[THU0090] SAFE, RAPID-ONSET, AND SUSTAINED BIOLOGICAL ACTIVITY OF IL-1 BETA REGULATING ANTIBODY XOMA 052 IN RESISTANT UVEITIS OF BEHÇET'S DISEASE: PRELIMINARY RESULTS OF A PILOT TRIAL
A. Gül1, B. Artim Esen1, A. Solinger2, L. Giustino2, I. Tugal Tutkun1 1Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey; 2XOMA (US) LLC, Berkeley, CA, United States
Background: Behçet's disease (BD) is a vasculitic multi-system inflammatory disorder of unknown etiology. Increased expression of proinflammatory cytokines, including IL-1β has been considered to play a critical role in the pathogenesis of BD. Uveitis is a major manifestation of BD, and recurrent attacks can cause permanent vision loss in patients resistant to immunosuppressive drugs, azathioprine and/or cyclosporine. XOMA 052 is a recombinant humanized monoclonal antibody. It binds and regulates IL-1β activity, and its administration may produce rapid and sustained reductions in symptoms in IL-1β-mediated systemic inflammatory diseases.
Objectives: To evaluate the safety and PK of XOMA 052 in BD uveitis. Additional assessments were planned as exploratory measures of biologic and clinical activity, particularly of uveitis.
Methods: This pilot open-label study enrolled BD patients who developed a posterior/panuveitis or retinal vasculitis attack despite cyclosporine and/or azathioprine treatment. XOMA 052 was administered as a single 0.3 mg/kg intravenous infusion. Subjects suspended their immunosuppressive treatments and continued to receive ≤10 mg prednisolone without any increase. Patients were followed for safety, PK and uveitis.
Results: Four BD patients (3 male, 1 female) enrolled into the study as of January 2010. No adverse events related to drug treatment were observed so far. Findings of intraocular inflammation were resolved in all patients starting from Day 1 following infusion, and complete resolution of retinal findings and vitreous haze was achieved in 7-14 days despite discontinuation of immunosuppressive drugs and no increase in corticosteroids. First patient presented with a unilateral panuveitis attack causing hypopyon. The hypopyon disappeared and laser flare score decreased from 467 to 45 ph/ms within 24 hr of XOMA 052 infusion. The third patient, who had no light perception in one eye, presented with a very poor vision (counting fingers from 2 meters) in the other eye. Her visual acuity was improved to 20/200 within 24 hr, and to 20/125 in 1 wk on Snellen scale. First 3 patients were in remission on Day 28, and the efficacy sustained up to Day 56 in 2 patients as of January 2010. Retinitis foci were found without any complaint in these 2 patients who reached Day 56 visit, and they received a repeat XOMA 052 infusion according to the amended protocol. The uveitis findings of the fourth patient were resolved in 2 wk. However he developed new retinal foci in the other eye on Day 21, and corticosteroids were increased to 40mg on Day 25 as rescue. Two patients had recurrences of oral aphthous ulcers despite resolution of intraocular inflammation.
Conclusion: Preliminary findings of this pilot trial suggest that IL-1β plays a major role in BD uveitis. Administration of XOMA 052 appears safe, and regulation of IL-1β using XOMA 052 shows a rapid-onset effect for the treatment of intraocular inflammatory attack. This favorable effect of XOMA 052, lasting up to 56 days, was observed despite discontinuation of immunosuppressives as of infusion day and without any increase in corticosteroids.
Disclosure of Interest: A. Gül: None Declared, B. Artim Esen: None Declared, A. Solinger Employee of: XOMA (US) LLC, L. Giustino Employee of: XOMA (US) LLC, I. Tugal Tutkun: None Declared
Citation: Ann Rheum Dis 2010;69(Suppl3):178
Cytokines and inflammatory mediators