ADAMTS5 is a biomarker for prediction of response to infliximab in patients with rheumatoid arthritis.
OBJECTIVE
To identify a biomarker for prediction of the response to infliximab (IFX) in patients with rheumatoid arthritis (RA), we focused on a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5) that seems to play a key role in aggrecan degradation in cartilage.


METHODS
Seventy-three randomly selected patients with active RA were treated with IFX. Peripheral blood samples were collected at baseline and ADAMTS5 messenger RNA (mRNA) was quantified using real-time polymerase chain reaction.


RESULTS
Baseline ADAMTS5 mRNA levels in the good responder group were significantly lower (1.84 +/- 1.56; p = 0.0408) than those in the moderate and nonresponder groups (2.54 +/- 1.70) at 38 weeks of treatment with IFX. The 28-joint count Disease Activity Score (DAS28) at 38 weeks of treatment was significantly lower in the low ADAMTS5 group (2.30 +/- 1.28; p = 0.0038) than in the high ADAMTS5 group (3.90 +/- 1.61). The percentage reduction of the DAS28 was significantly higher in the low ADAMTS5 group (52.5% +/- 28.8%; p = 0.0156) than in the high ADAMTS5 group (29.4% +/- 27.2%). Further, the Delta Health Assessment Questionnaire (DeltaHAQ) score, an estimate of the improvement in the HAQ score, at 38 weeks of treatment was significantly higher in the low ADAMTS5 group (1.18 +/- 0.60; p = 0.0102) than in the high ADAMTS5 group (0.21 +/- 0.78). The positive predictive value of a low baseline ADAMTS5 level for predicting good response and remission (DAS28 < 2.6 at 38 weeks) was 90.0% and 70.0%, respectively.


CONCLUSIONS
The baseline ADAMTS5 mRNA level is a candidate biomarker for prediction of the response to IFX in patients with RA.
Department of Internal Medicine, Tokyo Dental College Ichikawa General Hospital, Chiba 272-8513, Japan. kentsu@tdc.ac.jp
Kensei
K
Tsuzaka
Yuka
Y
Itami
Tsutomu
T
Takeuchi
Naoshi
N
Shinozaki
Tetsuo
T
Morishita
D051722:ADAM Proteins / Q000097:blood* / Q000235:genetics; D000071116:ADAMTS5 Protein; D000328:Adult; D000368:Aged; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D019540:Area Under Curve; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000188:drug therapy*; D015415:Biomarkers / Q000097:blood*; D005260:Female; D006801:Humans; D000069285:Infliximab; D008875:Middle Aged; D012313:RNA / Q000097:blood; D012720:Severity of Illness Index; D011795:Surveys and Questionnaires; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D015415:Biomarkers; D012313:RNA; D000069285:Infliximab; D051722:ADAM Proteins; D000071116:ADAMTS5 Protein; C121532:ADAMTS5 protein, human