Tarja Ruuska, Peter Küster, Lena Grahnquist, Fredrik Lindgren, Anne Vibeke Wewe, World J Gastroenterol 2016 May 7; 22(17): 4389-4396

To investigate efficacy and safety for granulocyte, monocyte apheresis in a population of pediatric patients with ulcerative colitis. METHODS: The ADAPT study was a prospective, openlabel, multicenter study in pediatric patients with moderate, active ulcerative colitis with pediatric ulcerative colitis activity index (PUCAI) of 35-64. Patients received one weekly apheresis with Adacolumn® granulocyte, monocyte/macrophage adsorptive (GMA) apheresis over 5 consecutive weeks, optionally followed by up to 3 additional apheresis treatments over 3 consecutive weeks. The primary endpoint was the change in mean PUCAI between baseline and week 12; the secondary endpoint was improvement in PUCAI categorized as (Significant Improvement, PUCAI decrease of ≥ 35), Moderate Improvement (PUCAI decrease of 20 < 35), Small Improvement (PUCAI decrease of 10 < 20) or No change (PUCAI decrease of < 10). RESULTS: Twenty-five patients (mean age 13.5 years; mean weight 47.7 kg) were enrolled. In the intention-to-treat set (ITT), the mean value for PUCAI improvement was 22.3 [95%CI: 12.9-31.6; n = 21]. In the per-protocol (PP) set, the mean improvement was 36.3 [95%CI: 31.4-41.1; n = 8]. Significant Improvement was recorded for 9 out of 20 patients (45%); 5 out of 20 patients (25%) had Moderate Improvement and one patient (5%) had No Change in PUCAI score at week 12. In the PP set, six out of eight patients (75%) showed Significant Improvement; and in two out of eight patients (25%) Moderate Improvement was recorded. The endoscopic activity index (EAI) decreased by 3 points on average. Seven (7) out of 21 (33%) patients in ITT and 4 out of 8 (50%) patients in PP have used steroids during the clinical investigation. The mean steroid dosage for these patients in the ITT set decreased from a mean 12.4 mg to 10 mg daily on average from Baseline to week 12. CONCLUSION: In conclusion, GMA apheresis with Adacolumn® was safe and effective in pediatric patients with moderate active Ulcerative Co­litis. The present data contribute to considering GMA apheresis as a therapeutic option in pediatric patients having failed first line therapy.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4853697/pdf/WJG-22-4389.pdf

Masashi Ohno ¹, Shigeki Koyama, Mariko Ohara, Kazumi Shimamoto, Yu Kobayashi, Fumiyasu Nakamura, Kazuki Mitsuru, Akira Andoh, Intern Med. 2016;55(1):25-30.

 These results suggest that a combination of GMA and corticosteroids might be recommendable to induce the remission of serious PG complicated with UC.

https://pubmed.ncbi.nlm.nih.gov/26726081/

https://www.jstage.jst.go.jp/article/internalmedicine/55/1/55_55.5422/_article

Zhenfei Liu ¹, Xueliang Jiang ², Chengcheng Sun ³ , Eur J Intern Med. 2016 Dec;36:e26-e27. 

https://pubmed.ncbi.nlm.nih.gov/27614377/

Keiji Shimazu ¹, Takumi Fukuchi ², Insung Kim ³, Yuki Noguchi ³, Megumi Iwata ¹, Shintaro Koyama ^2 4, Satoshi Ubukata ², Atsuo Tanaka ¹ , Ther Apher Dial 2016 Aug;20(4):383-9.

Intensive granulocyte and monocyte adsorptive apheresis (GMA) twice weekly is effective and safe for patients with active ulcerative colitis (UC), but the requirement for maintaining two blood access routes is problematic. Here we compared the efficacy and safety of one-route blood access intensive GMA using a single-needle (SN) and conventional two-route blood access intensive GMA using a double-needle (DN) in patients with active UC not undergoing corticosteroid therapy. Among 80 active UC patients, 38 patients received SN intensive GMA and 42 patients received DN intensive GMA. The clinical remission ratio and mucosal healing ratio at 6 weeks, and the cumulative non-relapse ratio at 52 weeks did not differ significantly between groups. In addition, no serious or mild adverse effects were observed in SN intensive GMA. SN intensive GMA may be an adequate and novel therapeutic option for active UC as an alternative therapy before using corticosteroids.

https://pubmed.ncbi.nlm.nih.gov/27523079/

T Sagawa ¹, S Kakizaki ¹, T Tomizawa ¹, T Nakayama ¹, H Tanaka ¹, H Tojima ¹, K Sato ¹, M Kusano ², S Okamura ³, M Yamada ¹,Colorectal Dis. 2016 Jul;18(7):696-702. 

