Clinical and immunological changes in patients with active moderate-to-severe Graves̕ orbitopathy treated with very low-dose rituximab

Abstract

Introduction: Glucocorticoids represent the therapy of choice for active and moderate-to-severe Graves' orbitopathy (GO). In some patients, rituximab, a monoclonal antibody against the cluster of differentiation (CD) 20 receptor of B-lymphocytes, can serve as a second-line or an alternative treatment. The effect of very low-dose of rituximab on the clinical activity of GO and corresponding clinical or laboratory changes is reported. Material and methods: Changes of Clinical Activity Score (CAS) for GO, proptosis, levels of thyroid-stimulating hormone receptor antibodies, and depletion of CD19+ and CD20+ B-lymphocytes were determined in ten patients (two men and eight women) with active moderate-to-severe GO treated with a single 100-mg dose of rituximab. Correlations between differences of clinical and laboratory parameters were performed. Results: A significant decrease of CAS was found during subsequent examinations compared to the baseline values. A significant depletion of CD19+ and CD20+ B-lymphocytes was detected after rituximab administration. Differences between follow-up and baseline levels of CD20+ positively correlated with differences in CAS after six (p < 0.05) and 12 months (p < 0.01). Differences in CD19+ levels correlated with differences in CAS after 12 months (p < 0.05) of the treatment. Two patients developed dysthyroid optic neuropathy (DON) requiring orbital decompression. No other rituximab side effects were reported during the whole study duration. Conclusions: A single very low-dose of rituximab appears to be very well tolerated and effective enough to reduce clinical activity in active moderate-to-severe GO patients without impending DON. (Endokrynol Pol 2017; 68 (5): 498-504)

The effects of Rituximab on Graves’orbitopathy: A retrospective study of 14 patients

“…Improvement in CAS score was slightly inferior to some promising outcomes shown in previous case series. 7,12,14,21…”

“…This was endorsed by other authors who suggested that RTX does not have an effect on either thyroid or orbital autoantibody production, while targeting a different way on the compartments of lymphocytic infiltrates of the thyroid and the orbit tissues. 7,9,11,15…”

“…Secondary end points included CAS improved by ⩾ 2 points or inactivation of GO (CAS < 3) at 12 weeks, improvement in each item of the CAS score, decrease of 2 mm or greater in proptosis, improvement in total eye score (TES) calculated by multiplying each class of the NOSPECS system (except class 0) by its grade of severity (0–3). Improvement in eye motility was defined by an improvement in one class or greater in the Gorman score for diplopia 7 between baseline and 12 or 24 weeks. Relapse was defined as a reactivation of GO with a CAS score ⩾ 3 and evaluated from 6 to 12 months after RTX therapy.…”

“…Its immunosuppressive actions are mediated by three mechanisms: reduced activity of B cells as antigen-presenting cells, decreased production of inflammatory cytokines and potential blockage of pathogenic autoantibody generation. 3,6,7 Approved for clinical use in rheumatoid arthritis (RA) and non-Hodgkin's lymphoma, the potential efficacy of RTX has been investigated since 2006 through several uncontrolled studies [7][8][9][10][11][12][13][14][15][16][17][18][19] , and it was assumed that it might become an effective option even as a first-line treatment for GO. 20 In February 2015, two randomised controlled studies, both focused on clinical activity score (CAS), showed contradictory conclusions regarding the efficacy of RTX.…”

Early low‐dose rituximab for active thyroid eye disease: An effective and well‐tolerated treatment

“…This was found to be effective in reducing clinical activity with few adverse side effects . A clinical trial by Salvi et al demonstrated efficacy of a single 500 mg dose, and recent studies have shown 100 mg rituximab to be efficacious in B cell depletion and reducing inflammation …”