Adipose tissue-derived stromal vascular fraction for treating hands of patients with systemic sclerosis: a multicentre randomized trial Autologous AD-SVF versus placebo in systemic sclerosis

Aurélie Daumas (1, 2) , Jérémy Magalon (2, 3) , Elisabeth Jouve (4) , Dominique Casanova (5) , Cécile Philandrianos (5) , Maxime Abellan Lopez (5) , Stéphanie Mallet (5) , Julie Veran (3) , Isabelle Auquit-Auckbur (6, 7) , Dominique Farge (8, 9, 10) , Hervé Levesque (11, 12) , Ygal Benhamou (11, 12) , Laurent Arnaud (3) , Laurent Giraudo (3) , Chloé Dumoulin (3) , Camille Giverne (7, 6) , Olivier Boyer (7, 6) , Alexandra Giuliani (5) , Véronique Bourgarel (5, 13) , Jean-Robert Harlé (5) , Nicolas Schleinitz (5) , Julie Brunet (5) , Yves-Marie Pers (14, 15) , Rosanna Ferreira (14) , Audrey Cras (8, 16) , David Bocara (8) , Jérôme Larghero (16, 8) , Joseph Château (17) , Arnaud Hot (18) , Françoise Dignat-George (5) , Guy Magalon (5) , Florence Sabatier (5, 3) , Brigitte Granel (3, 5)

1 LA CONCEPTION - Hôpital de la Conception [CHU - APHM]
2 C2VN - Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research
3 CIC - Centre d'Investigation Clinique [Hôpital de la Conception - APHM]
4 Hôpital Nord [CHU - APHM]
5 APHM - Assistance Publique - Hôpitaux de Marseille
6 CHU Rouen
7 PANTHER - Physiopathologie, Autoimmunité, maladies Neuromusculaires et THErapies Régénératrices
8 AP-HP - Hopital Saint-Louis [AP-HP]
9 URP_3518 - Recherche clinique appliquée à l'hématologie
10 McGill University = Université McGill [Montréal, Canada]
11 Service de Médecine Interne [CHU Rouen]
12 EnVI - Endothélium, valvulopathies et insuffisance cardiaque
13 CRCM - Centre de Recherche en Cancérologie de Marseille
14 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]
15 Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB)
16 HIPI (UMR_S_976 / U976) - Immunologie humaine, physiopathologie & immunothérapie
17 Hôpital privé Jean Mermoz [Lyon]
18 Hôpital Edouard Herriot [CHU - HCL]

Objective: To assess the superiority of adipose tissue-derived stromal vascular fraction (AD-SVF) injection into the fingers vs placebo in reducing hand disability in systemic sclerosis (SSc) patients. Methods: We performed a double-blind, multicentre, phase II trial from October 2015 to January 2018 in France. SSc patients with a Cochin Hand Function Scale (CHFS) ≥20/90 were randomized 1:1 to receive injection of AD-SVF or placebo. AD-SVF was obtained using the automated processing Celution®800/CRS system. The placebo was lactated Ringer's solution. The primary efficacy end point was the change of the CHFS score from baseline to 3 months. Secondary efficacy endpoints included the CHFS score at 6 months, hands function, vasculopathy, hands pain, skin fibrosis, sensitivity of the finger' pulps, Scleroderma Health Assessment Questionnaire, patients and physician satisfaction and the safety. Results: 40 patients were randomized. The AD-SVF and placebo groups were comparable for age, sex ratio, disease duration, skin fibrosis of the hands and main cause of hand disability. After 3 month-follow-up, hand function significantly improved in both groups with no between-group difference of CHFS (mean change of -9.2 ± 12.2 in the AD-SVF group vs -7.6 ± 13.2 in the placebo group). At 6 months, hand function improved in both groups. Conclusion: This study showed an improvement of hand function in both groups other time, with no superiority of the AD-SVF. Considering the limits of this trial, studies on a larger population of patients with homogeneous phenotype and hand handicap, should be encouraged to accurately assess the benefit of AD-SVF therapy. Trial registration: ClinicalTrials.gov, https://clinicaltrials.gov, NCT02558543. Registered on September 24, 2015.

Mots clés: Cochin Hand Function Scale; Systemic sclerosis; Autologous adipose tissue-derived stromal vascular fraction; Regenerative medicine

Domaines: Rhumatologie et système ostéo-articulaire

Aurélie Daumas, Jérémy Magalon, Elisabeth Jouve, Dominique Casanova, Cécile Philandrianos, et al.. Adipose tissue-derived stromal vascular fraction for treating hands of patients with systemic sclerosis: a multicentre randomized trial Autologous AD-SVF versus placebo in systemic sclerosis. Rheumatology, 2021, pp.keab584. ⟨10.1093/rheumatology/keab584⟩. ⟨hal-03652426⟩