Long-term safety and efficacy of certolizumab pegol in the treatment of Crohn's disease: 7-year results from the PRECiSE 3 study

Aliment Pharmacol Ther. 2014 Oct;40(8):903-16. doi: 10.1111/apt.12930. Epub 2014 Aug 22.

Abstract

Background: The efficacy and safety of certolizumab pegol (CZP) in moderate-to-severe Crohn's disease were demonstrated in two 26-week double-blind studies (PRECiSE 1 & 2).

Aim: To report the safety and efficacy outcomes of long-term, CZP therapy from PRECiSE 3, in which patients received treatment up to 7 years treatment.

Methods: Patients completing PRECiSE 1 or 2 were eligible to enter PRECiSE 3 in which they received CZP 400 mg, open-label, every 4 weeks (without additional induction therapy) for up to 7 years, for up to 91 doses from study start. Safety (adverse events, including infections and malignancies) and efficacy (Harvey-Bradshaw Index, faecal calprotectin, C-reactive protein) were prospectively monitored. Remission was analysed using observed cases, last observation carried forward imputation and nonresponder imputation.

Results: A total of 595 patients entered the study; 117 (20%) completed 7 years. Discontinuation rates were 29.2%, 13.6%, 16.1%, 7.9%, 5.0%, 4.5% and 3.9% (years 1-7 respectively). During 1920 patient-years of exposure to CZP, no new safety signals were observed. Incidence rates (new cases/100 patient-years) for serious infections and malignant neoplasms were 4.37 and 1.06 respectively. No lymphoproliferative malignancies were reported. Clinical remission rates were ≥68% at each year (observed cases); rates by last observation carried forward and nonresponder imputation were 58% and 45% at year 1, 56% and 26% at year 3 and 55% and 13% at year 7 respectively.

Conclusion: Certolizumab pegol was well tolerated in the long-term treatment of Crohn's disease, with sustained remission in some patients continuing in the study for up to 7 years. ClinicalTrials.gov identifier NCT00552058.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • C-Reactive Protein / metabolism
  • Certolizumab Pegol
  • Crohn Disease / drug therapy*
  • Double-Blind Method
  • Female
  • Humans
  • Immunoglobulin Fab Fragments / adverse effects
  • Immunoglobulin Fab Fragments / therapeutic use*
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / therapeutic use*
  • Leukocyte L1 Antigen Complex / metabolism
  • Male
  • Middle Aged
  • Polyethylene Glycols / adverse effects
  • Polyethylene Glycols / therapeutic use*
  • Remission Induction
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal, Humanized
  • Immunoglobulin Fab Fragments
  • Immunosuppressive Agents
  • Leukocyte L1 Antigen Complex
  • Polyethylene Glycols
  • C-Reactive Protein
  • Certolizumab Pegol

Associated data

  • ClinicalTrials.gov/NCT00552058