R. Sacco, V. D’Ovidio, +18 authors G. Bresci Abstracts of the 20th National Congress of Digestive Diseases / Digestive and Liver Disease 46S (2014) S1–S144

Background and aim: Granulocyte-monocyte-apheresis (GMA) is effective in the treatment of ulcerative colitis (UC). However, all published studies evaluated a low number of patients, with an overall limited follow-up. This observational study investigates the long-term efficacy of GMA in a large number of patients included in the Italian Registry of Therapeutic Apheresis. Material and methods: Data of patients with mild/moderate UC treated with a standard protocol of GMA (5 sessions in 5 weeks) were evaluated. All patients had failed to respond to mesalamine or sulphasalazine, and were under steroid treatment. Clinical evaluations were performed at 3, 12 and 24 months since the end of GMA session. The following parameters were assessed: incidence of clinical remission (CAI [Colits Active Index] <4); CAI; erythrocyte sedimentation rate (ESR); c-reactive protein (CRP); white cells blood count (WBC). Endoscopical evaluations were performed at a 3- month follow-up: the incidence of endoscopical remission (EAI [endoscopical activity index] 0/1) was assessed. Results: Data for 347 patients (214 males, age 46.3 years; CAI 7.47) were available; 288 patients were either steroid-resistant or steroid-dependent. The proportion of patients with remission of disease was 66% at 3 months, 77% at 12 months and 78% at 24 months. At 24 months, all other efficacy parameters had improved from baseline: CAI (7.47 vs 3.47), ESR (35.87 vs 24.1 mm/h), CRP (4.31 vs 2.75 mg/dl) and WBC (8.61 vs 7.19) (p<0.001 for all comparisons). Endoscopic data were available for 107 patients. The incidence of mucosal healing was 47% and all patients with mucosal healing presented a clinical remission over the entire follow-up period. No major adverse events were reported during GMA sessions. Conclusions: Data collected on a large sample of steroid-resistant or steroidrefractory patients included in the Italian Registry of Therapeutic Apheresis show that GMA is a safe and effective procedure over a long-term follow-up. Mucosal healing appears strongly associated with clinical remission.

https://www.semanticscholar.org/paper/OC.11.4-LONG-TERM-EFFICACY-OF-IN-ULCERATIVE-THE-OF-Sacco-D’Ovidio/b4286829a8f80e152dc3974444e1c307c1d4e9ef#citing-papers

Takumi Fukuchi, Hiroshi Nakase ¹, Satoshi Ubukata, Minoru Matsuura, Takuya Yoshino, Takahiko Toyonaga, Keiji Shimazu, Hideaki Koga, Hiroshi Yamashita, Dai Ito, Kiyoshi Ashida, BMC Gastroenterol. 2014 Jul 11;13:124.

Combination therapy with intensive GMAA and thiopurines administration rapidly induced high remission in patients with active early-diagnosed CD without serious adverse effect. Mucosal healing was observed in 50.0% of enrolled patients. This combination therapy might be a rational option for patients with early-diagnosed CD.

https://pubmed.ncbi.nlm.nih.gov/25015328/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4105052/pdf/1471-230X-14-124.pdf

Valeria D’Ovidio ¹, Donatella Meo, Maria Gozer, Marco E Bazuro, Piero Vernia, J Clin Apher. 2015 Feb;30(1):55-7.

To minimize symptoms and the risk of severe clinical relapse, a maintenance GMA treatment was performed throughout pregnancy. The course of pregnancy was uneventful with no side effects; the mother and the baby were all healthy and well at the delivery.

https://pubmed.ncbi.nlm.nih.gov/25181523/

Bruce E Sands ¹, Seymour Katz, Douglas C Wolf, Brian G Feagan, Tao Wang, Lisa-Marie Gustofson, Cindy Wong, Margaret K Vandervoort, Stephen Hanauer, Gut. 2013 Sep;62(9):1288-94.

