• clinical efficacy
• granulocyte and monocyte adsorptive apheresis (GMA)
• palmoplantar pustulosis
• pustulotic arthro‐osteitis

• Humans
• Female
• Male
• Middle Aged
• Prospective Studies
• Psoriasis/therapy
• Psoriasis/complications
• Psoriasis/immunology
• Psoriasis/blood
• Granulocytes/immunology
• Monocytes
• Adult
• Treatment Outcome
• Blood Component Removal/methods
• Blood Component Removal/adverse effects
• Aged
• Skin/pathology
• Skin/immunology
• Osteitis/therapy
• Osteitis/immunology
• Japan
• Arthritis, Psoriatic/therapy
• Arthritis, Psoriatic/immunology

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

For the optimal management of refractory ulcerative colitis (UC), secondary loss of response (LOR) and primary non-response to biologics is a critical issue. This article aimed to summarize the current literature on the use of cytapheresis (CAP) in patients with UC showing a poor response or LOR to biologics and discuss its advantages and limitations. Further, we summarized the efficacy of CAP in patients with UC showing insufficient response to thiopurines or immunomodulators (IM). Eight studies evaluated the efficacy of CAP in patients with UC with inadequate responses to thiopurines or IM. There were no significant differences in the rate of remission and steroid-free remission between patients exposed or not exposed to thiopurines or IM. Three studies evaluated the efficacy of CAP in patients with UC showing an insufficient response to biologic therapies. Mean remission rates of biologics exposed or unexposed patients were 29.4 % and 44.2%, respectively. Fourteen studies evaluated the efficacy of CAP in combination with biologics in patients with inflammatory bowel disease showing a poor response or LOR to biologics. The rates of remission/response and steroid-free remission in patients with UC ranged 32%-69% (mean: 48.0%, median: 42.9%) and 9%-75% (mean: 40.7%, median: 38%), respectively. CAP had the same effectiveness for remission induction with or without prior failure on thiopurines or IM but showed little benefit in patients with UC refractory to biologics. Although heterogeneity existed in the efficacy of the combination therapy with CAP and biologics, these combination therapies induced clinical remission/response and steroid-free remission in more than 40% of patients with UC refractory to biologics on average. Given the excellent safety profile of CAP, this combination therapy can be an alternative therapeutic strategy for UC refractory to biologics. Extensive prospective studies are needed to understand the efficacy of combination therapy with CAP and biologics.

• Ulcerative colitis
• Inflammatory bowel disease
• Cytapheresis
• Granulocyte and monocyte adsorptive apheresis
• Anti-tumor necrosis factor-α antibody
• Combination therapy

• Biological Products/adverse effects
• Colitis, Ulcerative/diagnosis
• Colitis, Ulcerative/drug therapy
• Cytapheresis
• Humans
• Immunologic Factors/therapeutic use
• Remission Induction
• Steroids/therapeutic use
• Treatment Outcome

Drug therapy of immune-mediated inflammatory arthropathies is not always satisfactory, and there is a risk of adverse events. Granulocyte and monocyte/macrophage apheresis (GMA) is a non-pharmacological therapeutic option that is beneficial and very well tolerated. GMA involves passing blood through a column with cellulose acetate beads to remove increased and activated myeloid lineage cells and improve the cytokine profile. The technique reduces pain and inflammation. We present four clinical reports that illustrate the clinical uses of GMA with the medical device Adacolumn^® in patients with different backgrounds and immune-mediated inflammatory arthritis. The results were positive, and no adverse events were reported.

• disease-modifying anti-rheumatic drugs
• leukapheresis
• non-steroidal anti-inflammatory agents
• pain
• psoriatic arthritis
• rheumatoid arthritis
• tumour necrosis factor inhibitors

• Crohn’s disease
• leukocytapheresis
• ulcerative colitis

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

• Extracorporeal photopheresis
• Leukodepletion
• Plasma exchange
• Therapeutic apheresis

• Anaemia
• Crohn’s disease
• Elderly patient
• GMA
• Granulocyte and monocyte adsorptive apheresis
• Immunosuppressant
• Inflammatory bowel disease
• Paediatric patient
• Special situation
• Ulcerative colitis

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

Calprotectin is a stable neutrophil protein, which can be measured in faecal samples. The faecal level of calprotectin increases during disease activity in ulcerative colitis (UC). Nonetheless, the relevance of faecal calprotectin (FC) measurement during granulomonocytapheresis (GMA) for UC has not yet been fully evaluated. This prospective study was to investigate the value of FC for assessing disease activity and predicting clinical course in UC patients undergoing GMA therapy.

