The impact of rituximab infusion protocol on the long‐term outcome in anti‐MuSK myasthenia gravis

Cortés-Vicente, Elena; Rojas‐García, Ricard; Díaz‐Manera, Jordi; Querol, Luís; Casasnovas, Carlos; Guerrero-Solá, A.; Muñoz-Blanco, José Luís; J, Bárcena-Llona; Márquez-Infante, Celedonio; Pardo, Julio; Martínez-Fernández, E; Usón, María José Sánchez; Oliva‐Nacarino, Pedro; Sevilla, Teresa; Illa, Isabel

doi:10.1002/acn3.564

Cited by 39 publications

(38 citation statements)

References 39 publications

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“…These studies have demonstrated 100% complete stable remission for the use of RTX in MuSK MG (125,174), while 56% of AChR patients experienced a relapse within an average of 36 months after treatment -a finding that was replicated in another similar independent study (125,167). Although MuSK MG patients respond very well to treatment with RTX, relapses do occur, and the relapse rate is dependent on the applied RTX treatment protocol (176). Consistent reductions in AChR autoantibody titers and clinical improvement were demonstrated in a cohort study involving six patients (174).…”

Section: B Cell Targeting Therapiesmentioning

confidence: 88%

Autoimmune Pathology in Myasthenia Gravis Disease Subtypes Is Governed by Divergent Mechanisms of Immunopathology

et al. 2020

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Myasthenia gravis (MG) is a prototypical autoantibody mediated disease. The autoantibodies in MG target structures within the neuromuscular junction (NMJ), thus affecting neuromuscular transmission. The major disease subtypes of autoimmune MG are defined by their antigenic target. The most common target of pathogenic autoantibodies in MG is the nicotinic acetylcholine receptor (AChR), followed by muscle-specific kinase (MuSK) and lipoprotein receptor-related protein 4 (LRP4). MG patients present with similar symptoms independent of the underlying subtype of disease, while the immunopathology is remarkably distinct. Here we highlight these distinct immune mechanisms that describe both the B cell-and autoantibody-mediated pathogenesis by comparing AChR and MuSK MG subtypes. In our discussion of the AChR subtype, we focus on the role of long-lived plasma cells in the production of pathogenic autoantibodies, the IgG1 subclass mediated pathology, and contributions of complement. The similarities underlying the immunopathology of AChR MG and neuromyelitis optica (NMO) are highlighted. In contrast, MuSK MG is caused by autoantibody production by short-lived plasmablasts. MuSK MG autoantibodies are mainly of the IgG4 subclass which can undergo Fab-arm exchange (FAE), a process unique to this subclass. In FAE IgG4, molecules can dissociate into two halves and recombine with other half IgG4 molecules resulting in bispecific antibodies. Similarities between MuSK MG and other IgG4-mediated autoimmune diseases, including pemphigus vulgaris (PV) and chronic inflammatory demyelinating polyneuropathy (CIDP), are highlighted. Finally, the immunological distinctions are emphasized through presentation of biological therapeutics that provide clinical benefit depending on the MG disease subtype.

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Section: B Cell Targeting Therapiesmentioning

confidence: 88%

Autoimmune Pathology in Myasthenia Gravis Disease Subtypes Is Governed by Divergent Mechanisms of Immunopathology

et al. 2020

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“…Rituximab is increasingly being used for MG treatment. In recent years, several studies showed that rituximab is efficient in reducing the number of exacerbations in patients with refractory MG [10][11][12][13]. In the AAN guidelines, it is recommended to use nonsteroid IST to reduce doses of steroids.…”

Section: Discussionmentioning

confidence: 99%

“…A total of 16 patients (55.1%) were receiving non-steroid IST, of whom 11 were also receiving steroids. In all, 22 patients were treated using Protocol A, three using Protocol B, one using Protocol C and three using Protocol D, with a mean cumulative dose of 4.26 g [1][2][3][4][5][6][7][8][9][10]. The mean (range) follow-up after initiation of rituximab was 20.06 (0.17-68.93) months.…”

Section: Patientsmentioning

confidence: 99%

Efficacy and safety of rituximab in myasthenia gravis: a French multicentre real‐life study

