Giant cell arteritis (GCA) is a severe granulomatous occlusive vasculitis affecting medium to large arteries of the head and neck.
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GCA can cause intense myointimal proliferation and vessel occlusion of the ophthalmic artery, central retinal artery, and short posterior ciliary arteries leading to irreversible vision loss.2
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Steroids remain the mainstay of treatment but usually require a slow taper over 1–3 years and lead to significant side effects in >80% of patients.4
The Trial of Tocilizumab in Giant Cell Arteritis (GiACTA) in 2017 demonstrated the effectiveness of the recombinant monoclonal antibody interleukin-6 inhibitor tocilizumab (TCZ) combined with accelerated prednisone taper in achieving sustained glucocorticoid-free remission in GCA patients.5
The purpose of our retrospective study was to compare outcomes of GCA patients treated with steroids alone versus patients treated with steroids and adjunctive tocilizumab in a single neuro-ophthalmology practice, as well as to compare outcomes from real-world practice with the outcomes reported from the prospectively designed GiACTA.The study protocol was approved by the University of Oklahoma Health Sciences Center Institutional Review Board (IRB) and adhered to the tenets of the Declaration of Helsinki. We identified all biopsy-proven GCA patients managed by a single neuro-ophthalmologist (A.D.P.) from 2005 to 2022 and queried the medical records for cumulative steroid exposure (milligrams of prednisone), including planned taper and escape dosing necessary to maintain disease quiescence, and TCZ use. This provider's practice pattern includes initiating oral prednisone 1 mg/kg per day with tapering by 10 mg/month for steroid-only patients and tapering by 10 mg every 2 weeks for patients approved for concurrent subcutaneous TCZ 162 mg/0.9 mL weekly or biweekly. Length of steroid therapy (in months) required to achieve disease remission (cessation of prednisone or indefinite daily 1 mg dose), disease recurrence, defined by the return of GCA symptoms or new ocular ischemia; adverse events requiring medical intervention; and ocular ischemic complications at presentation (i.e., ischemic optic neuropathy, retinal/ophthalmic artery occlusion, ophthalmoplegia, or transient monocular vision loss) also were recorded. Excluded were patients lost to follow-up prior to 3 months of planned treatment, patients whose steroid dosing was not managed primarily by us, and patients with insufficient documentation.
A demographic and clinical summary of the 79 patients meeting study criteria appears in Table 1. Outcome measures of patients treated with steroid therapy alone versus patients treated with steroids and adjunctive TCZ appear in Table 2. There was a statistically significant reduction in mean cumulative steroid dose and length of steroid therapy, and outcomes of the TCZ group were not inferior to those of the steroid-only group regarding disease recurrence and adverse events requiring medical intervention—most frequently, hyperglycemia and infection/sepsis. However, we did not record mild or chronic adverse effects that were more difficult to quantify, such as insomnia, weight gain, fatigue, and quality-of-life indicators.
