Long-term effects of sirolimus treatment for slow-flow vascular malformations: Real-world evidence from the French observational multicentre SIROLO study
This article relates to:
-
Long-term sirolimus in SFVMs: A critical appraisal of the SIROLO study
- Journal of the European Academy of Dermatology and Venereology
- First Published online: May 30, 2025
Cécilia Maillet
Unit of Pediatric Dermatology, Department of Dermatology, University Hospital Center (CHRU) of Tours, Tours, France
Reference Center for Genodermatoses and Rare Skin Diseases (MAGEC-Tours), Tours, France
Search for more papers by this authorOlivia Boccara
Department of Dermatology and Reference Center for Genodermatoses and Rare Skin Diseases (MAGEC), AP-HP, Paris University, Necker-Enfants Malades Hospital, Paris Centre University, Imagine Institute, Paris, France
On behalf of the Groupe de Recherche de la Société Française de Dermatologie Pédiatrique (Research Group of the French Society for Pediatric Dermatology)
Search for more papers by this authorStéphanie Mallet
Department of Dermatology, Assistance Publique-Hôpitaux de Marseille (AP-HM), Marseille, France
On behalf of the Groupe de Recherche de la Société Française de Dermatologie Pédiatrique (Research Group of the French Society for Pediatric Dermatology)
Search for more papers by this authorDidier Bessis
Department of Dermatology, University Hospital Center (CHU) of Montpellier, Montpellier, France
On behalf of the Groupe de Recherche de la Société Française de Dermatologie Pédiatrique (Research Group of the French Society for Pediatric Dermatology)
Search for more papers by this authorChristine Labrèze
Department of Dermatology, University Hospital Center (CHU) of Bordeaux, Bordeaux, France
BRIC (BoRdeaux Institute of onCology), UMR1312, INSERM, University of Bordeaux, Bordeaux, France
On behalf of the Groupe de Recherche de la Société Française de Dermatologie Pédiatrique (Research Group of the French Society for Pediatric Dermatology)
Search for more papers by this authorSorilla Mary-Prey
Department of Dermatology, University Hospital Center (CHU) of Bordeaux, Bordeaux, France
BRIC (BoRdeaux Institute of onCology), UMR1312, INSERM, University of Bordeaux, Bordeaux, France
Search for more papers by this authorLaurent Guibaud
University Hospital Center (CHU) Lyon, Mère-Enfant Hospital, Reference Center for Superficial Vascular Anomalies, Lyon Bron, France
Search for more papers by this authorAnnouk Bisdorff
Department of Neuroradiology/Vascular Anomalies Clinic, AP-HP, Lariboisière Hospital, Paris, France
Search for more papers by this authorAnne Dompmartin
Department of Dermatology, University Hospital Center (CHU) of Caen, University Caen-Normandie, Caen, France
On behalf of the Groupe de Recherche de la Société Française de Dermatologie Pédiatrique (Research Group of the French Society for Pediatric Dermatology)
Search for more papers by this authorJuliette Mazereeuw-Hautier
Department of Dermatology, University Hospital Center (CHU) of Toulouse, Reference Center for Rare Skin Diseases, Paul Sabatier University, Toulouse, France
On behalf of the Groupe de Recherche de la Société Française de Dermatologie Pédiatrique (Research Group of the French Society for Pediatric Dermatology)
Search for more papers by this authorChristine Chiaverini
Department of Dermatology, Reference Center for Genodermatoses and Rare Skin Diseases (MAGEC-Sud), University Hospital Center (CHU) of Nice, Nice, France
On behalf of the Groupe de Recherche de la Société Française de Dermatologie Pédiatrique (Research Group of the French Society for Pediatric Dermatology)
Search for more papers by this authorThomas Hubiche
Department of Dermatology, Reference Center for Genodermatoses and Rare Skin Diseases (MAGEC-Sud), University Hospital Center (CHU) of Nice, Nice, France
On behalf of the Groupe de Recherche de la Société Française de Dermatologie Pédiatrique (Research Group of the French Society for Pediatric Dermatology)
Search for more papers by this authorBertille Bonniaud
Department of Dermatology, University Hospital Center (CHU) of Dijon, Dijon, France
