Granulocyte and monocyte adsorption apheresis (GMA) is a therapeutic option for remission induction in the active ulcerative colitis (UC) patients. Effects of high processed blood volume of GMA as remission induction therapy on the long-term prognosis of UC patients have remained unclear. For this study, we investigated the relation between re-exacerbation of UC and the processed blood volume of GMA performed as induction therapy.

Data from UC patients treated using a total of 10 GMA sessions as remission induction therapy during 2012 - 2022 were retrospectively collected and analyzed. The relation between the GMA dose, processed blood volume of GMA divided by body weight, and UC re-exacerbation requiring inpatient treatment within 1 year was evaluated.

This study examined data of 72 active UC patients, with median age of 44.4 years (65% male) and median GMA dose of 34.2 mL/kg/session. Kaplan-Meier analysis showed the 1-year exacerbation-free rate was significantly higher in the higher GMA dose group than in the lower GMA dose group (P = 0.008). Cox proportional hazards regression analyses revealed a higher GMA dose as inversely associated with the re-exacerbation of UC within 1 year (hazard ratio: 0.36, 95% confidence interval: 0.17 - 0.78). Extended treatment time of GMA session beyond 60 min contributed to achieving the higher GMA dose and did not increase unexpected treatment termination because of clotting.

Greater processed blood volume of GMA per patient body weight may be associated with a lower 1-year exacerbation rate in UC patients.

Granulocyte/monocyte adsorptive apheresis (GMA) therapy is a treatment method for ulcerative colitis (UC). Twice-weekly GMA regimens are usually administered to treat severe UC. Although GMA efficacy is considered frequency-dependent, there is no uniformly accepted optimal GMA regimen, and there is insufficient evidence regarding optimal GMA therapy frequency for acute fulminant UC. Case 1 was of a 33-year-old man, and case 2 was of a 20-year-old woman. They were diagnosed with acute fulminant UC and treated with steroid therapy, but exhibited exacerbated UC, and their conditions worsened. We, therefore, initiated intensive frequent GMA therapy (conducted 10-11 times during a 13-day period). In both cases, remission was achieved within two weeks of therapy induction. Herein, we describe two consecutive cases in which rapid remission of acute fulminant UC was achieved without adverse events using intensive frequent GMA therapy. These cases suggest that intensive frequent GMA therapy might induce rapid remission in acute fulminant UC cases and may be more effective than twice-weekly GMA regimens.

Granulocyte and monocyte apheresis is the main non-pharmacological treatment for inflammatory bowel disease (IBD), but we do not know how well accepted it is by patients in our setting.

To determine how granulocyte and monocyte apheresis is perceived by patients in clinical practice in Spain.

Outpatients treated with granulocyte and monocyte apheresis in five IBD Units in Spain were asked to fill in a 14-item questionnaire.

Fifty-two patients completed the questionnaire (88% ulcerative colitis, 12% Crohn's disease; 44% female; age 35 years [IQR 23-51]). Granulocyte and monocyte apheresis was generally well tolerated and well accepted. Very few of the participants regarded the length of the sessions as a limitation. The gastrointestinal symptoms, however, were a frequent concern, both in terms of attending to receive treatment and during the sessions. Overall, 44% were satisfied with the treatment effectiveness. Sixty percent (60%) claimed to be satisfied with the therapy overall, but this was influenced by the patients' clinical response to the therapy. Eighty-two percent (82%) of participants said they would agree to be treated with this technique again in the future, regardless of the response to the treatment.

Granulocyte and monocyte apheresis is well tolerated and accepted by patients with IBD. Although we found no significant differences according to type of IBD or apheresis regimen, patient perception was affected by clinical effectiveness.

The aim of the study was to analyze the effect of granulocyte and monocyte apheresis (GMA) with mesalazine for induction of remission in pediatric patients with newly onset chronic inflammatory bowel disease (IBD) colitis.

Thirteen pediatric patients with newly onset extensive IBD colitis were investigated per the ECCO/ESPGHAN IBD protocol. Of these 13, 12 received 10 treatments with Adacolumn (ADA) during a median of 6.25 weeks in combination with low-to-moderate doses of mesalazine, which was continued after apheresis. A control colonoscopy was performed 12 to 16 weeks after GMA treatment. Primary outcomes were mucosal healing (Mayo endoscopic score) and histopathologic grading of biopsies. A secondary outcome was disease activity as measured by the Pediatric Ulcerative Colitis Activity Index.

