Risk factors of serious infections in patients with rheumatoid arthritis treated with tocilizumab in the French Registry REGATE

Rheumatology (Oxford). 2017 Oct 1;56(10):1746-1754. doi: 10.1093/rheumatology/kex238.

Abstract

Objectives: Observational studies have already reported the risk of serious infections in RA treated with tocilizumab, but in limited samples. The aim of this study was to investigate the predictive risk factors for serious infections in the largest European registry of patients treated with tocilizumab for RA.

Methods: A total of 1491 RA patients included in the French REGistry-RoAcTEmra were analysed to calculate the incidence rate of first serious infections rate after initiation of tocilizumab. To identify independent factors associated with serious infections, a Cox model was performed.

Results: Among the 1491 patients, average age 56.6 (13.6) years, 125 serious infections occurred in 122 patients (incidence rate of serious infection: 4.7/100 patient-years). Univariate analysis identified initial ACPA positivity as the only factor associated with a lower risk of serious infection [hazard ratio (HR) = 0.56, 95% CI: 0.36, 0.88]. Other factors significantly associated with a higher risk of serious infections were DAS28, concomitant Leflunomide (LEF) treatment, and absolute neutrophil count (ANC) at baseline. Initial ANC above 5.0 × 109/l (HR = 1.94, 95% CI: 1.32, 2.85; P < 0.001), negative ACPA (HR = 1.79, 95% CI: 1.15, 2.78; P = 0.012) at baseline and concomitant LEF treatment (LEF alone vs no treatment, HR = 2.18, 95% CI: 1.22, 3.88; P = 0.009) remained significantly associated with first serious infections in multivariate analysis after imputation for missing data.

Conclusion: The rate of first serious infections in current practice is similar to that reported in clinical trials. High ANC (above 5.0 × 109 at baseline), negative ACPA and concomitant therapy with LEF are predictive factors of serious infection, requiring in this case a tighter surveillance.

Keywords: DMARDs; observational study; registry; rheumatoid arthritis; risk factors; safety; serious infection; steroids; tocilizumab; tolerance.

Publication types

  • Evaluation Study

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal, Humanized / adverse effects*
  • Antirheumatic Agents / adverse effects*
  • Arthritis, Rheumatoid / blood
  • Arthritis, Rheumatoid / drug therapy*
  • Autoantibodies / blood
  • Drug Therapy, Combination
  • Female
  • France / epidemiology
  • Humans
  • Incidence
  • Isoxazoles / adverse effects
  • Leflunomide
  • Leukocyte Count
  • Male
  • Middle Aged
  • Neutrophils
  • Opportunistic Infections / chemically induced*
  • Opportunistic Infections / epidemiology
  • Peptides, Cyclic / immunology
  • Proportional Hazards Models
  • Registries
  • Risk Factors

Substances

  • Antibodies, Monoclonal, Humanized
  • Antirheumatic Agents
  • Autoantibodies
  • Isoxazoles
  • Peptides, Cyclic
  • cyclic citrullinated peptide
  • Leflunomide
  • tocilizumab