Treatment options for children and adolescents with inflammatory bowel disease: is granulomonocytapheresis an effective alternative to drug therapy?

Introduction: Patients with inflammatory bowel diseases (IBD) require life-long medications, which even if effective have the potential to cause adverse effects as additional morbidity factors. In pediatric patients, drug therapy has more serious limitations, including impaired physical and mental development. A non-drug therapeutic option is believed to be depletion of elevated and activated granulocytes and monocytes known to release inflammatory cytokines, like the CD14+CD16+ monocyte phenotype known to release tumor necrosis factor-α.

Areas covered: Granulomonocyteapheresis (GMA) with an Adacolumn as a treatment option for IBD patients has been applied for the past 15 years. This article reviews the argument that GMA is a relevant and effective non-pharmacologic intervention in pediatric IBD setting.

Expert commentary: GMA with an Adacolumn has shown promise in adult, pediatric, and adolescent patients with active IBD. There is evidence of post-GMA immunomodulation in terms of increased regulatory T-cell and B-cell activities. Additionally, patients who respond to GMA may attain a favorable long-term clinical course by avoiding pharmacologicals during an early phase of their active IBD. GMA has a good safety profile, especially in difficult-to-treat and pediatric settings. An additional trial is warranted to assess the efficacy of GMA in the early phase of pediatric IBD to optimize patient selection.     

Treating inflammatory bowel disease by adsorptive leucocytapheresis:A desire to treat without drugs

Ulcerative colitis and Crohn’s disease are the major phenotypes of the idiopathic inflammatory bowel disease(IBD),which afflicts millions of individuals throughout the world with debilitating symptoms,impairing function and quality of life.Current medications are aimed at reducing the symptoms or suppressing exacerbations.However,patients require life-long medications,and this can lead to drug dependency,loss of response together with adverse side effects.Indeed,drug side effects become additional morbidity factor in many patients on long-term medications.Nonetheless,the efficacy of anti-tumour necrosis factors(TNF)-αbiologics has validated the role of inflammatory cytokines notably TNF-αin the exacerbation of IBD.However,inflammatory cytokines are released by patients’own cellular elements including myeloid lineage leucocytes,which in patients with IBD are elevated with activation behaviour and prolonged survival.Accordingly,these leucocytes appear logical targets of therapy and can be depleted by adsorptive granulocyte/monocyte apheresis(GMA)with an Adacolumn.Based on this background,recently GMA has been applied to treat patients with IBD in Japan and in the European Union countries.Efficacy rates have been impressive as well as disappointing.In fact the clinical response to GMA seems to define the patients’disease course,response to medications,duration of active disease,and severity at entry.The best responders have been first episode cases(up to 100%)followed by steroid nave and patients with a short duration of active disease prior to GMA.Patients with deep ulcers together with extensive loss of the mucosal tissue and cases with a long duration of IBD refractory to existing medications are not likely to benefit from GMA.It is clinically interesting that patients who respond to GMA have a good long-term disease course by avoiding drugs including corticosteroids in the early stage of their IBD.Additionally,GMA is very much favoured by patients for its good safety profile.GMA in 21st century reminds us of phlebotomy as a major medical practice at the time of Hippocrates.However,in patients with IBD,there is a scope for removing from the body the sources of proinflammatory cytokines and achieve disease remission.The bottom line is that by introducing GMA at an early stage following the onset of IBD or before patients develop extensive mucosal damage and become refractory to medications,many patients should respond to GMA and avoid pharmacologics.This should fulfill the desire to treat without drugs.     

Positions of selective leukocytapheresis in the medical therapy of ulcerative colitis

INTRODUCTIONUlcerative colitis (UC) and Crohn’s disease (CD) are the major forms of idiopathic inflammatory bowel diseases (IBD) of the intestine. UC and CD are both debilitating chronic disorders that afflict millions of individuals throughout the world…     