On behalf of the Groupe de Recherche de la Société Française de Dermatologie Pédiatrique (Research Group of the French Society for Pediatric Dermatology)
Search for more papers by this authorCaroline Degrugillier-Chopinet
Department of Cardiovascular Functional Explorations and Pediatric Cardiology, Coeur-Poumons Institute, University Hospital Center (CHRU) of Lille, Lille, France
Search for more papers by this authorAnne-Claire Bursztejn
Department of Dermatology and Allergology, University Hospital Center (CHU) of Nancy, Brabois Hospital, Nancy, France
On behalf of the Groupe de Recherche de la Société Française de Dermatologie Pédiatrique (Research Group of the French Society for Pediatric Dermatology)
Search for more papers by this authorHélène Aubert
Department of Dermatology, University Hospital Center (CHU) of Nantes, Nantes, France
On behalf of the Groupe de Recherche de la Société Française de Dermatologie Pédiatrique (Research Group of the French Society for Pediatric Dermatology)
Search for more papers by this authorMaella Severino
Department of Dermatology, University Hospital Center (CHU) of Toulouse, Reference Center for Rare Skin Diseases, Paul Sabatier University, Toulouse, France
On behalf of the Groupe de Recherche de la Société Française de Dermatologie Pédiatrique (Research Group of the French Society for Pediatric Dermatology)
Search for more papers by this authorSophie Leducq
Unit of Pediatric Dermatology, Department of Dermatology, University Hospital Center (CHRU) of Tours, Tours, France
Reference Center for Genodermatoses and Rare Skin Diseases (MAGEC-Tours), Tours, France
INSERM 1246-SPHERE, University of Tours & University of Nantes, Tours, France
On behalf of the Groupe de Recherche de la Société Française de Dermatologie Pédiatrique (Research Group of the French Society for Pediatric Dermatology)
Search for more papers by this authorMathilde Tardieu
Department of Dermatology, University Hospital Center (CHU) of Grenoble-Alpes, Couple Enfant Hospital, Grenoble, France
On behalf of the Groupe de Recherche de la Société Française de Dermatologie Pédiatrique (Research Group of the French Society for Pediatric Dermatology)
Search for more papers by this authorAline Joly
Unit of Pediatric Dermatology, Department of Dermatology, University Hospital Center (CHRU) of Tours, Tours, France
Department of Maxillofacial Surgery, University Hospital Center (CHRU) of Tours, Tours, France
Search for more papers by this authorGrégoire Boulouis
Unit of Pediatric Dermatology, Department of Dermatology, University Hospital Center (CHRU) of Tours, Tours, France
Department of Interventional Neuroradiology, University Hospital Center (CHRU) of Tours, Tours, France
Search for more papers by this authorAnne Le Touze
Unit of Pediatric Dermatology, Department of Dermatology, University Hospital Center (CHRU) of Tours, Tours, France
Department of Pediatric Surgery, University Hospital Center (CHRU) of Tours, Clocheville Hospital, Tours, France
Search for more papers by this authorArnaud Paré
Unit of Pediatric Dermatology, Department of Dermatology, University Hospital Center (CHRU) of Tours, Tours, France
Department of Maxillofacial Surgery, University Hospital Center (CHRU) of Tours, Tours, France
Search for more papers by this authorElsa Tavernier
INSERM 1246-SPHERE, University of Tours & University of Nantes, Tours, France
Clinical Investigation Center (CIC) INSERM 1415, University Hospital Center (CHRU) of Tours, Tours, France
Search for more papers by this authorCorresponding Author
Annabel Maruani
Unit of Pediatric Dermatology, Department of Dermatology, University Hospital Center (CHRU) of Tours, Tours, France
Reference Center for Genodermatoses and Rare Skin Diseases (MAGEC-Tours), Tours, France
INSERM 1246-SPHERE, University of Tours & University of Nantes, Tours, France
On behalf of the Groupe de Recherche de la Société Française de Dermatologie Pédiatrique (Research Group of the French Society for Pediatric Dermatology)
Correspondence
Annabel Maruani, Unit of Pediatric Dermatology, Department of Dermatology, Center of Reference of Vascular Anomalies MAGEC-Tours, CHRU Tours, 37044 Tours Cedex 9, France.
