Background/Purpose: Chronic inflammatory diseases such as Ankylosing Spondylitis (AS) are diverse and therefore hard to clearly diagnose and treat. Conventional biomarkers for AS, as CRP and ESR, often reflect systemic inflammation rather than local joint inflammation. We therefore investigated the effect of anti-TNFa treatment on the level biomarkers of tissue degradation end products reflecting cartilage and synovial turnover in AS patients and whether specific biomarker profiles could be identified for anti-TNFa response.

Methods: Serum samples from AS patients (n=114, age 19-78yrs, 80% males) were collected at baseline and 3 months following standard anti-TNF-a treatment; Infliximab (n=46), Etanercept (n=28), Adalimumab (n=25) and Golimumab (n=15). Biomarkers of tissue turnover were measured: i) MMP-degraded and citrullinated vimentin (VICM), i) MMP-degraded CRP (CRPM), iii) MMP-degraded type II and III collagen (C2M. C3M), iv) conventional CRP, v) MMP-3, and vi) ESR.  All values are presented as geometric mean ± 95% CI. Data was log transformed prior to statistical analysis. Differences between before and after treatment were determined using paired Student’s t-test. Pearson’s correlation was used to determine correlations between the biomarkers.

Results: Serum C3M (p<0.0002), CRPM (p<0.0001), and VICM (P=0.0011) all decreased significantly after three months of anti-TNF-alpha therapy. There was no significant difference in serum C2M (p>0.05) and MMP-3 (p>0.05) before and after anti-TNF-alpha therapy, although 1/3 of the patients did decrease in response to treatment. CRP (p<0.0001) and ESR (p<0.0001) decreased significantly with treatment. There was a significant correlation between CRPM and the conventional biomarkers before treatment. However, this correlation was lost after 3 months of treatment (table). VICM was strongly correlated to C3M at both time points and to CRPM after treatment, but not at baseline. There was a significant correlation between C2M and VICM at baseline, which was lost after treatment. Before treatment CRP was correlated to C3M, but not after treatment.

Conclusion: Biomarkers of cartilage degradation (C2M), synovial inflammation (C3M, CRPM. VICM and MMP3) and systemic biomarkers (CRP and ESR) were decreased in response to anti-TNF-alpha treatment in these AS patients. Whereas the level of CRP and ESR was completely blocked by treatment in a majority of the patients, the suppression in the level of the other markers was patient-dependent. It was clear that each marker reflects different molecular processes in the tissue and responded differentially to the treatment. Thus specific profiles for treatment efficacy may be generated by measuring a biomarker panel of tissue degradation end products.