Treatment Of Large Vessel Vasculitis Research Articles

Diagnostics and treatment of large vessel vasculitis

Giant cell arteritis (GCA) and Takayasu arteritis (TAK), as the main representatives of large vessel vasculitis, are rheumatological autoimmune disorders associated with inflammatory vessel wall changes in the arterial system that can lead to many types of organ damage. In this review the current scientific evidence on the diagnostics and treatment of large vessel vasculitis is evaluated and discussed. In addition to the medical history and clinical presentation, imaging techniques nowadays represent the core of large vessel vasculitis diagnostics and have largely replaced the histological confirmation of GCA. After the diagnosis, acute treatment with glucocorticoids should be initiated as rapidly as possible but in the long term this should be tapered out or replaced by asteroid-sparing basic treatment. In contrast to GCA with already available options and other biologic disease-modifying antirheumatic drugs (DMARDs) about to be approved, there are still no approved biologic DMARD treatment options available for the less common TAK. In contrast to the substantial progress in imaging diagnostics of large vessel vasculitis and with respect to the treatment of GCA, the much rarer TAK still requires intensive research efforts, especially to improve the treatment situation.

Multiple systemic arterial aneurysms in large-vessel vasculitis

Large-vessel vasculitis (LVVs) is a rare inflammatory disease that predominantly affects young females' aorta and its main branches, coronary arteries, and pulmonary arteries. Clinical manifestations result from vascular stenosis, occlusion, and dilation, sometimes complicated by aneurysm rupture or dissection. Early diagnosis and treatment of LVVs are paramount to reducing the risk of ischemic complications such as visual loss and strokes, vascular stenosis and occlusion, and aortic aneurysm formation. The diagnosis of LVVs is often challenging because the presenting clinical features are nonspecific in many cases and are often shared by different types of autoimmune and inflammatory diseases including other systemic vasculitides. Prompt identification of vasculitides is important because they are associated with an increased risk of mortality. Left undiagnosed or mismanaged, these conditions may result in serious adverse outcomes that might otherwise have been avoided or minimized. We report a rare case of the LVVs with multisystemic vascular aneurysms and catastrophic complications of ruptured abdominal aortic aneurysm. Our case highlights that an early diagnosis of the diverse manifestations of vasculitis and a high index of clinical suspicion is essential to avoid delays in disease recognition that may result in permanent or life-threatening morbidity.

Pros and cons of TNF inhibitors and tocilizumab in the treatment of large-vessel vasculitis.

Large-vessel vasculitides (LVVs) include giant cell arteritis (GCA) and Takayasu's arteritis (TAK). Even if similar, these two entities differ in terms of treatment and outcomes.High doses of glucocorticoids (GCs) are still the first choice for the treatment of both conditions. However, adjunctive therapies are recommended in selected patients in order to decrease the risk of relapse and the amount of side effects related to GCs. Tumour necrosis factor α inhibitors (TNFis) and tocilizumab (TCZ) are used for the treatment of LVVs, with some differences. In GCA, TCZ has been proved to be effective and safe in inducing remission with some open questions still remaining, whereas data about TNFis are scarce and non-conclusive. On the contrary, in TAK either TNFis or TCZ seem to be able to control symptoms and angiographic progression in refractory forms.However, their place in the management of treatment must still be clarified, and as a result the American College of Rheumatology and EULAR guidelines slightly differ in the recommendations about when and what treatment to start. Thus, the aim of this review is to look at the evidence on the use of TNFis and TCZ in LVVs, outlining the pros and cons of both therapies.

Giant cell arteritis successfully treated with subcutaneous tocilizumab monotherapy.

Glucocorticoid remains the mainstay for treatment of large vessel vasculitis (LVV) including giant cell arteritis (GCA); however, the disease affects the elderly for whom the adverse effects of glucocorticoid are problematic. Recently, some reports have suggested that intravenous tocilizumab (TCZ) monotherapy is effective for this disease. To date, it remains unknown whether subcutaneous TCZ monotherapy is also effective. Here, we present a first case of GCA successfully treated with subcutaneous TCZ monotherapy. A 75-year-old woman presented with shoulder and hip pain. She was diagnosed with polymyalgia rheumatica (PMR) and treated with low-dose prednisolone (15mg daily); however, she discontinued glucocorticoid therapy at her discretion due to the psychiatric adverse effect (cognitive dysfunction). Seven months later, her shoulder and hip pain relapsed. Furthermore, 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) revealed uptake in the descending thoracic aorta, indicating a complication of LVV. She refused to take glucocorticoid for fear of psychiatric adverse effects and chose subcutaneous TCZ monotherapy (162mg weekly) for treating this life-threatening urgent condition. Nine months later, her shoulder and hip pain resolved and FDG-PET/CT demonstrated no uptake in the descending thoracic aorta, indicating a successful treatment with subcutaneous TCZ monotherapy for the disease. No adverse events and disease relapse were found during observation period. Our case and the literature review suggest that not only intravenous injection but also subcutaneous injection of TCZ monotherapy can serve as an alternative treatment for patients with GCA who have comorbidities or refuse to take glucocorticoid.

