Long-Term Safety and Efficacy of Adalimumab in Patients With Noninfectious Intermediate Uveitis, Posterior Uveitis, or Panuveitis

Eric B Suhler; Glenn J Jaffe; Eric Fortin; Lyndell L Lim; Pauline T Merrill; Andrew D Dick; Antoine P Brezin; Quan Dong Nguyen; Jennifer E Thorne; Joachim Van Calster; Luca Cimino; Alfredo Adan; Hiroshi Goto; Toshikatsu Kaburaki; Michal Kramer; Albert T Vitale; Martina Kron; Alexandra P Song; Jianzhong Liu; Sophia Pathai; Kevin M Douglas; Ariel Schlaen; Cristina Muccioli; Mirjam E J Van Velthoven; Manfred Zierhut; James T Rosenbaum

doi:10.1016/j.ophtha.2020.10.036

Long-Term Safety and Efficacy of Adalimumab in Patients With Noninfectious Intermediate Uveitis, Posterior Uveitis, or Panuveitis

Eric B Suhler, Glenn J Jaffe, Eric Fortin, Lyndell L Lim, Pauline T Merrill, Andrew D Dick, Antoine P Brezin, Quan Dong Nguyen, Jennifer E Thorne, Joachim Van Calster, Luca Cimino, Alfredo Adan, Hiroshi Goto, Toshikatsu Kaburaki, Michal Kramer, Albert T Vitale, Martina Kron, Alexandra P Song, Jianzhong Liu, Sophia PathaiKevin M Douglas, Ariel Schlaen, Cristina Muccioli, Mirjam E J Van Velthoven, Manfred Zierhut, James T Rosenbaum

Medical retina and Uveitis

Research output: Contribution to journal › Article › Research › peer-review

Abstract

PURPOSE: To evaluate long-term efficacy and safety of extended treatment with adalimumab in patients with noninfectious intermediate, posterior, or panuveitis.

DESIGN: Open-label, multicenter, phase 3 extension study (VISUAL III).

PARTICIPANTS: Adults who had completed a randomized, placebo-controlled phase 3 parent trial (VISUAL I or II) without treatment failure (inactive uveitis) or discontinued after meeting treatment failure criteria (active uveitis).

METHODS: Patients received subcutaneous adalimumab 40 mg every other week. Data were collected for ≤362 weeks. Adverse events (AEs) were recorded until 70 days after the last dose of study drug.

MAIN OUTCOME MEASURES: Main outcome measures were long-term safety and quiescence; other efficacy variables included inflammatory lesions, anterior chamber cell and vitreous haze grade, macular edema, visual acuity, and dose of uveitis-related corticosteroids.

RESULTS: Of 424 patients enrolled, 67% (283/424) had active uveitis and 33% (141/424) had inactive uveitis at study entry; 60 patients subsequently met exclusion criteria, and 364 patients were included in the intent-to-treat analysis. Efficacy variables were analyzed through week 150 when approximately 50% of patients (214/424) remained in the study. The percentage of patients in quiescence increased from 34% (122/364) at week 0 to 85% (153/180) at week 150. Corticosteroid-free quiescence was achieved by 54% (66/123) and 89% (51/57) of patients with active or inactive uveitis at study entry, respectively, by week 150. Mean daily dose of corticosteroids was reduced from 9.4±17.1 mg/day at week 0 (n=359) to 1.5±3.9 mg/day at week 150 (n=181). The percentage of patients who achieved other efficacy variables increased over time for those with active uveitis at study entry and was maintained for those with inactive uveitis. The most frequently reported treatment-emergent AEs of special interest for adalimumab were infections (n=275; 78.7 events/100 patient-years); AEs and serious AEs occurred at a rate of 396 events/100 patient-years and 15 events/100 patient-years, respectively.

