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Different Monoclonal Antibodies in Myasthenia Gravis: A Bayesian Network Meta-Analysis

ABSTRACT: Background: Myasthenia gravis (MG) is a common autoimmune disease with acquired neuromuscular transmission disorders. Recently, monoclonal antibodies have been shown to successfully treat a variety of diseases. Methods: In this meta-analysis, an appropriate search strategy was used to search eligible randomized controlled trials (RCTs) on different monoclonal antibodies to treat patients with MG published up to September 2021 from the embase, PubMed, and Cochrane Library. We assessed the average difference or odds ratio between each drug and placebo and summarized them as the average and 95% confidence interval (CI), respectively. Results: In indicators of efficacy, patients receiving eculizumab (MD, −1.9; 95% CI, −3.2–0.76) had decreases in MG-ADL scores compared to placebo. In addition, only eculizumab (MD, −3.1; 95% CI, −4.7–1.5) and efgartigimod (MD, −1.4; 95% CI, −2.1–0.68) showed a significant difference from placebo in the amount of reduction in QMG scores, while neither of the other two monoclonal antibodies was statistically significant. With regard to the safety of monoclonal antibody therapy, there was no significant difference in the probability of AE in subjects treated with any of the four monoclonal antibodies compared to placebo. Conclusions: eculizumab was effective in reducing MG-ADL scores and QMG scores in myasthenia gravis. Meanwhile, eculizumab also caused fewer AE. As an emerging therapy, monoclonal antibodies are prospective in the treatment of MG. However, more researches are required to be invested in the future as the results obtained from small sample sizes are not reliable enough.

SUBMITTER: Song Z

PROVIDER: S-EPMC8804097 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Myasthenia gravis (MG) is an autoimmune disease affecting the neuromuscular junction, whose clinical hallmark is muscle weakness and early fatigability. Azathioprine (AZA) is commonly used in Myasthenia Gravis therapy. AZA is a purine antagonist, which inhibits the cell cycle in the resting and DNA synthesis phases. It is usually used as an immunosuppressant to block T- and B-cell proliferation. AZA, bioconverted to 6-mercaptopurine by glutathione S-transferase (GST), can be metabolized either through the hypoxanthine phosphoribosyl transferase pathway to active 6-thioguanine nucleotides (6-TGN) or through the thiopurine S-methyltransferase (TPMT) pathway to inactive methyl-thiopurine metabolites. The incorporation of active 6-TGNs into DNA, causing breaks in DNA strands resulting in interference with RNA production and thereby protein synthesis, is responsible for the drug effect. The response to AZA is determined by which metabolic pathway is being favored. While balanced use of both HPRT and TPMT pathways results in responsiveness to AZA, hyperactivity of TPMT skews the balance towards the TPMT pathway and results in unresponsiveness to AZA with no pharmacological effect. In contrast, low TPMT activity skews the balance towards the HPRT pathway, resulting in increasing side-effects due to the accumulation of 6-TGNs. Current treatments for MG therapy are often inadequate because less than 40% of patients achieve complete remission with available drugs. This reflects the lack of drugs acting on target sites for which there is strong evidence of pathogenicity and the inability to identify responder patients. No criteria for responsiveness are available, exposing patients to unpredictable failures and unpredictable side effects. These individuals are at particular risk for adverse drug reaction (ADRs) or therapeutic failure. Genetic profiling with the Affymetrix drug metabolizing enzymes and transports genotyping array offers the ability to determine 1,931 variants and 225 genes involved in drug metabolism and disposition. Accordingly, the study of well-known drug-metabolizing genes can be involved in the specific metabolic pathway of a drug, which is more likely to define genotype-phenotype association and thereby genotype profiles relevant to drug response that can be applied as predictive biomarkers for pharmacological treatment.

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Different Monoclonal Antibodies in Myasthenia Gravis: A Bayesian Network Meta-Analysis

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