Idiopathic Non-atherosclerotic Carotid Artery Disease.

The purpose of this review is to provide an overview of idiopathic non-atherosclerotic causes of carotid artery disease and its manifestations. Four major causes of non-atherosclerotic carotid artery disease including dissection, fibromuscular dysplasia, moyamoya disease, and inflammatory large vessel vasculitis are discussed. While there is a dearth of clinical trials involving some of the rarer conditions, recent data from clinical trials supporting antiplatelet over anticoagulation treatment of cervical artery dissection, recent consensus statements on the management of fibromuscular dysplasia, and guideline approaches to diagnosis and treatment of large vessel vasculitis are summarized. Idiopathic non-atherosclerotic causes of carotid artery disease are under appreciated and may lead to significant morbidity and mortality. While less common compared with atherosclerotic disease, non-atherosclerotic disease may affect younger patient populations and result in non-cerebrovascular arterial involvement and systemic organ damage. Therefore, prompt recognition of these disorders is key to their management.

EULAR recommendations for the use of imaging in large vessel vasculitis in clinical practice summary.

Large vessel vasculitis (LVV) is the most common form of primary vasculitis comprising of giant cell arteritis (GCA), Takayasu's arteritis (TAK) and idiopathic aortitis. Early diagnosis and treatment of LVV are paramount to reduce the risk of ischemic complications such as visual loss and strokes, vascular stenosis and occlusion, and aortic aneurysm formation. Use of imaging modalities [ultrasound (US), magnetic resonance imaging (MRI), computed tomography (CT) and [18F]-fluorodeoxyglucose positron emission tomography (PET)] has steadily increased to enable assessment of cranial and extracranial arteries, as well as the aorta. These imaging modalities are less invasive, more sensitive and readily available compared to temporal artery biopsy (TAB). Modern imaging methods have changed the role of TAB in diagnosing GCA and have replaced diagnostic angiography. Over the last two decades, several studies have evaluated the use of US, MRI, CT and PET in LVV. However, these various imaging tools are not yet uniformly used in routine clinical practice and controversy exists as to which imaging modality best provides meaningful assessments of disease activity and damage in LVV. In January 2018, evidence-based recommendations for the use of imaging modalities in LVV were published. The aim of this review is to summarize the current evidence of imaging in patients with or suspected of having LVV, and to highlight the clinical implications of the EULAR recommendations.

PET/CT for Diagnosis and Management of Large-Vessel Vasculitis.

This review aims to discuss the use of fluorodeoxyglucose (FDG) positron emission tomography (PET/CT) for diagnosis and management of patients with large-vessel vasculitis (LVV). Incidence of LVV is likely underestimated, in part due to its non-specific symptoms. Nevertheless, early diagnosis of LVV is essential to initiate timely therapy in order to prevent vascular complications, such as stenoses and aneurysms. FDG PET/CT imaging has the ability to detect LVV during the acute phase, prior to edema and other vascular structural changes, with its high sensitivity for inflammatory activity. FDG PET/CT was shown to be a powerful prognostic marker by allowing identification of patients at risk of vascular complications. Additionally, preliminary data support the use of FDG PET/CT to follow therapy efficacy. FDG PET/CT allows early detection of inflammation, before morphological and irreversible vascular changes can be observed, allowing prompt diagnosis and treatment of LVV.

Tocilizumab in Large Vessel Vasculitis - Different Routes of Administration.

