Ocrelizumab: A New B-cell Therapy for Relapsing Remitting and Primary Progressive Multiple Sclerosis

Stahnke, Amanda M.; Holt, Kathryn M.

doi:10.1177/1060028017747635

Cited by 21 publications

(24 citation statements)

References 12 publications

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“…The management of multiple sclerosis (MS) is evolving with revised diagnostic criteria and new treatments based on different targeting strategies approved in recent years or in the pipeline, mainly for relapsing-remitting multiple sclerosis (RRMS). [1][2][3][4][5] In addition, first treatments that show clinical benefits in progressive disease stages (primary-progressive multiple sclerosis (PPMS) and secondaryprogressive multiple sclerosis (SPMS)) are emerging. 2,4,5 However, the risk-benefit assessment of treatments as well as the overall therapeutic decisions are gaining in complexity.…”

Section: Introductionmentioning

confidence: 99%

Factors associated with time from first-symptoms to diagnosis and treatment initiation of Multiple Sclerosis in Switzerland

Kaufmann

Kuhle

Puhan

et al. 2018

Multiple Sclerosis Journal - Experimental, Translational and Cl

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BackgroundRecent studies emphasise the importance of timely diagnosis and early initiation of disease-modifying treatment in the long-term prognosis of multiple sclerosis.ObjectivesThe objective of this study was to investigate factors associated with extended time to diagnosis and time to disease-modifying treatment initiation in the Swiss Multiple Sclerosis Registry.MethodsWe used retrospective data (diagnoses 1996–2017) of the survey-based Swiss Multiple Sclerosis Registry and fitted logistic regression models (extended time to diagnosis ≥2 years from first symptoms, extended time to disease-modifying treatment initiation ≥1 year from diagnosis) with demographic and a priori defined variables.ResultsOur study, based on 996 persons with multiple sclerosis, suggests that 40% had an extended time to diagnosis, and extended time to disease-modifying treatment initiation was seen in 23%. Factors associated with extended time to diagnosis were primary progressive multiple sclerosis (odds ratio (OR) 5.09 (3.12–8.49)), diagnosis setting outside of hospital (neurologist (private practice) OR 1.54 (1.16–2.05)) and more uncommon first symptoms (per additional symptom OR 1.17 (1.06–1.30)). Older age at onset (per additional 5 years OR 0.84 (0.78–0.90)) and gait problems (OR 0.65 (0.47–0.89)) or paresthesia (OR 0.72 (0.54–0.95)) as first symptoms were associated with shorter time to diagnosis. Extended time to disease-modifying treatment initiation was associated with older age at diagnosis (per additional 5 years OR 1.18 (1.09–1.29)). In more recent years, time to diagnosis and time to disease-modifying treatment initiation tended to be shorter.ConclusionsEven in recent periods, substantial and partially systematic variation regarding time to diagnosis and time to disease-modifying treatment initiation remains. With the emerging paradigm of early treatment, the residual variation should be monitored carefully.

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Section: Introductionmentioning

confidence: 99%

Factors associated with time from first-symptoms to diagnosis and treatment initiation of Multiple Sclerosis in Switzerland

Kaufmann

Kuhle

Puhan

et al. 2018

Multiple Sclerosis Journal - Experimental, Translational and Cl

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“…Im klinischen Studienprogramm wurde bei Patienten, die mit Ocrelizumab behandelt wurden, eine verglichen mit den Kontrollgruppen höhere Anzahl maligner Erkrankungen (einschließlich Mammakarzinom) beobachtet [53,54].…”