CONCLUSIONS: Long-term treatment with adalimumab led to quiescence and reduced corticosteroid use for patients who entered VISUAL III with active uveitis and maintenance of quiescence for those with inactive uveitis. AEs were comparable to those reported in the parent trials and consistent with the known safety profile of adalimumab.

Original language	English
Pages (from-to)	899-909
Number of pages	11
Journal	Ophthalmology
Volume	128
Issue number	6
DOIs	https://doi.org/10.1016/j.ophtha.2020.10.036
Publication status	Published - Jun 2021

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10.1016/j.ophtha.2020.10.036

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Suhler, E. B., Jaffe, G. J., Fortin, E., Lim, L. L., Merrill, P. T., Dick, A. D., Brezin, A. P., Nguyen, Q. D., Thorne, J. E., Van Calster, J., Cimino, L., Adan, A., Goto, H., Kaburaki, T., Kramer, M., Vitale, A. T., Kron, M., Song, A. P., Liu, J., ... Rosenbaum, J. T. (2021). Long-Term Safety and Efficacy of Adalimumab in Patients With Noninfectious Intermediate Uveitis, Posterior Uveitis, or Panuveitis. Ophthalmology, 128(6), 899-909. https://doi.org/10.1016/j.ophtha.2020.10.036

@article{e24c845103bf44d093119fe05c868790,

title = "Long-Term Safety and Efficacy of Adalimumab in Patients With Noninfectious Intermediate Uveitis, Posterior Uveitis, or Panuveitis",

abstract = "PURPOSE: To evaluate long-term efficacy and safety of extended treatment with adalimumab in patients with noninfectious intermediate, posterior, or panuveitis.DESIGN: Open-label, multicenter, phase 3 extension study (VISUAL III).PARTICIPANTS: Adults who had completed a randomized, placebo-controlled phase 3 parent trial (VISUAL I or II) without treatment failure (inactive uveitis) or discontinued after meeting treatment failure criteria (active uveitis).METHODS: Patients received subcutaneous adalimumab 40 mg every other week. Data were collected for ≤362 weeks. Adverse events (AEs) were recorded until 70 days after the last dose of study drug.MAIN OUTCOME MEASURES: Main outcome measures were long-term safety and quiescence; other efficacy variables included inflammatory lesions, anterior chamber cell and vitreous haze grade, macular edema, visual acuity, and dose of uveitis-related corticosteroids.RESULTS: Of 424 patients enrolled, 67% (283/424) had active uveitis and 33% (141/424) had inactive uveitis at study entry; 60 patients subsequently met exclusion criteria, and 364 patients were included in the intent-to-treat analysis. Efficacy variables were analyzed through week 150 when approximately 50% of patients (214/424) remained in the study. The percentage of patients in quiescence increased from 34% (122/364) at week 0 to 85% (153/180) at week 150. Corticosteroid-free quiescence was achieved by 54% (66/123) and 89% (51/57) of patients with active or inactive uveitis at study entry, respectively, by week 150. Mean daily dose of corticosteroids was reduced from 9.4±17.1 mg/day at week 0 (n=359) to 1.5±3.9 mg/day at week 150 (n=181). The percentage of patients who achieved other efficacy variables increased over time for those with active uveitis at study entry and was maintained for those with inactive uveitis. The most frequently reported treatment-emergent AEs of special interest for adalimumab were infections (n=275; 78.7 events/100 patient-years); AEs and serious AEs occurred at a rate of 396 events/100 patient-years and 15 events/100 patient-years, respectively.CONCLUSIONS: Long-term treatment with adalimumab led to quiescence and reduced corticosteroid use for patients who entered VISUAL III with active uveitis and maintenance of quiescence for those with inactive uveitis. AEs were comparable to those reported in the parent trials and consistent with the known safety profile of adalimumab.",

