TY - JOUR
T1 - A double-masked, randomized study to investigate the safety and efficacy of daclizumab to treat the ocular complications related to Behçet's disease
AU - Buggage, Ronald R.
AU - Levy-Clarke, Grace
AU - Sen, Hatice N.
AU - Ursea, Roxana
AU - Srivastava, Sunil K.
AU - Suhler, Eric B.
AU - Altemare, Chandra
AU - Velez, Gisela
AU - Ragheb, Jack
AU - Chan, Chi Chao
AU - Nussenblatt, Robert B.
AU - Bamji, Alison T.
AU - Sran, Puspha
AU - Waldmann, Thomas
AU - Thompson, Darby J.S.
N1 - Funding Information:
Acknowledgement: This research was supported in part by the Intramural Research Program of the National Eye Institute of the National Institutes of Health. Correspondence and reprint requests to: Grace Levy-Clarke, M.D., National Eye Institute, National Institutes of Health, 10 Center Drive, Bldg 10, Room 10N112, Bethesda, MD, 20892-1857, USA. e-mail: Clarkeg@nei.nih.gov
PY - 2007/3
Y1 - 2007/3
N2 - Purpose: To investigate the safety and efficacy of daclizumab (Zenapax, humanized anti-Tac, HAT) in controlling the ocular manifestations of Behçet's disease. Design: Randomized, placebo-controlled, double-masked clinical trial. Participants: Seventeen participants with Behçet's disease experiencing at least two prior ocular attacks and requiring treatment with immunosuppressive agents for the ocular complications of Behçet's disease. Methods: Participants received either intravenous placebo or daclizumab (1 mg/kg) infusions every two weeks for six weeks, then every four weeks while continuing their standard immunosuppressive regimens. If clinically indicated, tapering of the standard immunosuppressive medications was allowed after six months of study enrollment. Complete ocular and physical examinations and an adverse event assessment were performed at baseline and prior to each study infusion. Main Outcome Measures: Primary safety endpoints were the development of a life-threatening complication or a severe opportunistic infection. Primary efficacy outcomes were the number of ocular attacks and an assessment of systemic immunosuppressive medications required during the study, including the ability to taper concomitant immunosuppressive therapy. Results: Nine participants randomized to daclizumab and eight to placebo were followed monthly. Follow-up ranged from one to 34 months, with a median follow-up of 15 months. Two participants randomized to daclizumab discontinued study therapy prior to the end of the study for personal reasons. No participant experienced a safety endpoint, and visual acuity remained stable in all participants during the course of the study. Ten participants (six daclizumab, four placebo) experienced ocular attacks requiring therapy. The median ocular attack rate during the study was greater in the daclizumab arm than the placebo arm (median 1.27 vs. 0.17 attacks/year, respectively). Participants in the placebo arm also experienced a greater reduction in the immunosuppressive medication score compared to participants receiving daclizumab (median -4.0 vs. -1.0, respectively). Conclusions: The observed results in the placebo group demonstrate that careful follow-up and treatment with standard combination immunosuppressive therapy can be effective for the management of the ocular complications of Behçet's disease. In our small study, there was no suggestion that daclizumab was beneficial in comparison with placebo. However, the low observed attack rate limited our ability to make a definitive treatment group comparison.
AB - Purpose: To investigate the safety and efficacy of daclizumab (Zenapax, humanized anti-Tac, HAT) in controlling the ocular manifestations of Behçet's disease. Design: Randomized, placebo-controlled, double-masked clinical trial. Participants: Seventeen participants with Behçet's disease experiencing at least two prior ocular attacks and requiring treatment with immunosuppressive agents for the ocular complications of Behçet's disease. Methods: Participants received either intravenous placebo or daclizumab (1 mg/kg) infusions every two weeks for six weeks, then every four weeks while continuing their standard immunosuppressive regimens. If clinically indicated, tapering of the standard immunosuppressive medications was allowed after six months of study enrollment. Complete ocular and physical examinations and an adverse event assessment were performed at baseline and prior to each study infusion. Main Outcome Measures: Primary safety endpoints were the development of a life-threatening complication or a severe opportunistic infection. Primary efficacy outcomes were the number of ocular attacks and an assessment of systemic immunosuppressive medications required during the study, including the ability to taper concomitant immunosuppressive therapy. Results: Nine participants randomized to daclizumab and eight to placebo were followed monthly. Follow-up ranged from one to 34 months, with a median follow-up of 15 months. Two participants randomized to daclizumab discontinued study therapy prior to the end of the study for personal reasons. No participant experienced a safety endpoint, and visual acuity remained stable in all participants during the course of the study. Ten participants (six daclizumab, four placebo) experienced ocular attacks requiring therapy. The median ocular attack rate during the study was greater in the daclizumab arm than the placebo arm (median 1.27 vs. 0.17 attacks/year, respectively). Participants in the placebo arm also experienced a greater reduction in the immunosuppressive medication score compared to participants receiving daclizumab (median -4.0 vs. -1.0, respectively). Conclusions: The observed results in the placebo group demonstrate that careful follow-up and treatment with standard combination immunosuppressive therapy can be effective for the management of the ocular complications of Behçet's disease. In our small study, there was no suggestion that daclizumab was beneficial in comparison with placebo. However, the low observed attack rate limited our ability to make a definitive treatment group comparison.
KW - Behcet's disease
KW - Clinical trial
KW - Daclizumab
KW - Uveitis
UR - http://www.scopus.com/inward/record.url?scp=34250177933&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34250177933&partnerID=8YFLogxK
U2 - 10.1080/09273940701299370
DO - 10.1080/09273940701299370
M3 - Article
C2 - 17558830
AN - SCOPUS:34250177933
SN - 0927-3948
VL - 15
SP - 63
EP - 70
JO - Ocular Immunology and Inflammation
JF - Ocular Immunology and Inflammation
IS - 2
ER -