Treatment of giant-cell arteritis: from broad spectrum immunosuppressive agents to targeted therapies

Abstract For decades, the treatment of GCA has relied on glucocorticoids. Work over the past two decades has supported a modest efficacy of MTX but no clear benefit from anti-TNF-based therapies. More recently, the therapeutic armamentarium for GCA has expanded. The availability of agents targeting specific cytokines, cytokine receptors or signalling pathways, along with a better, although still limited, understanding of the immunopathology of GCA, are opening further therapeutic possibilities. Blocking IL-6 receptor with tocilizumab has been effective in maintaining remission and reducing glucocorticoid exposure and tocilizumab has been approved for the treatment of GCA. However, nearly half of the patients do not benefit from tocilizumab and additional options need to be investigated. This review focuses on standard therapeutic approaches and on targeted therapies that have been or are currently under investigation.

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Severe Intracranial Involvement in Giant Cell Arteritis: 5 Cases and Literature Review

The Journal of Rheumatology ◽

10.3899/jrheum.150143 ◽

2016 ◽

Vol 43 (3) ◽

pp. 648-656 ◽

Cited By ~ 19

Author(s):

Roaa S. Alsolaimani ◽

Sankalp V. Bhavsar ◽

Nader A. Khalidi ◽

Christian Pagnoux ◽

Jennifer L. Mandzia ◽

...

Keyword(s):

Literature Review ◽

Giant Cell Arteritis ◽

Giant Cell ◽

Treatment Options ◽

Immunosuppressive Agents ◽

Oral Prednisone ◽

Temporal Artery Biopsy ◽

Neurologic Complications ◽

Conventional Angiography ◽

Acr Criteria

Objective.Involvement of intracranial arteries in giant cell arteritis (GCA) is rare. We describe the neurologic complications of intracranial GCA (IC GCA) and available treatment options.Methods.We describe 5 IC GCA cases from 3 Canadian vasculitis centers and review the literature. We searched English-language publications reporting similar patients meeting American College of Rheumatology (ACR) criteria for GCA and having intracranial artery involvement diagnosed by autopsy, magnetic resonance angiography, computed tomography angiography, or conventional angiography.Results.All 5 cases of IC GCA met ACR criteria for GCA; 4 cases had a temporal artery biopsy that was consistent with GCA. All cases experienced cerebrovascular accident(s). Arteritis involved the following vessels: intracranial internal carotid (n = 1), vertebrobasilar arteries (n = 1), or both (n = 3). All cases received aspirin and oral prednisone (preceded by intravenous methylprednisone in 3 cases), combined with an immunosuppressant in 4 cases. All patients survived; 2 had complete neurological recovery, 3 had residual neurologic sequelae. The literature review included 42 cases from 28 publications. The clinical features of the reported cases were similar to those of our 5 cases. However, mortality was 100% in untreated cases (n = 2), 58% in those treated with corticosteroid alone (n = 31), and 40% in those treated with corticosteroid and an immunosuppressant (n = 10).Conclusion.IC GCA appears to be associated with neurologic complications and mortality. In some cases corticosteroid alone was not sufficient to prevent neurologic complications. The role of additional immunosuppressive agents needs further investigation.

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The Birmingham Vasculitis Activity Score as a Measure of Disease Activity in Patients with Giant Cell Arteritis

The Journal of Rheumatology ◽

10.3899/jrheum.151063 ◽

2016 ◽

Vol 43 (6) ◽

pp. 1078-1084 ◽

Cited By ~ 14

Author(s):

Tanaz A. Kermani ◽

David Cuthbertson ◽

Simon Carette ◽

Gary S. Hoffman ◽

Nader A. Khalidi ◽

...

Keyword(s):

Disease Activity ◽

Giant Cell Arteritis ◽

Giant Cell ◽

Rank Correlation ◽

Activity Score ◽

Birmingham Vasculitis Activity Score ◽

Persistent Symptoms ◽

The Past ◽

Spearman’S Rank Correlation ◽

Spearman’S Correlation

Objective.To evaluate the performance of the Birmingham Vasculitis Activity Score (BVAS) in the assessment of disease activity in giant cell arteritis (GCA).Methods.Patients with GCA enrolled in a prospective, multicenter, longitudinal study with symptoms of active vasculitis during any visit were included. Spearman’s rank correlation was used to explore the association of the BVAS with other measures of disease activity.Results.During a mean (SD) followup of 2.3 (1.6) years, symptoms of active GCA were present in 236 visits in 136 subjects (100 female, 74%). Median (range) BVAS1 (new/worse symptoms) was 1 (0–10) and median (range) BVAS2 (persistent symptoms) was 0 (0–5). Median (range) physician’s global assessment (PGA) was 4 (0–9) for disease activity in the past 28 days and 2 (0–9) for activity on the day of the visit. Important ischemic manifestations of active vasculitis not recorded by the BVAS included tongue/jaw claudication (27%), upper extremity claudication (15%), lower extremity claudication (5%), carotidynia (7%), and ischemic retinopathy (5%). During 25 visits (11%) with active disease, all symptoms of active vasculitis were placed in the “Other” category yet still resulted in a BVAS1 and BVAS2 of 0. BVAS1 moderately correlated with PGA for the past 28 days (Spearman’s correlation 0.50) and physician-rated disease activity for the past 28 days (Spearman’s correlation 0.46).Conclusion.The BVAS has limited utility in GCA. Patients with active GCA can have a BVAS of 0. Many important ischemic symptoms attributable to active vasculitis are not included in the composite score.

