Kyoya Sakimura · Toshihide Omori · Etsuro Iwashita ·Takeshi Yoshida · Yoshikazu Tsuzuki · Kenji Fujimori ·Fumio Konishi · Yukio Yoshida · Hiroo Anzai ·Hiromichi Suzuki · Souichi Sugawara · Yuji Takeda ·Katsuya Hiraishi · Abbi R. Saniabadi · Tatsuo Ide ·Soichiro Miura · Shinichi Ota

Dig Dis Sci 2006 Sep;51(9):1525-31. doi: 10.1007/s10620-005-9012-1. Epub 2006 Aug 12.

Depletion of granulocytes and monocytes (GM) by selective apheresis (GMA) with an Adacolumn exerts
an anti-inflammatory effect in patients with ulcerative colitis (UC) or rheumatoid arthritis. However, the mechanism of the
anti-inflammatory effect of GMA is not fully understood yet. We investigated the effect of GMA on the plasma concentration of interleukin-1 receptor antagonist (IL-1ra), a potent anti-inflammatory cytokine. Twenty-six patients with active UC received GMA at one session per week for 5 consecutive weeks. Clinical response was defined as
clinical activity index (
CAI = CAI at entry – CAI at post) ≥ 4, while clinical remission was defined as CAI ≤ 4. Twenty-one of twenty-six patients (80.8%) responded to GMA. In the first session, plasma from responder patients showed a significant (P < 0.01) increase in IL-1ra in the Adacolumn outflow. In contrast, there was no change in IL-1ra in nonresponders. In conclusion, release of IL-1ra during GMA might be one mechanism of clinical efficacy associated with this therapy.

https://pubmed.ncbi.nlm.nih.gov/16902810/

https://link.springer.com/article/10.1007%2Fs10620-005-9012-1

H Okada ¹, C Makidono, R Takenaka, S Hiraoka, A Fujiwara, J Kato, Y Kawahara, H Kawamoto, M Mizuno, Y Shiratori

Digestion 2006;74(1):15-8. doi: 10.1159/000095478. Epub 2006 Aug 29.

Leukocytapheresis has recently been used to induce remission in patients with ulcerative colitis (UC) who fail to respond to corticosteroids. We could not find a report in the literature on leukocytapheresis for UC with gestational exacerbation. We have recently encountered this unique condition and report the details here. A 30-year-old Japanese woman with left-sided severe UC was corticosteroid-dependent and had recurrence of the active disease during tapering of corticosteroid. She declined any dose increase and the use of any immunosuppressive agent because she was in the 13th week of pregnancy. Then, concomitant leukocytapheresis was performed without increasing the corticosteroid dose. Recovery was rapid and dramatic. Mucous and bloody stool decreased after the first session, and she had remission 2 weeks later. She underwent a total of four sessions without complications. After 6 weeks, she was discharged from our hospital and underwent maintenance treatment as an outpatient with mesalazine and corticosteroid tapering. Subsequently, she gave birth to a healthy baby girl by an uncomplicated vaginal delivery while keeping the remitted stage of UC.

https://pubmed.ncbi.nlm.nih.gov/16940730/

Takuro Kanekura ¹, Katsuya Hiraishi, Koichi Kawahara, Ikuro Maruyama, Tamotsu Kanzaki

Ther Apher Dial 2006 Jun;10(3):247-56. doi: 10.1111/j.1744-9987.2006.00369.x.

In the present study, we have shown that granulocyte and monocyte adsorption apheresis (GCAP), an extracorporeal apheresis instrument whose column contains cellulose acetate (CA) beads, is useful for skin diseases attributable to activated granulocytes and psoriatic arthritis (PsA). We assessed the clinical effectiveness of GCAP and investigated the mechanisms underlying the adsorption of pathogenic granulocytes. The effect of GCAP was assessed in 14 patients with neutrophilic dermatoses and 16 with PsA. The mechanisms by which the instrument adsorbs activated granulocytes were investigated using an in vitro mini-column system that mimics the GCAP. Skin lesions and arthropathy improved in 22 of 29 patients (75.9%) and 14 of 18 (77.8%), respectively. Mac-1 (CD11b/CD18) expression on the peripheral neutrophils, increased compared with normal subjects, was reduced by GCAP. In the mini-column system, CA beads adsorbed 50% neutrophils; and adsorption was inhibited significantly by treating plasma with EDTA and blood cells with antihuman CD11b monoclonal antibody. GCAP was useful for treating neutrophilic dermatoses and PsA. GCAP adsorbs Mac-1-expressing neutrophils to the CA beads by the binding of complement component (iC3b) on CA beads and CD11b expressed on activated neutrophils.

https://pubmed.ncbi.nlm.nih.gov/16817789/

Takuro Kanekura ¹, Noriko Yoshii, Koichi Kawahara, Ikuro Maruyama, Tamotsu Kanzaki

Ther Apher Dial 2006 Jun;10(3):287-90. doi: 10.1111/j.1744-9987.2006.00335.x.

