Higher baseline levels of C-reactive protein (CRP), a marker of systemic inflammation, may help predict long-term treatment persistence with tumour necrosis factor inhibitors (TNFi), but not interleukin-17 inhibitors (IL-17i), in patients with axial spondyloarthritis (axSpA), according to a nationwide real-world study published in RMD Open. The study also demonstrated that elevated baseline CRP was associated with higher remission rates regardless of the biologic class used.
Axial spondyloarthritis is a chronic inflammatory rheumatic disease affecting the spine and sacroiliac joints, often leading to persistent back pain, stiffness, and reduced physical function. Although both TNF inhibitors and IL-17 inhibitors are recommended biologic therapies for active disease, biomarkers that reliably predict treatment response and long-term persistence remain limited. CRP has previously been linked to improved responses to TNF inhibitors, but its role in patients receiving IL-17 inhibitors has been less clear.
To address this gap, investigators analysed data from the nationwide Danish DANBIO registry, including 3,387 adults with axSpA who initiated their first biologic therapy between January 2015 and March 2024. Of these, 2,786 patients started their first TNF inhibitor, while 601 initiated their first IL-17 inhibitor. Baseline CRP concentrations were categorised as low (<5 mg/L), intermediate (5–10 mg/L), or high (>10 mg/L). The primary outcomes included 12-month treatment retention and remission, defined as a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score below 2.
The study population reflected differences in treatment history between the two groups. Nearly all patients receiving TNF inhibitors (99%) were biologic-naïve, whereas 95% of those starting IL-17 inhibitors had previously received TNF inhibitor therapy, reflecting current treatment practices in which IL-17 inhibitors are often prescribed after TNF inhibitor failure or intolerance.
Among patients receiving IL-17 inhibitors, treatment persistence remained largely unaffected by baseline CRP levels. Twelve-month retention rates were 51%, 53%, and 55% in the low, intermediate, and high CRP groups, respectively. Multivariable Cox regression analyses found no significant association between baseline CRP levels and the risk of treatment discontinuation. These findings remained consistent after stratification by sex and radiographic status, suggesting that baseline inflammatory burden does not influence IL-17 inhibitor retention.
In contrast, baseline CRP showed a clear relationship with TNF inhibitor persistence. Twelve-month retention rates increased progressively with higher CRP levels, from 63% in the low CRP group to 66% in the intermediate group and 72% in the high CRP group. Patients with intermediate and high baseline CRP experienced a significantly lower risk of discontinuing TNF inhibitor therapy than those with low CRP, indicating that elevated inflammatory activity at treatment initiation may predict sustained benefit from TNF blockade.
The researchers also observed that remission rates increased with higher baseline CRP for both treatment classes. BASDAI remission was achieved by 6%, 8%, and 11% of patients receiving IL-17 inhibitors across low-, intermediate-, and high-CRP groups, respectively. Corresponding remission rates among TNF inhibitor users were substantially higher at 19%, 22%, and 32%, highlighting a stronger association between elevated CRP and favourable clinical outcomes with TNF inhibition.
The findings suggest that baseline CRP remains a clinically useful biomarker for predicting treatment persistence and remission in patients initiating a first TNF inhibitor in routine practice. However, for patients receiving IL-17 inhibitors, baseline CRP does not appear to predict treatment retention, despite being associated with improved remission rates.
The authors noted that these findings may help clinicians individualise biologic therapy by incorporating baseline inflammatory status into treatment decision-making. They also emphasised that further studies are needed to identify additional biomarkers capable of predicting response to IL-17 inhibitors, particularly in patients with previous biologic exposure.
Reference
Høegh Pedersen A, Jensen KY, Hetland ML, et al. Impact of C reactive protein on effectiveness of interleukin-17 and tumour necrosis factor inhibitors in axial spondyloarthritis: a Danish nationwide observational study. RMD Open. 2026;12:e006807.