Santos¹,

Noury

Genestet

et al. 2020

Euro J of Neurology

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Background and purpose: Fifteen percent of patients with myasthenia gravis (MG) are refractory to conventional treatment. Case reports and a few studies show probable benefit of rituximab in these cases. Our objective was to assess the efficacy and the safety of rituximab in patients with MG, in a multicentric real-life study. Method: Inclusion criteria were: age > 18 years; MG with anti-acetylcholine receptor (AChR) antibodies, anti-muscle-specific kinase (MuSk) antibodies or significant decrement after repetitive nerve stimulation; Myasthenia Gravis Foundation of America (MGFA) class >II; refractory or steroid-dependent MG; and treatment with rituximab. Efficacy was assessed at 6 months using the MGFA-post-intervention status (PIS) score, the myasthenic muscle score (MMS) and the number of patients receiving steroids <10 mg/day. Data on adverse events were collected. Results: Twenty-nine patients were included: 20 with anti-AChR MG, five with anti-MuSK MG and four with seronegative MG. MGFA-PIS score was improved or better (improved, minimal manifestations or remission) in 86.2% of patients after 6 months of treatment (P < 0.0001). The mean MMS increased from 68.8 to 83.1 (P < 0.0001). A decrease in steroid dosage (<10 mg/day) was effective in 57.9% of treated patients. In all, 42.8% of patients experienced adverse events: infections (21.4% of patients); infusion reaction (7%); bradycardia (3.7%); and cytopenia (7%). Conclusion: The present study demonstrates the efficacy and safety of rituximab in patients with MG. Additional studies remain necessary to determine the role of rituximab in the pharmacopeia of MG treatment and to establish precise recommendations for the infusion protocol.

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“…The discrepancy may be explained by differences in the definition of clinical relapse, corticosteroid tapering schedule and rituximab dosing regimen. 38…”

Section: Discussionmentioning

confidence: 99%

Repeated low-dose rituximab treatment based on the assessment of circulating B cells in patients with refractory myasthenia gravis

Choi

Hong

Ahn

et al. 2019

Ther Adv Neurol Disord

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Background: The objective of this study was to evaluate the efficacy and safety of repeated low-dose rituximab treatment guided by monitoring circulating CD19+ B cells in patients with refractory myasthenia gravis (MG). Methods: Patients with refractory MG who had received rituximab treatment at two teaching hospitals between September 2013 and January 2017 were reviewed retrospectively. The treatment protocol consisted of an induction treatment with low-dose rituximab (375 mg/m2 twice with a 2-week interval), followed by retreatment (375 mg/m2 once). Retreatment was based on either circulating CD19+ B-cell repopulation or clinical relapse. Outcome measures included the MG Foundation of America (MGFA) clinical classification and postintervention status, prednisolone dose, CD19+ B-cell counts, clinical relapse, and adverse effects. Results: Of 17 patients, 11 (65%) achieved the primary endpoint, defined as the minimal manifestation or better status with prednisolone ⩽5 mg/day, after median 7.6 months (range, 2–17 months) following rituximab treatment. Over a median follow up of 24 months (range, 7–49 months), a total of 30 retreatments were undertaken due to clinical relapse without B-cell repopulation ( n = 6), on the basis of B-cell repopulation alone ( n = 16) and both ( n = 8). B-cell recovery appeared to be in parallel with clinical relapse on the group level, although the individual-level association appeared to be modest, with B-cell repopulation observed only at 57% (8/14) of clinical relapses. Conclusions: The repeated low-dose rituximab treatment based on the assessment of circulating B-cell depletion could be a cost-effective therapeutic option for refractory MG. Further studies are needed to verify the potentially better cost-effectiveness of low-dose rituximab, and to identify biomarkers that help optimize treatment in MG patients.

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The impact of rituximab infusion protocol on the long‐term outcome in anti‐MuSK myasthenia gravis

Cited by 39 publications

References 39 publications

Autoimmune Pathology in Myasthenia Gravis Disease Subtypes Is Governed by Divergent Mechanisms of Immunopathology

Autoimmune Pathology in Myasthenia Gravis Disease Subtypes Is Governed by Divergent Mechanisms of Immunopathology

Efficacy and safety of rituximab in myasthenia gravis: a French multicentre real‐life study

Repeated low-dose rituximab treatment based on the assessment of circulating B cells in patients with refractory myasthenia gravis

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