Long-term Outcome of Early Combined Immunosuppression Versus Conventional Management in Newly Diagnosed Crohn's Disease

J Crohns Colitis. 2018 Apr 27;12(5):517-524. doi: 10.1093/ecco-jcc/jjy014.

Abstract

Background and aims: Long-term outcomes of early combined immunosuppression [top-down] compared to conventional management [step-up] in recently diagnosed Crohn's disease [CD] are unknown. We aimed to investigate long-term outcomes of participants of the Step-up/Top-down-trial.

Methods: Trial participants' medical records were reviewed retrospectively. For 16 semesters following the 2-year trial, we recorded: clinical activity, medication use, flares, hospitalization, surgery and fistulas. Colonoscopy reports were scored as: endoscopic remission, aphthous/small ulcers or large ulcers. The primary endpoint was the proportion of semesters in remission.

Results: Data were available from 119/133 patients [step-up n = 60]. During a median follow-up of 8 years, clinical remission rates were similar (70% vs 73% [p = 0.85] in step-up and top-down patients, respectively). A shorter time to flare was observed in step-up patients [median five vs nine semesters, p = 0.01]. Cumulatively, 62% of step-up patients used corticosteroids compared to 41% of top-down patients [p = 0.02]. Anti-tumour necrosis factor [anti-TNF] use was higher in the step-up group [73% vs 54%, p = 0.04]. No differences were found in to time to CD hospitalization [respectively 13 vs 14 semesters, p = 0.30], new fistula [14 vs 15 semesters, p = 0.20] or CD surgery [14 vs 15 semesters, p = 0.25]. Mucosal healing 2 years after treatment was associated with a reduced anti-TNF use, but not with differences in other long-term outcomes. Endoscopic remission occurred at similar rates between groups.

Conclusions: Top-down treatment did not result in increased clinical remission during long-term follow-up, compared to step-up treatment. However, lower relapse rates and a reduced use of anti-TNF agents and corticosteroids were observed. No difference was found in rates of endoscopic remission, hospitalization, surgery or new fistulas.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adrenal Cortex Hormones / therapeutic use*
  • Adult
  • Azathioprine / therapeutic use
  • Biological Products / therapeutic use*
  • Colonoscopy
  • Crohn Disease / complications
  • Crohn Disease / drug therapy*
  • Crohn Disease / surgery
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • Hospitalization
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Infliximab / therapeutic use
  • Intestinal Fistula / etiology*
  • Intestinal Mucosa / physiopathology
  • Male
  • Mercaptopurine / therapeutic use
  • Methotrexate / therapeutic use
  • Retrospective Studies
  • Symptom Flare Up
  • Time Factors
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Wound Healing
  • Young Adult

Substances

  • Adrenal Cortex Hormones
  • Biological Products
  • Immunosuppressive Agents
  • Tumor Necrosis Factor-alpha
  • Infliximab
  • Mercaptopurine
  • Azathioprine
  • Methotrexate