Treatment Of Giant Cell Arteritis Research Articles

Biologic Therapies for Giant Cell Arteritis

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.

Presentation characteristics and clinical outcome of patients with giant cell arteritis followed by a single center

Giant cell arteritis (GCA) is a large vessel vasculitis that may cause significant morbidity in the elderly population. We aimed to evaluate presentation characteristics, treatment, and outcome in a cohort of patients with GCA diagnosed and followed in a single center. A retrospective chart review revealed 84 (41 M/43 F) registered patients diagnosed as GCA between 1990 and 2020 patients. Clinical features at presentation and follow-up, radiographical imaging, temporal artery biopsy (TAB), and laboratory findings were retrieved from digital medical records or hard-copy patient files. Of these, 33 patients? follow-up period was less than 12 months; hence, relapses and treatment outcomes were examined in the remaining 51 (60.5%) patients. A total of 84 patients were included in the cohort. The mean age at diagnosis was 68.4 ± 7.9 years (range 49-85). At presentation, 60 (71.4%) patients had headache, 22 (26.2%) had symptoms compatible with polymyalgia rheumatica (PMR) and 23 (27.4%) had a visual loss. Three (3.6%) patients had solid organ malignancies while two had hematologic malignancies (2.4%) before GCA diagnosis. TAB was obtained in 63 (75%) patients, of whom 47 (74.6%) the pathological findings were consistent with GCA. A PET/CT scan has been performed before glucocorticoids (GCs) initiation in 43 (51.2%) patients and of these 37 (86.0%) revealed uptake consistent with large vessel involvement. The median follow-up time of the 51 patients was 3.7 (IQR: 1.8-6.8) years. GCs were started promptly after the diagnosis. During the follow-up period, 28 (54.9%) patients experienced a relapse. Thirty-nine (78%) patients were under GC treatment, with a mean dosage of 4.8±2.8 g/day at the final visit. At the final visit, 20.3% (17:84) had died whereas 9.8% (5:51) had permanent vision loss. Treatment of GCA is challenging. GCA causes serious morbidities and increased mortality. PET/CT is highly effective in detecting large vessel vasculitis in GCA and could perhaps replace TAB in the future.

Clinical pathways for patients with giant cell arteritis during the COVID-19 pandemic: an international perspective.

Giant cell arteritis, a common primary systemic vasculitis affecting older people, presents acutely as a medical emergency and requires rapid specialist assessment and treatment to prevent irreversible vision loss. Disruption of the health-care system caused by the COVID-19 pandemic exposed weak points in clinical pathways for diagnosis and treatment of giant cell arteritis, but has also permitted innovative solutions. The essential roles played by all professionals, including general practitioners and surgeons, in treating these patients have become evident. Patients must also be involved in the reshaping of clinical services. As an international group of authors involved in the care of patients with giant cell arteritis, we reflect in this Viewpoint on rapid service adaptations during the first peak of COVID-19, evaluate challenges, and consider implications for the future.

Current advances in giant cell arteritis.

The aim of this study was to present the latest advances in giant cell arteritis (GCA) care, and recent national and international rheumatology societies guidance which influences clinical practice. Cranial ultrasound reduces diagnostic delay and improves clinical outcomes. Immediate high dose glucocorticoids remain the standard treatment for GCA. Controlled trial evidence using Tocilizumab, an interleukin-6 receptor antagonist, shows good clinical efficacy with steroid-sparing effects. Improved patient outcomes require formalizing pathways to diagnosis and closer liaison with rheumatology for long-term management with second-line therapies.

An update on giant cell arteritis

Giant cell arteritis (GCA) is a primary granulomatous systemic vasculitis involving the aorta and its main branches that affects people aged over 50 years with a genetic predisposition. Its main phenotypes are cranial and extracranial involvement, with or without symptoms of polymyalgia rheumatica. These phenotypes can overlap. The extracranial form can be oligosymptomatic and must be sought directly. The main complications of the disease are ischemia of essential territories such as the optic nerve or cerebral circulation, and aneurysmal dilations of the aorta and its large branches. Clinicians must be aware of all the presentation forms of the disease, to start a timely treatment and avoid potentially serious or fatal consequences. To date, the diagnosis of GCA is based on clinical and pathological criteria, with the temporal artery biopsy as the "gold standard" for diagnosis, although its sensitivity is variable. This can lead to an underdiagnosis in patients with negative biopsies or predominant extra-cranial symptoms. The emergence of new and valuable imaging tools substantially improved the timely diagnosis, mainly in subclinical and oligosymptomatic forms. Among them we highlight ultrasonography of the temporal and axillary arteries, Computed Tomography Angiography, Magnetic Resonance Angiography, and PET-CT. These imaging techniques are complementary, and their use is highly recommended. GCA treatment is based on steroidal therapy, often associated with a corticosteroid-sparing immunosuppressive agent. The follow-up is eminently clinical.

