Background While the introduction of anti-tumor necrosis tumor (TNF) biologic agents can significantly improve signs/symptoms of ankylosing spondylitis (AS) and reduce magnetic resonance imaging (MRI)-detected spinal inflammation, the effect of such therapy on future radiographic progression is less clear. Serum C-reactive protein (CRP) associates with radiographic progression in AS patients untreated with TNF-antagonists.
Objectives We assessed correlations between serum CRP after 2 years of anti-TNF therapy and radiographic progression/inflammation in the GO-RAISE trial.
Methods Active AS patients receiving golimumab/placebo through week-16 (early-escape) or week-24 (crossover by design), followed by golimumab through 4 years, had sera/images obtained through week 208. Lateral spinal radiographs and spinal MRIs were scored using the modified Stoke AS spine score (mSASSS) and AS spinal MRI activity (ASspiMRI-a) score, respectively. Analyses of variance assessed differences based on CRP levels and mSASSS progression. The relationships between CRP levels and mSASSS/ASspiMRI-a score were assessed by Spearman correlation and logistic regression.
Results 299/356 (84.0%) randomized GO-RAISE patients had spinal radiographs available at both timepoints. Larger proportions of patients with week-104 CRP ≥0.5mg/dL (n=47) vs. <0.5mg/dL (n=236) (40.4% vs. 22.9%; p=0.0121) had mSASSS changes ≥2 at week-104 (Figure). Across several visits, serum CRP demonstrated weak associations with mSASSS change (rs= -0.33–0.54; p<0.05; n=65–89). Higher baseline CRP was associated with increased risk for syndesmophytes at week-104/week-208, while large decreases in CRP from baseline to week-14/week-24 yielded decreased risk of new bone formation (Figure 1).
Conclusions This is the first study to show that CRP level is not only a useful marker at baseline of the initiation of anti-TNF therapy but also at follow up examinations. Thus, elevated CRP after 2 years of anti-TNF treatment correlated with greater radiographic progression risk at 4 years. Intermittent measurements of serum CRP weakly predicted subsequent radiographic progression and modestly predicted residual spinal inflammation in anti-TNF treated AS patients. Thus, incomplete suppression of inflammation in AS patients may be a relevant factor for new bone formation, and serum CRP appears to be a pertinent predictive biomarker for long-term AS progression among patients receiving TNF-antagonists. It is possible that higher doses of anti-TNF agents are necessary for patients with persistently elevated CRP values to prevent new bone formation more effectively.
Disclosure of Interest J. Braun Grant/research support from: Janssen R & D, LLC, X. Baraliakos Grant/research support from: Janssen R & D, LLC, K.-G. Hermann Grant/research support from: Janssen R & D, LLC, S. Xu Employee of: Janssen R & D, LLC, B. Hsu Employee of: Janssen R & D, LLC