title: Long-term Outcomes in Steroid-refractory Ulcerative Colitis Treated with Tacrolimus Alone or in Combination with Purine Analogues.
abstract: OBJECTIVE
  Tacrolimus is recommended for the treatment of steroid-refractory ulcerative colitis (UC). Concomitantly started purine analogues (PAs) are used for the maintenance of remission, though their therapeutic relevance remains uncertain. Here we studied the role of PAs in the long-term outcome of steroid-refractory UC after tacrolimus treatment.
  
  
  METHODS
  In five centres, charts of tacrolimus-treated UC patients with a steroid-refractory moderate to severe course were reviewed. Long-term efficacy was determined by colectomy rates and clinical remission in cases of colectomy-free survival for 3 months.
  
  
  RESULTS
  We identified 156 patients (median age 34 years) with a median Lichtiger score of 12 (4-17) and pancolitis (E3) in 65% (101). The Kaplan-Meier curve for colectomy-free survival after month 3 showed a benefit in the PA group (p = 0.02). In patients treated with PA clinical remission was achieved in 82% (65/79) vs 67% (39/58) in those not treated with PA (p = 0.02). Time to colectomy was 2 years (median, 0.7-5.8) in the PA group and 0.8 years (0.3-4.7) in the group not treated with PAs (p = 0.02). Time to relapse was 1.2 years (median, 0.3-6.2) in patients with PA treatment and 0.5 years (0.3-3.9) in those without PA treatment (p = 0.05). Overall, clinical remission was achieved in 67% (104/156) of patients. Colectomy was performed in 29% (45/156) 0.5 years (median, 0.04-5.79) after initiation of tacrolimus. Ten (6%) patients had to stop tacrolimus due to adverse events and two (without PA treatment) died.
  
  
  CONCLUSIONS
  Our study supports the efficacy of tacrolimus in steroid-refractory UC. Purine analogues appear to be beneficial for the long-term outcome of these patients.
authors.affiliation: Department of Internal Medicine I, University Hospital of Schleswig-Holstein, Lübeck, Germany.
authors.forename: K J
authors.initials: KJ
authors.lastname: Schmidt
authors.affiliation: Department of Internal Medicine I, University Hospital of Schleswig-Holstein, Lübeck, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Müller
authors.affiliation: Department of Internal Medicine I, Agaplesion Markus Hospital, Frankfurt, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Dignass
authors.affiliation: Department of Gastroenterology and Hepatology, Charite Medical School, Humboldt University of Berlin, Berlin, Germany.
authors.forename: D C
authors.initials: DC
authors.lastname: Baumgart
authors.affiliation: Department of Internal Medicine I, University Hospital of Schleswig-Holstein, Lübeck, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Lehnert
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Robert Bosch Hospital, Stuttgart, Germany.
authors.forename: E F
authors.initials: EF
authors.lastname: Stange
authors.affiliation: Department of Internal Medicine I, Asklepios Klinik Nord, Hamburg, Germany.
authors.forename: K R
authors.initials: KR
authors.lastname: Herrlinger
authors.affiliation: Department of Internal Medicine I, University Hospital of Schleswig-Holstein, Lübeck, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Fellermann
authors.affiliation: Department of Internal Medicine I, University Hospital of Schleswig-Holstein, Lübeck, Germany juergen.buening@uk-sh.de.
authors.forename: J
authors.initials: J
authors.lastname: Büning
mesh_terms: D000328:Adult; D000368:Aged; D015331:Cohort Studies; D003082:Colectomy / Q000379:methods / Q000706:statistics & numerical data; D003093:Colitis, Ulcerative / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery; D003113:Colonoscopy / Q000379:methods; D016208:Databases, Factual; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D005858:Germany; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000473:pathology; D053208:Kaplan-Meier Estimate; D008297:Male; D015122:Mercaptopurine / Q000008:administration & dosage*; D008875:Middle Aged; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D018570:Risk Assessment; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D013256:Steroids / Q000008:administration & dosage / Q000009:adverse effects; D015996:Survival Rate; D016559:Tacrolimus / Q000008:administration & dosage*; D013997:Time Factors; D016896:Treatment Outcome; D014945:Wound Healing / Q000187:drug effects / Q000502:physiology; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D013256:Steroids; D015122:Mercaptopurine; D016559:Tacrolimus
keywords: Ulcerative colitis; tacrolimus; purine analogues