treatment with conventional and modern hypolipidemic agents before starting lipoprotein apheresis therapy and simultaneously with apheresis to reduce and achieve target LDL-C levels. LA does not need to precede drug therapy; on the contrary, clinical trials have shown the possibility of weaning from LA when using investigational new drugs. The combined use of lipoprotein apheresis and novel hypolipidemics (PCSK9 inhibitors, lomitapide and evinacumab) offers a valuable therapeutic approach for patients with difficult-to-control LDL-C levels. Lipoprotein apheresis remains an important tool for the treatment of patients with severe treatment-resistant dyslipidemias, especially those with homozygous FH.