• Aféresis de granulocitos-monocitos
• Colitis ulcerosa
• Enfermedad inflamatoria intestinal
• Granulocyte–monocyte apheresis
• Inflammatory bowel disease
• Ulcerative colitis
• Ustekinumab

• Humans
• Retrospective Studies
• Ustekinumab/therapeutic use
• Male
• Middle Aged
• Female
• Adult
• Monocytes
• Granulocytes
• Colitis, Ulcerative/therapy
• Colitis, Ulcerative/drug therapy
• Combined Modality Therapy
• C-Reactive Protein/analysis
• Leukapheresis/methods
• Blood Component Removal/methods
• Treatment Outcome

• Aféresis de granulocitos-monocitos
• Colitis ulcerosa
• Enfermedad inflamatoria intestinal
• Granulocyte–monocyte apheresis
• Inflammatory bowel disease
• Tofacitinib
• Ulcerative colitis

• Humans
• Retrospective Studies
• Female
• Middle Aged
• Pyrimidines/therapeutic use
• Piperidines/therapeutic use
• Piperidines/administration & dosage
• Male
• Colitis, Ulcerative/therapy
• Colitis, Ulcerative/drug therapy
• Monocytes
• Adult
• Granulocytes
• Combined Modality Therapy
• Pyrroles/therapeutic use
• Pyrroles/administration & dosage
• C-Reactive Protein/analysis
• Treatment Outcome
• Leukapheresis/methods
• Protein Kinase Inhibitors/therapeutic use

• adsorptive cytapheresis
• efficacy
• inflammatory bowel diseases
• mechanisms of action
• safety
• side effects
• ulcerative colitis

• Humans
• Aged
• Colitis, Ulcerative/therapy
• Biosimilar Pharmaceuticals/therapeutic use
• Cytapheresis
• Adrenal Cortex Hormones/therapeutic use
• Remission Induction
• Tumor Necrosis Factor-alpha
• Treatment Outcome
• Granulocytes
• Monocytes

• apoptotic neutrophils
• inflammatory bowel disease
• interleukin-10
• mucosal lesions
• myeloid lineage leukocytes
• pediatrics and adolescents
• regulatory b-cells
• therapeutic granulomonocytapheresis

• Lichtiger clinical activity index
• corticosteroids
• granulocyte and monocyte absorption apheresis
• mucosal healing
• ulcerative colitis

Ulcerative colitis (UC) is an intractable disease associated with high morbidity and healthcare costs. Metabolites and gut microbes are areas of interest for mainstream and complementary and alternative medicine. We, therefore, aimed to contribute to the discovery of an integrative medicine for UC by comparing and analyzing gut microbes and metabolites in patients with UC and in healthy individuals. This was an observational case-control study. Blood and stool samples were collected from the participants, and metabolite and gut microbial studies were performed. Among metabolites, formate, glycolate, trimethylamine, valine, and pyruvate levels were significantly different between the two groups. Among gut microbes, the abundance of Bacteroidetes at the phylum level; Bacteroidia at the class level; Bacteroidales and Actinomycetales at the order level; Prevotellaceae, Acidaminococcaceae, and Leptotrichiaceae at the family level; and Prevotella, Roseburia, Paraprevotella, Phascolarctobacterium, Ruminococcus, Coprococcus, Clostridium_XIVB, Atopobium, and Leptotrichia at the genus level was also significantly different. Most of the metabolites and gut microbes significantly different between the two groups were involved in energy metabolism and inflammatory processes, respectively. The results of this study could be helpful for the identification of targets for integrative medicine approaches for UC.