Leucocytapheresis for inflammatory bowel disease in the era of biologic therapy

(Table is included in full-text article.)The development of biologicals such as infliximab to intercept TNF-alpha validates the current perception that certain cytokines are major factors in the immunopathogenesis of inflammatory bowel disease (IBD), ulcerative colitis and Crohn's disease. Furthermore, major sources of inflammatory cytokines include activated peripheral granulocytes and monocytes (GM), which in patients with IBD are elevated with increased survival time and are found in vast numbers within the inflamed intestinal mucosa. Hence, elevated GM should be appropriate targets of therapy in IBD. Accordingly, in recent years technologies such as the Adacolumn have been developed for selective depletion of elevated GM by extracorporeal adsorption (GMA). Published data show that GMA in patients with steroid-dependent or steroid-refractory IBD is associated with striking efficacy and tapering or discontinuation of steroids, whereas in steroid-na?ve patients GMA spared patients from steroids. Likewise, GMA at appropriate intervals in patients at a high risk of clinical relapse significantly suppressed relapse, thus sparing the patients from the morbidity associated with active IBD. First ulcerative colitis episode, steroid naivety and short disease duration seem to be good predictors of response to GMA and on the basis of our experience, GMA seems to have an excellent safety profile.     

Progression of inflammatory bowel disease in China

The epidemiology and phenotype of inflammatory bowel disease (IBD) in the Chinese population is not well-known. We performed a comprehensive search of the Chinese biomedical literature database from 1989 to 2007 using the following key words: inflammatory bowel disease (IBD), ulcerative colitis (UC), Crohn's disease (CD). The investigation of hospitalized IBD patients from 1990 to 2003 was also carried out in 23 medical centers of 11 cities over China. There are some notable epidemiological and phenotypical differences between Chinese IBD and Caucasian IBD, including a lack of familial clustering, male predominance, a relatively later onset of the illness with no second peak age occurrence after 50 years old, a milder clinical course, less extra-intestinal manifestations and complications, and less fistulous and peri-anal complications in Chinese CD. The data indicate an increased incidence of IBD in China with many complicated clinical problems, which offers potential opportunities to study the disease prospectively and identify the etiological factors, leading also to the better management of this disease in China.     

Current status and future perspectives of leukocytapheresis for inflammatory bowel disease

Ulcerative colitis (UC) and Crohn's disease (CD) comprise the idiopathic inflammatory bowel diseases (IBD) of the gut. The etiology of IBD is poorly understood, but an autoimmune disturbance has been suggested to play an important role in this incurable disease. Extracorporeal leukocytapheresis (CAP) is an additional adjunct for IBD patients refractory to other conventional therapies, including steroids. The primary aim of CAP should be to suppress such unwanted immunological response by removing circulating inflammatory cells from the blood stream. The first decade has been passed since CAP was approved by Japanese social health insurance policy. It is therefore now an appropriate opportunity to upgrade and summarize our current understandings and/or future perspectives of this unique non-pharmacological and non-surgical strategy for IBD patients. According to several clinical and basic research reports, an early introduction of CAP should produce higher efficacy as compared with CAP applied sometime after a clinical relapse. Likewise, CAP therapy adjusted to patients' body-weight as well as two treatment sessions per week (intensive regimen) should benefit the efficacy rate. The etiology of IBD is not fully elucidated yet. As a result, the major therapeutic strategies in the Western world have been immunosuppressive therapy, including biologics. CAP is an unusual treatment modality for IBD because it seems to have both effectiveness and safety, which should generally be balanced in this type of illness. We now have to develop future strategies with and without combining biologics to improve the quality of life of IBD patients.     

Vedolizumab for inflammatory bowel disease:from randomized controlled trials to real-life evidence

The biologic antitumor necrosis factor alpha(anti-TNFα) agents have revolutionised the treatment of inflammatorybowel disease(IBD). However,some patients experience primary nonresponse,loss of response,or intolerance. Therefore,introducing a newer class of therapy with a mechanism of action that acts on different inflammatory pathways involved in IBD pathogenesis is appealing. Vedolizumab is a fully humanised monoclonal antibody that selectively targets α4β7 integrin. Based on the results of the pivotal clinical GEMINI trials,vedolizumab was approved for the treatment of adult patients with moderately to severely active ulcerative colitis(UC) and Crohn's disease(CD) refractory or intolerant to either conventional therapy or TNFα inhibitors. This review describes the efficacy,safety,and tolerability of vedolizumab reported in both randomized,controlled,clinical trials and from real-world experience in patients with UC and CD in order to identify its place in treatment algorithms for IBD.     

