A Phase I/II Dose-Ranging, Randomized Clinical Trial of Abatacept (Orencia) in the Treatment of Refractory Non-Infectious Uveitis: Preliminary Results

Abstract

Purpose: To ascertain the safety and effectiveness of abatacept (Orencia, Bristol-Myers-Squibb), a recombinant fusion protein which inhibits T-cell costimulation by binding CTLA-4 antigen, for the treatment of refractory non-infectious uveitis.

Methods: We received IRB and FDA approval to recruit 20 patients into a 24 week open-label study of the effectiveness of abatacept 10 mg/kg infusions for the treatment of refractory uveitis, followed by randomization to either 5 or 10 mg doses for another 80 weeks. Patients characterized as refractory had failed treatment with corticosteroids and at least one standard immunosuppressive. Initial treatment outcome was ascertained at 24 weeks after study initiation by a composite clinical endpoint comprised of improvement in visual acuity, intraocular inflammation, ability to taper corticosteroids or immunosuppressives, and fluorescein angiography or ocular coherence tomography. Patients who meet criteria for clinical success at 24 weeks will be allowed to complete up to two years of therapy at the randomized 5 or 10 mg/kg dose, with repeat outcome assessment at weeks 52, 76, and 104.

Results: Study recruitment began in April 2012 and three subjects have enrolled thus far, two of whom have reached the 24 week timepoint at this writing. Both of these patients met the composite endpoint for clinical success at week 24. One patient had improvement in vision and was able to taper off corticosteroids at week 24, but subsequently flared symptomatically at week 28 and left the study. One patient achieved control of active inflammation and was able to taper off corticosteroids at week 24. The third patient has demonstrated preliminary benefit at week 8, having reduced prednisone from 30 to 15 mg daily and with improvement in inflammation as well. Significant adverse effects have included upper respiratory infection and fungal skin rash in the second patient, both which were treated with antimicrobials and neither of which required study discontinuation.

Conclusions: Our preliminary results suggest that abatacept may be effective for the treatment of refractory uveitis. No treatment-limiting toxicity was noted. Enrollment is ongoing and further study is required to define patient populations who may derive the most benefit from abatacept therapy.

Keywords: 746 uveitis-clinical/animal model • 466 clinical (human) or epidemiologic studies: treatment/prevention assessment/controlled clinical trials • 555 immunomodulation/immunoregulation