Email: [email protected]
Search for more papers by this authorCécilia Maillet
Unit of Pediatric Dermatology, Department of Dermatology, University Hospital Center (CHRU) of Tours, Tours, France
Reference Center for Genodermatoses and Rare Skin Diseases (MAGEC-Tours), Tours, France
Search for more papers by this authorOlivia Boccara
Department of Dermatology and Reference Center for Genodermatoses and Rare Skin Diseases (MAGEC), AP-HP, Paris University, Necker-Enfants Malades Hospital, Paris Centre University, Imagine Institute, Paris, France
On behalf of the Groupe de Recherche de la Société Française de Dermatologie Pédiatrique (Research Group of the French Society for Pediatric Dermatology)
Search for more papers by this authorStéphanie Mallet
Department of Dermatology, Assistance Publique-Hôpitaux de Marseille (AP-HM), Marseille, France
On behalf of the Groupe de Recherche de la Société Française de Dermatologie Pédiatrique (Research Group of the French Society for Pediatric Dermatology)
Search for more papers by this authorDidier Bessis
Department of Dermatology, University Hospital Center (CHU) of Montpellier, Montpellier, France
On behalf of the Groupe de Recherche de la Société Française de Dermatologie Pédiatrique (Research Group of the French Society for Pediatric Dermatology)
Search for more papers by this authorChristine Labrèze
Department of Dermatology, University Hospital Center (CHU) of Bordeaux, Bordeaux, France
BRIC (BoRdeaux Institute of onCology), UMR1312, INSERM, University of Bordeaux, Bordeaux, France
On behalf of the Groupe de Recherche de la Société Française de Dermatologie Pédiatrique (Research Group of the French Society for Pediatric Dermatology)
Search for more papers by this authorSorilla Mary-Prey
Department of Dermatology, University Hospital Center (CHU) of Bordeaux, Bordeaux, France
BRIC (BoRdeaux Institute of onCology), UMR1312, INSERM, University of Bordeaux, Bordeaux, France
Search for more papers by this authorLaurent Guibaud
University Hospital Center (CHU) Lyon, Mère-Enfant Hospital, Reference Center for Superficial Vascular Anomalies, Lyon Bron, France
Search for more papers by this authorAnnouk Bisdorff
Department of Neuroradiology/Vascular Anomalies Clinic, AP-HP, Lariboisière Hospital, Paris, France
Search for more papers by this authorAnne Dompmartin
Department of Dermatology, University Hospital Center (CHU) of Caen, University Caen-Normandie, Caen, France
On behalf of the Groupe de Recherche de la Société Française de Dermatologie Pédiatrique (Research Group of the French Society for Pediatric Dermatology)
Search for more papers by this authorJuliette Mazereeuw-Hautier
Department of Dermatology, University Hospital Center (CHU) of Toulouse, Reference Center for Rare Skin Diseases, Paul Sabatier University, Toulouse, France
On behalf of the Groupe de Recherche de la Société Française de Dermatologie Pédiatrique (Research Group of the French Society for Pediatric Dermatology)
Search for more papers by this authorChristine Chiaverini
Department of Dermatology, Reference Center for Genodermatoses and Rare Skin Diseases (MAGEC-Sud), University Hospital Center (CHU) of Nice, Nice, France
On behalf of the Groupe de Recherche de la Société Française de Dermatologie Pédiatrique (Research Group of the French Society for Pediatric Dermatology)
Search for more papers by this authorThomas Hubiche
Department of Dermatology, Reference Center for Genodermatoses and Rare Skin Diseases (MAGEC-Sud), University Hospital Center (CHU) of Nice, Nice, France
On behalf of the Groupe de Recherche de la Société Française de Dermatologie Pédiatrique (Research Group of the French Society for Pediatric Dermatology)
Search for more papers by this authorBertille Bonniaud
Department of Dermatology, University Hospital Center (CHU) of Dijon, Dijon, France
On behalf of the Groupe de Recherche de la Société Française de Dermatologie Pédiatrique (Research Group of the French Society for Pediatric Dermatology)
Search for more papers by this authorCaroline Degrugillier-Chopinet
Department of Cardiovascular Functional Explorations and Pediatric Cardiology, Coeur-Poumons Institute, University Hospital Center (CHRU) of Lille, Lille, France
Search for more papers by this authorAnne-Claire Bursztejn
Department of Dermatology and Allergology, University Hospital Center (CHU) of Nancy, Brabois Hospital, Nancy, France
On behalf of the Groupe de Recherche de la Société Française de Dermatologie Pédiatrique (Research Group of the French Society for Pediatric Dermatology)
Search for more papers by this authorHélène Aubert
Department of Dermatology, University Hospital Center (CHU) of Nantes, Nantes, France
On behalf of the Groupe de Recherche de la Société Française de Dermatologie Pédiatrique (Research Group of the French Society for Pediatric Dermatology)
Search for more papers by this authorMaella Severino
Department of Dermatology, University Hospital Center (CHU) of Toulouse, Reference Center for Rare Skin Diseases, Paul Sabatier University, Toulouse, France
On behalf of the Groupe de Recherche de la Société Française de Dermatologie Pédiatrique (Research Group of the French Society for Pediatric Dermatology)
Search for more papers by this authorSophie Leducq
Unit of Pediatric Dermatology, Department of Dermatology, University Hospital Center (CHRU) of Tours, Tours, France
Reference Center for Genodermatoses and Rare Skin Diseases (MAGEC-Tours), Tours, France
