Quantitative ultrasound to monitor the vascular response to tocilizumab in giant cell arteritis

Rheumatology (Oxford). 2021 Nov 3;60(11):5052-5059. doi: 10.1093/rheumatology/keab484.

Abstract

Objectives: To characterize the effect of ultra-short glucocorticoids followed by Tocilizumab monotherapy on the intima-media thickness (IMT) in GCA.

Methods: Eighteen GCA patients received 500 mg for 3 consecutive days (total of 1500mg) i.v. methylprednisolone on days 0-2, followed by i.v. Tocilizumab (8 mg/kg) on day 3 and thereafter weekly s.c. Tocilizumab injections (162 mg) over 52 weeks. US of temporal (TAs), axillary (AAs) and subclavian (SAs) arteries was performed at baseline, on days 2-3, and at weeks 4, 8, 12, 24 and 52. The largest IMT of all segments and IMT at landmarks of AA/SA were recorded. IMT was scaled by mean normal values and averaged. Each segment was classified according to diagnostic cut-offs.

Results: Of the 18 GCA patients, 16 patients had TA and 6 had extracranial large artery involvement. The IMT showed a sharp decline on day 2/3 in the TAs and AAs/SAs. In TAs, this was followed by an increase to baseline levels at week 4 and a subsequent slow decrease, which was paralleled by decreasing symptoms and achievement of clinical remission. The AAs/SAs showed a new signal of vasculitis at week 4 in three patients, with an IMT increase up to week 8.

Conclusion: Glucocorticoid pulse therapy induced a transient decrease of the IMT in TAs and AAs/SAs. Tocilizumab monotherapy resulted in a slow and steady decrease in IMT of the TAs and a smaller and delayed effect on the AAs/SAs. The data strongly support a remission-inducing effect of Tocilizumab and argue the case for US having an important role in monitoring disease activity in GCA.

Trial registration: ClinicalTrials.gov, www.clinicaltrials.gov, NCT03745586.

Keywords: giant cell arteritis; glucocorticoids; tocilizumab; ultrasound; vascular response; vasculitis.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antibodies, Monoclonal, Humanized / pharmacology
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Arteries / diagnostic imaging
  • Arteries / drug effects
  • Female
  • Giant Cell Arteritis / diagnostic imaging*
  • Giant Cell Arteritis / drug therapy*
  • Glucocorticoids / pharmacology
  • Glucocorticoids / therapeutic use*
  • Humans
  • Male
  • Proof of Concept Study
  • Tunica Intima / diagnostic imaging
  • Tunica Intima / drug effects
  • Ultrasonography

Substances

  • Antibodies, Monoclonal, Humanized
  • Glucocorticoids
  • tocilizumab

Associated data

  • ClinicalTrials.gov/NCT03745586