Twelve children (6 girls) with a median age of 14.6 years and a median duration of symptoms at diagnosis of 3.2 months received all planned 10 treatment sessions with ADA. Ten of 12 patients had pancolitis and 2 of 12 extensive colitis. A final diagnosis, however, indicated ulcerative colitis in 10 children and Crohn disease in 2 children. At control colonoscopy, 8 of 12 children were in clinical remission and the Mayo endoscopic score showed significant improvement in 9 of 12 patients (P = 0.006). Complete microscopic remission, according to the Geboes score, was observed in 2 patients.

In this small study GMA for induction of remission of newly onset pediatric IBD colitis was effective in 8 of 12 patients. Further controlled studies are warranted to confirm the efficacy of this treatment model.

Medical treatment has progressed significantly over the past decade towards achieving and maintaining clinical remission in patients with refractory ulcerative colitis (UC). Proposed mediators of inflammation in UC include pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-2, and the cell-surface adhesive molecule integrin α4β7. Conventional therapeutics for active UC include 5-aminosalicylic acid, corticosteroids and purine analogues (azathioprine and 6-mercaptopurine). Patients who fail to respond to conventional therapy are treated with agents such as the calicineurin inhibitors cyclosporine and tacrolimus, the TNF-α inhibitors infliximab or adalimumab, or a neutralizing antibody (vedolizumab) directed against integrin α4β7. These therapeutic agents are of benefit for patients with refractory UC, but are not universally effective. Our recent research on TNF-α shedding demonstrated that inhibition of annexin (ANX) A2 may be a new therapeutic strategy for the prevention of TNF-α shedding during inflammatory bowel disease (IBD) inflammation. In this review, we provide an overview of therapeutic treatments that are effective and currently available for UC patients, as well as some that are likely to be available in the near future. We also propose the potential of ANX A2 as a new molecular target for IBD treatment.

Granulocyte-monocyte apheresis (GMA) is an emerging therapeutic option in active course of ulcerative colitis (UC). Appropriate GMA dose, including total number, frequency, and duration of the individual GMA session, is a matter of debate. It was the aim of the present study to evaluate the efficacy of a dose-intensified GMA regimen in patients with moderately to severely active UC. A prospective open-label, single-center study was performed in 10 patients with active UC (Rachmilewitz Clinical Activity Index [CAI] ≥ 8 points; Rachmilewitz Endoscopic Index ≥ 7 points). Patients had failed to improve after treatment with steroids and/or immunomodulators. GMA was performed twice weekly for 2 h to a maximum of 10 sessions. In each GMA session, the adsorber was changed after 1 h of treatment time. Four patients achieved remission with a CAI ≤ 4 points. Three patients had a response with an improvement of CAI of ≥3 points. Three patients showed no benefit from GMA. The quality of life score determined by the inflammatory bowel disease questionnaire-Deutschland increased by 26 points in median. First and second filters had similar efficiency in granulocyte and monocyte adsorption. No major adverse effects were observed. Dose-intensified GMA as reported in this study provided an encouraging short-term response rate of 70% in patients with moderately to severely active UC not responding to standard steroid or immunomodulator therapy. Although all patients relapsed not later than 16 weeks, GMA might be useful to reduce steroid and immunomodulator usage, or to delay surgery in this patient group.

Safe and effective treatments are required for patients with ulcerative colitis. It was suggested that granulocyte and monocyte adsorption apheresis might play an important role for ulcerative colitis. Therefore, a meta-analysis was performed.

Medline and the Cochrane controlled trials register were used to identify randomized controlled trials comparing granulocyte and monocyte adsorption apheresis with corticosteroids, and comparing intensive with conventional apheresis in patients with ulcerative colitis.

Nine randomized trials were eligible for inclusion criteria. According to pooled data, granulocyte and monocyte adsorption apheresis is effective for inducing clinical remission in patients with ulcerative colitis compared with corticosteroids (odds ratio, 2.23; 95% confidence interval: 1.38-3.60). However, the efficacy of granulocyte and monocyte adsorption apheresis was not dependent on the number of apheresis sessions. The intensive apheresis (≥2 sessions per week) is more effective for inducing clinical remission than weekly apheresis (odds ratio, 2.10; 95% confidence interval: 1.12-3.93). The rate of adverse events by apheresis was significantly lower than that by corticosteroids (odds ratio, 0.24; 95% confidence interval: 0.15-0.37).

Our meta-analysis reveals that intensive granulocyte and monocyte adsorption apheresis is a safe and effective treatment with higher rates of clinical remission and response for ulcerative colitis compared with corticosteroids.

Leukocyte removal therapy (LRT) is recognized as an effective treatment for active ulcerative colitis (UC). In this study, factors associated with the efficacy and long-term effects of LRT were evaluated.

