Changes in biomarkers of inflammation and bone turnover and associations with clinical efficacy following infliximab plus methotrexate therapy in patients with early rheumatoid arthritis.
OBJECTIVE
To determine if changes in biomarkers of inflammation and bone turnover in response to treatment with infliximab plus methotrexate (MTX) versus MTX alone are associated with improvement in clinical measures of signs, symptoms, and structural damage in early rheumatoid arthritis.


METHODS
Sera were collected from patients in the ASPIRE study who received 3 mg/kg (n = 48) or 6 mg/kg infliximab plus MTX (n = 55), or MTX alone (n = 41). Several baseline biomarker levels correlated with changes in median percentage of American College of Rheumatology improvement (ACR-N), 50% improvement in ACR response (ACR50), and van der Heijde-modified Sharp score (vdHSS) at Week 54.


RESULTS
Infliximab plus MTX treatment resulted in more rapid decreases in levels of matrix metalloproteinase-3 (MMP-3), intercellular cell adhesion molecule-1, interleukin 8 (IL-8), and tumor necrosis factor-a than treatment with MTX alone. Baseline levels and decreases from baseline to Weeks 6 and 54 in MMP-3 correlated with improvement in ACR-N response at Week 54. An increase in IL-8 levels from baseline to Week 54 correlated with worsening in vdHSS at Week 54 in the MTX-alone group. Regression analysis of markers at baseline showed that MMP-3 was the only variable associated with ACR50 response and less worsening in vdHSS at Week 54.


CONCLUSIONS
Treatment with infliximab plus MTX resulted in a rapid decrease in inflammation markers. MMP-3 levels at different timepoints were consistently associated with clinical improvements at Week 54 in the infliximab plus MTX group, while increases in IL-8 levels correlated with a worsening in vdHSS at Week 54 in the MTX-alone group.
Visvanathan
Sudha
S
Centocor, Inc., Malvern, Pennsylvania, USA. SVisvana@CNTUS.JNJ.COM
Marini
Joseph C
JC
Smolen
Josef S
JS
Clair
E William St
EW
Pritchard
Charles
C
Shergy
William
W
Pendley
Charles
C
Baker
Daniel
D
Bala
Mohan
M
Gathany
Timothy
T
Han
John
J
Wagner
Carrie
C
D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D015415:Biomarkers / Q000097:blood*; D016723:Bone Remodeling / Q000187:drug effects* / Q000502:physiology; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D000069285:Infliximab; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use*; D008875:Middle Aged; D012720:Severity of Illness Index
D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D015415:Biomarkers; D018836:Inflammation Mediators; D000069285:Infliximab; D008727:Methotrexate