• Adacolumn
• Crohn’s disease
• Ulcerative colitis
• adsorptive granulocyte and monocyte apheresis
• biomarkers
• inflammatory bowel disease

• inflammatory bowel disease
• inflammatory bowel disease quality care evaluation center
• quality of care
• secondary indicators

• China
• Chronic Disease
• Humans
• Inflammatory Bowel Diseases/therapy
• Program Evaluation
• Quality of Health Care

• Anti-DNA Ab
• granulocytes
• immune tolerance and regulation
• pConsensus peptide (pCons)
• polymorphonuclear cells (PMNs)
• regulatory B cells
• systemic lupus erythematosus

• corticosteroid naïve
• granulocyte and monocyte adsorptive apheresis
• immunomodulators
• ulcerative colitis

Granulocyte and monocyte adsorptive apheresis (GMA) has been used for therapy of steroid-dependent/refractory ulcerative colitis (UC). The aim of this study was to investigate the effectiveness of GMA in UC patients not receiving steroids.

We conducted a single-arm, open-label, and multicenter prospective clinical trial. UC patients who had insufficient responses to 5-aminosalicylic acid received GMA twice a week for 5 weeks.

The response rate of all patients was 58.2% (39/67). Of the 39 patients who achieved a response, 74.4% achieved endoscopically confirmed mucosal healing.

GMA shows effectiveness in inducing remission in UC patients not receiving steroid.

EXPECT study demonstrates that granulocyte and monocyte adsorptive apheresis has promising effectiveness with regard to inducing remission in patients with active ulcerative colitis (UC) who are not receiving steroid treatment. The first episode of UC was an independent predictor of a response in multiple logistic regression.

• COVID-19
• granulocyte and monocyte adsorptive apheresis
• inflammatory bowel disease
• steroid naive

The etiology and pathogenesis of inflammatory bowel disease (IBD), including ulcerative colitis and Crohn’s disease, are not fully understood so far. Therefore, IBD still remains incurable despite the fact that significant progress has been achieved in recent years in its treatment with innovative medicine. About 20 years ago, selective granulocyte and monocyte apheresis (GMA) was invented in Japan and later approved by the Japanese health authority for IBD treatment. From then on this technique was extensively used for IBD patients in Japan and later in Europe. Clinical trials from Japan and European countries have verified the effectiveness and safety of GMA therapy in patients with IBD. In 2013, GMA therapy was approved by China State Food and Drug Administration for therapeutic use for the Chinese IBD patients. However, GMA therapy has not been extensively used in China, although a few clinical studies also showed that it was effective in clinical and endoscopic induction of remission in Chinese IBD patients with a high safety profile. This article reviews past history, present clinical application as well as the future prospective of GMA therapy for patients with IBD.

• Inflammatory bowel disease
• Ulcerative colitis
• Crohn’s disease
• Granulocyte and monocyte apheresis
• Therapy
• Efficacy

Myeloid‐derived leucocytes, a major source of inflammatory cytokines, play an important role in the exacerbation of ulcerative colitis (UC). Selective depletion of myeloid leucocytes by adsorptive granulomonocytapheresis (GMA) with an Adacolumn should alleviate inflammation and promote remission. However, there are discrepancies among the reported efficacy outcomes. This study aimed to evaluate the efficacy and safety of GMA in UC patients with a focus on factors affecting clinical efficacy.

This was a retrospective analysis of 50 patients with active UC who had received GMA therapy. GMA efficacy was evaluated based on the Rachmilewitz's clinical activity index (CAI) and Mayo endoscopic score for mucosal healing. Laboratory findings were analyzed to demonstrate any relationship with the GMA‐responder or nonresponder feature. Adverse events were recorded during and after GMA therapy.

The overall clinical remission rate (CAI ≤4) was 79.2%, and among these, the mucosal healing rate was 59.2%. The clinical remission rate was 69.2% in patients who received 5 GMA sessions and 82.3% in patients who received 10 sessions. Significantly higher baseline CAIs and lower albumin and hemoglobin levels were observed in nonremission cases compared with those who achieved remission. Four patients (8%) experienced transient adverse events, but none were severe.

GMA was favored by patients because of its safety and nonpharmacological treatment options. Accordingly, UC patients were spared from pharmaceuticals after applying GMA therapy.

