scholarly journals Management of everolimus-associated adverse events in patients with tuberous sclerosis complex: a practical guide

2017 ◽  
Vol 12 (1) ◽  
Author(s):  
Mark Davies ◽  
Anurag Saxena ◽  
John C. Kingswood
Keyword(s):  
Adverse Events ◽  
Tuberous Sclerosis ◽  
Tuberous Sclerosis Complex ◽  
Practical Guide

scholarly journals A randomized controlled trial with everolimus for IQ and autism in tuberous sclerosis complex

Neurology ◽  
2019 ◽  
Vol 93 (2) ◽  
pp. e200-e209 ◽  
Author(s):  
Iris E. Overwater ◽  
André B. Rietman ◽  
Sabine E. Mous ◽  
Karen Bindels-de Heus ◽  
Dimitris Rizopoulos ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Adverse Events ◽  
Tuberous Sclerosis ◽  
Tuberous Sclerosis Complex ◽  
Behavioral Problems ◽  
Neuropsychological Functioning ◽  
Controlled Trial ◽  
Full Scale ◽  
Neuropsychological Deficits ◽  
Secondary Outcomes

ObjectiveTo investigate whether mammalian target of rapamycin inhibitor everolimus can improve intellectual disability, autism, and other neuropsychological deficits in children with tuberous sclerosis complex (TSC).MethodsIn this 12-month, randomized, double-blind, placebo-controlled trial, we attempted to enroll 60 children with TSC and IQ <80, learning disability, special schooling, or autism, aged 4–17 years, without intractable seizures to be assigned to receive everolimus or placebo. Everolimus was titrated to blood trough levels of 5–10 ng/mL. Primary outcome was full-scale IQ; secondary outcomes included autism, neuropsychological functioning, and behavioral problems.ResultsThirty-two children with TSC were randomized. Intention-to-treat analysis showed no benefit of everolimus on full-scale IQ (treatment effect −5.6 IQ points, 95% confidence interval −12.3 to 1.0). No effect was found on secondary outcomes, including autism and neuropsychological functioning, and questionnaires examining behavioral problems, social functioning, communication skills, executive functioning, sleep, quality of life, and sensory processing. All patients had adverse events. Two patients on everolimus and 2 patients on placebo discontinued treatment due to adverse events.ConclusionsEverolimus did not improve cognitive functioning, autism, or neuropsychological deficits in children with TSC. The use of everolimus in children with TSC with the aim of improving cognitive function and behavior should not be encouraged in this age group.Clinicaltrials.gov identifierNCT01730209.Classification of evidenceThis study provides Class I evidence that for children with TSC, everolimus does not improve intellectual disability, autism, behavioral problems, or other neuropsychological deficits.

scholarly journals Low-Dose Everolimus Maintenance Therapy for Renal Angiomyolipoma Associated With Tuberous Sclerosis Complex

2021 ◽  
Vol 8 ◽  
Author(s):  
Cong Luo ◽  
Wen-Rui Ye ◽  
Xiong-Bin Zu ◽  
Min-Feng Chen ◽  
Lin Qi ◽  
...  
Keyword(s):  
Adverse Events ◽  
Maintenance Therapy ◽  
Tuberous Sclerosis ◽  
Induction Therapy ◽  
Tuberous Sclerosis Complex ◽  
Low Dose ◽  
Standard Dose ◽  
Gene Mutations ◽  
Renal Angiomyolipoma ◽  
Significance Level

Objective: To assess the safety and efficacy of low-dose everolimus maintenance therapy for tuberous sclerosis complex-related renal angiomyolipoma (TSC-RAML) patients that had previously undergone standard-dose treatment for a minimum of 6 months.Materials and Methods: In total, 24 patients with a definitive TSC diagnosis were enrolled from April 2018 – April 2019 at Xiangya Hospital, Central South University. All patients underwent low-dose everolimus maintenance therapy following standard-dose everolimus induction therapy for a minimum of 6 months. Patients additionally underwent TSC1/TSC2 genetic testing, And they were followed-up at 3, 6, 12, 18, and 24 months. The Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) criteria were used to monitor patient RAML responses, while adverse events (AEs) were assessed as per the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE, version 4.0). P &lt; 0.05 was the significance level for all analyses, which were performed using SPSS 19.0.Results: TSC1/TSC2 gene mutations were present in all 24 patients, all of whom achieved a significant reduction in TSC-RAML volume within the initial 6-month induction therapy period, and exhibited volume stabilization during the low-dose maintenance therapy treatment period without any instances of TSC-RAML regrowth. Adverse events (AEs) were significantly less severe and less frequent over the course of maintenance therapy relative to standard therapy.Conclusions: Low-dose everolimus maintenance therapy represents an effective approach to achieving TSC-RAML control following a minimum of 6 months of full-dose induction therapy, and may be associated with decreases in everolimus-related AE frequency and severity.

