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

Abstract

Purpose: Management of Graves’ ophthalmopathy remains challenging. Over the last decade, previous studies have shown promising results for Rituximab in the treatment of Graves’ ophthalmopathy. We present the response of 14 individuals with active moderate-to-severe Graves’ ophthalmopathy to Rituximab, representing one of the largest retrospective case series reported to date. Methods: Rituximab was administered intravenously, 1000 mg twice at a 2-week interval. The primary end point was a clinical activity score reduction (improvement by ⩾ 2 points or disease inactivation: clinical activity score < 3) at 24 weeks. Secondary end points included clinical activity score improved by ⩾ 2 points or inactivation of Graves’ ophthalmopathy at 12 weeks, improvement in each item of the clinical activity score, in proptosis, in severity disease by the total eye score and in diplopia according to the Gorman score. Results: A limited improvement in clinical activity score was observed (median improvement at 24 weeks by 1 point, p = 0.002, (5/14 patients, 35.7%). Disease inactivation occurred in 50% of patients (7/14 patients). At 12 weeks, clinical activity score improved by ⩾ 2 points in 2/14 patients (14.3%) and inactivation of Graves’ ophthalmopathy occurred in four patients (28.6%). Improvement in proptosis and total eye score was observed in 3/9 patients (33%) and in 4/14 patients (28.6%) at 24 weeks, respectively. Only one patient experienced moderate adverse event. Conclusion: Rituximab is a well-tolerated treatment with a good safety profile, but offered limited and partial improvement for active moderate-to-severe Graves’ ophthalmopathy with a long duration of disease.

Overview of Graves Ophthalmopathy Literature From 1999 to 2019: Bibliometric Analysis

“…There has been substantial research into the effects of rituximab in Graves ophthalmopathy therapy, and many clinical trials have demonstrated that rituximab has therapeutic effects, with limited side effects [ 29 ]. As an anti-CD20 monoclonal antibody, rituximab can inhibit B cell activation and decrease inflammatory cytokine secretion [ 29 ].…”

“…There has been substantial research into the effects of rituximab in Graves ophthalmopathy therapy, and many clinical trials have demonstrated that rituximab has therapeutic effects, with limited side effects [ 29 ]. As an anti-CD20 monoclonal antibody, rituximab can inhibit B cell activation and decrease inflammatory cytokine secretion [ 29 ]. As modern therapy strategies for Graves ophthalmopathy are concerned with individualization and precision, immune-based therapies have become increasingly popular, and numerous antibodies have been applied as new therapies.…”

“…As modern therapy strategies for Graves ophthalmopathy are concerned with individualization and precision, immune-based therapies have become increasingly popular, and numerous antibodies have been applied as new therapies. As one such antibody therapy method, rituximab has been researched in randomized controlled trials and fundamental research [ 29 - 32 ]. Additional research into this burst keyword will provide more detailed data in the coming years.…”

Novel Approaches for Immunosuppression in Graves’ Hyperthyroidism and Associated Orbitopathy

“…In fact, B cell infiltration was absent in some immunohistochemically analyzed GO orbital tissues [36], and this might explain why some patients failed to respond to RTX. A recent French retrospective series also found limited efficacy of RTX in steroid-refractory active moderate-to-severe GO with long disease duration (median 26 months) [64]. A few patients in the RTX groups of both randomized trials developed a transient increase in proptosis or visual loss, and 2 patients even developed frank DON.…”

Cytokines as Targets of Novel Therapies for Graves’ Ophthalmopathy

“…Furthermore, 14 patients with active and moderate-to-severe GO, of whom 11 CS-refractory, were administered with ivRTX (1000 mg twice with a 2-week interval), reporting that RTX was well-tolerated (49). A modest amelioration of CAS, and disease inactivation in half of the patients, were reported.…”