A randomised, open-label trial to assess the optimal treatment strategy in early diffuse cutaneous systemic sclerosis: The UPSIDE study protocol

Research output: Contribution to journalArticle

Abstract

Introduction Systemic sclerosis (SSc) is a chronic, autoimmune connective tissue disease associated with high morbidity and mortality, especially in diffuse cutaneous SSc (dcSSc). Currently, there are several treatments available in early dcSSc that aim to change the disease course, including immunosuppressive agents and autologous haematopoietic stem cell transplantation (HSCT). HSCT has been adopted in international guidelines and is offered in current clinical care. However, optimal timing and patient selection for HSCT are still unclear. In particular, it is unclear whether HSCT should be positioned as upfront therapy or rescue treatment for patients refractory to immunosuppressive therapy. We hypothesise that upfront HSCT is superior and results in lower toxicity and lower long-term medical costs. Therefore, we propose this randomised trial aiming to determine the optimal treatment strategy for early dcSSc by comparing two strategies used in standard care: (1) upfront autologous HSCT versus (2) immunosuppressive therapy (intravenous cyclophosphamide pulse therapy followed by mycophenolate mofetil) with rescue HSCT in case of treatment failure. Methods and analysis The UPSIDE (UPfront autologous hematopoietic Stem cell transplantation vs Immunosuppressive medication in early DiffusE cutaneous systemic sclerosis) study is a multicentre, randomised, open-label, controlled trial. In total, 120 patients with early dcSSc will be randomised. The primary outcome is event-free survival at 2 years after randomisation. Secondary outcomes include serious adverse events, functional status and health-related quality of life. We will also evaluate changes in nailfold capillaroscopy pattern, pulmonary function, cardiac MR and high-resolution CT of the chest. Follow-up visits will be scheduled 3-monthly for 2 years and annually in the following 3 years. Ethics and dissemination The study was approved by the Dutch Central Committee on Research Concerning Human Subjects (NL72607.041.20). The results will be disseminated through patient associations and conventional scientific channels. Trial registration numbers NCT04464434; NL 8720.

Details

Authors
  • Julia Spierings
  • Anna Van Rhenen
  • Paco M.W. Welsing
  • Anne C.A. Marijnissen
  • Ellen De Langhe
  • Nicoletta Del Papa
  • Daan Dierickx
  • Karina R. Gheorghe
  • Joerg Henes
  • Tessa Kerre
  • Per Ljungman
  • Arjan A. Van De Loosdrecht
  • Erik W.A.F. Marijt
  • Miro Mayer
  • Marc Schmalzing
  • Roland Schroers
  • Vanessa Smith
  • Reinhard E. Voll
  • Madelon C. Vonk
  • Alexandre E. Voskuyl
  • Jeska K. De Vries-Bouwstra
  • Ulrich A. Walker
  • Jacob M. Van Laar
Organisations
External organisations
  • University Medical Center Utrecht
  • Istituto Ortopedico Gaetano Pini
  • Karolinska University Hospital
  • University Hospital of Tubingen
  • Skåne University Hospital
  • Ghent University Hospital
  • Amsterdam UMC - Vrije Universiteit Amsterdam
  • Leiden University Medical Centre
  • University Hospital of Wϋrzburg
  • Ruhr-University Bochum
  • University Hospital Basel
  • University Hospitals Leuven
  • Karolinska Institutet
  • University Hospital Centre Zagreb
  • Ghent University
  • University Medical Center Freiburg
  • Radboud University Medical Center
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Rheumatology and Autoimmunity

Keywords

  • bone marrow transplantation, clinical trials, immunology, rheumatology, transplant medicine
Original languageEnglish
Article numbere044483
JournalBMJ Open
Volume11
Issue number3
Publication statusPublished - 2021
Publication categoryResearch
Peer-reviewedYes