From April 1998 to March 2010, 98 patients with moderate to severe UC were randomly assigned to granulocyte and monocyte/macrophage adsorptive apheresis (GMA) (n = 47) or leukocytapheresis (LCAP) (n = 51) treatment. Patients received two sessions of LRT in the first week, followed by three weekly administrations. All patients were treated with 5-aminosalicylic acid and corticosteroid. Steroid doses were tapered if patients achieved clinical improvement. Clinical remission was defined as a decrease in clinical activity index to < 4 and endoscopic findings to Matts' grade 1 or 2. When clinical activity index decreased but still remained ≥ 5 and Matts' grading was 1 or 2, the patient was considered to have improved. Patients were observed for at least 1 year and diagnosed as relapsed when additional treatment was required.

Seventy-one (73%) patients achieved clinical remission or improvement. No significant difference was found between LCAP and GMA. Increased age, ≥ 3 attacks of UC, and ≥ 2 sessions of LRT were indicative of refractoriness to LRT. During 1 year observation, 28 patients were relapsed. Duration of UC, ≥ 3 attacks of UC, and ≥ 2 sessions of LRT were indicative of refractoriness to the long-term effects of LRT.

Both GMA and LCAP were effective to treat active UC. However, long duration of UC, multiple UC attacks, and past history of LRT reduce the efficacy.

The effect of granulocyte and monocyte adsorption apheresis (GMA) on prevention of relapse of ulcerative colitis (UC) is not clear. This was a pilot open-labeled, prospective, randomized, unblinded study to compare the tolerability and efficacy of intermittent GMA (once every 2 weeks) with mercaptopurine to maintain remission of UC. Twenty-one patients with UC, who had achieved remission by induction therapies were randomly assigned to receive either intermittent GMA (N = 10) or oral mercaptopurine (0.5 mg/kg per day; N = 11). The study period was 24 months. The rate of the patients maintaining remission and the incidences of adverse effects were compared between the two groups. At 24 months, seven of 10 patients (70.0%) on intermittent GMA and seven of 11 patients (63.6%, P = 1.00) on oral mercaptopurine were still in remission. Three patients relapsed in each group. One patient taking mercaptopurine, but none receiving intermittent GMA, dropped out because of adverse effects. Intermittent therapy with GMA was well tolerated and a substantial proportion of patients maintained remission. Intermittent GMA therapy in maintaining remission of UC merits further investigation.

This prospective study was to assess the safety and feasibility of daily granulocyte and monocyte adsorptive apheresis (GMA) therapy in patients with active ulcerative colitis (UC).

Thirty consecutive patients with moderately or severely active UC received daily GMA treatment (5 sessions over 5 consecutive days) with the Adacolumn. Adverse events (AE), patient tolerability, and clinical symptoms were monitored daily.

Sixteen patients (53%) experienced AE during at least one GMA session. The most frequent AE was mild headache followed by fatigue and fever. None of the AE was serious, and all patients completed the 5 consecutive GMA sessions. Clinical symptoms (stool frequency and/or rectal bleeding) were improved in 21 patients (70%) during the course of GMA therapy. Clinical remission defined as normal stool frequency and no rectal bleeding was achieved in 7 patients (23%) after 5 GMA sessions. Seven of 20 patients (35%) with moderately active disease achieved clinical remission, whereas none of the 10 patients with severely active disease achieved clinical remission. Total and differential leukocyte counts, platelet count, and hemoglobin level did not significantly change, but C-reactive protein level significantly decreased during the course of GMA therapy.

This is the first report on daily GMA in the treatment of patients with UC. Daily GMA was safe and well tolerated without serious AE. Furthermore, daily GMA was associated with rapid improvement of clinical symptoms in patients with moderately active UC. However, controlled trials are warranted to assess a definite efficacy for daily GMA therapy.

Intravenous cyclosporine A (CsA) is an effective treatment for patients with severe, steroid-refractory ulcerative colitis (UC). Like the response to CsA, clinical trials have shown that two-thirds of patients with refractory UC respond to tacrolimus therapy. However, it is unclear how/when this agent should be used for patients with active UC.

We reviewed the results of previous studies regarding calcineurin inhibitors in UC patients. We examined the best way to use tacrolimus to obtain maximum efficacy by comparing the results from clinical trials with those from a recent survey in Japan.

Calcineurin inhibitors are useful to induce remission in patients with refractory UC; however, the long-term prognosis has not been shown to be improved by CsA. Early intervention with CsA/tacrolimus may improve the long-term prognosis of UC patients just as infliximab does for Crohn's disease patients. Recent studies have indicated that a fasting state and administration of a higher dosage of tacrolimus at the beginning of therapy are critical in ensuring that the target trough concentration of the agent is reached.

