Yasuo Suzuki 1, Naoki Yoshimura, Katsuyuki Fukuda, Koji Shirai, Yasushi Saito, Abbi R Saniabadi
Tag: ulcerative colitis
Scientific corner
A retrospective search for predictors of clinical response to selective granulocyte and monocyte apheresis in patients with ulcerative colitis
Recently, selective granulocytapheresis (Adacolumn) has appeared as a new treatment for patients with inflammatory bowel disease. This study sought to determine predictors of response to this new nonpharmacologic mode of therapy by retrospectively evaluating 28 patients who received granulocytapheresis after experiencing active ulcerative colitis (UC). Between April 2000 and March 2004, 28 consecutive patients received granulocytapheresis for active UC with the Adacolumn, which is filled with cellulose acetate beads as the column leukocytapheresis carriers; the carriers adsorb granulocytes, monocytes/macrophages, and a small fraction of lymphocytes (FcgammaR and complement receptors bearing leukocytes). Each patient could receive up to 10 Adacolumn sessions, at 2 sessions per week. In 2004, clinical response was retrospectively evaluated. Seven days after the last Adacolumn session, 20 of 28 patients had remission (colitis activity index [CAI] < or =4) including all 8 patients who had their first UC episode. The mean duration of UC in the 8 first episode cases was 3.4 months compared with 40.2 months for all 28 patients and 65.4 months for the 8 nonresponders. The response to Adacolumn was independent of basal CAI. The 8 nonresponders were given conventional medication (CM) or cyclosporine (CsA) if the former failed. Two responded to CM, 3 to CsA, and 3 underwent colectomy. First UC episode and short disease duration appear good predictors of response to granulocytapheresis. Selective granulocytapheresis might be an effective first-line treatment.
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Clinical Response Is Associated with Elevated PlasmaInterleukin-1 Receptor Antagonist During Selective Granulocyte and Monocyte Apheresis in Patients with Ulcerative Colitis
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.
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Therapeutic efficacy of leukocytapheresis in a pregnant woman with severe active ulcerative colitis
H Okada 1, C Makidono, R Takenaka, S Hiraoka, A Fujiwara, J Kato, Y Kawahara, H Kawamoto, M Mizuno, Y Shiratori
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.
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Pilot Feasibility Studies of Leukocytapheresis With the Adacolumn Apheresis System in Patients With Active Ulcerative Colitis or Crohn Disease
Bruce E Sands 1, William J Sandborn, Douglas C Wolf, Seymour Katz, Michael Safdi, David A Schwartz, Stephen B Hanauer, J Clin Gastroenterol. 2006 Jul;40(6):482-9.
Treatment with Adacolumn may be feasible and effective in patients with moderate-to-severe refractory inflammatory bowel disease. Larger sham-controlled studies are ongoing.
Scientific corner
Preliminary data on the use of apheresis in inflammatory bowel disease
William J Sandborn, Inflamm Bowel Dis. 2006 Jan;12 Suppl 1:S15-21
Multiple studies have suggested that selective apheresis may be of benefit as a steroid-sparing treatment. In an unblinded randomized trial in 69 steroid-dependent patients with active UC randomized to selective apheresis with Adacolumn or an increased dose of prednisolone, 83% of patients receiving Adacolumn achieved remission compared with 65% of those receiving an increased dose of prednisolone. In another uncontrolled study of 60 patients with active UC, treatment with Adacolumn selective apheresis enabled nearly 70% of steroid-dependent patients to discontinue prednisolone. An unblinded randomized controlled trial of a different selective apheresis device (Cellsorba) versus high-dose prednisolone in patients with active UC showed a greater therapeutic effect (74%) than high-dose prednisolone (38%) and lower frequency of adverse effects (24% versus 68%).
Scientific corner
Down-regulation of interfeferon-γ parallels clinical response to selective leukocyte apheresis in patients with inflammatory bowel disease:a 12-month follow-up study
V Muratov 1, J Lundahl, A K Ulfgren, K Elvin, I Fehrman, N Ahlborg, A Ost, N Hittel, A Saniabadi, R Löfberg, Int J Colorectal Dis . 2006 Sep;21(6):493-504.
Leukocyte apheresis is a novel and safe nonpharmacological adjunct therapy that may prove useful in steroid refractory or dependent patients when conventional drugs have failed. Down-regulation of IFN-gamma in mucosal biopsies and in peripheral leukocytes may be a predictive marker for sustained, long-term response.
Scientific corner
Efficacy and endoscopic prediction of cytapheresis therapy in patients with refractory and steroid-dependent ulcerative colitis
Koichiro Watanabe, December 2006Alimentary Pharmacology & Therapeutics 24(1):147 – 152,
Scientific corner
Positions of selective leukocytapheresis in the medical therapy of ulcerative colitis
Hiroyuki Hanai, World J Gastroenterol. 2006 Dec 21;12(47):7568-77.
The Adacolumn is a medical device developed for selective depletion of GM by receptor-mediated adsorption (GMA). Clinical data show GMA, in patients with steroid dependent or steroid refractory UC, is associated with up to 85% efficacy and tapering or discontinuation of steroids, while in steroid naive patients (the best responders), GMA spares patients from exposure to steroids. Likewise, GMA at appropriate intervals in patients at a high risk of clinical relapse suppresses relapse thus sparing the patients from the morbidity associated with IBD relapse. Further, GMA appears to reduce the number of patients being submitted to colectomy or exposure to unsafe immunosupressants. First UC episode, steroid naivety and short disease duration appear good predictors of response to GMA and based on the available data, GMA seems to have an excellent safety profile.
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Treatment of active steroid-refractory inflammatory bowel diseases with granulocytapheresis: Our experience with a prospective study
Bresci Giampaolo 1, Parisi Giuseppe, Bertoni Michele, Mazzoni Alessandro, Scatena Fabrizio, Capria Alfonso, World J Gastroenterol. 2006 Apr 14;12(14):2201-4.
Even if the number of our patients with steroid-refractory IBDs was not big, we can assert that GCAP is well tolerated and effective, especially in the first six months after the treatment, in a significant percentage of cases. The rate of sustained response drops slightly after 6 mo and significantly after 12 mo, however the absence of severe side effects can be a stimulus for further evaluating new schedules of treatment.
Scientific corner
Leukocyte removal therapy before surgery in ulcerative colitis.
Toshiyuki Matsui, Journal of Gastroenterology volume 41, pages923–924 (2006)
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