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

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), ^99mTc-labeled diethylene triamine pentaacetic acid (^99mTc DTPA) single photon emission computed tomography and magnetic resonance imaging. Rituximab (RTX) was given as weekly infusions of 375 mg/m² 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/cm³ and decreased to 11.97 ± 2.36 MBq/cm³ 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.

• Biological treatment
• endocrine orbitopathy
• Graves’disease
• hyperthyroidism
• thyroid

Acknowledgements

The authors would like to thank Dr. Laszlo Rejto of the Division of Hematology, University of Debrecen, for consulting on the prevention of putative side effects of the RTX therapy.