Role of the combination of biologics and/or small molecules in the treatment of patients with inflammatory bowel disease

Inflammatory bowel disease (IBD) is a group of chronic diseases that includes ulcerative colitis, Crohn’s disease, and indeterminate colitis. Patients with IBD require prolonged treatment and high utilization of healthcare resources for proper management. The treatment of patients with IBD is focused on achieving therapeutic goals including clinical, biochemical, and endoscopic variables that result in improvement of the quality of life and prevention of disability. Advanced IBD treatment includes tumor necrosis factor inhibitors, integrin antagonist, antagonist of the p40 subunit of interleukin 12/23, and small molecule drugs. However, despite the multiple treatments available, about 40% of patients are refractory to therapy and present with persistent symptoms that have a great impact on their quality of life, with hospitalization and surgery being necessary in many cases. Dual therapy, a strategy sometimes applicable to refractory IBD patients, includes the combination of two biologics or a biologic in combination with a small molecule drug. There are two distinct scenarios in IBD patients in which this approach can be used: (1) Refractory active luminal disease without extraintestinal manifestations; and (2) patients with IBD in remission, but with active extraintestinal manifestations or immune-mediated inflammatory diseases. This review provides a summary of the results (clinical response and remission) of different combinations of advanced drugs in patients with IBD, both in adults and in the pediatric population. In addition, the safety profile of different combinations of dual therapy is analyzed. The use of newer combinations, including recently approved treatments, the application of new biomarkers and artificial intelligence, and clinical trials to establish effectiveness during long-term follow-up, are needed to establish new strategies for the use of advanced treatments in patients with refractory IBD.     

Retrospective Single Center Study of Granulocyte Monocyte Adsorption Apheresis Treatment in Inflammatory Bowel Disease

Patients with active inflammatory bowel disease (IBD) have elevated and activated myeloid leukocytes, which infiltrate the intestinal mucosa. A significant proportion of IBD patients do not respond adequately to conventional treatment regimes. Studies have suggested that treatment with granulocyte monocyte apheresis (GMA) could be a safe and efficacious alternative for these patients. We evaluated the efficacy and safety of granulocyte/monocyte apheresis in patients with IBD in a retrospective cohort study, conducted from a single center in Stockholm. Clinical details from consecutive apheresis treated patients were retrospectively reviewed from 2004 to 2012. A total of 37 patients were included, 23 patients with ulcerative colitis (UC) and 14 with Crohn's disease (CD). Clinical response was seen in 11 patients (30%) and complete remission in 11 patients (30%). The remission rate was higher in UC patients compared to CD patients, 39% (N = 9) and 14% (N = 2) respectively. A total of 9 patients experienced adverse events. Most frequently reported was headache (N = 4). GMA seems to be a valuable adjuvant treatment regime in the care of patients with refractory IBD.     

Inflammatory bowel disease in the 21(st) century in China: turning challenges into opportunities

Inflammatory bowel disease (IBD) has been an international hot spot for research for a long period of time. In China, the prevalence of IBD is rapidly increasing in recent years, mimicking the same fast growing footsteps of the developed world. Chinese literature of the 20(th) century shows that the total number of IBD cases increased by approximately 2.5-fold over the previous decade, in particular a 15.7-fold in patients with Crohn's disease (CD). Articles on basic research have increased 4.3-fold, with a particular 9.9-fold increase on immunological mechanisms. The predominantly Traditional Chinese Medicine (TCM) related clinical trials implied tendency to use a combination of Western Medicine and TCM in the management of Chinese IBD patients. IBD research and collaborations overseas have been markedly promoted since the Chinese Organization for the Study of Inflammatory Bowel Disease (COIBD) was founded at the beginning of the 21(st) century. From the second decade of the century onwards, we need to focus on the research hot spots to catch up with the rapid advances worldwide. Big challenges and present achievements provide us with great opportunities for further developments of the study on IBD. The development of some novel target pathogenic factors of the disease will provide us with more effective roll for modern management and optimistic treatment of IBD during this century.     

The risk for opportunistic infections in inflammatory bowel disease with biologics: an update

ABSTRACT

Introduction: Crohn’s disease and Ulcerative Colitis are forms of inflammatory bowel disease (IBD), chronic diseases treated with medical and surgical therapy. Patients with IBD are treated with potent immunomodulatory agents, leading to immunosuppression, and the potential for opportunistic infections. In 2014, the ECCO guidelines were released to guide the prevention, diagnosis and treatment of a variety of these opportunistic infections. Since 2014, there have been a number of new agents released as well as a significant expansion in our knowledge of the safety profile of IBD medications. In this article, we review the literature after 2014 regarding opportunistic infections and updates on safety data.