scholarly journals Quality of life and its predictors in adults with tuberous sclerosis complex (TSC): a multicentre cohort study from Germany

2021 ◽  
Vol 3 (1) ◽  
Author(s):  
Johann Philipp Zöllner ◽  
Nadine Conradi ◽  
Matthias Sauter ◽  
Markus Knuf ◽  
Susanne Knake ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Regression Analysis ◽  
Adverse Events ◽  
Tuberous Sclerosis ◽  
Tuberous Sclerosis Complex ◽  
Neurological Disorders ◽  
Organ Manifestations ◽  
Neuropsychiatric Manifestations ◽  
Active Epilepsy

Abstract Background Tuberous sclerosis complex (TSC) is a monogenetic, multisystemic disease characterised by the formation of benign tumours that can affect almost all organs, caused by pathogenic variations in TSC1 or TSC2. In this multicentre study from Germany, we investigated the influence of sociodemographic, clinical, and therapeutic factors on quality of life (QoL) among individuals with TSC. Methods We assessed sociodemographic and clinical characteristics and QoL among adults with TSC throughout Germany using a validated, three-month, retrospective questionnaire. We examined predictors of health-related QoL (HRQoL) using multiple linear regression analysis and compared the QoL among patients with TSC with QoL among patients with other chronic neurological disorders. Results We enrolled 121 adults with TSC (mean age: 31.0 ± 10.5 years; range: 18–61 years, 45.5% [n = 55] women). Unemployment, a higher grade of disability, a higher number of organ manifestations, the presence of neuropsychiatric manifestations or active epilepsy, and a higher burden of therapy-related adverse events were associated with worse QoL, as measured by two QoL instruments (EuroQoL-5 dimensions [EQ-5D] and Quality of Life in Epilepsy Patients [QOLIE-31]). Neuropsychiatric and structural nervous system manifestations, the number of affected organs, and therapy-related adverse events were also associated with higher depression, as measured by the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E). In multiple regression analysis, more severe therapy-related adverse events (large effect, p < 0.001), active epilepsy (large effect, p < 0.001), and neuropsychiatric manifestations (medium effect, p = 0.003) were independently associated with worse HRQoL, explaining 65% of the variance (p < 0.001). The HRQoL among patients with active TSC-associated epilepsy was worse than that among patients with drug-refractory mesial temporal lobe epilepsy (p < 0.001), and the generic QoL among patients with more than three TSC organ manifestations was similar to those of patients with severe migraine and uncontrolled asthma. Conclusions Active epilepsy, neuropsychiatric manifestations (such as anxiety and depression), and therapy-related adverse events are important independent predictors of worse quality of life among adults with TSC. Generic quality of life in TSC with several manifestations is similar to uncontrolled severe chronic diseases and significantly negatively correlates with TSC severity. Trial registration DRKS, DRKS00016045. Registered 01 March 2019.

scholarly journals Mutational analysis of renal angiomyolipoma associated with tuberous sclerosis complex and the outcome of short-term everolimus therapy

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Jianxin Ni ◽  
Fengqi Yan ◽  
Weijun Qin ◽  
Lei Yu ◽  
Geng Zhang ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Adverse Events ◽  
Tuberous Sclerosis ◽  
Tuberous Sclerosis Complex ◽  
Gene Mutations ◽  
Chinese Patients ◽  
Term Therapy ◽  
Renal Angiomyolipoma ◽  
Efficacy And Safety ◽  
Short Term

