Trial reportPloS one2017
Everolimus long-term use in patients with tuberous sclerosis complex: Four-year update of the EXIST-2 study.
Trial report in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00790400 (A Randomized, Double-blind, Placebo-controlled Study of RAD0001 in the Treatment of Angiomyolipoma in Patients With Either Tuberous Sclerosis Complex), which is not on this map. Cited by 66 papers, 4 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Randomized, Double-blind, Placebo-controlled Study of RAD0001 in the Treatment of Angiomyolipoma in Patients With Either Tuberous Sclerosis Complex (TSC) or Sporadic Lymphangioleiomyomatosis (LAM)
Who cites it
66 citing papers in PubMed, 4 syntheses or guidelines pooled it, 164 citations in OpenAlex.
- Rapamycin and rapalogs for tuberous sclerosis complex.The Cochrane database of systematic reviews · 2023Pooled it
- Treatment of Cardiac Rhabdomyomas with mTOR Inhibitors in Children with Tuberous Sclerosis Complex-A Systematic Review.International journal of environmental research and public health · 2021Pooled it
- The efficacy and safety of pharmacological treatments for lymphangioleiomyomatosis.Respiratory research · 2020Pooled it
- The efficacy and adverse events of mTOR inhibitors in lymphangioleiomyomatosis: systematic review and meta-analysis.Orphanet journal of rare diseases · 2018Pooled it
- Effectiveness and safety of everolimus treatment in patients with tuberous sclerosis complex in real-world clinical practice.Orphanet journal of rare diseases · 2023Trial
- Effect of everolimus on renal function in patients with tuberous sclerosis complex: evidence from EXIST-1 and EXIST-2.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2019Trial
- Assessing the outcomes of everolimus on renal angiomyolipoma associated with tuberous sclerosis complex in China: a two years trial.Orphanet journal of rare diseases · 2018Trial
- Trial
- Features and management of kidney manifestations of tuberous sclerosis complex: a real-world study in a Brazilian patient cohort.BMC nephrology · 2026Observational
- Real-world management of tuberous sclerosis complex-associated renal angiomyolipomas: the impact of mTOR inhibitors.Clinical kidney journal · 2026Article
- Tumor fat composition predicts response to everolimus and supports low-dose therapy in TSC-associated renal angiomyolipomas: a multicenter prospective study.Frontiers in oncology · 2026Article
- Vascular malformations: from genetics to therapeutics.EMBO molecular medicine · 2026Review
- Rapamycin Does Not Compromise Exercise-Induced Muscular Adaptations in Female Mice.Aging cell · 2025Article
- mTOR pathway diseases: challenges and opportunities from bench to bedside and the mTOR node.Orphanet journal of rare diseases · 2025Review
- Insights into Tuberous Sclerosis Complex : From Genes to Clinics.Journal of Korean Neurosurgical Society · 2025Article
- The prospect of novel orphan therapeutic protocol for TSC2/PKD1 contiguous gene syndrome: a case report.BMC nephrology · 2025Article
- Focal postnatal deletion ofFrontiers in molecular neuroscience · 2025Article
- mTORC1-selective inhibitors rescue cellular phenotypes in TSC iPSC-derived neurons.Frontiers in neuroscience · 2025Article
- Central nervous system manifestations of tuberous sclerosis complex: A single centre experience in Qatar.Saudi medical journal · 2024Article
- Effects of Target of Rapamycin and Phosphatidylinositol 3-Kinase Inhibitors and Other Autophagy-Related Supplements on Life Span inInternational journal of molecular sciences · 2024Article
6 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 10 institutions in 7 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivesWe examined the long-term effects of everolimus in patients with renal angiomyolipoma associated with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis.
methodsFollowing favorable results from the double-blind core phase of EXIST-2 (NCT00790400), patients were allowed to receive open-label everolimus (extension phase). Patients initially randomly assigned to everolimus continued on the same dose; those who were receiving placebo crossed over to everolimus 10 mg/day. Dose modifications were based on tolerability. The primary end point was angiomyolipoma response rate, defined as a ≥50% reduction from baseline in the sum volume of target renal angiomyolipomas in the absence of new target angiomyolipomas, kidney volume increase of >20% from nadir, and angiomyolipoma-related bleeding grade ≥2. The key secondary end point was safety.
resultsOf the 112 patients who received ≥1 dose of everolimus, 58% (95% CI, 48.3% to 67.3%) achieved angiomyolipoma response. Almost all patients (97%) experienced reduction in renal lesion volumes at some point during the study period. Median duration of everolimus exposure was 46.9 months. Sixteen (14.3%) patients experienced angiomyolipoma progression at some point in the study. No angiomyolipoma-related bleeding or nephrectomies were reported. One patient on everolimus underwent embolization for worsening right flank pain. Subependymal giant cell astrocytoma lesion response was achieved in 48% of patients and skin lesion response in 68% of patients. The most common adverse events suspected to be treatment-related were stomatitis (42%), hypercholesterolemia (30.4%), acne (25.9%), aphthous stomatitis and nasopharyngitis (each 21.4%). Ten (8.9%) patients withdrew because of an adverse event. Renal function remained stable, and the frequency of emergent adverse events generally decreased over time.
conclusionsEverolimus treatment remained safe and effective over approximately 4 years. The overall risk/benefit assessment supports the use of everolimus as a viable treatment option for angiomyolipoma associated with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis.
trial registrationClinicalTrials.gov NCT00790400.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.