Efficacy and safety of alemtuzumab versus fingolimod in RRMS after natalizumab cessation

Pfeuffer, Steffen; Schmidt, René; Straeten, Frederike Anne; Pul, Refik; Kleinschnitz, Christoph; Wieshuber, Marinus; Lee, Dong Hoon; Linker, Ralf A.; Doerck, Sebastian; Straeten, Vera; Windhagen, Susanne; Pawlitzki, Marc; Aufenberg, Christoph; Lang, Michael; Eienbroeker, Christian; Tackenberg, Björn; Limmroth, Volker; Wildemann, Brigitte; Haas, Jürgen; Klotz, Luisa; Wiendl, Heinz; Ruck, Tobias; Meuth, Sven G.

doi:10.1007/s00415-018-9117-z

Cited by 20 publications

(18 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…10 Disease reactivation following natalizumab is a well-known phenomenon and is observed in patients switching to fingolimod 11 but can be controlled by subsequent use of high-efficacy treatment including alemtuzumab or rituximab. 12,13 We were unable to demonstrate superiority or inferiority of cladribine or fingolimod to each other since disease activity in this group mostly restricted to the early period following switch.…”

Section: Discussionmentioning

confidence: 86%

Effectiveness and safety of cladribine in MS: Real-world experience from two tertiary centres

Pfeuffer

Rolfes

Hackert³

et al. 2021

Mult Scler

Self Cite

View full text Add to dashboard Cite

Background: Oral cladribine has been approved for the treatment of relapsing multiple sclerosis (MS) yet real-world evidence regarding its effectiveness and safety remains scarce. Objective: To evaluate efficacy and safety outcomes of MS patients following induction of cladribine. Methods: We evaluated our prospective cohort of cladribine-treated MS patients from two tertiary centres in Germany. Relapses, disability worsening and occurrence of new or enlarging T2-hyperintense magnetic resonance imaging (MRI) lesions were assessed as well as lymphocyte counts and herpes virus infections. Results: Among 270 patients treated with cladribine, we observed a profound reduction of both relapses and new or enlarging MRI lesions. Treatment appeared more efficacious, especially in patients without previous therapy or following platform substances. Patients switching from natalizumab were prone to re-emerging disease activity. Among patients following dimethyl fumarate pre-treatment, severe lymphopenia was common and associated with increased rates of herpes virus manifestations. Conclusion: Overall, we observed an efficacy and safety profile of cladribine consistent with data from the phase 3 clinical trial. However, patients switching from natalizumab experienced suboptimal disease control beyond rebound activity following cessation of natalizumab. Furthermore, dimethyl fumarate pre-treatment was associated with a profound risk of developing severe lymphopenia and subsequent herpes virus infections.

show abstract

Section: Discussionmentioning

confidence: 86%

Effectiveness and safety of cladribine in MS: Real-world experience from two tertiary centres

Pfeuffer

Rolfes

Hackert³

et al. 2021

Mult Scler

Self Cite

View full text Add to dashboard Cite

show abstract

“…Indeed, consensus is still lacking in regard to DMT sequencing following NAT withdrawal. Studies addressing treatment switch from NAT to another DMT revealed a superiority of rituximab and alemtuzumab vs. fingolimod in controlling disease activity (48,49). Recent studies suggested ocrelizumab as a possible choice to reduce the risk of MS disease activity reactivation in patients previously treated with NAT SID and EID (50).…”

Section: Discussionmentioning

confidence: 99%

Natalizumab Pharmacokinetics and -Dynamics and Serum Neurofilament in Patients With Multiple Sclerosis

