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Influence of Methylprednisolone Pulse Therapy on Liver Function in Patients with Graves' Orbitopathy.

ABSTRACT: Purpose:Intravenous methylprednisolone (IVMP) pulse therapy is the first-line treatment in active moderate-to-severe Graves' orbitopathy (GO) and dysthyroid optic neuropathy (DON). One of the adverse effects of this therapy is liver dysfunction that can be mild (ALT??300?U/L). ALI can be irreversible and fatal. The aim of the study was to evaluate the influence of two different schemes of therapy with IVMP in moderate-to-severe GO and DON on biochemical liver parameters. Materials and Methods:49 patients with moderate-to-severe GO were treated with IVMP in every week schedule (cumulative dose 4.5?g), and 19 patients with DON received 3.0?g IVMP (1.0?g/day for 3 consecutive days). AST, ALT, and total bilirubin were measured before treatment and after IVMP in the following selected pulses: after 0.5?g (A1), 3.0?g (A2), and 4.5?g (A3) in the group with moderate-to-severe GO and after 3.0?g IVMP in the group with DON (B1). Results:We observed a statistically higher level of AST and ALT after therapy with 3.0?g of IVMP (B1) than after 0.5?g (A1), 3.0?g (A2), and 4.5?g of IVMP (A3). Mild elevation of ALT was found in 4% and 11% of patients with moderate-to-severe GO and DON, respectively. Moderate elevation of ALT was found in 0% and 21% of patients with moderate-to-severe GO and DON, respectively. There were no cases of ALI. Conclusion:Therapy of GO with higher doses (1.0?g) of IVMP in consecutive days is associated with higher risk of liver damage than treatment with moderate doses (?0.5?g) in every week schedule. This trial is registered with NCT03667157.

SUBMITTER: Miskiewicz P

PROVIDER: S-EPMC6215562 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Influence of Methylprednisolone Pulse Therapy on Liver Function in Patients with Graves' Orbitopathy.

Miśkiewicz Piotr P Jankowska Anna A Brodzińska Kinga K Milczarek-Banach Justyna J Ambroziak Urszula U

International journal of endocrinology 20181021

<h4>Purpose</h4>Intravenous methylprednisolone (IVMP) pulse therapy is the first-line treatment in active moderate-to-severe Graves' orbitopathy (GO) and dysthyroid optic neuropathy (DON). One of the adverse effects of this therapy is liver dysfunction that can be mild (ALT < 100 U/L), moderate (ALT: 100-300 U/L), and severe defined as acute liver injury (ALI) (ALT > 300 U/L). ALI can be irreversible and fatal. The aim of the study was to evaluate the influence of two different schemes of therap ...[more]

PMID: 30420883

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Project description:BackgroundThyroid stimulating immunoglobulins (TSI) play a central role in the pathogenesis of Graves' orbitopathy (GO), while soluble interleukin-2 receptor (sIL-2R) is a marker for T-cell activity. We investigated TSI and sIL-2R levels in relation to thyroid function, disease activity and severity and response to treatment with intravenous methylprednisolone (IVMP) in patients with GO.MethodsTSI (bridge-based TSI binding assay), sIL-2R, TSH and fT4 levels were measured in biobank serum samples from 111 GO patients (37 male, 74 female; mean age 49.2 years old) and 25 healthy controls (5 male, 20 female; mean age 39.8 years old). Clinical characteristics and response to treatment were retrospectively retrieved from patient files.ResultsHigher sIL-2R levels were observed in GO patients compared to controls (p < 0.001). sIL-2R correlated with fT4 (r = 0.26), TSH (r = -0.40) and TSI (r = 0.21). TSI and sIL-2R concentrations were higher in patients with active compared to inactive GO (p < 0.001 and p < 0.05, respectively). Both TSI and sIL-2R correlated with total clinical activity score (CAS; r = 0.33 and r = 0.28, respectively) and with several individual CAS items. Cut-off levels for predicting active GO were 2.62 IU/L for TSI (AUC = 0.71, sensitivity 69%, specificity 69%) and 428 IU/mL for sIL-2R (AUC = 0.64, sensitivity 62%, specificity 62%). In multivariate testing higher TSI (p < 0.01), higher age (p < 0.001) and longer disease duration (p < 0.01) were associated with disease activity. TSI levels were higher in patients with a poor IVMP response (p = 0.048), while sIL-2R levels did not differ between responders and non-responders. TSI cut-off for predicting IVMP response was 19.4 IU/L (AUC = 0.69, sensitivity 50%, specificity 91%). In multivariate analysis TSI was the only independent predictor of response to IVMP (p < 0.05).ConclusionsHigh TSI levels are associated with active disease (cut-off 2.62 IU/L) and predict poor response to IVMP treatment (cut-off 19.4 IU/L) in GO. While sIL-2R correlates with disease activity, it is also related to thyroid function, making it less useful as an additional biomarker in GO.

Project description:BackgroundImmunosuppressive therapy of Graves' orbitopathy (GO) is indicated during the active phase of disease. Intravenous steroids (IVGC) are effective in about 70% of patients, although unresponsiveness or relapse are observed. In previous studies, rituximab (RTX) has been shown to be effective in inactivating moderate-to-severe GO when used early in the disease, but its optimal dosage has never been studied in randomized clinical trials. Aim of this study was to compare the efficacy and safety of different doses of RTX, based on a post-hoc analysis of two open label studies and one prospective trial randomized to IVGC.Methodsof 40 patients (35 women, 5 men), with active moderate-to-severe GO treated with RTX, 14 received a single dose of 100 mg (Group 1), 15 a single dose of 500 mg (Group 2) and 11 two 1000 mg doses, administered one week apart (Group 3). Thyroid function, TSH-receptor antibodies (TRAb) and peripheral CD19+ cells were measured. Primary endpoint was disease inactivation, measured as a decrease of the Clinical Activity Score (CAS) of at least two points. Secondary endpoints were improvement of proptosis, diplopia, quality of life and safety.ResultsBaseline CAS decreased significantly in all groups (P<0.0001), independently of GO duration or whether patients had newly occurring or relapsing GO after IVGC. Proptosis did not significantly change. There was an inverse correlation between the Gorman score for diplopia and RTX dose (P<0.01). The appearance score of the GO-QoL improved in Group 1 (P=0.015), and the visual function score, in Group 2 (P=0.04). A reduction of serum TRAb was observed in Group 1 (P=0.002) and Group 2 (P<0.0002), but not in Group 3. CD19+ cell decreased in all groups (P<0.01), independently of the dose.ConclusionsWe studied the optimal dosage of RTX in the treatment of active moderate-to-severe GO. In this analysis, we considered the efficacy of RTX in inactivating GO, in changing its natural course, its effect on disease severity and on the patients' quality of life. Based on our clinical findings, and balancing the cost of therapy, a single 500 mg dose regimen is suggested in the majority of patients.

Dataset Information

Influence of Methylprednisolone Pulse Therapy on Liver Function in Patients with Graves' Orbitopathy.

Publications

Influence of Methylprednisolone Pulse Therapy on Liver Function in Patients with Graves' Orbitopathy.

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