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Exploratory Study of the Effectiveness of Granulocyte and Monocyte Adsorptive Apheresis Before Initiation of Steroids in Patients With Active Ulcerative Colitis (EXPECT Study): A Multicenter Prospective Clinical Trial

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Granulocyte and monocyte adsorption apheresis for psoriatic arthritis

Takuro Kanekura

poster at ISFA 2019 pag 58

Adsorptive granulocyte and monocyte apheresis (GMA) with the Adacolumn is an extracorporeal treatment, which uses cellulose acetate (CA) beads as adsorptive leucocytapheresis carriers designed to remove elevated and potentially activated myeloid lineage leucocytes. Case series studies on the clinical effectiveness of GMA on skin diseases and associated arthropathy attributable to activated myeloid lineage leucocytes returned remarkable outcome without any serious adverse events. Psoriatic arthritis (PsA) is a chronic inflammatory arthropathy associated with psoriasis. PsA is an intractable immune disorder and refractory to pharmacological intervention. Efficacy of selective depletion of myeloid lineage leucocytes in patients with PsA was assessed.in a multicenter setting. A total of 20 patients with moderate to severe PsA refractory to conventional and biological disease-modifying antirheumatic drugs were enrolled. Each patient received 5 sessions of GMA once a week. The primary efficacy outcome was 20% or more decrease in the American College of Rheumatology score 20 (ACR20). Partial responders received an additional 5 GMA sessions. Of 20 patients, 2 did not complete the study, 9 responded to 5 GMA sessions and 9 received 10 sessions. At the first evaluation 2 weeks after the last GMA session, 13 of the 20 (65.0%) patients achieved ACR20. ACR20 was maintained in 7 of 10 (70%) and 5 of 10 (50%) patients at the follow-up evaluation points 8 and 20 weeks after the last GMA session, respectively. GMA was well tolerated without any safety concern. This multicenter study demonstrated that GMA was effective with good safety profile in patients with PsA refractory to pharmacologicals, We present the results of this study and mode of action of GMA.

http://www.atalacia.com/isfa/data/abstract.pdf

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SY5-01 Granulocyte and monocyte adsorption apheresis for generalized pustular psoriasis

Mariko Seishima

poster at ISFA 2019 pag 57

Generalized pustular psoriasis (GPP) is a rare inflammatory skin disorder characterized by a fever, edema, and generalized erythema with neutrophilic pustules. It sometimes occurs in the course of psoriasis vulgaris, or develops suddenly without any history of psoriasis. Mutations of the IL36RN (deficiency of interleukin thirty-six receptor antagonist: DITRA), CARD14 and AP1S3 genes underlie monogenic auto-inflammatory disorders causing GPP. GPP patients are usually treated with oral administration of etretinate, cyclosporine, and metrexate, biologics including TNF α inhibitors, antibodies to IL-17, IL-17 receptor, and IL-23 p19, and granulocyte and monocyte adsorption apheresis (GMA). Cyclosporine, TNF α inhibitors, and GMA are used for GPP in pediatric, pregnant, or lactating patients. GMA is an extracorporeal apheresis that removes activated granulocytes and monocytes using a column packed with cellulose acetate beads. Multicenter study was performed to access efficacy of selectively depleting the myeloid lineage leukocytes in GPP patients. Fifteen patients with persistent moderate to severe GPP despite conventional therapy were included. Based on the GPP severity scores relative to entry, the overall scores improved, and the area of erythroderma, pustules, and edema decreased. Likewise, Dermatology Life Quality Index (DLQI) improved, reflecting better daily function and quality of life. Twelve out of 14 patients were judged as responders (85.7%), and 10 out of 12 patients maintained the clinical response for10 weeks after the last GMA session without any change in medication. Thus, GMA is estimated to be safe and effective, suggesting a major role of granulocytes/ monocytes in the immunepathogenesis of GPP. Recent study showed that GMA was effective for 100% of DITRA patients and for 64.7% of the patients with IL36RN mutation-negative GPP. Thus, GMA is effective therapy for both DITRA and non-DITRA GPP patients. GMA may be a useful therapy for all GPP patients

http://www.atalacia.com/isfa/data/abstract.pdf

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SY4-03 The efficacy of combination therapy of intensive GMA with biologics or a JAK inhibitor for refractory inflammatory bowel disease

Satoshi Tanida

poster at ISFA 2019 pag 56

Background and Aim: A monotherapy with intensive GMA, biologics or a JAK inhibitor are limited in patients with intractable Crohn’s disease (CD) or ulcerative colitis (UC). We retrospectively evaluated the 10- and 52-week efficacy and safety of combination therapy of intensive GMA with biologics or a JAK inhibitor for intractable UC or CD.
Method: A combination of intensive GMA (2 sessions a week, total 10 times) with tofacitinib (TOF) for active UC was performed and that of intensive GMA with ustekinumab (UST) for active CD was done. Results: Of 6 consecutive UC patients receiving a combination therapy of TOF (20 mg daily for 8 weeks as induction therapy and subsequently 10 mg daily) plus intensive GMA for moderately-to-severely active UC and loss of response to corticosteroids, azathioprine, and/ or biologic therapies, 67% (4 cases) displayed clinical remission according to Mayo score and 100% displayed mucosal healing at 10 weeks. A temporary increase in CPK were seen. Of 5 consecutive CD patients receiving a combination therapy of ustekinumab (every 8 weeks) plus intensive GMA for moderately-to-severely active CD and loss of response to corticosteroids, azathioprine, and/or biologic therapies, 75% displayed cumulative steroid-free clinical remission at 10 weeks and did such remission over 52 weeks under subsequent maintenance monotherapy of UST. The mean CDAI at baseline were 257. Its values at 10 and 52 weeks after the combination therapy with UST plus intensive GMA were 48 and 68, respectively. One case showed mucosal healing at 52 weeks according to SES-CD. No adverse events were observed. Conclusions: Combination therapy of intensive GMA with biologics or a JAK inhibitor appeared to be effective and safe for refractory UC or CD.