• adsorptive granulomonocytapheresis
• albumin
• hemoglobin
• myeloid lineage leucocytes
• ulcerative colitis

• Adsorption
• Adult
• Colitis, Ulcerative/epidemiology
• Colitis, Ulcerative/therapy
• Female
• Granulocytes/cytology
• Hemoglobins/analysis
• Humans
• Leukapheresis/methods
• Male
• Middle Aged
• Monocytes
• Patient Safety
• Remission Induction
• Retrospective Studies
• Treatment Outcome

• Adsorptive granulocyte and monocyte apheresis
• Colonoscopy
• Inflammatory bowel disease
• Mayo score
• Steroid free
• Ulcerative colitis

• adsorptive granulocytes and monocytes apheresis
• complement activation fragments
• granulomonocytapheresis
• inflammatory bowel disease
• myeloid lineage leucocytes
• treating inflammatory bowel disease without drugs

Adsorptive granulomonocytapheresis (GMA) with the Adacolumn has been introduced as a non-pharmacologic treatment for ulcerative colitis (UC). However, a subset of patients who might respond well to GMA needs to be targeted. This study was conducted at three IBD centers to determine factors affecting the efficacy of GMA in patients with moderately-to-severely active UC.

From January 2008 to December 2017, a total of 894 active episodes (first attack or relapse) in 593 patients were treated with GMA. Clinical remission was defined as normal stool frequency and no rectal bleeding. Multiple clinical and laboratory parameters at entry were considered for efficacy assessment.

Clinical remission was achieved during 422 (47%) of the 894 treatment cases. In the multivariate analysis, predictors for favorable response to GMA were age ≤60 years, UC duration <1 year, Mayo endoscopic subscore 2 (vs. 3), steroid naïve UC, and biologic naïve UC. Clinical remission rate was 70% in patients with four of the five factors, 52% in patients with three factors, 46% in patients with two factors, 39% in patients with one factor, and 18% in patients with none of these factors. Overall, the clinical remission rate was significantly higher in patients with a greater number of the five predictors (P < 0.0001).

GMA appeared to be effective in steroid naïve and biologic naïve patients with short duration of UC. Elderly patients (>60 years) and those with severe endoscopic activity did not respond well to GMA. Additional, well designed, prospective, controlled trials should strengthen our findings.

• adverse effect
• elderly
• granulocyte adsorption apheresis
• ulcerative colitis

Granulocyte-monocyte apheresis has been proposed for the treatment of ulcerative colitis, although it is limited by costs and variability of results.

To assess effectiveness of granulocyte-monocyte apheresis in patients with steroid-dependent, azathioprine-intolerant/resistant moderate ulcerative colitis.

Consecutive patients fulfilling inclusion criteria were prospectively enrolled, treated by apheresis, and followed up for 12 months. The primary end point of the study was steroid-free clinical remission at 12 months, with no need for biologic therapy or surgery.

From January to December 2013, 33 patients were enrolled. After one year of follow-up, 12 (36%) patients had clinical remission, were steroid-free, and had no need for biological therapy or surgery; 3 (9%) cases showed a clinical response (but not clinical remission). Moreover, 12 (36%) patients required biologic therapy, 4 (12%) underwent colectomy, and in the other 2 (6%) a reduction, but not withdrawal, of steroid dose was achieved.

Our study shows that a standard course of granulocyte-monocyte apheresis is associated with a 36% steroid-free clinical remission in patients with steroid-dependent, azathioprine-intolerant or resistant moderate ulcerative colitis. Apheresis might represent an alternative to biologic therapy or surgery in this specific subgroup of patients. This trial is registered with Clinicaltrial.gov NCT03189888.

