Title | Reply to Should Tocilizumab Be Used Routinely in New Patients With a Diagnosis of Giant Cell Arteritis? |
Creator | Lynn K. Gordon; Alfredo A. Sadun; Greg Van Stavern; Andrew G. Lee |
Affiliation | Ophthalmology, Stein Eye Institute, UCLA, Los Angeles, California. Ophthalmology, Doheny Eye Institute, UCLA, Los Angeles, California. Department of Ophthalmology and Visual Sciences, Washington University, St. Louis, Missouri. Blanton Eye Institute, Houston Methodist Hospital, Houston, Texas |
Subject | Humanized Monoclonal Antibodies; Giant Cell Arteritis; Glucocorticoids |
OCR Text | Show Letters to the Editor clinics we often see patients who have been suspected of having a flare of GCA, but in reality, have other causes for their visual symptoms such as cataracts that are accelerated by long-term steroid therapy or ocular surface disease. Tocilizumab is a potentially exciting therapeutic option and the GiACTA study demonstrates that it can be beneficial in tapering off steroids more quickly without disease relapse in some patients. However, this study does have important limitations: half of the enrolled subjects were enrolled many months after the time of diagnosis when most patients should be completely weaned off or be on a very low dose of steroids and the definition of relapse which shaped study conclusions was vague. Thus, we believe there is still a critical lack of evidence that tocilizumab is indicated in all patients with a new diagnosis of GCA. Laura Donaldson, MD, PhD Kirill Zaslavsky, MD, PhD Department of Ophthalmology and Vision Sciences, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada Edward Margolin, MD Department of Ophthalmology and Vision Sciences, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada Division of Neurology, Department of Medicine, Faculty of Medicine, Reply to Should Tocilizumab Be Used Routinely in New Patients With a Diagnosis of Giant Cell Arteritis? T he authors would like to thank Donaldson et al for their comments in response to our point counter-point publication that discussed the pros and cons of the routine use of tocilizumab in new patients with a diagnosis of giant cell arteritis (1). They raise some important limitations about the GiACTA study, a randomized prospective clinical trial (2). Many of their points were reasonable and, indeed, consistent with our own published considerations. However, they are incorrect in stating that the 2017 New England Journal of Medicine (NEJM) publication was the basis for our “main conclusions.” Our initial point counter-point publication was rooted not solely on the Letters to the Editor: J Neuro-Ophthalmol 2022; 42: e533-e538 University of Toronto, Toronto, Ontario, Canada The authors report no conflicts of interest. REFERENCES 1. Stone JH, Tuckwell K, Dimonaco S, Klearman M, Aringer M, Blockmans D, Brouwer E, Cid MC, Dasgupta B, Rech J, Salvarani C, Schett G, Schulze-Koops H, Spiera R, Unizony SH, Collinson N. Trial of tocilizumab in giant-cell arteritis. New Engl J Med. 2017;377:317–328. 2. Salvarani C, Pipitone N, Versari A, Hunder GG. Clinical features of polymyalgia rheumatica and giant cell arteritis. Nat Rev Rheumatol. 2012;8:509–521. 3. Hellmich B, Agueda A, Monti S, Buttgereit F, de Boysson H, Brouwer E, Cassie R, Cid MC, Dasgupta B, Dejaco C, Hatemi G, Hollinger N, Mahr A, Mollan SP, Mukhtyar C, Ponte C, Salvarani C, Sivakumar R, Tian X, Tomasson G, Turesson C, Schmidt W, Villiger PM, Watts R, Young C, Luqmani RA. 2018 Update of the EULAR recommendations for the management of large vessel vasculitis. Ann Rheum Dis. 2020;79:19–30. 4. Dejaco C, Ramiro S, Duftner C, Besson FL, Bley TA, Blockmans D, Brouwer E, Cimmino MA, Clark E, Dasgupta B, Diamantopoulos AP, Direskeneli H, Iagnocco A, Klink T, Neill L, Ponte C, Salvarani C, Slart RHJA, Whitlock M, Schmidt WA. EULAR recommendations for the use of imaging in large vessel vasculitis in clinical practice. Ann Rheum Dis. 2018;77:636–643. 5. Kermani TA, Warrington KJ, Cuthbertson D, Carette S, Hoffman GS, Khalidi NA, Koening CL, Langford CA, MaksimowiczMcKinnon K, McAlear CA, Monach PA, Seo P, Merkel PA, Ytterberg SR; Vasculitis Clinical Research Consortium. Disease relapses among patients with giant cell arteritis: a prospective, longitudinal cohort study. J Rheumatol. 2015;42:1213–1217. 6. Aiello PD, Trautmann J, McPhee T, Kunselman AR, Hunder GG. Visual prognosis in giant cell arteritis. Ophthalmology. 1993;100:550–555. 7. Alba MA, García-Martínez A, Prieto-González S, Tavera-Bahillo I, Corbera-Bellalta M, Planas-Rigol E, Espígol-Frigolé G, Butjosa M, Hernández-Rodríguez J, Cid MC. Relapses in patients with giant cell arteritis: prevalence, characteristics, and associated clinical findings in a longitudinally followed cohort of 106 patients. Medicine (Baltimore). 