Dataset Information

Favorable Effects of Tacrolimus Monotherapy on Myasthenia Gravis Patients.

ABSTRACT: Background and Purpose: Tacrolimus (TAC) has been proven to be a rapid-acting, steroid-sparing agent for myasthenia gravis (MG) therapy. However, evidence related to the effectiveness of TAC alone is rare. Therefore, this study was performed to investigate the effect of TAC monotherapy in MG patients. Methods: Forty-four MG patients who received TAC monotherapy were retrospectively analyzed. A mixed effect model was used to analyze improvements in MG-specific activities of daily living scale (MG-ADL), quantitative MG score (QMG) and MG-ADL subscores. Kaplan-Meier analysis was used to estimate the cumulative probability of minimal manifestations (MM) or better. Adverse events (AEs) were recorded for safety analyses. Results: Of the patients receiving TAC monotherapy, MG-ADL scores were remarkably improved at 3, 6 and 12 months compared with scores at baseline (mean difference and 95% CIs: -3.29 [-4.94, -1.64], -3.97 [-5.67, -2.27], and -4.67 [-6.48, -2.85], respectively). QMG scores significantly decreased at 6 and 12 months, with mean differences and 95% CIs of -4.67(-6.88, -2.45) and -5.77 (-7.55, -4.00), respectively. Estimated median period to achieve "MM or better" was 5.0 (95% CIs, 2.8, 7.2) months. Ocular MG (OMG) and generalized MG (GMG) showed similar therapeutic effects in cumulative probabilities of "MM or better" (P-value = 0.764). A better response was observed in MG-ADL subscores for ptosis and bulbar symptoms. AEs occurred in 37.5% of patients and were generally mild and reversible. Conclusions: TAC monotherapy is a promising option to rapidly alleviate all symptoms of MG, especially for ptosis and bulbar symptoms.

SUBMITTER: Fan Z

PROVIDER: S-EPMC7652845 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Favorable Effects of Tacrolimus Monotherapy on Myasthenia Gravis Patients.

Fan Zhirong Z Li Zunbo Z Shen Faxiu F Zhang Xueping X Lei Lin L Su Shengyao S Lu Yan Y Di Li L Wang Min M Xu Min M Da Yuwei Y

Frontiers in neurology 20201027

<b>Background and Purpose:</b> Tacrolimus (TAC) has been proven to be a rapid-acting, steroid-sparing agent for myasthenia gravis (MG) therapy. However, evidence related to the effectiveness of TAC alone is rare. Therefore, this study was performed to investigate the effect of TAC monotherapy in MG patients. <b>Methods:</b> Forty-four MG patients who received TAC monotherapy were retrospectively analyzed. A mixed effect model was used to analyze improvements in MG-specific activities of daily li ...[more]

PMID: 33193063

Similar Datasets

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.

Project description:BackgroundOral prednisone has been recognized as the first-line therapy for the treatment of ocular myasthenia gravis (OMG). However, its long-term use is complicated by numerous adverse effects and is ineffective for some OMG patients in reaching remission. This study aimed to evaluate the effectiveness and safety of intravenous methylprednisolone (IVMP) and tacrolimus monotherapy for OMG patients with unsatisfactory responses to conventional prednisone therapy.MethodsWe retrospectively reviewed 57 OMG patients who had not achieved satisfactory improvement after prednisone therapy and thereby received IVMP or tacrolimus monotherapy for at least 6 months. Ocular symptoms were evaluated by the ocular-quantitative MG (QMG) score at each time point. A ≥ 2-point fall in ocular QMG score was defined as the cut-off point to indicate clinical improvement. Logistic regression analysis was performed to identify factors associated with the efficacy of IVMP at discharge. Adverse events were recorded.ResultsBoth IVMP and tacrolimus monotherapy demonstrated significant clinical efficacy, with no statistical differences observed at the study endpoint. The proportions of patients who reached the cut-off point for efficacy evaluation were higher in the IVMP group than in the tacrolimus group (1, 3, and 6 months: 51.7% (15/29) vs 12.0% (3/25), p = 0.002; 69.0% (20/29) vs 40.0% (10/25), p = 0.033; 69.0% (20/29) vs 46.4% (13/28), p = 0.085, respectively). Multivariate logistics analysis showed that high ocular QMG scores at baseline indicated favourable responses to IVMP treatment (OR = 1.781; 95% CI 1.066-2.975; p = 0.028). All the adverse events were transient and tolerable.ConclusionOur findings suggest that both IVMP and tacrolimus monotherapy hold promise as viable treatment options for OMG patients with unsatisfactory responses to oral prednisone. The study supports the safety and effectiveness of both therapies, with IVMP exhibiting faster improvement and favourable efficacy in patients with high ocular QMG scores.

Dataset Information

Favorable Effects of Tacrolimus Monotherapy on Myasthenia Gravis Patients.

Publications

Favorable Effects of Tacrolimus Monotherapy on Myasthenia Gravis Patients.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets