Granulocyte And Monocyte Apheresis Research Articles

P727 Clinical efficacy of apheresis in Ulcerative Colitis. The experience of four tertiary centers

Abstract Background Selective depletion of myeloid lineage leucocytes by adsorptive granulocyte and monocyte apheresis (GMA) with Adacolumn ® was introduced as a nonpharmacologic treatment for ulcerative colitis (UC) in 2000. It has been reported that GMA may be effective in combination with immunosuppressive treatment in a subset of patients. Τhe purpose of our study is the evaluation of the effectiveness and safety of GMA as a complementary treatment in patients with refractory ulcerative colitis. Methods Prospective data collection of a patient cohort with refractory UC receiving Adacolumn ® as an adjunct to their medical treatment. The therapeutic protocol has 2 phases: The induction phase entails two sessions per week for at least 3 weeks. The maintenance includes one weekly session for one month, one session every 15 days for one the next month, and monthly sessions thereafter. The patients’ medical treatment was maintained during the sessions. As a failure to GMA was considered the need for colectomy, the switch to a different treatment and inability to discontinue steroids. Response was evaluated after completion of at least 6 sessions of GMA. Results Ten patients with refractory UC were offered Adacolumn® between February 2021 and September 2023. Mean age was 39.6 years (22-61years). All patients had failed at least one biologic treatment and two-thirds two biologics. Their treatment which was maintained during GMA was: tofacitinib 10mg bid for 4 patients, ustekinumab 90mg sc every 8 weeks for 3, vedolizumab 300 mg every 8 weeks for 2, and corticosteroids 16mg for one. The median duration of treatment was 5.1 months (2-13 months), while the median number of sessions was 16 (6-45). Clinical and endoscopic remission was achieved in two cases (20%), after 13 sessions for both (in brackets in the Table) whereas two patients (20%) responded clinically according to partial Mayo score. Treatment failure was documented for 6 patients (60%) after 6-45 sessions. Patient number 4 performed 45 sessions in different hospitals because he was reluctant to be operated. Three underwent colectomy and three discontinued due to non-response. No adverse effects were observed. The initial median of partial Mayo score was 6 (5-9) while at the end of the evaluation was 4.5 (0-9). Table 1 summarizes the results of our study. Conclusion 1) GMA may be beneficial as an adjunct to biologics in refractory to medical treatment UC patients. 2) Interestingly, all patients on tofacitinib showed a favorable response after the addition of GMA. This observation may help define a subset of UC patients who may benefit the most.

Selective granulocyte–monocyte apheresis during induction with vedolizumab in moderate–severe ulcerative colitis: Experience in a tertiary hospital

AimGranulocyte and monocyte apheresis (GMA) is a potential therapeutic option when combined with various drugs for treatment of ulcerative colitis (UC). In this study, we analyze the efficacy and safety of GMA combined with vedolizumab (VDZ) during induction in patients with moderate–severe UC and incomplete response to steroids. Patients and methodsSingle-center retrospective review of patients receiving GMA+VDZ. Data on the disease and previous treatments were collected. Clinical response was classified as no response, response without remission, and remission. Available data on biochemical and endoscopic response were included. Adverse events (AEs) were recorded. ResultsThe study population comprised 6 patients with UC who had received GMA+VDZ during induction after failure of an anti-TNF agent. The median number of GMA sessions was 5 (IQR 4–5; 3–10). All the patients received VDZ 300mg iv at 0, 2, and 6 weeks, and 5 (83%) received an additional dose at week 10. During maintenance, all the patients continued VDZ iv every 8 weeks. The median follow-up was 57.6 months (IQR: 39–74). Four of the 6 patients achieved clinical remission after GMA+VDZ and continued in deep remission until the end of follow-up. A median, non-significant decrease of 1378μg/g (IQR: 924–5778μg/g) was observed for calprotectin and 42.2mg/l (IQR: 15.3–113.5) for CRP vs. baseline. No patient underwent colectomy. No treatment-related AEs were observed. ConclusionsGMA+VDZ during induction can be effective and safe in selected patients with moderate–severe UC and partial response to steroids.