• Adsorptive granulocyte/monocyte apheresis
• Colitis, ulcerative
• Mayo score
• Myeloid lineage leucocytes
• Receiver operating characteristic curve

• Adacolumn granulomonocytapheresis
• Crohn’s disease
• Inflammatory bowel disease
• adolescents
• myeloid lineage leukocytes
• pediatrics
• ulcerative colitis

• cytapheresis
• erythema nodosum
• extra-intestinal manifestation
• granulocytes and monocytes
• pyoderma gangrenosum
• remission induction therapy
• ulcerative colitis

• antibiotics
• granulocyte and monocyte apheresis
• pouchitis
• proctocolectomy
• ulcerative colitis

• long-term prognosis
• myeloid lineage leucocytes
• platelets
• predictive factor of response to therapy
• ulcerative colitis

• colonoscopy
• granulocyte and monocyte apheresis
• loss of mucosal tissue
• mucosal biopsy
• neutrophil infiltration
• neutrophils and monocytes
• ulcerative colitis

• Ascites
• Gene therapy
• Immunotherapy
• Macrophage
• Transfection

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)-α biologics has validated the role of inflammatory cytokines notably TNF-α in 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 naïve 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 21^st 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 pro-inflammatory 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.

• Inflammatory bowel disease
• Myeloid lineage leucocytes
• Adsorptive granulocytes/monocytes apheresis
• Corticosteroid sparing effect
• Complement activation fragments
• Treating inflammatory bowel disease without drugs

• Colitis, Ulcerative/blood
• Colitis, Ulcerative/diagnosis
• Colitis, Ulcerative/economics
• Colitis, Ulcerative/immunology
• Colitis, Ulcerative/therapy
• Colonoscopy
• Cost-Benefit Analysis
• Crohn Disease/blood
• Crohn Disease/diagnosis
• Crohn Disease/economics
• Crohn Disease/immunology
• Crohn Disease/therapy
• Cytokines/metabolism
• Health Care Costs
• Humans
• Inflammation Mediators/metabolism
• Leukapheresis/economics
• Leukapheresis/methods
• Predictive Value of Tests
• Treatment Outcome

• Crohn's Disease
• Granulocytapheresis
• Steroid-dependence
• Steroid-resistance
• Ulcerative Colitis

• granulocyte and monocyte apheresis
• inflammatory cytokines
• restorative proctocolectomy
• septic complications
• ulcerative colitis

• Adolescent
• Adult
• Anti-Inflammatory Agents/therapeutic use
• Anti-Inflammatory Agents, Non-Steroidal/therapeutic use
• Blood Component Removal/adverse effects
• Child
• Colitis, Ulcerative/blood
• Colitis, Ulcerative/therapy
• Combined Modality Therapy
• Female
• Granulocytes
• Humans
• Male
• Mesalamine/therapeutic use
• Monocytes
• Prednisolone/therapeutic use
• Remission Induction/methods
• Severity of Illness Index
• Sulfasalazine/therapeutic use
• Treatment Failure
• Young Adult

Background. Tacrolimus (FK506) is effective for patients with ulcerative colitis (UC). However, there are few reports on tacrolimus therapy (TT) with respect to the relationship with endoscopic and clinicopathologic findings. Methods. Thirty patients with moderate/severe active UC refractory to or dependent on corticosteroid were treated with oral tacrolimus. The expression of ectopic MUC5AC in the colon was pathologically analyzed before and at 12 weeks after TT, evaluating the Mayo score and steroid-sparing effects. Results. Both mean disease and endoscopic activity index scores were reduced at levels of statistical significance in 26 UC patients receiving more than one month of TT (P < 0.0001). The dose of prednisolone was reduced by a statistically significant amount (P = 0.00022), and 14 of the 26 patients (53.8%) had steroid-free status 12 weeks after TT. The decrease in ectopic MUC5AC expression in the mucous cells of the colon was significantly associated with endoscopic improvement of inflammation in the UC patients with TT (P = 0.043). Loss of ectopic MUC5AC expression was detected in all patients who had complete response. Conclusions. Tacrolimus appears to be effective for the treatment of moderate/severe UC patients. Loss of ectopic MUC5AC expression may be important for pathologic remission in the colon of UC patients.

