Safety and Efficacy of Adalimumab in Patients with Noninfectious Uveitis in an Ongoing Open-Label Study

VISUAL III

Eric Suhler, Alfredo Adán, Antoine P. Brézin, Eric Fortin, Hiroshi Goto, Glenn J. Jaffe, Toshikatsu Kaburaki, Michal Kramer, Lyndell L. Lim, Cristina Muccioli, Quan Dong Nguyen, Joachim Van Calster, Luca Cimino, Martina Kron, Alexandra P. Song, Jianzhong Liu, Sophia Pathai, Anne Camez, Ariel Schlaen, Mirjam E.J. van Velthoven & 4 others Albert T. Vitale, Manfred Zierhut, Samir Tari, Andrew D. Dick

Research output: Contribution to journalArticle

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Abstract

Purpose: To evaluate safety and efficacy of adalimumab in patients with noninfectious intermediate, posterior, or panuveitis. Design: Phase 3, open-label, multicenter clinical trial extension (VISUAL III). Participants: Adults meeting treatment failure (TF) criteria or who completed VISUAL I or II (phase 3, randomized, double-masked, placebo-controlled) without TF. Methods: Patients received adalimumab 40 mg every other week. Interim follow-up data were described from VISUAL III weeks 0 through 78. Main Outcome Measures: Disease quiescence, steroid-free quiescence, active inflammatory chorioretinal/retinal vascular lesions, anterior chamber cell grade, vitreous haze grade, best-corrected visual acuity (BCVA), and corticosteroid dose. Binary data were reported using nonresponder imputation (NRI), continuous data using last observation carried forward and as-observed analysis, and corticosteroid dose using observed-case analysis. Adverse events (AEs) were reported from first adalimumab dose in VISUAL III through interim cutoff. Results: Of 424 patients enrolled, 371 were included in intent-to-treat analysis. At study entry, 242 of 371 (65%) patients had active uveitis; 60% (145/242, NRI) achieved quiescence at week 78, and 66% (95/143, as-observed) of those were corticosteroid free. At study entry, 129 of 371 (35%) patients had inactive uveitis; 74% (96/129, NRI) achieved quiescence at week 78, and 93% (89/96, as-observed) of those were corticosteroid free. Inflammatory lesions, anterior chamber grade, and vitreous haze grade showed initial improvement followed by decline in patients with active uveitis and remained stable in patients with inactive uveitis. BCVA improved in patients with active uveitis from weeks 0 to 78 (0.27 to 0.14 logMAR; left and right eyes; as-observed) and remained stable in patients with inactive uveitis. Mean corticosteroid dose decreased from 13.6 mg/day (week 0) to 2.6 mg/day (week 78) in patients with active uveitis and remained stable in those with inactive uveitis (1.5-1.2 mg/day). AEs (424 events/100 patient-years) and serious AEs (16.5 events/100 patient-years) were comparable with previous VISUAL trials. Conclusions: Patients with active uveitis at study entry who received adalimumab therapy were likely to achieve quiescence, improve visual acuity, and reduce their daily uveitis-related systemic corticosteroid use. Most patients with inactive uveitis at study entry sustained quiescence without a systemic corticosteroid dose increase. No new safety signals were identified.

Original languageEnglish (US)
JournalOphthalmology
DOIs
StateAccepted/In press - Jan 1 2018

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Uveitis
Safety
Adrenal Cortex Hormones
Visual Acuity
Anterior Chamber
Adalimumab
Treatment Failure
Panuveitis
Retinal Vessels
Multicenter Studies

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Safety and Efficacy of Adalimumab in Patients with Noninfectious Uveitis in an Ongoing Open-Label Study : VISUAL III. / Suhler, Eric; Adán, Alfredo; Brézin, Antoine P.; Fortin, Eric; Goto, Hiroshi; Jaffe, Glenn J.; Kaburaki, Toshikatsu; Kramer, Michal; Lim, Lyndell L.; Muccioli, Cristina; Nguyen, Quan Dong; Van Calster, Joachim; Cimino, Luca; Kron, Martina; Song, Alexandra P.; Liu, Jianzhong; Pathai, Sophia; Camez, Anne; Schlaen, Ariel; van Velthoven, Mirjam E.J.; Vitale, Albert T.; Zierhut, Manfred; Tari, Samir; Dick, Andrew D.

In: Ophthalmology, 01.01.2018.

