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

  • Oculoplastics and Orbit
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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.

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Acknowledgments

We gratefully acknowledge Brigitte Dessome (Nantes University Hospital) and Matthieu Wargny (L’institut du thorax, CIC Endocrinology, and Inserm UMR 1087) for their helpful advice in statistical analysis. We thank Dr. Sophie Arsène, Dr. Peggy Pierre, Dr. Laurence Leenhardt, Dr. Claire Bournaud, Dr. Claire Briet, Dr. Bernard Goichot, Dr. Isabelle Raingeard, Dr. Nathalie Roudaut, Dr. Matthieu Pichelin, Dr. Ester Landau, Dr. Maëlle Le Bras, and Dr. Bertrand Vabres for providing us with their clinical data. We also thank the members of the French Thyroid Research Group (GRT).

Funding

This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.

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Author notes

  1. Delphine Drui and Pierre Lebranchu are senior authors contributed equally.

Authors and Affiliations

  1. Department of Ophthalmology, Hotel Dieu, CHU Nantes, 44093, Nantes Cedex 1, France

    Jean-Baptiste Deltour & Pierre Lebranchu

  2. Department of Endocrinology Diabetes and Nutrition, L’institut du thorax, CHU Nantes, 44093, Nantes Cedex 1, France

    Marie d’Assigny Flamen, Bertrand Cariou & Delphine Drui

  3. Department of Endocrinology CHRU Lille, 59037, Lille Cedex, France

    Miriam Ladsous

  4. Department of Internal Medicine, Section of Endocrinology, Fondation Ophtalmologique A de Rothschild, 75019, Paris, France

    Lama Giovansili

  5. Department of Endocrinology, Metabolic Diseases and Nutrition, Pôle Cardio-Vasculaire et Métabolique, CHU Toulouse, 9, 31059, Toulouse Cedex, France

    Philippe Caron

Authors
  1. Jean-Baptiste Deltour
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Corresponding author

Correspondence to Jean-Baptiste Deltour.

Ethics declarations

All procedures performed were in accordance with the 1964 Helsinki Declaration and its later amendments.

The study protocol was accepted by the local ethics committee (GNEDS: “Groupe Nantais d’Ethique dans le Domaine de la Santé”). Informed consent was not required for this non-interventional retrospective study.

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The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of this study.

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Deltour, JB., d’Assigny Flamen, M., Ladsous, M. et al. Efficacy of rituximab in patients with Graves’ orbitopathy: a retrospective multicenter nationwide study. Graefes Arch Clin Exp Ophthalmol 258, 2013–2021 (2020). https://doi.org/10.1007/s00417-020-04651-6

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  • DOI: https://doi.org/10.1007/s00417-020-04651-6

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