Therapeutic effect of intensive granulocyte and monocyte adsorption apheresis combined with thiopurines for steroid- and biologics-naïve Japanese patients with early-diagnosed Crohn's disease.

Takumi Fukuchi,Dai Ito,Hiroshi Yamashita,Satoshi Ubukata,Takahiko Toyonaga,Hideaki Koga,Minoru Matsuura,Takuya Yoshino,Hiroshi Nakase,Kiyoshi Ashida,Keiji Shimazu

doi:10.1186/1471-230x-14-124

Abstract

BackgroundEarly induction with biologics can reduce complications in patients with Crohn’s disease (CD) and improve their quality of life. The safety of biologics, however, is uncertain. Granulocyte and monocyte adsorptive apheresis (GMAA) is a natural biologic therapy that selectively removes granulocytes and monocytes/macrophages and has few severe adverse effects. The effects of GMAA on patients with early-diagnosed CD are unclear. We investigated the effects of GMAA combined with thiopurines on patients with early-diagnosed CD.MethodsTwenty-two corticosteroid- and biologic-naïve patients with active early-diagnosed CD were treated with intensive GMAA (twice per week) combined with thiopurines administration. Active early-diagnosed CD was defined as follows: (i) within 2years after diagnosis of CD, (ii) with no history of both surgical treatment and endoscopic dilation therapy, and (iii) Crohn’s Disease Activity Index (CDAI) was higher than 200. We investigated the ratios of clinical remission defined as CDAI was less than or equal to 150 at 2, 4, 6 and 52weeks and mucosal healing defined as a Simplified Endoscopic Activity Score for Crohn’s Disease (SES-CD) as 0 at 6 and 52weeks. Adverse events were recorded at each visit.ResultsThe ratios of clinical remission at 2, 4, and 6 weeks were 6 of 22 (27.2%), 12 of 22 (54.5%), and 17 of 22 (77.2%), respectively. At 52 weeks, 18 of 21 patients (81.8%) were in clinical remission. The ratios of mucosal healing at 6 and 52 weeks were 5 of 22 (22.7%) and 11 of 22 (50%), respectively. The difference in the mucosal healing ratio was significant between 6 and 52 weeks (p = 0.044). No serious adverse effects were observed during this study.ConclusionsCombination therapy with intensive GMAA and thiopurines administration rapidly induced high remission in patients with active early-diagnosed CD without serious adverse effect. Mucosal healing was observed in 50.0% of enrolled patients. This combination therapy might be a rational option for patients with early-diagnosed CD.

Highlights

Induction with biologics can reduce complications in patients with Crohn’s disease (CD) and improve their quality of life
In the present study we firstly demonstrated that intensive Granulocyte and monocyte adsorptive apheresis (GMAA) in combination with thiopurines resulted in higher ratios of clinical remission and mucosal healing at 52weeks in corticosteroid- and biologics-naïve patients with early-diagnosed CD
The remarkable usefulness of intensive GMAA for the induction of remission and mucosal healing in patients with active ulcerative colitis (UC) compared with weekly GMAA suggests that the therapeutic effects of GMAA are associated with frequency of therapy per week [11,12]

Summary

Introduction

Induction with biologics can reduce complications in patients with Crohn’s disease (CD) and improve their quality of life. The efficacy of TNF-α antagonists suggests a new concept that early induction with intensive therapy may reduce complications associated with conventional treatment and improve the patient’s quality of life [5]. In this regard, intensive therapy with early use of this biologic agent has been proposed and is known as ‘top-down’ therapy. Use of anti-TNF therapy, is associated with the development of serious life-threatening infections in addition to other well-documented hematologic, immunologic, cardiovascular, and malignant adverse effects [6]. Whether long-term use of anti-TNF therapy is suitable for all patients with CD remains unclear

Methods

Results

Discussion

Conclusion