author = "Suhler, {Eric B} and Jaffe, {Glenn J} and Eric Fortin and Lim, {Lyndell L} and Merrill, {Pauline T} and Dick, {Andrew D} and Brezin, {Antoine P} and Nguyen, {Quan Dong} and Thorne, {Jennifer E} and {Van Calster}, Joachim and Luca Cimino and Alfredo Adan and Hiroshi Goto and Toshikatsu Kaburaki and Michal Kramer and Vitale, {Albert T} and Martina Kron and Song, {Alexandra P} and Jianzhong Liu and Sophia Pathai and Douglas, {Kevin M} and Ariel Schlaen and Cristina Muccioli and {Van Velthoven}, {Mirjam E J} and Manfred Zierhut and Rosenbaum, {James T}",

year = "2021",

month = jun,

doi = "10.1016/j.ophtha.2020.10.036",

language = "English",

volume = "128",

pages = "899--909",

number = "6",

}

Suhler, EB, Jaffe, GJ, Fortin, E, Lim, LL, Merrill, PT, Dick, AD, Brezin, AP, Nguyen, QD, Thorne, JE, Van Calster, J, Cimino, L, Adan, A, Goto, H, Kaburaki, T, Kramer, M, Vitale, AT, Kron, M, Song, AP, Liu, J, Pathai, S, Douglas, KM, Schlaen, A, Muccioli, C, Van Velthoven, MEJ, Zierhut, M & Rosenbaum, JT 2021, 'Long-Term Safety and Efficacy of Adalimumab in Patients With Noninfectious Intermediate Uveitis, Posterior Uveitis, or Panuveitis', Ophthalmology, vol. 128, no. 6, pp. 899-909. https://doi.org/10.1016/j.ophtha.2020.10.036

TY - JOUR

T1 - Long-Term Safety and Efficacy of Adalimumab in Patients With Noninfectious Intermediate Uveitis, Posterior Uveitis, or Panuveitis

AU - Suhler, Eric B

AU - Jaffe, Glenn J

AU - Fortin, Eric

AU - Lim, Lyndell L

AU - Merrill, Pauline T

AU - Dick, Andrew D

AU - Brezin, Antoine P

AU - Nguyen, Quan Dong

AU - Thorne, Jennifer E

AU - Van Calster, Joachim

AU - Cimino, Luca

AU - Adan, Alfredo

AU - Goto, Hiroshi

AU - Kaburaki, Toshikatsu

AU - Kramer, Michal

AU - Vitale, Albert T

AU - Kron, Martina

AU - Song, Alexandra P

AU - Liu, Jianzhong

AU - Pathai, Sophia

AU - Douglas, Kevin M

AU - Schlaen, Ariel

AU - Muccioli, Cristina

AU - Van Velthoven, Mirjam E J

AU - Zierhut, Manfred

AU - Rosenbaum, James T

PY - 2021/6

Y1 - 2021/6

N2 - PURPOSE: To evaluate long-term efficacy and safety of extended treatment with adalimumab in patients with noninfectious intermediate, posterior, or panuveitis.DESIGN: Open-label, multicenter, phase 3 extension study (VISUAL III).PARTICIPANTS: Adults who had completed a randomized, placebo-controlled phase 3 parent trial (VISUAL I or II) without treatment failure (inactive uveitis) or discontinued after meeting treatment failure criteria (active uveitis).METHODS: Patients received subcutaneous adalimumab 40 mg every other week. Data were collected for ≤362 weeks. Adverse events (AEs) were recorded until 70 days after the last dose of study drug.MAIN OUTCOME MEASURES: Main outcome measures were long-term safety and quiescence; other efficacy variables included inflammatory lesions, anterior chamber cell and vitreous haze grade, macular edema, visual acuity, and dose of uveitis-related corticosteroids.RESULTS: Of 424 patients enrolled, 67% (283/424) had active uveitis and 33% (141/424) had inactive uveitis at study entry; 60 patients subsequently met exclusion criteria, and 364 patients were included in the intent-to-treat analysis. Efficacy variables were analyzed through week 150 when approximately 50% of patients (214/424) remained in the study. The percentage of patients in quiescence increased from 34% (122/364) at week 0 to 85% (153/180) at week 150. Corticosteroid-free quiescence was achieved by 54% (66/123) and 89% (51/57) of patients with active or inactive uveitis at study entry, respectively, by week 150. Mean daily dose of corticosteroids was reduced from 9.4±17.1 mg/day at week 0 (n=359) to 1.5±3.9 mg/day at week 150 (n=181). The percentage of patients who achieved other efficacy variables increased over time for those with active uveitis at study entry and was maintained for those with inactive uveitis. The most frequently reported treatment-emergent AEs of special interest for adalimumab were infections (n=275; 78.7 events/100 patient-years); AEs and serious AEs occurred at a rate of 396 events/100 patient-years and 15 events/100 patient-years, respectively.CONCLUSIONS: Long-term treatment with adalimumab led to quiescence and reduced corticosteroid use for patients who entered VISUAL III with active uveitis and maintenance of quiescence for those with inactive uveitis. AEs were comparable to those reported in the parent trials and consistent with the known safety profile of adalimumab.