MicroRNA and granulocyte-monocyte adsorption apheresis combotherapy after inadequate response to anti-TNF agents in ulcerative colitis.

Ulcerative colitis (UC) is an inflammatory bowel disease characterized by chronic inflammation of the gastrointestinal tract, affecting millions of individuals throughout the world, and producing an impaired health-related quality of life. Granulocyte and monocyte apheresis (GMA) is a therapeutic option for UC management to induce remission by selective removal of activated leukocytes from bloodstream. Despite the knowledge of the important role of epigenetics in UC pathogenesis, and in the response to different treatments, nothing is known about the role of microRNAs in GMA therapy in UC patients. Seven consecutively UC patients who started GMA in combo therapy with infliximab were recruited. Peripheral blood samples were taken before the apheresis session, at the start of the induction (S0) and at the end (S10). They were follow-up during the induction phase (10 sessions: 2 sessions for a week during 3 wk and 1 session for a week during 4 wk) of the treatment at a tertiary hospital (Hospital la Fe) and 6 mo after finishing the GMA induction therapy. MiRNA was extracted and analyzed by RT-PCR. R software and GraphPad were used. Clinical disease activity significantly decreased after induction therapy with GMA (median partial Mayo score 2 (IQR, 1-6) (P < .05). Fecal calprotectin value and CRP value significantly decreased after induction therapy. Five microRNAs modified their expression during GMA (unsupervised analysis): miR-342-3p, miR-215-5p, miR-376c-3p, miR-139-5p, and miR-150-5p. When a sub-analysis was performed in those patients who showed good response to apheresis treatment (n = 5), two microRNAs showed to be implicated: miR-215-5p and miR-365a-3p. These are preliminary but promising and novel results, as it is the first time, to our knowledge that microRNA profiles have been studied in the context of GMA treatment for IBD.

Use of granulocyte and monocyte adsorption apheresis in dermatology (Review).

Adsorptive granulocyte and monocyte apheresis (GMA) is an extracorporeal treatment that selectively removes activated myeloid lineage leukocytes from peripheral blood. This technique consists of a column with cellulose acetate beads as absorptive leukocytapheresis carriers, and was initially used to treat ulcerative colitis. A literature search was conducted to extract recently published studies about the clinical efficacy of GMA in patients with different skin disorders, reporting information on demographics, clinical symptoms, treatment and clinical course. Dermatological diseases, in which GMA has been performed, include generalized pustular psoriasis, pyoderma gangrenosum, palmoplantar pustular psoriasis, Behcet's disease, Sweet's syndrome, adult-onset Still's disease, impetigo herpetiformis, reactive arthritis, acne and hidradenitis suppurativa syndrome, cutaneous allergic vasculitis and systemic lupus erythematosus. In most patients, GMA was started after the failure of conventional therapeutic options and it was helpful in the majority of cases. Based on the information summarized, GMA could be considered a valid non-pharmacological treatment option for patients with several dermatological conditions, which are difficult to treat with other pharmacological preparations.

Granulocyte and monocyte apheresis as an adjunctive therapy to induce and maintain clinical remission in ulcerative colitis: a systematic review and meta-analysis.

ObjectiveThe goal of treatment in ulcerative colitis (UC) is to induce and maintain remission. The addition of granulocyte and monocyte apheresis (GMA) to conventional therapy may be a promising therapeutic alternative. In this meta-analysis, we aimed to assess the efficacy and safety profile of GMA as an adjunctive therapy.DesignSystematic review and meta-analysis.MethodsWe searched four databases (MEDLINE, Embase, Web of Science and Cochrane Central Register of Controlled Trials) for randomised or minimised controlled trials which discussed the impact of additional GMA therapy on clinical remission induction and clinical remission maintenance compared with conventional therapy alone. Primary outcomes were clinical remission induction and maintenance, secondary outcomes were adverse events (AEs) and steroid-sparing effect. ORs with 95% CIs were calculated. Trial Sequential Analyses were performed to adjusts for the risk of random errors in meta-analyses.ResultsA total of 11 studies were eligible for meta-analysis. GMA was clearly demonstrated to induce and maintain clinical remission more effectively than conventional therapy alone (598 patients: OR: 1.93, 95% CI 1.28 to 2.91, p=0.002, I2=0.0% for induction; 71 patients: OR: 8.34, 95% CI 2.64 to 26.32, p<0.001, I2=0.0% for maintenance). There was no statistically significant difference in the number of AEs (OR: 0.27, 95% CI 0.05 to 1.50, p=0.135, I2=84.2%).ConclusionGMA appears to be more effective as an adjunctive treatment in inducing and maintaining remission in patients with UC than conventional therapy alone.PROSPERO registration numberCRD42019134050.