Treatment of Giant Cell Arteritis and Takayasu Arteritis-Current and Future.

Purpose of ReviewGuidelines for the management of large vessel vasculitides have been recently updated by several scientific societies. We have evaluated the current recommendations for treatment of giant cell arteritis (GCA) and Takayasu arteritis (TA) and addressed potential future therapeutic strategies.Recent FindingsWhile glucocorticoids (GCs) remain the gold standard for induction of remission, many patients relapse and acquire high cumulative GC exposure. Thus, GC-sparing therapies such as methotrexate are recommended for selected patients with GCA and all patients with TA. Recent high-quality evidence shows that tocilizumab is an effective GC-sparing agent in GCA. Non-biologic and biologic immunomodulators also appear to have GC-sparing properties in TA.SummaryTocilizumab is now considered to be part of the standard treatment for GCA, particularly with relapsing disease, but questions on its use such as length of treatment and monitoring of disease activity remain open. High-quality evidence to guide treatment of TA is still lacking.

Comment on: British Society for Rheumatology guideline on diagnosis and treatment of giant cell arteritis: reply.

Comment on: British Society for Rheumatology guideline on diagnosis and treatment of giant cell arteritis: reply.

S2524 Severe Drug Induced Liver Injury Secondary to Tociluzamab in the Treatment of Giant Cell Arteritis

INTRODUCTION: Drug-induced liver injury (DILI) is one of the most common causes of liver damage in the United States with potentially fatal complications from acute liver failure Herein lies a case of severe DILI as a result of tocilizumab therapy prescribed for Giant Cell Arteritis CASE DESCRIPTION/METHODS: A 67 year-old female with a history of biopsy proven giant cell arteritis, on chronic prednisone and tocilizumab, was admitted for jaundice Prior to hospitalization, the patient had a normal Total Bilirubin (TB) of 0 1 mg/dL (cutoff 1 0), however initial labs showed a TB of 7 5 mg/dL with a Direct Bilirubin (DB) of 5 8 mg/dL (cutoff 0 3) Patient was initially thought to have acute hepatitis However, imaging revealed no obstructive processes and an extensive serological workup (including AFP, ANA, ASMA, AMA, IgG, iron studies, ceruloplasmin, viral panel) was unremarkable The patient gradually worsened with DB 10 2 mg/dL and she was exhibiting signs of hepatic encephalopathy A liver biopsy was performed showing cholestatic hepatitis with zone 3 hepatocellular and canalicular cholestasis, mild lobular activity, prominent lymphocytic cholangitis with acute and chronic pericholangitis and fibrous expansion of the portal tracts These finds were consistent with a drug-induced liver injury (DILI) At that point in her stay, her ALT was 778 u/L (cutoff 31) and an AST of 346 u/L (cutoff 31) Unfortunately, due to the extensive damage done from the offending agent, the patient had severe and permanent liver damage Her MELD score was 27 and she was referred for liver transplant evaluation Despite these measures, her overall clinical picture was poor from extensive comorbidities and ongoing hepatic encephalopathy She was admitted again for deteriorating mental status and expired a few months later DISCUSSION: Drug induced liver injury due to Tocilizumab is a rare complication Although a few case reports exist of Tocilizumab leading to liver injury in patients with Rheumatoid Arthritis and Still's disease, we have found no cases thus far in a patient with Giant Cell Arteritis The exact mechanism of injury is not well understood, but may be due to Toculizimab's effect on the IL-6 pathway which is important in liver regeneration Health care professionals should be aware of the hepatotoxic potential associated with Tocilizumab, especially during the current time period, given it's prevalent use for SARS-CoV-2 Prompt recognition, monitoring of liver function tests and drug discontinuation are imperative

Neurovascular Causes of Acute Monocular Visual Loss

Acute monocular visual loss may result from a diverse set of neurovascular and systemic disorders and requires urgent evaluation. The goal of this review is to describe the most current understanding of the clinical features, pathophysiology, diagnosis, and treatment of these disorders. 1. Acute central retinal artery occlusion (CRAO) should be treated as an equivalent to acute ischemic stroke. 2. Several recent clinical trials are evaluating the treatment of non-arteritic anterior ischemic optic neuropathy (NAION). 3. Tocilizumab is emerging as a first-line steroid-sparing immunomodulatory therapy for the treatment of giant cell arteritis (GCA). 4. Optical coherence tomography (OCT) imaging of the retina has led to the appreciation that retinal capillary ischemia in the form of paracentral acute middle maculopathy (PAMM) is a distinct form of acute monocular visual loss with relatively normal-appearing fundus examination and good prognosis for recovery. Accurate diagnosis and timely treatment of disorders resulting in acute monocular visual loss may reduce the likelihood of additional visual and neurologic complications.