The use of higher initial doses of tacrolimus ensured that patients achieved their target levels. Further studies will be needed to elucidate the efficacy of top-down therapy with tacrolimus in patients with UC. Physicians must know how to use calcineurin inhibitors to obtain maximum efficacy.

Patients with ulcerative colitis (UC) that is chronically active despite 5-aminosalicylates or immunomodulators, or who are dependent on corticosteroids to maintain remission, have limited treatment options. Granulocyte/monocyte adsorptive apheresis (GMAA) may have a role in this situation.

To conduct a systematic review of GMAA in UC.

MEDLINE, EMBASE and the Cochrane central register of controlled trials were searched to identify randomized controlled trials (RCTs) comparing GMAA with conventional medical therapy, sham procedure or 'intensive' with 'conventional' GMAA regimens in adult UC patients. Studies reported clinical remission or response rates.

Ten RCTs were eligible. Formal meta-analysis was not undertaken due to concerns about methodological quality of identified studies. Compared with medical therapy, remission rates with GMAA were generally higher, and corticosteroid-sparing effects were observed. Compared with sham procedure, GMAA did not achieve significantly higher remission rates. 'Intensive' GMAA regimens demonstrated generally higher remission rates, and time to remission was shorter compared with 'conventional' regimens. Only two RCTs were at low risk of bias. Six were conducted in Japanese patients, which may limit generalizability.

Granulocyte/monocyte adsorptive apheresis appears of some benefit in UC. High-quality RCTs comparing granulocyte/monocyte adsorptive apheresis with conventional medical therapy or sham procedure in Western populations, with disease activity confirmed endoscopically, are required.

In the last few years, a new non-pharmacological treatment, termed apheresis, has been developed to lessen the burden of ulcerative colitis (UC). Several methods can be used to establish treatment recommendations, but over the last decade an informal collaboration group of guideline developers, methodologists, and clinicians has developed a more sensible and transparent approach known as the Grading of Recommendations, Assessment, Development and Evaluation (GRADE). GRADE has mainly been used in clinical practice guidelines and systematic reviews. The aim of the present study is to describe the use of this approach in the development of recommendations for a new health technology, and to analyse the strengths, weaknesses, opportunities, and threats found when doing so.

A systematic review of the use of apheresis for UC treatment was performed in June 2004 and updated in May 2008. Two related clinical questions were selected, the outcomes of interest defined, and the quality of the evidence assessed. Finally, the overall quality of each question was taken into account to formulate recommendations following the GRADE approach. To evaluate this experience, a SWOT (strengths, weaknesses, opportunities and threats) analysis was performed to enable a comparison with our previous experience with the SIGN (Scottish Intercollegiate Guidelines Network) method.

Application of the GRADE approach allowed recommendations to be formulated and the method to be clarified and made more explicit and transparent. Two weak recommendations were proposed to answer to the formulated questions. Some challenges, such as the limited number of studies found for the new technology and the difficulties encountered when searching for the results for the selected outcomes, none of which are specific to GRADE, were identified. GRADE was considered to be a more time-consuming method, although it has the advantage of taking into account patient values when defining and grading the relevant outcomes, thereby avoiding any influence from literature precedents, which could be considered to be a strength of this method.

The GRADE approach could be appropriate for making the recommendation development process for Health Technology Assessment (HTA) reports more explicit, especially with regard to new technologies.

The purpose of this meta-analysis was to determine whether selective adsorptive granulocyte and monocyte apheresis (GMA apheresis) using the Adacolumn device can effectively reduce clinical symptoms and endoscopic signs of inflammation in patients with ulcerative colitis (UC). A comprehensive search for randomized controlled trials (RCTs) published up to May 2008 was performed. Each study's quality was evaluated, and the data reported in the results were abstracted. Pooled relative risk (RR) estimates and 95% confidence intervals (CIs) were calculated using the fixed-effects model. Heterogeneity was quantified statistically and explained by the variation in the trial design. Seven RCTs including 594 patients were found, and six RCTs on active UC contributed to the main analyses. In half of the trials, GMA apheresis was compared to steroids. Only one trial was fully blinded. A response or remission after 6 weeks was achieved more often in patients treated with GMA apheresis (RR 1.42; CI 1.15-1.75). Also, after 12 weeks, GMA apheresis produced significantly higher remission rates (RR 1.41; CI 1.08-1.83), but long-term data were sparse. In the trials that compared GMA apheresis and steroids (n = 220 patients), side effects were much less frequent in the GMA apheresis groups (RR 0.19; CI 0.11-0.34). Homogeneous evidence from seven RCTs shows that GMA apheresis induces a clinical remission in a higher proportion of UC patients as compared to conventional medical therapy.