Areas covered: We review updates in immunomodulatory therapies for IBD and opportunistic infections since the 2014 ECCO guidelines were published.

Expert commentary: The prevention, diagnosis, and treatment of opportunistic infections continue to evolve, as new drugs are approved, and the use of a combination of biologic agents are considered for therapy in clinical trials. What causes some patients to fail to respond to vaccination, or for others to develop severe infections, remains unclear. Improved risk stratification for opportunistic infections in IBD patients and updated ECCO 2014 guidelines would be of significant benefit.     

Management of the pregnant inflammatory bowel disease patient on antitumour necrosis factor therapy: State of the art and future directions

Antitumour necrosis factor (anti-TNF) therapy has been a major advance in the treatment of inflammatory bowel disease (IBD) by improving rates of mucosal healing, steroid-free remission, and decreasing rates of hospitalization and surgery. Because IBD affects women in their reproductive years, clinicians have and will continue to be asked in the future about the safety profile of these agents and their potential impact on pregnancy, the developing fetus and newborn. Immunoglobulin G transfer from the mother to fetus begins in the second trimester, with an elevation starting at 22 weeks of gestation and the largest amount transferred in the third trimester. Although research investigating the long-term outcomes of children exposed to anti-TNF therapy in utero is limited, there is no known adverse effect on either pregnancy or newborn outcomes including infectious complications with this class of drugs. The World Congress of Gastroenterology consensus statement on biological therapy for IBD considered infliximab and adalimumab to be low risk and compatible with use during conception and during pregnancy in at least the first two trimesters. Based on a clinical algorithm used at the University of Calgary Pregnancy and IBD clinic (Calgary, Alberta), recommendations have been provided on the management of pregnant patients on anti-TNF therapy, particularly with regard to third-trimester dosing, taking into account disease characteristics of individual patients. When educated about the safety of anti-TNF therapy during pregnancy, patients often choose to continue on therapy during the third trimester.     

Safety of biologic therapy

Several biologic agents have been assessed in patients with inflammatory bowel disease (IBD; Crohn's disease [CD] and ulcerative colitis [UC]). Until recently, only infliximab (humanized monoclonal anti-TNF-alpha antibody) had been approved by the Food and Drug Administration (FDA) to induce and maintain remission in patients with active mild to moderate and/or fistulizing Crohn's disease who are refractory to conventional therapy. Two recent trials, ACT 1 and ACT2, observed high efficacy of infliximab in inducing and maintaining clinical remission, mucosal healing, and corticosteroid-sparing effects in patients with moderate to severe UC. This agent also was recently approved by the FDA for the treatment of ulcerative colitis to reduce signs and symptoms, to induce clinical remission and healing of the intestinal mucosa, and to eliminate the use of corticosteroids in patients with moderately to severely active UC who have had an inadequate response to conventional therapy. There have been many randomized, double-blind, controlled and open-label uncontrolled studies of large and small numbers of patients assessing the efficacy and safety of various biologic agents considered potentially useful in the treatment of IBD. Among all the biologic agents, infliximab has the most robust data on safety. This is because it has been evaluated in many more trials than has any other biologic agent. In addition, postmarketing experience provides very valuable information about adverse events occurring during treatment with this agent.     

Efficacy of a Novel Granulocyte Monocyte Apheresis Adsorber Device in the Treatment of Inflammatory Bowel Diseases: A Pilot Study

Granulocyte monocyte apheresis (GMA) is a non‐pharmacological treatment for inflammatory bowel disease. In our study, we tested a novel GMA adsorber device in terms of clinical efficacy and safety in patients’ non‐response to pharmacological therapy. Secondary outcomes were the evaluation of adsorber's technical performance, the reduction of inflammatory markers and the improvement of patients' life quality. The prospective study included 18 patients enrolled from 2011 to 2012 with a monitoring of 48 weeks. All patients with Crohn's disease achieved a clinical remission after GMA treatments, sustained until the end of follow up, while 80% of ulcerative colitis patients obtained a clinical benefit, maintained after 48 weeks of monitoring. Leukocytes, neutrophils, monocytes and platelets, compared to erythrocytes and lymphocytes, were effectively removed from peripheral blood. There was no statistically significant result about serological markers of inflammation. A consistent improvement of the patients' quality of life was observed up to the end of follow up. No significant side‐effects were recorded. Our study underlines the efficacy and the safety of this novel GMA adsorber device; a prospective randomized clinical trial with adequate sample size should be performed.     

