Dataset Information

Effective Early Treatment of AChR Antibody-Positive Myasthenia Gravis with Rituximab; the Experience from a Neuroimmunology Clinic in a Developing Country.

ABSTRACT:

Background

Rituximab is reserved for treating refractory myasthenia gravis (MG) patients. Here we report our experience with rituximab in AChR antibody positive generalized MG (gMG) and impending myasthenic crisis (IMC).

Methods

This retrospective, observational study, conducted at a tertiary care, neuroimmunology clinic, analyzed the data of patients with AChR antibody positive gMG, treated with rituximab between 1st January 2016 and 30th October 2018.

Results

Eleven patients with AChR antibody positive gMG received rituximab. Mean age of the cohort was 50.54 ± 18.71 years with 9 males. Seven out of 11 patients received rituximab in the early stage (<2 years from onset) and had good response to treatment. Four of the 5 patients with IMC improved with rituximab alone. In the 10 patients who regularly followed up, there was a significant difference between the QMG scores at baseline and at 1, 2, 6, 12, and 18 months (P < .0001).

Conclusion

Rituximab appears to be a potentially effective early treatment option for AChR antibody positive generalized MG and impending myasthenic crisis.

SUBMITTER: Mathew T

PROVIDER: S-EPMC8135199 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Publications

Effective Early Treatment of AChR Antibody-Positive Myasthenia Gravis with Rituximab; the Experience from a Neuroimmunology Clinic in a Developing Country.

Mathew Thomas T Thomas Kurian K K John Saji S Venkatesh Shruthi S Nadig Raghunandan R Badachi Sagar S Souza Delon D DD Sarma Grk G Parry Gareth J GJ

Journal of central nervous system disease 20210517

<h4>Background</h4>Rituximab is reserved for treating refractory myasthenia gravis (MG) patients. Here we report our experience with rituximab in AChR antibody positive generalized MG (gMG) and impending myasthenic crisis (IMC).<h4>Methods</h4>This retrospective, observational study, conducted at a tertiary care, neuroimmunology clinic, analyzed the data of patients with AChR antibody positive gMG, treated with rituximab between 1st January 2016 and 30th October 2018.<h4>Results</h4>Eleven patie ...[more]

PMID: 34045914

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Project description:ImportanceUse of biologic agents in generalized myasthenia gravis is generally limited to therapy-refractory cases; benefit in new-onset disease is unknown.ObjectiveTo assess rituximab in refractory and new-onset generalized myasthenia gravis and rituximab vs conventional immunotherapy in new-onset disease.Design, setting, and participantsA retrospective cohort study with prospectively collected data was conducted on a county-based community sample at Karolinska University Hospital, Stockholm, Sweden. Participants included 72 patients with myasthenia gravis, excluding those displaying muscle-specific tyrosine kinase antibodies, initiating rituximab treatment from January 1, 2010, to December 31, 2018, and patients with new-onset disease initiating conventional immunotherapy from January 1, 2003, to December 31, 2012, with 12 months or more of observation time. The present study was conducted from March 1, 2019, to January 31, 2020.ExposuresTreatment with low-dose rituximab (most often 500 mg every 6 months) or conventional immunosuppressants.Main outcomes and measuresTime to remission (main outcome) as well as use of rescue therapies or additional immunotherapies and time in remission (secondary outcomes).ResultsOf the 72 patients included, 31 patients (43%) were women; mean (SD) age at treatment start was 60 (18) years. Twenty-four patients had received rituximab within 12 months of disease onset and 48 received rituximab at a later time, 34 of whom had therapy-refractory disease. A total of 26 patients (3 [12%] women; mean [SD] age, 68 [11] years at treatment start) received conventional immunosuppressant therapy. Median time to remission was shorter for new-onset vs refractory disease (7 vs 16 months: hazard ratio [HR], 2.53; 95% CI, 1.26-5.07; P = .009 after adjustment for age, sex, and disease severity) and for rituximab vs conventional immunosuppressant therapies (7 vs 11 months: HR, 2.97; 95% CI, 1.43-6.18; P = .004 after adjustment). In addition, fewer rescue therapy episodes during the first 24 months were required (mean [SD], 0.38 [1.10] vs 1.31 [1.59] times; mean difference, -1.26; 95% CI, -1.97 to -0.56; P < .001 after adjustment), and a larger proportion of patients had minimal or no need of additional immunotherapies (70% vs 35%; OR, 5.47; 95% CI, 1.40-21.43; P = .02 after adjustment). Rates of treatment discontinuation due to adverse events were lower with rituximab compared with conventional therapies (3% vs 46%; P < .001 after adjustment).Conclusions and relevanceClinical outcomes with rituximab appeared to be more favorable in new-onset generalized myasthenia gravis, and rituximab also appeared to perform better than conventional immunosuppressant therapy. These findings suggest a relatively greater benefit of rituximab earlier in the disease course. A placebo-controlled randomized trial to corroborate these findings is warranted.

Project description:Neuromuscular transmission failure in myasthenia gravis (MG) is most commonly elicited by autoantibodies (ab) to the acetylcholine receptor or the muscle-specific kinase, constituting AChR-MG and MuSK-MG. It is controversial whether these MG subtypes arise through different T helper (Th) 1, Th2 or Th17 polarized immune reactions and how these reactions are blunted by immunosuppression. To address these questions, plasma levels of cytokines related to various Th subtypes were determined in patients with AChR-MG, MuSK-MG and healthy controls (CON). Peripheral blood mononuclear cells (PBMC) were activated in vitro by anti-CD3, and cytokines were quantified in supernatants. In purified blood CD4+ T cells, RNA of various cytokines, Th subtype specific transcription factors and the co-stimulatory molecule, CD40L, were quantified by qRT-PCR. Plasma levels of Th1, Th2 and Th17 related cytokines were overall not significantly different between MG subtypes and CON. By contrast, in vitro stimulated PBMC from MuSK-MG but not AChR-MG patients showed significantly increased secretion of the Th1, Th17 and T follicular helper cell related cytokines, IFN-γ, IL-17A and IL-21. Stimulated expression of IL-4, IL-6, IL-10 and IL-13 was not significantly different. At the RNA level, expression of CD40L by CD4+ T cells was reduced in both AChR-MG and MuSK-MG patients while expression of Th subset related cytokines and transcription factors were normal. Immunosuppression treatment had two effects: First, it reduced levels of IL12p40 in the plasma of AChR-MG and MuSK-MG patients, leaving other cytokine levels unchanged; second, it reduced spontaneous secretion of IFN-γ and increased secretion of IL-6 and IL-10 by cultured PBMC from AChR-MG, but not MuSK-MG patients. We conclude that Th1 and Th17 immune reactions play a role in MuSK-MG. Immunosuppression attenuates the Th1 response in AChR-MG and MuSK-MG, but otherwise modulates immune responses in AChR-MG and MuSK-MG patients differentially.

Dataset Information

Effective Early Treatment of AChR Antibody-Positive Myasthenia Gravis with Rituximab; the Experience from a Neuroimmunology Clinic in a Developing Country.

Background

Methods

Results

Conclusion

Publications

Effective Early Treatment of AChR Antibody-Positive Myasthenia Gravis with Rituximab; the Experience from a Neuroimmunology Clinic in a Developing Country.

Similar Datasets

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