http://www.atalacia.com/isfa/data/abstract.pdf

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SY3-04 Real-world experiences of cytapheresis therapy for ulcerative colitis; results from large-scale multicenter observational studies

Taku Kobayashi

poster at ISFA 2019 pag 53

There are two types of extracorporeal therapy for treating active ulcerative colitis (UC), granulocyte and monocyte adsorption (GMA) and leukocytapheresis (LCAP). Although Sawada et al reported the efficacy of LCAP by the randomized controlled trial (Sawada K et al. Am J Gastroenterol 2005), the larger sham-controlled multicenter trial of GMA failed to prove its efficacy (Sands BE et al. Gastroenterol 2008). Therefore, evidence to show their efficacy relies more on the real-world data, including the post-marketing surveillance (PMS). The large-scale PMS for LCAP was named as REFINE study, involving 847 patients from 116 medical facilities in Japan (Yokoyama Y, Kobayashi T et al. J Crohn Colitis 2014). Adverse events were seen only in 10.3% and the vast majority were mild. The overall clinical remission rate was 68.9%, and the mucosal healing rate was 62.5%. These results were very consistent with the results from PMS of 697 patients treated with GMA, which also demonstrated its real-world effectiveness and safety (Hibi T et al. Dig Liver Dis 2008). In addition, a retrospective observational study aimed to evaluate the clinical outcome at 1 year and identify risk factors for relapse after LCAP was recently conducted among patients who had achieved remission in the PMS (Kobayashi T et al. J Gastroenterol 2018). The 1-year cumulative relapse free rate was 63.6%. Following LCAP, a high clinical activity and a high leukocyte count were associated with a greater risk of relapse. Intensive LCAP was associated with favorable long-term outcomes in corticosteroidrefractory patients. The response rate of re-treatment upon relapse was as high as 85%. These results on the risks of relapse as well as effectiveness of re-treatment may help to overcome the weakness of cytapheresis therapy in maintaining remission. Results from the clinical trial evaluating the clinical efficacy of intermittent maintenance cytapheresis therapy are also warranted.

http://www.atalacia.com/isfa/data/abstract.pdf

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Tu1711 – Safety and Effectiveness of Granulocyte and Monocyte Adsorptive Apheresis in 125 Elderly Patients with Inflammatory Bowel Disease: A Multicenter Cohort Study

Hiroki Tanaka, Satoshi Motoya, Tomoyoshi Shibuya, Satoshi Tanida, Seiichiro Kokuma, Eiji Hosoi Gastroenterology 2018 154 (6) Suppl.S-996–S-997

Background: There are few studies on the usefulness of granulocyte and monocyte adsorptive apheresis (GMA) in elderly patients with inflammatory bowel disease (IBD). We investigated the safety and effectiveness of GMA in elderly patients who participated in the Post-marketing Surveillance Study of GMA Using Adacolumn® for Patients with Inflammatory Bowel Disease Who Have Special Situations (PARTICULAR). Methods: The PARTICULAR study is a retrospective, multicenter cohort study that included patients with ulcerative colitis (UC) or Crohn’s disease (CD) who received GMA between November 2013 and March 2017. Patients with at least one special situation, including elderly patients, patients with anemia, and patients undergoing concomitant treatment with multiple immunosuppressants (IMs) were enrolled. Patients aged # 64 years were excluded from this study. GMA was performed using Adacolumn® (JIMRO, Takasaki, Japan). Each patient received up to a maximum of 11 GMA sessions. The safety of GMA was assessed in all patients. The effectiveness of GMA was assessed in patients with UC with a partial UC disease activity index (pUC-DAI) score of $ 3. Remission was defined as a pUC-DAI score of # 2. Patients receiving concomitant treatment with infliximab, adalimumab, or calcineurin inhibitors were excluded from the effectiveness assessment. The incidence of adverse events (AEs) and remission rates were compared between elderly patients with and without any special situation using univariate and multivariate logistic regression analysis. Results: A total of 125 elderly patients (118 UC, 7 CD) from 93 institutions were included. The median age was 73.2 years. Fifty-six patients did not have any special situation, and 69 had at least one or more special situations. The incidence of AEs was 11.2% in all patients. The incidence of AEs was significantly lower in elderly patients without any special situation (3.6%) than in those with at least one or more special situations (17.4%) (Figure 1A). AEs significantly occurred in elderly patients with anemia (21.9%) and on multiple concomitant IMs (23.8%) compared to those without any special situation (3.6%). Anemia and multiple concomitant IMs were identified as independent predictors for a higher incidence of AEs (Table 1). The effectiveness of GMA was assessed in 92 patients with UC. The remission rate was 48.9%. No difference was observed in the remission rate between elderly patients without any special situation (52.2%) and those with at least one or more special situations (45.7%) (Figure 1B). Conclusions: A low incidence of AEs (3.6%) was found in elderly IBD patients receiving GMA without any special situation. Remission was achieved by GMA in 48.6% of the elderly UC patients. Care should be taken when using GMA in elderly IBD patients with anemia or on multiple concomitant IMs

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