The faecal lactoferrin level is a useful biomarker of the mucosal findings in ulcerative colitis. Although endoscopy is the gold standard, the faecal lactoferrin level can be used as a biomarker during GMA therapy in patients with ulcerative colitis.

https://pubmed.ncbi.nlm.nih.gov/26748553/

Hisako Saito ¹, Norio Hanafusa ¹, Junko Kishikawa ², Eisei Noiri ¹, Eiji Sunami ², Soichiro Ishihara ², Toshiaki Watanabe ², Masaomi Nangaku ¹ , J Clin Apher. 2016 Dec;31(6):584-586.

Results show that GMA is a safe and efficacious strategy against UC complicated by HBV without affecting hepatitis because GMA had no remarkable effect on HBV activity.

https://pubmed.ncbi.nlm.nih.gov/26876484/

Yoshioka, Shinichiro; Mitsuyama, Keiichi; Kuwaki, Kotaro; Yamauchi, Ryosuke; Yamasaki, Hiroshi; Fukunaga, Shuhei; Takedatsu, Hidetoshi; Tsuruta, Osamu; Torimura, Takuji (2016). Tu1987 A Longitudinal Study of FDG-PET in Crohn’s Disease Patients Receiving Granulocyte/Monocyte Apheresis Therapy. Gastroenterology, 2016 150(4), S998–. doi:10.1016/s0016-5085(16)33380-7 

Background: Endoscopy is the gold standard for the diagnosis and follow-up of patients with Crohn’s disease (CD). However, a less invasive approach is now being sought for the management of these patients. The objective of this study was to examine whether 18Ffluorodeoxyglucose (FDG)-positron emission tomography (PET) might be relevant for monitoring the disease activity in CD patients undergoing granulocyte/monocyte apheresis (GMA). Methods: This study was conducted in 12 patients with CD, who were receiving treatment with 10, once a week GMA sessions with the Adacolumn. The response to treatment was monitored by measuring the standard laboratory variables, the Crohn’s disease activity index (CDAI) score, the international organization for the study of inflammatory bowel diseases (IOIBD) score, and the regional and global bowel uptakes on FDG-PET. Results: In 6 of the 12 patients, significant improvement of the CDAI was observed after the final session of GMA. The patients who showed clinical response to GMA had a decrease in the regional and global bowel uptakes on FDG-PET, whereas those who did not respond showed no change. In the patients who responded to the GMA, the decrease in regional bowel uptake on FDG-PET in each disease area of the same patient varied in parallel. There was a significant correlation between decrease in the global bowel uptake on FDG-PET and improvement of
the CDAI and IOIBD scores. Conclusion: The longitudinal changes in FDG-PET uptakes are of potential clinical interest for assessing the regional and global bowel disease activity in CD patients undergoing GMA therapy.

https://www.gastrojournal.org/article/S0016-5085(16)33380-7/pdf

Sei-ichiro Motegi ¹, Akihiko Uchiyama ¹, Sayaka Toki ¹, Kazuya Yamada ¹, Hiroo Amano ¹, Osamu Ishikawa ¹ , J Dermatol. 2015 Aug;42(8):836-7.

https://pubmed.ncbi.nlm.nih.gov/25917419/

Wolfgang Kruis ¹, Phuong Nguyen, Julia Morgenstern, Digestion. 2015;92(1):39-44.

Background and Aims: Adsorptive granulocyte/monocyte apheresis (GMA) has shown promising efficacy in the treatment of patients with ulcerative colitis (UC). But a sham-controlled study was negative. A post-hoc analysis of this trial may haul out patients responding to GMA. Methods: A total of 168 UC patients with a disease activity (DAI) between 6 and 11 were enrolled in this study. Out of 168 patients, 112 received GMA and 56 sham apheresis. The basis for this post hoc analysis is the clinical study report issued by Otsuka America Pharmaceutical. Results: Baseline histology was available for 165 patients. Only 38% (63 of 165) of patients showed microscopic erosion/ulceration (group P). The remaining 62% of patients did not show microscopic erosion/ulceration (group A). The patients in group P showed significantly higher DAI, flexible proctosigmoidoscopy score and neutrophil infiltration into the colonic mucosa than those in group A (p = 0.0132, p = 0.0243 and p < 0.0001, respectively). Likewise, group P patients had a significantly (p = 0.0275) higher remission rate (11 of 46; 23.9%) when treated with GMA than with sham procedure (0 of 17; 0%). Conclusions: Patients in group P who had more active UC than those in group A showed clear clinical efficacy in response to GMA. We believe that true DAI should be specified for further randomized controlled trials.

https://pubmed.ncbi.nlm.nih.gov/26112696/

Satoshi Tanida ¹, Tsutomu Mizoshita ¹, Hirotada Nishie ¹, Keiji Ozeki ¹, Takahito Katano ¹, Eiji Kubota ¹, Hiromi Kataoka ¹, Takeshi Kamiya ¹, Takashi Joh ¹ , J Clin Med Res. 2015 Nov;7(11):884-9.

It was concluded that combination therapy with ADA plus intensive GMA is useful for induction of clinical remission in refractory UC patients, and is well tolerated.

https://pubmed.ncbi.nlm.nih.gov/26491502/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4596271/pdf/jocmr-07-884.pdf