Rituximab in the Treatment of Refractory Scleritis and Non-Infectious Orbital Inflammation: Interim Results from a Phase I/II Prospective, Randomized, Dose-Ranging Pilot Study

Abstract

Purpose: : To determine the safety and efficacy of rituximab (Rituxan, Genentech), a chimeric monoclonal antibody against the CD20 molecule expressed on B lymphocytes, in the treatment of scleritis and orbital inflammatory disease (OID).

Methods: : Patients with non-infectious scleritis and OID were enrolled in our prospective FDA- and IRB-approved study. Patients were randomized to receive two rituximab infusions at study days 1 and 15 at either 500 mg or 1000 mg doses. Primary endpoints of the study were ability to taper corticosteroids (CS), improvement in patient quality of life assessment, and physician assessment of disease activity. The protocol permitted retreatment between 6 and 12 months after initial infusion. The protocol duration is 48 weeks, with monthly safety assessment and outcome assessment at 24 and 48 weeks.

Results: : 15 patients have currently been enrolled; 7 subjects each with scleritis and OID and one patient with active disease at enrollment in both categories. Among primary outcome variables, 2 scleritis and 2 OID patients accomplished steroid tapering, with all but one other remaining on stable doses of steroid and immunosuppression. Patient and physician global health assessment improved in 4/8 and 6/8 scleritis patients, respectively, and in 4/8 and 8/8 OID patients. Vision was stable or improved in all patients excepting one with scleritis, and pain was improved in 5/8 and 6/8 scleritis and OID patients. Seven of 9 patients treated initially had inflammatory exacerbations shortly after infusion; with brief use of adjunctive corticosteroids, we have had no similar occurrences with the last six patients enrolled. No treatment limiting side effects were noted. Six patients have been reinfused thus far (4 scleritis and 2 OID, range; 7-11 months) for disease recurrence; none have suffered peri-infusional exacerbations.

Conclusions: : Rituximab appears to be safe in the treatment of ocular and orbital inflammation, and may have benefit in selected cases. Transient exacerbation of ocular, orbital, or systemic inflammatory disease may occur and may be successfully managed with adjunctive corticosteroids. Further follow-up and study is required to clarify optimal dosing schedules and patient subsets that will benefit most from rituximab treatment for scleritis or orbital inflammatory disease.

Clinical Trial: : www.clinicaltrials.gov NCT00415506

Keywords: autoimmune disease • clinical (human) or epidemiologic studies: treatment/prevention assessment/controlled clinical trials • sclera