Published online Mar 7, 2021. doi: 10.3748/wjg.v27.i9.886
Peer-review started: October 17, 2020
First decision: December 13, 2020
Revised: December 25, 2020
Accepted: January 12, 2021
Article in press: January 12, 2021
Published online: March 7, 2021
Blood concentration has been proved to be an important predictor of outcomes in inflammatory bowel disease (IBD) patients during biological therapy. It has also been acknowledged that disparate therapeutic targets correspond to specific blood concentrations. The greater the therapeutic expectation required by IBD patients, the higher the value of blood concentration suggested by IBD specialists.
Given the invasive, painful, and expensive examinations, such as endoscopy, for disease evaluation in IBD patients, identification of biologic blood concentration for predicting endoscopic inactivity in IBD patients may contribute to better, less painful, less risky, less expensive treatments.
To identify the predictive value of biologic blood concentration on endoscopic inactivity in IBD patients and explore factors relevant to predictive value.
A comprehensive search target was utilized to search PubMed/MEDLINE, Embase, and Web of Science systematically. Two authors screened and extracted the literature according to the inclusion and exclusion criteria. The quality of the included literature was assessed using the Newcastle Ottawa Scale. Authors assisted by a biostatistician extracted, synthesized, and reviewed the data in accordance with the research topic.
A total of 23 articles with 30 clinical studies and 1939 IBD patients were included. All studies verified the correlation between biologic blood concentration and endoscopic inactivity in IBD patients. Thirteen studies focused on infliximab and demonstrated that blood concentration reaching 4.0-10.6 μg/mL could predict the mucosal healing in Crohn’s disease (CD) patients while ulcerative colitis (UC) patients with a blood concentration higher than 2.7-10.5 μg/mL were more likely to achieve mucosal healing under maintenance therapy. Whereas infliximab blood concentration of perianal fistulizing Crohn's disease (pfCD) patients reaching 5.0-12.7 μg/mL or more increased the probability of mucosal healing. Eleven studies focused on adalimumab and indicated that blood concentration reaching 7.2-16.2 μg/mL or more could predict mucosal healing in IBD patients while patients with a blood concentration lower than 4.9 μg/mL showed no mucosal healing under maintenance therapy. What’s more, the predictive cut off value of adalimumab blood concentration on fistula healing/closed should be 5.9-9.8 μg/mL in pfCD. Four studies focused on vedolizumab and verified that blood concentration surpassing 25.0 μg/mL indicated mucosal healing in UC patients under maintenance therapy and the predictive cut off value of blood concentration on mucosal healing or endoscopic remission under induction therapy in IBD could be 8.0-28.9 μg/mL. However, different studies had several discrepancies in the disease phenotype and demographics of study cohorts as well as the therapeutic stage, therapeutic course, injection dose, and injection frequency of biologic management. In addition, the definition of primary endpoints was not consistent in all studies. Fifteen studies considered mucosal healing as the main endpoint, three studies including pfCD patients adopted fistula healing/closure, and four adopted endoscopic remission alone or in combination with clinical remission as the main endpoint. Additionally, five studies identified the desirable endpoint as histological healing or histological remission.
Considering the discrepancies in study design, study cohort, and biological management among different clinical studies, the best predictive cut-offs of biologic blood concentration on endoscopic inactivity published in 23 studies varied and the biological blood concentration might not be an appropriate predictor of endoscopic inactivity in IBD patients currently.
In view of the fact that conduction of intensive monitoring for biological management plays a vital role in precise treatment of IBD patients, much larger and more stringent prospective studies are warranted to provide the best predictive cut-offs for biologic blood concentration as acknowledged globally in allusion to different types of IBD patients for distinguishing endoscopic inactivity from endoscopic activity.