An open-label prospective randomized multicenter study of intensive versus weekly granulocyte and monocyte apheresis in active crohn's disease.

Naoki Yoshimura,Kenji Watanabe,Takashi Kagaya,Keiichi Mitsuyama,Taro Osada,Reiko Kunisaki,Tomoo Nakagawa,Hiroyuki Hanai,Satoshi Motoya,Toshifumi Hibi,Katsuyoshi Matsuoka,Yoko Yokoyama,Hiroshi Nakase,Shinji Tanaka,Nobuhito Kashiwagi,Satoshi Tanida,Shingo Kato,Sakiko Hiraoka,Takumi Fukuchi,Shunji Ishihara,Hiroki Takahashi,Michiro Otaka,Fumihito Hirai,Yasuo Suzuki,Takayuki Yamamoto,Ryuichi Iwakiri,Yoh Ishiguro

doi:10.1186/s12876-015-0390-3

Abstract

BackgroundGranulocyte and monocyte adsorptive apheresis (GMA) has shown efficacy in patients with active Crohn’s disease (CD). However, with routine weekly therapy, it may take several weeks to achieve remission. This study was performed to assess clinical efficacy and safety of intensive GMA in patients with active CD.MethodsIn an open-label, prospective, randomized multicentre setting, 104 patients with CD activity index (CDAI) of 200 to 450 received intensive GMA, at two sessions per week (n = 55) or one session per week (n = 49). Clinical remission was defined as a CDAI score <150. Patients in each arm could receive up to 10 GMA sessions. However, GMA treatment could be discontinued when CDAI decreased to <150 (clinical remission level).ResultsOf the 104 patients, 99 were available for efficacy evaluation as per protocol, 45 in the weekly GMA group, and 54 in the intensive GMA group. Remission was achieved in 16 of 45 patients (35.6 %) in the weekly GMA and in 19 of 54 (35.2 %) in the intensive GMA (NS). Further, the mean time to remission was 35.4 ± 5.3 days in the weekly GMA and 21.7 ± 2.7 days in the intensive GMA (P = 0.0373). Elevated leucocytes and erythrocyte sedimentation rate were significantly improved by intensive GMA, from 8005/μL to 6950/μL (P = 0.0461) and from 54.5 mm/hr to 30.0 mm/hr (P = 0.0059), respectively. In both arms, GMA was well tolerated and was without safety concern.ConclusionsIn this study, with respect to remission rate, intensive GMA was not superior to weekly GMA, but the time to remission was significantly shorter in the former without increasing the incidence of side effects. UMIN registration # 000003666.Electronic supplementary materialThe online version of this article (doi:10.1186/s12876-015-0390-3) contains supplementary material, which is available to authorized users.

Highlights

Granulocyte and monocyte adsorptive apheresis (GMA) has shown efficacy in patients with active Crohn’s disease (CD)
Patient randomization and demography A total of 104 patients who were registered after screening were randomized to the weekly GMA arm (n = 49) or to the intensive GMA arm (n = 55)
Five patients in the weekly GMA could not be included in the efficacy analysis, two had not reached CD activity index (CDAI) score ≥200 at screening, one patient was not available for GMA therapy and the remaining two patients were found to have received GMA prior to assignment

Summary

Introduction

Granulocyte and monocyte adsorptive apheresis (GMA) has shown efficacy in patients with active Crohn’s disease (CD). Biologics, such as anti-tumour necrosis factor (TNF)-α antibodies or conventional medications with 5-aminosali cylic acid, prednisolone, and immunomodulators like azathioprine or 6-mercaptopurine are being used to treat patients with active Crohn’s disease (CD) [1,2,3,4,5,6]. These drugs have often been associated with adverse side effects that add to disease complexity [7,8,9,10,11]. GMA has shown efficacy in patients with CD refractory to conventional medication [22, 23]

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Conclusion