E Domènech ¹, J Hinojosa, M Esteve-Comas, F Gomollón, J M Herrera, G Bastida, A Obrador, R Ruiz, C Saro, M A Gassull, Spanish Group for the Study of Crohn’s Disease and Ulcerative Colitis (GETECCU)

Aliment Pharmacol Ther. 2004 Dec;20(11-12):1347-52. doi: 10.1111/j.1365-2036.2004.02288.x.

Background: Uncontrolled studies suggest that granulocyteaphaeresis might be useful in the management of active ulcerative colitis. Aim: To assess the efficacy of granulocyteaphaeresis treatment in active steroid-dependent inflammatory bowel disease. Methods: We conducted a multicentre, prospective, open, pilot study in patients with steroid-dependent inflammatory bowel disease. All patients were started on 60 mg/day of prednisone; after 1 week, a five-session programme of granulocyteaphaeresis (once per week) was started. The steroid dose was tapered weekly if there was clinical improvement. Remission was defined as an inactive clinical activity index together with complete withdrawal of steroids at week 6. The patients were followed up for at least 6 months or until disease relapse. Results: Twenty-six patients (14 ulcerative colitis, 12 Crohn’s disease) were included. More than a half had been previously treated with immunomodulators. Remission was achieved in 62 and 70% of ulcerative colitis and Crohn’s disease, respectively. During a median follow-up of 12.6 months, six of eight ulcerative colitis patients maintained their clinical remission; however, only one Crohn’s disease patient remained in remission after the first 6 months of follow-up. Conclusions: Granulocyteaphaeresis is a safe treatment option in inflammatory bowel disease. A five-session programme of granulocyteaphaeresis seems to be efficient in the treatment of steroid-dependent ulcerative colitis, but not in Crohn’s disease.

https://pubmed.ncbi.nlm.nih.gov/15606397/

https://onlinelibrary.wiley.com/doi/epdf/10.1111/j.1365-2036.2004.02288.x

Purushothaman Premchand ¹, Ken Takeuchi, Ingvar Bjarnason Eur J Gastroenterol Hepatol 2004 Sep;16(9):943-5. doi: 10.1097/00042737-200409000-00023.

Refractory ulcerative colitis that fails conventional intense medical treatment often leads to colectomy. Although ciclosporin and infliximab may avert colectomy in certain cases, these treatments come with substantial toxicity and may only act as a bridge to avert emergency surgery. Granulocyte monocyte/macrophage adsorption apheresis is a new treatment and has shown efficacy for refractory colitis in up to 80% of cases in a Japanese study and is apparently only associated with negligible side effects. We report a case of severe refractory proctitis destined for colectomy effectively treated with granulocyte monocyte/macrophage adsorption apheresis. After two of five sessions the patient achieved full clinical remission, which has been sustained with the addition of azathioprine for more than 1 year.

https://pubmed.ncbi.nlm.nih.gov/15316424/

Takuro Kanekura ¹, Akira Gushi, Masahiro Iwata, Seita Fukumaru, Ryoko Sakamoto, Koichi Kawahara, Ikuro Maruyama, Tamotsu Kanzaki

J Am Acad Dermatol. 2004 Aug;51(2 Suppl):S83-7. doi: 10.1016/j.jaad.2003.12.023.

The painful orogenital ulcerations of Behçet’s disease are among the major symptoms of patients and are often intractable. We assessed the efficacy of granulocyte and monocyte adsorption apheresis therapy in two patients, a 21-year-old man with orogenital ulcerations and a 50-year-old woman with genital ulceration and abdominal pain. They underwent 5 and 8 granulocyte and monocyte adsorption apheresis treatments at 5-day intervals, respectively. The painful orogenital ulcerations of the man responded dramatically and the genital ulcer of the woman decreased in size and her abdominal pain was improved. Our results demonstrate that granulocyte and monocyte adsorption apheresis may be useful for treating orogenital ulcerations of Behçet’s disease.

https://pubmed.ncbi.nlm.nih.gov/15280820/

Cuenca, F & Paredes, J & Mendoza, J & Cruz, D & Herrero, A & Díaz-Rubio, M.Revista española de enfermedades digestivas : organo oficial de la Sociedad Española de Patología Digestiva .2004,96. 501-3, 504. DOI:10.4321/S1130-01082004000700007.

Objective: To describe our experience with granulocyte apheresis to induce remission in patients with active Crohn’s disease refractory to conventional treatment. We summarize the results previously obtained with this technique.

