title: Topical treatment with the Toll-like receptor agonist DIMS0150 has potential for lasting relief of symptoms in patients with chronic active ulcerative colitis by restoring glucocorticoid sensitivity.
abstract: BACKGROUND
  Patients with chronic active ulcerative colitis (UC) are regarded as treatment failures and represent an area of high unmet medical need, as normally the only remaining option is colectomy.
  
  
  METHODS
  We treated a total of eight chronic active severe UC outpatients with the immunomodulatory agent DIMS0150 as an add-on to current therapies. Seven patients received a single topical dose of 30 mg and one special case subject received three doses with 4 weeks between dosing occasions. All patients were classed as treatment failures and were elected for colectomy. Efficacy evaluation was determined in terms of colitis activity index, endoscopic improvement, and histologic disease activity assessed primarily at week 12 with a follow-up period of over 2 years. Glucocorticoid sensitivity was assayed by in vitro measurement of interleukin 6.
  
  
  RESULTS
  All patients demonstrated a pronounced and rapid reduction in their colitis activity index within 1 week following a single intracolonic administration via colonoscope of the agent DIMS0150. Further improvements were evident at week 4, resulting in a clinical response rate for the single-dose treatment of 71%, with 43% in clinical remission. By week 12 the clinical response and remission rates had reached 82% and 71%, respectively. A follow-up period of over 2 years posttreatment indicated that all but one of the treated patients had avoided the need for colectomy, with the longest patient being in symptom-free remission for over 27 months. Treatment with DIMS0150 restored glucocorticoid sensitivity.
  
  
  CONCLUSIONS
  DIMS0150 may have the potential to be an effective agent to treat chronic active UC patients with the prospect to avoid colectomy on a long-term basis and is currently the subject of a clinical phase III study (EudraCT number: 2011-003130-14).
authors.affiliation: Clinic of Colo-Proctology and Intestine Center the Marienhospital, Bottrop, Germany.
authors.forename: Eugen
authors.initials: E
authors.lastname: Musch
authors.forename: Tamim
authors.initials: T
authors.lastname: Lutfi
authors.forename: Petra
authors.initials: P
authors.lastname: von Stein
authors.forename: Arezou
authors.initials: A
authors.lastname: Zargari
authors.forename: Charlotte
authors.initials: C
authors.lastname: Admyre
authors.forename: Mouhamad
authors.initials: M
authors.lastname: Malek
authors.forename: Robert
authors.initials: R
authors.lastname: Löfberg
authors.forename: Oliver D
authors.initials: OD
authors.lastname: von Stein
mesh_terms: D000287:Administration, Topical; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D003093:Colitis, Ulcerative / Q000188:drug therapy* / Q000378:metabolism; D003106:Colon / Q000378:metabolism; D003113:Colonoscopy; D004247:DNA / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D005938:Glucocorticoids / Q000627:therapeutic use*; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D011239:Prednisolone / Q000627:therapeutic use*; D011446:Prospective Studies; D051217:Toll-Like Receptor 9 / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; C582905:DIMS0150; D005938:Glucocorticoids; C508600:IL6 protein, human; D007155:Immunologic Factors; D015850:Interleukin-6; C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9; D004247:DNA; D011239:Prednisolone