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Pathogenesis of giant-cell arteritis: how targeted therapies are influencing our understanding of the mechanisms involved

Rheumatology ◽

10.1093/rheumatology/kex423 ◽

2018 ◽

Vol 57 (suppl_2) ◽

pp. ii51-ii62 ◽

Cited By ~ 10

Author(s):

Nekane Terrades-Garcia ◽

Maria C Cid

Keyword(s):

Giant Cell Arteritis ◽

Giant Cell ◽

Targeted Therapies

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Visual Manifestations in Giant Cell Arteritis: Trend over 5 Decades in a Population-based Cohort

The Journal of Rheumatology ◽

10.3899/jrheum.140188 ◽

2014 ◽

Vol 42 (2) ◽

pp. 309-315 ◽

Cited By ~ 55

Author(s):

Abha G. Singh ◽

Tanaz A. Kermani ◽

Cynthia S. Crowson ◽

Cornelia M. Weyand ◽

Eric L. Matteson ◽

...

Keyword(s):

Giant Cell Arteritis ◽

Giant Cell ◽

Optic Neuropathy ◽

Vision Loss ◽

Population Based ◽

Ischemic Optic Neuropathy ◽

Visual Symptoms ◽

The Past ◽

Trends Over Time ◽

Visual Changes

Objective.To evaluate clinical characteristics, treatment, and outcomes of patients with visual changes from giant cell arteritis (GCA) and to examine trends over the last 5 decades.Methods.We reviewed the medical records of a population-based cohort of patients with GCA diagnosed between 1950 and 2004. The clinical, ophthalmological, and laboratory features of patients with visual manifestations attributable to GCA were compared to patients without visual complications. Trends over time were examined using logistic regression modeling adjusted for age and sex.Results.In a cohort of 204 cases of GCA (mean age 76.0 ± 8.2 yrs, 80% female), visual changes from GCA were observed in 47 patients (23%), and 4.4% suffered complete vision loss. A higher proportion of patients with visual manifestations reported jaw claudication than did patients without visual changes (55% vs 38%, p = 0.04). Over a period of 55 years, we observed a significant decline in the incidence of visual symptoms due to GCA. There was a lower incidence of ischemic optic neuropathy in the 1980–2004 cohort vs 1950–1979 (6% vs 15%, p = 0.03). Patients diagnosed in later decades were more likely to recover from visual symptoms (HR 1.34, 95% CI 1.06–1.71). Chances of recovery were poor in patients with anterior ischemic optic neuropathy or complete vision loss.Conclusion.Incidence of visual symptoms has declined over the past 5 decades, and chances of recovery from visual symptoms have improved. However, complete loss of vision is essentially irreversible. Jaw claudication is associated with higher likelihood of development of visual symptoms.

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Innate and Adaptive Immunity in Giant Cell Arteritis

Frontiers in Immunology ◽

10.3389/fimmu.2020.621098 ◽

2021 ◽

Vol 11 ◽

Author(s):

Mitsuhiro Akiyama ◽

Shozo Ohtsuki ◽

Gerald J. Berry ◽

David H. Liang ◽

Jörg J. Goronzy ◽

...

Keyword(s):

Immune Responses ◽

Autoimmune Diseases ◽

Giant Cell Arteritis ◽

Blood Vessels ◽

Giant Cell ◽

T Regulatory Cells ◽

Cell Function ◽

Immunological Tolerance ◽

Therapeutic Approaches ◽

Effector Cells

Autoimmune diseases can afflict every organ system, including blood vessels that are critically important for host survival. The most frequent autoimmune vasculitis is giant cell arteritis (GCA), which causes aggressive wall inflammation in medium and large arteries and results in vaso-occlusive wall remodeling. GCA shares with other autoimmune diseases that it occurs in genetically predisposed individuals, that females are at higher risk, and that environmental triggers are suspected to beget the loss of immunological tolerance. GCA has features that distinguish it from other autoimmune diseases and predict the need for tailored diagnostic and therapeutic approaches. At the core of GCA pathology are CD4+ T cells that gain access to the protected tissue niche of the vessel wall, differentiate into cytokine producers, attain tissue residency, and enforce macrophages differentiation into tissue-destructive effector cells. Several signaling pathways have been implicated in initiating and sustaining pathogenic CD4+ T cell function, including the NOTCH1-Jagged1 pathway, the CD28 co-stimulatory pathway, the PD-1/PD-L1 co-inhibitory pathway, and the JAK/STAT signaling pathway. Inadequacy of mechanisms that normally dampen immune responses, such as defective expression of the PD-L1 ligand and malfunction of immunosuppressive CD8+ T regulatory cells are a common theme in GCA immunopathology. Recent studies are providing a string of novel mechanisms that will permit more precise pathogenic modeling and therapeutic targeting in GCA and will fundamentally inform how abnormal immune responses in blood vessels lead to disease.

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