Adequate tacrolimus concentration for myasthenia gravis treatment

Kanai, Tetsuya; Uzawa, Akiyuki; Kawaguchi, Naoki; Himuro, Keiichi; Oda, Fumiko; Ozawa, Yukiko; Kuwabara, Satoshi

doi:10.1111/ene.13189

Cited by 30 publications

(22 citation statements)

References 22 publications

(47 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Another possible explanation is that, although the initial prescribed dose is usually 3 mg/day under the national health insurance system in Japan, the minimal effective dose is actually lower in most patients. Patients with an adequate trough serum concentration of tacrolimus (≥4.8 ng/mL) achieve minimal manifestation status or better more frequently than those with low concentrations (<4.8 ng/mL) . Data on the trough serum tacrolimus concentrations would help to clarify the possible explanations and to determine the minimal effective dose in tacrolimus‐naive or well‐controlled MG; unfortunately these data were unavailable in our study.…”

Section: Discussionmentioning

confidence: 93%

Safety of tapering tacrolimus dose in patients with well‐controlled anti‐acetylcholine receptor antibody‐positive myasthenia gravis

Nishida

Takahashi

Kanai

et al. 2019

Euro J of Neurology

Self Cite

View full text Add to dashboard Cite

Background and purpose Tapering immunosuppressants is desirable in patients with well‐controlled myasthenia gravis (MG). However, the association between tapering of calcineurin inhibitor dosage and reduction‐associated exacerbation is not known. The aim of this study was to clarify the frequency of reduction‐associated exacerbation when tacrolimus is tapered in stable patients with anti‐acetylcholine receptor antibody‐positive MG, and to determine the factors that predict exacerbations. Methods We retrospectively analyzed 115 patients in whom tacrolimus dosage was tapered. The reduction‐associated exacerbation was defined as the appearance or worsening of one or more MG symptoms <3 months after the reduction. Results Tacrolimus dosage was successfully tapered in 110 patients (96%) without any exacerbation. Five patients (4%) experienced an exacerbation, but symptoms were reversed in all patients when the tacrolimus dose was increased to the previous maintenance level. No patient developed an MG crisis. The age at onset was significantly earlier (30 vs. 56 years, P = 0.025) and the reduction in dosage was significantly larger (2.0 vs. 1.0 mg/day, P = 0.002) in patients with reduction‐associated exacerbation than in those without exacerbation. The cut‐off values determined in a receiver‐operating characteristic curve analysis were 52 years (sensitivity, 57%; specificity, 100%) for the age at onset and 1.5 mg (sensitivity, 80%; specificity, 100%) for the dose reduction. Conclusion Tapering of tacrolimus was possible in most patients with well‐controlled anti‐acetylcholine receptor antibody‐positive MG. Early age at onset and a large reduction from maintenance dosage were associated with exacerbation. Reductions ≤1.5 mg/day from the maintenance dosage should be considered for patients with late‐onset disease.

show abstract

Section: Discussionmentioning

confidence: 93%

Safety of tapering tacrolimus dose in patients with well‐controlled anti‐acetylcholine receptor antibody‐positive myasthenia gravis

Nishida

Takahashi

Kanai

et al. 2019

Euro J of Neurology

Self Cite

View full text Add to dashboard Cite

show abstract

“…Accordingly, for young patients with diplopia who refuse corticosteroids due to potential AEs or cosmetic problems, doctors are suggested to persuade them to accept corticosteroids or in conjunction with TAC to achieve adequate responses quickly. Several studies demonstrated that early stages of disease, thymoma and adequate TAC concentration were associated with responsiveness to TAC co-administered with corticosteroids (21,25). Differential sensitivity for MG symptoms might be a potential predictive factor for effectiveness of TAC monotherapy.…”

Section: Discussionmentioning

confidence: 99%

“…All patients were treated with an initial daily dose of TAC 2 mg. TAC was increased or Wuzhi tablets were added to achieve adequate TAC concentrations (4.8-10 ng/ml) (21). The maintenance dose ranged from 2 to 4 mg and was adjusted depending on clinical efficacy, side effects, and TAC concentrations.…”

Section: Tacrolimus Therapeutic Regimensmentioning

confidence: 99%

Favorable Effects of Tacrolimus Monotherapy on Myasthenia Gravis Patients

Fan

Shen

et al. 2020

Front. Neurol.

View full text Add to dashboard Cite

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.

show abstract

“…The thymic abnormalities have been proved to be mediated by overexpression of interferon (IFN)-β in the myasthenia gravis thymus 4 . Although a variety of types of drugs have been developed to treat myasthenia gravis, prognosis of patients with this disease is still not satisfactory, possibly due to the lack of medication standard and complex pathogenesis 5 .…”

Section: Introductionmentioning

confidence: 99%

Upregulation of miR150-5p in generalized myasthenia gravis patients is associated with decreased serum levels of IL-17 and increased serum levels of IL-10

Tian

et al. 2020

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub

View full text Add to dashboard Cite

Background. MiR150-5p has been reported to be involved in generalized myasthenia gravis, in which different cytokines play critical roles. The regulatory network of cytokines in generalized myasthenia gravis has not been fully elucidated. Our study aimed to investigate the interactions between miR150-5p and different cytokines in generalized myasthenia gravis. Materials and Method. Serum levels of miR150-5p and different cytokines including IL-2, IL-17, IL-10, IL-19, IL-20 and IL-35 were detected by qRT-PCR and ELISA, respectively. ROC curve analysis was performed to evaluate the diagnostic value of miR150-5p for generalized myasthenia gravis. Correlation between serum levels of miR150-5p and different cytokines were analyzed by Pearson correlation coefficient. Results. Compared with healthy controls, decreased serum levels of IL-2 and IL-17 and increased serum levels of miR150-5p, IL-10, IL-19, IL-20 and IL-35 were observed in patients with generalized myasthenia gravis. Serum levels of miR150-5p were positively correlated with IL-10 and negatively correlated with IL-17. After treatments, serum levels of miR150-5p and IL-10 decreased, while serum levels of IL-2 and IL-17 increased. Conclusion. Upregulation of miR150-5p is involved in generalized myasthenia gravis patients and is associated with decreased serum levels of IL-17 as well as increased serum levels of IL-10.

show abstract

Adequate tacrolimus concentration for myasthenia gravis treatment

Abstract: An adequate tacrolimus concentration is required for better MG prognosis.

Cited by 30 publications

References 22 publications

Safety of tapering tacrolimus dose in patients with well‐controlled anti‐acetylcholine receptor antibody‐positive myasthenia gravis

Safety of tapering tacrolimus dose in patients with well‐controlled anti‐acetylcholine receptor antibody‐positive myasthenia gravis

Favorable Effects of Tacrolimus Monotherapy on Myasthenia Gravis Patients

Upregulation of miR150-5p in generalized myasthenia gravis patients is associated with decreased serum levels of IL-17 and increased serum levels of IL-10

Contact Info

Product

Resources

About