Akiko Suzuki ¹, Kunitaka Haruna, Yuki Mizuno, Yoshiyuki Kuwae, Yuka Ono, Kazuko Okumura, Osamu Negi, Yasuko Kon, Kaori Takeuchi, Kenji Takamori, Shigaku Ikeda, Yasushi Suga,Ther Apher Dial. 2012 Oct;16(5):445-8.

Generalized pustular psoriasis (GPP) is a rare form of psoriasis characterized by the presence of variable numbers of sterile pustules appearing in erythematous and scaly lesions, which are associated with moderate to severe constitutional symptoms. It can be life-threatening especially in the elderly; therefore, medical care must be performed in rapid succession of treatment especially in refractory cases. We have performed granulocyte and monocyte adsorption apheresis (GCAP) on three GPP cases associated with several systemic and laboratory findings. As a result, the edema, erythema and numbers of sterile pustules on the skin lesions were reduced dramatically in all three patients after the first sessions of GCAP therapy. The sizes of the psoriatic lesions were reduced in all three patients following a weekly GCAP treatment for 5 consecutive weeks. Psoriasis area and severity index on discharge had improved in all three patients. No serious adverse effects were observed for up to at least 8 months after treatment. We therefore considered GCAP as one effective alternative to currently existing therapies, especially for recalcitrant cases of GPP.

https://pubmed.ncbi.nlm.nih.gov/23046369/

J L Cabriada ¹, E Domènech, N Ibargoyen, V Hernández, J Clofent, D Ginard, I Gutiérrez-Ibarluzea, J Hinojosa, J clin. Exp.dermatology 2012 (37),3, 241-244 doi.org/10.1111/j.1365-2230.2011.04181.x

Reiter disease (RD) is characterized by a triad of sterile arthritis, urethritis and conjunctivitis. The conditions occur concomitantly or sequentially, and are associated with mucocutaneous features such as circinate balanitis and stomatitis. Arthritis usually occurs in attacks followed by recovery, but it sometimes progresses to permanent damage of the affected joints. Because the symptoms of this disorder are attributable to activated neutrophils, we assessed the efficacy of granulocyte and monocyte adsorption apheresis (GCAP) in a 73-year-old man with RD who had skin rashes on his penis, scrotum and right hand, with severe arthralgia. The patient’s skin rash and joint pain responded dramatically to five sessions of GCAP delivered at intervals of 5 days. We present a detailed description of the patient and discuss the mechanisms of GCAP, and suggest that GCAP may be useful for treating RD.

https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2230.2011.04181.x

Ryoko SHUKUYA,Toshio HASEGAWA,Yusuke NIWA,Keiko OKUMA,Shigaku IKEDA, Journal of dermatology First published: 18 October 2011

In both patients, GCAP resulted in an immediate improvement in skin lesions and fever reduction, without any adverse effects. We suggest that GCAP is an effective therapy for refractory GPP.

https://onlinelibrary.wiley.com/doi/10.1111/j.1346-8138.2011.01279.x

Kazuko Nagase ¹, Ken Fukunaga, Shinichiro Kashiwamura, Tomoaki Kono, Koji Kamikozuru, Yoko Yokoyama, Nobuyuki Hida, Yoshio Ohda, Naohisa Takeda, Koji Yoshida, Masaki Iimuro, Risa Kikuyama, Kyoichi Kato, Hiroto Miwa, Takayuki Matsumoto, Ther Apher Dial. 2011 Aug;15(4):367-73.

In Japan, adsorptive granulocyte/monocyte apheresis (GMA) is an approved treatment option in patients with active Crohn’s disease (CD). However, there is inadequate knowledge regarding the mechanism(s) of therapeutic effects of this non-pharmacologic treatment strategy. Further, recently we have been interested in the regulatory T-cell (Treg) profile which has an essential immunoregulatory function. Thirteen CD patients were treated with a single GMA session. The mean CD activity index (CDAI) and duration of CD were 218.5 and 9.8 years, respectively. Eight healthy volunteers participated as a control group. From CD patients, whole blood was taken immediately before and after the GMA session directly from the GMA column inflow and outflow lines. Broad spectrum serum key cytokines and chemokines were measured by suspension-array and ELISA. At baseline, almost all assayed inflammatory cytokines were significantly elevated in CD patients. Treg-associated cytokines including IL-10 (P < 0.02) and transforming growth factor (TGF)-β1 (P < 0.03), were higher in the GMA column outflow vs. inflow. In contrast, the Th1/Th2 balance, defined as IFN-γ/IL-10 was lower during hemofiltration (P = 0.05), potentially due to an elevated IL-10 (P < 0.02) because an elevation of pro-inflammatory IFN-γ (Th1) was not observed at the GMA column outflow. A single GMA session had a significant impact on the Treg profile. Treg-related cytokines like IL-10 and TGF-β1 in the blood returning to the patients from the GMA column outflow were elevated, while pro-inflammatory cytokines like IFN-γ were not. This action of GMA is potentially very interesting in patients with immune disorders, like CD patients.

https://pubmed.ncbi.nlm.nih.gov/21884471/

Shingo Kato ¹, Kazuhito Kani, Hidehiko Takabayashi, Ryuichi Yamamoto, Tomonari Ogawa, Akihiko Matsuda, Koji Yakabi, Intern ed. 2011;50(15):1591-3.