One hundred and eighty-four patients with moderately active UC with endoscopic activity (Mayo endoscopic subscore [MES] = 2 or 3) received Adacolumn GMA therapy (10 apheresis sessions over consecutive 5 weeks). Patients who achieved clinical remission were subsequently given maintenance medications for 12 months. FC levels were measured at entry and after treatment.

After GMA, 80 of the 184 patients (43%) achieved clinical remission, and 51 (28%) achieved mucosal healing (MH; MES = 0 or 1). The median FC level significantly decreased in patients who achieved MH (P = 0.02), but not in those without MH. Thirty-four patients (43%) relapsed during the 12-month follow-up. The median FC level at the end of GMA therapy was significantly higher in patients who subsequently relapsed than in those who maintained remission (149.5 vs 45.5 μg/g, P < 0.001). A cut off value of 114 μg/g had a sensitivity of 76% and a specificity of 85% to predict future relapse.

Our findings indicate that FC is a relevant biomarker, which is convenient to measure for assessing endoscopic activity and predicting relapse in patients who achieve remission following a course of GMA therapy.

• Endoscopic activity
• Faecal calprotectin
• Granulomonocytapheresis
• Predicting relapse
• Ulcerative colitis

Ulcerative colitis (UC) is 1 of the 2 major phenotypes of chronic inflammatory bowel disease (IBD), which afflicts millions of individuals throughout the world with debilitating symptoms that impair function and quality of life. Further, IBD often affects women during childbearing age. Indeed, UC activity frequently increases during pregnancy, and the medications used to induce remission may adversely affect the health of the mother and the unborn child. We report successful induction of a remission in a UC case who experienced a flare-up in the first trimester of pregnancy. Upon relapse, she was treated with steroids and adsorptive granulomonocytapheresis (GMA) with the Adacolumn plus tacrolimus. This combination therapy induced a stable remission that was maintained during her entire pregnancy. She gave birth to a healthy child at 36 weeks of pregnancy with no maternal or fetal complications. Our experience indicates that GMA, as a non-drug therapeutic intervention with a favorable safety profile, plus tacrolimus might be a relevant treatment option for patients with active IBD during pregnancy. A future study of a large cohort of pregnant patients should strengthen our findings.

• Colitis, ulcerative
• Granulomonocytapheresis
• Pregnancy
• Tacrolimus

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.

• granulocyte and monocyte apheresis
• iC3b
• inflammatory cytokines
• myeloid lineage leukocyte
• myeloid-derived suppressor cell

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

• Cytapheresis
• Cytokines
• Granulocyte and monocyte apheresis
• Inflammatory bowel disease
• Leukocytapheresis
• Ulcerative colitis

Overwhelming activation of granulocytes and monocytes is central to inflammatory responses during sepsis. Granulocyte and monocyte adsorptive apheresis (GMA) is an extracorporeal leukocyte apheresis device filled with cellulose acetate beads and selectively adsorbs granulocytes and monocytes from the peripheral blood.

In this study, septic rats received the GMA treatment for 2 h at 18 h after cecal ligation and puncture.

GMA selectively adsorbed activated neutrophils and monocytes from the peripheral blood, reduced serum inflammatory cytokine expression, and seemed to improve organ injuries and animal survival. GMA potentially reduced lung injury by alleviating the infiltration of inflammatory cells and the secretion of cytokines.

This study showed that selective granulocyte and monocyte adsorption with cellulose acetate beads might ameliorate cecal ligation and puncture (CLP)-induced sepsis and improve survival and organ function.

• Adsorption
• Cellulose acetate
• Granulocyte
• Inflammation
• Monocyte
• Sepsis

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

• Crohn’s disease
• Current medical treatment of inflammatory bowel disease
• Extracorporeal treatment
• Future therapeutical strategies
• Inflammatory bowel disease
• Psychological aspects in inflammatory bowel disease
• Step up/top down
• Ulcerative colitis

Inflammatory bowel disease (IBD) is an idiopathic, chronic, nonspecific inflammatory disease. IBD is comprised of two major types, ulcerative colitis (UC) and Crohn's disease (CD), and is hard to be cured. Currently, aminosalicylic acid preparations, corticosteroids and immunosuppressant drugs are the main treatments for the disease, but there exists poor drug efficacy in some cases, and patients are prone to side effects. Biological agents greatly improve the efficacy, but for a small number of refractory patients, comprehensive intervention containing non-drug treatments is needed. Non-drug treatments like fecal microbiota transplantation (FMT), stem cell transplantation, and granulocyte and monocyte apheresis (GMA) have shown enormous potential for the treatment of IBD, and have become a hot spot of IBD treatment research in recent years. In this paper, we review the non-drug treatments for IBD, in order to broaden the horizons of clinicians in the treatment of IBD.

