Rapid response to and long-term effectiveness of anti-CD20 antibody in conventional therapy resistant Graves' orbitopathy: A five-year follow-up study

Autoimmunity. 2014 Dec;47(8):548-55. doi: 10.3109/08916934.2014.939266. Epub 2014 Jul 21.

Abstract

Abstract The aim of this investigations was to study the effectiveness of anti-CD20 antibody therapy in Graves' orbitopathy (GO) resistant to glucocorticoids. Five patients were entered in the study. The protocol required no improvement of orbital status after a recent course of glucocorticoids. Activity of GO was confirmed by three independent techniques: clinical activity score (CAS), (99m)Tc-labeled diethylene triamine pentaacetic acid ((99m)Tc DTPA) single photon emission computed tomography and magnetic resonance imaging. Rituximab (RTX) was given as weekly infusions of 375 mg/m(2) body surface area for four weeks. The mean follow-up period was 67 (range 58-81) months. Improvement of GO has been observed in all patients: CAS before therapy was 6.5 ± 1.7 and decreased to 3.4 ± 1.6 by one month (p < 0.05) and remained unchanged (3.2 ± 1.7) at 12 months. No further CAS change, in either direction, was detected during the yearly follow-up visits. The mean DTPA uptake before therapy was 16.52 ± 4.51 MBq/cm(3) and decreased to 11.97 ± 2.36 MBq/cm(3) at one year (p < 0.002). The mean of T2 relaxation times before and one year after therapy were 96.91 ± 17.61 ms and 84.29 ± 9.41 ms, respectively (p < 0.001). The mean serum TSH receptor antibody (TRAb) levels before therapy, at the one month and one year control visits were 7.4 ± 3.4 U/L, 5.6 ± 4.5 U/L and 1.7 ± 1.5 U/L, respectively (p < 0.004). No correlation between changes of TRAb and activity parameters has been found. Anti-CD20 treatment seems to influence positively the clinical course of GO, and this effect seems to be stable for five years. To our knowledge, this is the longest published follow-up of RTX treatment in GO.

Keywords: Biological treatment; Graves’disease; endocrine orbitopathy; hyperthyroidism; thyroid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Monoclonal, Murine-Derived / administration & dosage*
  • Female
  • Follow-Up Studies
  • Graves Ophthalmopathy / blood
  • Graves Ophthalmopathy / drug therapy*
  • Graves Ophthalmopathy / pathology
  • Humans
  • Immunoglobulins, Thyroid-Stimulating / blood
  • Immunosuppressive Agents / administration & dosage*
  • Infusions, Intravenous
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Rituximab
  • Thyrotropin / blood
  • Thyroxine / blood
  • Tomography, Emission-Computed, Single-Photon
  • Triiodothyronine / blood

Substances

  • Antibodies, Monoclonal, Murine-Derived
  • Immunoglobulins, Thyroid-Stimulating
  • Immunosuppressive Agents
  • thyrotropin-binding inhibitory immunoglobulin
  • Triiodothyronine
  • Rituximab
  • Thyrotropin
  • Thyroxine