Remarkable advances have been made in the area of pharmacotherapy such as immunosuppressants and biologics in recent years. However, there is always the possibility that adequate pharmacotherapy cannot be carried out due to resistance, organ damage, allergies, and adverse drug reactions. The idea of aiming for treatment that is safer and more effective by using concomitant therapeutic apheresis to mitigate drug therapies that cause severe tissue injury has surfaced. In the present report, I would like to discuss new findings related to disorders such as rheumatoid arthritis, ulcerative colitis, and chronic hepatitis C that are already covered by insurance and the indications, methods, and clinical efficacy of therapeutic apheresis for disorders such as dilatative cardiomyopathy, pyoderma gangrenosum, and pulmonary fibrosis that are currently being evaluated and investigated in the hope that they will be covered in the future.

Granulocyte and monocyte adsorptive apheresis (GMA) has shown efficacy in patients with active ulcerative colitis (UC). However, with routine weekly treatment, it may take several weeks to achieve remission, and to date, the efficacy of a more frequent treatment schedule remains unknown. The aim of this study was to assess the clinical efficacy and safety of intensive GMA treatment in patients with active UC.

This was an open-label, prospective, randomized multicenter study to compare an intensive, two GMA sessions per week, with the routine, one GMA session per week. A total of 163 patients with mild-to-moderately active UC were randomly assigned to routine weekly treatment or intensive treatment. The maximum number of sessions of GMA permitted was 10. However, when patients achieved remission, GMA was discontinued. Remission rate at the end of the study, time to remission, and adverse events were assessed in both groups.

Of the 163 patients, 149 were available for efficacy analysis as per protocol, 76 were in weekly GMA, and 73 were in intensive GMA. At the end of the study period, clinical remission was achieved in 41 of 76 patients (54.0%) in weekly GMA and in 52 of 73 patients (71.2%) in intensive GMA (P=0.029). The mean time to remission was 28.1+/-16.9 days in the weekly GMA treatment group and 14.9+/-9.5 days in the intensive GMA group (P<0.0001). Intensive GMA was well tolerated without GMA-related serious adverse side effects.

Intensive GMA in patients with active UC seems to be more efficacious than weekly treatment, and significantly reduced the patients' morbidity time without increasing the incidence of side effects.

Ulcerative colitis is a chronic inflammatory disease that affects the colon and rectum. Its pathogenesis is probably multifactorial including the influx of certain cytokines into the colonic mucosa, causing disease activity and relapse. The hypothesis of removing such cytokines from the circulation by leukocytapheresis was implemented to reduce disease activity, maintain remission, and prevent relapse. Many recent reports not only in Japan, but also in the West, have highlighted its beneficial effects in both adult and pediatric patients. Large placebo-controlled studies are needed to confirm the available data in this regard. In this article, we shed some light on the use of leukocyte apheresis in the management of autoimmune diseases, especially ulcerative colitis.

Activated granulocytes and monocytes/macrophages are implicated in the pathogenesis of ulcerative colitis. Open-label studies and clinical experience in Japan and Europe have suggested that granulocyte/monocyte apheresis is safe and effective in treating ulcerative colitis.

We evaluated the efficacy of granulocyte/monocyte apheresis in a randomized, double-blind, sham-controlled trial in patients with active moderate-to-severe ulcerative colitis (Mayo score 6-11) in community-based and tertiary care centers. As intervention, we used granulocyte/monocyte apheresis with the Adacolumn Apheresis System (JIMRO, Ltd, Takasaki, Japan) or sham apheresis in a 2:1 ratio for 9 weeks of treatment in a North American pivotal study (N = 168) and in a smaller, companion study of identical design conducted in Europe and Japan (N = 47).

In the pivotal study, clinical remission rates (Mayo score 0-2, with scores of 0 on rectal bleeding and 0 or 1 on endoscopic examination) were 17% and 11% for the granulocyte/monocyte apheresis (n = 112)- and sham-treatment groups, respectively (n = 56; P = .361). Clinical response (Mayo score reduction of >/=3 points from baseline) was observed in 44% and 39% of patients, respectively (P = .620). Similar changes were observed for the apheresis- and sham-treatment groups for endoscopic remission and response, and changes in Mayo and quality-of-life scores. The companion study and pooled data from both studies also yielded similar results.

In this study, granulocyte/monocyte apheresis was well tolerated but did not demonstrate efficacy for induction of clinical remission or response in patients with moderate-to-severe ulcerative colitis.