GMA was well tolerated, but this study did not demonstrate its effectiveness over a sham procedure in inducing clinical remission or response in patients with moderate to severe CD.

https://pubmed.ncbi.nlm.nih.gov/22760005/

Hiroki Takahashi ¹, Kaori Sugawara, Mikako Sugimura, Masahiro Iwabuchi, Yutaka Mano, Katsuaki Ukai, Keiichi Tadokoro, Arch Gynecol Obstet. 2013 Aug;288(2):341-7.

In these three cases with active ulcerative colitis during pregnancy, granulocytapheresis as a non-pharmacologic treatment was effective and safe. In case 3 that did not respond well to the initial granulocytapheresis sessions, a moderate dose of prednisolone enhanced the efficacy of granulocytapheresis and tapering of prednisolone shortly after administration was not associated with relapse.

https://pubmed.ncbi.nlm.nih.gov/23404436/

Yuko Higashi ¹, Mitsuyoshi Shimokawa, Kazuhiro Kawai, Takuro Kanekura, J Dermatol. 2013 Dec;40(12):1042-4.

We present a 39-year-old pregnant woman with Behçet’s disease who was treated successfully with granulocyte and monocyte adsorption apheresis (GMA). There were no complications or adverse effects during her pregnancy and delivery. The neonate manifested no abnormalities.

https://pubmed.ncbi.nlm.nih.gov/24303809/

Keiichi Tominaga ¹, Masakazu Nakano, Mina Hoshino, Kazunari Kanke, Hideyuki Hiraishi

BMC Gastroenterol. 2013 Mar 1;13:41. doi: 10.1186/1471-230X-13-41.

Background: 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. Methods: 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. Results: 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). Conclusions: 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.

https://pubmed.ncbi.nlm.nih.gov/23452668/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3599731/

Yusuke Okuyama,Akira Andoh,Masakazu Nishishita,Ken Fukunaga,Koji Kamikozuru,Yoko Yokoyama,Yoshitaka Ueno,Shinji Tanaka,Hiroyuki Kuge,Syusaku Yoshikawa,Atsushi Sugahara,Emi Anami,Yoshinori Munetomo,Chiyuki Watanabe,Yoshihide Fujiyama &Takayuki Matsumoto Scand. J. Gastro. 2013, 48 (4), 412-418. https://doi.org/10.3109/00365521.2012.763175

Objective. This study aimed to assess the efficacy and tolerability of leukocytapheresis (LCAP) and to investigate predictive factors for mucosal healing and a sustained clinical response in steroid-free and steroid-refractory patients with ulcerative colitis (UC). Material and methods. Thirty-one steroid-free or steroid-refractory patients with active UC were enrolled. Five or ten consecutive sessions of LCAP were performed in each patient. The efficacy and tolerability was then evaluated at weeks 3 and 6. Endoscopic examination was performed at week 6 to evaluate the mucosal healing, and the sustained cumulative response rate was evaluated at 12 months. Results. At week 6, the mean Mayo clinical activity score had decreased significantly from 8.0 to 4.6 in the steroid-free patients and from 8.3 to 3.9 in the steroid-refractory patients. Rachmilewitz’s endoscopic index had also decreased significantly from 9.1 to 6.1 in the steroid-free patients and from 10.0 to 5.7 in the steroid-refractory patients. Forty-seven percent of the steroid-free patients and 33% of the steroid-refractory patients achieved mucosal healing. The peripheral platelet counts had decreased significantly at weeks 3 and 6 in the mucosal healing group, compared with the non-mucosal healing group. The patients with a more than 15% platelet reduction had a significantly higher cumulative response rate, compared with the patients without a platelet reduction (p = 0.015). Conclusions. LCAP is beneficial for the induction of mucosal healing in steroid-free and steroid-refractory patients with UC. The degree of platelet reduction during LCAP might be a predictive marker for mucosal healing and a sustained clinical response.