Use of granulocyte/monocytapheresis in ulcerative colitis: A practical review from a European perspective

Half of the patients with ulcerative colitis require at least one course of systemic corticosteroids in their lifetime. Approximately 75% of these patients will also require immunosuppressive drugs (i.e., thiopurines or biological agents) in the mid-term to avoid colectomy. Immunosuppressive drugs raise some concerns due to an increased risk of serious and opportunistic infections and cancer, particularly in elderly and co-morbid patients, underlining the unmet need for safer alternative therapies. Granulocyte/monocytapheresis (GMA), a CE-marked, non-pharmacological procedure for the treatment of ulcerative colitis (among other immune-mediated diseases), remains the only therapy targeting neutrophils, the hallmark of pathology in ulcerative colitis. GMA has proven its efficacy in different clinical scenarios and shows an excellent and unique safety profile. In spite of being a first line therapy in Japan, GMA use is still limited to a small number of centres and countries in Europe. In this article, we aim to give an overview from a European perspective of the mechanism of action, recent clinical data on efficacy and practical aspects for the use of GMA in ulcerative colitis.     

Immunoregulatory effects of adsorptive granulocyte and monocyte apheresis in patients with drug refractory Crohn's disease

In Japan, adsorptive granulocyte/monocyte apheresis (GMA) is an approved treatment option in patients with active Crohn's disease (CD). However, there is inadequate knowledge regarding the mechanism(s) of therapeutic effects of this non-pharmacologic treatment strategy. Further, recently we have been interested in the regulatory T-cell (Treg) profile which has an essential immunoregulatory function. Thirteen CD patients were treated with a single GMA session. The mean CD activity index (CDAI) and duration of CD were 218.5 and 9.8 years, respectively. Eight healthy volunteers participated as a control group. From CD patients, whole blood was taken immediately before and after the GMA session directly from the GMA column inflow and outflow lines. Broad spectrum serum key cytokines and chemokines were measured by suspension-array and ELISA. At baseline, almost all assayed inflammatory cytokines were significantly elevated in CD patients. Treg-associated cytokines including IL-10 (P < 0.02) and transforming growth factor (TGF)-β1 (P < 0.03), were higher in the GMA column outflow vs. inflow. In contrast, the Th1/Th2 balance, defined as IFN-γ/IL-10 was lower during hemofiltration (P = 0.05), potentially due to an elevated IL-10 (P < 0.02) because an elevation of pro-inflammatory IFN-γ (Th1) was not observed at the GMA column outflow. A single GMA session had a significant impact on the Treg profile. Treg-related cytokines like IL-10 and TGF-β1 in the blood returning to the patients from the GMA column outflow were elevated, while pro-inflammatory cytokines like IFN-γ were not. This action of GMA is potentially very interesting in patients with immune disorders, like CD patients.     

Regulatory T cells in patients with inflammatory bowel diseases treated with adacolumn granulocytapheresis

AIM： To investigate if the clinical efficacy of granulocytes and monocytes by adsorption （GMA） is associated with an increased frequency of peripheral regulatory T cells （Tregs）, as these cells have proven to be successful in suppressing inflammatory bowel disease （IBD） in animal models. METHODS： We report four cases of corticosteroiddependent ulcerative colitis （UC） and two Crohn’s disease （CD） cases with severe cutaneous lesions who received GMA therapy. The frequency of CD4＋ CD25^high （Tregs） in peripheral blood was analyzed by flow cytometry and the expression of FoxP3 and TGF beta in purified CD^4＋ T cells was determined by real time PCR prior to and one month after the last apheresis session, and at the time of endoscopic and clinical assessing. RESULTS： Increased expression of Fox P3 mRNA was found in all five patients who responded to cytapheresis with remission of clinical symptoms, mucosal inflammation and cutaneous lesions, and an increased frequency of circulating Tregs was found in four patients. These changes were not observed in the patient with UC who did no respond to GMA. Variations in TGF-β （mRNA） did not parallel that of FoxP3 mRNA. CONCLUSION： The clinical efficacy of GMA on IBD and related extra intestinal manifestations was associated with an expansion of circulating CD^4＋ CD25^＋ Tregs and higher expression of FoxP3 in CD^4＋ T cells. Accordingly, an elevated CD^4＋ CD25^＋ FoxP3 may be a valuable index of remission in patients with IBD and other chronic relapsing-remitting inflammatory conditions during treatment with GMA.     

