Dataset Information

High-dose intravenous methylprednisolone therapy in patients with Graves' orbitopathy is associated with the increased activity of factor VIII.

ABSTRACT:

Purpose

Venous thromboembolic events (VTE), with their life-threatening manifestation as pulmonary embolism, are potential adverse effects of intravenous methylprednisolone (IVMP) pulse therapy, partially due to a hypercoagulable state. The aim of the study was to analyze the influence of IVMP on selected hemostatic parameters in patients with moderate-to-severe Graves' orbitopathy (GO).

Methods

26 euthyroid patients with GO were treated with 12 pulses of IVMP (6?×?0.5, 6?×?0.25 g every week). Hemostatic variables [factor (F) II, FV, FVII, FVIII, fibrinogen, antithrombin, activated partial thromboplastin time (aPTT), prothrombin time, international normalized ratio of prothrombin time, platelets and D-dimer] were analysed before, 24 and 48 h after 1st, 6th and 12th pulse.

Results

A constant, transient trend in changes of some hemostatic variables was observed after all assessed pulses. We discovered an increase in median activity of FVIII 24 and 48 h after pulses, with a shortening of aPTT 24 h after each IVMP pulse (p?ConclusionsThe increase of FVIII activity is a consequence of treatment with IVMP and occurs after each pulse. In patients with additional risk factors of VTE, anticoagulation prophylaxis should be considered.

SUBMITTER: Miskiewicz P

PROVIDER: S-EPMC6394431 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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High-dose intravenous methylprednisolone therapy in patients with Graves' orbitopathy is associated with the increased activity of factor VIII.

Miśkiewicz P P Milczarek-Banach J J Rutkowska-Hinc B B Kondracka A A Bednarczuk T T

Journal of endocrinological investigation 20180609 2

<h4>Purpose</h4>Venous thromboembolic events (VTE), with their life-threatening manifestation as pulmonary embolism, are potential adverse effects of intravenous methylprednisolone (IVMP) pulse therapy, partially due to a hypercoagulable state. The aim of the study was to analyze the influence of IVMP on selected hemostatic parameters in patients with moderate-to-severe Graves' orbitopathy (GO).<h4>Methods</h4>26 euthyroid patients with GO were treated with 12 pulses of IVMP (6 × 0.5, 6 × 0.25 g ...[more]

PMID: 29949121

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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.

Project description:Background: Intravenous glucocorticoid (GC) has been proposed to treat moderately severe Graves' orbitopathy (GO); however, the optimal regime remains debatable. We therefore performed this network meta-analysis to objectively determine the comparative efficacy and safety of different intravenous GC regimes, including daily, weekly, or monthly intravenous regimes, for the treatment of GO. Methods: We electronically searched Medline (via PubMed), EMBASE (via OVID), and the Cochrane Central Register of Controlled Trials (CENTRAL) (via OVID) to retrieve randomized controlled trials (RCTs) investigating the comparative efficacy and safety of different intravenous GC regimes in GO patients from the inception of each database to March 2021. The latest search was updated in June 2021. The risk of bias of original studies was assessed using the Cochrane risk bias assessment tool. A random-effects Bayesian network meta-analysis was conducted using the Markov chain Monte Carlo (MCMC) simulation. Ranking probabilities of all regimes were calculated to rank all regimes. Statistical analysis was conducted using the ADDIS software. Results: A total of 10 studies involving 593 patients met the selection criteria. Network meta-analysis suggested that the weekly intravenous GC regime (WR) [response: odds ratio (OR), 4.27; 95% creditable interval (CrI); 1.82 to 11.02; clinical activity score change (CASC): standard mean difference (SMD), -0.59; 95% CrI; -1.19 to -0.03) and monthly intravenous regime (MR) (response: OR, 6.32; 95% CrI; 1.25 to 34.96; CASC: SMD, -1.17; 95% CrI; -2.32 to -0.01) were superior to the oral GC (OGC) regime in response and CASC. Meanwhile, pooled results also indicated that the WR was related to the decreased risk of AEs compared with the OGC regime (OR, 0.22; 95% CrI; 0.08-0.62) and daily intravenous GC regime (DR) (OR, 0.19; 95% CrI; 0.03-0.97). Ranking probabilities indicated that the MR and WR have a relatively higher probability of becoming the best option for response, proptosis, and AEs. Conclusion: Based on limited evidence, the WR or MR should be preferentially prescribed to treat patients with moderately severe GO. However, more studies with a large sample size should be conducted to further confirm our findings and compare the WR with the MR.

Dataset Information

High-dose intravenous methylprednisolone therapy in patients with Graves' orbitopathy is associated with the increased activity of factor VIII.

Purpose

Methods

Results

Publications

High-dose intravenous methylprednisolone therapy in patients with Graves' orbitopathy is associated with the increased activity of factor VIII.

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