Conclusions: Granulocyte apheresis is a safe and well tolerated therapeutic modality that can be a valid therapeutic alternative in the induction of remission in inflammatory bowel disease, although controlled clinical trials must be conducted to define long-term efficacy, as well as to establish „optimal patient“ selection, re-treatment interval, and number of sessions.

https://pubmed.ncbi.nlm.nih.gov/15283632/

Midori Hasegawa ¹, Nahoko Kawamura, Masamitsu Murase, Shigehisa Koide, Hiroko Kushimoto, Kazutaka Murakami, Makoto Tomita, Yoshiyuki Hiki, Masahiko Shikano, Satoshi Sugiyama, Ther Apher Dial. 2004 Jun;8(3):212-6.

We concluded that combined therapy of GCAP or LCAP and corticosteroids is effective for the treatment of RPGN and lung hemorrhage due to microscopic polyangiitis.

https://pubmed.ncbi.nlm.nih.gov/15154873/

Kazuo Kusugami ¹, Kenji Ina, Takafumi Ando, Kenji Hibi, Yuji Nishio, Hidemi Goto, J Gastroenterol. 2004 Dec;39(12):1129-37.

Patients with inflammatory bowel disease (IBD) have intestinal and extraintestinal symptoms that can greatly impair their quality of life. They must rely on multiple medications with aminosalicylates, corticosteroids, and purine analogues to control these symptoms. Although decades of clinical experience in IBD management has led to optimized approaches for achieving the induction and maintenance of remission, the disease in some patients is still refractory to conventional medical treatment, or the effectiveness of these drugs can be limited by treatment-related side effects. Significant progress in our understanding of the pathogenesis of IBD has yielded several immunomodulatory approaches with novel biological agents or apparatus, such as cyclosporine, cytoprotective agents, infliximab, and leukocytapheresis. Further immunomodulatoy therapy, aiming at the inhibition of molecular and cellular mediators, is anticipated, in parallel with the clarification of immunoinflammatory pathways in IBD. An additional goal will be to identify factors predictive of response to treatment with each novel immunomodulatory agent or apparatus. This will help provide each patient with optimized and individualized therapy, thereby increasing therapeutic efficacy and reducing possible side effects.

https://pubmed.ncbi.nlm.nih.gov/15622475/

Takeshi Kusaka ¹, Ken Fukunaga, Kunio Ohnishi, Tadashi Kosaka, Toshihiko Tomita, Yoko Yokoyama, Koji Sawada, Yoshihiro Fukuda, Hiroto Miwa, Takayuki Matsumoto J Clin Apher. 2004;19(4):168-73. doi: 10.1002/jca.20023.

Six patients with active Crohn’s disease (CD) unresponsive to conventional medications (CM) were treated with Monocyte-granulocytapheresis (M-GCAP). CD patients who scored 200-400 points in Crohn’s disease activity index (CDAI) in spite of receiving CM, including enteral nutrition, for at least 2 weeks were enrolled in our double series trial. Each series had 5 weekly M-GCAP and 2 follow-up weeks, and each M-GCAP treated 1,800 ml of patient’s peripheral blood. After the 1st series, patients who decreased more than 50 points on the CDAI were deemed responders and enrolled in the second series. Patients with a CDAI score less than 150 points were considered in remission. The patients‘ quality of life was evaluated using an index (IBDQ) before and after the 1st series. The CDAI was significantly decreased comparing before and after the 1st series (258.2 +/- 36.2 vs. 166.5 +/- 16.6; P < 0.02). 50% of patients (3/6) responded to the therapy, and one case (16.7%) could be induced to remission. Significant removal was revealed only for white blood cells (25.6 +/- 16.9%; P < 0.05), especially granulocytes (29.5 +/- 22.5%; P < 0.05). A statistically significant improvement of IBDQ was revealed in the responders‘ group (162.3 +/- 17.2 vs. 189.3 +/- 11.5; P < 0.03). M-GCAP could be an effective adjunctive therapy for active CD patients unresponsive to CM allowing them to maintain a high QOL. However, it might be difficult to improve patients who could not be induced to remission after the 1st series by applying another series.

https://pubmed.ncbi.nlm.nih.gov/15597346/

Yasuo Suzuki ¹, Naoki Yoshimura, Abby R Saniabadi, Yasushi Saito

Dig Dis Sci. 2004 Apr;49(4):565-71. doi: 10.1023/b:ddas.0000026299.43792.ae.

