Efficacy of rituximab in patients with Graves' orbitopathy: a retrospective multicenter nationwide study

Graefes Arch Clin Exp Ophthalmol. 2020 Sep;258(9):2013-2021. doi: 10.1007/s00417-020-04651-6. Epub 2020 May 13.

Abstract

Purpose: The clinical utility of rituximab (RTX) in Graves' orbitopathy (GO) treatment remains controversial since the discrepant results from 2 prospective randomized studies (Stan M et al. J Clin Endocrinol Metab 2015; Salvi M et al. J Clin Endocrinol Metab 2015). The aim of this study was to assess in real life the characteristics and the clinical outcomes of patients with GO treated with RTX in cases of corticosteroid resistance or corticosteroid dependence.

Methods: Multicenter French retrospective study including patients with moderate-to-severe GO requiring second-line treatment with RTX. Patients were classified according to three main baseline characteristics: clinical inflammation (CAS ≥ 3), oculomotor limitation, and visual dysfunction. Patients were considered as responders if, at 24 weeks (week 24), at least 1 of these 3 parameters improved with no worsening elsewhere.

Results: Forty patients were included (65% smokers, 38% dysthyroidism). Thirty-two patients were treated with RTX alone (one patient excluded owing to side effects): 64.5% had favorable responses at week 24 and significant reduction in baseline CAS (3.29 ± 1.6) at 12 weeks (1.93 ± 1.1; P < 0.001) and at week 24 (1.59 ± 1.1; P < 0.001); reduction in anti-TSH receptor antibodies at week 24 (P < 0.01); and significant improvement of visual acuity (P = 0.04) and ocular hypertonia (P = 0.04) at week 12, but no improvement in oculomotor dysfunction. Eight patients needed emergency treatment with concomitant RTX and orbital decompression, with favorable outcome for 5 patients. Predictive factors for a poor response to RTX were low baseline CAS, smoker, and baseline ocular hypertonia. All patients reported good tolerance except one serious side effect (a cytokine release syndrome).

Conclusions: The efficiency results of RTX in reducing CAS in this cohort are just between those of Stan and Salvi. This could be explained by our delay before treatment initiation, quicker than Stan but longer than Salvi. RTX appears to be effective as a second-line treatment for the inflammatory component of GO, especially if the disease is highly active and recent.

Keywords: Anti-CD20 antibody; Basedow’s disease; Clinical activity score (CAS); Graves’ orbitopathy; Rituximab.

Publication types

  • Multicenter Study
  • Observational Study

MeSH terms

  • Female
  • Follow-Up Studies
  • France / epidemiology
  • Graves Ophthalmopathy / drug therapy*
  • Graves Ophthalmopathy / epidemiology
  • Graves Ophthalmopathy / physiopathology
  • Humans
  • Immunologic Factors / administration & dosage
  • Incidence
  • Injections, Intravenous
  • Male
  • Middle Aged
  • Population Surveillance / methods*
  • Retrospective Studies
  • Rituximab / administration & dosage*
  • Treatment Outcome
  • Visual Acuity*

Substances

  • Immunologic Factors
  • Rituximab