Efficacy of rituximab treatment for thyroid-associated ophthalmopathy as a result of intraorbital B-cell depletion in one patient unresponsive to steroid immunosuppression

Abstract

One patient with Graves' hyperthyroidism and ophthalmopathy in its active phase and unresponsive to steroid, was treated with the anti-CD20 monoclonal antibody, rituximab (RTX), as part of an open study. The effect of RTX in the thyroid and the orbital tissues was studied. The ophthalmopathy responded to RTX therapy by ameliorating the eye signs with a decrease in the clinical activity score from 5 to 2 in 3 months, while the patient had peripheral B-cell depletion. Hyperthyroidism did not improve during the 6 months of B-cell depletion and serum TSH-receptor antibodies (TRAb) levels did not significantly change after RTX therapy. Therefore, the patient underwent total thyroidectomy and few B-cells were found in the thyroid tissue specimens. While the patient eye disease remained stable (clinical activity score ¼ 2), we performed corrective orbital decompression and we found absence of lymphocytes in the orbital tissue specimens. We believe that RTX treatment in Graves' disease may cause amelioration of ophthalmopathy by depleting total lymphocytes population in the orbit. The persistence of Graves' hyperthyroidism suggests that a single cycle of RTX does not result in complete lymphocyte depletion in thyroid tissue and thus no decline in serum TRAb was observed.European Journal of Endocrinology 154 511-517

MANAGEMENT OF ENDOCRINE DISEASE: Rituximab therapy for Graves’ orbitopathy – lessons from randomized control trials

“…Alternatively, RTX has been shown to interfere with the production of inflammatory cytokines and with B cell-driven antigen presentation (7), suggesting that RTX might be indirectly responsible for the depletion of autoreactive T cells also. Lack of T cell infiltration after B cell depletion with RTX has been reported in the orbital tissues of patients with GO (3,10), suggesting that this might be a likely mechanism for its effect. Preliminary studies have suggested that RTX can be effective either as first-line treatment for moderateto-severe GO or as additional therapy in patients resistant to intravenous steroids (6).…”

“…Rituximab (RTX), a chimeric mouse-human monoclonal antibody directed against the CD 20 antigen on B lymphocytes, has been associated with very encouraging responses in treating patients with active moderate-tosevere GO since 2006 (1,2,3). B cell depletion induced by RTX may affect pathogenic TSH-R autoantibody or directly interfere with B cells' antigen-presenting cell function (4,5).…”

THERAPY OF ENDOCRINE DISEASE: Endocrine dilemma: management of Graves’ orbitopathy

“…Following the first report on a successful treatment of one patient with moderate-to-severe GO (107), several noncontrolled studies on the effects of rituximab (RTX) in GO have appeared in the literature (108). More recently, two randomized controlled trials in moderateto-severe GO comparing RTX with placebo (109) and to steroids (110), respectively, have just been published.…”

“…In earlier reports (107,114), RTX has been employed in patients with active steroid-resistant GO. In an open study, RTX has subsequently been used as a first-line therapy in previously untreated patients (115).…”

“…The infusion of 1000 mg twice, with a 2-week interval, has been employed as the standard treatment of RA and other autoimmune diseases. This dose has been initially used in most open studies (115,118) and in case reports (107,114) in patients with GO. Rapid and complete peripheral B-cell depletion following very low-dose (100 mg) RTX was shown in a study by Salvi et al (112).…”