Efficacy of rituximab in refractory RRMS

Durozard, Pierre; Maarouf, Adil; Boutière, Clémence; Ruet, Aurélie; Brochet, Bruno; Vukusic, Sandra; Carra‐Dallière, Clarisse; Labauge, Pierre; Mathey, Guillaume; Debouverie, Marc; Papeix, Caroline; Maillart, Élisabeth; Lubetzki, Catherine; Bensa, Caroline; Gout, Olivier; Giannesini, C.; Stankoff, Bruno; Ciron, Jonathan; Brassat, David; Pelletier, Jean; Lamy, Audrey Rico; Audoin, Bertrand

doi:10.1177/1352458518772748

Cited by 30 publications

(16 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Accordingly, the B celldepleting agent rituximab has found to be a successful application both in conditions caused by pathogenic autoantibodies, such as autoimmune thrombotic thrombocytopenic purpura and hemolytic anemia, as well as in diseases presumably driven by autoreactive T lymphocytes, such as progressive multiple sclerosis and rheumatoid arthritis. [33][34][35][36][37] Rituximab is also highly effective in patients with IgG 4 -RD, a primarily fibrotic disorder in which the relevance of autoantibodies and T cells to fibrosis is still being explored. 5,38 Our recent studies have implicated antibodies to galectin-3 in a subset of patients with IgG 4 -RD, and others have identified autoantibodies to a recombinant truncated form of laminin 511, but definitive proof of a pathogenic role of these antibodies has not yet been demonstrated.…”

Section: Discussionmentioning

confidence: 99%

B lymphocytes directly contribute to tissue fibrosis in patients with IgG4-related disease

Della‐Torre

Rigamonti

Perugino

et al. 2020

Journal of Allergy and Clinical Immunology

101

View full text Add to dashboard Cite

Background: IgG 4-related disease (IgG 4-RD) is a fibroinflammatory condition marked by rapid clinical improvement after selective depletion of B lymphocytes with rituximab. This feature suggests that B cells might participate in fibrogenesis and wound healing. Objective: In the present work we aimed to demonstrate that B lymphocytes contribute directly to tissue fibrosis in patients with IgG 4-RD. Methods: Total circulating CD19 1 B lymphocytes, naive B cells, memory B cells, or plasmablasts from patients with IgG 4-RD were cultivated with human fibroblasts. Profibrotic soluble factors and collagen production in cocultures were assessed by using ELISAs and Luminex assays. RNA sequencing and quantitative RT-PCR were used to assess fibroblast activation in the presence of B cells, as well as induction of profibrotic pathways in B-cell subsets. Relevant profibrotic and inflammatory molecules were confirmed in vitro by using functional experiments and on IgG 4-RD tissue sections by using multicolor immunofluorescence studies. Results: B cells from patients with IgG 4-RD (1) produced the profibrotic molecule platelet-derived growth factor B and stimulated collagen production by fibroblasts; (2) expressed enzymes implicated in extracellular matrix remodeling, such as lysyl oxidase homolog 2; (3) produced the chemotactic factors CCL4, CCL5, and CCL11; and (4) induced production of these same chemokines by activated fibroblasts. Plasmablasts expressed sets of genes implicated in fibroblast activation and proliferation and therefore represent cells with intrinsic profibrotic properties. Conclusion: We have demonstrated that B cells contribute directly to tissue fibrosis in patients with IgG 4-RD. These unanticipated profibrotic properties of B lymphocytes, particularly plasmablasts, might be relevant for fibrogenesis in patients with other fibroinflammatory disorders and for woundhealing processes in physiologic conditions.

show abstract

Section: Discussionmentioning

confidence: 99%

B lymphocytes directly contribute to tissue fibrosis in patients with IgG4-related disease

Della‐Torre

Rigamonti

Perugino

et al. 2020

Journal of Allergy and Clinical Immunology

101

View full text Add to dashboard Cite

show abstract

“…4 A nationwide retrospective study revealed the efficacy of rituximab in patients with aggressive RRMS showing inflammatory activity despite second-line immunosuppressive therapies. 5 A retrospective multicentric Italian–Swiss study confirmed the strong efficacy of rituximab in reducing disease activity. 6 Finally, Naegelin et al evidenced that rituximab may significantly reduce the risk of disability progression in patients with secondary progressive MS. 7…”

Section: Introductionmentioning

confidence: 90%

Comparison of rituximab originator (MabThera^®) to biosimilar (Truxima^®) in patients with multiple sclerosis

et al. 2020

Self Cite

View full text Add to dashboard Cite

Background: Rituximab’s originator MabThera® or Rituxan® has demonstrated high efficacy in multiple sclerosis (MS). Because of the patent expiration, rituximab biosimilars have been developed. However, because a biosimilar is not the exact copy of the originator, the efficacy and safety of a biosimilar may significantly differ. Objectives: To compare the efficacy and safety of the biosimilar Truxima® and the originator MabThera® in MS. Methods: Consecutive MS patients receiving MabThera® or Truxima® were prospectively followed during 1 year after treatment introduction. Allocation to each treatment depended on the period of introduction and not the physician’s choice. Lymphocyte count, clinical and magnetic resonance imaging (MRI) activity, Expanded Disability Status Scale (EDSS), and adverse events were compared. Results: In total, 105 and 40 patients received MabThera® and Truxima®, respectively. The two groups did not differ in baseline characteristics. Effect on CD19+ lymphocytes and disease activity were similar during follow-up. EDSS remained stable, with no difference between groups. Adverse events were similar between groups. Conclusion: The efficacy and safety of the rituximab biosimilar Truxima® seem equivalent to the originator MabThera® in MS patients. Truxima® could represent a relatively cheap and safe therapeutic alternative to MabThera® and could improve access to highly efficient therapy for MS in low- or middle-income countries.

show abstract

“…Ferner lieferten zahlreiche retrospektive Analysen und eine Subgruppenanalyse Hinweise dafür, dass Rituximab sowohl effektiv bei aggressiver RMS bzw. progressiver MS sein kann [33][34][35][36][37][38][39] als auch den MS-Therapien der 1. Generation (i.e.…”

Section: Zusammenfassung • Abstractunclassified

Ocrelizumab zur Behandlung der Multiplen Sklerose

et al. 2020

View full text Add to dashboard Cite

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

show abstract

Efficacy of rituximab in refractory RRMS

Abstract: This study provides level IV evidence that rituximab reduces clinical and MRI disease activity in patients with active RRMS despite immunosuppressive DMT.

Cited by 30 publications

References 13 publications

B lymphocytes directly contribute to tissue fibrosis in patients with IgG4-related disease

B lymphocytes directly contribute to tissue fibrosis in patients with IgG4-related disease

Comparison of rituximab originator (MabThera^®) to biosimilar (Truxima^®) in patients with multiple sclerosis

Ocrelizumab zur Behandlung der Multiplen Sklerose

Contact Info

Product

Resources

About

Efficacy of rituximab in refractory RRMS

Abstract: This study provides level IV evidence that rituximab reduces clinical and MRI disease activity in patients with active RRMS despite immunosuppressive DMT.

Cited by 30 publications

References 13 publications

B lymphocytes directly contribute to tissue fibrosis in patients with IgG4-related disease

B lymphocytes directly contribute to tissue fibrosis in patients with IgG4-related disease

Comparison of rituximab originator (MabThera®) to biosimilar (Truxima®) in patients with multiple sclerosis

Ocrelizumab zur Behandlung der Multiplen Sklerose

Contact Info

Product

Resources

About

Comparison of rituximab originator (MabThera^®) to biosimilar (Truxima^®) in patients with multiple sclerosis