et al. 2021

View full text Add to dashboard Cite

Background: Natalizumab (NAT) is a high-efficacy treatment for relapsing remitting multiple sclerosis (RRMS). However, it is associated with an increased risk of progressive multifocal leukoencephalopathy that sometimes requires treatment cessation with a risk of returning disease activity. The aim of this study was to characterize the pharmacokinetics and -dynamics as well as neurodestruction marker serum neurofilament light chain (sNfL) in patients with RRMS and secondary progressive MS (SPMS) stopping NAT in correlation to clinical data.Methods: In this study, 50 RRMS and 9 SPMS patients after NAT cessation were included. Five RRMS patients on NAT treatment holiday were evaluated. Clinical and radiological disease activity were systemically assessed by frequent exams after NAT stop. Free NAT concentration, cell bound NAT, α4-integrin expression and α4-integrin-receptor saturation as well as immune cell frequencies were measured for up to 4 months after NAT withdrawal. Additionally, sNfL levels were observed up to 12 months in RRMS and up to 4 months in SPMS patients.Results: NAT cessation was associated with a return of disease activity in 38% of the RRMS and 33% of the SPMS patients within 12 and 7 months, respectively. Concentration of free and cell bound NAT as well as α4-integrin-receptor saturation decreased in the RRMS and SPMS patients whereas α4-integrin expression increased over time. NAT induced increase of lymphocytes and its subsets normalized and a non-significant drop of NK and Th17 T-cells counts could be detected. All RRMS patients showed physiological sNfL levels <8pg/ml 1 month after last NAT infusion. During follow-up period sNfL levels peaked up to 16-fold and were linked to return of disease activity in 19 of the 37 RRMS patients. Treatment holiday was also associated with a return of disease activity in 4 of 5 patients and with an increase of sNfL at an individual level.Conclusions: We demonstrate the reversibility of NAT pharmacodynamic and -kinetic markers. sNfL levels are associated with the recurrence of disease activity and can also serve as an early marker to predict present before onset of clinical or radiological disease activity on the individual level.

show abstract

“…Until now, additional disease modifying and immunomodulatory therapies for RRMS have been licensed. Among those glatirameracetate [34], dimethyl fumarate [35], teriflunomide [36], fingolimod (Sphingosin-1-Phosphat receptor agonist) [37], and cladribine [38], as well as the humanized monoclonal antibodies Natalizumab, that inhibits lymphocyte migration into the CNS by blocking the adhesion molecule very late antigen-4 (VLA-4) [39], Alemtuzumab, that recognizes CD52 on lymphocytes resulting in T and B cell depletion [40,41], and Ocrelizumab, an anti-CD20 antibody specifically depleting B cells, have been approved [42]. Notably, beside its approval for RRMS, Ocrelizumab has been additionally licensed for treating PPMS.…”

Section: Introductionmentioning

confidence: 99%

Interferon β-Mediated Protective Functions of Microglia in Central Nervous System Autoimmunity

Scheu

Ali

Mann-Nüttel

et al. 2019

IJMS

Self Cite

View full text Add to dashboard Cite

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) leading to demyelination and axonal damage. It often affects young adults and can lead to neurological disability. Interferon β (IFNβ) preparations represent widely used treatment regimens for patients with relapsing-remitting MS (RRMS) with therapeutic efficacy in reducing disease progression and frequency of acute exacerbations. In mice, IFNβ therapy has been shown to ameliorate experimental autoimmune encephalomyelitis (EAE), an animal model of MS while genetic deletion of IFNβ or its receptor augments clinical severity of disease. However, the complex mechanism of action of IFNβ in CNS autoimmunity has not been fully elucidated. Here, we review our current understanding of the origin, phenotype, and function of microglia and CNS immigrating macrophages in the pathogenesis of MS and EAE. In addition, we highlight the emerging roles of microglia as IFNβ-producing cells and vice versa the impact of IFNβ on microglia in CNS autoimmunity. We finally discuss recent progress in unraveling the underlying molecular mechanisms of IFNβ-mediated effects in EAE.

show abstract

Efficacy and safety of alemtuzumab versus fingolimod in RRMS after natalizumab cessation

Cited by 20 publications

References 22 publications

Effectiveness and safety of cladribine in MS: Real-world experience from two tertiary centres

Effectiveness and safety of cladribine in MS: Real-world experience from two tertiary centres

Natalizumab Pharmacokinetics and -Dynamics and Serum Neurofilament in Patients With Multiple Sclerosis

Interferon β-Mediated Protective Functions of Microglia in Central Nervous System Autoimmunity

Contact Info

Product

Resources

About