Biologic Therapy for the Treatment of Giant Cell Arteritis.
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ABSTRACT:
SUBMITTER: Ostrowski RA
PROVIDER: S-EPMC5123077 | biostudies-other | 2014
REPOSITORIES: biostudies-other
Publications
Biologic Therapy for the Treatment of Giant Cell Arteritis.
Ostrowski Rochella A RA Bussey Melissa R MR Tehrani Rodney R Jay Walter W
Neuro-ophthalmology (Aeolus Press) 20140402 3
Giant cell arteritis (GCA), a vasculitis of the medium and large arteries, is traditionally managed with glucocorticoids. However, the side effects of chronic glucocorticoid use and the occurrence of refractory cases warrant the consideration of steroid-sparing agents, including biologic agents. Interleukin-6 (IL-6) inhibition shows the most promise as biologic therapy for refractory cases of GCA, but data to support the use of other existing biologic agents are currently lacking. A better under ...[more]
Similar Datasets
Project description:Glucocorticoids have been the mainstay of treatment in giant cell arteritis (GCA) for the past 70 years. Conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) have largely failed to show significant clinical efficacy or reduction of the glucocorticoid burden in GCA. Tocilizumab is the first biologic to make a substantial impact in GCA treatment. With the current understanding of GCA pathogenesis implicating multiple cytokines, notably interleukin (IL) 6, IL-12, IL-23, IL-1β, and the role of janus kinases (JAKs) and the signal transducer and activator of transcription (STAT) pathway in these cytokines, many biologics are currently being investigated in GCA. This review article looks at the existing evidence for biologic agents in GCA. In addition to tocilizumab, the potential role of ustekinumab, abatacept, JAK inhibitors and other promising biologics in GCA are discussed in detail. A treatment algorithm based on the best evidence to date is also presented.
| S-EPMC7797292 | biostudies-literature
Project description:ObjectiveIdentify predictors of treatment failure in patients with giant cell arteritis (GCA) receiving tocilizumab in combination with glucocorticoids and in patients with GCA receiving only glucocorticoids.MethodsPosthoc analysis of the Giant-Cell Arteritis Actemra trial including 250 patients who received tocilizumab every week plus a 26-week prednisone taper (n=100), tocilizumab every-other-week plus a 26-week prednisone taper (n=49) or placebo plus a 26-week (n=50) or 52-week (n=51) prednisone taper in the intention-to-treat population. Responders for this analysis were patients who maintained remission (no GCA signs/symptoms and no erythrocyte sedimentation rate elevation) through week 52. Treatment failure was defined as inability to achieve remission by week 12 or relapse between weeks 12 and 52. Predictors investigated in univariate and multivariable analyses included patient characteristics, disease-related and treatment-related factors and patient-reported outcomes (PROs).Results149 patients received tocilizumab plus prednisone (TCZ/PDN) and 101 received placebo plus prednisone (PBO+PDN). After adjustment for confounders, treatment failure was significantly less likely in the TCZ/PDN group than the PBO/PDN group (OR, 0.2; 95% CI, 0.1 to 0.3; p<0.0001). Risk for treatment failure was significantly higher in women than men in the PBO/PDN group (OR, 5.2; 95% CI, 1.6 to 17.2; p=0.007) but not in the TCZ/PDN group. Predictors of treatment failure in the TCZ/PDN group included lower baseline prednisone doses and worse PROs at baseline.ConclusionThe strongest risk factors for treatment failure in GCA are treatment with prednisone alone and female sex. Lower starting prednisone doses and impaired PROs are associated with failure to respond to tocilizumab.Trial registration numberNCT01791153.
| S-EPMC8522464 | biostudies-literature
Project description:Background: Giant cell arteritis (GCA) is the most common primary systemic vasculitis predominantly affecting large and medium sized vessels. In rare cases, the vasculitis can affect the vessels of the brain. Results: We describe four cases of GCA with involvement of the cerebral vessels causing stroke. These cases were unresponsive to aggressive immunosuppression and we opted to treat with endovascular balloon dilatation of the stenotic areas. The procedure was safe. The four patients were treated in nine sessions and a total of 16 vessels were treated. We observed two dissections with no clinical influence on the patients. Discussion: In patients with stroke due to progressive GCA that is non-responsive to immunosuppression, endovascular therapy is feasible.
