E-selectin, interleukin 18, serum amyloid a, and matrix metalloproteinase 9 are associated with clinical response to golimumab plus methotrexate in patients with active rheumatoid arthritis despite methotrexate therapy.
OBJECTIVE
To assess the effect of golimumab (human monoclonal antibody to tumor necrosis factor-alpha) plus methotrexate (MTX) on selected inflammatory biomarkers, and to determine if these effects predict clinical response in rheumatoid arthritis (RA).


METHODS
Sera from adults with active RA despite MTX therapy, who received subcutaneous injections of placebo + MTX (MTX alone, n = 34) or golimumab 50 or 100 mg every 2 or 4 weeks + MTX (n = 137), were analyzed for levels of C-reactive protein (CRP), serum amyloid A (SAA), interleukin 18 (IL-18), E-selectin, matrix metalloproteinase 9 (MMP-9), and tissue inhibitor of matrix metalloproteinase 1 (TIMP-1).


RESULTS
Golimumab + MTX treatment significantly decreased serum CRP, SAA, IL-18, E-selectin, TIMP-1, and MMP-9 levels (median percent changes of -4.1% to -74.3% across treatment groups) versus MTX alone (-5.8% to 9.7%) when first measured at Week 4; decreases were sustained through Week 16. Larger magnitudes of decrease in all biomarkers were observed for clinical responders versus nonresponders. For golimumab + MTX, regression analyses including all biomarkers and select clinical measures showed that reductions in levels of several markers (SAA, E-selectin, MMP-9) as early as Week 4 correlated significantly with improvement in swollen joint count (SJC) at Week 16, as did reductions in E-selectin with improvement in tender joint count at Week 16. After accounting for the biomarkers, however, treatment group was no longer significant for SJC.


CONCLUSIONS
Significant decreases in several inflammatory biomarkers were associated with golimumab + MTX therapy. Decreases in serum levels of SAA, E-selectin, and MMP-9 at Week 4 may be useful in predicting clinical response at Week 16.
Visvanathan
Sudha
S
Centocor Research and Development, Inc., Malvern, Pennsylvania, USA. Svisvana@eits.jnj.com
Wagner
Carrie
C
Rojas
Jeannie
J
Kay
Jonathan
J
Dasgupta
Bhaskar
B
Matteson
Eric L
EL
Mack
Michael
M
Baker
Daniel G
DG
Rahman
Mahboob U
MU
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000188:drug therapy*; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D019040:E-Selectin / Q000097:blood*; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D020382:Interleukin-18 / Q000097:blood*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D008727:Methotrexate / Q000008:administration & dosage / Q000627:therapeutic use*; D008875:Middle Aged; D000685:Serum Amyloid A Protein / Q000378:metabolism*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood
D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D015415:Biomarkers; D019040:E-Selectin; D020382:Interleukin-18; D000685:Serum Amyloid A Protein; D019715:Tissue Inhibitor of Metalloproteinase-1; D002097:C-Reactive Protein; C529000:golimumab; D020780:Matrix Metalloproteinase 9; D008727:Methotrexate