Cutaneous allergic vasculitis (CAV) is characterized clinically by purpuric patches with secondary ulcerations, and histologically by leukocytoclastic vasculitis with neutrophil infiltrates. Granulocyte and monocyte adsorption apheresis (GCAP) is an extracorporeal apheresis instrument using a column containing cellulose acetate beads designed to remove pathogenic granulocytes. Here we report our assessment of the efficacy of GCAP for recurrent leg ulcers in a 49-year-old woman with CAV. She underwent five GCAP treatments at one-week intervals. In each treatment session, 1800 mL of blood was processed. Her leg ulcers responded well and her white blood cell and neutrophil counts and the expression level of CD11b/CD18, a marker for activated neutrophils, on her peripheral neutrophils were reduced from 7500/microL to 6500/microL, 4350/microL to 3315/microL, and 64.9 MFI (mean fluorescence intensity) to 27.0 MFI (normal controls: 10.5 +/- 1.2 MFI) by GCAP, respectively. These results suggest that GCAP is useful for skin disorders with leucocytoclastic vasculitis.

https://pubmed.ncbi.nlm.nih.gov/16817796/

P. Gonzalez Carro, F. Perez Roldan, O. Roncero Garcıa Escribano,R. Lafuente, M.L. Legaz Huidobro, and A. Amigo Echenagusıa

Journal of Clinical Apheresis 21: 249–251 (2006)

To our knowledge, no cases of combined therapy with infliximab and granulocyte apheresis have been previously reported. Our results suggest that this combined therapy is a possible alternative to treat CD patients in the event of loss of response to infliximab.

https://onlinelibrary.wiley.com/doi/10.1002/jca.20093

Wolfgang Kruis, Axel Dignass, Elisabeth Steinhagen-Thiessen, Julia Morgenstern, Joachim Mössner,
Stephan Schreiber, Maurizio Vecchi, Alberto Malesci, Max Reinshagen, Robert Löfberg

World J Gastroenterol 2005;11(44):7001-7006

AIM: To study the efficacy, safety, and feasibility of a granulocyte adsorptive type apheresis system for the treatment of patients with chronically active ulcerative colitis despite standard therapy. METHODS: An open label multicenter study was carried out in 39 patients with active ulcerative colitis (CAI 6-8) despite continuous use of steroids (a minimum total dose of 400 mg prednisone within the last 4 wk). Patients received a total of five aphereses using a granulocyte adsorptive technique (Adacolumn®, Otsuka Pharmaceutical Europe, UK). Assessments at wk 6 and during follow-up until 4 mo comprised clinical (CAI) and endoscopic (EI) activity index, histology, quality of life (IBDQ), and laboratory tests. RESULTS: Thirty-five out of thirty-nine patients were qualified for intent-to-treat analysis. After the apheresis treatment at wk 6, 13/35 (37.1%) patients achieved clinical remission and 10/35 (28.6%) patients had endoscopic remission (CAI<4, EI<4). Quality of life (IBDQ) increased significantly (24 points, P <0.01) at wk 6. Apheresis could be performed in all but one patient. Aphereses were well tolerated, only one patient experienced anemia. CONCLUSION: In patients with steroid refractory ulcerative colitis, five aphereses with a granulocyte/ monocyte depleting filter show potential short-term efficacy. Tolerability and technical feasibility of the procedure are excellent.

https://www.wjgnet.com/1007-9327/full/v11/i44/7001.htm

R Sanmartí ¹, S Marsal, J Valverde, E Casado, R Lafuente, N Kashiwagi, J-R Rodriguez-Cros, A Erra, D Reina, J Gratacós Rheumatology (Oxford) 2005 Sep;44(9):1140-4. doi: 10.1093/rheumatology/keh701. Epub 2005 May 31.

Objective: To assess the efficacy and safety of adsorptive granulocyte and monocyte apheresis (GCAP) in patients with refractory rheumatoid arthritis (RA). Methods: Patients with active and refractory RA were treated with weekly GCAP sessions using a column filled with acetate beads (Adacolumn) over five consecutive weeks. Clinical assessments and response to therapy were analysed at weeks 5, 7, 12 and 20 in an open multicentre trial. The primary outcome measure of clinical response was 20% improvement in the American College of Rheumatology criteria (ACR20) at week 20. EULAR (European League Against Rheumatism) response criteria, based on the disease activity score for 28 joints (DAS28) and disability using the Health Assessment Questionnaire (HAQ), were also assessed. Results: Of 27 patients, 81.5% were women with mean disease duration of 14.4 yr. The mean number of previous disease-modifying antirheumatic drugs (DMARDs) was 3.7, and 48.1% of patients had previously failed on biologicals. On an intention-to-treat basis, 40.7% of patients achieved an ACR20 and 44.4% a therapeutic EULAR response at week 20. These percentages were 50 and 54.5% in 22 patients who completed the trial. In the 10 completers who had previously failed on biologicals, an ACR response was achieved in four patients (ACR20, two; ACR50, one; ACR70, one). A significant decrease was recorded in different ACR response components, including the tender joint and swollen joint counts, pain score and patient and physician global disease assessments, as well as the DAS28 index; most of them improved after week 5. ESR and CRP, but not the HAQ score, had decreased significantly at week 20. The treatment was well tolerated and only one serious adverse event related to the study procedure was documented (sepsis due to a catheter infection). Conclusions: GCAP treatment led to significant clinical improvement in a subset of patients with RA who had failed to respond to DMARDs or biologicals. Further large, placebo-controlled studies are warranted to fully assess the therapeutic value of GCAP for refractory RA.