• Inflammatory bowel disease
• Fecal microbiota transplantation
• Stem cell transplantation
• Granulocyte and monocyte apheresis
• Research advance

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

AIM: To evaluate whether the effectiveness of Granulo-monocyto apheresis (GMA), a technique that consists of the extracorporeal removal of granulocytes and monocytes from the peripheral blood, might vary according to the severity of ulcerative colitis (UC) in patients with mild to moderate-severe disease UC activity.

METHODS: We retrospectively reviewed prospectively collected data of patients undergoing GMA at our inflammatory bowel disease centre who had at least a 6 mo of follow-up. The demographics, clinical and laboratory data were extracted from the patients’ charts and electronic records. The severity of UC was scored according to the Modified Truelove Witts Severity Index (MTWSI). A clinical response was defined as a decrease from baseline of ≥ 2 points or a value of MTWSI ≤ 2 points.

RESULTS: A total of 41 (24 males/17 females; mean age 47 years) patients were included in the study. After GMA cycle completion, 21/28 (75%) of mild UC patients showed a clinical response compared with 7/13 (54%) of patients with moderate to severe disease (P = 0.27). At 6-mo, 14/28 (50%) of the mild UC patients maintained a clinical response compared with 2/13 (15%) of the patients with moderate to severe disease (P = 0.04). After the GMA cycle completion and during the 6-mo follow up period, 13/16 (81%) and 9/16 (56%) of mild UC patients with intolerance, resistance and contraindications to immunosuppressants and/or biologics showed a clinical response compared with 2/6 (33%) and 0/6 (0%) of patients with moderate to severe disease activity with these characteristics (P = 0.05 and P = 0.04, respectively).

CONCLUSION: Patients with mild UC benefit from GMA more than patients with moderate to severe disease in the short-term period. GMA should be considered a valid therapeutic option in cases of contraindications to immunosuppressants, corticosteroids and/or biologics.

• Ulcerative colitis
• Granulo-monocyto-apheresis
• Inflammatory bowel disease
• Therapy
• Severity

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Colitis, Ulcerative/blood
• Colitis, Ulcerative/diagnosis
• Colitis, Ulcerative/immunology
• Colitis, Ulcerative/therapy
• Female
• Granulocytes/immunology
• Humans
• Leukapheresis/methods
• Male
• Middle Aged
• Monocytes/immunology
• Retrospective Studies
• Severity of Illness Index
• Time Factors
• Treatment Outcome
• Young Adult

• granulocyte-monocyte-apheresis
• pregnancy
• ulcerative colitis

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

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

• 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

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Child
• Colitis, Ulcerative/diagnosis
• Colitis, Ulcerative/therapy
• Colonoscopy
• Female
• Humans
• Leukapheresis
• Male
• Middle Aged
• Remission Induction
• Young Adult

Patients with IBD and chronic inflammation refractory to conventional therapy often demonstrate higher risk of serious complications. Combinations of immunosuppression and biological treatment as well as surgical intervention are often used in this patient group. Hence, there is need for additional treatment options. In this observational study, focused on re-treatment and long-term results, Granulocyte/Monocyte Adsorption (GMA, Adacolumn^®) treatment has been investigated to study efficacy, safety and quality of life in IBD-patients with chronic activity.

Fifteen patients with ulcerative colitis and 25 patients with Crohn's disease, both groups with chronically active inflammation refractory to conventional medication were included in this observational study. The patients received 5-10 GMA sessions, and the clinical activity was assessed at baseline, after each completed course, and at week 10 and 20 by disease activity index, endoscopy and quality of life evaluation. Relapsed patients were re-treated by GMA in this follow-up study up to 58 months.

Clinical response was seen in 85% and complete remission in 65% of the patients. Ten patients in the UC-group (66%) and 16 patients in the CD-group (64%) maintained clinical and endoscopic remission for an average of 14 months. Fourteen patients who relapsed after showing initial remission were re-treated with GMA and 13 (93%) went into a second remission. Following further relapses, all of seven patients were successfully re-treated for the third time, all of three patients for the fourth time and one for a fifth time.

IBD-patients with chronic inflammation despite conventional therapy seem to benefit from GMA. Re-treatment of relapsing remission patients seems to be effective.