Adsorptive granulocyte and monocyte apheresis: A potentially relevant therapeutic option for COVID-19

The overproduction of proinflammatory cytokines and subsequent thromboembolism are major problems of coronavirus disease 2019 (COVID-19). Adsorptive granulocyte and monocyte apheresis (GMA), used for ulcerative colitis, is an extracorporeal therapy designed to remove activated myeloid lineage cells. Previous studies have demonstrated that GMA decreases proinflammatory cytokines and neutrophil–platelet aggregates. The effect of GMA on COVID-19 in a patient with ulcerative colitis was recently reported. The modes of action of GMA together with the findings of this case report indicate that GMA could be a relevant treatment option for COVID-19.

Selective granulocyte and monocyte apheresis in inflammatory bowel disease: Its past, present and future.

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.

Adsorptive Granulocyte and Monocyte Apheresis Is Effective in Ulcerative Colitis Patients Both with and without Concomitant Prednisolone

Background: The number of ulcerative colitis (UC) patients is increasing in Japan and other countries. Selective depletion of myeloid lineage leucocytes by adsorptive granulocyte and monocyte apheresis (GMA) with an Adacolumn (JIMRO, Takasaki, Japan) was introduced as a nonpharmacologic treatment strategy in UC patients in 2000. GMA has been reported to be effective in clinical trials; however, the effect of concomitant prednisolone (PSL) on GMA needs to be clarified. Methods: Thirty-nine patients with active UC were treated with GMA at our institute between June 2009 and September 2018. All patients received GMA therapy once or twice a week with the Adacolumn. Conventional medication was to be continued during the whole GMA treatment course. The clinical response was retrospectively evaluated. Results: According to the partial Mayo score, remission was 33.3%, significant efficacy 25.6%, effective 25.6%, and no response 15.4%. The average partial Mayo score was 6.2 ± 1.4 at entry and significantly declined to 1.8 ± 1.8 after GMA sessions (p < 0.0001). The average number of bowel movements was 9.5 ± 5.6 at entry and significantly declined to 3.0 ± 2.8 after GMA sessions (p < 0.0001). In a comparison between the group treated with concomitant PSL and the group without PSL, the change in partial Mayo score or the number of bowel movements from entry to after GMA sessions was not significantly different. Among 24 patients treated by GMA with concomitant PSL, 75% (18/24) became steroid free. Conclusions: The effect of GMA with concomitant PSL and that of GMA without PSL were not different, and GMA was effective irrespective of PSL administration. The present study showed that GMA had efficacy and led many UC patients treated by PSL to be steroid free with no safety concern in the real world, although there is the possibility of recruitment bias due to the retrospective nature of the study.

Single Needle Granulocyte and Monocyte Apheresis for Ulcerative Colitis: A Retrospective Safety Analysis

Granulocyte and monocyte apheresis (GMA) is an effective treatment strategy for active ulcerative colitis (UC) in Japan. Single needle (SN) apheresis reduces needle puncture pain in patients because it requires only one puncture site. We evaluated whether single-needle apheresis could be a safe and effective means of reducing patient burden. We performed a retrospective study of active UC patients who were treated with either SN apheresis or conventional double-needle (DN) apheresis at the Kurume university hospital from April 2014 to March 2018. All the patients treated with GMA after September 2016 underwent SN apheresis. Thus, the two groups predominantly belonged to different time periods. We assessed the safety of SN apheresis. Six patients underwent SN apheresis, and 6 underwent DN apheresis. The average time to the start of apheresis was significantly reduced from 23.1 minutes in the case of DN apheresis to 12.6 minutes for SN apheresis. In addition, the number of difficult punctures was significantly reduced with SN apheresis. There were no differences in adverse events between SN and DN apheresis. Treatment benefits, remission rate and disease activity were similar between SN and DN apheresis. SN apheresis reduced both the time to treatment initiation and pain during puncture, and there was no difference in the number of blood clotting episodes as compared with DN. Although further comparative studies are needed, SN apheresis may be a safe alternative for patients to reduce the strain of treatment.