Multicenter prospective study for clinical and endoscopic efficacies of leukocytapheresis therapy in patients with ulcerative colitis – PubMed (nih.gov)

Multicenter prospective study for clinical and endoscopic efficacies of leukocytapheresis therapy in patients with ulcerative colitis: Scandinavian Journal of Gastroenterology: Vol 48, No 4 (tandfonline.com)

Ken Fukunaga ¹, Takayuki Matsumoto, J Gastroenterol Hepatol. 2012 Jun;27(6):997-1003.

Ulcerative colitis (UC) and Crohn’s disease (CD) comprise the idiopathic inflammatory bowel diseases (IBD) of the gut. The etiology of IBD is poorly understood, but an autoimmune disturbance has been suggested to play an important role in this incurable disease. Extracorporeal leukocytapheresis (CAP) is an additional adjunct for IBD patients refractory to other conventional therapies, including steroids. The primary aim of CAP should be to suppress such unwanted immunological response by removing circulating inflammatory cells from the blood stream. The first decade has been passed since CAP was approved by Japanese social health insurance policy. It is therefore now an appropriate opportunity to upgrade and summarize our current understandings and/or future perspectives of this unique non-pharmacological and non-surgical strategy for IBD patients. According to several clinical and basic research reports, an early introduction of CAP should produce higher efficacy as compared with CAP applied sometime after a clinical relapse. Likewise, CAP therapy adjusted to patients’ body-weight as well as two treatment sessions per week (intensive regimen) should benefit the efficacy rate. The etiology of IBD is not fully elucidated yet. As a result, the major therapeutic strategies in the Western world have been immunosuppressive therapy, including biologics. CAP is an unusual treatment modality for IBD because it seems to have both effectiveness and safety, which should generally be balanced in this type of illness. We now have to develop future strategies with and without combining biologics to improve the quality of life of IBD patients.

https://pubmed.ncbi.nlm.nih.gov/22414250/

Shingo Kato ¹, Eriko Hosomi, Fumi Amano, Taisuke Kobayashi, Kazuhito Kani, Ryuichi Yamamoto, Tomonari Ogawa, Akihiko Matsuda, Yoshiki Sato, Seiichi Izaki, Tetsuya Mitarai, Koji Yakabi, J Crohns Colitis. 2012 Aug;6(7):787-91.

Background and aims: Subcutaneous aseptic abscess is one phenotype of neutrophilic dermatitis. We were interested to see if a case of steroid refractory Crohn’s disease (CD) complicated by subcutaneous aseptic neutrophilic abscesses responds to intensive granulocyte/monocyte adsorptive apheresis (GMA). Methods: The patient was a 21-year-old male with worsening severe CD while on oral prednisolone (30 mg/day). His symptoms included fever, bloody diarrhoea and multiple painful subcutaneous nodules throughout his body. Skin biopsy showed chronic panniculitis with neutrophilic infiltrates. Further, colonoscopy showed oedematous sigmoid colon, while colonic biopsy showed non-caseous granuloma. Because biologics were feared to increase the risk of bacteraemia as the result of germ culture on his pus was not known at the time, we decided to treat this case with GMA. Five GMA sessions with the Adacolumn over 5 consecutive days (daily GMA) were initiated. Results: On admission, his CD activity index (CDAI) was 355, C-reactive protein (CRP) 11.2 mg/dL. After 5 GMA sessions, CDAI decreased to 170, and CRP fell to 5.0 mg/dL, with no fever. GMA was restarted at 2 sessions/week (total 10 sessions). The patient’s CDAI fell to <150, and the skin lesions re-epithelialized. Conclusions: In this CD case complicated by subcutaneous aseptic neutrophilic abscesses, GMA appeared to be effective. Our impression is that when biopsy reveals neutrophil infiltrate is a major feature of the lesions, GMA should be considered. As GMA appears to have no safety concerns, a frequent GMA protocol, like daily followed by 2 to 3 times/week should be preferred over the routine weekly GMA.

https://pubmed.ncbi.nlm.nih.gov/22386738/