• Adsorption
• Adult
• Blood Component Removal
• Colitis, Ulcerative/blood
• Cytokines/blood
• Female
• Granulocytes/metabolism
• Humans
• Interleukin-10/blood
• Male
• Monocytes/metabolism

Patients with ulcerative colitis (UC) are treated with prednisolone (PSL), which causes adverse side effects. Extracorporeal granulocyte/monocyte adsorption (GMA) with an Adacolumn depletes elevated/activated myeloid lineage leucocytes as sources of inflammatory cytokines. We were interested to evaluate the efficacy, safety and the treatment cost for PSL and GMA.

Forty-one patients with active UC had achieved remission with GMA, at 1 or 2 sessions/week, up to 10 sessions (n=24) or with orally administered PSL (1mg/kg bodyweight, n=17). Clinical activity index (CAI) ≤4 was considered clinical remission. Following remission, patients received 5-aminosalicylic acid (2250-3000mg/day) or sulphasalazine (4000-6000mg/day) as maintenance therapy and were followed for 600 days. The total treatment cost was assessed based on 1€=150JPY.

PSL was tapered after two weeks, and discontinued when a patient achieved remission. The average time to the disappearance of at least one major UC symptom (haematochezia, diarrhoea, or abdominal discomfort) was 15.3 days in the GMA group and 12.7 days in the PSL group, while time to remission was 27.9 days in the GMA group and 27.6 days in the PSL group, CAI 0.8 and 2.0, respectively. The Kaplan-Meier plots showed similar remission maintenance rates over the 600 days follow-up period. The average medical cost was 12739.4€/patient in the GMA group and 8751.3€ in the PSL group (P<0.05). In the GMA group, 5 transient adverse events were observed vs 10 steroid related adverse events in the PSL group (P<0.001).

In appropriately selected patients, GMA has significant efficacy with no safety concern. The higher cost of GMA vs PSL should be compromised by good safety profile of this non-pharmacological treatment intervention.

Granulocyte-monocyte apheresis is a relatively new therapy that has been proposed, sometimes with controversial results, for the treatment of inflammatory bowel disease, particularly ulcerative colitis. The aim of the present study was to perform a thorough review of the literature on the application of this type of treatment in ulcerative colitis and discuss the results, in order to provide an opinion on its use which is shared by the involved experts. The review of the literature was performed by searching PubMed with appropriate key words. The results obtained suggest that the major role for this treatment at this moment is for those patients with steroid dependency or with major contraindications to use of steroids. However, promising, albeit very preliminary, results have also been observed in steroid-naïve subjects, and this is of particular interest in consideration of the safety profile of this therapeutic method. As such, the Adacolumn may prove useful in specific subgroups of patients. Future phenotypic, genotypic, and molecular characterization of patients with inflammatory bowel disease might prove useful in defining better those subjects who might benefit most from this treatment modality.

• apheresis
• guidelines
• inflammatory bowel disease
• ulcerative colitis

Active ulcerative colitis (UC) is frequently associated with infiltration of a large number of leukocytes into the bowel mucosa. Leukocytapheresis is a novel nonpharmacologic approach for active UC, in which leukocytes are mechanically removed from the circulatory system. Current data indicate that leukocytapheresis is efficacious in improving response and remission rates with excellent tolerability and safety in patients with UC. Corticosteroid therapy remains a mainstay in the treatment of active UC; however, long-term, high doses of corticosteroids usually produce predictable and potentially serious side effects. If leukocytapheresis can spare patients from exposure to corticosteroids, the risk of steroid-induced adverse events should be minimized. This may be of great benefit to patients because severe side effects of steroids seriously impair health-related quality of life. In this article, we reviewed current evidence on whether leukocytapheresis can avoid or reduce the use of corticosteroids in the management of patients with UC. Several studies have shown that leukocytapheresis was effective for steroid-naïve patients with active UC. Furthermore, both short-term and long-term studies have demonstrated the steroid-sparing effects of leukocytapheresis therapy in patients with UC. Although the evidence level is not striking, the available data suggest that leukocytapheresis can avoid or reduce the use of corticosteroids in the management of UC. Large, well-designed clinical trials are necessary to more accurately evaluate the steroid-sparing effects of leukocytapheresis in the management of UC.