| S-EPMC7177021 | biostudies-literature
Project description:Glucocorticoids remain the cornerstone of medical therapy in giant cell arteritis (GCA) and should be started immediately to prevent severe consequences of the disease, such as blindness. However, glucocorticoid therapy leads to significant toxicity in over 80% of the patients. Various steroid-sparing agents have been tried, but robust scientific evidence of their efficacy and safety is still lacking. Tocilizumab, a monoclonal IL-6 receptor blocker, has shown promising results in a number of case series and is now being tested in a multi-centre randomized controlled trial. Other targeted treatments, such as the use of abatacept, are also now under investigation in GCA. The need for surgical treatment is rare and should ideally be performed in a quiescent phase of the disease. Not all patients follow the same course, but there are no valid biomarkers to assess therapy response. Monitoring of disease progress still relies on assessing clinical features and measuring inflammatory markers (C-reactive protein and erythrocyte sedimentation rate). Imaging techniques (e.g., ultrasound) are clearly important screening tools for aortic aneurysms and assessing patients with large-vessel involvement, but may also have an important role as biomarkers of disease activity over time or in response to therapy. Although GCA is the most common form of primary vasculitis, the optimal strategies for treatment and monitoring remain uncertain.
| S-EPMC4468893 | biostudies-other
Project description:Giant cell arteritis (GCA) and Takayasu Arteritis (TAK) are two systemic granulomatous vasculitides affecting medium- and large-sized arteries. Similarities in GCA and TAK regarding the clinical presentation, the systemic inflammatory response and the distribution of the arterial lesions, have triggered a debate over the last decade about whether GCA and TAK represent two different diseases, or are age-associated different clinical phenotypes of the same disease. On the other hand, there are differences regarding epidemiology, several clinical features (eg, polymyalgia rheumatica in GCA) and treatment. The aim of this review is to present the latest data regarding this question and to shed some light on the differences and similarities between GCA and TAK regarding epidemiology, genetics, pathogenesis, histopathology, clinical presentation, imaging and treatment. The existing data in literature support the opinion that GCA and TAK are different clinical entities.
| S-EPMC7362112 | biostudies-literature
Project description:To compare patterns of arteriographic lesions of the aorta and primary branches in patients with Takayasu's arteritis (TAK) and giant cell arteritis (GCA).Patients were selected from two North American cohorts of TAK and GCA. The frequency of arteriographic lesions was calculated for 15 large arteries. Cluster analysis was used to derive patterns of arterial disease in TAK versus GCA and in patients categorised by age at disease onset. Using latent class analysis, computer derived classification models based upon patterns of arterial disease were compared with traditional classification.Arteriographic lesions were identified in 145 patients with TAK and 62 patients with GCA. Cluster analysis demonstrated that arterial involvement was contiguous in the aorta and usually symmetric in paired branch vessels for TAK and GCA. There was significantly more left carotid (p=0.03) and mesenteric (p=0.02) artery disease in TAK and more left and right axillary (p<0.01) artery disease in GCA. Subclavian disease clustered asymmetrically in TAK and in patients ?55 years at disease onset and clustered symmetrically in GCA and patients >55 years at disease onset. Computer derived classification models distinguished TAK from GCA in two subgroups, defining 26% and 18% of the study sample; however, 56% of patients were classified into a subgroup that did not strongly differentiate between TAK and GCA.Strong similarities and subtle differences in the distribution of arterial disease were observed between TAK and GCA. These findings suggest that TAK and GCA may exist on a spectrum within the same disease.
| S-EPMC3729734 | biostudies-literature
Project description:ObjectiveTo identify and validate, using computer-driven methods, patterns of arterial disease in Takayasu arteritis (TAK) and giant cell arteritis (GCA).MethodsPatients with TAK or GCA were studied from the Diagnostic and Classification Criteria for Vasculitis (DCVAS) cohort and a combined North American cohort. Case inclusion required evidence of large-vessel involvement, defined as stenosis, occlusion, or aneurysm by angiography/ultrasonography, or increased 18 F-fluorodeoxyglucose (FDG) uptake by positron emission tomography (PET) in at least 1 of 11 specified arterial territories. K-means cluster analysis identified groups of patients based on the pattern of arterial involvement. Cluster groups were identified in the DCVAS cohort and independently validated in the North American cohort.ResultsA total of 1,068 patients were included (DCVAS cohort: TAK = 461, GCA = 217; North American cohort: TAK = 225, GCA = 165). Six distinct clusters of patients were identified in DCVAS and validated in the North American cohort. Patients with TAK were more likely to have disease in the abdominal vasculature, bilateral disease of the subclavian and carotid arteries, or focal disease limited to the left subclavian artery than GCA (P < 0.01). Patients with GCA were more likely to have diffuse disease, involvement of bilateral axillary/subclavian arteries, or minimal disease without a definable pattern than TAK (P < 0.01). Patients with TAK were more likely to have damage by angiography, and patients with GCA were more likely to have arterial FDG uptake by PET without associated vascular damage.ConclusionArterial patterns of disease highlight both shared and divergent vascular patterns between TAK and GCA and should be incorporated into classification criteria for large-vessel vasculitis.
