Eric B Suhler1, Alfredo Adán2, Antoine P Brézin3, Eric Fortin4, Hiroshi Goto5, Glenn J Jaffe6, Toshikatsu Kaburaki7, Michal Kramer8, Lyndell L Lim9, Cristina Muccioli10, Quan Dong Nguyen11, Joachim Van Calster12, Luca Cimino13, Martina Kron14, Alexandra P Song15, Jianzhong Liu15, Sophia Pathai16, Anne Camez14, Ariel Schlaen17, Mirjam E J van Velthoven18, Albert T Vitale19, Manfred Zierhut20, Samir Tari15, Andrew D Dick21. 1. Oregon Health & Science University, Casey Eye Institute, Portland, Oregon, and VA Portland Health Care System, Portland, Oregon. Electronic address: suhlere@ohsu.edu. 2. Hospital Clinic de Barcelona, Barcelona, Spain. 3. Université Paris Descartes, Hôpital Cochin, Paris, France. 4. University of Montreal, Montreal, Canada. 5. Tokyo Medical University, Tokyo, Japan. 6. Duke University, Durham, North Carolina. 7. University of Tokyo, Tokyo, Japan. 8. Rabin Medical Center, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel. 9. Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, Australia. 10. Federal University of São Paulo, São Paulo, Brazil. 11. Byers Eye Institute, Stanford University, Palo Alto, California. 12. University Hospitals Leuven, Leuven, Belgium. 13. Ocular Immunology Unit, Azienda USL IRCCS, Reggio Emilia, Italy. 14. AbbVie Deutschland GmbH & Co KG, Ludwigshafen, Germany. 15. AbbVie Inc, North Chicago, Illinois. 16. AbbVie Ltd, Maidenhead, United Kingdom. 17. Austral University, Buenos Aires, Argentina. 18. Rotterdam Eye Hospital, Rotterdam, Netherlands. 19. John A. Moan Eye Center, University of Utah, Salt Lake City, Utah. 20. University of Tübingen, Tübingen, Germany. 21. 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.
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 receivedadalimumab 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.
RCT Entities:
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.
Authors: Carmen Antía Rodríguez-Fernández; Manuel Busto Iglesias; Begoña de Domingo; Kelly Conde-Pérez; Juan A Vallejo; Lorena Rodríguez-Martínez; Miguel González-Barcia; Victor Llorenç; Cristina Mondelo-Garcia; Margarita Poza; Anxo Fernández-Ferreiro Journal: Int J Mol Sci Date: 2022-06-24 Impact factor: 6.208