• Corticosteroid
• Granulocyte and monocyte adsorptive apheresis
• Leukocytapheresis
• Steroid-naïve patients
• Steroid-sparing effect
• Ulcerative colitis

• Adalimumab
• Chronic myeloid leukemia
• Crohn’s disease
• Intensive granulocyte and monocyte adsorptive apheresis

• Adalimumab
• Antibodies, Monoclonal, Humanized/therapeutic use
• Colonoscopy
• Combined Modality Therapy
• Crohn Disease/drug therapy
• Crohn Disease/therapy
• Granulocytes
• Humans
• Immunosuppressive Agents/administration & dosage
• Immunosuppressive Agents/therapeutic use
• Leukapheresis
• Leukocyte Reduction Procedures
• Male
• Mercaptopurine/administration & dosage
• Mercaptopurine/therapeutic use
• Mesalamine/administration & dosage
• Mesalamine/therapeutic use
• Metronidazole/administration & dosage
• Metronidazole/therapeutic use
• Monocytes
• Parenteral Nutrition, Total
• Prednisolone/administration & dosage
• Prednisolone/therapeutic use
• Remission Induction
• Young Adult

• Adolescent
• Adult
• C-Reactive Protein/metabolism
• Colitis, Ulcerative/therapy
• Female
• Humans
• Leukapheresis/methods
• Male
• Middle Aged
• Remission Induction
• Safety
• Steroids/therapeutic use
• Treatment Outcome

The immunosuppressant azathioprine (AZA) is widely used in the treatment of inflammatory bowel disease (IBD) for both inducing and maintaining remission. However, the adverse effects of AZA can often necessitate a dose reduction or discontinuation. Bone marrow suppression is one of the most serious complications with AZA treatment. On the other hand, some reports have suggested that neutropenia during AZA therapy reduced the relapse rates of IBD patients, and there have been some cases where eradication of the sensitized leukocytes by leukapheresis or bone marrow transplantation improved the IBD, which may explain the relevant role of neutropenia in controlling disease activity. This report describes the case of a 22-year-old male patient who had Crohn's colitis and complicated perianal fistulas that required immunosuppression; he achieved endoscopically determined remission and showed accelerated mucosal healing as well as clinical remission following the AZA-induced pancytopenia.

• Crohn's disease
• Improvement
• Pancytopenia

AIM: To identify factors predicting the clinical response of ulcerative colitis patients to granulocyte-monocyte apheresis (GMA).

METHODS: Sixty-nine ulcerative colitis patients (39 F, 30 M) dependent upon/refractory to steroids were treated with GMA. Steroid dependency, clinical activity index (CAI), C reactive protein (CRP) level, erythrocyte sedimentation rate (ESR), values at baseline, use of immunosuppressant, duration of disease, and age and extent of disease were considered for statistical analysis as predictive factors of clinical response. Univariate and multivariate logistic regression models were used.

RESULTS: In the univariate analysis, CAI (P = 0.039) and ESR (P = 0.017) levels at baseline were singled out as predictive of clinical remission. In the multivariate analysis steroid dependency [Odds ratio (OR) = 0.390, 95% Confidence interval (CI): 0.176-0.865, Wald 5.361, P = 0.0160] and low CAI levels at baseline (4 < CAI < 7) (OR = 0.770, 95% CI: 0.425-1.394, Wald 3.747, P = 0.028) proved to be effective as factors predicting clinical response.

CONCLUSION: GMA may be a valid therapeutic option for steroid-dependent ulcerative colitis patients with mild-moderate disease and its clinical efficacy seems to persist for 12 mo.

• Granulocyte-monocyte apheresis
• Ulcerative colitis
• Steroid therapy
• Long-term follow-up
• Predictive factors