Efficacy and safety of certolizumab pegol without methotrexate co-administration in Japanese patients with active rheumatoid arthritis: the HIKARI randomized, placebo-controlled trial

Mod Rheumatol. 2014 Jul;24(4):552-60. doi: 10.3109/14397595.2013.843764. Epub 2013 Nov 1.

Abstract

Objective: This 24-week, placebo-controlled, double-blind, randomized study (NCT00791921) investigated efficacy and safety of certolizumab pegol (CZP) in Japanese rheumatoid arthritis (RA) patients in whom methotrexate (MTX) cannot be administered.

Methods: A total of 230 patients were randomized to subcutaneous CZP 200 mg (induction dosing: 400 mg at Weeks 0, 2 and 4) or placebo every 2 weeks.

Results: ACR20 responses with CZP were rapid and significant versus placebo at Week 1, sustained to Week 12 (67.2% vs. 14.9%) and Week 24 (63.8% vs. 11.4%). Week 24-modified Total Sharp Score (mTSS) change from baseline (CFB) was 0.48 (CZP) versus 2.45 (placebo). CZP treatment was associated with higher Week 12 ACR20 responses versus placebo (with non-MTX disease modifying antirheumatic drugs [DMARDs], 74.2% vs. 20.0%; without [monotherapy], 59.3% vs. 8.2%) and inhibition of radiographic progression at Week 24 (mTSS CFB; with non-MTX DMARDs, 0.24 vs. 1.61; monotherapy, 0.68 vs. 3.65). Incidences of serious adverse events were 11.2% (CZP) and 2.6% (placebo); one CZP patient died of dissecting aortic aneurysm.

Conclusion: CZP treatment with and without non-MTX DMARDs in Japanese patients in whom MTX cannot be administered resulted in rapid, sustained reductions in RA signs and symptoms. Notably, CZP monotherapy showed significant inhibition of radiographic progression.

Keywords: Certolizumab pegol; Monotherapy; Randomized controlled trial; Rheumatoid arthritis; Tumor necrosis factor-alpha inhibitor.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Antirheumatic Agents / adverse effects
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Rheumatoid / drug therapy*
  • Certolizumab Pegol
  • Disease Progression
  • Double-Blind Method
  • Female
  • Humans
  • Immunoglobulin Fab Fragments / adverse effects
  • Immunoglobulin Fab Fragments / therapeutic use*
  • Japan
  • Male
  • Methotrexate / adverse effects
  • Methotrexate / therapeutic use*
  • Middle Aged
  • Polyethylene Glycols / adverse effects
  • Polyethylene Glycols / therapeutic use*
  • Treatment Outcome
  • Young Adult

Substances

  • Antibodies, Monoclonal, Humanized
  • Antirheumatic Agents
  • Immunoglobulin Fab Fragments
  • Polyethylene Glycols
  • Certolizumab Pegol
  • Methotrexate

Associated data

  • ClinicalTrials.gov/NCT00791921