Research output: Contribution to journalArticle

Suhler, E, Adán, A, Brézin, AP, Fortin, E, Goto, H, Jaffe, GJ, Kaburaki, T, Kramer, M, Lim, LL, Muccioli, C, Nguyen, QD, Van Calster, J, Cimino, L, Kron, M, Song, AP, Liu, J, Pathai, S, Camez, A, Schlaen, A, van Velthoven, MEJ, Vitale, AT, Zierhut, M, Tari, S & Dick, AD 2018, 'Safety and Efficacy of Adalimumab in Patients with Noninfectious Uveitis in an Ongoing Open-Label Study: VISUAL III', Ophthalmology. https://doi.org/10.1016/j.ophtha.2017.12.039
Suhler, Eric ; Adán, Alfredo ; Brézin, Antoine P. ; Fortin, Eric ; Goto, Hiroshi ; Jaffe, Glenn J. ; Kaburaki, Toshikatsu ; Kramer, Michal ; Lim, Lyndell L. ; Muccioli, Cristina ; Nguyen, Quan Dong ; Van Calster, Joachim ; Cimino, Luca ; Kron, Martina ; Song, Alexandra P. ; Liu, Jianzhong ; Pathai, Sophia ; Camez, Anne ; Schlaen, Ariel ; van Velthoven, Mirjam E.J. ; Vitale, Albert T. ; Zierhut, Manfred ; Tari, Samir ; Dick, Andrew D. / Safety and Efficacy of Adalimumab in Patients with Noninfectious Uveitis in an Ongoing Open-Label Study : VISUAL III. In: Ophthalmology. 2018.
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title = "Safety and Efficacy of Adalimumab in Patients with Noninfectious Uveitis in an Ongoing Open-Label Study: VISUAL III",
abstract = "Purpose: To evaluate safety and efficacy of adalimumab in patients with noninfectious intermediate, posterior, or panuveitis. Design: Phase 3, open-label, multicenter clinical trial extension (VISUAL III). Participants: Adults meeting treatment failure (TF) criteria or who completed VISUAL I or II (phase 3, randomized, double-masked, placebo-controlled) without TF. Methods: Patients received adalimumab 40 mg every other week. Interim follow-up data were described from VISUAL III weeks 0 through 78. Main Outcome Measures: Disease quiescence, steroid-free quiescence, active inflammatory chorioretinal/retinal vascular lesions, anterior chamber cell grade, vitreous haze grade, best-corrected visual acuity (BCVA), and corticosteroid dose. Binary data were reported using nonresponder imputation (NRI), continuous data using last observation carried forward and as-observed analysis, and corticosteroid dose using observed-case analysis. Adverse events (AEs) were reported from first adalimumab dose in VISUAL III through interim cutoff. Results: Of 424 patients enrolled, 371 were included in intent-to-treat analysis. At study entry, 242 of 371 (65{\%}) patients had active uveitis; 60{\%} (145/242, NRI) achieved quiescence at week 78, and 66{\%} (95/143, as-observed) of those were corticosteroid free. At study entry, 129 of 371 (35{\%}) patients had inactive uveitis; 74{\%} (96/129, NRI) achieved quiescence at week 78, and 93{\%} (89/96, as-observed) of those were corticosteroid free. Inflammatory lesions, anterior chamber grade, and vitreous haze grade showed initial improvement followed by decline in patients with active uveitis and remained stable in patients with inactive uveitis. BCVA improved in patients with active uveitis from weeks 0 to 78 (0.27 to 0.14 logMAR; left and right eyes; as-observed) and remained stable in patients with inactive uveitis. Mean corticosteroid dose decreased from 13.6 mg/day (week 0) to 2.6 mg/day (week 78) in patients with active uveitis and remained stable in those with inactive uveitis (1.5-1.2 mg/day). AEs (424 events/100 patient-years) and serious AEs (16.5 events/100 patient-years) were comparable with previous VISUAL trials. Conclusions: Patients with active uveitis at study entry who received adalimumab therapy were likely to achieve quiescence, improve visual acuity, and reduce their daily uveitis-related systemic corticosteroid use. Most patients with inactive uveitis at study entry sustained quiescence without a systemic corticosteroid dose increase. No new safety signals were identified.",
author = "Eric Suhler and Alfredo Ad{\'a}n and Br{\'e}zin, {Antoine P.} and Eric Fortin and Hiroshi Goto and Jaffe, {Glenn J.} and Toshikatsu Kaburaki and Michal Kramer and Lim, {Lyndell L.} and Cristina Muccioli and Nguyen, {Quan Dong} and {Van Calster}, Joachim and Luca Cimino and Martina Kron and Song, {Alexandra P.} and Jianzhong Liu and Sophia Pathai and Anne Camez and Ariel Schlaen and {van Velthoven}, {Mirjam E.J.} and Vitale, {Albert T.} and Manfred Zierhut and Samir Tari and Dick, {Andrew D.}",
year = "2018",
month = "1",
day = "1",
doi = "10.1016/j.ophtha.2017.12.039",
language = "English (US)",
journal = "Ophthalmology",
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TY - JOUR

T1 - Safety and Efficacy of Adalimumab in Patients with Noninfectious Uveitis in an Ongoing Open-Label Study

T2 - VISUAL III

AU - Suhler, Eric

AU - Adán, Alfredo

AU - Brézin, Antoine P.

AU - Fortin, Eric

AU - Goto, Hiroshi

AU - Jaffe, Glenn J.

AU - Kaburaki, Toshikatsu

AU - Kramer, Michal

AU - Lim, Lyndell L.

AU - Muccioli, Cristina

AU - Nguyen, Quan Dong

AU - Van Calster, Joachim

AU - Cimino, Luca

AU - Kron, Martina

AU - Song, Alexandra P.