Corticosteroid therapy of ulcerative colitis (UC) is associated with frequent adverse side effects and poor quality of life. Recently, adsorptive granulocyte and monocyte/macrophage apheresis has shown efficacy in patients with severe steroid refractory UC. The objective of this study was to investigate if, instead of corticosteroids, adsorptive leukocytapheresis has efficacy as the first-line therapy for steroid-naïve patients with active UC. Twenty patients, aged 15-49 years, with a mean clinical activity index (CAI) of 8.6 were recruited. Adsorptive leukocytapheresis was done with Adacolumn, which contains cellulose acetate beads as adsorptive carriers for granulocytes and monocytes (FcgammaR and complement receptors expressing leukocytes). Each patient received 6 to 10 leukocytapheresis sessions of 60-min duration, at 2 sessions/week. Efficacy was assessed 1 week after the last session. Post treatment, the mean CAI was 3.0 (P = 0001), and 17 of 20 patients (85%) were in remission. There were significant falls in C-reactive protein (P = 0.0003), total white cell counts (P = 0.003), neutrophils (P = 0.0029), and monocytes (P = 0.0038), an increase in lymphocytes (P = 0.001), and increases in the blood levels of soluble TNF-alpha receptors I (P = 0.0007) and II (P = 0.0045) in the column outflow (blood return to the patients). Further, at 8 months, 60% of patients had maintained their remission. No severe side effects were reported. In conclusion, adsorptive leukocytapheresis should reduce corticosteroid therapy in patients with moderate UC; cases with early-stage active disease may benefit most.

https://pubmed.ncbi.nlm.nih.gov/15185858/

Takeshi Tomomasa ¹, Akio Kobayashi, Hiroaki Kaneko, Sasaki Mika, Shun-Ichi Maisawa, Yoshie Chino, Hohkibara Syou, Atsushi Yoden, Jyunko Fujino, Makoto Tanikawa, Takafumi Yamashita, Shigeru Kimura, Maiko Kanoh, Koji Sawada, Akihiro Morikawa

Dig Dis Sci. 2003 Apr;48(4):750-4. doi: 10.1023/a:1022892927121.

Granulocytapheresis (GCAP) has produced efficacy in adult patients with ulcerative colitis (UC) by adsorbing activated granulocytes and monocytes/macrophages. We retrospectively investigated efficacy and safety of GCAP in pediatric patients with active UC. Twelve steroid-refractory children (12.2 +/- 3.1 years old) were treated with GCAP, one session/week for 5-10 consecutive weeks. In 8 patients, clinical symptoms improved after two GCAP sessions. Normal body temperature, stool frequency, and disappearance of blood in stool were seen after 24.3 +/- 11.5 days. The endoscopic grade improved from 2.6 +/- 0.3 to 0.4 +/- 0.2. One patient who initially responded, developed bloody diarrhea later and 2 cases remained unchanged. The dose of steroid was tapered during GCAP therapy by 50%. No serious adverse effects were noted. Four of 8 cases relapsed 3.5 +/- 2.2 months after the last GCAP while on maintenance therapy, the other 4 were in remission up to 22.8 +/- 18.1 months. In conclusion, GCAP appears to be effective and well tolerated in children with steroid-refractory UC.

https://pubmed.ncbi.nlm.nih.gov/12741466/

K Kondo ¹, T Shinoda, H Yoshimoto, M Takazoe, T Hamada

Ther Apher. 2001 Dec;5(6):462-5. doi: 10.1046/j.1526-0968.2001.00379.x.

We prospectively examined the effect of leukocytapheresis (LA) on the maintenance of remission in 7 patients with ulcerative colitis (UC) who were initially refractory to corticosteroid therapy (steroid resistant or steroid dependent). The patients with refractory UC had been in remission due to LA (induction LA) in combination with the steroid therapy. They were then treated with LA once or twice a month for the purpose of maintaining remission (maintenance LA). The maintenance LA was performed by either a centrifuge method in 5 patients or a polyester adsorbent column method in 2 patients. Steroid dosage was gradually tapered as little as possible without recurrence based on clinical and/or colonoscopical judgments. Four patients were maintained in remission without steroids over 12 months. Recurrence was observed in 3 patients at 3, 3, and 6 months after the beginning of the maintenance LA, respectively. Two of the 3 patients were again conducted to remission by the second induction LA and maintained in remission by the second maintenance LA. Two patients finally underwent total colectomy because of recurrence of UC in a severe form. It is concluded that the maintenance LA therapy might be effective in some patients with steroid dependent or resistant UC for the maintenance of remission without steroids.

https://pubmed.ncbi.nlm.nih.gov/11800081/

https://onlinelibrary.wiley.com/doi/epdf/10.1046/j.1526-0968.2001.00379.x