Abstract
GCA is a chronic, idiopathic, granulomatous vasculitis of medium and large arteries. It comprises overlapping phenotypes including classic cranial arteritis and extra-cranial GCA, otherwise ...termed large-vessel GCA (LV-GCA). Vascular complications associated with LV-GCA may be due, in part, to delayed diagnosis, highlighting the importance of early identification and prompt initiation of effective therapy. Advancements in imaging techniques, including magnetic resonance angiography, CT angiography, PET and colour duplex ultrasonography, have led to improvements in the diagnosis of LV-GCA; however, the role imaging modalities play in the assessment of disease activity and long-term outcomes remains unclear. Glucocorticoids are the mainstay of therapy in LV-GCA, but their prolonged use is associated with multiple, sometimes serious, adverse effects. Recent data suggest that biologic therapies, such as tocilizumab, may be effective and safe steroid-sparing options for patients with GCA. However, data specifically evaluating the management of LV-GCA are limited.
VEXAS syndrome (vacuoles in myeloid progenitors, E1 ubiquitin activating enzyme, X-linked, autoinflammatory manifestations and somatic) is an autoinflammatory condition caused by somatically acquired ...UBA1 mutations. Heiblig et al report on an international retrospective analysis of 30 patients with VEXAS syndrome treated with different Janus kinase (JAK) inhibitors, finding encouraging evidence supporting the use of the JAK1/2 inhibitor ruxolitinib with clinical remissions and reductions in steroid use seen in the majority of patients.
To evaluate characteristics of relapse, relapse rates, treatment and outcomes among patients with biopsy-proven GCA in a large, single-institution cohort.
We conducted a retrospective review of all ...patients with biopsy-proven GCA from 1998 to 2013. Demographic, clinical, laboratory and treatment data at presentation and during follow-up were collected. Comparisons by relapse rate were performed using chi-square tests. Prednisone discontinuation by initial oral dose ≤40 and >40 mg/day was compared using Cox models.
The cohort included 286 patients 74% female, mean age at diagnosis 75.0 years (s.d. 7.6), median follow-up 5.1 years). During follow-up, 73 patients did not relapse, 80 patients had one relapse and 133 had two or more relapses. The first relapse occurred during the first year in 50% of patients, by 2 years in 68% and by 5 years in 79%. More patients with established hypertension (P = 0.007) and diabetes (P = 0.039) at GCA diagnosis were in the high relapse rate group ( ≥ 0.5 relapses/year) and more females were in the low or high relapse groups than in the no relapse group (P = 0.034). Patients receiving an initial oral prednisone dose >40 mg/day were able to reach a dose of <5 mg/day hazard ratio (HR) 1.46 (95% CI 1.09, 1.96) and discontinue prednisone HR 1.56 (95% CI 1.09, 2.23) sooner than patients receiving ≤40 mg/day without an increase in observed glucocorticoid-associated adverse events.
Females and patients with hypertension or diabetes at GCA diagnosis have more relapses during follow-up. Patients treated with an initial oral prednisone dose >40 mg/day achieved earlier prednisone discontinuation.
PURPOSE OF REVIEWThis article critically reviews the advances in medical management of giant cell arteritis (GCA) and Takayasu arteritis (TAK) with a focus on recent developments in targeted biologic ...therapy.
RECENT FINDINGSThe role of biologics in the treatment of large vessel vasculitis (LVV) is expanding. TNFα inhibitors appear to be effective in the treatment of TAK but have little benefit in GCA. Preliminary clinical trial data suggest that abatacept and tocilizumab reduce the risk of relapse in GCA. Increasing observational evidence supports the use of interleukin-6 inhibitors in TAK. Based on a small open-label study, ustekinumab appears safe and potentially effective for refractory GCA. A possible role of B cell dysregulation may contribute to pathogenic mechanisms in LVV, but support for the use of B cell depleting therapy is limited.
SUMMARYInterleukin-6 inhibitors appear efficacious in the treatment of refractory cases of LVV; however, utility in newly diagnosed immunosuppressive-naïve patients is less well established. Abatacept and ustekinumab are promising targets for therapy in LVV but further investigation is needed before routine use is considered.
Giant cell arteritis (GCA) is the most common primary systemic vasculitis in adults 50 years or older. Expanded use of advanced arterial imaging has assisted both in the diagnosis of GCA and ...recognition of disease subsets. Although glucocorticoids have been the mainstay of treatment for almost 7 decades, new therapeutic options have emerged. This review aims to provide the clinician with a pragmatic approach to evaluating and managing patients with GCA while also addressing recent diagnostic and therapeutic developments.
Abstract
VEXAS (
V
acuoles,
E
1 enzyme,
X
-linked,
A
utoinflammatory,
S
omatic) syndrome is a newly identified disease caused by somatic mutations in the
UBA1
gene resulting in refractory ...autoinflammatory features, frequently accompanied by cytopenias. Although the prevalence of this syndrome is yet unknown, understanding the clinical phenotype can assist clinicians in prompt recognition of cases among patients with glucocorticoid-responsive but immunosuppressive-resistant inflammatory symptoms. The pathophysiology, clinical presentation, diagnostic methods, treatment, and prognosis of VEXAS are herein reviewed.
PDF