Clinical and immunological effects of adsorptive myeloid lineage leukocyte apheresis in patients with immune disorders.

Adsorptive granulocyte and monocyte apheresis (GMA) with the Adacolumn® is an extracorporeal treatment, which uses cellulose acetate (CA) beads as adsorptive leukocytapheresis carriers designed to remove elevated and potentially activated myeloid lineage leukocytes. Reports on the clinical efficacy of GMA in patients with skin lesions have appeared in the published work. Dermatological diseases, which are known to respond to GMA, include pyoderma gangrenosum, skin lesions of Behçet's disease, rheumatoid arthritis, pustular psoriasis, psoriatic arthritis, adult-onset Still's disease, Sweet's syndrome, cutaneous allergic vasculitis and systemic lupus erythematosus rashes. In association with clinical studies, efforts to understand the mechanisms of GMA have made significant progress. GMA selectively depletes elevated myeloid lineage leukocytes through binding between blood immunoglobulin G or complement iC3b, which form on the surface of CA beads and the Fcγ receptors or complement receptors expressed on the myeloid lineage cells. However, GMA has immunomodulatory effects including down-modulation of inflammatory cytokine profile, changes in leukocyte surface receptors and induction of regulatory T cells. These actions render GMA a unique non-pharmacological treatment option for patients with chronic dermatoid conditions, which are difficult to treat with pharmacological preparations.

Efficacy of cytapheresis for remission induction and dermatological manifestations of ulcerative colitis.

In ulcerative colitis (UC) patients, cytapheresis depletes elevated and activated leucocytes, which are known to release inflammatory cytokines including tumor necrosis factor (TNF)-α. Further, there are UC patients who develop erythema nodosum (EN) or pyoderma gangrenosum (PG) as extra-intestinal manifestations of UC. Between 2008 and 2015, 181 consecutive patients with active UC received cytapheresis with either a granulocyte and monocyte apheresis (GMA) column or with a leucocyte removal filter (LCAP) as remission induction therapy. Each patient received weekly or intensive (2-3 sessions/week) cytapheresis up to 10 sessions. In 13 patients, UC was complicated by EN or PG. Lichtiger's clinical activity index (CAI) ≤4 meant remission, while ≥3 decrease in CAI meant response to therapy. Prednisolone sparing and the changes in the extra-intestinal manifestations were factored for assessing treatment efficacy. The overall remission and response rates were 52.5% and 71.8%, respectively, CAI fell from 9.4 ± 3.3 to 4.9 ± 3.5 (P < 0.001). The efficacy rates in subgroups on concomitant corticosteroid, anti-TNF or tacrolimus, and those without concomitant medications were not significantly different (P > 0.05). However, in 84 patients on prednisolone, the average daily prednisolone dose was reduced from 18.15 to 12.43 mg/day (P < 0.001) with 21.7% being corticosteroid free. All patients with EN or PG showed favorable response to cytapheresis, notably 2 EN patients achieving remission after just 2 cytapheresis sessions without concomitant medication. In this retrospective efficacy evaluation, cytapheresis was effective as remission induction therapy with steroid sparing effect and desirable safety profile. Further, patients with EN or PG responded favorably to cytapheresis.

Efficacy of granulocyte and monocyte apheresis for antibiotic-refractory pouchitis after proctocolectomy for ulcerative colitis: an open-label, prospective, multicentre study.

