Published online Jun 21, 2022. doi: 10.3748/wjg.v28.i23.2582
Peer-review started: October 30, 2021
First decision: March 11, 2022
Revised: March 25, 2022
Accepted: May 7, 2022
Article in press: May 7, 2022
Published online: June 21, 2022
Existing studies have confirmed that infliximab (IFX) blood concentration is closely related to remission and recurrence of Crohn's disease (CD) patients under IFX therapy. In addition, monitoring inflammatory biomarkers regularly is another important tool for prognosis assessment of CD patients. Current studies have confirmed that C-reactive protein (CRP) and fecal calprotectin (FCP) are good predictors of disease activity, but there is still a lack of reliable evidence for predicting disease remission. Therefore, in the early stage of IFX treatment, combination of IFX blood concentration and inflammatory biomarkers may contribute to predict the change of CD outcomes.
The best therapeutic goal of CD was initially defined as clinical remission, and then the definition was converted to endoscopic remission with precise therapy. Nowadays, some clinicians even pursue whole-wall healing with individualized therapy. However, long-term clinical prognosis rather than long-term endoscopic prognosis is still a research priority of clinical studies contrapose to CD patients under IFX therapy. Therefore, prediction on long-term endoscopic prognosis of CD patients under IFX therapy has been based solely on models because of a lack of available data.
To explore the predictive value of blood drug concentration on long-term endoscopic outcomes of IFX therapy for CD and establish a comprehensive outcome prediction model combining IFX blood drug concentration, CRP and FCP, so as to provide a basis for clinical decision making.
A single-center retrospective research has been implemented in the First Affiliated Hospital of Zhejiang Chinese Medical University. CD patients under IFX therapy from January 2012 to December 2020 were collected. One hundred and eighty-one CD patients underwent IFX treatment. One hundred and fifty-three CD patients underwent endoscopy as well as serum concentration monitoring at week 14 after the third dose of IFX induction therapy. Inclusion criteria: (1) Endoscopic remission at week 14 [Crohn’s disease endoscopic index of severity (CDEIS) score ≤ 2 points or Rutgeerts ≤ i1]; (2) Clinical remission after IFX induction therapy without corticosteroids more than 6 mo; and (3) Therapeutic strategy during maintenance stage was designed as IFX 5 mg/kg every 8 wk combined with azathioprine 50 mg every day. The study was divided into two stages, the Step I study was conducted from week 14 to 54 of IFX treatment, and the Step II study was conducted from week 54 to 108 of IFX treatment. Endoscopic outcomes were defined as endoscopic activity (CDEIS score > 2 points or Rutgeerts score > i1) and endoscopic remission (CDEIS score ≤ 2 points or Rutgeerts ≤ i1). Endoscopic relapse free survival was defined as endoscopic remission at the beginning of the study stage and maintaining endoscopic remission during the study stage.
In step I study, 67/93 CD patients (72.04%) sustained endoscopic remission at week 54. Multivariable regression analysis demonstrated that only ITL [odds ratio (OR) = 0.666, 95% confidence interval (CI): 0.514-0.862, P = 0.002] and FCP (OR = 1.002, 95%CI: 1.001-1.004, P = 0.002) were independent risk of endoscopic activity at week 54. The receiver-operating characteristic analysis demonstrated that the best cut off level of ITL and FCP at week 14 on predicting endoscopic relapse at week 54 was 5.60 μg/mL [area under the curve (AUC) = 0.83, 95%CI: 0.73-0.90, P < 0.001] and 238 μg/g (AUC = 0.82, 95%CI: 0.72-0.89, P < 0.001). The median time to endoscopic relapse of CD patients with ITL ≤ 5.6 μg/ml was 32.00 wk shorter than those with ITL > 5.6 μg/mL [hazard ratio (HR) = 16.19, 95%CI: 7.44-35.22, P < 0.0001]. The median time to endoscopic relapse of CD patients with FCP > 238 μg/g was 21.00 wk shorter than those with FCP ≤ 238 μg/g (HR = 11.25, 95%CI: 4.26-29.73, P < 0.0001). (II) In step II study, 42/54 CD patients (77.78%) sustained endoscopic remission at week 108. Multivariable regression analysis found that only ITL (OR = 0.466, 95%CI: 0.247-0.877, P = 0.018) and CRP (OR = 1.590, 95%CI: 1.007-2.510, P = 0.047) were independent risks of endoscopic activity at week 108. The receiver-operating characteristic analysis demonstrated that the best cut off level of ITL and CRP at week 54 on predicting endoscopic relapse at week 108 was 2.10 μg/ml (AUC = 0.85, 95%CI: 0.72-0.93, P < 0.001) and 3.00 mg/L (AUC = 0.73, 95%CI: 0.60-0.84, P = 0.012). The median time to endoscopic relapse of CD patients with ITL ≤ 2.1 μg/mL was 40.00 w shorter than those with ITL > 2.1 μg/mL (HR = 13.14, 95%CI: 3.07-56.27, P < 0.0001). The median time to endoscopic relapse of CD patients with CRP > 3.00 mg/L was 50.00 wk shorter than those with CRP ≤ 3.00 mg/L (HR = 7.85, 95%CI: 1.31-46.85, P< 0.0001).
The best cut off values of ITL for predicting endoscopic activity within 1-year follow up was 5.60 μg/mL at week 14 and 2.10 μg/mL at week 54. In addition, ITL ≤ 5.60 μg/mL in combination with FCP > 238 μg/g at week 14 as well as ITL ≤ 2.10 μg/mL in combination with CRP > 3.00 mg/L at week 54 increased the precision of prediction on endoscopic outcomes at week 54 and week 108, respectively.
In view of the fact that conduction of intensive monitoring for biological management plays a vital role in precise treatment for CD patients, much larger and more stringent prospective studies are warranted to provide the best predictive models as acknowledged globally in allusion to long-term endoscopic outcomes of CD patients under IFX therapy.