2014;93:194–201. findings of the GiACTA study but also on several additional studies, basic science as well as clinical, that both preceded and followed the trial reported in the NEJM article. Specifically, we commented on the limitations of the GiACTA trial. For example, in Gordon's section, the following statement was made: “Thus, the conclusions from this trial may not be entirely relevant in considering with the patient who presents to the neuro-ophthalmologist with an acute arteritic anterior optic neuropathy from GCA.” The authors' last statement is quite in agreement with our conclusions. They state that: “Thus we believe there is still a critical lack of evidence that tocilizumab is indicated in all patients with a new diagnosis of GCA.” That sentiment was articulated in our publication and summed up in the conclusions, authored by Lee and Van Stavern: “GCA is still best managed on an individualized, patient-by-patient basis, but the addition of tocilizumab is indeed a game changer and provides an evidence-based treatment alternative for selected patients with this condition.” e535 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Letters to the Editor Andrew G. Lee, MD Blanton Eye Institute, Houston Methodist Hospital, Houston, Texas Lynn K. Gordon, MD, PhD Ophthalmology, Stein Eye Institute, UCLA, Los Angeles, California Alfredo A. Sadun, MD, PhD Ophthalmology, Doheny Eye Institute, UCLA, Los Angeles, California Greg Van Stavern, MD Department of Ophthalmology and Visual Sciences, Washington University, St. Louis, Missouri Comments on a Case Entitled “Gazing Into the Crystal Ball” W e read with interest the case report by Cherayil et al (1), detailing a patient with crystalline deposits, retinal arteriolar whitening, disc pallor, iris neovascularization, and calcinosis cutis. The authors attributed the constellation of findings to a rare condition called calciphylaxis. Clinically, calciphylaxis is characterized by the presence of intensely painful necrotic ulcerating lesions of the skin because of an obliterative intradermal and subcutaneous arteriolopathy (2). The authors do not report that their patient developed such lesions. The histological hallmark is of dermal and subcutaneous adipose capillary medial and intimal calcification, with frequent fibrin thrombi causing occlusion (2). The presented histological images demonstrate calcinosis cutis and not calciphylaxis, the former not being a histological precursor of the latter. It would be useful to know what the visual function and fundus appearance were preoperatively. The possibility of perioperative nonarteritic ischemic optic neuropathy (NAION) comes to mind. Patients with end-stage renal disease (ESRD) are already at a greater risk of NAION, even after adjustment for diabetes, hypertension, and hypotension (3). They are often anemic, have atherosclerosis, and widespread vascular calcification, visible on plain radiographs and even within the ophthalmic artery on computed tomography (4). Such considerations make ocular ischemia unsurprising in this patient. Similar retinal arteriolar calcification has been reported in 3 patients with ESRD, 2 of which did not have systemic calciphylaxis, but were more striking in appearance than the other (5–7). It is also noteworthy that 8 cases of vision impairment with clinically and histologically confirmed calciphylaxis in the ophthalmic literature do not report such a finding (6,8–14). Only one of these cases also had crystale536 The authors report no conflicts of interest. REFERENCES 1. Sadun A, Gordon L. Should tocilizumab be used routinely in new patients with a diagnosis of giant cell arteritis? J Neuroophthalmol. 2020;40:117–121. 2. Stone JH, Tuckwell K, Dimonaco S, Klearman M, Aringer M, Blockmans D, Brouwer E, Cid MC, Dasgupta B, Rech J, Salvarani C, Schett G, Schulze-Koops H, Spiera R, Unizony SH, Collinson N. Trial of tocilizumab in giant-cell arteritis. N Engl J Med. 2017;377:317–328. line retinal deposits (6). An optical coherence tomography might be useful in determining whether the crystals in the presented case were due to high oxalate (15). As the authors outlined, calciphylaxis has been suggested as the cause of a number of ischemic optic neuropathy cases (6,8–14). Three of these erroneously diagnosed calciphylaxis based on temporal artery calcification alone (16–18). Currently, the ophthalmic findings of patients with true calciphylaxis cannot be disentangled from those because of ESRD. Hence, the term “ocular calciphylaxis” is not truly defined, and its relationship with skin calciphylaxis is not determined, but warrants further study. In our view, the authors have made a significant leap from calcinosis cutis to calciphylaxis, and we would argue there was insufficient evidence presented in favor of this. The crystal ball is perhaps not always crystal clear. Rupa D. Patel, BSc, MSc, BM, FRCOphth Department of Neuro-Ophthalmology, Moorfields Eye Hospital, London, United Kingdom Smeeta Sinha, MBChB, MRCP, PhD Salford Royal Hospital NHS Foundation Trust, Salford, United Kingdom Faculty of Biology, Medicine, and Health, University of Manchester, Manchester, United Kingdom There authors report no conflicts of interest. REFERENCES 1. Cherayil NR, Scoles D, Moran AM, Elder DE, Tamhankar MA. Gazing into the crystal ball: calciphylaxis causing striking retinal vascular calcification, ocular ischemic syndrome, crystalline retinopathy, and ischemic optic neuropathy. J Neuroophthalmol. 2021;41:e212–e214. Letters to the Editor: J Neuro-Ophthalmol 2022; 42: e533-e538 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. |
Date | 2022-06 |
Language | eng |
Format | application/pdf |
Type | Text |
Publication Type | Journal Article |
Source | Journal of Neuro-Ophthalmology, June 2023, Volume 43, Issue 2 |
Collection | Neuro-Ophthalmology Virtual Education Library: Journal of Neuro-Ophthalmology Archives: https://novel.utah.edu/jno/ |
Publisher | Lippincott, Williams & Wilkins |
Holding Institution | Spencer S. Eccles Health Sciences Library, University of Utah |
Rights Management | © North American Neuro-Ophthalmology Society |
ARK | ark:/87278/s67ppjh7 |
Setname | ehsl_novel_jno |
ID | 2307909 |
Reference URL | https://collections.lib.utah.edu/ark:/87278/s67ppjh7 |