C-reactive protein level at 2 weeks following initiation of infliximab induction therapy predicts outcomes in patients with ulcerative colitis: a 3 year follow-up study.
BACKGROUND
Poor response to anti-tumour necrosis factor biologicals like infliximab (IFX) is observed in patients with ulcerative colitis (UC), which may lead to prolonged morbidity and waste of medical resources. We aimed to look for potential biomarkers of response to IFX in patients with UC who were to undergo IFX induction therapy.


METHODS
Seventy-two IFX naïve UC patients with partial Mayo (pMayo) score of 4-9 received IFX infusion at weeks 0, 2 and 6 as induction therapy. The pMayo score, trough IFX and C-reactive protein (CRP) concentrations were measured. At week 14, patients who achieved a pMayo score of ≤ 2 with no individual subscore exceeding 1 were judged as responders, while patients who responded, but did not achieve a pMayo score of ≤ 2 were judged as partial responders. Likewise, patients who showed unchanged pMayo score or worsened were judged as non-responders. Patients were followed for up to 3.3 years.


RESULTS
Response, partial response and no response rates were 40.3, 33.3, and 26.4%, respectively. CRP level at week 2 in responders was significantly lower vs partial-responders (P = 0.0135) or non-responders (P = 0.0084) in spite of similar trough IFX level. Further, the median CRP (week 2/week 0) ratio was significantly lower in patients who responded vs partial-responders or non-responders, 0.06, 0.39 and 1.00, respectively. When the cut-off value was set at 0.19 for the CRP (week 2/week 0) ratio, this ratio could predict partial-responders with 79.1% sensitivity and 75.9% specificity. Patients with the CRP (week 2/week 0) ratio greater than 0.19 were likely to be partial-responder, with odds ratio 10.371 (P < 0.0001; 95% confidence interval 3.596-33.440).


CONCLUSIONS
In this study, CRP level at week 2 following initiation of IFX induction therapy appeared to be a clinically relevant biomarker of response to IFX in UC patients.
Department of Internal Medicine, Toho University, Sakura Medical Centre, 564-1 Shimoshizu, Sakura, Chiba, 285-8741, Japan. r-iwasa@sakura.med.toho-u.ac.jp.
Ryota
R
Iwasa
Department of Internal Medicine, Toho University, Sakura Medical Centre, 564-1 Shimoshizu, Sakura, Chiba, 285-8741, Japan. taro-dog@sakura.med.toho-u.ac.jp.
Akihiro
A
Yamada
Department of Internal Medicine, Toho University, Sakura Medical Centre, 564-1 Shimoshizu, Sakura, Chiba, 285-8741, Japan. sono-04@sakura.med.toho-u.ac.jp.
Koji
K
Sono
Department of Internal Medicine, Toho University, Sakura Medical Centre, 564-1 Shimoshizu, Sakura, Chiba, 285-8741, Japan. 600432fr@sakura.med.toho-u.ac.jp.
Ryuichi
R
Furukawa
Department of Internal Medicine, Toho University, Sakura Medical Centre, 564-1 Shimoshizu, Sakura, Chiba, 285-8741, Japan. ken.takeuchi@med.toho-u.ac.jp.
Ken
K
Takeuchi
Department of Internal Medicine, Toho University, Sakura Medical Centre, 564-1 Shimoshizu, Sakura, Chiba, 285-8741, Japan. yasuo-suzuki@sakura.med.toho-u.ac.jp.
Yasuo
Y
Suzuki
D000328:Adult; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism*; D003093:Colitis, Ulcerative / Q000097:blood* / Q000188:drug therapy*; D005260:Female; D005500:Follow-Up Studies; D005765:Gastrointestinal Agents / Q000627:therapeutic use*; D006801:Humans; D060828:Induction Chemotherapy; D000069285:Infliximab / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
D015415:Biomarkers; D005765:Gastrointestinal Agents; D002097:C-Reactive Protein; D000069285:Infliximab