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Corrigendum
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10.1172/JCI189023
Crizanlizumab for retinal vasculopathy with cerebral leukoencephalopathy in a phase II clinical study
Wilson X. Wang,1 Dan Spiegelman,1 P. Kumar Rao,1 Rennie L. Rhee,2 Andria L. Ford,3 Jonathan J. Miner,4 and Rajendra S. Apte1,5
1John F. Hardesty, MD Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, Missouri, USA.
2Department of Medicine and RVCL Research Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
3Department of Neurology, Washington University School of Medicine, St. Louis, Missouri, USA.
4Departments of Medicine and Microbiology, Colton Center for Autoimmunity, and RVCL Research Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
5Department of Medicine, Washington University, St. Louis, Missouri, USA.
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1John F. Hardesty, MD Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, Missouri, USA.
2Department of Medicine and RVCL Research Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
3Department of Neurology, Washington University School of Medicine, St. Louis, Missouri, USA.
4Departments of Medicine and Microbiology, Colton Center for Autoimmunity, and RVCL Research Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
5Department of Medicine, Washington University, St. Louis, Missouri, USA.
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1John F. Hardesty, MD Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, Missouri, USA.
2Department of Medicine and RVCL Research Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
3Department of Neurology, Washington University School of Medicine, St. Louis, Missouri, USA.
4Departments of Medicine and Microbiology, Colton Center for Autoimmunity, and RVCL Research Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
5Department of Medicine, Washington University, St. Louis, Missouri, USA.
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1John F. Hardesty, MD Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, Missouri, USA.
2Department of Medicine and RVCL Research Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
3Department of Neurology, Washington University School of Medicine, St. Louis, Missouri, USA.
4Departments of Medicine and Microbiology, Colton Center for Autoimmunity, and RVCL Research Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
5Department of Medicine, Washington University, St. Louis, Missouri, USA.
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1John F. Hardesty, MD Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, Missouri, USA.
2Department of Medicine and RVCL Research Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
3Department of Neurology, Washington University School of Medicine, St. Louis, Missouri, USA.
4Departments of Medicine and Microbiology, Colton Center for Autoimmunity, and RVCL Research Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
5Department of Medicine, Washington University, St. Louis, Missouri, USA.
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1John F. Hardesty, MD Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, Missouri, USA.
2Department of Medicine and RVCL Research Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
3Department of Neurology, Washington University School of Medicine, St. Louis, Missouri, USA.
4Departments of Medicine and Microbiology, Colton Center for Autoimmunity, and RVCL Research Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
5Department of Medicine, Washington University, St. Louis, Missouri, USA.
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1John F. Hardesty, MD Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, Missouri, USA.
2Department of Medicine and RVCL Research Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
3Department of Neurology, Washington University School of Medicine, St. Louis, Missouri, USA.
4Departments of Medicine and Microbiology, Colton Center for Autoimmunity, and RVCL Research Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
5Department of Medicine, Washington University, St. Louis, Missouri, USA.
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Published December 16, 2024 - More info
J Clin Invest. 2024;134(24):e189023. https://doi.org/10.1172/JCI189023.
© 2024 Wang et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Related article:
Abstract
Background Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) is a rare, autosomal dominant, universally fatal disease without effective treatment options. This study explores the safety and preliminary efficacy of crizanlizumab, a humanized monoclonal antibody against P-selectin approved for the prevention of sickle cell crises, in slowing retinal nonperfusion and preserving vision in patients with RVCL-S.METHODS Eleven patients with RVCL-S with confirmed exonuclease 3 prime repair exonuclease 1 (TREX1) mutations received monthly crizanlizumab infusions over 2 years. The study measured the nonperfusion index within 3 retinal zones and the total retina with fluorescein angiography, visual acuity, intraocular pressure (IOP), and optical coherence tomography central subfield thickness (CST) at baseline, 1 year, and 2 years. A mixed repeated-measures analysis was performed to assess the progression rates and changes from baseline.RESULTS Eleven participants received crizanlizumab infusions. All of the participants tolerated crizanlizumab well, with 8 of 11 (72.7%) reporting mild adverse effects such as nausea, fatigue, and gastrointestinal symptoms. The change in total retinal nonperfusion was 7.22% [4.47, 9.97] in year 1 and –0.69% [–4.06, 2.68] in year 2 (P < 0.001). In the mid periphery, the change in nonperfusion was 10.6% [5.1, 16.1] in year 1 and –0.68% [–3.98, 5.35] in year 2 (P < 0.01), demonstrating a reduction in progression of nonperfusion in the second year of treatment. Visual acuity, IOP, and CST remained stable.CONCLUSION Crizanlizumab has an acceptable safety profile. These results show promising potential for examining crizanlizumab in larger studies of RVCL-S and similar small-vessel diseases and for using the retina as a biomarker for systemic disease.Trial registration ClinicalTrials.gov NCT04611880.FUNDING The Clayco Foundation; DeNardo Education and Research Foundation Grant; Jeffrey T. Fort Innovation Fund; Siteman Retina Research Fund; unrestricted grant from Research to Prevent Blindness Inc.; National Heart,Lung, and Blood Institute (NHLBI), NIH (R01HL129241); National Institute of Neurological Disorders and Stroke (NINDS), NIH (RF1NS116565).
Authors
Wilson X. Wang, Dan Spiegelman, P. Kumar Rao, Rennie L. Rhee, Andria L. Ford, Jonathan J. Miner, Rajendra S. Apte
Original citation: J Clin Invest. 2024;134(12):e180916. https://doi.org/10.1172/JCI180916
Citation for this corrigendum: J Clin Invest. 2024;134(24):e189023. https://doi.org/10.1172/JCI189023
Jonathan J. Miner and Rennie Rhee were omitted from the author list. Dr. Miner designed, initiated, obtained funding for, and oversaw the clinical trial while serving at Washington University, and continued to work on it after relocating his laboratory and practice to the University of Pennsylvania Perelman School of Medicine (Penn), the clinical trial’s second site. Dr. Miner is cocorresponding author for this article. Dr. Miner declares compensation by Novartis for an educational P-selectin lecture presented to Novartis staff prior to initiation of the clinical trial. Dr. Rennie Rhee was the principal investigator at Penn. The HTML and PDF versions of this article have been updated with the correct author and affiliation lists.
In addition, information regarding the primary endpoint was omitted from the discussion. Progression in brain lesions on MRI was designated as the primary endpoint of the “Crizanlizumab for RVCL” clinical trial, and the methodology for assessing retinal nonperfusion was developed as a post hoc analysis after the clinical trial was completed. In RVCL-S patients receiving crizanlizumab, we have observed clear progression of brain lesions based on MRI results. A detailed analysis of the brain MRI results, including information about the rate of disease progression, is in preparation.
The authors regret the errors.
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