The value of serum type II collagen epitope measurement in assessing early clinical response to treatment with anti-tumour necrosis factor alpha therapy in rheumatoid arthritis

Current guidelines on the use of anti-tumour necrosis factor alpha (anti-TNF-α) therapies in rheumatoid arthritis (RA) recommend a 3-month trial of the drug before a clinical assessment of treatment efficacy can be made. The serum level of the type II collagen propeptide CPII correlates with type II collagen synthesis, and is elevated in RA. The collagen cleavage neo-epitope C2C is specific for the destruction of type II collagen by the collagenases MMP-1, MMP-8 and MMP-13. Previously we have shown that the ratio of C2C/CPII is increased in osteoarthritis and correlates with cartilage destruction. The current pilot study assessed the utility of serum measurement of C2C and CPII in predicting early response to treatment with anti-TNF-α therapy in a group of 20 RA patients.

Twenty patients were assessed before commencement of either infliximab (n = 5) or etanercept (n = 15) therapy, and at 1-month and 3-month time-points after therapy was commenced. Measurements of 28 swollen and tender joint counts for DAS28 score, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were taken at the time of each assessment. Additional serum was collected for measurement of CPII and C2C by ELISA. The change in serum levels of ESR, CRP, C2C, CPII and a ratio of C2C/CPII between 0 and 1 month was calculated, and then correlated with clinical outcomes at 3 months to assess their predictive value, using the Spearman Rank Correlation Coefficient.

The median DAS28 score fell from 6.20 to 3.74 following 3 months of treatment (P = 0.0004, Wilcoxon Sign Rank Test). The change in C2C/CPII at 1 month of therapy was more closely associated with the change in swollen joint count at 3 months (P = 0.16) than either CRP (P = 0.62) or ESR (P = 0.24). The change in C2C/CPII at 1 month was more closely associated with tender joint count at 3 months (P = 0.19) than either the ESR (P = 0.59) or CRP (P = 0.52). One-month changes in C2C and CPII when used individually were not predictive of swollen joint count at 3 months (P = 0.55 and P = 0.74, respectively) or tender joint count at 3 months (P = 0.4 and P = 0.8, respectively).

The ratio of C2C/CPII appears to offer a better method of predicting early response to biological therapy than the standard acute phase markers CRP and ESR. Measurement of the C2C/CPII ratio may more closely reflect cartilage changes in RA through measurement of both the synthesis and destruction of type II collagen. A further trial with larger patient numbers is required to fully assess the utility of this measure in predicting outcome to therapeutic intervention in the treatment of RA.

Affiliations

1. University College Dublin, Ireland
   • RH Mullan
   • , C Walsh
   • , O FitzGerald
   • , B Bresnihan
   • , U Fearon
   •  & DJ Veale
2. Shriners Hospital, Cedar Avenue, Montreal, PQ, Canada
   • T Lobanok
   •  & R Poole
3. Ibex Pharmaceuticals, Montreal, PQ, Canada
   • L King

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