A double-masked, randomized study to investigate the safety and efficacy of daclizumab to treat the ocular complications related to Behçet's disease

Ronald R. Buggage, Grace Levy-Clarke, Hatice N. Sen, Roxana Ursea, Sunil K. Srivastava, Eric Suhler, Chandra Altemare, Gisela Velez, Jack Ragheb, Chi Chao Chan, Robert B. Nussenblatt, Alison T. Bamji, Puspha Sran, Thomas Waldmann, Darby J S Thompson

Research output: Contribution to journalArticle

84 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)63-70
Number of pages8
JournalOcular Immunology and Inflammation
Volume15
Issue number2
DOIs
StatePublished - Mar 2007
Externally publishedYes

Fingerprint

Double-Blind Method
Immunosuppressive Agents
Safety
Placebos
Aptitude
Therapeutics
Eye Manifestations
daclizumab
Opportunistic Infections
Visual Acuity
Physical Examination
Outcome Assessment (Health Care)
Clinical Trials

Keywords

  • Behcet's disease
  • Clinical trial
  • Daclizumab
  • Uveitis

ASJC Scopus subject areas

  • Ophthalmology
  • Immunology and Allergy

Cite this

A double-masked, randomized study to investigate the safety and efficacy of daclizumab to treat the ocular complications related to Behçet's disease. / Buggage, Ronald R.; Levy-Clarke, Grace; Sen, Hatice N.; Ursea, Roxana; Srivastava, Sunil K.; Suhler, Eric; Altemare, Chandra; Velez, Gisela; Ragheb, Jack; Chan, Chi Chao; Nussenblatt, Robert B.; Bamji, Alison T.; Sran, Puspha; Waldmann, Thomas; Thompson, Darby J S.

In: Ocular Immunology and Inflammation, Vol. 15, No. 2, 03.2007, p. 63-70.

Research output: Contribution to journalArticle

Buggage, RR, Levy-Clarke, G, Sen, HN, Ursea, R, Srivastava, SK, Suhler, E, Altemare, C, Velez, G, Ragheb, J, Chan, CC, Nussenblatt, RB, Bamji, AT, Sran, P, Waldmann, T & Thompson, DJS 2007, 'A double-masked, randomized study to investigate the safety and efficacy of daclizumab to treat the ocular complications related to Behçet's disease', Ocular Immunology and Inflammation, vol. 15, no. 2, pp. 63-70. https://doi.org/10.1080/09273940701299370
Buggage, Ronald R. ; Levy-Clarke, Grace ; Sen, Hatice N. ; Ursea, Roxana ; Srivastava, Sunil K. ; Suhler, Eric ; Altemare, Chandra ; Velez, Gisela ; Ragheb, Jack ; Chan, Chi Chao ; Nussenblatt, Robert B. ; Bamji, Alison T. ; Sran, Puspha ; Waldmann, Thomas ; Thompson, Darby J S. / A double-masked, randomized study to investigate the safety and efficacy of daclizumab to treat the ocular complications related to Behçet's disease. In: Ocular Immunology and Inflammation. 2007 ; Vol. 15, No. 2. pp. 63-70.
@article{e396d496fc5f444dbf61cfbce3d88d13,
title = "A double-masked, randomized study to investigate the safety and efficacy of daclizumab to treat the ocular complications related to Beh{\cc}et's disease",
abstract = "Purpose: To investigate the safety and efficacy of daclizumab (Zenapax, humanized anti-Tac, HAT) in controlling the ocular manifestations of Beh{\cc}et's disease. Design: Randomized, placebo-controlled, double-masked clinical trial. Participants: Seventeen participants with Beh{\cc}et's disease experiencing at least two prior ocular attacks and requiring treatment with immunosuppressive agents for the ocular complications of Beh{\cc}et'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 Beh{\cc}et'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.",
keywords = "Behcet's disease, Clinical trial, Daclizumab, Uveitis",
author = "Buggage, {Ronald R.} and Grace Levy-Clarke and Sen, {Hatice N.} and Roxana Ursea and Srivastava, {Sunil K.} and Eric Suhler and Chandra Altemare and Gisela Velez and Jack Ragheb and Chan, {Chi Chao} and Nussenblatt, {Robert B.} and Bamji, {Alison T.} and Puspha Sran and Thomas Waldmann and Thompson, {Darby J S}",
year = "2007",
month = "3",
doi = "10.1080/09273940701299370",
language = "English (US)",
volume = "15",
pages = "63--70",
journal = "Ocular Immunology and Inflammation",
issn = "0927-3948",
publisher = "Informa Healthcare",
number = "2",

}

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

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

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

VL - 15

SP - 63

EP - 70

JO - Ocular Immunology and Inflammation

JF - Ocular Immunology and Inflammation

SN - 0927-3948

IS - 2

ER -