Early changes in serum type II collagen biomarkers predict radiographic progression at one year in inflammatory arthritis patients after biologic therapy.
OBJECTIVE
To investigate whether short-term changes in serum biomarkers of type II collagen degradation (C2C) and types I and II collagen degradation (C1,2C), as well as the biomarker for the synthesis of type II procollagen (CPII) can predict radiographic progression at 1 year following initiation of biologic therapy in patients with inflammatory arthritis.


METHODS
Serum levels of biomarkers were measured at baseline and at 1, 3, 6, 9, and 12 months after initiation of biologic therapy. A composite score reflecting changes from baseline in all 3 biomarkers (DeltaCOL) was calculated. Associations with clinical responses according to the 28-joint count Disease Activity Score and with radiographic progression according to the modified Sharp/van der Heijde score (SHS) were assessed.


RESULTS
The 1-year increase in the SHS correlated with the 1-month change in C2C results (r = 0.311, P = 0.028) and the DeltaCOL score (r = 0.342, P = 0.015). Radiographic progression was predicted by increases in serum C2C at 1 month (P = 0.031). The DeltaCOL score was significantly associated with 1-year radiographic progression after 1 (P = 0.022), 3 (P = 0.015), 6 (P = 0.048), and 9 (P = 0.019) months of therapy. Clinical remission was predicted by 1-month decreases in serum levels of C2C (P = 0.008) and C1,2C (P = 0.036). By regression analysis, 1-month changes in C2C, C1,2C, and CPII levels were independently associated with, and correctly predicted radiographic outcome in, 88% of the patients.


CONCLUSIONS
Short-term changes in serum levels of collagen biomarkers following initiation of biologic therapy may better predict long-term clinical and radiographic outcomes. These collagen biomarkers may therefore be valuable new early indicators of short-term biologic treatment efficacy in clinical trials and in individual patients with inflammatory erosive arthritis.
Mullan
Ronan H
RH
St. Vincent's University Hospital, Dublin, Ireland.
Matthews
Clare
C
Bresnihan
Barry
B
FitzGerald
Oliver
O
King
Lindsay
L
Poole
A Robin
AR
Fearon
Ursula
U
Veale
Douglas J
DJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D015535:Arthritis, Psoriatic / Q000097:blood* / Q000000981:diagnostic imaging* / Q000628:therapy; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000000981:diagnostic imaging* / Q000628:therapy; D001691:Biological Therapy; D015415:Biomarkers / Q000097:blood; D024043:Collagen Type II / Q000097:blood*; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011859:Radiography; D013997:Time Factors
D015415:Biomarkers; D024043:Collagen Type II