| S-EPMC7035996 | biostudies-literature
Project description:To characterize the microbiome of the temporal artery in patients with giant cell arteritis (GCA), and to apply an unbiased and comprehensive shotgun sequencing-based approach to determine whether there is an enrichment of candidate pathogens in the affected tissue.Temporal artery biopsy specimens were collected from patients at a single institution over a period of 4 years, and unbiased DNA sequencing was performed on 17 formalin-fixed, paraffin-embedded specimens. Twelve of the 17 patients fulfilled the clinical and histopathologic criteria for GCA, and the other 5 patients served as controls. Using PathSeq software, human DNA sequences were computationally subtracted, and the remaining non-human DNA sequences were taxonomically classified using a comprehensive microbial sequence database. The relative abundance of microbes was inferred based on read counts assigned to each organism. Comparison of the microbial diversity between GCA cases and controls was carried out using hierarchical clustering and linear discriminant analysis of effect size.Propionibacterium acnes and Escherichia coli were the most abundant microorganisms in 16 of the 17 samples, and Moraxella catarrhalis was the most abundant organism in 1 control sample. Pathogens previously described to be correlated with GCA were not differentially abundant in cases compared to controls. There was not a significant burden of likely pathogenic viruses.DNA sequencing of temporal artery biopsy specimens from GCA cases, in comparison with non-GCA controls, showed no evidence of previously identified candidate GCA pathogens. A single pathogen was not clearly and consistently associated with GCA in this case series.
| S-EPMC4113339 | biostudies-literature
Project description:Giant-cell arteritis (GCA), also referred to as temporal arteritis, is the most common primary vasculitis of the elderly involving the extracranial branches of the carotid arteries, in particular, the temporal artery. Patients usually present with temporal headaches, visual impairment, fever, and scalp tenderness. Scalp necrosis associated with GCA is a rare occurrence with approximately 100 cases reported in the literature to date. It is a therapeutic emergency requiring urgent management as it may lead to irreversible loss of vision. To increase awareness of this severe complication, we report a patient with a scalp necrosis revealing a GCA.
| S-EPMC7443249 | biostudies-literature
Project description:Objectives:To evaluate damage and variables associated with damage in GCA. Methods:Patients with GCA enrolled in a prospective, multicentre, longitudinal study were included. Per-protocol assessments were made with the Vasculitis Damage Index and the Large-Vessel Vasculitis Index of Damage. Results:The study included 204 patients: 156 women (76%), mean age at diagnosis 71.3 years (s.d. 8.3), mean follow-up of 3.5 years (s.d. 1.9). One or more damage item was present in 54% at baseline and 79% at the last follow-up on the Vasculitis Damage Index, and 60% at baseline and 82% at the last follow-up on the Large-Vessel Vasculitis Index of Damage. The most frequently observed damage items were large-artery complications (29% cohort) and ocular (22%). Among 117 patients with new damage, most new items were ocular (63 patients), cardiac/vascular (48) and musculoskeletal (34). Of these, treatment-associated items were frequently observed, including cataracts (46 patients), osteoporosis (22) and weight gain (22). Disease-associated new damage included ischaemic optic neuropathy (3 patients), limb claudication (13), arterial occlusions (10) and damage requiring vascular intervention (10). In univariate analysis, the risk of damage increased 22% for every additional year of disease duration [odds ratio (OR) 1.22 (95% CI 1.04, 1.45)]. In 94 patients enrolled within ?90 days of diagnosis of GCA, the risk of new damage at the last follow-up decreased 30% for each additional relapse [OR 0.70 (95% CI 0.51, 0.97)]. Conclusions:Large-artery complications and ocular manifestations are the most commonly occurring items of damage in GCA. Most new damage is associated with treatment. These findings emphasize the cumulative burden of disease in GCA.
| S-EPMC5850105 | biostudies-literature