title: Treatment of children and adolescents with ulcerative colitis by adsorptive depletion of myeloid lineage leucocytes as monotherapy or in combination with low dose prednisolone after failure of first-line medications.
abstract: BACKGROUND
  Currently available drugs for the treatment of ulcerative colitis (UC) include salicylates, thiopurines, corticosteroids and new anti-tumour necrosis factor (TNF)-α biologics. Among these medications, corticosteroids in children and adolescents may adversely affect the patients' growth and development. Further, UC patients have elevated and activated myeloid lineage leucocytes including the CD14 + CD16+ monocytes, which release TNF-α as a significant exacerbating factor. Accordingly, depletion of these cells by granulocyte/monocyte adsorption (GMA) should alleviate inflammation and promote UC remission. The objective of this study was to evaluate the efficacy of GMA in children and adolescents in whom conventional first-line medications had failed to induce remission.
  
  
  METHODS
  In a single centre setting, between 2007 and 2012, a total of 24 consecutive children and adolescents, age 11-19 years were given mesalazine or sulphasalazine as a first-line medication. Seventeen patients relapsed or did not respond to the first-line medications, and received GMA with the Adacolumn, 2 sessions in the first week, and then weekly, up to 11 sessions. Patients who achieved a decrease of ≥5 in the clinical activity index (CAI) were to continue with GMA, while non-responders were to receive 0.5 to 1.0 mg/kg/day prednisolone (PSL) plus additional GMA sessions similar to GMA responder cases. At entry and week 12, patients were clinically and endoscopically evaluated, allowing each patient to serve as her/his own control.
  
  
  RESULTS
  Seven patients achieved remission with the first-line medications and did not receive GMA. Five patients did not respond to the first 5 GMA sessions and received PSL plus GMA, while 12 patients responded to the first 5 GMA sessions and received additional sessions. At entry, the average CAI was 12.7 ± 2.5, range 8-17, and the average endoscopic index was 8.5 ± 1.5, range 7-11. The corresponding values at week 12 were 2.1 ± 0.2, range 1-4 (P < 0.001) and 2.4 ± 0.2, range 1-4 (P < 0.001). PSL was tapered to 0 mg within 3 months.
  
  
  CONCLUSIONS
  With the strategy we applied in this study, all 24 consecutive patients achieved remission. In growing patients with active UC refractory to first-line medications, GMA was associated with clinical remission and mucosal healing, while in non-responders to GMA monotherapy, addition of a low dose PSL enhanced the efficacy of GMA and tapering of the PSL dose soon after remission was not associated with UC relapse. Therefore, the majority of young corticosteroid naive UC patients in whom first-line salicylates have failed may respond to GMA and be spared from additional drug therapy. Avoiding corticosteroids at an early stage of UC should ensure better long-term clinical course.
authors: Department of Gastroenterology, Akitsu Prefectural Hospital, 4388 Akitsu cho, Hiroshima 739-2402, Japan. tomotaka@c.do-up.com
authors: Tomotaka
authors: T
authors: Tanaka
authors: Shinichiro
authors: S
authors: Sugiyama
authors: Hirokazu
authors: H
authors: Goishi
authors: Tsuyoshi
authors: T
authors: Kajihara
authors: Morihisa
authors: M
authors: Akagi
authors: Toshio
authors: T
authors: Miura
mesh_terms: D000293:Adolescent; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D001781:Blood Component Removal / Q000009:adverse effects; D002648:Child; D003093:Colitis, Ulcerative / Q000097:blood / Q000628:therapy*; D003131:Combined Modality Therapy; D005260:Female; D006098:Granulocytes; D006801:Humans; D008297:Male; D019804:Mesalamine / Q000627:therapeutic use; D009000:Monocytes; D011239:Prednisolone / Q000627:therapeutic use*; D012074:Remission Induction / Q000379:methods; D012720:Severity of Illness Index; D012460:Sulfasalazine / Q000627:therapeutic use; D017211:Treatment Failure; D055815:Young Adult
chemical_list: D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D012460:Sulfasalazine; D019804:Mesalamine; D011239:Prednisolone
references: Dig Dis Sci. 1983 Sep;28(9):833-42
references: 6136396
references: Gastroenterology. 1987 Jun;92(6):1894-8
references: 3569765
references: Dig Dis Sci. 2004 Apr;49(4):565-71
references: 15185858
references: Aliment Pharmacol Ther. 2013 Jan;37(2):195-203
references: 23151246
references: BMJ. 1989 Jan 14;298(6666):82-6
references: 2563951
references: Inflamm Bowel Dis. 2012 May;18(5):985-1002
references: 21936033
references: J Immunol. 2002 Apr 1;168(7):3536-42
references: 11907116
references: Gut. 1998 Apr;42(4):470-6
references: 9616306
references: J Crohns Colitis. 2012 Aug;6(7):750-5
references: 22398094
references: Am J Gastroenterol. 2008 May;103(5):1210-6
references: 18177452
references: BMC Gastroenterol. 2013 Feb 12;13:27
references: 23399416
references: Arthritis Rheum. 2002 Dec;46(12):3151-8
references: 12483718
references: Dig Dis Sci. 2002 Jun;47(6):1334-41
references: 12064810
references: Gastroenterology. 2008 Aug;135(2):400-9
references: 18602921
references: Inflamm Bowel Dis. 2000 Feb;6(1):48-57; discussion 58
references: 10701150
references: Ther Apher Dial. 2003 Feb;7(1):48-59
references: 12921115
references: J Clin Gastroenterol. 1995 Jun;20(4):280-4
references: 7665814
references: Transfus Apher Sci. 2007 Oct;37(2):191-200
references: 17974479
references: Dig Dis Sci. 2006 Nov;51(11):2031-8
references: 17004123
references: Dig Liver Dis. 2007 Jul;39(7):617-25
references: 17531555
references: Clin Exp Immunol. 1991 Dec;86(3):489-93
references: 1684141
references: Dig Liver Dis. 2007 May;39(5):430-4
references: 17379588
references: Digestion. 2012;85(4):308-19
references: 22688404
references: Dig Liver Dis. 2007 May;39(5):435-7
references: 17379590
references: Dig Dis Sci. 2007 Oct;52(10):2725-31
references: 17404876
references: Lancet. 1974 Jun 1;1(7866):1067-70
references: 4135487
references: N Engl J Med. 2002 Aug 8;347(6):417-29
references: 12167685
references: Inflamm Bowel Dis. 2008 Oct;14(10):1413-8
references: 18521900
references: Aliment Pharmacol Ther. 2004 Dec;20(11-12):1347-52
references: 15606397
references: Gastroenterology. 2000 Jul;119(1):15-22
references: 10889150
references: Dig Liver Dis. 2008 Sep;40(9):731-6
references: 18387860
references: Gastroenterol Clin Biol. 2010 Dec;34(12):687-95
references: 20934287