Background:Granulocyte and monocyte apheresis (GMA) has shown therapeutic efficacy in active ulcerative colitis (UC). We thought that in patients with pouchitis after proctocolectomy for UC, GMA might produce immunological effects in the intestinal mucosa, and improve clinical symptoms. This prospective study was to evaluate the efficacy of GMA for antibiotic-refractory pouchitis after proctocolectomy for UC.Methods:A total of 13 patients with pouchitis disease activity index (PDAI) > 7 unresponsive to 2 weeks of antibiotic therapy were included. All patients received 10 GMA sessions at 2 sessions/week over 5 consecutive weeks. The primary endpoints were response (a decrease of ⩾3 points in the PDAI) and remission (PDAI < 4). Secondary endpoints included reduction of white blood cells (WBCs), C-reactive protein (CRP), faecal markers (calprotectin and lactoferrin), reduction of the PDAI endoscopic subscore, and GMA safety.Results:The median PDAI score was significantly decreased from 11 (range, 9–15) at entry to 9 (range, 6–13) after the GMA therapy (p = 0.02). A total of six patients (46%) responded to the treatment, but none achieved remission. The median endoscopic subscore (maximum: 6) was 5 (range, 4–6) at entry and 5 (range, 1–6) after the treatment (p = 0.10). None of the laboratory markers (WBCs, CRP, faecal calprotectin and lactoferrin) significantly changed during the treatment. Transient adverse events (AEs) were observed in two patients (15%), dyspnoea in one and headache in one. The AEs were not serious, and all patients completed the 10 GMA sessions.Conclusions:GMA has a good safety profile, but its efficacy appears to be limited in the management of chronic refractory pouchitis. However, a large controlled study should be conducted to evaluate the efficacy of GMA therapy in patients with pouchitis at an earlier clinical stage, before the disease has become refractory to conventional medical therapy.

P556. A randomized, multicentre, clinical trial to compare prednisone plus granulocyte and monocyte apheresis (GMA) versus prednisone alone for inducing steroid-free remission in patients with steroid dependent Ulcerative Colitis (UC)

P556. A randomized, multicentre, clinical trial to compare prednisone plus granulocyte and monocyte apheresis (GMA) versus prednisone alone for inducing steroid-free remission in patients with steroid dependent Ulcerative Colitis (UC)

Therapeutic granulocyte and monocyte apheresis (GMA) for treatment refractory sarcoidosis: a pilot study of clinical effects and possible mechanisms of action.

Sarcoidosis is a systemic, inflammatory disorder, which in a proportion of patients runs a chronic progressive course despite immunosuppressive treatment. Therapeutic granulocyte and monocyte apheresis (GMA) has been shown to be an effective treatment option for other systemic inflammatory disorders, but has not yet been investigated in sarcoidosis. The aim of this study was to evaluate the response to GMA in sarcoidosis. Seven patients with sarcoidosis refractory to standard immunosuppressive therapy received 10 GMA sessions. All patients underwent chest X-ray, spirometry, a Chronic Respiratory Disease Questionnaire (CRQ-SAS), blood tests and bronchoscopy with bronchoalveolar lavage (BAL) before treatment and at 2-4 weeks and 3 months (except bronchoscopy) after the last treatment session. Bronchoalveolar lavage fluid (BALF) cell differential counts were recorded and T cells from blood and BALF were analysed for markers of activity, differentiation and T regulatory function. Compared to baseline, five of seven patients reported an improvement in dyspnoea score. In BALF there was an increase in the percentage of macrophages and a decrease in the percentage of lymphocytes and CD4(+) /FoxP3(+) T cells. Furthermore, the decrease in BALF CD4(+) /FoxP3(+) T cells correlated significantly with an improvement in dyspnoea score. In peripheral blood there was a statistically significant increase in the percentage of CD4(+) /CD27(-) T cells and a trend towards an initial increase in the percentage of CD4(+) /FoxP3(+) T cells, followed by a statistically significant decrease. The effects of GMA on regulatory T cells are consistent with those observed in other inflammatory disorders and could potentially translate into a clinical benefit.

