Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.
Safe, Rapid-Onset, and Sustained Biological Activity of IL-1 Regulating Antibody XOMA 052 in Resistant Uveitis of Behet's Disease: Results of a Pilot Trial.
Gul2, Ahmet, Artim-Esen2, Bahar, Solinger4, Alan M., Giustino4, Linda, Dinarello3, Charles, Tugal-Tutkun1, Ilknur M.
Behçet's disease (BD) is a vasculitic multi-system inflammatory disorder of unknown etiology. Increased expression of proinflammatory cytokines, including IL-1b 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. XOMA 052 is a recombinant humanized monoclonal antibody. It binds and regulates IL-1b activity, and its administration may produce rapid and sustained reductions in symptoms in IL-1b-mediated systemic inflammatory diseases.
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.
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 maintained prednisolone at <=10 mg/day (6 patients) or 20mg/day (one patient) without any increase.
Seven patients enrolled in and completed the study period of 98 days. No adverse events related to XOMA 052 were observed. Preliminary PK analysis of the first 6 patients showed a clearance of 2.6 mL/day/kg, a beta half-life 26.7 days and a volume of distribution for the central compartment of 54 mL/kg. Intraocular inflammation started to resolve in all patients on Day 1, and complete resolution of retinal findings and vitreous haze was achieved in 4 to 21 days. Five patients were in remission on Day 28, and one was still in remission at Day 98 with a single infusion. One of the patients received increased doses of prednisolone for new retinitis attack in the contralateral eye on Day 25, and other received intravitreal methyl prednisolone for cystoid macular edema (CME) on Day 22 as rescue. After a protocol amendment, five patients received a second infusion for new retinal infiltrates between Day 49 and Day 95, and one patient for CME in the contralateral eye on Day 29. All patients responded to the repeat infusions. Five patients, who had recurrent oral ulcers and folliculitis before the trial, experienced recurrences of those manifestations despite resolution of intraocular inflammation.
Findings of this pilot trial suggest that IL-1b plays a major role in BD uveitis. Administration of XOMA 052 appears safe, and regulation of IL-1b using XOMA 052 shows a rapid-onset effect for the treatment of intraocular inflammatory attack. This favorable effect of XOMA 052 was observed despite discontinuation of immunosuppressives as of infusion day and without any increase in corticosteroids. Results of this pilot trial warrant additional studies. Responses of non-ocular disease manifestations to XOMA 052 need also be studied further.
To cite this abstract, please use the following information:
Gul, Ahmet, Artim-Esen, Bahar, Solinger, Alan M., Giustino, Linda, Dinarello, Charles, Tugal-Tutkun, Ilknur M.; Safe, Rapid-Onset, and Sustained Biological Activity of IL-1 Regulating Antibody XOMA 052 in Resistant Uveitis of Behet's Disease: Results of a Pilot Trial. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1308