Eric B Suhler1, Glenn J Jaffe2, Eric Fortin3, Lyndell L Lim4, Pauline T Merrill5, Andrew D Dick6, Antoine P Brezin7, Quan Dong Nguyen8, Jennifer E Thorne9, Joachim Van Calster10, Luca Cimino11, Alfredo Adan12, Hiroshi Goto13, Toshikatsu Kaburaki14, Michal Kramer15, Albert T Vitale16, Martina Kron17, Alexandra P Song18, Jianzhong Liu18, Sophia Pathai19, Kevin M Douglas18, Ariel Schlaen20, Cristina Muccioli21, Mirjam E J Van Velthoven22, Manfred Zierhut23, James T Rosenbaum24. 1. Casey Eye Institute, Oregon Health & Science University, OHSU-PSU School of Public Health, and VA Portland Health Care System, Portland, Oregon. Electronic address: suhlere@ohsu.edu. 2. Department of Ophthalmology, Duke University, Durham, North Carolina. 3. Department of Ophthalmology, University of Montreal, Montreal, Canada. 4. Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, Australia. 5. Department of Ophthalmology, Rush University Medical Center, Chicago, Illinois. 6. Translational Health Sciences (Ophthalmology), University of Bristol, Bristol Eye Hospital, Bristol, United Kingdom, and National Institute for Health Research (NIHR) Biomedical Research Centre at Moorfields Eye Hospital and University College London, Institute of Ophthalmology, London, United Kingdom. 7. Department of Ophthalmology, Université Paris Descartes, Hôpital Cochin, Paris, France. 8. Department of Ophthalmology, Byers Eye Institute, Stanford University, Palo Alto, California. 9. Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, and Department of Epidemiology, Center for Clinical Trials, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland. 10. Department of Ophthalmology, University Hospitals Leuven, Leuven, Belgium. 11. Ocular Immunology Unit, Azienda USL IRCCS, Reggio Emilia, Italy. 12. Facultad de Medicina, Hospital Clinic de Barcelona, Barcelona, Spain. 13. Department of Ophthalmolgy, Medical University, Tokyo, Japan. 14. Department of Ophthalmology, University of Tokyo, Tokyo, Japan. 15. Department of Ophthalmology, Rabin Medical Center, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel. 16. Department of Ophthalmology and Visual Sciences, John A. Moran Eye Center, University of Utah, Salt Lake City, Utah. 17. AbbVie Deutschland GmbH & Co KG, Ludwigshafen, Germany. 18. AbbVie, Inc., North Chicago, Illinois. 19. Johnson & Johnson Vision, Singapore, Republic of Singapore. 20. Department of Ophthalmology, Austral University, Buenos Aires, Argentina. 21. Department of Ophthalmology and Visual Sciences, Federal University of São Paulo, São Paulo, Brazil. 22. Rotterdam Eye Hospital, Rotterdam, The Netherlands. 23. Centre for Ophthalmology, University of Tübingen, Tübingen, Germany. 24. Departments of Ophthalmology and Medicine, Oregon Health & Science University and Legacy Devers Eye Institute, Portland, Oregon.
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 who discontinued the study 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. MAIN OUTCOME MEASURES: 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 systemic corticosteroids. RESULTS: At study entry, 67% of patients (283/424) showed active uveitis and 33% (141/424) showed inactive uveitis; 60 patients subsequently met exclusion criteria, and 364 were included in the intention-to-treat analysis. Efficacy variables were analyzed through week 150, when approximately 50% of patients (214/424) remained in the study. Patients showing 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. Mean daily dose of systemic 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 were infections (n = 275; 79 events/100 patient-years [PY]); AEs and serious AEs occurred at a rate of 396 events/100 PY and 15 events/100 PY, respectively. CONCLUSIONS: Long-term treatment with adalimumab led to quiescence and reduced corticosteroid use for patients who entered VISUAL III with active uveitis and led to maintenance of quiescence for those with inactive uveitis. AEs were comparable with those reported in the parent trials and consistent with the known safety profile of adalimumab.
RCT Entities:
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 who discontinued the study 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. MAIN OUTCOME MEASURES: 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 systemic corticosteroids. RESULTS: At study entry, 67% of patients (283/424) showed active uveitis and 33% (141/424) showed inactive uveitis; 60 patients subsequently met exclusion criteria, and 364 were included in the intention-to-treat analysis. Efficacy variables were analyzed through week 150, when approximately 50% of patients (214/424) remained in the study. Patients showing 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. Mean daily dose of systemic 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 were infections (n = 275; 79 events/100 patient-years [PY]); AEs and serious AEs occurred at a rate of 396 events/100 PY and 15 events/100 PY, respectively. CONCLUSIONS: Long-term treatment with adalimumab led to quiescence and reduced corticosteroid use for patients who entered VISUAL III with active uveitis and led to maintenance of quiescence for those with inactive uveitis. AEs were comparable with those reported in the parent trials and consistent with the known safety profile of adalimumab.
Authors: Jonas J W Kuiper; Fleurieke H Verhagen; Sanne Hiddingh; Roos A W Wennink; Anna M Hansen; Kerry A Casey; Imo E Hoefer; Saskia Haitjema; Julia Drylewicz; Mehmet Yakin; H Nida Sen; Timothy R D J Radstake; Joke H de Boer Journal: Ophthalmol Sci Date: 2022-05-31