Comment on: British Society for Rheumatology guideline on diagnosis and treatment of giant cell arteritis: reply.

Comment on: British Society for Rheumatology guideline on diagnosis and treatment of giant cell arteritis: reply.

A Multicentre, Randomised, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of Sirukumab in the Treatment of Giant Cell Arteritis.

IntroductionTo evaluate the efficacy and safety of sirukumab in giant cell arteritis (GCA).MethodsIn this multicentre, randomised, double-blind, placebo-controlled, two-part phase 3 trial (NCT02531633; Part A [52-week double-blind treatment]; Part B [104-week follow-up]), patients with GCA were randomised (3:3:2:2:2) to sirukumab 100 mg every 2 weeks plus 6-month or 3-month prednisone taper, sirukumab 50 mg every 4 weeks plus 6-month prednisone taper, or placebo every 2 weeks plus 6-month or 12-month prednisone taper. The primary endpoint was the proportion of patients in sustained remission at week 52. Secondary endpoints included disease flare and safety. The study was terminated early (October 2017; sponsor decision).ResultsOf 161 patients randomised (sirukumab: n = 107; placebo: n = 54), 28 (17.4%) completed week 52 (median treatment duration: 24–30 weeks). In a revised intent-to-treat (ITT) subgroup (completed week 52 or discontinued before study termination [n = 55]); six patients (all receiving sirukumab) achieved the primary endpoint. In the ITT population (n = 161), the proportion of patients with flares (week 2–52) was lower with sirukumab (18.4–30.8%) than placebo (37.0–40.0%). The proportion of patients with flares (week 2–12) was highest with sirukumab 100 mg every 2 weeks plus 3-month prednisone taper (23.1%). In Part A, 94.4% of patients reported ≥ 1 treatment-emergent adverse event (TEAE); 19.3% reported serious TEAEs. The proportions of patients with TEAEs were generally similar across treatment arms. No deaths occurred.ConclusionsAlthough data were limited due to early termination and shortened treatment duration, sirukumab treatment resulted in numerically lower proportions of patients with flare by week 52 versus placebo, with no unexpected safety findings.Trial RegistrationClinicaltrials.gov: NCT02531633.Electronic supplementary materialThe online version of this article (10.1007/s40744-020-00227-2) contains supplementary material, which is available to authorized users.

Comment on: British Society for Rheumatology guideline on diagnosis and treatment of giant cell arteritis.

Comment on: British Society for Rheumatology guideline on diagnosis and treatment of giant cell arteritis.

Timing of cataract surgery in patients with giant cell arteritis.

To determine a safe timeframe and parameters for performing cataract surgery after diagnosis and treatment of giant cell arteritis (GCA). Single institution in the United States. Retrospective chart review. This retrospective study used ICD-9/10 and Current Procedural Terminology codes to identify all patients with biopsy-proven GCA who underwent cataract surgery from 2005 to 2019 at a single institution. Excluded from the study were patients whose date of biopsy diagnosis or dose of corticosteroids at the time of cataract surgery was unknown. Chart review identified 15 eyes of 10 patients that met inclusion criteria; 80% of patients were women, and mean age was 74.4 years. Two patients had a history of arteritic ischemic optic neuropathy. There were no perioperative or postoperative complications in the 15 eyes that underwent cataract surgery with varying doses of prednisone at the time of surgery (1 to 25 mg daily prednisone ± 10 to 25 mg weekly methotrexate; median prednisone dose of 10.75 mg) and varying time from biopsy diagnosis of GCA to surgery of at least 7 months (median 13.75 months). Cataract surgery seemed safe for patients with GCA on varying doses of prednisone at the time of surgery at least 7 months from time of biopsy diagnosis. There is a need for a larger cohort of data from neuro-ophthalmologists and cataract surgeons nationally to establish guidelines for safe cataract surgery in patients with GCA.

Comment on: British Society for Rheumatology guideline on diagnosis and treatment of giant cell arteritis.

Comment on: British Society for Rheumatology guideline on diagnosis and treatment of giant cell arteritis.

Monitoring and long-term management of giant cell arteritis and polymyalgia rheumatica.