https://pubmed.ncbi.nlm.nih.gov/15927997/

https://academic.oup.com/rheumatology/article/44/9/1140/1784472?login=false

Takuro Kanekura,Koichi Kawahara,Ikuro Maruyama,Tamotsu Kanzaki Ther Apher Dial 2005 Aug;9(4):292-6. doi: 10.1111/j.1744-9987.2005.00284.x.

Pyoderma gangrenosum is an intractable skin disorder characterized by the development of erythematous pustules or nodules that rapidly progress to destructive, necrotizing, non-infective ulcers. We assessed the efficacy of granulocyte and monocyte adsorption apheresis (GCAP) therapy in two new patients, a 67-year-old man with ulcerations on his lower leg, and a 44-year-old man with turgid erythematous lesions with burrowing abscesses and sinus formation on his hip, groin, and thighs. Both patients received 10 GCAP treatments at 5-day intervals. Their skin lesions responded well. The 9 cmx6 cm ulcer on the lower right leg of the 67-year-old patient was completely covered by regenerated skin at the completion of therapy. The turgid skin lesions containing pustules and ulcers of the other patient showed amelioration and a marked decrease in the volume of exudate. Our results suggest that GCAP is a useful treatment modality for pyoderma gangrenosum.

https://pubmed.ncbi.nlm.nih.gov/16076369/

Ritsuko Yanaru-Fujisawa, Takayuki Matsumoto, Shotaro Nakamura, Shuji Kochi, Mitsuo Iida, Futoshi Kohda, Minako Hirahashi, Takashi Yao, Ryuichi Case Reports Inflamm Bowel Dis. 2005 Aug;11(8):780 DOI: 10.1097/01.mib.0000172558.39767.b7

Our case and the case of Kanekura et al⁸ suggest that circulating leukocytes may play an important role in the pathogenesis of PG and that GCAP in combination with corticosteroids may be a promising strategy for intractable PG. Furthermore, as has been the case for active UC, GCAP may be a choice for severe pouchitis. An accumulation of data with respect to the effect of GCAP on pouchitis seems to be warranted.

https://pubmed.ncbi.nlm.nih.gov/16043996/

https://academic.oup.com/ibdjournal/article/11/8/780/4685895

Akira Andoh,Tomoyuki Tsujikawa,Osamu Inatomi,Yasuyuki Deguchi,Kazunori Hata,Katsuyuki Kitoh,Masaya Sasaki,Keiichi Mitsuyama,Yoshihide Fujiyama Therap Apher Dial(2005) 9, 2; 23-127, https://doi.org/10.1111/j.1774-9987.2005.00229.x

To elucidate the molecular mechanisms involved in the therapeutic effects of granulocyte/monocyte adsorption apheresis, changes were investigated in the cytokine responses of peripheral blood mononuclear cells (PBMC) before and after granulocyte/monocyte adsorptive apheresis in ulcerative colitis (UC) patients. Four patients with active UC were enrolled. All patients responded to granulocyte/monocyte adsorptive apheresis. A total of 20 sessions of four patients were analyzed. Peripheral blood mononuclear cells were isolated from peripheral venous blood within 5min before and after each session of granulocyte/monocyte adsorptive apheresis. The cells were stimulated with interleukin (IL)-1β and tumor necrosis factor (TNF)-α for 24h, and the secreted IL-8 and IL-6 levels were determined by enzyme-linked immunosorbent assay (ELISA). IL-1β-induced IL-8 and IL-6 secretion was significantly decreased after granulocyte/monocyte adsorptive apheresis. TNF-α-induced IL-8 secretion was also significantly decreased after apheresis, but there was no significant difference in TNF-α-induced IL-6 secretion (P = 0.052). In conclusion, granulocyte/monocyte adsorptive apheresis down-regulates the IL-1β- and TNF-α-induced inflammatory responses in PBMC. The induction of hyporesponsiveness to pro-inflammatory cytokines may be an important factor mediating the clinical effects of granulocyte/macrophage adsorptive apheresis in UC patients.

https://pubmed.ncbi.nlm.nih.gov/15828923/

https://onlinelibrary.wiley.com/doi/10.1111/j.1774-9987.2005.00229.x