Background:Tocilizumab is increasingly used in the treatment of large vessel vasculitis with recent approval for giant cell arteritis.Objective:To determine the efficacy and safety of tocilizumab in large vessel vasculitis in a real-life setting using different routes of administration.Methods:Retrospective analysis of consecutive patients at a tertiary rheumatology department who received tocilizumab for large vessel vasculitis.Results:A total of 11 patients were treated with tocilizumab (8 giant cell arteritis, 2 large vessel vasculitis associated with rheumatoid arthritis, 1 Takayasu arteritis) after a median of 2 other steroid-sparing agents (range 1-4). Of these, 9 received tocilizumab as salvage therapy for active vasculitis and 2 due to the toxicity of their former steroid-sparing medication. After a mean follow-up of 23 months 7 patients were in remission as to vasculitis under a mean prednisolone dose of 1.7 ± 1.5 mg; one patient relapsed after long term remission having discontinued tocilizumab for elective surgery; one patient stopped tocilizumab after attributable infectious complications, and two patients died: one due to complications of vascular surgery, probably not attributable to tocilizumab; and the other due to sepsis secondary to sigmoiditis. Only 3 relapses occurred under continuous tocilizumab treatment. In all these 3 cases, renewed remission could be achieved by switching from subcutaneous (162 mg qw) to intravenous tocilizumab (8mg/kg q4w).Conclusion:Tocilizumab is efficacious in patients with large vessel vasculitis in a real-life situation. Safety appears to be acceptable, but infectious complications have to be considered. Intravenous tocilizumab may be used in patients who relapse under subcutaneous application.

Use of FDG-PET Scan for the Assessment of Large Vessel Vasculitis

Temporal artery biopsy will only detect (part of) the cranial forms of giant cell arteritis. For the large vessel variant of this type of vasculitis, FDG-PET is the technique of choice. Since treatment of large vessel vasculitis implies long-term treatment with steroids, it is important to have a firm diagnosis. I suggest performing a FDG-PET scan in every patient in whom large vessel vasculitis is suspected and in whom the temporal artery biopsy is negative. In the follow-up of giant cell arteritis patients, we can rely on clinical symptoms and inflammatory parameters to monitor disease activity and to adapt our treatment and do not need to repeat FDG-PET scan. In Takayasu arteritis, follow-up FDG-PET scans are probably necessary to assess ongoing inflammation, but prospective studies are lacking.

Recent advances in the clinical management of giant cell arteritis and Takayasu arteritis.

This 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. The 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. Interleukin-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.

Takayasu arteritis and antiphospholipid antibody syndrome in an elderly woman

Takayasu arteritis and antiphospholipid antibody syndrome in an elderly woman

E62. Is Mycophenolate Mofetil Effective in the Treatment of Large Vessel Vasculitis?

E62. Is Mycophenolate Mofetil Effective in the Treatment of Large Vessel Vasculitis?

SAT0161 The Role of Biological Agents in the Management of Large Vessel Vasculitis (LVV): A Systematic Review

BackgroundLarge vessel vasculitis (LVV) includes two major variants with similar histopathology - giant cell arteritis (GCA) and Takayasu’s arteritis (TAA). High dose glucocorticoids are the mainstay for treatment; however, many...

AB0762 Biological therapy for large vessel vasculitis: A systematic review

BackgroundTreatment of large-vessel vasculitis (LVV) is mainly based on high doses of corticosteroids (CS). There is controversy on the use of methotrexate and azathioprine as steroid-sparing. Cytokines like IL-6 or...

SP0077 Vasculitis: Year in Review

A major achievement in nosology has been the development of novel classification criteria for Behçet disease (BD), called “International criteria for Behçet’s disease” (ICBD) (1). Data on 2556 patients with...

Tocilizumab: a novel therapy for patients with large-vessel vasculitis

Treatment of large-vessel vasculitis (LVV) remains challenging. Patients usually respond to glucocorticoid (GC) therapy, but often relapse on tapering of the GC dose or after GC withdrawal. In addition, GCs are fraught with numerous adverse events. The aim of this study was to assess the efficacy and safety of the anti-IL-6 receptor (IL-6R) antibody tocilizumab (TCZ) in patients with LVV. Four patients with active LVV (two with GCA and two with Takayasu arteritis) received monthly TCZ infusions (8 mg/kg bodyweight) for 6 consecutive months. Two patients were treatment naïve, while two had relapsing disease. Disease activity and drug tolerability were assessed clinically and by laboratory tests at study entry and subsequently every month for 6 months of TCZ treatment, while an [(18)F]fluorodeoxyglucose PET (PET/CT) scan was performed before and after treatment. In addition, a semi-quantitative clinical evaluation was performed at baseline and at 3 and 6 months using the Indian Takayasu activity score and the Kerr indices. After TCZ, MTX was used as maintenance therapy. All patients treated with TCZ therapy had a satisfactory clinical and laboratory response, while PET/CT findings significantly improved in all cases. No serious adverse events were noted. Only one patient had a transient increase in liver enzymes. In this small group of patients with LVV, treatment with TCZ was effective and well tolerated. Further, larger studies are required to confirm our findings.