Giant cell arteritis (GCA) is the most common type of primary vasculitis in Western countries. Polymyalgia rheumatica (PMR) is the second most common inflammatory rheumatic disease of the elderly after rheumatoid arthritis. Glucocorticoids are the cornerstone of treatment for GCA and PMR, which are interrelated diseases. Glucocorticoids are effective, but adverse effects occur in a high proportion of patients. Careful use of glucocorticoids and the application of preventive strategies can minimize these adverse effects. Possible long-term complications of GCA include aneurysm and stenosis of vessels, even in patients with apparently clinically inactive disease; acute blindness is rare during glucocorticoid treatment. In PMR, whether subclinical chronic inflammation can lead to long-term damage is less clear. Management of both GCA and PMR is hampered by the lack of universally accepted definitions of remission and other disease states, such as low disease activity or vessel damage without active disease. In this Review, we outline current evidence on the monitoring and long-term management of patients with GCA and PMR, including the tapering of treatment.

An Extreme Case of Corticosteroid-induced Psychosis in the Treatment of Giant Cell Arteritis

An Extreme Case of Corticosteroid-induced Psychosis in the Treatment of Giant Cell Arteritis

Corticosteroid Usage in Giant Cell Arteritis

ABSTRACT Giant cell arteritis (GCA) is a condition that can cause irreversible visual loss if untreated. While corticosteroids remain the mainstay of treatment to prevent visual loss, the type, dose, route, and duration of corticosteroid treatment of GCA remain controversial. Our study surveyed neuro-ophthalmologists to determine commonly prescribed dosages of corticosteroids for the treatment of GCA with or without visual loss. For patients with acute visual loss, 52% would use intravenous (IV), 46% would use IV or oral and 2% would use oral corticosteroids. Seventy-three per cent would use 500 to 1000 mg IV methylprednisolone in this group. For patients with GCA without acute visual loss, 67% would use the oral route, 30% would use IV or oral, and 3% indicated they would use IV route of treatment. Seventy-five per cent would use 1.0 to 1.5 mg/kg oral prednisone in this group. Our results suggest a majority but not a complete consensus for route and dose of corticosteroid treatment in GCA and confirm conventional recommendations for high dose IV corticosteroids for GCA with visual loss and lower dose oral regimens for GCA without visual loss.

OP0144 EFFECT OF TOCILIZUMAB ON VASCULAR INFLAMMATION BY 18F-FLUORODEOXYGLUCOSE POSITRON EMISSION TOMOGRAPHY: A PROSPECTIVE, LONGITUDINAL STUDY

Background:Two randomized controlled trials have demonstrated clinical efficacy of tocilizumab for the treatment of giant cell arteritis (GCA)(1, 2). In these trials, clinical and laboratory measures were used to define the outcome measures. The direct effect of tocilizumab on vascular inflammation remains poorly characterized.Objectives:To prospectively evaluate vascular inflammation as measured by18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in a longitudinal cohort of patients with GCA treated with tocilizumab over a several year follow-up period.Methods:Patients with GCA were recruited into a prospective, observational cohort. All patients fulfilled modified 1990 American College of Rheumatology (ACR) Classification Criteria for GCA. All patients underwent FDG-PET computed tomography (CT) prior to initiation of tocilizumab. A single reader reviewed all PET scans, blinded to clinical data. Qualitative assessment of FDG uptake relative to liver uptake by visual assessment (scale 0-3) was assessed in 9 arterial territories. A summary score, PET Vascular Activity Score (PETVAS), was calculated (scale 0-27).Patients underwent imaging at 6-12 month intervals per a standardized imaging protocol. In a subset of patients in whom tocilizumab was discontinued due to established remission, a repeat FDG-PET scan was obtained within 6 months of drug discontinuation.Change in PET activity over time was measured by linear regression. PET activity during established remission was compared to PET activity after discontinuation of tocilizumab. For some patients, tocilizumab was added to the existing treatment regimen without a substantive change in concomitant glucocorticoid dose. In a secondary analysis, patients were stratified by prednisone dosing (high dose prednisone >10mg/day prednisone, low dose prednisone ≤10mg/day prednisone during the imaging interval) to determine if tocilizumab had an effect on vascular inflammation independent of glucocorticoids.Results:22 patients were included in the study. All patients had clinically active disease at baseline with median baseline PETVAS 24.5 (23-27). There was a significant reduction in PETVAS over 2 years follow up (p<0.01 for linear trend) (Figure). Of note, there was continued progressive improvement in PETVAS in both year 1 and year 2 of treatment. Eight patients received concomitant high dose glucocorticoids and 14 patients remained on low dose glucocorticoids with the addition of tocilizumab. In patients who only received low dose prednisone, significant reduction in PETVAS was still observed with addition of tocilizumab (PETVAS 25.5 to 19.5, p=0.04). In a subset of 5 patients who discontinued tocilizumab due to established remission [median PETVAS 19 (17.5-22) at time of remission], a repeat FDG-PET scan within 6 months after treatment discontinuation showed worsening PET activity in 4 out of 5 patients [median PETVAS 23 (20-23)]. Two of these patients subsequently experienced a clinical disease relapse.Conclusion:Tocilizumab was associated with improved vascular inflammation as assessed by FDG-PET. There was continued improvement of vascular inflammation at both year 1 and year 2 of treatment, and early evidence suggests a rebound of vascular inflammation when tocilizumab was discontinued. These data provide rationale for long-term tocilizumab therapy in patients with GCA and for consideration of FDG-PET as an outcome measure in future clinical trials.

