Rituximab Treatment as Second-line Therapy in Glucocorticoid Non-responsive Graves' Orbitopathy: a Non-randomized, Controlled, Interventional Study.

Objective: In moderate-to-severe Graves' orbitopathy (GO), rituximab is recommended as second-line therapy in patients non-responsive to intravenous glucocorticoids. We aimed to evaluate rituximab as early second-line therapy, as data is scarce and contradictory.

Methods: In this non-randomized, controlled, interventional study, patients with GO started on intravenous glucocorticoids. After 4 weeks, patients with <2 points improvement in clinical activity score (CAS) were switched to rituximab [Non-Responders Rituximab (NR-RTX) group] and were compared to the remaining patients who continued with intravenous glucocorticoids for 12 weeks [Responders-Glucocorticoid (R-GC) group]. A retrospective group of non-responsive patients who were provided regular care with intravenous glucocorticoids for 12 weeks was used as control [Non-Responders-Regular Care (NR-RC) group]. Background data and CAS were recorded for all groups at 0, 4, 12, 18, and 68 weeks. Quality of life (QoL) and safety data were collected from the NR-RTX and R-GC groups.

Results: The NR-RTX group (n=12) was similar to the others at baseline except for a 1-point lower median CAS compared to the NR-RC group (n=12) (p=0.03), and for having twice as many men compared to the R-GC group (n=13) (p=0.03). At 4 weeks, a linear mixed model indicated that the R-GC group had a 1.21-point (95%CI: -2.40 to -0.02) lower value for CAS compared to the NR-RTX group. CAS for all groups converged over time. Similar models for QoL revealed no treatment or time effects.

Conclusion: Switch to RTX early in the treatment course did not result in better CAS or QoL, compared to continuous intravenous glucocorticoids.