AB - PURPOSE: To evaluate long-term efficacy and safety of extended treatment with adalimumab in patients with noninfectious intermediate, posterior, or panuveitis.DESIGN: Open-label, multicenter, phase 3 extension study (VISUAL III).PARTICIPANTS: Adults who had completed a randomized, placebo-controlled phase 3 parent trial (VISUAL I or II) without treatment failure (inactive uveitis) or discontinued after meeting treatment failure criteria (active uveitis).METHODS: Patients received subcutaneous adalimumab 40 mg every other week. Data were collected for ≤362 weeks. Adverse events (AEs) were recorded until 70 days after the last dose of study drug.MAIN OUTCOME MEASURES: Main outcome measures were long-term safety and quiescence; other efficacy variables included inflammatory lesions, anterior chamber cell and vitreous haze grade, macular edema, visual acuity, and dose of uveitis-related corticosteroids.RESULTS: Of 424 patients enrolled, 67% (283/424) had active uveitis and 33% (141/424) had inactive uveitis at study entry; 60 patients subsequently met exclusion criteria, and 364 patients were included in the intent-to-treat analysis. Efficacy variables were analyzed through week 150 when approximately 50% of patients (214/424) remained in the study. The percentage of patients in quiescence increased from 34% (122/364) at week 0 to 85% (153/180) at week 150. Corticosteroid-free quiescence was achieved by 54% (66/123) and 89% (51/57) of patients with active or inactive uveitis at study entry, respectively, by week 150. Mean daily dose of corticosteroids was reduced from 9.4±17.1 mg/day at week 0 (n=359) to 1.5±3.9 mg/day at week 150 (n=181). The percentage of patients who achieved other efficacy variables increased over time for those with active uveitis at study entry and was maintained for those with inactive uveitis. The most frequently reported treatment-emergent AEs of special interest for adalimumab were infections (n=275; 78.7 events/100 patient-years); AEs and serious AEs occurred at a rate of 396 events/100 patient-years and 15 events/100 patient-years, respectively.CONCLUSIONS: Long-term treatment with adalimumab led to quiescence and reduced corticosteroid use for patients who entered VISUAL III with active uveitis and maintenance of quiescence for those with inactive uveitis. AEs were comparable to those reported in the parent trials and consistent with the known safety profile of adalimumab.

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U2 - 10.1016/j.ophtha.2020.10.036

DO - 10.1016/j.ophtha.2020.10.036

M3 - Article

C2 - 33157077

SN - 0161-6420

VL - 128

SP - 899

EP - 909

JO - Ophthalmology

JF - Ophthalmology

IS - 6

ER -

Long-Term Safety and Efficacy of Adalimumab in Patients With Noninfectious Intermediate Uveitis, Posterior Uveitis, or Panuveitis

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