FRI0216 STEROID SPARING EFFECT, LOWER INCIDENCE OF DISEASE RELAPSE AND DIABETES IN GIANT CELL ARTERITIS TREATED WITH IMMUNOSUPPRESSORS AB INITIO OR VERY EARLY: A MULTICENTER RETROSPECTIVE CASE-CONTROL STUDY

Background:Glucocorticoids (GC) are associated with serious side effects in giant cell arteritis (GCA). Immunosuppressive therapies (IT) gave conflicting results in GCA, regarding GC sparing effect. Recently, tocilizumab by blocking IL-6, has been licensed as first biologic treatment for GCA, being clinically effective and saving GC (1).Objectives:To evaluate the usefulness of IT for GCA in: 1) minimizing the rate of GC-induced adverse events (AEs) and 2) reducing the risk of relapse.Methods:A multicenter retrospective case-control study included 165 GCA was performed. The first group of patients (GCA-IT) included 114 patients who were treated with at least one IT given ab initio or within 3 months from the start of GC. The control group included 51 GCA who received only GC or an IT later than 3 months (GCA-steroid). The primary endpoints were the rate of GC-related side effects: infections, hospitalized infections, new onset systemic arterial hypertension, GC-induced diabetes and osteoporotic fractures.Results:Methotrexate up to 20 mg/week (138 patients), followed by cyclophosphamide (48 patients) and tocilizumab (27 patients) were the most frequently used IT. No difference was observed as concerns the follow-up time between the two groups [48.5 (IQR 26-72) vs 40 (IQR 24-69), p=0,3, rank-sum test)]. The two groups were similar as concerns sex (p=0,13), while the first group (69±8 yrs) was slightly younger than the second one (72±7 yrs) (p=0,005). Comorbidity was similar between groups. Patients in the GCA-IT group showed a significant lower incidence of GC-induced diabetes (8/114, 7% vs 12/51, 23,5%; p=0,003, chi-square test), while no differences were documented for rate of infections (p=0,64), including hospitalized infections (p=0,44), new onset systemic arterial hypertension (p=0,68), or osteoporotic fractures (p=0,32). Forty-four patients in the GCA-IT group (38,6%), while 34 patients in the GCA-steroid group (66,7%) experienced at least one relapse (p=0,001, chi square test). There was no difference in terms of time to first relapse between the two groups (p=0,53, log-rank test). GCA-IT group was exposed to lower dose of GC at first (p<0,0001, rank-sum test) and third (p<0,0001, rank-sum test) month, while no differences were recorded at the other time points. Clinical outcomes were similar between the two groups.Conclusion:Very early introduction of IT in GCA provided a greater steroid sparing in the first 3 months of treatment, leading to a lower incidence of diabetes. Relapse rate was even lower. IT was usually well tolerated without an increase incidence of infections. A randomized prospective trial is required to support this strategy in the management of GCA.

Treatment of giant cell arteritis: what is in the pipeline?

Glucocorticoids (GC) represent the standard treatment in remission induction and maintenance in the treatment of giant cell arteritis (GCA). Additive immunosuppressants are currently only recommended in special situations, such as refractory or relapsing disease or in cases of glucocorticoid-induced side effects. Methotrexate has been the standard steroid-sparing agent for many years. Meanwhile, tocilizumab is the first choice for steroid reduction, which was the first biological to be licensed for the treatment of GCA; however, long-term data over more than 3years are lacking. Anumber of promising bDMARD and tsDMARD are currently being investigated in randomized controlled trials (RCT), which could contribute to additional effective steroid-sparing options in the treatment of GCA and help to establish an additive GC-sparing medication as the standard treatment in the future. This article gives an overview on current treatment studies for GCA.