High frequency of antidrug antibodies and association of random drug levels with efficacy in certolizumab pegol-treated patients with rheumatoid arthritis: results from the BRAGGSS cohort

Ann Rheum Dis. 2017 Jan;76(1):208-213. doi: 10.1136/annrheumdis-2015-208849. Epub 2016 May 31.


Objectives: To evaluate (i) the association between random certolizumab drug levels, antidrug antibodies (ADAbs) and treatment response in patients with rheumatoid arthritis (RA); (ii) longitudinal factors associated with ADAbs and certolizumab drug levels.

Methods: This prospective cohort included 115 patients with RA treated with certolizumab. Serum samples were collected at 3, 6 and 12 months following treatment initiation. Drug levels and ADAbs were measured using ELISA and radioimmunoassay, respectively, at 3, 6 and 12 months. Disease Activity Score in 28 joints (DAS28) were measured at each visit and 12 months European League Against Rheumatism (EULAR) response was calculated. Patient self-reported adherence was collected longitudinally. Ordinal logistic regression and generalised estimating equation were used to test the association: (i) between drug levels, from serum sampled and treatment response; (ii) between ADAbs and drug levels; (iii) patient-centred factors and drug levels.

Results: ADAbs were detected in 37% (42/112 patients by 12 months). The presence of ADAbs were significantly associated with lower drug levels over 12 months (β=-0.037, 95% CI -0.055 to 0.018, p<0.0001) but not independently with 12 months EULAR response (β=0.0013 (95% CI -0.0032 to 0.00061), p=0.18). Drug level was associated with 12 months EULAR response (β=0.032 (95% CI 0.0011 to 0.063), p=0.042). In the multivariate model, ADAb level and adherence were significantly associated with drug concentrations.

Conclusions: This is the first study to demonstrate that higher certolizumab drug levels are associated with better 12 months EULAR response. ADAbs in certolizumab-treated patients with RA were detected at higher levels than previous studies and help determine the aetiology of a low drug level.

Keywords: Anti-TNF; DMARDs (biologic); Rheumatoid Arthritis; TNF-alpha; Treatment.

Publication types

  • Multicenter Study
  • Observational Study

MeSH terms

  • Adult
  • Aged
  • Antibodies / blood*
  • Antirheumatic Agents / administration & dosage
  • Antirheumatic Agents / blood
  • Antirheumatic Agents / immunology*
  • Antirheumatic Agents / therapeutic use
  • Arthritis, Rheumatoid / blood
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / immunology
  • Certolizumab Pegol / administration & dosage
  • Certolizumab Pegol / blood
  • Certolizumab Pegol / immunology*
  • Certolizumab Pegol / therapeutic use
  • Cohort Studies
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Male
  • Middle Aged
  • Prospective Studies
  • Severity of Illness Index
  • Treatment Outcome


  • Antibodies
  • Antirheumatic Agents
  • Certolizumab Pegol