Granulocyte and monocyte adsorption apheresis (GMA) is one therapeutic option for induction of remission in patients with inflammatory bowel diseases. Recently intensive GMA (2 sessions per week) was reported to be strikingly better than weekly GMA, both in remission rate and time to remission. Here we report two cases of Crohn’s disease refractory to weekly GMA who responded to intensive GMA. One patient had not received immunosuppressive therapy while the other had been refractory to combination therapy with infliximab and azathioprine. Intensive GMA induced remission in these 2 patients. Intensive GMA may represent a therapeutic choice for remission induction and maintenance with infliximab.

https://pubmed.ncbi.nlm.nih.gov/21804287/

https://www.jstage.jst.go.jp/article/internalmedicine/50/15/50_15_1591/_pdf/-char/en

John K Triantafillidis, Emmanuel Merikas, and Filippos Georgopoulos Drug Des Devel Ther. 2011; 5: 185–210. doi: 10.2147/DDDT.S11290

During the last decade a large number of biological agents against tumor necrosis factor-α (TNF-α), as well as many biochemical substances and molecules specifically for the medical treatment of patients with inflammatory bowel disease (IBD), have been developed. This enormous progress was a consequence of the significant advances in biotechnology along with the increased knowledge of the underlying pathophysiological mechanisms involved in the pathogenesis of IBD. However, conventional therapies remain the cornerstone of treatment for most patients. During recent years conventional and biologic IBD therapies have been optimized. Newer mesalazine formulations with a reduced pill size and only one dose per day demonstrate similar efficacy to older formulations. New corticosteroids retain the efficacy of older corticosteroids while exhibiting a higher safety profile. The role of antibiotics and probiotics has been further clarified. Significant progress in understanding thiopurine metabolism has improved the effective dose along with adjunctive therapies. Quite a large number of substances and therapies, including biologic agents other than TNF-α inhibitors, unfractionated or low-molecular-weight heparin, omega-3 polyunsaturated fatty acids, microbes and microbial products, leukocytapheresis, and other substances under investigation, could offer important benefits to our patients. In this paper we review the established and emerging therapeutic strategies in patients with Crohn’s disease and ulcerative colitis.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3084301/

M.I wamoto K.Shigetoh H. Maruyama T. Kondo Transfusion and Apheresis Science Volume 43, Supplement, September 2010, Pages S6-S7 doi.: .10.1016/S1473-0502(10)70013-6

https://www.sciencedirect.com/science/article/abs/pii/S1473050210700136

Annelie Lindberg ¹, Michael Eberhardson, Mats Karlsson, Per Karlén, BMC Gastroenterol. 2010 Jul 6;10:73.

Background: 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.

Methods: 15 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.

Results: Clinical response was seen in 85% and complete remission in 65% of the patients. 10 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.14 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 7 patients were successfully re-treated for the third time, all of3 patients for the fourth time and 1 for a fifth time.

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

https://pubmed.ncbi.nlm.nih.gov/20604939/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2914086/pdf/1471-230X-10-73.pdf

T Hibi ¹, Y Sameshima, Y Sekiguchi, Y Hisatome, F Maruyama, K Moriwaki, C Shima, A R Saniabadi, T Matsumoto

Dig Liver Dis. 2009 Aug;41(8):570-7. doi: 10.1016/j.dld.2008.11.020. Epub 2009 Feb 10.

Background/aim: The Adacolumn selectively depletes granulocytes and monocytes/macrophages, which are thought to be part of the immunopathogenesis of ulcerative colitis. This work aims at evaluating the safety and clinical efficacy of the Adacolumn in patients with ulcerative colitis in large population-based data sets. Methods: The Adacolumn post marketing surveillance in Japan was undertaken on 697 patients in 53 medical institutions over 7 years from 29 October 1999 to 28 October 2006. Clinical efficacy and safety data were provided by patients’ physicians in the participating institutes. Results: Safety was evaluated in all the 697 patients and efficacy in 656 patients. At entry, 92% of the patients were on salicylates, 74% on prednisolone and only 9% on immunomodulators. Approximately 40% of patients had severe ulcerative colitis and over 70% had ulcerative colitis that was refractory to conventional medications. There was no serious adverse events; mild to moderate adverse events were seen in 7.7% of the patients. The overall response (remission or significantly improved) was 77.3%; the remission rate based on clinical activity index was 71.1%, while 17.1% remained unchanged and 5.6% worsened. Patients were subgrouped into severe, moderate and mild ulcerative colitis based on clinical activity index (n=578), the response rates were 63.2%, 65.7% and 80.4%, respectively (P<0.001). Endoscopic assessment of efficacy showed very significant mucosal healing, Matts’ endoscopic index improved from 3.2+/-0.04 to 2.1+/-0.7 (n=219, P<0.001); reduction in prednisolone dose (P<0.0001); leucocyte count (n=358, P<0.0001) and C-reactive protein (n=314, P<0.0001). Patients who received > or =6 Adacolumn sessions (n=319) did better than patients who received < or =5 sessions (n=188, P=0.004) and multivariate logistic regression analysis revealed that baseline granulocyte count was the strongest predictor of clinical response to Adacolumn (P=0.0191, odds ratio 1.151). Conclusion: This post marketing surveillance provides the largest ever efficacy and safety data on the Adacolumn therapeutic leucocytapheresis in patients with ulcerative colitis. As a non-pharmacologic treatment for patients with active ulcerative colitis most of whom were refractory to conventional drug therapy, the observed efficacy was very significant. Baseline granulocyte count was convincingly an independent predictor of clinical response.

https://pubmed.ncbi.nlm.nih.gov/19211314/