Clinical Trials Study
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 7, 2016; 22(17): 4389-4396
Published online May 7, 2016. doi: 10.3748/wjg.v22.i17.4389
Efficacy and safety of granulocyte, monocyte/macrophage adsorptive in pediatric ulcerative colitis
Tarja Ruuska, Peter Küster, Lena Grahnquist, Fredrik Lindgren, Anne Vibeke Wewer
Tarja Ruuska, Department of Pediatrics, Tampere University Hospital, 33521 Tampere, Finland
Peter Küster, Department of Pediatrics and Adolescent Medicine, Clemenshospital, 48153 Münster, Germany
Lena Grahnquist, Karolinska University Hospital, Astrid Lindgren Children’s Hospital, 17176 Solna, Sweden
Fredrik Lindgren, Department of Pediatrics, Karolinska University Hospital, Huddinge, 14186 Stockholm, Sweden
Anne Vibeke Wewer, Department of Pediatrics, Hvidovre Hospital, 2650 Hvidovre, Denmark
Author contributions: All the authors contributed equally to this work and were equally involved in revisions of the manuscript; Ruuska T, Küster P, Lindgren F and Wewer AV approved the final manuscript.
Supported by Otsuka Frankfurt Research Institute, the legal and financial sponsor for this clinical trial, Otsuka Pharmaceutical Europe Ltd. supported the realization of this paper.
Institutional review board statement: The ADAPT study was reviewed and approved as per Attachment 62, No.18/2008, by the Joint Municipal Authority for Medical Services of Pirkanmaa, Tampere, Finland.
Clinical trial registration statement: The ADAPT study is registered at www.ClinicalTrials.gov (identifier: NCT00781638).
Informed consent statement: This investigation was conducted in accordance with GCP, the Declaration of Helsinki and EN ISO 14155:2003. All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: All authors have received fees and honoraries for consultancy as an advisory board member and as investigator of the ADAPT trial from Otsuka Frankfurt Research Institute.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Tarja Ruuska, MD, Department of Pediatrics, Tampere University Hospital, 33521 Tampere, Finland. tarja.ruuska@pshp.fi
Telephone: +358-3-31164538 Fax: +358-3-31165655
Received: December 1, 2015
Peer-review started: December 4, 2015
First decision: December 31, 2015
Revised: February 15, 2016
Accepted: March 2, 2016
Article in press: March 2, 2016
Published online: May 7, 2016
Abstract

AIM: 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, open-label, 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: Adacolumn® GMA apheresis treatment was effective in pediatric patients with moderate active Ulcerative Colitis. No new safety signals were reported. The present data contribute to considering GMA apheresis as a therapeutic option in pediatric patients having failed first line therapy.

Keywords: Granulocyte-monocyte apheresis, Pediatric, Ulcerative colitis, Inflammatory bowel disease, Therapy, Steroids, Clinical trial

Core tip: For a considerable group of children with ulcerative colitis (UC), treatment options are limited especially after failure of conventional treatment. The ADAPT trial was designed to generate prospective cohort data on efficacy and safety levels in moderate active pediatric UC patients when treated with Adacolumn granulocyte, monocyte/macrophage adsorptive (GMA). The present data contribute to considering GMA apheresis as a therapeutic option in pediatric patients having failed first line therapy.