选择性白细胞吸附疗法治疗溃疡性结肠炎的疗效及安全性分析

目的探讨选择性白细胞吸附疗法(granulocyte and monocyte adsorption apheresis,GMA)治疗溃疡性结肠炎(ulcerative colitis,UC)的疗效及安全性。方法回顾性收集2018年5月至2019年5月在山东中医药大学第二附属医院行GMA治疗的18例UC患者的临床资料,所有入组患者均行1周2次、5次为1个疗程的治疗方案,重度患者适当延长疗程,分析治疗前、治疗1个疗程后的内镜检查、改良Mayo评分、红细胞沉降率(ESR)、C-反应蛋白(CRP)、白细胞计数(WBC)、中性粒细胞计数(NEUT)、白蛋白(ALB)、血红蛋白(HGB),同时观察患者治疗后的不良反应。结果与治疗前比较,GMA治疗1个疗程结束后,改良Mayo评分、ESR、CRP均显著降低(P<0.05),ALB、HGB均显著升高(P<0.05),WBC、NEUT差异无统计学意义(P>0.05)。18例患者在GMA治疗过程中及治疗后均无明显不良反应发生,安全性良好。结论GMA可明显降低炎症活动度及改善临床症状,且不良反应发生率较低,具有良好的疗效及安全性。     

炎症性肠病发生消化道狭窄的临床特点分析

目的探讨住院炎症性肠病(inflammatory bowel disease,IBD)患者发生消化道狭窄的临床特点。方法纳入2010年1月至2018年12月在中国人民解放军总医院第七医学中心住院诊治的IBD患者,对发生消化道狭窄患者的诊治过程和随访情况进行回顾性分析。结果发生消化道狭窄患者118例(23.14%),其中克罗恩病(Crohn’s disease,CD)、溃疡性结肠炎(ulcerative colitis,UC)和IBD类型待定(IBD unclassified,IBDU)的消化道狭窄发生率分别为59.02%、6.67%和34.25%,三者比较,差异有统计学意义(P<0.001)。病程0~10年的消化道狭窄发生率为25.06%,而病程>10年的发生率为14.29%,二者比较,差异有统计学意义(χ2=4.880,P=0.027)。发生消化道狭窄患者中,33.90%(40例)的患者经单纯药物治疗有效;55.93%(66例)的患者予以外科手术治疗,术后并发症发生率为18.46%(12例),10.61%(7例)的患者予以再次手术治疗。27.12%(32例)的患者予以内镜下治疗,内镜治疗有效率为81.25%(26例),18.75%(6例)的患者经内镜治疗无效后行外科手术治疗,内镜治疗术后并发症发生率为3.13%(1例)。结论消化道狭窄是IBD的严重并发症之一,CD的消化道狭窄发生率显著高于UC。有效的内科药物及营养治疗可降低消化道狭窄发生率、手术率。内镜治疗消化道狭窄具有较高的有效性、安全性,可有效避免外科手术的发生。     

Faecal calprotectin: Management in inflammatory bowel disease

Inflammatory bowel disease (IBD) is a chronic and relapsing disorder which leads to an inflammation of the gastrointestinal tract. A tailored therapy to achieve mucosal healing with the less adverse events has become a key issue in the management of IBD. In the past, the clinical remission was the most important factor to consider for adapting diagnostic procedures and therapeutic strategies. However, there is no a good correlation between symptoms and intestinal lesions, so currently the goals of treatment are to achieve not only the control of symptoms, but deep remission, which is related with a favourable prognosis. Thus, the determination of biological markers or biomarkers of intestinal inflammation play a crucial role. Many biomarkers have been extensively evaluated in IBD showing significant correlation with endoscopic lesions, risk of recurrence and response to treatment. One of the most important markers is faecal calprotectin (FC). Despite calprotectin limitations, this biomarker represents a reliable and noninvasive alternative to reduce the need for endoscopic procedures. FC has demonstrated its performance for regular monitoring of IBD patients, not only to the diagnosis for discriminating IBD from non-IBD diagnosis, but for assessing disease activity, relapse prediction and response to therapy. Although, FC provides better results than other biomarkers such as C-reactive protein and erythrocyte sedimentation rate, these surrogate markers of intestinal inflammation should not be used isolation but in combination with other clinical, endoscopic, radiological or/and histological parameters enabling a comprehensive assessment of IBD patients.