P475 Granulocyte and Monocyte Apheresis (GMA) – Adacolumn® in mild to moderate ulcerative colitis patients with steroid resistance or dependence and azathioprine intolerance or resistance: a prospective multicenter study (preliminary data)

P475 Granulocyte and Monocyte Apheresis (GMA) Adacolumn® in mild to moderate ulcerative colitis patients with steroid resistance or dependence and azathioprine intolerance or resistance: a prospective multicenter study (preliminary data) G. Imperiali1 *, M.M. Terpin2, A. Amato1, A. Bortoli3, G. Meucci4. 1Valduce Hospital, Gastroenterology, Como, Italy, 2Legnano Hospital, Gastroenterology, Legnano, Italy, 3Rho Hospital, Gastroenterology, Rho, Italy, 4S. Giuseppe Hospital, Gastroenterology, Milano, Italy

P476 Gender specific differences in quality of life in Danish paediatric patients with inflammatory bowel disease

P475 Granulocyte and Monocyte Apheresis (GMA) Adacolumn® in mild to moderate ulcerative colitis patients with steroid resistance or dependence and azathioprine intolerance or resistance: a prospective multicenter study (preliminary data) G. Imperiali1 *, M.M. Terpin2, A. Amato1, A. Bortoli3, G. Meucci4. 1Valduce Hospital, Gastroenterology, Como, Italy, 2Legnano Hospital, Gastroenterology, Legnano, Italy, 3Rho Hospital, Gastroenterology, Rho, Italy, 4S. Giuseppe Hospital, Gastroenterology, Milano, Italy

Effects of preoperative leukocytapheresis on inflammatory cytokines following surgery for ulcerative colitis: A prospective randomized study

Targeted extracorporeal granulocyte and monocyte apheresis (GMA) has produced clinical efficacy together with down modulation of specific inflammatory cytokines in patients with ulcerative colitis (UC). This study was to investigate if preoperative GMA produces immunological effect on dysregulated immune activity after restorative proctocolectomy (RPC) in patients with UC. Forty patients requiring RPC were included. Twenty randomly selected patients received five GMA sessions with the Adacolumn over two consecutive weeks before RPC (GMA group). RPC was performed within 2 weeks following the last GMA session. The other 20 patients did not receive GMA before RPC (non-GMA group). Blood samples were obtained immediately before surgery, at 1 h after surgery, and on postoperative Days 1, 3, and 7 from all patients. Abdominal exudate was obtained from the drainage tube at 1 h after surgery, and on postoperative Days 1, 3, and 7. Concentrations of interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α in plasma and peritoneal fluid from a drainage tube were measured by enzyme linked immunosorbent assay. Between the two groups, patients were matched with respect to age, sex, UC duration, severity, extent and the dose of prednisolone at surgery. IL-1β, IL-6, and TNF-α levels in plasma and peritoneal fluid were not significantly different between the two groups during the entire study period. Based on the assays of IL-1β, IL-6, and TNF-α levels in the plasma and the peritoneal fluid, this study did not find any effect on these inflammatory cytokines by preoperative GMA in patients with UC who underwent RPC.

Looking for predictive factors of clinical response to adsorptive granulocyte and monocyte apheresis in patients with ulcerative colitis: markers of response to GMA

BackgroundAdsorptive granulocyte and monocyte apheresis (GMA) with an Adacolumn in patients with ulcerative colitis (UC) has been applied as a non-pharmacological treatment strategy, but the efficacy has been encouraging as well as discouraging, depending on patients’ demography at entry. In this study, we looked for predictive factors for clinical response to GMA in patients with UC.MethodsIn a retrospective setting, 43 outpatients who had been treated with GMA for active UC were evaluated. Patients were divided into remission group and non-remission group based on Lichtiger’s clinical activity index (CAI) before and after 10, once a week GMA sessions. The efficacy was analysed in relation to patients’ demographic variables. To determine predictive factors that closely related to the response to GMA, receiver operating characteristic (ROC) curve, and multiple logistic regression analyses were applied.ResultsAfter 10 GMA sessions, the overall clinical remission rate (CAI < 4) was 53.5%. Multiple logistic regression and ROC analyses showed that the interval between relapse and the first GMA session was a significant and independent predictive factor for clinical response to GMA (P = 0.016); the clinical response was better in patients who received GMA immediately after a relapse and vice versa. Likewise, univariate analyses showed that, the duration of UC (P = 0.036) and the cumulative prednisolone (PSL) dose (P = 0.006) before the first GMA session were significantly greater in the GMA non-responder group as compared with the responder group. Additionally, a lower white blood cell (WBC) count at first GMA session was related to clinical response to GMA (P = 0.032).ConclusionsIn this study, patients with a short duration of UC and low cumulative PSL dose seemed to respond well to GMA. However, we found that the best responders were patients who received GMA immediately after a clinical relapse. Additionally, GMA was effective in patients with low WBC count at the first GMA session. The findings of this study should spare medical cost and reduce morbidity time for many patients, relevant for decision making in clinical settings.