Section: Malignomeunclassified

Ocrelizumab zur Behandlung der Multiplen Sklerose

et al. 2020

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Abb. 1 8 Zelluläre Ziele der CD20-Depletion. Während der B-Zell-Reifung werden unterschiedliche Differenzierungsantigene auf der Oberfläche der Zellen exprimiert, die von den therapeutisch eingesetzten monoklonalen Antikörpern erkannt werden. Die Bindung führt schließlich über antikörper-oder komplementabhängige zytotoxische Mechanismen zur Depletion. Von Bedeutung ist, dass die frühesten und spätesten Reifungsstufen wegen fehlender CD20-Expression nicht depletiert werden. Somit ist die Fähigkeit zur B-Zell-Repopulation erhalten sowie auch das humorale Immungedächtnis unbeeinträchtigt. Dadurch werden natürliche Abwehrmechanismen in ihrer Funktionalität bewahrt. Atacicept ist ein Wirkstoff, der die Differenzierung der B-Zelle hemmt. Atacicept ist ein rekombinantes Fusionsprotein, welches zwei für B-Zell-Reifung,-Funktion und-Überleben notwendige Zytokine, "B-lymphocyte stimulator" (BlyS) und "A proliferation-inducing ligand" (APRIL), über den Fc-Teil von Immunglobulin bindet und somit neutralisiert. (Adaptiert aus [7]) T-Zelle B-Zelle Makrophage ZNS-gerichtete Autoimmunantwort Relativ homogen, warten passiv auf T-Zell-Hilfe, um Antikörper zu produzieren Proinflammatorische Makrophagen (IL-12, IL-23, IL-6 and IL-1b) Anti-inflammatorische Makrophagen

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“…Ocrelizumab has a MW of approximately 145 kDa and is able to cross the placenta after the first trimester 168 . Its half-life is 26 days 169 .…”

Section: Ocrelizumabmentioning

confidence: 99%

Pregnancy-related issues in women with multiple sclerosis: an evidence-based review with practical recommendations

Canibaño

Deleu

Mesraoua

et al. 2020

Journal of Drug Assessment

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Objective: To review the current evidence regarding pregnancy-related issues in multiple sclerosis (MS) and to provide recommendations specific for each of them. Research design and methods: A systematic review was performed based on a comprehensive literature search. Results: MS has no effect on fertility, pregnancy or fetal outcomes, and pregnancies do not affect the long-term disease course and accumulation of disability. There is a potential risk for relapse after use of gonadotropin-releasing hormone agonists during assisted reproduction techniques. At short-term, pregnancy leads to a reduction of relapses during the third trimester, followed by an increased risk of relapses during the first three months postpartum. Pregnancies in MS are not per se high risk pregnancies, and MS does not influence the mode of delivery or anesthesia unless in the presence of significant disability. MRI is not contraindicated during pregnancy; however, gadolinium contrast media should be avoided whenever possible. It is safe to use pulse dose methylprednisolone infusions to manage acute disabling relapses during pregnancy and breastfeeding. However, its use during the first trimester of pregnancy is still controversial. Women with MS should be encouraged to breastfeed with a possible favorable effect of exclusive breastfeeding. Disease-modifying drugs can be classified according to their potential for pregnancy-associated risk and impact on fetal outcome. Interferon beta (IFNb) and glatiramer acetate (GA) may be continued until pregnancy is confirmed and, after consideration of the individual risk-benefit if continued, during pregnancy. The benefit of continuing natalizumab during the entire pregnancy may outweigh the risk of recurring disease activity, particularly in women with highly active MS. GA and IFNb are considered safe during breastfeeding. The use of natalizumab during pregnancy or lactation requires monitoring of the newborn. Conclusions: This review provides current evidence and recommendations for counseling and management of women with MS preconception, during pregnancy and postpartum.

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Ocrelizumab: A New B-cell Therapy for Relapsing Remitting and Primary Progressive Multiple Sclerosis

Abstract: Ocrelizumab demonstrated efficacy in the treatment of relapsing and PPMS and is the first therapy approved for patients with PPMS.

Cited by 21 publications

References 12 publications

Factors associated with time from first-symptoms to diagnosis and treatment initiation of Multiple Sclerosis in Switzerland

Factors associated with time from first-symptoms to diagnosis and treatment initiation of Multiple Sclerosis in Switzerland

Ocrelizumab zur Behandlung der Multiplen Sklerose

Pregnancy-related issues in women with multiple sclerosis: an evidence-based review with practical recommendations

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