INSERM 1246-SPHERE, University of Tours & University of Nantes, Tours, France
On behalf of the Groupe de Recherche de la Société Française de Dermatologie Pédiatrique (Research Group of the French Society for Pediatric Dermatology)
Search for more papers by this authorMathilde Tardieu
Department of Dermatology, University Hospital Center (CHU) of Grenoble-Alpes, Couple Enfant Hospital, Grenoble, France
On behalf of the Groupe de Recherche de la Société Française de Dermatologie Pédiatrique (Research Group of the French Society for Pediatric Dermatology)
Search for more papers by this authorAline Joly
Unit of Pediatric Dermatology, Department of Dermatology, University Hospital Center (CHRU) of Tours, Tours, France
Department of Maxillofacial Surgery, University Hospital Center (CHRU) of Tours, Tours, France
Search for more papers by this authorGrégoire Boulouis
Unit of Pediatric Dermatology, Department of Dermatology, University Hospital Center (CHRU) of Tours, Tours, France
Department of Interventional Neuroradiology, University Hospital Center (CHRU) of Tours, Tours, France
Search for more papers by this authorAnne Le Touze
Unit of Pediatric Dermatology, Department of Dermatology, University Hospital Center (CHRU) of Tours, Tours, France
Department of Pediatric Surgery, University Hospital Center (CHRU) of Tours, Clocheville Hospital, Tours, France
Search for more papers by this authorArnaud Paré
Unit of Pediatric Dermatology, Department of Dermatology, University Hospital Center (CHRU) of Tours, Tours, France
Department of Maxillofacial Surgery, University Hospital Center (CHRU) of Tours, Tours, France
Search for more papers by this authorElsa Tavernier
INSERM 1246-SPHERE, University of Tours & University of Nantes, Tours, France
Clinical Investigation Center (CIC) INSERM 1415, University Hospital Center (CHRU) of Tours, Tours, France
Search for more papers by this authorCorresponding Author
Annabel Maruani
Unit of Pediatric Dermatology, Department of Dermatology, University Hospital Center (CHRU) of Tours, Tours, France
Reference Center for Genodermatoses and Rare Skin Diseases (MAGEC-Tours), Tours, France
INSERM 1246-SPHERE, University of Tours & University of Nantes, Tours, France
On behalf of the Groupe de Recherche de la Société Française de Dermatologie Pédiatrique (Research Group of the French Society for Pediatric Dermatology)
Correspondence
Annabel Maruani, Unit of Pediatric Dermatology, Department of Dermatology, Center of Reference of Vascular Anomalies MAGEC-Tours, CHRU Tours, 37044 Tours Cedex 9, France.
Email: [email protected]
Search for more papers by this authorCécilia Maillet and Olivia Boccara equal contributions.
Abstract
Rationale
Sirolimus is a treatment for slow-flow vascular malformations (SFVMs). However, the long-term management remains challenging.
Objectives
The SIROLO study assessed the long-term effects and real-life management of oral sirolimus for SFVMs by investigating data from 15 French tertiary centres for vascular anomalies.
Methods
Participants were retrospectively included if they had a SFVM that was being/had been treated with sirolimus for at least 3 years in total. Data were collected on treatment goals when initiating sirolimus, investigator-reported efficacy, safety, dosages and treatment withdrawal.
Results
The cohort involved 67 patients with various SFVM entities (mean [±SD] age 19.6 ± 12.5 years, 35 children, 52.2%). We found a heterogeneity of predefined treatment goals, the most frequent being cessation of pain. The investigators considered that sirolimus had persistent efficacy for bleeding, ulceration and pain but only slight efficacy for reducing volume. It was reported to be well-tolerated, although serious adverse events (mainly infections and also two ovarian cysts) were reported in 6 patients (9.0%) and required definitive sirolimus discontinuation for one. Overall, 11 patients (16.4%) had at least one temporary withdrawal period, leading to symptom recurrence and sirolimus resumption at a mean of 6.4 ± 9.6 months. The mean sirolimus concentration was 6.4 ± 3.7 ng/mL during the first 6 months and decreased over time (mean concentration during the last 6 months: 4.2 ± 3.2 ng/mL), probably to target the minimal efficient dosage. Eight patients (11.9%) switched to alpelisib because of insufficient efficacy of sirolimus.
Conclusions
This real-life study gives answers to frequent questions patients and parents ask before sirolimus initiation for SFVMs, such as persistence of efficacy over time, long-term side effects and time to recurrence in case of withdrawal.
Graphical Abstract
Overall, 67 patients were included from 15 French centres (35 children and 32 adults). After the first sirolimus temporary withdrawal, mean time to recurrence of symptoms was 6.4 ± 9.6 months (survival curve). Sirolimus was overall well-tolerated (radar chart). Serious adverse events occurred in six patients (9.0%), especially respiratory infections. There were two cases of ovarian cysts. Conclusion. The real-life study SIROLO provides answers on persistence of efficacy over time, long-term side effects and time to recurrence in case of sirolimus withdrawal.
CONFLICT OF INTEREST STATEMENT
None declared.
Open Research
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available from the corresponding author upon reasonable request.
Supporting Information
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