Prospective Evaluation of Difficult-to-Manage and Treatment-Refractory Axial Spondyloarthritis

Background

A substantial proportion of patients with axial spondyloarthritis (axSpA) continue to experience significant symptom burden despite appropriate anti-inflammatory treatment. The recently defined ASAS concepts of Difficult-to-Manage (D2M) and Treatment-Refractory (TR) axSpA aim to capture this clinical complexity, enabling a structured understanding of treatment non-response and supporting the identification of both inflammation-related and non-inflammatory contributors to disease burden.

Initial studies applying these concepts have been retrospective in nature and reveal considerable heterogeneity in the assessment tools used. For prospective research, there is a need for standardization of the assessment of D2M and TR axSpA – especially for the domains outside of axSpA. Moreover, previous studies included only a small number of TR axSpA making it difficult to draw conclusion regarding potential causes and thereby making it difficult to make recommendations regarding possible management.

To address this gap, we want to develop a standardized, digital study platform under the umbrella of ASAS incorporating a predefined assessment set of characteristics, domains and instruments to be collected and reported in patients with axSpA, with and without D2M disease. This infrastructure will support harmonized, prospective assessment of D2M and TR axSpA across centers, facilitating cross-study comparisons and enabling future research to build on a consistent and scalable foundation.

Aim:

  1. To define a consensus-based standardized assessment set to evaluate D2M and TR axSpA and to compare this group to a non-D2M axSpA population in a prospective study setting.
    2. To implement this set in a dedicated digital platform (ASAS D2M/TR Platform) accessible to all ASAS members for research purposes.
    3. To use the platform for cross-sectional and longitudinal studies assessing frequency, trajectory, and factors contributing to D2M and TR axSpA (ASAS D2M/TR cohort).

Methods

  1. Selection of the steering committee and the working group

Several ASAS members participate in the steering committee and the working group (WG). The WG also includes 3 Young ASAS members and 2 patient representatives (in collaboration with the Axial Spondyloarthritis International Federation (ASIF)).

  1. Instrument Consensus
    A structured expert consensus process will identify and endorse assessment tools, including PROMs and clinical metrics.
  2. Platform Development
    Implementation of the chosen tools into a central digital platform, hosted and supported by ASAS. The instrument selection and implementation will be aligned with the ASAS core set and with the recommendations on reporting axSpA in clinical trials.
  3. Active Data Collection
    Multicenter rollout (all ASAS members will be invited to contribute, we expect that 50-100 centers led by ASAS members or collaborating with them will be able to contribute 500-1000 D2M / TR patients and 500-1000 control patients within approximately 12 months of recruitment, enabling both cross-sectional and longitudinal evaluations of D2M/TR axSpA in real-world practice.

 

Timeline: 2026-2028

 

Project team

PIs: Astrid van Tubergen, Floris van Gaalen, Denis Poddubnyy

Steering committee:

  • Xenofon Baraliakos
  • Victoria Navarro-Compán

 

Working group:

  • Simone Battista (co-opted member)
  • Wilson Bautista-Molano
  • Mohamad Bittar
  • Rodrigo García-Salinas
  • Marco Garrido-Cumbrera (patient representative)
  • Ihsane Hmamouchi
  • Uta Kiltz
  • Robert Landewé
  • Katy Leung
  • Clementina López-Medina (Y-ASAS)
  • Jo Lowe (patient representative)
  • Pedro Machado
  • Marina Magrey
  • Philip Mease
  • Elena Nikiphorou
  • Sofia Ramiro
  • Martin Rudwaleit
  • Davy Paap (Y-ASAS)
  • Laura Passalent
  • Raj Sengupta
  • Alexandre Sepriano
  • Fernando Sommerfleck
  • Anneke Spoorenberg
  • Murat Torgutalp (Y-ASAS)
  • Nelly Ziade