Treatment of Large Vessel Vasculitis

Giant-cell arteritis (GCA) and Takayasus arteritis (TAK) are chronic and relapsing inflammatory diseases involving large and medium sized arteries. While symptoms derived from large-vessel involvement characterize TAK clinical presentation, cranial symptoms and complications usually dominate the clinical picture of GCA. However, delayed consequences of large-artery involvement are being increasingly recognized. Glucocorticoids are the mainstay of treatment for both conditions but flares and relapses are common when glucocorticoids are tapered or discontinued and adverse effects are frequent. Methotrexate has shown modest efficacy as glucocorticoid-sparing agent in GCA whereas infliximab did not demonstrate benefit in a randomized clinical trial. Adjuvant treatment for TAK is only supported by open-label trials and observational studies and small series, and methotrexate is the most widely used immunosuppressive agent. Infliximab shows promise for refractory/relapsing TAK as supported by an open label study with long-term follow up. Abatacept is currently being tested for both diseases in a randomized controlled trial. Other investigational agents in the horizon such as rituximab and tocilizumab have been anecdotally used but their efficacy needs to be confirmed. Revascularization procedures, mainly angioplasty, play a crucial role in the management of patients with TAK. Keywords: Giant-cell arteritis, Takayasu's disease, treatment, aortitis, aorta, Vasculitis, systemic vasculitis, revascularisation, biologic therapies

APOE epsilon2-4 and -491 polymorphisms are not associated with MS.

<h3>Background</h3> The mainstay of treatment for large vessel vasculitis is glucocorticoids. Immuno-suppressants, including mycophenolate mofetil (MMF) and methotrexate (MTX) are used as steroid-sparing agents.¹ A previous study at our centre showed MMF to have a steroid sparing effect in 97% of patients and to reduce C-reactive protein (CRP) in 80%.² <h3>Objectives</h3> This study was undertaken to compare the efficacy of MMF or MTX combined with prednisolone or prednisolone alone in the treatment of large vessel vasculitis. <h3>Methods</h3> Patients with large vessel vasculitis (LVV) confirmed on positron emission tomography (PET) scan and those meeting ACR criteria for a diagnosis of giant cell arteritis (GCA), treated with prednisolone alone, prednisolone with MMF or prednisolone with MTX started within 3 months of prednisolone being commenced and with a minimum follow up of 24 months were included in a retrospective single centre study. CRP and prednisolone doses were recorded at baseline, after 3, 6, 9, 12, 18 and 24 months of treatment and area under the curve (AOC) calculated for CRP and prednisolone doses. Median AOC prednisolone dose for patients treated with MMF or MTX was then compared with that of patients treated with prednisolone alone. A quantile regression model was also constructed to compare prednisolone dose between the 3 treatment groups, adjusted for CRP. StataCorp. 2013. <i>Stata Statistical Software: Release 13</i>. College Station, TX: StataCorp LP was used for all statistical calculations. <h3>Results</h3> 65 patients were included in the study, 41 with GCA and 24 LVV. 49 were female and 16 male. Mean age at diagnosis was 68; range 21 to 87. 37 patients were treated with prednisolone alone; 35 had GCA and 2 LVV. 20 were treated with MMF and prednisolone; 4 with GCA and 16 LVV. 8 were treated with MTX and prednisolone; 2 had GCA and 6 LVV. The AOC for prednisolone and CRP were not normally distributed across the cohort, and non-parametric methods were therefore used for comparisons. Median AOC prednisolone dose for the prednisolone only group was 68.0, (interquartile range (IQR) 17.7, n=37), for the MMF treated group 70.8 (IQR 28.7, n=20) and for the MTX treated group 67.8 (IQR 20.4 n=8). Median AOC CRP was highest in the group treated with prednisolone alone (58.9, IQR 34.5) compared to MMF (43.8, IQR 26.5) and MTX (49.3 IQR 67.5) but there were no statistical differences between median AOC prednisolone dose or CRP in either the unadjusted or regression models. <h3>Conclusions</h3> No significant difference was shown between the groups. MMF is as effective as MTX and prednisolone alone in the treatment of LVV. However, there are limitations to the study. The patient group was small. There was no randomisation to treatment group; treatment choice was based on clinician preference. There was potential bias in that patients perceived to be more difficult to treat may have been given MMF or MTX in addition to prednisolone, and there was a higher proportion of patients with LVV compared to GCA in the MMF and MTX treated groups. <h3>References</h3> [1] Mukhtyar C, et al. EULAR recommendations for the management of large vessel vasculitis. Ann Rheum Dis2009:68:318–23. [2] Smith R et al.Is Mycophenolate Mofetil Effective in the Treatment of Large Vessel Vasculitis? <i>Rheumatology</i>54, Issue suppl_1, 1 April 2015, Pages i194. <h3>Disclosure of Interest</h3> None declared