Certolizumab Pegol Efficacy Across Methotrexate Regimens: A Pre-Specified Analysis of Two Phase III Trials

Arthritis Care Res (Hoboken). 2016 Mar;68(3):299-307. doi: 10.1002/acr.22676.


Objective: Anti-tumor necrosis factor (anti-TNF) agents are frequently used in combination with methotrexate (MTX) to treat rheumatoid arthritis (RA). We investigated the effect of a background MTX dose, in combination with anti-TNF certolizumab pegol (CZP), on treatment efficacy and safety in RA patients.

Methods: A pre-specified subgroup analysis comparing 2 MTX dosage categories (<15 mg/week and ≥15 mg/week) was carried out using data pooled from phase III clinical trials, Rheumatoid Arthritis Prevention of Structural Damage 1 (RAPID 1) and RAPID 2, according to treatment group: CZP 200 mg, CZP 400 mg, or placebo, every 2 weeks. Inclusion criteria required MTX dosage ≥10 mg/week. Efficacy end points included week 24 American College of Rheumatology criteria for 20%, 50%, and 70% improvement (ACR20/50/70) responses analyzed by logistic regression, and changes from baseline in the Disease Activity Score in 28 joints using the erythrocyte sedimentation rate (DAS28-ESR) and the modified Sharp/van der Heijde score (SHS) were analyzed by analysis of covariance. Incidence rates of treatment-emergent adverse events (TEAEs) were categorized by baseline MTX dose. Post hoc sensitivity analysis investigated 3 MTX dose categories: ≤10 mg/week, >10 and ≤15 mg/week, and >15 mg/week.

Results: A total of 638, 635, and 325 patients received CZP 200 mg, CZP 400 mg, and placebo, respectively. At week 24, treatment responses in both CZP groups were uninfluenced by baseline MTX dose category, and were superior to the placebo group for all investigated end points: ACR20/50/70, DAS28-ESR, and SHS. TEAE incidence rates were higher in patients receiving MTX ≥15 mg/week for most TEAE types across treatment groups.

Conclusion: CZP efficacy was not affected by background MTX dose category. It can be hypothesized that to minimize TEAEs, background MTX doses could be tailored to individual patient tolerance without affecting CZP efficacy.

Trial registration: ClinicalTrials.gov NCT00152386 NCT00160602.

Publication types

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

MeSH terms

  • Antirheumatic Agents / adverse effects
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Rheumatoid / diagnostic imaging
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / immunology
  • Certolizumab Pegol / adverse effects
  • Certolizumab Pegol / therapeutic use*
  • Disease Progression
  • Drug Therapy, Combination
  • Humans
  • Methotrexate / adverse effects
  • Methotrexate / therapeutic use*
  • Radiography
  • Remission Induction
  • Time Factors
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Tumor Necrosis Factor-alpha / immunology


  • Antirheumatic Agents
  • Tumor Necrosis Factor-alpha
  • Certolizumab Pegol
  • Methotrexate

Associated data

  • ClinicalTrials.gov/NCT00152386
  • ClinicalTrials.gov/NCT00160602