Endocrine Abstracts (2007) 14 OC1.3

Persistence of decreased peripheral B-lymphocytes after Rituximab treatment is associated to inactive disease in patients with thyroid-associated ophthalmopathy

Irene Campi1, Guia Vannucchi1, Danila Covelli1, Paola Bonara2, Nicola Currò3, Davide Dazzi4, Giacinta Pirola3, Stefania Rossi5, Claudio Guastella6, Paolo Beck-Peccoz1 & Mario Salvi1

1Endocrine Unit Department of Medical Science; 2Internal Medicine; 3Ophthalmology; Fondazione Policlinico IRCC, University of Milan, Milan, Italy; 4Internal Medicine, Ospedale di Fidenza, Fidenza, Italy; 5Pathology Unit, Department of Medicine, Surgery and Dentistry, University of Milan, Ospedale S. Paolo and Fondazione Policlinico IRCCS, Milan, Italy; 6Otolaryngology, Fondazione Policlinico IRCC, University of Milan, Milan, Italy.

The anti-CD20 antibody Rituximab (RTX) induces peripheral B cells depletion. Aim of the present study was to evaluate changes of lymphocytes after RTX therapy, administered at the dosage of 1000 mg twice at 2-week interval, in 10 patients with Graves’ disease, 8 of whom had associated ophthalmopathy (TAO). In all patients, we studied the standard immunophenotypic panel before therapy and monthly for up to 2 years. Total CD20+ (and CD19+) cell depletion was observed after the first infusion in 9 patients while one patient had persistence of <5% CD19+CD5+ lymphocytes. 8/10 patients were depleted for 4–6 months after RTX, while 1 and 1 patients after 2 and 10 months respectively. A reduction of CD20+ cells of about 50% from baseline was observed in 6 patients at 18 months and in 3 at 26 months. While after RTX there was no significant change of serum thyroid autoantibodies levels, nor correlation with CD20+ depletion, we observed a stable improvement of TAO with a significant decrease of the clinical activity score. Although progression to inactive TAO did not correlate with CD20+ cells, since at 5 months they began repopulating, we did not observe relapse of active TAO even after B cell return. In contrast, in the patient with persistence of CD19+5+, severe TAO relapsed at the time of CD20+ cells return. Another cycle of RTX (1000 mg) was then administered but again we observed persistence of <7% CD19+5+ with no definite improvement of the clinical signs of TAO. At subsequent orbital decompression we were able to detect CD19+5+ in the orbital tissues. In conclusion, in patients with TAO a reduction of CD20+ of about 50% from the baseline is still present at 18–24 months after RTX treatment. This may explain the consistent improvement of TAO and the lack of relapse, in patients after total B-cells depletion. Persistence of CD19+5+ lymphocytes in the peripheral blood and, perhaps, in the orbit, may associate to a not completely satisfactory therapeutic response.