Soft tissue involvement was graded according to the Color Atlas, available at www.eugogo.eu (15). Study design The study was designed to include 60 patients, 30 randomized to receive ivMP and 30 RTX according to the schedule shown in Tolfenamic acid Figure 1. was never observed in RTX patients but was observed in five after ivMP. Patients treated with RTX scored better motility at 52 weeks in both the right (= .014) and the left eye (= .026). Overall rehabilitative surgical procedures carried out during follow-up (at 76 wk) were 12 in 16 ivMP patients and 5 in 15 RTX patients (= .049). Conclusions: The results of this trial confirm preliminary reports on a better therapeutic outcome of RTX in active moderate to severe GO, when compared with ivMP, even after a lower RTX dose. The better eye motility outcome, visual functioning of the quality of life assessment, and the reduced number of surgical procedures in patients after RTX seem to suggest a disease-modifying effect of the drug. Graves’ orbitopathy (GO), the most frequent extrathyroidal manifestation of Graves’ disease (GD), is a rare disorder that occurs in approximately 2 per 10 000 population per year and in about 25%C40% of patients with GD in a clinically relevant form (1). GO pathogenesis is based on immunological cross-reactivity between thyroid and orbital tissue (2) in which the putative autoantigens, and the mechanisms involved, are still unclear (3). Glucocorticoids have been the therapy of choice Tolfenamic acid in active moderate to severe GO, and treatment effectiveness has been reported in as many as 75%C80% of patients (4, 5). In approximately 30% of patients, this therapy is either ineffective or does not prevent disease reactivation (6) and progression toward severe degrees of muscle dysfunction or even dysthyroid optic neuropathy. A very recent multicenter clinical trial of European Group on Graves’ Orbitopathy (4) has suggested a treatment schedule with 830 mg iv methylprednisolone (ivMP) administered weekly for 6 weeks followed by 415 mg for another 6 weeks for a cumulative dose of 7.47 g. B cell depletion with rituximab (RTX), a chimeric mouse-human monoclonal antibody directed against the CD 20 antigen on B lymphocytes has been reported to be effective for the treatment of active moderate to severe GO since 2006 (7, 8). RTX may affect pathogenic TSH receptor (TSH-R) autoantibody by directly targeting B cells in their antigen-presenting cell function (9). Several noncontrolled studies have shown that RTX is potentially useful in the treatment of GO, in particular for the control of the early active, inflammatory phase of the disease (10). Several questions need to be answered before we can consider using RTX in GO. Does RTX modify the course of GO? Given the potentially serious side effects of systemic immunosuppression induced by RTX, can we trustfully use this treatment in patients who are affected by a progressive and often disfiguring disease but also known to be self-limiting and Tolfenamic acid with consequences that Tolfenamic acid can also be satisfactorily corrected by surgery? For these reasons, we have conducted a randomized, double-blind, controlled trial in which patients with active moderate to severe GO were treated with either RTX or ivMP. Materials and Methods Patients The study included adult Caucasian, Asian, Hispanic, or Tolfenamic acid black males and Rabbit Polyclonal to Keratin 17 females, aged 18C75 years, smokers and nonsmokers, euthyroid for at least 6C8 weeks (based on the measurement of normal free thyroid hormone concentrations), affected with active GO, defined by a clinical activity score (CAS) of 4 of 10 or greater or 3 of 7 or greater (11), of moderate to severe degree, as defined by the NOSPECS (no signs or symptoms; only.