AU - Liu, Jianzhong

AU - Pathai, Sophia

AU - Camez, Anne

AU - Schlaen, Ariel

AU - van Velthoven, Mirjam E.J.

AU - Vitale, Albert T.

AU - Zierhut, Manfred

AU - Tari, Samir

AU - Dick, Andrew D.

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Purpose: To evaluate safety and efficacy of adalimumab in patients with noninfectious intermediate, posterior, or panuveitis. Design: Phase 3, open-label, multicenter clinical trial extension (VISUAL III). Participants: Adults meeting treatment failure (TF) criteria or who completed VISUAL I or II (phase 3, randomized, double-masked, placebo-controlled) without TF. Methods: Patients received adalimumab 40 mg every other week. Interim follow-up data were described from VISUAL III weeks 0 through 78. Main Outcome Measures: Disease quiescence, steroid-free quiescence, active inflammatory chorioretinal/retinal vascular lesions, anterior chamber cell grade, vitreous haze grade, best-corrected visual acuity (BCVA), and corticosteroid dose. Binary data were reported using nonresponder imputation (NRI), continuous data using last observation carried forward and as-observed analysis, and corticosteroid dose using observed-case analysis. Adverse events (AEs) were reported from first adalimumab dose in VISUAL III through interim cutoff. Results: Of 424 patients enrolled, 371 were included in intent-to-treat analysis. At study entry, 242 of 371 (65%) patients had active uveitis; 60% (145/242, NRI) achieved quiescence at week 78, and 66% (95/143, as-observed) of those were corticosteroid free. At study entry, 129 of 371 (35%) patients had inactive uveitis; 74% (96/129, NRI) achieved quiescence at week 78, and 93% (89/96, as-observed) of those were corticosteroid free. Inflammatory lesions, anterior chamber grade, and vitreous haze grade showed initial improvement followed by decline in patients with active uveitis and remained stable in patients with inactive uveitis. BCVA improved in patients with active uveitis from weeks 0 to 78 (0.27 to 0.14 logMAR; left and right eyes; as-observed) and remained stable in patients with inactive uveitis. Mean corticosteroid dose decreased from 13.6 mg/day (week 0) to 2.6 mg/day (week 78) in patients with active uveitis and remained stable in those with inactive uveitis (1.5-1.2 mg/day). AEs (424 events/100 patient-years) and serious AEs (16.5 events/100 patient-years) were comparable with previous VISUAL trials. Conclusions: Patients with active uveitis at study entry who received adalimumab therapy were likely to achieve quiescence, improve visual acuity, and reduce their daily uveitis-related systemic corticosteroid use. Most patients with inactive uveitis at study entry sustained quiescence without a systemic corticosteroid dose increase. No new safety signals were identified.

AB - Purpose: To evaluate safety and efficacy of adalimumab in patients with noninfectious intermediate, posterior, or panuveitis. Design: Phase 3, open-label, multicenter clinical trial extension (VISUAL III). Participants: Adults meeting treatment failure (TF) criteria or who completed VISUAL I or II (phase 3, randomized, double-masked, placebo-controlled) without TF. Methods: Patients received adalimumab 40 mg every other week. Interim follow-up data were described from VISUAL III weeks 0 through 78. Main Outcome Measures: Disease quiescence, steroid-free quiescence, active inflammatory chorioretinal/retinal vascular lesions, anterior chamber cell grade, vitreous haze grade, best-corrected visual acuity (BCVA), and corticosteroid dose. Binary data were reported using nonresponder imputation (NRI), continuous data using last observation carried forward and as-observed analysis, and corticosteroid dose using observed-case analysis. Adverse events (AEs) were reported from first adalimumab dose in VISUAL III through interim cutoff. Results: Of 424 patients enrolled, 371 were included in intent-to-treat analysis. At study entry, 242 of 371 (65%) patients had active uveitis; 60% (145/242, NRI) achieved quiescence at week 78, and 66% (95/143, as-observed) of those were corticosteroid free. At study entry, 129 of 371 (35%) patients had inactive uveitis; 74% (96/129, NRI) achieved quiescence at week 78, and 93% (89/96, as-observed) of those were corticosteroid free. Inflammatory lesions, anterior chamber grade, and vitreous haze grade showed initial improvement followed by decline in patients with active uveitis and remained stable in patients with inactive uveitis. BCVA improved in patients with active uveitis from weeks 0 to 78 (0.27 to 0.14 logMAR; left and right eyes; as-observed) and remained stable in patients with inactive uveitis. Mean corticosteroid dose decreased from 13.6 mg/day (week 0) to 2.6 mg/day (week 78) in patients with active uveitis and remained stable in those with inactive uveitis (1.5-1.2 mg/day). AEs (424 events/100 patient-years) and serious AEs (16.5 events/100 patient-years) were comparable with previous VISUAL trials. Conclusions: Patients with active uveitis at study entry who received adalimumab therapy were likely to achieve quiescence, improve visual acuity, and reduce their daily uveitis-related systemic corticosteroid use. Most patients with inactive uveitis at study entry sustained quiescence without a systemic corticosteroid dose increase. No new safety signals were identified.

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