Higher baseline CRP predicts better TNFi retention and remission in axial spondyloarthritis, but not for IL-17 inhibitors
Background
Patients with axial spondyloarthritis (axSpA) experience chronic inflammation, leading to pain and structural damage. Biologic disease-modifying antirheumatic drugs (bDMARDs), specifically tumour necrosis factor inhibitors (TNFi) and interleukin-17 inhibitors (IL-17i), have revolutionized treatment. However, not all patients respond equally, and identifying biomarkers to predict treatment effectiveness remains a critical unmet need. C-reactive protein (CRP) is a common inflammatory biomarker, and its role in guiding bDMARD selection, particularly for IL-17i versus TNFi, is not fully understood, leaving a gap in personalized treatment strategies.
Study Design
This nationwide observational study utilized data from the DANBIO registry, including 3387 patients with axial spondyloarthritis initiating their first IL-17i (601 patients) or first TNFi (2786 patients) between 2015 and 2024. Patients were stratified by baseline C-reactive protein (CRP) levels: low (<5 mg/L), intermediate (5-10 mg/L), and high (>10 mg/L). Primary outcomes were 12-month treatment retention and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) remission. Kaplan-Meier plots and Cox regression models were used to assess treatment retention and hazard of discontinuation, with adjustments for sex and radiographic status.
Results
Baseline CRP levels were low/intermediate/high in 57%/17%/26% for IL-17i users and 48%/20%/32% for TNFi users. Notably, 95% of IL-17i patients were TNFi-experienced, while 99% of TNFi patients were biologic-naïve. The 12-month retention rates for IL-17i across low/intermediate/high CRP strata were 51%/53%/55%, showing no clear association. In contrast, TNFi retention rates were 63%/66%/72%, indicating better retention with higher CRP. Cox models confirmed no clear association between CRP and IL-17i retention (intermediate CRP: HR 0.96, 95% CI 0.68 to 1.19; high CRP: HR 0.90, 95% CI 0.68 to 1.19).
Key Findings
- Higher baseline CRP levels (>10 mg/L) were associated with significantly lower risk of TNFi discontinuation (HR 0.72, 95% CI 0.62 to 0.84).
- TNFi 12-month retention rates increased with higher baseline CRP: 63% (low), 66% (intermediate), 72% (high).
- IL-17i 12-month retention rates showed no clear association with baseline CRP: 51% (low), 53% (intermediate), 55% (high).
- Remission rates for TNFi were higher with increasing CRP: 19% (low), 22% (intermediate), 32% (high).
- IL-17i remission rates were lower overall and showed a modest increase with CRP: 6% (low), 8% (intermediate), 11% (high).
Why It Matters
This study provides crucial real-world evidence for guiding biologic selection in axial spondyloarthritis. For biologic-naïve patients, a higher baseline CRP level suggests a greater likelihood of successful TNFi treatment retention and remission. This finding supports a more personalized approach, where CRP can serve as a predictive biomarker for TNFi efficacy. Conversely, the effectiveness of IL-17i appears less dependent on baseline CRP, which is important for patients who have failed TNFi. This could lead to refined treatment algorithms, potentially improving patient outcomes and reducing trial-and-error prescribing, although further prospective studies are needed to integrate this into clinical protocols.
axial spondyloarthritis
axspa
crp
tnf-inhibitor
il-17-inhibitor
biologic