Table 1Demographic and clinical characteristics of the study population
| Characteristic | Steroids only (n = 49) | Steroids + TCZ (n = 30) | p Value | Test |
|---|---|---|---|---|
| Age, mean, (SD; range) | 76.6 (7.6; 60–95) | 74.1 (8.8; 58–92) | 0.094 | t Test |
| Sex | ||||
| Female, % (n) | 67.3 (33) | 60.0 (18) | 0.629 | Fisher's exact test |
| Male, % (n) | 32.7 (16) | 40.0 (12) | ||
| Ocular manifestations of GCA, % (n) | 69.4 (34) | 73.3 (22) | 0.805 | Fisher's exact test |
TCZ, tocilizumab; GCA, giant cell arteritis
Table 2Comparison of outcome measures of patients treated with steroid therapy alone versus patients treated with steroids and adjunctive TCZ
| Characteristic | Steroids only (n = 49) | Steroids + TCZ (n = 30) | p Value | Test |
|---|---|---|---|---|
| Cumulative steroid exposure, mean mg of prednisone (SD) | 11,139.5 (6257.5) | 8263.6 (4263.2) | 0.015 | t Test |
| Length of steroid therapy, months (SD) | 26.5 (31.9) | 14.8.0 (11.6) | 0.029 | t Test |
| Disease recurrence by GCA symptoms or ocular ischemia, % (n) | 24.5 (12) | 23.3 (7) | 0.609 | Fisher's exact test |
| Adverse events requiring medical intervention, % (n) | ||||
| Any | 46.9 (23) | 53.3 (16) | 0.647 | Fisher's exact test |
| Sepsis/infection | 16.3 (8) | 20.0 (6) | ||
| Hyperglycemia or diabetic ketoacidosis | 10.2 (5) | 20.0 (6) | ||
| Musculoskeletal (osteoporosis, osteopenia, avascular hip necrosis, spinal compression fracture) | 4.1 (2) | 6.7 (2) | ||
| Uncontrolled hypertension | 4.1 (2) | 0 | ||
| Gastrointestinal (melena, ulcer, or perforation) | 2.0 (1) | 0 | ||
| Mean follow-up time, months (SD) | 51.7 (47.4) | 29.2 (17.9) | 0.0083 | t Test |
TCZ, tocilizumab; GCA, giant cell arteritis
Notably, TCZ profoundly suppresses C-reactive protein and erythrocyte sedimentation rate independent of disease activity
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; therefore, disease recurrence was defined as the return of previously resolved cranial (e.g., jaw claudication, temporal headache, and scalp tenderness) or polymyalgia rheumatica symptoms as opposed to elevation of acute-phase reactants.GiACTA has primarily guided the use of TCZ for GCA, but several criticisms of this study should be considered in real-world practice, as demonstrated by our study. First, GiACTA used much more rapid, unconventional 26- and 52-week steroid tapering protocols (in turn, much lower cumulative steroid exposure) than those commonly encountered in real-world practice. Second, only 0.8% of GiACTA participants had ischemic optic neuropathy (ION)
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; 44.3% of our study population presented with ION, and 70.9% presented with ocular ischemia of any kind, suggesting that the GiACTA population was comprised of patients with milder forms of disease. Our study, as well as that of Hayreh et al.,8
suggests that patients with severe forms of GCA present to neuro-ophthalmologists, and our study demonstrates that these patients require much higher cumulative steroid exposure than those encountered in GiACTA (nearly a fourfold increase in both steroid-only and TCZ groups). Therefore, adjunctive TCZ should be strongly considered to reduce cumulative steroid exposure in these patients.Footnotes and Disclosure
The authors have no proprietary or commercial interest in any materials discussed in this article.
This work was supported by the Eaton Balyeat Resident Research Fund at the University of Oklahoma Health Sciences Center, Dean McGee Eye Institute, Oklahoma City, OK.
References
- Giant cell arteritis and polymyalgia rheumatica.Med Clin North Am. 1997; 81: 195-219
- Prednisolone combined with adjunctive immunosuppression is not superior to prednisolone alone in terms of efficacy and safety in giant cell arteritis: meta-analysis.Clin Rheumatol. 2014; 33: 227-236
- Current understanding and management of giant cell arteritis and polymyalgia rheumatica.Expert Rev Clin Immunol. 2010; 6: 913-928
- for the European Vasculitis Study Group. EULAR recommendations for the management of large vessel vasculitis.Ann Rheum Dis. 2009; 68: 318-323
- Trial of tocilizumab in giant-cell arteritis.N Engl J Med. 2017; 377: 317-328
- Tocilizumab for the treatment of large-vessel vasculitis (giant cell arteritis, Takayasu arteritis) and polymyalgia rheumatica.Arthritis Care Res (Hoboken). 2012; 64: 1720-1729
- Newly diagnosed vs. relapsing giant cell arteritis: baseline data from the GiACTA trial.Semin Arthritis Rheum. 2017; 46: 657-664
- Giant cell arteritis: validity and reliability of various diagnostic criteria.Am J Ophthalmol. 1997; 123: 285-296
Article info
Publication history
Published online: September 17, 2022
Accepted:
August 24,
2022
Received in revised form:
August 19,
2022
Received:
August 8,
2022
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Copyright
© 2022 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.