Abstract To identify clinical characteristics and mutation spectra in Chinese patients with renal angiomyolipoma (AML) associated with the tuberous sclerosis complex (TSC, TSC-AML), examined the efficacy and safety of short-term everolimus therapy (12 weeks). We analyzed the frequency distribution of each TSC-related clinical feature and investigated gene mutations by genetic testing. Some subjects received everolimus for 12 weeks at a dose of 10 mg/day, and the efficacy and safety of short-term everolimus therapy were examined. Finally, 82 TSC-AML patients were enrolled for analysis in this study. Of the 47 patients who underwent genetic testing, 22 patients (46.81%) had at least one detectable mutation in the TSC1 or TSC2 gene: 7 were TSC1 gene mutations, 13 were TSC2 gene mutations, and 2 were found in both TSC1 and TSC2. Everolimus treatment had a statistically significant effect on the renal AML volume reduction during follow-up (P < 0.05), and the mean reduction rate of volume for all cases was 56.47 ± 23.32% over 12 weeks. However, 7 patients (7/25; 28.00%) experienced an increase in renal AML tumor volume within 12 weeks after discontinuation of the everolimus treatment. Although most patients (27/30, 90.00%) experienced some adverse events during the treatment period, all such events were mild, and no patients discontinued or needed dose reduction because of adverse events. Overall, in this study, the mutation rate of TSC-AML patients is much lower than other reports. Short-term everolimus treatment for TSC-AML is effective and safe, but the stability is much lower than long-term therapy.

scholarly journals Everolimus Versus Sirolimus for Angiomyolipoma Associated with Tuberous Sclerosis Complex: A Multi-Institutional Retrospective Study in China

2021 ◽  
Author(s):  
luo cong ◽  
Yu-shi Zhang ◽  
Ming-Xin Zhang ◽  
Min-Feng Chen ◽  
Yuan Li ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Adverse Events ◽  
Tuberous Sclerosis ◽  
Oral Mucositis ◽  
Tuberous Sclerosis Complex ◽  
National Cancer Institute ◽  
Therapeutic Efficacy ◽  
Efficacy And Safety ◽  
First Choice ◽  
Significant Difference

Abstract Purpose To evaluate the efficacy and safety of everolimus and sirolimus in patients with tuberous sclerosis complex-associated angiomyolipomas (TSC-AML). Materials and Methods We performed a multi-institutional retrospective study of TSC-AML patients treated with oral everolimus or sirolimus. Angiomyolipoma volume was estimated using orthogonal measurements by MRI or CT. Adverse events (AEs) were assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events. All analyses were performed using SPSS 19.0 software. Results There were high response rates in both two groups. With the prolonged medication time, the therapeutic efficacy of two agents became more significant. Everolimus had a more significant TSC-AML volume reduction after 6 and 12 months than sirolimus. More than 1/2 of everolimus patients had ≥ 50% reduction and approximately 80% of them had ≥ 30% reduction, higher than that of the sirolimus patients. Regarding safety, there was no significant difference in the incidence of AEs between the two groups. And the most common AE was oral mucositis. Conclusions Both everolimus and sirolimus are excellent therapeutic choices for TSC-AML. However, everolimus had a better therapeutic efficacy than sirolimus, especially in reducing TSC-AML volume. Therefore, everolimus is recommended as the first choice.

scholarly journals Everolimus versus sirolimus for angiomyolipoma associated with tuberous sclerosis complex: a multi-institutional retrospective study in China

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Cong Luo ◽  
Yu-Shi Zhang ◽  
Ming-Xin Zhang ◽  
Min-Feng Chen ◽  
Yuan Li ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Adverse Events ◽  
Tuberous Sclerosis ◽  
Tuberous Sclerosis Complex ◽  
National Cancer Institute ◽  
Therapeutic Efficacy ◽  
Efficacy And Safety ◽  
First Choice ◽  
Significant Difference ◽  
Choice Of Therapy

Abstract Purpose To evaluate the efficacy and safety of everolimus and sirolimus in patients with tuberous sclerosis complex-associated angiomyolipomas (TSC-AML). Materials and methods We performed a multi-institutional retrospective study of TSC-AML patients treated with oral everolimus 10 mg or sirolimus 2 mg per day for at least 3 months. Angiomyolipoma volume was estimated using orthogonal measurements by MRI or CT. Adverse events (AEs) were assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events. All analyses were performed using SPSS 19.0 software. Results Response rates were high in both groups. With the prolonged medication durations, the therapeutic efficacy of both agents became more significant. The TSC-AML volume reduction after 6 and 12 months was more pronounced in patients with everolimus than those with sirolimus. More than half of the patients treated with everolimus had ≥ 50% reduction, and approximately 80% of them had ≥ 30% reduction, which was higher than that in patients treated with sirolimus. Regarding safety, there was no significant difference in the incidence of AEs between the two groups. Conclusions Both everolimus and sirolimus are excellent therapeutic options for TSC-AML. However, everolimus has a better therapeutic efficacy than sirolimus, particularly in reducing TSC-AML volume. Everolimus is therefore recommended as the first choice of therapy for TSC-AML.

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