Tocilizumab as an add-on therapy to glucocorticoids during the first 3 months of treatment of Giant cell arteritis: A prospective study

Eur J Intern Med. 2018 Nov;57:96-104. doi: 10.1016/j.ejim.2018.06.008. Epub 2018 Jul 24.

Abstract

Background: The aim of this study was to evaluate tocilizumab (TCZ) as an add-on therapy to glucocorticoids (GC) during the first 3 months of treatment of giant cell arteritis (GCA).

Methods: GCA patients, as defined by ≥3/5 ACR criteria and positive temporal artery biopsy (TAB) or angio-CT-scan or PET-scan-proven aortitis, were included in this prospective open-label study. Prednisone was started at 0.7 mg/kg/day and then tapered according to a standardized protocol. All patients received four infusions of TCZ (8 mg/kg/4 weeks) after inclusion. The primary endpoint was the percentage of patients in remission with ≤0.1 mg/kg/day of prednisone at week 26 (W26). Patients were followed for 52 weeks and data prospectively recorded.

Results: Twenty patients with a median (IQR) age of 72 (69-78) years were included. TAB were positive in 17/19 (90%) patients and 7/16 (44%) had aortitis. Remission was obtained in all cases. At W26, 15 (75%) patients met the primary endpoint. Ten patients experienced relapse during follow-up, mainly patients with aortitis (P = 0.048), or CRP >70 mg/L (P = 0.036) or hemoglobin ≤10 g/dL (P = 0.015) at diagnosis. Among 64 adverse events (AE) reported in 18 patients, three were severe and 30, mostly non-severe infections (n = 15) and hypercholesterolemia (n = 8), were imputable to the study.

Conclusion: This study shows that an alternative strategy using a short-term treatment with TCZ can be proposed to spare GC for the treatment of GCA. However, 50% of patients experienced relapse during the 9 months following TCZ discontinuation, especially patients with aortitis, or CRP > 70 mg/L or Hb ≤ 10 g/dL at diagnosis.

Trial registration: ClinicalTrials.gov (NCT01910038).

Keywords: Aortitis; Clinical trial; Giant cell arteritis; Relapse; Tocilizumab.

Publication types

  • Clinical Trial
  • Multicenter Study

MeSH terms

  • Aged
  • Antibodies, Monoclonal, Humanized / administration & dosage*
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Aortitis / complications*
  • C-Reactive Protein / analysis
  • Drug Administration Schedule
  • Female
  • France
  • Giant Cell Arteritis / drug therapy*
  • Giant Cell Arteritis / mortality
  • Glucocorticoids / administration & dosage*
  • Glucocorticoids / adverse effects
  • Humans
  • Interleukin-6 / blood
  • Male
  • Positron-Emission Tomography
  • Prednisone / administration & dosage*
  • Prednisone / adverse effects
  • Proof of Concept Study
  • Prospective Studies
  • Recurrence
  • Remission Induction
  • Temporal Arteries / pathology
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal, Humanized
  • Glucocorticoids
  • IL6 protein, human
  • Interleukin-6
  • C-Reactive Protein
  • tocilizumab
  • Prednisone

Associated data

  • ClinicalTrials.gov/NCT01910038