Difficult-to-Treat Axial Spondyloarthritis: Insights from a Cross-Sectional Study

A cross-sectional study published in Rheumatology assessing difficult-to-treat (D2T) axial spondyloarthritis (axSpA) found that a small proportion of patients required multiple biologic or targeted synthetic DMARDs (b/ts-DMARDs) and that objective evidence of inflammation was present in fewer than half of non-responders. These findings highlight the complexity of therapy non-response (NR) in axSpA, suggesting a mix of noninflammatory and true refractory disease. 

The study analyzed 680 patients with axSpA on b/ts-DMARDs treated at the Leeds Specialist Spondyloarthritis Service (October 2023 – May 2024). Patients were classified as D2T based on two definitions: 

• -Standard definition: failure of any 2 b/ts-DMARDs 
• -Strict definition: failure of ≥2 b/ts-DMARDs with differing mechanisms of action (MoA) 

Of the total cohort, 109 patients (16.0%) met the standard definition, while 58 patients (8.5%) met the strict definition. Both groups had similar demographics, with a mean age of ~49 years, male predominance (~62-65%), HLA-B27 positivity (~77-81%), and radiographic disease (~56-59%). 

At the last clinical review, the vast majority of patients with D2T remained on b/ts-DMARDs (91% in the standard definition group and 88% in the strict definition group). However, in the 2023/2024 subset, 73% of standard definition patients and 72% of strict definition patients had therapy nonresponse (BASDAI ≥4), indicating persistent disease activity despite ongoing treatment. 

Among nonresponders, CRP >5 mg/L was present in 49% (standard definition) and 47% (strict definition), suggesting that inflammation was not always a driving factor. MRI evidence of active inflammation was found in only 1 of 4 patients in the standard group and 0 of 2 in the strict group, with all MRI findings being non-axSpA related. 

"Objective evidence of inflammation was seen in less than 50% either by CRP, MRI, or both, suggesting a mix of non-inflammatory and true refractory disease," the study reported. 

These findings suggest that D2T axSpA may not always be driven by persistent inflammation, highlighting the need for further characterization of non-responders. 

"Further characterization of these populations in this and larger cohorts may identify predictors of non-response to b/tsDMARD therapy in axSpA," the authors concluded. 

For rheumatologists managing axSpA, these results emphasize the importance of carefully assessing therapy nonresponse, considering alternative disease mechanisms, and potentially re-evaluating treatment strategies in patients with persistent symptoms despite biologic or targeted therapy.

Reference
Weddell J, Duckett M, Harrison SR, et al. P004 Difficult to treat axial spondyloarthritis- insights from a tertiary rheumatology service. Lara D Veeken. 2024;63(Supplement_2). doi:10.1093/rheumatology/keae590.007