# Frequency of difficult-to-manage and treatment-refractory axial SpA: insights from the German RABBIT-SpA register using recent ASAS definitions

## TL;DR

This study analyzed real-world data to identify how common difficult-to-manage and treatment-refractory axial spondyloarthritis is, using new ASAS criteria.

## Contribution

The study applies new ASAS definitions to a large real-world cohort to identify subgroups of axial SpA patients.

## Key findings

- 8.5% of patients met the ASAS criteria for difficult-to-manage axial SpA.
- 2.5% of patients were classified as treatment-refractory.
- D2M patients showed distinct clinical features like higher opioid use and less inflammation markers.

## Abstract

To determine the frequency of axial SpA (axSpA) patients fulfilling the recently proposed Assessment of SpondyloArthritis International Society (ASAS) definitions for difficult-to-manage (D2M) and treatment-refractory (TR) axSpA, and to characterize these patients at initiation of their first advanced therapy.

Data were derived from the ongoing prospective, multicentre, longitudinal German RABBIT-SpA registry. Patients were eligible if they were biologic and targeted synthetic (b/ts) DMARD-naïve, had initiated a b/tsDMARD and had ≥12 months of follow-up. ASAS definitions were applied to identify cases of D2M and TR.

Of 1850 patients with axSpA, 881 (48%) were b/tsDMARD-naïve at the start of observation. A total of 75/881 patients (8.5%) fulfilled the ASAS criteria for D2M and 22/881 (2.5%) additionally met the criteria for TR. At baseline, D2M patients were more frequently female, more often HLA-B27-negative, and more commonly presented with arthritis and enthesitis compared with not-D2M (nD2M) patients. In addition, they exhibited fewer objective inflammatory markers such as elevated CRP or MRI lesions. Opioid use was higher across D2M patients compared with nD2M patients. In the TR group compared with the D2M/nTR, the proportion of female and of obesity was lower. Even at initiation of first-line b/tsDMARD, these patients showed more frequently signs of inflammation, including sacroiliac/spinal MRI lesions and elevated CRP, while peripheral arthritis was less frequent.

Applying the ASAS definitions in a large real-world cohort identified clinically relevant subgroups with D2M and TR. These findings support their clinical utility and highlight the need for phenotype-specific management strategies.