Therapeutic depletion of myeloid lineage leukocytes in patients with generalized pustular psoriasis indicates a major role for neutrophils in the immunopathogenesis of psoriasis

Generalized pustular psoriasis (GPP) is a chronic autoimmune disease characterized by fever, erythema, and neutrophilic pustules over large areas of the skin. GPP does not respond well to pharmacologic intervention. We sought to assess efficacy of selectively depleting the myeloid lineage leukocytes in patients with GPP. Fifteen patients with persistent moderate to severe GPP despite conventional therapy were included. Eligible patients had more than 10% of their skin area covered by pustules. Treatment with oral etretinate, cyclosporine, methotrexate, prednisolone, and topical prednisolone/vitamin D3 was continued if had been initiated well in advance of study entry. Five sessions of adsorptive granulocyte and monocyte apheresis (GMA) with the Adacolumn (JIMRO Co Ltd, Takasaki, Japan) were administered (1 session/wk over 5 weeks) to selectively deplete Fcγ receptor and complement receptor bearing leukocytes. Efficacy was assessed by measuring the skin areas covered by pustules at baseline and 2 weeks after the last GMA session. One patient did not complete the first GMA session. Based on the GPP severity scores relative to entry, the overall scores improved (n = 14, P = .0027), and the area of erythroderma (P = .0042), pustules (P = .0031), and edema (P = .0014) decreased. Likewise, Dermatology Life Quality Index improved (P = .0016), reflecting better daily function and quality of life. Twelve patients were judged as responders (85.7%), and 10 patients maintained the clinical response for 10 weeks after the last GMA session without any change in medication. This study was unblinded and without a placebo arm. GMA in this clinical setting was safe and effective, suggested a major role for granulocytes/monocytes in the immunopathogenesis of GPP.

Adsorptive Depletion of CD14+CD16+ Proinflammatory Monocyte Phenotype in Patients With Generalized Pustular Psoriasis: Clinical Efficacy and Effects on Cytokines

Generalized pustular psoriasis (GPP) is a subtype of psoriasis with strong association with activated neutrophils. Adsorptive granulocyte and monocyte apheresis (GMA) is an extracorporeal intervention for selective depletion of activated granulocytes and monocytes. However, the immunological mechanism(s) for the effect of GMA on patients is not fully defined yet. We investigated the effects of GMA on the ratio of CD14(+) CD16(+) proinflammatory monocytes/CD14(+) monocytes and cytokine/chemokine production by these leukocytes including CXCL8, CCL2, CCL3, CCL4, CCL5 and tumor necrosis factor (TNF)-α in five patients with active GPP. CD14(+) CD16(+) monocytes were significantly elevated in patients with active GPP, and GMA markedly reduced the CD14(+) CD16(+) /CD14(+) ratio together with improvement of patients' clinical symptoms. The serum levels of CXCL8, CCL3 and CCL4 were increased in active GPP patients. Likewise, CCL2 production from monocytes was increased in active GPP patients. Further, CCL3 and CCL4 production from monocytes in active GPP patients were reduced after a course of GMA. Serum CCL5 level and the release of CCL5 from monocytes in active GPP were significantly reduced, but TNF-α level in active GPP was similar to controls. Based on these results, we believe that in addition to neutrophils, elevated CD14(+) CD16(+) proinflammatory monocytes are part of the immune pathology in GPP. Accordingly, selective depletion of CD14(+) CD16(+) monocytes by GMA should be therapeutic in this condition.