Evidence map›Paper›PMID 38042867›Full record

Trial reportOrphanet journal of rare diseases2023

Effectiveness and safety of everolimus treatment in patients with tuberous sclerosis complex in real-world clinical practice.

Ine Cockerell, Jakob Christensen, Christina E Hoei-Hansen, Lotte Holst, Mikkel Grenaa Frederiksen, Aart Imran Issa-Epe, Bård Nedregaard, Ragnar Solhoff, Ketil Heimdal, Cecilie Johannessen Landmark and 2 more

Open access · goldAbstract readClinical Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Orphanet journal of rare diseases, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
4.2field-weighted citation impact, top 5% of its field
1 · What the graph read from 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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

16 citing papers in PubMed, 24 citations in OpenAlex.

  1. Advances in the management of pediatric low-grade glioma.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026
    Review
  2. Tuberous sclerosis complex.Nature reviews. Disease primers · 2026
    Review
  3. Review
  4. Review
  5. Review
  6. Article
  7. Review
  8. Review
  9. Review
  10. Review
  11. Surgical treatment of subependymal giant cell astrocytoma in patients with tuberous sclerosis complex-an institutional experience and results.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2025
    Article
  12. Article
  13. Review
  14. Observational
  15. Article
  16. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 4 institutions in 3 countries.

Ine CockerellDepartment of Rare Disorders and Disabilities, National Centre for Rare Epilepsy-Related Disorders, Oslo University Hospital, Pb 4950, 0424, Nydalen, Oslo, Norway. inec@ous-hf.no.ORCID 0000-0002-6810-3941
Jakob ChristensenDepartment of Clinical Medicine, Aarhus University, Aarhus, Denmark.
Christina E Hoei-HansenDepartment of Clinical Medicine, Copenhagen University, Copenhagen, Denmark.
Lotte HolstDepartment of Clinical Medicine, Aarhus University, Aarhus, Denmark.
Mikkel Grenaa FrederiksenDepartment of Paediatrics, University Hospital Rigshospitalet, Copenhagen, Denmark.
Aart Imran Issa-EpeSection of Abdominal Radiology, Department of Radiology, Oslo University Hospital, Oslo, Norway.
Bård NedregaardSection of Neuroradiology, Department of Radiology, Oslo University Hospital, Oslo, Norway.
Ragnar SolhoffDepartment of Neurology, Sørlandet Hospital, Arendal, Norway.
Ketil HeimdalDepartment of Medical Genetics, Oslo University Hospital, Oslo, Norway.
Cecilie Johannessen LandmarkDepartment of Pharmacy, Faculty of Health Sciences, Oslo Metropolitan University, Oslo, Norway.
Caroline LundDepartment of Rare Disorders and Disabilities, National Centre for Rare Epilepsy-Related Disorders, Oslo University Hospital, Pb 4950, 0424, Nydalen, Oslo, Norway.
Terje NærlandK.G. Jebsen Center for Neurodevelopmental Disorders, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Oslo University Hospital · NOAarhus University · DKRigshospitalet · DKSørlandet Hospital Arendal · NO

Funding

Stiftelsen Kristian Gerhard Jebsen SKGJ-MED-021
6 · The paper itself

Abstract

backgroundThe randomised double-blinded placebo-controlled EXIST-1-3 studies have showed everolimus effective with adverse effects reported as acceptable in treatment of symptoms in patients with tuberous sclerosis complex (TSC), although evidence of outcomes in clinical practice remains limited. This study aimed to investigate, in clinical practice, the effectiveness and safety of everolimus for epilepsy, renal angiomyolipoma (rAML), and subependymal giant cell astrocytoma (SEGA) in patients with TSC.

resultsThe study included 64 patients with TSC (median age: 19, range 0.9-54 years) receiving everolimus treatment (Norway: n = 35; Denmark: n = 29). Among 45 patients with epilepsy, 14 (31%) were responders experiencing ≥ 50% reduction in seizure frequency in the last 3 months of treatment compared with the last 3 months before treatment. Nineteen (42%) patients changed their anti-seizure medications (ASMs). Responders were more common among patients < 18 years (46%) than among patients ≥ 18 years (14%, p = 0.03). In 29 patients with rAML, everolimus reduced (≥ 30% decrease) and stabilized (< 20% increase, ≤ 30% decrease) longest diameter of rAML in 38% and 59%, respectively, after a mean treatment duration of 37 months. SEGA volume was reduced in three patients by 71%, 43%, and 48% after 39, 34, and 82 months. Adverse effects were reported in 61 of 64 patients (95%) after a median treatment duration of 31 months (range 0-106), with oral ulceration/stomatitis (63%) and upper respiratory tract infections (38%) being the most common. The most common laboratory abnormalities were increased cholesterol (41%), anaemia (30%), and leucopoenia (25%). Grade 3-4 adverse effects were reported in 36% of cases, and life-threatening conditions were reported in two patients. Nine patients discontinued everolimus treatment.

conclusionsSeizure reduction in this study sample was consistent with results from EXIST, but might be lower than expected, given that changes in concomitant ASMs are part of clinical practice. Seizure reduction was associated with younger age. As with EXIST, everolimus reduced or stabilised rAML size in most patients. SEGA volume was reduced in all three patients. Close follow-up is needed for this group, especially for children and patients who may not be able to report adverse effects.

Indexed as

AngiomyolipomaAntineoplastic AgentsAstrocytomaEpilepsyKidney NeoplasmsTuberous SclerosisAdolescentAdultChildChild, PreschoolEverolimusHumansInfantMiddle AgedSeizuresYoung AdultAntineoplastic AgentsEverolimusAdverse eventsEpilepsyEverolimusmTOR inhibitorRenal angiomyolipomaSirolimusSubependymal giant cell astrocytomaTuberous sclerosis complex

Identifiers

PMID38042867
PMCPMC10693167
OpenAlexW4389264073

What OpenQuestion holds

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Registered trials

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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.